Friday, July 31, 2009
Thursday, July 30, 2009
By Ed Langlois
CORVALLIS — The dean of Oregon’s Catholic campus ministry has died.
Sue Gifford, campus minister at Oregon State University here for more than 20 years, died in her sleep last weekend. She was 49.
“In the crazy life of the student these days, we can be a place to come, ask questions, have some fun and learn more about faith,” Gifford told the Sentinel in 2002. “We can provide a community where students can grow both in their field of study and in their faith and knowledge of God.”
Gifford’s simple Corvallis apartment was festooned with photos from friends and former students.
“She had an enormous vitality, love for the Lord and a tremendous sense of humor,” says Barb Anderson, pastoral associate at St. Mary Parish here. “She was a person who really believed in hospitality and accompanying people on their spiritual journey. She had a lot of patience for young people who were struggling and needed some guidance. She was very willing to be that guide, that friend.”
Friends say Gifford had suffered for decades with Cushing’s syndrome, an excess of the hormone cortisol related to a tumor on the pituitary gland. Prolonged exposure to cortisol can cause excess weight and high blood pressure. At one point, Gifford’s doctors told her she may not live to be 40.
She was was born July 4, 1960 in Greenfield, Mass., attending schools in Colrain and Shelburne Falls, and graduated from Mohawk Regional High School in 1978.
She graduated with a bachelor’s degree from St. Michael’s College in Colchester, Vt. in 1982, and went on to earn a master’s degree from Mundelein College in Chicago. She devoted her life to Catholic campus ministry at the University of Illinois and Oregon State University. She held positions on various archdiocesan and national committees associated with Newman Centers and the Catholic Campus Ministry Association.
Gifford played a key role in creating a new Newman Center at OSU.
Dedicated in 2002, it includes housing, common areas, a coffee house and a faith library.
“The sky is the limit on what we can do with this new space,” Gifford told the Sentinel. “There will be lots of places for students to just come and be. The Newman Center has to be their home away from home. We can be a place where kids can come in from the hubbub on campus and catch their breath.”
Taking a page from fraternities and sororities, each fall she made the second week of school Catholic Rush Week. Students ate ice cream, studied scripture, ate a simple supper and even attended a session of “Stupid Catholic Questions,” where any inquiry is fair.
Gifford led workshops on the sacraments and was the organizer of a group that explored all manner of vocations — single life, marriage, priesthood and religious life.
When Holy Names Sister Crystal Clark professed her first vows in 2006, the young OSU graduate cited Gifford as an important part of her faith development.
Gifford knew that public colleges and universities were focusing on educating the whole student and wanted spiritual formation to be part of that. She launched a university lecture series that focused on faith and higher education.
Dominican Father Michael Fones, who worked at campus ministry at the University of Oregon for six years, considered Gifford a sister. They led retreats together and even teased each other about collegiate allegiances.
“God gifted her with a tremendous ability to see strangers in the crowd and make them feel at home and really establish trust,” says Father Fones, who now lives in Tucson, Ariz. “For somebody who does not know Christ, that is the first threshhold they need to cross before they can really start exploring faith.”
Gifford is survived by her parents, Rolland and Lois Gifford, and her brother, Paul, of Shelburne Falls, Mass.
Sue enjoyed cooking and reading, and she loved spending time with students, her newly adopted dog, Tanner, and her wide circle of friends across the country.
A prayer service and vigil were held Tuesday and the funeral Mass was set for 3 p.m. Wednesday, July 29 at St Mary Church here.
In lieu flowers, donations can be made to the charity of one’s choice or to the Nancy Gifford Memorial Scholarship Fund c/o Paul Gifford, 19 South Maple Street, Shelburne Falls, MA, 01370.
Wednesday, July 29, 2009
In This Issue
The adrenal glands are small, yellowish organs that rest on the upper poles of the kidneys in the Gerota fascia. The right adrenal gland is pyramidal, whereas the left one is more crescentic, extending toward the hilum of the kidney. At age 1 year, each adrenal gland weighs approximately 1 g, and this increases with age to a final weight of 4-5 g. The arterial blood supply comes from 3 sources, with branches arising from the inferior phrenic artery, the renal artery, and the aorta. Venous drainage flows directly into the inferior vena cava on the right side and into the left renal vein on the left side. Lymphatics drain medially to the aortic nodes.
Each adrenal gland is composed of 2 distinct parts: the adrenal cortex and the adrenal medulla. The cortex is divided into 3 zones. From exterior to interior, these are the zona glomerulosa, the zona fasciculata, and the zona reticularis.
First detected at 6 weeks’ gestation, the adrenal cortex is derived from the mesoderm of the posterior abdominal wall. Steroid secretion from the fetal cortex begins shortly thereafter. Adult-type zona glomerulosa and fasciculata are detected in fetal life but make up only a small proportion of the gland, and the zona reticularis is not present at all. The fetal cortex predominates throughout fetal life. The adrenal medulla is of ectodermal origin, arising from neural crest cells that migrate to the medial aspect of the developing cortex.
The fetal adrenal gland is relatively large. At 4 months’ gestation, it is 4 times the size of the kidney; however, at birth, it is a third of the size of the kidney. This occurs because of the rapid regression of the fetal cortex at birth. It disappears almost completely by age 1 year; by age 4-5 years, the permanent adult-type adrenal cortex has fully developed.
Anatomic anomalies of the adrenal gland may occur. Because the development of the adrenals is closely associated with that of the kidneys, agenesis of an adrenal gland is usually associated with ipsilateral agenesis of the kidney, and fused adrenal glands (whereby the 2 glands join across the midline posterior to the aorta) are also associated with a fused kidney.
Adrenal hypoplasia occurs in the following 2 forms: (1) hypoplasia or absence of the fetal cortex with a poorly formed medulla and (2) disorganized fetal cortex and medulla with no permanent cortex present. Adrenal heterotopia describes a normal adrenal gland in an abnormal location, such as within the renal or hepatic capsules. Accessory adrenal tissue (adrenal rests), which is usually comprised only of cortex but seen combined with medulla in some cases, is most commonly located in the broad ligament or spermatic cord but can be found anywhere within the abdomen. Even intracranial adrenal rests have been reported.
The adrenal cortex secretes 3 types of hormones: (1) mineralocorticoids (the most important of which is aldosterone), which are secreted by the zona glomerulosa; (2) glucocorticoids (predominantly cortisol), which are secreted by the zona fasciculata and, to a lesser extent, the zona reticularis; and (3) adrenal androgen (mainly dehydroepiandrosterone [DHEA]), which is predominantly secreted by the zona reticularis, with small quantities released from the zona fasciculata.
All adrenocortical hormones are steroid compounds derived from cholesterol (see Media file 3).
Cortisol binds to proteins in the blood, mainly cortisol-binding globulin or transcortin. More than 90% of cortisol is transported in the blood in this bound form. In contrast, only 50% of aldosterone is bound to protein in the blood. All adrenocortical steroids are degraded in the liver and predominantly conjugated to glucuronides, with lesser amounts of sulfates formed. About 75% of these degradation products are excreted in the urine, and the rest is excreted in the stool by means of the bile.
Aldosterone accounts for 90% of mineralocorticoid activity, with some activity contributed by deoxycorticosterone, corticosterone, and cortisol. The normal concentration of aldosterone in the blood ranges from 2-16 ng/dL supine and 5-41 ng/dL upright, although the concentration exhibits diurnal variation, and the secretory rate is generally 150-250 mcg/d.
Aldosterone promotes sodium reabsorption and potassium excretion by the renal tubular epithelial cells of the collecting and distal tubules. As sodium is reabsorbed, water follows passively, leading to an increase in the extracellular fluid volume with little change in the plasma sodium concentration. Persistently elevated extracellular fluid volumes cause hypertension. This helps minimize further increases in extracellular fluid volume by causing a pressure diuresis in the kidney, a phenomenon known as aldosterone escape. Without aldosterone, the kidney loses excessive amounts of sodium and, consequently, water, leading to severe dehydration.
As sodium is actively reabsorbed, potassium is excreted. Imbalances in aldosterone thus lead to hypokalemia and muscle weakness if levels are increased and to hyperkalemia with cardiac toxicity if levels are decreased. In addition to sodium being exchanged for potassium at the renal tubules, hydrogen is also exchanged, although to a much lesser extent. Therefore, with aldosterone excess, mild metabolic alkalosis may develop.
In addition to the effects of aldosterone on the renal tubules, a smaller but similar effect is noted on the sweat glands and salivary glands. Aldosterone stimulates sodium chloride reabsorption and potassium secretion in the excretory ducts, which helps prevent excessive salivation and conserve body salt in hot climates. Aldosterone also affects sodium absorption in the intestine, especially the colon. Deficiency may cause a watery diarrhea from the unabsorbed sodium and water.
Many factors affect aldosterone secretion, the most important of which involve the renin-angiotensin system and changes in the plasma potassium concentration.
Activation of the renin-angiotensin system: The juxtaglomerular apparatus senses decreased blood flow to the kidney secondary to hypovolemia, hypotension, or renal artery stenosis and releases renin in response. Renin is an enzyme that activates angiotensinogen to release angiotensin I. In the lung, ACE converts angiotensin I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone release by the adrenal gland.
Concentration of potassium in the extracellular fluid: Increases in the plasma potassium concentration stimulate the release of aldosterone to encourage potassium excretion by the kidney.
Concentration of sodium in the extracellular fluid: Decreases in sodium concentration also stimulate aldosterone release.
Adrenocorticotropic hormone (ACTH) secretion: ACTH secreted by the anterior pituitary primarily affects release of glucocorticoids by the adrenal but, to a lesser extent, also stimulates aldosterone release.
Approximately 95% of glucocorticoid activity comes from cortisol, with corticosterone, a glucocorticoid less potent than cortisol, making up the rest. The normal cortisol concentration in the blood averages 12 mcg/dL, with a secretory rate averaging 15-20 mg/d. Cortisol release is almost entirely controlled by the secretion of ACTH by the anterior pituitary gland, which is controlled by corticotropin-releasing hormone (CRH) secreted by the hypothalamus. In normal situations, CRH, ACTH, and cortisol secretory rates demonstrate a circadian rhythm, with a zenith in the early morning and a nadir in the evening. Various stresses also stimulate increased ACTH and, thus, cortisol secretion. A negative feedback effect of cortisol on the anterior pituitary and the hypothalamus help control these increases and regulate plasma cortisol concentrations.
Cortisol has many effects on the body.
Cortisol stimulates gluconeogenesis in the liver by stimulating the involved enzymes and mobilizing necessary substrates, specifically amino acids from muscle and free fatty acids from adipose tissue. It simultaneously decreases glucose use by extrahepatic cells in the body. The overall result is an increase in serum glucose (ie, adrenal diabetes) and increased glycogen stores in the liver.
Cortisol decreases protein stores in the body, except in the liver, by inhibiting protein synthesis and stimulating catabolism of muscle protein.
Cortisol has clinically significant anti-inflammatory effects, blocking the early stages of inflammation by stabilizing lysosomal membranes, preventing excessive release of proteolytic enzymes, decreasing capillary permeability and, consequently, edema, and decreasing chemotaxis of leukocytes. In addition, it induces rapid resolution of inflammation that is already in progress.
Immunity is adversely affected. Eosinophil and lymphocyte counts in the blood decrease with atrophy of lymphoid tissue.
The adrenal cortex continually secretes several male sex hormones, including DHEA, DHEA sulfate (DHEAS), androstenedione, and 11-hydroxyandrostenedione, with small quantities of the female sex hormones progesterone and estrogen. Most of the effects result from extra-adrenal conversion of the androgens to testosterone. All have weak effects, but they likely play a role in early development of the male sex organs in childhood, and they have an important role in women during pubarche. ACTH has a definite stimulatory effect on androgen release by the adrenal. Therefore, secretion of these hormones parallels that of cortisol.
The adrenal medulla is a completely different entity. Epinephrine (80%) and norepinephrine (20%), with minimal amounts of dopamine, are secreted into the bloodstream due to direct stimulation by acetylcholine release from sympathetic nerves. Preganglionic sympathetic nerve fibers pass from the intermediolateral horn cells of the spinal cord through the sympathetic chains and splanchnic nerves, without synapsing, into the adrenal medulla. These hormones are responsible for an increase in cardiac output and vascular resistance and for all the physiologic characteristics of the stress response.
Radiology of the Adrenal Gland
CT scanning is the imaging procedure of choice for the evaluation of adrenal lesions, although ultrasonography and, increasingly, MRI have their advantages.
Plain radiography has limited value but may reveal mass effect or calcifications that suggest possible neuroblastoma, previous hemorrhage, or chronic granulomatous disease.
Ultrasonography is often the first imaging study performed in children. It is safe and easy to perform without sedation. It can differentiate cystic from solid adrenal masses and is useful to assess for vascular involvement and liver metastases.
CT scanning most accurately defines the size, location, and appearance of adrenal lesions. In addition, it is useful for assessing local and vascular invasion, involvement of lymph nodes, or distant metastases. For certain lesions (eg, simple cysts, myelolipomas, often hemorrhage), CT scanning enables definitive diagnosis because the image is classic. For solid lesions, unenhanced or delayed–contrast enhanced CT scanning may help in distinguishing benign from malignant lesions by their attenuation. Benign lesions tend to have decreased attenuation because of an increased fat content. However, overlap is substantial; therefore, this finding is not always useful.
MRI is also an excellent study to define the full extent of an adrenal lesion, including its relationship to adjacent organs and major vessels. Its main benefit over CT is its improved ability, with gadolinium enhancement or with chemical shift imaging, to help in differentiating benign from malignant lesions. This is most important in adults with an incidentally discovered adrenal mass.
Radioisotope scanning can be helpful in some situations. Iodocholesterol-labeled analogs (eg, iodine-131 6beta-iodomethyl-19-norcholesterol [NP-59]) are used to detect primary adrenocortical adenomas, carcinomas, or metastases. Dexamethasone administered before the scan enhances sensitivity by suppressing normal ACTH-responsive adrenal tissue. Metaiodobenzylguanidine (MIBG) scans may be used to detect adrenal medullary tumors, pheochromocytomas, and neuroblastomas. This is especially useful in localizing such tumors in extramedullary sites, enabling the entire body to be imaged at once.
More recently positron emission technology (PET) scanning has been introduced in the evaluation of recurrent or metastatic adrenal tumors, especially neuroblastoma. Its role has yet to be fully defined.
Adrenal pathology can manifest in various ways, including the following:
- Ambiguous genitalia with or without salt wasting in the newborn
- Palpable abdominal mass
- Incidental finding of an adrenal mass on imaging
- Glucocorticoid excess or Cushing syndrome
- Mineralocorticoid excess
- Androgen excess
- Catecholamine excess
- Adrenal insufficiency
- Paraneoplastic process
In the newborn period, ambiguous genitalia, with or without associated salt wasting, is strongly suggestive of congenital adrenal hyperplasia. This is an inherited autosomal recessive disorder caused by deficiency of 1 of the enzymes necessary for adrenal steroid production, especially cortisol. Cortisol deficiency leads to excessive secretion of adrenocorticotropic hormone (ACTH) with resultant bilateral adrenal hyperplasia; thus, a deficiency of the end products of blocked pathways and excess production of steroids in open pathways results.
The most common enzyme deficiency is 21-hydroxylase, which accounts for more than 90% of cases. This is seen in 2 forms: classic (more severe) and nonclassic (less severe).
The classic form, which occurs with an incidence of 1 case per 12,000-15,000 population, is characterized by cortisol deficiency and female virilization at birth secondary to excess adrenal androgen production, with salt wasting in 75% of cases secondary to aldosterone deficiency. This is the most common cause of ambiguous genitalia in a newborn girl. The diagnosis must be suspected early on and treatment instituted without delay because congenital adrenal hyperplasia can be life threatening in the newborn period.
The diagnosis is based on elevated baseline and ACTH-stimulated levels of serum 17-hydroxyprogesterone (17-OHP) and adrenal androgens, which are suppressed with the administration of glucocorticoids. When associated salt wasting occurs, the plasma renin-to-aldosterone ratio is also elevated.
Treatment involves replacement glucocorticoids aimed at decreasing ACTH secretion (maintenance hydrocortisone at 10-20 mg/m2/d orally [PO] divided 3 times per day [tid]), and, if salt wasting is prominent, a mineralocorticoid (9-alphafluorohydrocortisone, which is commonly known as fludrocortisone [Florinef], at 0.05-0.3 mg/d PO) and sodium chloride (1-3 g/d PO) are also used. Surgery for clitoral recession and vaginoplasty with correction of the urogenital sinus (usually present) may be performed in early infancy, if the degree of virilization in the newborn girl mandates it.
In the nonclassic (relatively mild) form, patients present late with precocious pubarche or problems related to androgen excess, including hirsutism, menstrual irregularities, and infertility. This is said to be the most common autosomal recessive disorder in humans.
The diagnosis is confirmed with elevated ACTH-stimulated levels of serum 17-OHP and adrenal androgens as in the classic form. Baseline levels are usually not as high because they are in the classic form and may even be normal.
Lowered doses of hydrocortisone can be administered as treatment, although some patients never require any therapy. See Congenital Adrenal Hyperplasia for more information.
Palpable Abdominal Mass
A palpable abdominal mass has a large differential diagnosis; adrenal lesions are included.
Neuroblastoma is a malignant tumor derived from neural crest cells in the adrenal medulla or anywhere along the sympathetic chain. About 75% of neuroblastomas arise from within the abdomen or pelvis, with half of these from the adrenal medulla itself, 20% originating from the posterior mediastinum, and 5% coming from the neck. With an overall incidence of 1 case per 10,000 population, it is the most common solid extracranial tumor of childhood. It can manifest in numerous ways, but the most common presentation is as a fixed abdominal mass extending from the flank towards the midline. See Neuroblastoma for more information. Ganglioneuroma, the benign counterpart of neuroblastoma, can also appear as a large palpable abdominal mass.
Another adrenal medullary tumor of neuroendocrine origin that can also be found in extra-adrenal sites is pheochromocytoma. This usually manifests with symptoms attributable to the excess catecholamine secretion by the tumor. In rare cases, an abdominal mass may be noted first.
Adrenal cortical tumors, and especially carcinomas because these tend to be larger than adenomas, can present with a palpable abdominal mass. However, signs and symptoms of excess adrenocortical hormone secretion usually prompt a workup and diagnosis of such tumors. Adrenal cysts are rare in childhood but can be large enough to produce a palpable mass.
Incidental Finding of Adrenal Mass
An adrenal lesion may be incidentally detected during abdominal ultrasonography or CT scanning performed for other reasons. The differential diagnosis of an adrenal mass is extensive.
The differential diagnosis of an adrenal mass is as follows:
- Nonneoplastic conditions
- Chronic granulomatous disease (eg, tuberculosis [TB], histoplasmosis)
- Neoplastic conditions
- Benign conditions
- Adrenocortical adenoma
- Malignant conditions
- Adrenocortical carcinoma
- Non-Hodgkin lymphoma
- Metastases (eg, malignant melanoma, breast carcinoma, hepatocellular carcinoma, squamous cell lung carcinoma)
The differential diagnosis of bilateral adrenal enlargement or mass is as follows:
- Cushing disease
- Adrenal nodular hyperplasia
- Ectopic ACTH or corticotropin-releasing hormone (CRH) production
In adults, most incidentally discovered adrenal solid masses are adenomas; therefore, such tumors less than 4-5 cm in size, of benign appearance on imaging, and with no extra-adrenal disease are simply observed. In children, the most common adrenal mass is neuroblastoma. In a study of 26 children with an incidentally detected adrenal mass, 30% were found to be malignant; upon review of the imaging, neither size nor appearance could distinguish between benign and malignant.1 Thus, all pediatric adrenal masses found incidentally should be resected.
Glucocorticoid Excess or Cushing Syndrome
The clinical findings associated with excess cortisol secretion in children most commonly include obesity with moonlike facies, growth failure, hirsutism, and acne. Other findings include hypertension, muscle weakness, osteoporosis, glucose intolerance, easy bruising, striae, hyperpigmentation and thin skin, menstrual irregularities, and psychiatric disturbances. Patients with cortisol excess also have impaired wound healing and an increased susceptibility to infection.
The differential diagnosis of Cushing syndrome is as follows:
- Use of exogenous steroids
- ACTH-independent causes
- Adrenal nodular hyperplasia
- Adrenocortical adenoma
- Adrenocortical carcinoma
- ACTH-dependent causes
- Pituitary adenoma (Cushing disease)
- Ectopic ACTH or CRH production from tumors (eg, medullary thyroid cancer, carcinoid tumor, thymoma, Wilms tumor, adrenal rest tumor, pancreatic tumor)
In children younger than 10 years, unlike in older children and adults, primary adrenal pathology (eg, adenoma, adrenal nodular hyperplasia) is the most common cause of Cushing syndrome after use of exogenous corticosteroids and instead of a pituitary adenoma.
In a patient with suspected Cushing syndrome, the first step is to confirm hypercortisolemia (see Media file 1). The best screening test is measurement of free cortisol or 17-hydroxycorticosteroid (17-OHCS) levels in 2-3 consecutive 24-hour urine collections. Normal 24-hour urinary free cortisol values are in the range of 25-75 mcg/m2/d. Plasma levels of cortisol can also be obtained. However, because of the normal diurnal variation, this test is less reliable than urine measurement. The low-dose or overnight dexamethasone suppression test should be used as a confirmatory test when 24-hour urinary levels of 17-OHCS or cortisol are borderline. This involves PO administration of dexamethasone (30 mcg/kg) at 11 pm, with measurement of plasma cortisol at 8 am the next morning. Plasma cortisol levels are normally suppressed to less than 5 mcg/dL. In Cushing syndrome, cortisol secretion is not suppressed.
The next step is to distinguish between ACTH-dependent and ACTH-independent causes, which involve plasma ACTH level measurement. ACTH levels are normally 10-100 pg/mL, with a diurnal variation that parallels that of cortisol but precedes it by 1-2 hours. However, plasma ACTH is low (<5 pg/mL) in patients with adrenocortical neoplasms, intermediate (15-500 pg/mL) in patients with pituitary adenomas and resultant adrenocortical hyperplasia, and highest (usually >1000 pg/mL) in patients with ectopic ACTH-producing tumors.
To further distinguish between the causes of ACTH-dependent Cushing syndrome, the high-dose dexamethasone suppression test is used. It is based on the principle that a high dose of dexamethasone at least partially suppresses adrenal cortisol secretion secondary to an ACTH-secreting pituitary adenoma, whereas secretion secondary to adrenal tumors and ectopic ACTH production is not. Dexamethasone (120 mcg/kg/d given PO divided 4 times a day [qid]) is given for 48 hours. On the second day, a 24-hour urine collection is obtained to measure free cortisol and 17-OHCS levels. In patients with a pituitary adenoma, urinary free cortisol levels are suppressed by 90% to less than 30 mcg/d in 60-70% of patients, and urinary 17-OHCS levels are reduced to less than 3 mg/d.
Another test that can be used to distinguish between Cushing disease and ectopic ACTH production is the metyrapone stimulation test. Because metyrapone blocks the enzyme 11-hydroxylase, which is responsible for conversion of 11-deoxycortisol to cortisol, its administration at 15 mg/kg (or 750 mg for adolescents) PO every 4 hours for 24 hours decreases plasma cortisol and increases ACTH values. The normal response is an increase in plasma 11-deoxycortisol levels to more than 10 mcg/dL and an increase in 24-hour urine 17-OHCS levels to twice the baseline. Patients with pituitary adenomas show this response, whereas those with ectopic ACTH secretion do not. The CRH stimulation test, whereby 1 mcg/kg of CRH is administered and ACTH levels are measured, is also performed to distinguish Cushing disease in most cases. Within 60-180 minutes, patients with Cushing disease had the normal increase in ACTH, and those with other causes of hypercortisolemia do not.
After these distinctions are made, imaging can be used to localize these lesions. Gadolinium-enhanced MRI of the sella turcica is the best imaging modality for assessing pituitary adenomas, with a sensitivity approaching 100%. Sampling of the bilateral inferior petrosal sinuses for ACTH can help identify a pituitary adenoma if imaging does not. Thin-section high-resolution CT scanning or MRI of the adrenals identifies adrenal abnormalities with more than 95% sensitivity. CT or MRI of the chest and abdomen may help in identifying an ectopic ACTH-producing or CRH-producing tumor.
Surgical resection of the offending lesion is the initial treatment of choice for all forms of Cushing syndrome, including bilateral adrenalectomy for bilateral nodular adrenal hyperplasia, transsphenoidal partial hypophysectomy for pituitary adenomas, and unilateral adrenalectomy for adrenal tumors.
Presenting features of mineralocorticoid excess include hypertension, headache, tachycardia, fatigue, proximal muscle weakness, polyuria, and polydipsia.
The differential diagnosis of hyperaldosteronism is as follows:
- Idiopathic adrenal nodular hyperplasia (idiopathic hyperaldosteronism)
- Glucocorticoid-suppressible hyperaldosteronism
- Adrenocortical adenoma
- Adrenocortical carcinoma
Secondary - Elevated renin secretion secondary to renal artery stenosis, a renin-producing tumor, congestive heart failure, and Bartter syndrome (ie, juxtaglomerular hyperplasia)
Primary hyperaldosteronism, characterized by elevated plasma aldosterone, low plasma renin levels, hypokalemia, and hypertension, is rare in children. Unlike in adults, the most common cause is bilateral adrenal hyperplasia, with only a handful of aldosterone-secreting adenomas (ie, Conn syndrome) reported.2 Because adenomas are a curable cause of hypertension, they must be considered in children presenting with hypertension, despite their rarity.
Bilateral adrenal hyperplasia as a cause of hyperaldosteronism occurs in nodular adrenal hyperplasia and in a unique autosomal dominant condition called glucocorticoid-suppressible hyperaldosteronism. This has all of the clinical and biochemical features noted in other causes of primary hyperaldosteronism but demonstrates complete and rapid suppression of aldosterone secretion by administration of dexamethasone.
Adrenocortical carcinoma as a cause of primary hyperaldosteronism is exceptionally rare, with an incidence of 1% in a large series of adults and no reported cases in children.
The first step in the workup of a patient with suspected hyperaldosteronism is to confirm the diagnosis (see Media file 2). Elevated plasma aldosterone levels, hypokalemia (<3.5 mEq/L), and kaliuresis (>30 mEq/d) confirm the diagnosis. A suppressed plasma renin level is compatible with a primary cause. In addition, patients with primary hyperaldosteronism exposed to salt-loading by ingestion of a high-sodium diet for 3-5 days (or by infusion of isotonic sodium chloride solution in a patient who is salt deprived) fail to show suppression of plasma or 24-hour urinary aldosterone. Upright posture and salt depletion also fail to cause a rise in plasma renin activity.
The next step is to distinguish among the various causes of primary hyperaldosteronism. Response to administration of dexamethasone rapidly confirms the diagnosis of glucocorticoid-suppressible hyperaldosteronism. The postural test is most helpful in distinguishing between nodular hyperplasia and adrenal neoplasm. This test is based on the observation that aldosteronomas are sensitive to ACTH and, therefore, exhibit a diurnal variation in aldosterone secretion, whereas adrenal nodular hyperplasia does not.
The patient is kept supine overnight. At 8 am, baseline plasma levels of cortisol, aldosterone, renin, and potassium are measured. The patient stands up and remains upright for 4 hours, at which point all laboratory studies are repeated. An aldosterone-secreting tumor typically results in a drop in aldosterone levels, paralleling the change of cortisol in its natural daytime fall, which the change in posture does not affect. In patients with adrenal hyperplasia, aldosterone responds to the postural change, increasing by more than 33%. Before any of these tests are performed, patients should be potassium replete and not taking any antihypertensive medications for at least 4 weeks.
If an aldosterone-secreting tumor is suspected, imaging is obtained. High-resolution CT scanning can be done to localize approximately 90% of such tumors. Because the lesions are often small, NP-59 scanning can be useful if CT fails to depict the tumor; sensitivity is 70-80% and specificity is 100% in this situation.
As an alternative, selective adrenal venous sampling can be used to definitively identify a tumor. However, it is invasive and technically difficult and, therefore, is used only rarely. Intravenous (IV) ACTH is administered, and adrenal venous blood samples are simultaneously obtained to measure aldosterone and cortisol. An aldosterone-to-cortisol ratio higher than 4:1 is diagnostic of an aldosteronoma and is unilateral as opposed to bilateral.
Aldosterone-secreting tumors are treated by surgical resection. Glucocorticoid-suppressible hyperaldosteronism is treated with glucocorticoids. Bilateral adrenal nodular hyperplasia is treated medically with potassium-sparing diuretics, such as spironolactone or amiloride. Surgery is reserved for cases refractory to medical therapy because less than 20-30% of patients with this disease are cured with adrenalectomy.
The predominant clinical feature of hyperandrogenism in the newborn girl is ambiguous genitalia.3 In the older child or adolescent, signs and symptoms include pseudoprecocious puberty in boys and hirsutism, acne, clitoromegaly, deepening of voice, and oligomenorrhea in girls. In both sexes, linear growth and skeletal maturation (ie, bone age) are accelerated.
The differential diagnosis of hyperandrogenism is as follows:
- Use of exogenous anabolic steroids
- Adrenal causes
- Congenital adrenal hyperplasia4
- Adrenocortical adenoma
- Adrenocortical carcinoma
- Exaggerated adrenarche
- Extra-adrenal causes
- Polycystic ovary
- Adrenal rests
- Ovarian tumors- most commonly arrhenoblastoma
- Testicular tumors- most commonly Leydig cell tumors
- Adrenal hyperplasia secondary to a pituitary adenoma or ectopic secretion of ACTH or CRH
In infants with failure to thrive, salt wasting and (most obviously in baby girls with clitoromegaly, fused labia, and a persistent urogenital sinus) congenital adrenal hyperplasia must be ruled out. The same is true in boys who present with pseudoprecocious puberty and in older girls with signs and symptoms of hyperandrogenism, although, in teenage girls, polycystic ovary is the most common cause.
Congenital adrenal hyperplasia can be reliably diagnosed with a dexamethasone suppression test. Apart from a few rare causes of hyperandrogenism including exaggerated adrenarche secondary to adrenal hyperresponsiveness to ACTH, hyperprolactinemia, and acromegaly, congenital adrenal hyperplasia is the only virilizing condition in which androgen secretion is suppressed by dexamethasone. ACTH levels can be used to confirm the diagnosis if it is still questionable. An increase in plasma 17-OHP to more than 1200 ng/dL at 60 minutes in response to an IV injection of 250 mcg of cosyntropin is diagnostic of congenital adrenal hyperplasia.
Adrenocortical tumors must always be considered in the differential diagnosis. They are reported to occur from infancy throughout adolescence and well into adulthood. The vast majority of these tumors are virilizing, with 50-80% causing virilization alone and an added 20-40% causing Cushing syndrome in addition to virilization. Rare adrenocortical tumors are predominantly mineralocorticoid secreting or feminizing.
As a group, these tumors are rare, with a childhood incidence of 0.3 per million. Certain children are at increased risk, including those with a family history of p53 mutations, those with Beckwith-Wiedemann syndrome, and those with isolated hemihypertrophy. Distinguishing between benign and malignant adrenocortical lesions is difficult, even pathologically, and the clinical behavior of the tumor is the best determinant of malignancy. Most common sites of metastases are lung and liver, with regional lymph nodes, bone, brain, and pancreatic metastases observed relatively infrequently.
Radical resection, including en bloc resection of locally invaded organs, offers the best chance for cure of adrenocortical tumors. Metastases should also be resected if possible. No survivors after partial resection of tumor have been reported. Adjuvant therapy has shown disappointing results. Mitotane is the most extensively used agent. Although it has not been shown to prolong survival, it can substantially ameliorate the symptoms of hyperandrogenism. It can, however, have significant GI and neurologic side effects. Other, more conventional chemotherapeutic drugs have shown poor results thus far, and radiotherapy has not been proven effective. Pediatric series reveal overall survival rates for adrenocortical tumors of 43-91%. (See Adrenal Carcinoma for more information.)
Distinguishing between ovarian and adrenal virilizing disorders in young girls depends on physical examination, biochemical test, and imaging study findings. Virilizing ovarian tumors are often large, and most are palpable on physical examination. Serum testosterone levels are virtually always elevated. In virilizing adrenocortical tumors, plasma levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione are high, whereas those of testosterone (mainly due to peripheral conversion of androstenedione to testosterone) are elevated much less often and to a lesser extent. Adrenal tumors also result in elevated urinary and plasma 17-ketosteroid levels that are normal or only minimally elevated in ovarian tumors.
In boys, a testicular examination can help determine the source of androgen excess. If both testes are enlarged, they are the most likely source of the androgens in response to gonadotropins (luteinizing hormone [LH], representing central precocious puberty) or a human chorionic gonadotropin (hCG)-secreting tumor. If both testes are prepubertal in size, the most likely source of the androgens is adrenal. Finally, if one testis is enlarged, the likely source is a testicular tumor.
The clinical manifestations of catecholamine excess include hypertension (either sustained or paroxysmal) orthostatic hypotension, tachycardia or bradycardia, arrhythmias, headache, fatigue, visual blurring, sweating and heat intolerance, weight loss, abdominal pain, and polyuria and polydipsia. These symptoms should prompt biochemical testing to confirm excess catecholamine secretion characteristic of pheochromocytoma.
Measurement of urinary catecholamines, epinephrine and norepinephrine, and their metabolites (ie, metanephrine, homovanillic acid, and vanillylmandelic acid) in a 24-hour urine collection is a sensitive (>90%) test for the diagnosis of pheochromocytoma. Plasma catecholamine levels can also be diagnostic when performed at rest. Levels of more than 2000 pg/mL are diagnostic of a pheochromocytoma. However, the diagnosis can be missed in patients with paroxysmal symptoms.
Various stimulation and suppression tests have been developed to improve diagnostic accuracy. The clonidine suppression test relies on the fact that clonidine suppresses centrally mediated release of catecholamines (to <500 pg/mL) within 2-3 hours of PO administration but does not affect release of catecholamines from a pheochromocytoma. The stimulation tests are dangerous and should only be performed in a monitored setting in situations in which the blood pressure and plasma catecholamine levels are near normal. The glucagon stimulation test demonstrates a more than 3-fold increase in catecholamines or an absolute plasma level of more than 2000 pg/mL after an IV bolus of glucagon in the presence of a pheochromocytoma. Neuroblastoma is also characterized and diagnosed by demonstrating increased catecholamine secretion. However, patients are typically asymptomatic.
Pheochromocytomas are rare tumors that arise from the neural crest–derived chromaffin cells found in the adrenal medulla and sympathetic ganglia. Compared with pheochromocytomas in adults, in children incidences of extra-adrenal tumors (30% vs 10%) and bilateral tumors (30% vs 10%) increase, as does the tendency for a familial occurrence, and the incidence of malignancy is lowered (3.5% vs 10%). Also, pheochromocytomas in children secrete norepinephrine more commonly than they secrete epinephrine; this change may simply reflect the heightened incidence of extra-adrenal tumors. The most common extra-adrenal site is the upper periaortic ganglia, followed by the organs of Zuckerkandl at the base of the inferior mesenteric artery. Other sites include the base of the brain, the chest, and bladder.
Patients at increased risk for pheochromocytomas include those with multiple endocrine neoplasia type II (MEN II) syndrome and neurocutaneous syndromes (eg, Von Recklinghausen disease, tuberous sclerosis, von Hippel–Lindau disease, Sturge-Weber syndrome). In children with a pheochromocytoma, headache is the most common symptom (75%), followed by sweating, nausea, and vomiting. Other frequent symptoms include visual complaints, weight loss, and polyuria and polydipsia.
Hypertension is seen in almost all patients and is sustained in 80-90%, unlike in adults who tend to have paroxysmal hypertension. The hypertension is also more severe in children than in adults, with more than 40% of affected individuals having signs of hypertensive retinopathy, and 40% having signs of cardiomyopathy.
Localization of pheochromocytomas is best accomplished with CT scanning or, particularly, MRI. CT scanning has 94% sensitivity for detection of adrenal tumors and 64% sensitivity for extra-adrenal tumors, with 98% specificity. MRI has 97% sensitivity for detection of adrenal tumors and 88% sensitivity for extra-adrenal tumors, with 100% specificity. Metaiodobenzylguanidine (MIBG) scanning is also highly specific for pheochromocytoma but is less sensitive than MRI. It is most useful to help localize an extra-adrenal pheochromocytoma, which can then be imaged in most detail with CT scanning or MRI.
After the diagnosis is confirmed and the tumor localized, preparations for surgical resection must be started. Patients should be treated with an alpha-adrenergic blocker, such as phenoxybenzamine, with the dose gradually increased to achieve blood pressure and symptom control (0.25-1 mg/kg/d PO in divided doses). Once alpha blockade is accomplished, a beta-adrenergic blocker (eg, propranolol) can be used if arrhythmias occur. Such treatment is begun preferably at least 3 weeks before planned surgery. During surgery, the anesthetist must be prepared for hypertensive episodes, which can be controlled with an agent such as nitroprusside, and for hypotension after the tumor is removed, which responds well to fluids.
The surgical approach of choice is transabdominal. This allows the exploration of both adrenal glands and the sympathetic chain, early ligation of the adrenal vein to prevent excessive catecholamine release with tumor manipulation, and resection of locally invaded organs if necessary. Despite this, extraperitoneal approaches have been used for small tumors. Also, increasingly, a laparoscopic approach is used in adults and children. An attempt should be made to resect the primary tumor in all cases, with resection of metastases if possible, because most of the morbidity and mortality associated with these tumors are the result of the excess catecholamine secretion.
Intensive chemotherapy, principally in the form of cisplatin and doxorubicin, can render some unresectable tumors resectable and should be tried in such cases. Adjuvant chemotherapy is also indicated for residual disease postsurgery and for metastatic disease. It has a response rate of approximately 50% and provides good palliation in a substantial number of patients for years. Radioactive MIBG treatment has also been used and has been shown to provide good palliation in metastatic disease.
As with adrenocortical tumors, the distinction between benign and malignant lesions is not obvious, even pathologically, and only the clinical course of the tumor can define malignancy (either local infiltration or metastases). The most common sites of metastases are the lungs, liver, lymph nodes, and bone. The long-term survival rate of patients with malignant pheochromocytoma is more than 50%.5 Long-term follow-up is essential to detect metastases and metachronous lesions, especially in patients with a familial syndrome. Such lesions have been reported to occur more than 10 years after resection of the initial tumor. Therefore, annual blood pressure and catecholamine measurements should be considered.
Some believe that patients with a familial syndrome should undergo bilateral adrenalectomy at the first operation because the risk of a metachronous tumor is approximately 50%. An important additional issue in children is screening. Children with a familial syndrome and a molecular genetic test that reveals a ret proto-oncogene mutation characteristic of MEN II should undergo annual screening for pheochromocytoma, starting at a young age.
This subject is covered extensively in Adrenal Insufficiency. In brief, adrenal insufficiency may be acute or chronic. Chronic adrenal insufficiency may be primary, secondary, or tertiary. Acute adrenal insufficiency results when an acute stress is superimposed on chronic adrenal insufficiency of any type.
Symptoms of chronic adrenal insufficiency may be explained by the lack of adrenal hormones and by the unopposed secretion of ACTH. Hypotension, fatigue, weight loss, anorexia, nausea, vomiting, abdominal pain, salt craving, hypoglycemia, and syncope can occur. Skin and mucous membrane hyperpigmentation result from unopposed secretion of ACTH and melanocyte-stimulating hormone. Hyponatremia, along with hyperkalemia, is sometimes observed and can be explained by the chronic insufficiency of aldosterone. The diagnosis should not be based on the presence or absence of these abnormalities. The loss of secondary sex characteristics is seen only in women with the disease.
Acute adrenal insufficiency is a medical emergency and must be identified and promptly treated. The hallmarks of acute adrenal insufficiency are circulatory collapse with abdominal pain that can simulate an acute abdomen. Profound hypoglycemia, elevated core temperature, and potentially cardiac dysrhythmias are also observed.
Chronic primary adrenal insufficiency results when the adrenal glands themselves are destroyed or infiltrated. Causes include congenital adrenal hyperplasia, bilateral hemorrhage (eg, as in the Waterhouse-Friderichsen syndrome), infection with TB, human immunodeficiency virus (HIV) infection, histoplasmosis, and infiltrative diseases (eg, sarcoidosis). Autoimmune destruction of the adrenal glands is referred to as Addison disease.
Secondary adrenal insufficiency results from diminished release of ACTH from the pituitary. Causes include trauma, pituitary tumors, and pituitary hemorrhage (Sheehan syndrome).
Tertiary adrenal insufficiency results from suppression of the hypothalamic-pituitary-adrenal axis. This is observed with the long-term administration of exogenous steroids. An important distinguishing feature of tertiary adrenal insufficiency is that adrenal medullary and androgen-secreting functions are preserved.
Treatment of chronic adrenal insufficiency is based on the replacement of missing adrenal hormones (hydrocortisone at 15-20 mg/m2/d PO divided tid; fludrocortisone at 0.05-0.1 mg/d). Stress doses of glucocorticoids must be given when any physiologic stress is encountered.
Treatment of acute adrenal insufficiency is life saving and often must be empirically started whenever the entity is suspected. Aggressive fluid resuscitation is the rule and support of the cardiovascular system with the use of exogenous catecholamines may be required in severe cases. Hypoglycemia requires early and often continuous administration of IV dextrose. Hydrocortisone is given as an IV bolus of 50-100 mg/m2 (approximately 50 mg for small children and 100-150 mg for large children and adolescents). Subsequent doses are administered as a continuous IV infusion with 100 mg/m2/d added to the IV fluid infusion or further IV boluses q4-6h until the patient can tolerate PO corticosteroids. Mineralocorticoid replacement is unnecessary in the acute management. Hyperkalemia should be controlled, if present.
Approximately 2% of children with neuroblastoma present with opsoclonus-myoclonus. The cause of this manifestation is unclear.
Prenatal Diagnosis of a Suprarenal Mass
With improvements in prenatal ultrasonography, an increasing number of abnormalities are being prenatally detected, including masses in the suprarenal region. These may be cystic, solid or mixed. The differential diagnosis of a suprarenal mass includes:
- Adrenal hemorrhage
- Extralobar sequestration
- Bronchogenic cyst
- Adrenal or renal cortical cysts
- Adrenocortical carcinoma
Distinguishing between these diagnoses on prenatal imaging alone is difficult and even on postnatal imaging. Adrenal hemorrhage and neuroblastoma are the most common. Unlike neuroblastoma diagnosed later in childhood, neonatal neuroblastoma is usually associated with favorable histology with no N-myc amplification, portending a very good prognosis. It can also spontaneously regress. An adrenocortical tumor is reportable in the newborn. The remaining diagnoses are not urgent. Therefore, babies born with prenatally detected suprarenal masses should undergo postnatal ultrasonography, metaiodobenzylguanidine (MIBG) scanning, and measurement of urinary catecholamine levels, although the latter may be normal even with a diagnosis of neuroblastoma. Small lesions, especially cystic ones that are known to regress more often, should be followed closely.
Monthly follow-up with physical examination and ultrasonography should ensue, with surgery reserved for masses that increase in size or persist. This helps avoid unnecessary surgery for adrenal hemorrhages and spontaneously regressing neuroblastomas. Of course, large masses or any mass that is concerning to family or physician may undergo earlier surgery for definitive diagnosis.
Surgical Approaches to the Adrenal Gland
The 2 main surgical approaches to the adrenal gland are transperitoneal and retroperitoneal, both of which can be used with an open or laparoscopic technique. Advantages of laparoscopic adrenalectomy are early mobilization and oral intake, shortened hospitalization, decreased requirement for narcotics, and similar surgical complication rates. With increasing experience in pediatric laparoscopic adrenalectomy, operative times are comparable with an open approach and the indications are expanding. In the past, larger tumors or suspicion of malignancy were considered contraindications to a laparoscopic approach; currently, absolute size is less important than tumor size in relation to patient size, and successful laparoscopic adrenalectomies for pheochromocytomas, neuroblastomas, and adrenocortical tumors have been reported.
The retroperitoneal laparoscopic approach, compared with a transperitoneal laparoscopic one, is associated with reduced respiratory and hemodynamic effects caused by the pneumoperitoneum and avoids the need to mobilize the abdominal organs to access the adrenal gland. When bilateral adrenal exploration is preferable (eg, for a pheochromocytoma), a transperitoneal approach is preferred. Otherwise, a unilateral lesion can easily be accessed from a retroperitoneal approach with decreased pain and postoperative ileus and with no intraperitoneal adhesion formation. In children, most laparoscopic adrenalectomies have been performed through the transperitoneal route.
The main advantages of a transperitoneal approach include access to the entire abdomen to search for synchronous lesions and metastases and the ability to rapidly identify and resect locally invaded organs en bloc with the primary tumor. In children, an open approach is still most often used mainly because most adrenal tumors in this age group are neuroblastomas that usually present as very large infiltrating lesions.
Tuesday, July 28, 2009
Posted by Thomas Repas, DO, FACP, FACE, CDE July 24, 2009 03:56 PM
Previously, I posted about a young woman who presented with rapid onset Cushing’s syndrome and a 9.0-cm adrenal mass. Her initial 24-hour urine-free cortisol was 1,095 mcg/24 hours (upper limits of normal, 45), one of the highest I have ever seen. She subsequently had surgical resection which confirmed moderately differentiated adrenocortical carcinoma as we had suspected. Fortunately, there was no evidence of extension beyond the adrenal gland or metastatic lymph nodes. Based on size, lack of extension outside the adrenal gland and no known metastasis, she is T2N0MX, stage 2 disease.
She is doing amazingly well. She has lost over 20 lbs, looks better and feels better, and her appetite has returned. We placed her on hydrocortisone for glucocorticoid replacement but are weaning her off as the previously suppressed contralateral adrenal recovers.
The question we have: Is there any persistent disease?
Adrenocortical cancer can be aggressive. Unfortunately, most patients present in stage III or IV. The prognosis for stage IV disease is dismal, with a five-year survival of only 15% to 25%. The only hope for cure is being fortunate enough to completely resect stage I or stage II disease.
The next step will be imaging by PET with F-18-fluorodeoxyglucose. Meta-analysis suggests that FDG-PET imaging is reliable in staging and follow-up of disease, with a sensitivity of 96% and specificity of 99%.
If persistent disease is detected, unfortunately, her prognosis will be poor. Multiple chemotherapeutic regimens have been tried, with limited results. One study reported that combination of etoposide, doxorubicin and cisplatin with mitotane (Lysodren, Bristol-Myers Squibb) had a response rate of as high as 54%. Most other studies have had much lower success rates.
She will be seeing our colleagues in oncology. I hope that we have cured this very pleasant young woman with our initial surgery. We will follow her very closely. If there is evidence of persistent disease, I will also advise her to be seen at a tertiary referral center for additional opinion and the possible option of participation in a clinical trial.
Monday, July 27, 2009
What causes adrenal cortical cancers and am I at risk?
Each year, there are approximately 500 cases of adrenal cortical cancers in the United States. These most commonly occur in patients between the ages of 30 and 50; however, children under the age of 5 develop adrenal cortical cancers at a higher rate than the rest of the population. Males are more likely to develop non-functioning adrenal carcinomas, while females are more likely to develop functioning adrenal carcinomas. In general, causes of adrenal cortical cancers are unknown. They are not associated with smoking, and do not run in families. Despite this, certain genetic mutations have been associated with adrenal cortical cancers, and research is ongoing in attempt to identify the causes of these cancers.
How can I prevent adrenal cortical cancers?
Given that the causes of adrenal cortical cancers are unclear, there are no known interventions that can reduce the risk of developing them.
How are adrenal cortical cancers diagnosed, and how do you tell them apart from adrenal adenomas?
Functioning adrenal cortical cancers and adenomas are frequently diagnosed because of the symptoms caused by steroid hormones. Patients with Cushing's syndrome need to be evaluated to see if the syndrome is caused by a problem in the adrenal glands, the pituitary gland, or another tumor somewhere else in the body. The first step is measuring the amount of cortisol in the urine (called a 24-hour urinary free cortisol test). This test is sometimes performed while giving the patient an extra dose of steroids to see how the body responds. After this is done, most patients undergo a dexamethasone suppression test where patients are given a high dose of the steroid dexamethasone. In normal patients and in patients with Cushing's syndrome due to a problem in the pituitary gland, a high dose of dexamethasone will cause the levels of cortisol in the blood and urine to decrease. In patients with adrenal tumors or another tumor in the body that produces ACTH, cortisol levels remain high even after a patient receives a high dose of dexamethasone.
In patients with excess levels of aldosterone, patients should be tested for blood levels of the chemical renin. In cases of hyperaldosteronism due to a tumor in the adrenal gland, renin levels will be low. In patients who have elevated aldosterone levels due to a problem with the blood vessels of the kidney (a condition called renal artery stenosis), renin levels in the blood are high.
In addition to tests for increased steroid production, radiographic imaging is an important part of the diagnosis of adrenal tumors. Computed Tomography (CT or CAT) scans are commonly used. CT scans use x-rays to form a three-dimensional picture of the inside of the body. If the adrenal tumor is larger than 6 centimeters (cm) on CT scan, it is much more likely to be an adrenal cancer than an adrenal adenoma. In most cases, CT scans can also differentiate between a normal adrenal gland and adrenal hyperplasia.
Ultrasound is sometimes used in the diagnosis of adrenal tumors. Ultrasounds use sound waves to form a picture of the inside of the body. At times, it can be difficult to tell if an adrenal tumor is an adenoma or a cancer. For tumors that are larger than 3 cm, ultrasound is a good method of telling the difference between the two.
Another type of imaging that is used when it is unclear if an adrenal tumor is an adenoma or cancer is Magnetic Resonance Imaging (MRI). MRI uses magnets to produce a very sharp picture of the inside of the body. Certain types of changes on MRI are more commonly seen in adrenal cancers than adenomas and can be used to tell the two apart.
Positron Emission Tomography (PET) scans use radioactively labeled sugar to find rapidly growing cells within the body. When cells are dividing quickly, they require a lot of energy, and the main source of energy in the body is sugar. Areas of actively dividing tissue will require more sugar than slowly dividing tissue. Because cancer cells are rapidly dividing and growing, they take up more the radioactively sugar than the surrounding tissue and this can be detected by the PET scanner. PET scans have been very useful in detect a number of different types of cancers. Its use in adrenal cancers is still being studied.
Ultimately, the only way to tell for sure if an adrenal tumor is an adrenal adenoma or cancer, part of the tumor must be examined underneath a microscope. In most cases of tumors or cancers, this is done by obtaining a biopsy of the tumor. A small piece of the tumor is taken, usually through a needle, and examined underneath a microscope. In the case of adrenal tumors, this procedure is usually performed while the patient is undergoing a CT scan, so that the radiologist can see where the needle is going in the body. In some cases, this can also be done using an ultrasound to guide the biopsy.
Saturday, July 25, 2009
Q. I am a third-year medical student doing a rotation in endocrinology. A patient I saw recently has type 2 diabetes, absence of menses, high cholesterol, hypothyroid, hypertension and obesity (especially in the upper body). She was tested for Cushing's, which showed a slightly elevated level of cortisol, but it was within normal range. Is it possible to have Cushing's if the level is still within normal range? What are other indicators of this disease? Are there other diagnoses to consider?
A.There are two parts to the diagnosis of Cushing's syndrome: an increased cortisol production and a failure to suppress endogenous cortisol secretion when dexamethasone is administered. Indicators appear in the physical examination (muscle weakness, cutaneous striae, bruising, moon facies, buffalo hump, truncal obesity) and the lab (osteoporosis, hypokalemia, hypochloremia, metabolic alkalosis). Since your patient has a normal cortisol level, however, Cushing's would be extremely unlikely.
Whenever you are confronted with a patient with multiple problems, it is nice to find a single diagnosis to explain all the findings. This will not usually happen, though. In this case many possible combinations of diseases might be suggested. For example, the diabetes, hypercholesterolemia, hypertension and obesity mean the patient might have Syndrome X. Also, hypothyroidism is often associated with amenorrhea. So it may be the patient has two problems (hypothyroidism and Syndrome X) instead of one (Cushing's). As you can see, there are many other possible combinations.
Hamiyet Yılmaz, MD, Neslihan Başıl Tütüncü, MD, Mustafa Şhin, MD
Başent University Faculty of Medicine, Department of Endocrinology
Objective: To evaluate the risk of developing endocrine hyperactivity and carcinoma during a period of up to five years in patients with apparently benign and nonfunctioning adrenal incidentalomas.
Patients and Methods: Thirty two patients (mean age: 57.0 ± 8.3 years) were investigated in a prospective follow-up study for a median time of 24 months. Twenty eight patients had unilateral and four had bilateral masses. Initial avarage mass diameter was 17.47 ± 6.60 mm. All patients were followed-up yearly by physical examination, metabolic parameters, hormonal evaluation (morning cortisol after 3mg dexamethasone suppression, urinary metanephrines and upright aldosterone/PRA)
Results: Among the clinical characteristics, 48% of patients were obese, 20% were hypertensive, 13 had type 2 diabetes and impaired glucose tolerance. During follow-up period no significant change in the functional status was observed and no malignant transformation occured. Only one patient developed subclinical Cushing syndrome at the end of the first year and referred to surgery. Change in mass size was correlated with HOMA-IR (p=0.002), upright aldosterone/PRA (p: 0.041), cortisol after dexamethasone suppression (p=0.048) and 24-hour urinary normetanephrine (p=0.005) levels. Gender, body mass index, glucose metabolism and blood pressure were not found to be correlated with change in mass size and functional status.
Conclusions: Due to the extremely low risk of developing malignancy during up to five years of follow-up, conservative approach for the management of adrenal incidentalomas is thought to be appropriate. However, possibility of evolution to hormonal hypersecretion makes long-term follow-up of two-to- five years seems to be obligatory.
Obesity leads to various ailments and psychological problems. The muscles of obese persons are weak and flabby. Arthritis is also common in obese persons. The weight bearing joints are under constant stress and strain due to excess weight of the body. Blood vessels of obese persons get constricted due to excess cholesterol, which form plaques (atheromas). This leads to high blood pressure, stabbing pain in the chest (angina pectoris), heart attacks and strokes. The digestive system of obese persons is prone to diseases like diverticular pathologies. Gall stones may be formed due to excess cholesterol. Cancers, diabetes are all products of obesity. Obesity also creates problems during pregnancy.
The various diseases and complications due to obesity shorten the lifespan of individuals and can lead to premature death. Mortality and morbidity are both to associate closely with obesity. An obese person not only suffers physical pains but also suffers psychological trauma. He feels inferior, and there may be psychological problems as he is often ridiculed and teased.
Causes of Obesity
The various causes of obesity include overeating, lack of exercise, sedentary lifestyle, genetic factors, endocrine (hormonal imbalances) – all constitute important causative factors of obesity. Among endocrinal causes we need to discuss certain syndromes. In syndromes we have a set of pathologies grouped in a very characteristic manner.
1. Cushing’s syndrome
This is due to excessive glucocorticoid hormones (cortical). This can also occur due to excessive corticosteroid administration. That is, both endogenous and exogenous cortisols can cause cushings.
The clinical features are:
• Wasting of tissue myopathy (weak muscles); thin skin, osteporosis, purple abdominal striations.
• Water retention oedema, high BP.
• Obesity of trunk, head, neck.
Apart from there they will be excessively prone to infection; poor wound healing, hirsuitism (hair growth in women).
2. Pickwickian syndrome
This syndrome is caused by many factors; obesity is one of the causes. Enlarged tonsils, acromegaly, myxoedema are all other causes. What happens in this syndrome? During sleep there is collapse of pharyngeal walls leading to respiratory obstruction, sometimes for well over a minute. O2 and CO2 disturb sleep and there is daytime somnolence. Personality changes, intellectual deterioration, headaches, enuresis are all presenting features. One of the important aspects of treatment is to lose weight.
3. Laurence moon biedl syndrome
There is polydaetyly (extra digits) retinitis pigmentos, cataract, microphthalmia, obesity, absent facial hair, hypogenitalism. This is a pituitary gland disorder. Also called Frohlichs syndrome or Adipose genital syndrome, some consider the fat boy of Pickwick Papers as an example of this syndrome. Others put him in the ‘pickwickian’ syndrome, i.e., obstructive sleep apnoea syndrome.
Thus we see in the above syndromes that either obesity is a cause or manifesting feature.
Thursday, July 23, 2009
By Catherine O'Hara, Review Staff
Shona Holmes has undergone medical treatments on both sides of the border. Now, U.S. lobbyists are shining a light on the Waterdown woman’s experience with the Canadian healthcare system to help put a halt to President Obama’s healthcare reform plan.
Holmes’s struggles with the Canadian healthcare system started back in 2005 when she suffered loss of vision. Appointments with local specialists could only be made months in advance.
As her vision steadily deteriorated, the Waterdown mom took matters into her own hands, making the trip to the Mayo Clinic in Scottsdale, Arizona where she was diagnosed with Rathke Cleft Cyst, a benign tumor pressing against her optic nerve.
“She was going blind,” said Holmes’s husband, David, who added that his wife’s underlying illness, Cushing’s disease, was also out of control at the time. Doctors at the Mayo Clinic alerted Holmes that if the Cushing’s disease wasn’t looked after soon, it would “kill her.”
“She would have been racing to her death,” stated the Waterdown man.
As a result of wait times in Ontario, Holmes and her family made the decision to seek treatment in Arizona, with procedures normally covered under Ontario’s Health Insurance Plan (OHIP).
Upon her return to Waterdown, Holmes’s claims for reimbursement for her medical expenses south of the border were rejected. The local resident, who spent nearly $100,000 on medical care in the States, has since been granted a new hearing, which is slated for the fall.
Holmes’s story makes the local family mediator the poster child for the American conservative movement in petitioning against President Obama’s healthcare plans. She has since been linked with the advocacy group, Americans for Prosperity Foundation, which opposes government involvement in health care.
Her plight with Canada’s healthcare system is now being broadcast across the United States through a national campaign ad aired in 50 states. She was also personally invited by the Committee of Energy and Commerce in Washington last month to share her story before lawmakers.
“She has the benefit of having had treatment on both sides of the border. She can speak, in that sense, of letting them know what’s happened on both sides,” said David, adding that his wife is only doing “a neighbourly thing” by advising top officials of the flaws associated with a government-run healthcare system.
“She says, ‘If you have a government-run healthcare system, it’s a slippery slope,’” said Holmes’s husband of her personal opinion.
“There is no doubt that the Americans need healthcare reform. We need healthcare reform in Canada, but the difference is that there is not a single politician (in Canada) that is talking about it. Shona is speaking.”
Wait times, noted David, are Canada’s healthcare system’s downfall. Local doctors are as talented as those south of the 49th parallel, he explained, but in Canada, “they just have their hands tied.”
“That’s the situation we have here.”
Ancaster-Dundas-Flamborough-Westdale MPP, Ted McMeekin, told the Review Tuesday that he is familiar with Holmes’s case and aware of the Waterdown resident’s views on Obama’s proposed healthcare reform.
“She obviously felt that she had a bad experience,” said McMeekin, adding that he could not comment further on the local woman’s case as it is under ongoing adjudication.
However, McMeekin did state that Canada’s healthcare system is often modeled in other countries. “Canada’s model is often lifted up as the model of healthcare,” said the MPP.
“There are millions of people who have no healthcare coverage (in the States). (Obama) is attempting, through legislation, which is before the House and the Senate as I understand it, to make some changes to hopefully...allow more people to receive health care.”
Currently in Washington and slated to return today (Friday), Holmes was invited to speak at a bloggers’ luncheon and tell her story before a group of Republicans. She has also been interviewed by a slew of U.S. media outlets, including Fox News and CNN.
According to David, Holmes has not received any financial contributions for her involvement in the campaign and in an email sent to friends and colleagues a few weeks ago, Holmes said: “I am getting out and getting involved, and learning more and more about health care and policy on both sides of the border,” an event she described as “interesting to say the least.”
Cancer stem-like cells have been implicated in the genesis of a variety of malignant cancers. Research scientists at Cedars-Sinai Medical Center's Maxine Dunitz Neurosurgical Institute have isolated stem-like cells in benign (pituitary) tumors and used these "mother" cells to generate new tumors in laboratory mice. Targeting the cells of origin is seen as a possible strategy in the fight against malignant and benign tumors.
Cells generated from the pituitary tumor cells had the same genetic makeup and characteristics as the original tumors and were capable of generating new tumors, according to an article in the July 2009 issue of the British Journal of Cancer, posted online June 30.
Normal stem cells have the ability to self-renew and the potential to "differentiate" into any of several types of cells. Tumor stem-like cells appear to have the same self-renewing and multipotent properties, but instead of producing healthy cells, they propagate tumor cells. In this study, benign tumor stem-like cells were analyzed for their genetic makeup and behavior.
Pituitary adenomas have unusual characteristics that provided significant clues about several types of stem cells. The pituitary gland, situated at the base of the brain behind the nose, is stimulated by hormones from the hypothalamus gland to produce a variety of hormones that control other glands throughout the body. About half of all pituitary adenomas - which arise from pituitary gland tissue - also have this hormone-producing capability.
In these studies, the scientists isolated stem-like cells from both hormone-producing and non-producing pituitary adenomas that had been surgically removed from eight patients. Laboratory experiments focused on tumor stem cells from one tumor that produced growth hormone and one tumor that produced no hormones. Both types of stem-like cells were found to be self-renewable and multipotent, meaning they expressed proteins that could enable their offspring to differentiate into several types of cells.
Studies also showed that both hormone-producing and non-producing tumor stem cells can be differentiated into hormone-producing cells, with the specific hormones produced being determined by the characteristics of the original pituitary tumor.
Consistent with the researchers' earlier findings in cancer stem-like cells of malignant brain tumors, the tumor stem cells - but not the "daughter" cells - appeared to be resistant to chemotherapy. This suggests that even if most of a tumor's cells can be killed, stem-like cells may survive and regenerate the tumor.
When tumor stem-like cells were implanted into laboratory mice, they generated new tumors that had the same genetic composition and characteristics as the original tumors. Cells from the new tumors, later transplanted into other mice, maintained the same tumor-specific properties.
"Although previous studies have offered evidence of the existence of stem-like cells in pituitary adenomas, in this study we scrutinized these cells for composition and function, demonstrating that stem-like cells exist in benign tumors," said neurosurgeon John S. Yu, M.D., director of Surgical Neuro-oncology at Cedars-Sinai Medical Center. He is senior author of the journal article.
Although pituitary adenomas are typically noncancerous, they can cause significant injury or illness, either by compressing important structures, such as the optic nerve, or by creating hormone imbalances that can have wide-ranging and serious consequences. Identifying the mechanisms that enable these and other tumors to form may provide unique targets for new, more effective therapies.
"From our work with cancer stem-like cells in malignant brain cancers, it appears that stem cells from different cancers - or possibly even within the same tumor - may use different signaling pathways and have different implications for disease progression and prognosis. Findings from the pituitary tumor study generally support the cancer stem cell hypothesis, suggesting that similar mechanisms may be involved in the generation of both malignant and benign tumors," said Keith L. Black, M.D., chairman of the Department of Neurosurgery at Cedars-Sinai.
"Confirmation of the existence of stem-like cells in benign tumors is intriguing," said Yu, "but many questions remain to be answered, particularly in defining the molecular mechanisms involved. We need to find out if there is any relationship between tumor stem cells and normal pituitary stem cells, and how stem cells from benign tumors are different from and similar to those of malignant tumors."
Research scientists from Cedars-Sinai's departments of Neurosurgery, Pathology and Laboratory Medicine, and Surgery participated in these studies, which were partly funded by the National Institutes of Health (NIH) and the Italian Association for Neurological Research (ARIN).
"Isolation of tumour stem-like cells from benign tumours." July 2009: http://www.nature.com/bjc/journal/v101/n2/abs/6605142a.html
British Journal of Cancer
Cedars-Sinai Medical Center
Master Of The Endocrines
The pituitary, which is located at the base of the brain, is considered the master gland because it controls the other endocrine glands and produces a number of hormones that stimulate growth, metabolic or sexual functions. Much is now known about this tiny organ, but three doctors at Yale University School of Medicine broke new ground more than 60 years ago by being the first to isolate a pituitary hormone in pure form.
On this date in 1937, Drs. Abraham White, Hubert Catchpole and Cyril Long announced their findings in the journal Science. Researchers have since isolated nine hormones in three sections of the pituitary.
1Department of Physiology and Pharmacology, University of Western Ontario, Ontario, Canada
2Department of Medicine, University of Western Ontario, Ontario, Canada
3GSK-CIHR Chair in Pediatric Clinical Pharmacology University of Western Ontario, Ontario, Canada
4Division of Endocrinology, Metabolism & Molecular Medicine,The Charles Drew University of Medicine and Sciences, Los Angeles, United States
5Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, Ontario, Canada
6Ivey Chair in Molecular Toxicology
The severity of Cushing's Syndrome (CS) depends on the duration and extent of the exposure to excess glucocorticoids. Current measurements of cortisol in serum, saliva and urine reflect systemic cortisol levels at the time of sample collection, but cannot assess past cortisol levels. Hair cortisol levels may be increased in patients with CS, and, as hair grows about 1 cm/month, measurement of hair cortisol may provide historical information on the development of hypercortisolism. We attempted to measure cortisol in hair in relation to clinical course in six female patients with CS and in 32 healthy volunteers in 1 cm hair sections. Hair cortisol content was measured using a commercially available salivary cortisol immune assay with a protocol modified for use with hair. Hair cortisol levels were higher in patients with CS than in controls, the medians (ranges) were 679 (279-2500) and 116 (26-204) ng/g respectively (P<0.001). Segmental hair analysis provided information for up to 18 months before time of sampling. Hair cortisol concentrations appeared to vary in accordance with the clinical course. Based on these data, we suggest that hair cortisol measurement is a novel method for assessing dynamic systemic cortisol exposure and provides unique historical information on variation in cortisol, and that more research is required to fully understand the utility and limits of this technique.
glucocorticoids - pituitary adenoma - cancer - adrenal gland - hormones - cushing hair
Monday, July 20, 2009
It's Our Birthday!
It's unbelievable but the idea for Cushing's Help and Support arrived 9 years ago tonight. I was talking with my dear friend Alice, who runs a wonderful menopause site called Power Surge, wondering why there weren't many support groups online (OR off!) for Cushing's and I wondered if I could start one myself and we decided that I could.
The first website (http://www.cushings-help.com) first went "live" July 21, 2000 and the message boards September 30, 2000. Hopefully, with these sites, I'm going to make some helpful differences in someone else's life!
The message boards are very active and we have weekly online text chats, weekly live interviews, local meetings, email newsletters, a clothing exchange, a Cushing's Awareness Day Forum, podcasts, phone support and much more.
Whenever one of the members of the boards gets into NIH, I try to go to visit them there. Other board members participate in the "Cushie Helper" program where they support others with one-on-one support, doctor/hospital visits, transportation issues and more.
Saturday, July 18, 2009
255.4 - Disorders of Adrenal Glands, Addisons Disease (Corticoadrenal Insufficiency)
255.5 - Disorders of Adrenal Glands, Other Adrenal Hypofunction; Adrenal Medullary Insufficiency
279.4 - Autoimmune Disease, Not Elsewhere Classified; Autoimmune Disease NOS
Addison's disease (adrenal insufficiency) occurs when the outer layer of the adrenal gland, the cortex, is damaged, causing it to produce insufficient amounts of certain corticosteroid hormones that are essential for life. The three types of corticosteroids are androgens and estrogens, which affect sexual development and reproduction; glucocorticoid hormones such as cortisol, which maintain glucose regulation, suppress immune responses, and provide stress responses; and mineralocorticoid hormones such as aldosterone, which regulate sodium and potassium balance.
Adrenal insufficiency can occur for a variety of reasons. In 70% of cases of primary adrenal insufficiency, the body's immune system attacks and slowly destroys the adrenal glands (autoimmune disease). Tuberculosis, once the most common cause of Addison's disease, is responsible for only about 20% of cases of primary adrenal insufficiency. Since the appearance of acquired immunodeficiency syndrome (AIDS), tuberculosis is once again on the rise and a corresponding increase in Addison's disease caused by tuberculosis is expected. Less common causes of primary adrenal insufficiency include chronic infections, particularly fungal infections and viral infections (cytomegalovirus or CMV) associated with AIDS; amyloidosis; hemorrhage of the adrenal glands; and surgical removal of the adrenal glands. Waterhouse-Friderichsen syndrome is primary adrenal insufficiency that occurs due to adrenal gland hemorrhage during meningococcal infection.
In secondary adrenal insufficiency, the adrenal glands are healthy but the body fails to stimulate them to release hormones. This occurs when the pituitary gland, which is located at the base of the brain, fails to secrete adrenocorticotrophic hormone (ACTH), which normally stimulates the adrenal gland to release cortisol. Causes of secondary adrenal insufficiency include long-term use of steroids such as prednisone or surgical removal of pituitary tumors, either cancerous or non-cancerous. Less common causes are loss of blood flow to the pituitary gland, surgical removal of a portion of the pituitary gland, or surgical removal of the area of the brain called the hypothalamus.
Risk: Addison's disease tends to run in families. Individuals who take steroids over a long period of time and then develop a severe infection, injury, or undergo a surgical procedure are at increased risk of developing Addison's disease. It is slightly more common among women than men. It can appear at any age but is more often diagnosed in individuals between the ages of 30 and 50 (Odeke). Other conditions that may be associated with adrenal insufficiency include diabetes mellitus, hypoparathyroidism, hypopituitarism, pernicious anemia, testicular dysfunction, Graves' disease, chronic thyroiditis, and myasthenia gravis.
Incidence and Prevalence: Addison's syndrome is a rare disorder, with a prevalence of 40 to 60 cases per 1 million people in the US and Europe (Odeke).
History: In most cases of Addison's disease, symptoms appear gradually. Individuals often complain of progressively increasing weakness and fatigue, loss of appetite (anorexia), and unintentional weight loss. Many report dizziness or light-headedness especially when rising from a seated position. Abdominal pain, decreased tolerance to cold, hair loss (alopecia) particularly in women, and cravings for salty foods may also be reported. Nausea, vomiting, and chronic diarrhea occur in about 50% of cases. Women may report that their menstrual cycles have become irregular (dysmenorrhea) or stopped altogether (amenorrhea). Moodiness, irritability, or depression may be evident. In advanced cases, the individual may experience what is known as an Addisonian crisis characterized by abdominal pain; severe vomiting and diarrhea; hypotension; agitation, confusion and loss of consciousness.
Physical exam: Findings usually include low blood pressure (hypotension) that may worsen when the individual stands after sitting or lying down (orthostatic hypotension). The individual may be dehydrated. Skin changes are also commonly noted and include freckling and darkening of the skin. The skin darkening may resemble a deep tan but will be present even on parts of the body not exposed to the sun. The skin darkening may also be more visible on scars; pressure points, such as elbows, knees, and toes; lips; mucus membranes; and in skin folds.
Tests: The most specific test for Addison's disease is the ACTH stimulation test. In this test, blood is drawn to measure baseline levels of the hormones cortisol and aldosterone. Synthetic ACTH (Cortrosyn, cosyntropin, or Synacthen) is administered intravenously or by intramuscular injection. Blood is drawn again at 30 minutes to measure changes in the cortisol and aldosterone levels. In order to rule out the diagnosis of Addison's disease, there must be an increase in the baseline cortisol value by 7 mcg/dL or more, and the cortisol level must rise to 20 mcg/dL or more in 30 minutes (Odeke). In a healthy individual, the cortisol levels are higher after the injection of synthetic ACTH; in individuals with Addison's disease, there is little or no change in cortisol levels.
If an abnormal result is obtained, a variation of this test in which ACTH is given over a 2 to 3 day period may be conducted. Blood and/or urine samples are collected before and during this 2 to 3 day period. In this longer ACTH stimulation test, the cause of adrenal insufficiency can be determined. Primary adrenal insufficiency results in little or no cortisol production for the entire 72 hour period; secondary adrenal insufficiency, on the other hand, will show an adequate response by the second or third day. Elevated morning ACTH levels confirm a primary adrenal cause.
If the ACTH stimulation test is inconclusive, other tests may be conducted either to help confirm the diagnosis or help rule out other conditions. An insulin-induced hypoglycemia test evaluates the functioning of the pituitary gland and the hypothalamus. In this test, blood sugar (glucose) and cortisol levels are measured and then fast-acting insulin is given. The normal response is for glucose to fall and cortisol to rise, indicating a normal pituitary gland and hypothalamus.
Other blood tests that may prove helpful include a complete metabolic panel (CMP), a complete blood count (CBC) and a thyroid-stimulating hormone level (TSH). Individuals with Addison's disease generally have low sodium and cortisol levels, but high potassium, calcium, blood urea nitrogen (BUN), and creatinine levels. If the individual has not eaten prior to the blood test, there may be low blood sugar (hypoglycemia) and high ACTH levels.
When an autoimmune disease is the cause of adrenal dysfunction, adrenal antibodies may be present in the blood. An abdominal or chest x-ray may help reveal calcium deposits in the adrenal glands—a sign of tuberculosis infection. An abdominal CT may be performed to determine if the adrenal glands are smaller or larger than normal. Small adrenal glands may be a sign of autoimmune adrenal disease and larger than normal adrenal glands may be an indication of hemorrhage or infiltrative disease. Biopsies of the adrenal glands can rule out cancer.
In the rare instances of Addisonian crisis, potentially life-threatening low blood pressure (hypotension), low blood sugar (hypoglycemia), and high levels of potassium (hyperkalemia) may occur. Individuals experiencing Addisonian crisis require immediate hospitalization. Treatment will include immediate intravenous (IV) or intramuscular (IM) injections of steroids along with saltwater (saline) fluid replacements and sugar (glucose). Oral steroid medications may also be given.
Most cases of Addison's disease, however, do not require inpatient treatment. The goal of therapy is to replace the hormones that the body is not producing. Oral steroid medications are usually a combination of glucocorticoids and mineralocorticoids and are taken for the remainder of the individual's life. The individual is counseled to avoid dehydration by drinking plenty of fluids. An identification and medical instruction bracelet is often advised, and individuals are urged to carry injectable steroid medication for emergency use if medical care is not available.
Individuals with Addison's disease need to recognize the consequences of not closely following their medical regimen. Any stress such as illness, fever, hot and humid weather, profuse sweating, and even emotional stress can precipitate a sudden worsening of the condition and must be met with an increase in replacement hormones. Most individuals with Addison's disease are taught to give themselves an emergency injection of hydrocortisone in times of stress.
If an underlying disease, such as tuberculosis, is responsible, treatment of the underlying disease is important for recovery or resolution of symptoms.
With careful management, an individual with Addison's disease can live a full, relatively active life. However, illness, stress, and even general anesthesia for surgery can bring on an adrenal crisis necessitating special care and adjustments in replacement hormone dosages.
Untreated, Addison's disease is a progressive condition that can gradually result in severe abdominal pain, extremely low blood pressure, and kidney failure. Addisonian crisis must be treated immediately or coma and death can occur.
Illness, injury, or any type of stress can result in an Addisonian crisis, a potentially life-threatening condition that is managed with an increase of the hydrocortisone dose.
Other possible complications include extremely high fever (hyperpyrexia), psychotic reactions, accidental overdose of steroid medications and, rarely, a temporary paralysis due to low levels of potassium.
Additional complications related to the individual's underlying disease might also occur and will vary depending upon the particulars of that disease.
In most cases, work accommodations or restrictions are not necessary for individuals with Addison's disease. Taxing physical labor, such as working in hot humid environments or work that carries a great deal of stress, is unsuitable for an individual with Addison's disease. The particulars of the necessary accommodations vary significantly depending on the individual, severity of symptoms, individual's response to treatment, and job requirements.
If an individual fails to recover within the expected maximum duration period, the reader may wish to consider the following questions to better understand the specifics of an individual's medical case.
- Was diagnosis of Addison's disease confirmed through an ACTH stimulation test?
- Was the cause of the adrenocortical insufficiency, such as an autoimmune disorder, infection, tumor, or hemorrhage in the adrenal glands identified?
- Were underlying causes also addressed?
- Is individual on oral cortisol with or without fludrocortisone?
- Does current method of treatment appear to be effective?
- Has individual continued to experience any symptoms of adrenal crisis, such as vomiting, diarrhea, fever, confusion, low blood pressure, or dehydration?
- If current treatment is not effective, is individual a candidate for surgery or radiation therapy?
- Is individual on and able to maintain a diet high in fluids, carbohydrates, and protein?
- Would individual benefit from instruction in stress management techniques?
- Does individual wear an identification/medical instruction bracelet?
- Does individual carry injectable steroid medication for use in an emergency if medical care is not available?
- Were underlying causes, such as autoimmune disorders, infection, tumor, or tuberculosis resolved or brought under control?
- Does individual realize that Addison's disease is a lifelong condition that requires careful management, including avoiding stress and infection?
- Is individual able to adhere to oral therapy and dietary recommendations?
- Does individual attend regular follow-up visits with physician?
- Has individual experienced any complications related to the Addison's disease?
- Does individual have an underlying condition that may impact recovery?
Odeke, Slyvester, and Steven B. Nagelberg. "Addison Disease." eMedicine. Eds. Daniel Einhorn, et al. 25 Nov. 2003. Medscape. 14 Sep. 2004 http://emedicine.com/med/topic42.htm.