Cushing’s Syndrome is Hazardous to Your Health

People with Cushing’s syndrome, even when treated, have higher morbidity and mortality rates that comparable controls. That is the conclusion of a new study published in the June issue of the Journal of Clinical Endocrinology Metabolism. The study by Olaf Dekkers et al, examined data records from the Danish National Registry of Patients and the Danish Civil Registration System of 343 patients with benign Cushing’s syndrome of adrenal or pituitary origin (i.e., Cushing’s disease) and a matched population comparison cohort (n=34,300).  Due to the lengthy delay of many patients being diagnosed with Cushing’s syndrome, morbidity was investigated in the 3 years before diagnosis while  morbidity and mortality were assessed during complete follow-up after diagnosis and treatment.

The study found that mortality was twice as high in Cushing’s syndrome patients (HR 2.3, 95% CI 1.8-2.9) compared with controls over a mean follow-up period of 12.1 years. Furthermore, patients with Cushing’s syndrome were at increased risk for:

• venous thromboembolism (HR 2.6, 95% CI 1.5-4.7)
• myocardial infarction (HR 3.7, 95% CI 2.4-5.5)
• stroke (HR 2.0, 95% CI 1.3-3.2)
• peptic ulcers (HR 2.0, 95% CI 1.1-3.6)
• fractures (HR 1.4, 95% CI 1.0-1.9)
• infections (HR 4.9, 95% CI 3.7-6.4).

The study also found that this increased multimorbidity risk was present before diagnosis indicating that it was due to cortisol overproduction rather than treatment.

Many of the Cushing’s syndrome patients underwent surgery to remove the benign tumor. For this group, the investigators performed a sensitivity analysis of the  long-term mortality and cardiovascular risk in this  subgroup (n=186)  considered to be cured after operation (adrenal surgery and patients with pituitary surgery in combination with a diagnosis of hypopituitarism in the first 6 months after operation).  The risk estimates for mortality (HR 2.31, 95% CI 1.62-3.28), venous thromboembolism (HR 2.03, 95% CI 0.75-5.48), stroke (HR 1.91, 95% CI 0.90-4.05), and acute myocardial infarction (HR 4.38, 95% CI 2.31-8.28) were also increased in this subgroup one year after the operation.

The standard treatment for endogenous Cushing’s syndrome is surgery. This past year, Signifor (pasireotide) was approved for treatment of adults patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative.  Cushing’s disease, which accounts for the majority of Cushing’s syndrome patients, is defined as the presence of an ACTH producing tumor on the pituitary grand. In the study by Dekker’s et al, the percentage of patients with Cushing’s disease is not known. We look forward to reexamination of this dataset in a few years following the introduction of more treatment options for Cushing’s disease as well as an analysis that explores the differences in mortality/morbidity rates in the different subsets of patients that make of Cushing’s syndrome (Cushing’s disease, ectopic Cushing’s syndrome, Exogenous Cyshing’s syndrome).

References

Dekkers OM, Horvath-Pujo, Jorgensen JOL, et al, Multisystem morbidity and mortality in Cushing’s syndrome: a cohort study. J Clin Endocrinol Metab 2013 98(6): 2277–2284. doi: 10.1210/jc.2012-3582

- See more at: http://www.raredr.com/medicine/articles/cushing%E2%80%99s-syndrome-hazardous-your-health-0

Pregnancy and pituitary disorders

Z Karaca, F Tanriverdi, K Unluhizarci and F Kelestimur
+ Author Affiliations

Department of Endocrinology,
Erciyes University Medical School, 38039 Kayseri, Turkey
(Correspondence should be addressed to F Kelestimur; Email: fktimur@erciyes.edu.tr)

Abstract

Major hormonal changes emerge during pregnancy. The pituitary gland is one of the most affected organs with altered anatomy and physiology. The pituitary gland is enlarged as a result of lactotroph hyperplasia. Due to physiological changes in the pituitary and target hormone levels, binding globulins, and placental hormones, hormonal evaluation becomes more complex in pregnant women. As a consequence of physiological hormonal changes, the evaluation of pituitary functions in pregnant women is quite different from that done in the prepregnant state. Pituitary adenomas may cause problems by their hormone secretion that affects the mother and the fetus besides causing an increased risk of tumor growth.

Furthermore, diagnosis, course, and treatment of pituitary diseases point out differences. The changes in anatomy and physiology of the pituitary gland during pregnancy are reviewed.

Pituitary disorders namely Cushing's disease; acromegaly; prolactinoma; TSH-secreting, gonadotropin-producing, and clinically nonfunctioning adenomas; craniopharyngioma; and Sheehan's syndrome, which is one of the most common causes of hypopituitarism, lymphocytic hypophysitis, and hypopituitarism, in relation to pregnancy are discussed. Being aware of all this information will prevent any serious problems which mother and child will be exposed to.

Read the entire article here: http://www.eje-online.org/content/162/3/453.full

Course of pregnancies in women with Cushing’s disease treated by gamma-knife

(doi:10.3109/09513590.2012.683057)

Francesco Ferraù1, Marco Losa2, Oana Ruxandra Cotta1, Maria Luisa Torre1, Marta Ragonese1, Francesco Trimarchi1, Salvatore Cannavò1

1Department of Medicine and Pharmacology, Section of Endocrinology, University of Messina, Messina, Italy

2Department of Neurosurgery, Istituto Scientifico San Raffaele, Milan, Italy

Correspondence: Francesco Ferraù, MD, Department of Medicine and Pharmacology, Section of Endocrinology, University of Messina, AOU Policlinico “G. Martino” (Pad. H, floor 4), Via Consolare Valeria 1, 98125 Messina, Italy. Tel: +39 090 2213507. Fax: +39 090 2213945. E-mail: ferrau1@interfree.it

 

Data concerning pregnancy in women with Cushing’s disease treated by gamma-knife (GK) are scanty. We present and discuss the course and outcome of five pregnancies in two women with Cushing’s disease (CD), the first of whom was treated only by GK, and the second one treated by surgery, GK and ketoconazole.

In the first patient, pregnancy was uneventful and full-term. During gestation, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were steady, and always in the normal range for healthy non-pregnant individuals. The newborn was healthy and normal-weight.

In the second woman, two pregnancies, occurring 3 years after GK and few months after ketoconazole withdrawal, were interrupted by spontaneous abortion or placental disruption despite normal cortisol levels. This patient became again pregnant 3 years later and delivered vaginally a healthy full-term infant.

Seven months after the delivery, the patient became pregnant again and at the 39th week of gestation delivered vaginally a healthy male. Hypoprolactinemia and/or central hypothyroidism occurred in both cases. In women with CD treated by GK, pregnancy can occur. However, pregnancy is at risk even when ACTH and cortisol levels are normalized by treatment. After GK, evaluation of pituitary function is mandatory due to the risk of hypopituitarism.

Read More: http://informahealthcare.com/doi/abs/10.3109/09513590.2012.683057

Psychological Manifestations of Pituitary Disease

From the May 2012 PNA Newsletter:

 

Psychological Manifestations of Pituitary Disease

Editor’s note: This is an introduction to a lecture given by Dr. Michael Weitzner. It makes many of the points that the PNA strives to promote.

The objectives of this lecture are to provide an overview of the psychological and neuropsychiatric problems faced by patients with pituitary disease, the impact on family, and the options for treatment.

Cushing, himself, believed that there was a need to differentiate the psychological effects that resulted from the pituitary tumor from those that resulted from the stress of illness. It is now recognized that the hypothalamic-pituitary axis is not only an integral element in the expression of behavior, but also an essential part of the limbic system which controls our emotions.

Many patients with pituitary tumors develop an apathy syndrome which is the result of this interplay between the limbic system and the hypothalamic-pituitary axis. An important task is the differentiation of this apathy syndrome from other psychiatric disturbances which are also seen in patients with pituitary disease. It is well recognized that depression and anxiety are present in many patients with hyperprolactinemia and Cushing’s disease. Personality change and anxiety are commonly seen in patients with acromegaly and hypopituitarism. There are several options for treatment, both pharmacological and psychological. One element that is unfortunately ignored in this illness is the effect on the family. Effective treatment of the patient with pituitary disease included treatment of the family.

Michael A. Weitzner, M.D., Department of Psychiatry,University of South Florida, Tampa, Florida

From www.pituitary.org

What Is the Best Approach for the Evaluation and Management of Endocrine Incidentalomas?

Key points include:  Advances and more frequent use of diagnostic radiology have led to the increased prevalence of endocrine incidentalomas;  Pituitary, thyroid, and adrenal incidentalomas must be assessed for dysfunctional hormone secretion and malignant potential; Inpatient management of endocrine incidentalomas should include consultation of endocrine or surgical teams in cases of dysfunctional or malignant lesions; Post-discharge instructions shouldclearly delineate timelines for repeat imaging, laboratory testing, and subspecialist follow-up.

by Darlene Tad-y, MD, Section of Hospital Medicine, University of Colorado Denver

Benign adrenal gland tumors.

Case

A 54-year-old man with a history of hypertension treated with hydrocholorothiazide and Type 2 diabetes mellitus is admitted with abdominal pain and found to have an incidental 2.1-cm left adrenal mass on CT scan of the abdomen. He denies symptoms of headache, palpitations, weight gain, or muscle weakness. His exam is significant for mildly elevated blood pressure. What is the best approach for evaluation and management of this incidental finding?

Overview

Incidentalomas are mass lesions that are inadvertently discovered during radiolographic diagnostic testing or treatment for other clinical conditions that are unrelated to the incidental mass. In recent decades, improvements in radiographic diagnostic techniques and sensitivity have led to increasing discovery of incidental lesions that are often in the absence of clinical signs or symptoms.¹ Three commonly discovered lesions by hospitalists are pituitary, thyroid, and adrenal incidentalomas.² The concerns associated with these findings relate to the potential for dysfunctional hormone secretion or malignancy.

Patients found with pituitary incidentalomas can be susceptible to several types of adverse outcomes: hormonal hypersecretion, hypopituitarism, neurologic morbidity due to tumor size, and malignancy in rare cases. Thyroid incidentalomas are impalpable nodules discovered in the setting of ultrasound or cross-sectional neck scans, such as positron emission tomography (PET) scans. Discovery of a thyroid incidentaloma raises concern for thyroid malignancy.³ The increased use of abdominal ultrasound, CT scans, and MRI has fueled the growing incidence of adrenal incidentalomas (AIs).

The discovery of an endocrine incidentaloma in the inpatient setting warrants a systematic approach that includes both diagnostic and potentially therapeutic management. A hospitalist should consider an approach that includes (see Table 1):

click for large version

Table 1. General inpatient approach to endocrine incidentalomas

1. Characterization of the incidentaloma, including clinical signs and symptoms, size, hormonal function, and malignant potential;
2. Immediate management, including medical versus surgical treatment; and
3. Post-discharge management, including monitoring.

Review of the Data

Pituitary incidentalomas. The prevalence of pituitary incidentalomas found by CT ranges from 3.7% to 20%, while the prevalence found by MRI approximates 10%. Autopsy studies have revealed a prevalence ranging from 1.5% to 26.7% for adenomas less than 10 mm, considered to be microadenomas. Broad categories of etiologies should be considered: pituitary adenoma, nonpituitary tumors, vascular lesions, infiltrative disorders, and others (see Table 2). The majority of pituitary adenomas secrete prolactin (30% to 40%) or are nonsecreting (30% to 40%). Adenomas secreting adrenocorticotropin hormone (ACTH, 2% to 10%), growth hormone (GH, 2% to 10%), thyroid-stimulating hormone (TSH, <1%), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are much less common.2 Significant morbidity and premature mortality are associated with hyperprolactinemia, acromegaly (growth hormone excess), Cushing’s syndrome, and hyperthyroidism. Additionally, up to 41% of patients with macroadenomas were found to have varying degrees of hypopituitarism due to compression of the hypothalamus, the hypothalamic-pituitary stalk, or the pituitary itself.⁴

TABLE 2. DIFFERENTIAL DIAGNOSIS FOR PITUITARY INCIDENTALOMAS^2,4,14

Pituitary adenoma:

• Secreting: prolactin, growth hormone, ACTH, glycopeptides (LH, FSH, TSH, a-subunit)
• Nonsecreting

Non-pituitary tumors:

• Germ cell tumors
• Craniopharyngioma
• Meningioma
• Metastatic disease

Vascular lesions:

• Aneurysms
• Hamartomas
• Infarctions

Infiltrative:

• Sarcoidosis
• Histiocytosis
• Lymphocytic hypophysitis
• Eosinophilic granulomas

Other:

• Rathke’s cleft cyst
• Anatomic abnormalities

ACTH=adrenocorticotropin hormone, GH=growth hormone, TSH=thyroid-stimulating hormone (thyrotropin), LH=luteinizing hormone, FSH=follicle-stimulating hormone

Recently, the Endocrine Society released consensus recommendations to guide the evaluation and treatment of pituitary incidentalomas, which are included in the approach outlined below.⁵ A detailed history and physical examination should be obtained with specific inquiry as to signs and symptoms of hormonal excess and mass effect from the tumor. Examples of symptoms of hormone excess can include:

• Prolactin: menstrual irregularity, anovulation, infertility, decreased libido, impotence, osteoporosis;
• Growth hormone: high frequency of colonic polyps and colon cancer (chronic excess);
• TSH: thyrotoxicosis, atrial fibrillation; and
• ACTH: hypertension, osteoporosis, accelerated vascular disease.

Symptoms related to the mass effect of the tumor include visual field defects and hypopituitarism related to the deficient hormone, including:

• FSH/LH: oligomenorrhea, decreased libido, infertility;
• TSH: hypothyroidism (weight gain, constipation, cold intolerance);
• ACTH: adrenal insufficiency (hypotension, hypoglycemia, weight loss); and
• ADH: polyuria, polydypsia.

The size and location of the pituitary lesion must be assessed. Lesions greater than 10 mm are considered macroademonas, and their size will affect their management. If the lesion was initially identified by CT scan, an MRI is recommended to better evaluate it.⁵ If the MRI locates the incidentaloma abutting the optic nerve or chiasm, then the patient should undergo a formal visual field examination.

Indications for an inpatient surgical referral for treatment include: a lesion larger than 2 cm, evidence of mass effect such as visual field defects, neurologic compromise, opthalmoplegia, hypopituitarism, a tumor abutting the optic nerve or chiasm, pituitary apoplexy, and hypersecretion of hormones other than prolactin. Patients with prolactinomas warrant an inpatient endo-crinology consult and may need medical management with a dopamine agonist. Hormone replacement therapy can also be provided for patients with hypopituitarism.^2,5

For patients who do not meet the criteria for inpatient surgical therapy, follow-up management must be arranged at the time of discharge. Clinical, laboratory assessment, and an MRI should be scheduled six months after the initial finding of the incidentaloma with the patient’s PCP or with an endocrinologist.⁵

Thyroid incidentalomas. The prevalence of thyroid nodules based on ultrasound studies ranges from 19% to 46%, with autopsy studies estimating an incidence of approximately 50%.^2,6 Incidence of thyroid nodules also increases with age, as almost 60% of people over the age of 60 harbor a thyroid incidentaloma. The rate of malignancy in the general population has ranged between 8% and 24%; however, in the last decade, the rates have increased by 2.4 times as more sophisticated ultrasound techniques and liberal use of fine-needle aspiration (FNA) biopsies have detected subclinical disease.^7,8

Etiologies for incidental thyroid nodules can be divided into benign and malignant causes. Benign etiologies include thyroid cyst (simple or complex), multinodular goiter, and Hashimoto’s thryoiditis, while malignant causes include papillary, medullary, follicular, Hurthle cell, and anaplastic carcinomas, thyroid lymphomas, and rare instances of metastatic cancers.^2,3

Targeted history and physical examination helps to characterize the thyroid incidentaloma. Historical features, such as palpitations, weight loss, anxiety, new onset atrial fibrillation, or menstrual irregularities, coupled with tachycardia, tremors, proximal muscle weakness, and a palpable nodule aid in the diagnosis of hyperthyroidism. Findings such as a family history of thyroid cancer, symptoms of hoarseness or dysphagia, rapid growth of the nodule, environmental or history of head or neck irradiation along with physical findings of a hard, fixed nodule, or cervical lymphadenopathy increase the suspicion for malignancy.^2,7

The functionality of the nodule can be assessed by checking TSH, free T3, and free T4 levels. Suppression of TSH (< 0.1 mU/L) with elevated levels of free T3 and T4 indicates nodule production of excess thyroid hormone and warrants thyroid scintography. Thyroid scintography will identify the nodule as “hot” (hyperfunctioning) or “cold” (nonfunctioning).²

Regardless of the radiographic modality that initially identified the thyroid incidentaloma, a dedicated thyroid high-resolution ultrasound should be ordered to assess the size, multiplicity (single or multinodular), location, and character (solid, cystic, or mixed).⁷

Recommendations for proceeding to FNA to evaluate for malignancy differ among subspecialty societies. Generally, nodules larger than 1 cm or nodules smaller than 1 cm with risk factors for malignancy should be referred for FNA.^2,7

If diagnostic workup identifies a patient with hyperthyroidism due to an autonomously functional nodule or a nodule that may be at high risk for malignancy, it is appropriate to involve an endocrinologist and possibly a surgical subspecialist prior to discharge. Management of hyperthyroidism can include starting antithyroid agents (methimazole or propylthiouracil), radioactive iodine ablation, or referral for surgery.

Preparation for discharge of the patient whose incidentaloma is nonfunctional or does not appear to be malignant should include appointments to recheck thyroid hormone levels, including TSH as well as a thyroid ultrasound within one year of the initial discovery.

Adrenal incidentaloma. The prevalence of AIs found by CT of the abdomen ranges from 0.4% to 4%, while autopsy studies have found a prevalence of 1.4% to 9% with increasing prevalence with age.^2,9,10 The majority of AIs are benign and nonfunctioning adenomas, in the absence of known malignancy. Other differential diagnoses include Cushing’s syndrome, pheochromocytoma, adrenocortical adenoma, aldosteronoma, and metastatic lesions.

Because functioning adrenal incidentalomas may be clinically silent, any patient found with an AI must undergo biochemical workup as part of their evaluation to assess for pheochromocytoma, Cushing’s syndrome, and if he or she has a history of hypertension or hyperaldosteronism (Conn’s syndrome). Table 3 outlines the approach for characterizing adrenal incidentalomas.^2,11,12 An important point is that imaging studies are not useful in distinguishing a functioning versus nonfunctioning tumor but rather can help to discriminate malignant lesions.¹¹

click for large version

Table 3. Characterization of the adrenal incidentaloma^2,11

Inpatient surgical consult for resection is indicated if the patient is found to have pheochromocytoma, clinically apparent functioning adrenocortical adenoma, or a tumor size greater than 4 cm. Consultation with an endocrinologist is also recommended if biochemical tests are positive. If the diagnostic workup leads to suspicion for infection or metastatic disease, the patient should be referred for FNA.^2,12

For patients whose lesions do not require surgical resection, repeat CT scan of the abdomen is recommended six months from the initial finding. Hospitalists should also arrange for the patient to repeat biochemical testing, including an overnight dexamethasone test.^12,13

Back to the Case

The patient underwent biochemical testing and was found to have normal levels of plasma-free metanephrines, a plasma aldosterone, plasma renin activity ratio less than 20, and a serum cortisol level of 7 mg/dL after his overnight dexamethasone suppression test. The 24-hour urine collection for free cortisol revealed elevated levels of cortisol in the urine, and the ACTH level was low.

Endocrinology and endocrine surgery teams were consulted, and recommended surgical resection. After surgical resection of his tumor, the patient was started on glucocorticoid replacement and was discharged with a follow-up appointment with endocrinology.

Bottom Line

An inpatient approach to endocrine incidentalomas should include characterization of the clinical signs and symptoms, size, function, and malignant potential of the lesion. Based on this, inpatient surgical or medical management can be determined. Post-discharge management should include arrangements for surveillance testing and follow-up with appropriate subspecialists.

Dr. Tad-y is assistant professor of medicine and a hospitalist at the University of Colorado Denver.

KEY POINTS

• Advances and more frequent use of diagnostic radiology have led to the increased prevalence of endocrine incidentalomas.
• Pituitary, thyroid, and adrenal incidentalomas must be assessed for dysfunctional hormone secretion and malignant potential.
• Inpatient management of endocrine incidentalomas should include consultation of endocrine or surgical teams in cases of dysfunctional or malignant lesions.
• Post-discharge instructions should clearly delineate timelines for repeat imaging, laboratory testing, and subspecialist follow-up.

ADDITIONAL READING

• Shirodkar M, Jabbour SA. Endocrine incidentalomas. Int J Clin Pract. 2008; 62:1423-1431.
• Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:894-904.
• Iyer NG, Shaha AR, Silver CE, et al. Thyroid incidentalomas: to treat or not to treat. Eur Arch Otorhinolaryngol. 2010;267:1019-1026.
• Zeiger MA, Siegelman SS, Hamrahian AH. Medical and surgical evaluation and treatment of adrenal incidentalomas. J Clin Endocrinol Metab. 2011;96:2004-2015.

References

1. Aron DC, Howlett TA. Pituitary incidentalomas. Endocrinol Metab Clin North Am. 2000;29:205-221.
2. Shirodkar M, Jabbour SA. Endocrine incidentalomas. Int J Clin Pract. 2008;62:1423-1431.
3. Burguera B, Gharib H. Thyroid incidentalomas. Prevalence, diagnosis, significance, and management.Endocrinol Metab Clin North Am. 2000;29:187-203.
4. Molitch ME. Nonfunctioning pituitary tumors and pituitary incidentalomas. Endocrinol Metab Clin North Am. 2008;37:151-171, xi.
5. Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:894-904.
6. Gough J, Scott-Coombes D, Fausto Palazzo F. Thyroid incidentaloma: an evidence-based assessment of management strategy. World J Surg. 2008;32:1264-1268.
7. Iyer NG, Shaha AR, Silver CE, et al. Thyroid incidentalomas: to treat or not to treat. Eur Arch Otorhinolaryngol. 2010;267:1019-1026.
8. Jin J, Wilhelm SM, McHenry CR. Incidental thyroid nodule: patterns of diagnosis and rate of malignancy. Am J Surg. 2009;197:320-324.
9. Davenport C, Liew L, Doherty B, et al. The prevalence of adrenal incidentaloma in routine clinical practice.Endocrine. 2011;40:80-83.
10. Zeiger MA, Siegelman SS, Hamrahian AH. Medical and surgical evaluation and treatment of adrenal incidentalomas. J Clin Endocrinol Metab. 2011;96: 2004-2015.
11. Zeiger MA, Thompson GB, Duh QY, et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas: executive summary of recommendations. Endocr Pract. 2009;15:450-453.
12. NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”).NIH Consens State Sci Statements. 2002;19:1-25.
13. Young WF. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. 2007;356:601-610.
14. Chidiac RM, Aron DC. Incidentalomas. A disease of modern technology. Endocrinol Metab Clin North Am. 1997;26:233-253.

 

From http://www.the-hospitalist.org/details/article/1380161/What_Is_the_Best_Approach_for_the_Evaluation_and_Management_of_Endocrine_Inciden.html

Pituitary autoimmunity is associated with hypopituitarism in patients with primary empty sella

Lupi I, Manetti L, Raffaelli V, Grasso L, Sardella C, Cosottini M, Iannelli A, Gasperi M, Bogazzi F, Caturegli P, Martino E; Journal of Endocrinological Investigation (May 2011)

Objective: some evidences suggest that late stage autoimmune hypophysitis (AH) may result in empty sella (ES). Aim of the study was to assess the prevalence of serum pituitary antibodies (PitAbs) and their correlation with pituitary function in patients with ES.

Design: in this case-control study 85 patients with primary ES, 16 patients with ES secondary to head trauma, 214 healthy controls, and 16 AH were enrolled in a tertiary referral center.

Methods: PitAbs were assessed in all cases and controls. Endocrine function was assessed by basal hormone measurement and dynamic testing in all ES cases.

Results: PitAbs prevalence was higher in primary ES (6%) than in healthy subjects (0.5% p=0.003) and lower than in AH patients (50%, p<0.0001). PitAbs were not found in patients with secondary ES. Hypopituitarism was found in 49% of primary ES and in 62% of secondary ES (p=0.34). A positive correlation between the presence of PitAbs and hypopituitarism was found in primary ES (p=0.02).

Conclusions: the significant association between pituitary autoimmunity and hypopituitarism suggests that ES, in selected cases, could be the final result of AH.

From http://www.docguide.com/pituitary-autoimmunity-associated-hypopituitarism-patients-primary-empty-sella?tsid=5

Prevalence and Incidence of Diabetes Mellitus in Adult Patients on Growth Hormone Replacement for Growth Hormone Deficiency

1. Andrea F. Attanasio,
2. Heike Jung,
3. Daojun Mo,
4. Philippe Chanson,
5. Roger Bouillon,
6. Ken K. Y. Ho,
7. Steven W. J. Lamberts,
8. David R. Clemmons and
9. for the HypoCCS International Advisory Board

- Author Affiliations

1. Cascina del Rosone (A.F.A.), 14041 Agliano Terme, Italy; Lilly Deutschland GmbH (H.J.), 61352 Bad Homburg, Germany; Lilly Research Center (D.M.), Eli Lilly and Co., Indianapolis, Indiana 46285; University Paris-Sud 11 and Institut National de la Santé et de la Recherche Médicale Unité 693 (P.C.), 94270 Le Kremlin-Bicêtre, France; Katholieke Universiteit Leuven (R.B.), Laboratory for Experimental Medicine and Endocrinology, 3000 Leuven, Belgium; Garvan Institute of Medical Research (K.K.Y.H.), St. Vincent's Hospital, Sydney, New South Wales 2010, Australia; Department of Internal Medicine (S.W.J.L.), Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands; Department of Medicine (D.R.C.), University of North Carolina, Chapel Hill, North Carolina 27599

1. Address all correspondence and requests for reprints to: Prof. David R. Clemmons, Division of Endocrinology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7170. E-mail: david_clemmons@med.unc.edu.

Abstract

Context: GH replacement in adult GH-deficient patients may cause insulin resistance, raising concerns of potential increased risk of developing diabetes mellitus (DM).

Objective: Our objective was to assess DM prevalence and incidence in the international Hypopituitary Control and Complications Study (HypoCCS) surveillance database.

Design and Participants: GH-treated patients enrolled into HypoCCS (2922 U.S. and 3709 European patients) were assessed for DM, defined as recorded on the clinical report form, reported as adverse events, fasting glucose at least 7 mmol/liter recorded at least twice, or insulin treatment reported.

Results: DM prevalence was 8.2% [95% confidence interval (CI) = 7.6–8.9] overall, 11.3% in the United States and 5.7% in Europe. Incidence (n/1000 patient-years) was 9.7 (95% CI = 8.4–10.9) overall, 14.1 (11.5–16.7) in the United States, and 7.0 (5.6–8.3) in Europe. Overall incidence was 2.1 (0.9–3.3) for patients with body mass index (BMI) below 25 kg/m² increasing to 16.4 (13.7–19.1) for BMI over 30 kg/m². Obesity (BMI > 30 kg/m²) prevalence was higher in the United States than Europe and higher in U.S. patients than a U.S. reference population. After age, gender, and BMI adjustment, U.S. HypoCCS DM incidence was 10.6 (8.1–13.0), compared with 7.1 (6.0–8.1) in the National Health Interview Survey. In Europe, incidence for French and German patients was comparable to reference populations; for Sweden, the point estimate was higher than the reference population, but 95% CI overlapped. GH dose was not correlated with DM incidence.

Conclusions: The present analysis showed no evidence for increased DM incidence in GH-treated adult hypopituitary patients. However, those more prone to develop DM exhibited a higher than normal prevalence of obesity.

From http://jcem.endojournals.org/content/early/2011/05/04/jc.2011-0448.abstract

Radiation Therapy in the Management of Pituitary Adenomas

Jay S. Loeffler and Helen A. Shih

Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School (J.S.L., H.A.S.), Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Helen A. Shih, M.D., M.S., M.P.H., Massachusetts General Hospital, 100 Blossom Street, Cox 3, Boston, Massachusetts 02114.

Context: Optimal management of pituitary adenomas involves consideration of the roles of medical therapy, surgery, and radiation therapy. The different forms of radiation therapy and their results are reviewed here.

Evidence Acquisition: A literature search through the U.S. National Library of Medicine was used to identify and review clinical experiences of radiation therapy in the management of pituitary adenomas. Emphasis was placed on studies within the last 5–10 yr, with 5 or more years of follow-up data, and of reasonable quality of data. Older studies with larger numbers or particular significance are also highlighted.

Evidence Synthesis: Success of radiation therapy in controlling tumor growth is high, 90–100% in most series, regardless of radiation technique and adenoma subtype. Success in achieving hormonal normalization in secretory tumors is more variable because of differences in patient population, radiation technique, and doses employed and variation of the definition of success. Complete biochemical remission is generally achieved in 50% of patients at 10 yr after treatment for most adenomas. Higher rates of normalization can be achieved with additional medical therapy. Hypopituitarism is an expectant result of radiation therapy. Overall rate of other treatment-related adverse effects is low.

Conclusions: Radiation therapy should be considered in the management of patients with pituitary adenomas, particularly when medical and surgical options have been exhausted. Because response evolves slowly over many years and because hypopituitarism is likely to occur, patients should be counseled on the importance of continued endocrinological surveillance and medical management.

From http://jcem.endojournals.org/cgi/content/abstract/jc.2011-0251v1

Endocrine Society Releases Guidelines on Pituitary Incidentalomas

Wednesday, April 20, 2011 - Elsevier Global Medical News
BY ELIZABETH MECHCATIE

Surgical treatment of a pituitary incidentaloma is recommended when the lesion is causing a visual field deficit or other visual abnormalities, such as ophthalmoplegia “or neurological compromise,” according to evidence-based clinical practice guidelines published by the Endocrine Society.

Surgery is also recommended when the lesion is abutting or compressing the optic nerves or chiasm on MRI, when a patient is experiencing pituitary apoplexy with visual disturbance, or if a patient has a hypersecreting tumor other than a prolactinoma, according to the guidelines, which appear in the society’s journal (J. Clin. Endocrinol. Metab. 2011;96:894-904).

The guidelines pertain to adults, as there are no available data on these lesions in the pediatric population.

A pituitary incidentaloma is defined as “a previously unsuspected pituitary lesion that is discovered on an imaging study performed for an unrelated reason.” That does not include a symptom such as visual loss that is related to the lesion, “but rather [a study done] for the evaluation of symptoms such as headache, or other head or neck neurological or CNS complaints or head trauma.”

Such surprise findings are not uncommon, according to a statement from the society, which noted that small incidentalomas were discovered in as many as 20% of adults who had head imaging with MRI or CT scans for unrelated reasons.

“Fortunately, incidentalomas are almost always benign and usually do not need surgery,” Dr. Pamela Freda, an endocrinologist at Columbia University in New York who chaired the task force that wrote the guidelines, said in the statement. The guidelines make recommendations about evaluating and treating such patients, “indicating when surgical therapy may be necessary,” she added.

Surgery may be considered for patients with pituitary incidentalomas if there is clinically significant growth of the lesion, loss of endocrinologic function, or an “unremitting headache,” or if a patient is planning a pregnancy and has a lesion close to the optic chiasm.

The guidelines include recommendations on the initial evaluation of patients, follow-up testing of patients who do not meet criteria for surgical removal of the lesion, and medical therapy. For example, after an incidentaloma is identified, a patient should undergo a complete history and physical examination “that includes evaluations for evidence of hypopituitarism and a hormone secretion syndrome,” as well as biochemical evaluations, if there is evidence for either of these conditions, the guidelines state.

None of the seven authors of the guidelines declared a “significant financial interest” or a “leadership position” within the pharmaceutical industry. Dr. Freda’s disclosure states that she has “financial, business or organization interests” in Novartis, Ipsen, and Pfizer. Other authors also disclosed financial, business, or organization interests in those three companies, and/or in Novo Nordisk, Tercica/Ipsen, or no relevant financial interests.

The guidelines are cosponsored by the European Society of Endocrinology.

The society’s patient-education affiliate, the Hormone Foundation, is publishing a related patient guide that can be found at www.hormone.org/Resources/upload/Pituitary-Incidentaloma-Web.pdf.

From http://www.medconnect.com.au/tabid/84/s22/neurology/ct1/c340891/Endocrine-Society-Releases-Guidelines-on-Pituitary-Incidentalomas-/Default.aspx

Radiosurgery for pituitary adenomas: evaluation of its efficacy and safety

Object: To assess the effects of radiosurgery (RS) on the radiological and hormonal control and its toxicity in the treatment of pituitary adenomas.

Methods: Retrospective analysis of 42 patients out of the first 48 consecutive patients with pituitary adenomas treated with RS between 1999 and 2008 with a 6 months minimum follow-up. RS was delivered with Gamma Knife as a primary or adjuvant treatment.

There were 14 patients with non-secretory adenomas and, among functioning adenomas, 9 were prolactinomas, 9 were adrenocorticotropic hormone-secreting and 10 were growth hormone-secreting tumors. Hormonal control was defined as hormonal response (decline of more than 50% from the pre-RS levels) and hormonal normalization.

Radiological control was defined as stasis or shrinkage of the tumor. Hypopituitarism and visual deficit were the morbidity outcomes.

Hypopituitarism was defined as the initiation of any hormone replacement therapy and visual deficit as loss of visual acuity or visual field after RS.

Results: The median follow-up was 42 months (6 -109 months). The median dose was 12,5 Gy (9 - 15 Gy) and 20 Gy (12 - 28 Gy) for non-secretory and secretory adenomas, respectively.

Tumor growth was controlled in 98% (41 in 42) of the cases and tumor shrinkage ocurred in 10% (4 in 42) of the cases. The 3-year actuarial rate of hormonal control and normalization were 62,4% and 37,6%, respectively, and the 5-year actuarial rate were 81,2% and 55,4%, respectively.

The median latency period for hormonal control and normalization was, respectively, 15 and 18 months. On univariate analysis, there were no relationships between median dose or tumoral volume and hormonal control or normalization.

There were no patients with visual deficit and 1 patient had hypopituitarism after RS.

Conclusions: RS is an effective and safe therapeutic option in the management of selected patients with pituitary adenomas. The short latency of the radiation response, the highly acceptable radiological and hormonal control and absence of complications at this early follow-up are consistent with literature.

Author: Douglas CastroSoraya CecilioMiguel Canteras
Credits/Source: Radiation Oncology 2010, 5:109

From: http://7thspace.com/headlines/364042/radiosurgery_for_pituitary_adenomas_evaluation_of_its_efficacy_and_safety.html

Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma-knife?

Josef Marek, Jana Jezkova, Vaclav Hana, Michal Krsek, Lubomira Bandurova, Ladislav Pecen, Vilibald Vladyka and Roman Liscak

J Marek, 3 Dept. of Medicine, Charles University in Prague, Prague, 128 08, Czech Republic
J Jezkova, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha 2, 12802, Czech Republic
V Hana, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha, Czech Republic
M Krsek, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha, Czech Republic
L Bandurova, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha, Czech Republic
L Pecen, Institute of Informatics of the Czech Academy of Science, Praha, Czech Republic
V Vladyka, Dept. of Stereotactic and Radiation Neurosurgery, Hospital na Homolce, Praha, Czech Republic
R Liscak, Dept. of Stereotactic and Radiation Neurosurgery, Hospital na Homolce, Praha, Czech Republic

Correspondence: Jana Jezkova, Email: fjjezek@cmail.cz

Objective: Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism.

Design and methods: We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary < 15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001- 2009 (40 patients), irradiated with a mean dose to pituitary > 15 Gy. Serum TSH, free thyroxine, testosterone or 17?–estradiol, IGF 1, prolactin and cortisol levels were evaluated before and every six months after LGN irradiation.

Results: Hypopituitarism after LGK irradiation developed only in one out of 45 (2.2%) patients irradiated with a mean dose to pituitary < 15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose 17 Gy.

Conclusion: Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.

 

From http://www.eje.org/cgi/content/abstract/EJE-10-0733v1

Acquired Hypopituitarism

The author: Professor Yasser Metwally

http://yassermetwally.com

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INTRODUCTION

October 8, 2010 — The most concerning cause of acquired hypopituitarism is a tumor in the hypothalamic-pituitary region. The most common tumor that arises in this region in childhood is a craniopharyngioma. While craniopharyngiomas are derived from epithelial remnants of Rathke’s pouch, the same tissue that forms the anterior pituitary gland, they are not usually found exclusively within the pituitary gland, but more likely they are confined to the suprasellar region or are found in both suprasellar and intrasellar locations.[1] The presenting symptoms are dependent both on the main location of the tumor and on the direction(s) that the tumor grows. For example, if the tumor grows downward, it may cause alterations in the anterior and posterior clinoid bones or in the floor of the sella turcica and/or compress the pituitary gland. If the tumor grows upward, it may compromise vision by effects on the optic nerves.

While medical textbooks typically describe the most common visual change in patients with craniopharyngioma as "bitemporal hemianopsia" (loss of the outer visual fields of both eyes) due to compression of the optic chiasm, this rarely occurs so precisely. More likely is the development of "quadrianopsias," which are smaller, more irregular field cuts. If the tumor grows even farther upward beyond the visual tracts, it may block the third ventricle and cause obstructive hydrocephalus, leading to headaches, vomiting, and/or blurry vision (in association with papilledema). Craniopharyngiomas are benign tumors histologically, but they are often described as "geographically malignant" based on their location and ability to wrap around vital structures (eg, optic nerves) precluding complete surgical removal. As stated previously, tumors originating in the pituitary gland are uncommon causes of acquired hypopituitarism in children. However, any surgery to remove a tumor in the hypothalamic-pituitary region may lead to hypopituitarism if it is not already present.

Figure 1. A, Craniopharyngioma, compressing the optic chiasma, hypothalamus and extending upward into the lateral ventricle. The tumour is partially cystic with calcified material. B, A sagittal section of the brain shows a large craniopharyngioma below the cerebral ventricle. Note the stippled pattern of the tumor.

Another cause of acquired hypopituitarism is radiation treatment of a cancerous tumor in the head or neck region. More specifically, the radiation that is required to cure the child’s tumor may, of necessity, damage normal tissue in its path or beyond. When hypopituitarism ensues in this situation, it is usually the result of radiation-induced damage to the hypothalamus, as the pituitary gland is relatively resistant to radiation. Different hypothalamic-pituitary axes have different sensitivities to radiation. Doses as low as 18 Gy using conventional fractionation can interfere with GH dynamics; doses higher than 40 Gy can cause deficiencies of gonadotropins, TSH, and ACTH, while >50 Gy may cause hyperprolactinemia, especially among young women.

Other causes of acquired hypopituitarism in childhood include previous brain infection (encephalitis and/or meningitis), hydrocephalus (even without an underlying tumor), vascular abnormalities (such as a varix in the hypothalamic-pituitary area)[2], and major head trauma usually associated with a significant loss of consciousness.[3]

• Potential Anterior Pituitary Hormone Deficiencies

In childhood hypopituitarism, GH is the most commonly underproduced pituitary hormone, often as the result of loss of hypothalamic GH-releasing hormone (GHRH) (Table 2). The deficiency of GH primarily leads to short stature and slow height velocity. Untreated GH deficiency in children also causes disturbed body composition, with a reduction in lean body mass (ie, muscle) and an excess of fat, the latter accumulating predominantly in the cheeks of the face and in the abdomen, creating a cherubic or angel-like appearance.[4]

Table 2. Hierarchy of Hypothalamic-Pituitary-Target Organ Hormones

Hypothalamus

Pituitary

Target Organ

Hormone/Function

Growth hormone-releasing hormone (GHRH)

Anterior:

Growth hormone (GH)

Cartilage/liver

Insulin-like growth factor-1 (IGF-1)

Thyrotropin-releasing hormone (TRH)

Anterior:

Thyroid-stimulating hormone (TSH)

Thyroid gland

T4/T3

Gonadotropin-releasing hormone (GnRH)

Anterior:

Luteinizing hormone (LH)

Ovary

Estradiol

Follicle-stimulating hormone (FSH)

Testicle

Testosterone

Corticotropin-releasing hormone (CRH)

Anterior:

Corticotropin (ACTH)

Adrenal glands

Cortisol

Prolactin-inhibitory factor

Anterior:

Prolactin

Breast

Milk

Hypothalamic factors

Posterior:

Antidiuretic hormone (ADH)

Kidney

Urine concentration

Deficiency of hypothalamic thyrotropin-releasing hormone (TRH) or pituitary TSH causes central hypothyroidism. Unlike children whose hypothyroidism is due to thyroid gland damage, those with hypopituitarism typically have somewhat higher thyroid hormone levels and thus may have few or no symptoms. In other cases, as occurs in patients with primary thyroid disease, short stature and slow height velocity, relative weight excess, constipation, dry skin, cold intolerance, and fatigue may be present.

Younger children with deficiencies of either hypothalamic gonadotropin-releasing hormone (GnRH) or the pituitary gonadotropins typically show no abnormalities since luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are normally low prior to puberty. In contrast, adolescent-aged children with deficiencies of the gonadotropins present with failure to start or progress through puberty (breast development and menstrual periods in girls and enlargement of the testicles and penis in boys). Infrequently and paradoxically, central sexual precocity can be seen in the setting of hypopituitarism.

Loss of hypothalamic corticotropin-releasing hormone (CRH) or pituitary ACTH results in an ability of the adrenal zonas fasciculata and reticularis to manufacture normal amounts of cortisol (central adrenal insufficiency). If deficient, this hormone is most likely to place a child in a life-threatening situation. While there would likely be no symptoms under normal circumstances, except maybe mild fatigue, lack of cortisol in the setting of infection, fever, surgery, trauma, etc, may cause vomiting, dehydration, shock, and even death. Biochemical correlates of cortisol deficiency include hypoglycemia and hyponatremia (with normokalemia). In this setting, mineralocorticoid function is completely normal, as aldosterone production by the zona glomerulosa of the adrenal cortex is regulated by the renin-angiotensin and not the CRH-ACTH system.

• Potential Anterior Pituitary Hormone Excess

Serum levels of prolactin are usually normal or only mildly increased (if there is disruption of the hypothalamic-pituitary stalk) secondary to the loss of a normally predominant inhibitory signal from the hypothalamus. Although there are typically no symptoms in this situation, in rare cases a small amount of galactorrhea might occur.

• Potential Posterior Pituitary Hormone Excess

As stated previously, a deficiency of ADH causes central or neurogenic DI. Infants and toddlers manifest DI with excessively wet diapers. If unrecognized and hence untreated, dehydration with elevated serum sodium concentrations will ensue in this age group as young children cannot report and easily satisfy heightened thirst. Older children with DI typically present with excessive day-and night-time urination, new onset of bed-wetting, and increased thirst. DI most often occurs unintentionally as a result of surgical treatment of a hypothalamic-pituitary tumor, such as a craniopharyngioma. In some cases, DI is temporary due to local postsurgical edema, but it will be permanent if surgical sacrifice close to the hypothalamus or of the stalk itself is required for complete cure of a brain tumor in the suprasellar region.[5] DI may also occur in association with a diencephalic germinoma.

Figure 2. Craniopharyngioma. (A) Sagittal T1-weighted image shows a cystic mass in the suprasellar region. (B) Coronal T1-weighted image shows a large cystic mass in the suprasellar region with compression of the optic chiasm. (C) Coronal postcontrast T1-weighted image shows enhancement of the irregular cyst wall. (D) Sagittal postcontrast T1-weighted image demonstrates enhancement of the cyst wall with a nodular area on the right side.

Figure 3. Craniopharyngioma. (A) Axial postcontrast CT scan shows a cystic mass with rim enhancement in the suprasellar region. (B) Sagittal T1-weighted image shows a large cystic mass involving the sellar and suprasellar regions. The mass shows high signal intensity on T1-weighted imaging, consistent with high protein content. A fluid-fluid level is seen within the cystic lesion. (C) Coronal T2-weighted image demonstrates a high signal intensity mass with suprasellar extension and slight parasellar extension into the cavernous sinuses.

Figure 4. Sarcoidosis. (A) Coronal T1-weighted image demonstrates a suprasellar isointense mass. (B) Coronal postcontrast T1-weighted image shows intense enhancement of the mass just inferior to the optic chiasm.

Figure 5. Histiocytosis. (A) Sagittal postcontrast T1-weighted image demonstrates an enhancing mass in the suprasellar region involving the infundibulum. (B) Coronal postcontrast T1-weighted image shows an enhancing mass in the suprasellar region along the infundibulum. Compression of the optic chiasm is seen. (C) Coronal postcontrast T1-weighted image obtained 3 months later after treatment shows a significant decrease in the size of the mass lesion along the infundibulum.

Figure 6. A, Postmortem case of hypothalamic tuberculoma. B, Tuberculous infection of the hypothalamus (arrow)

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References

1. Lafferty AR, Chrousos GP. Pituitary tumors in children and adolescents. J Clin Endocrinol Metab. 1999;84:4317-4323.

2. Martin NA, Macagba-Crain CL, Geffner ME, et al. Isolated growth hormone deficiency associated with a giant arteriovenous varix. Neurosurgery. 1990;27:295-298.

3. Benvenga S, Campenni A, Ruggeri RM, et al. Clinical review 113: hypopituitarism secondary to head trauma. J Clin Endocrinol Metab. 2000;85:1353-1361.

4. Carrel AL,Allen DB. Effects of growth hormone on body composition and bone metabolism. Endocrine. 2000;12:163-172.

5. Blevins LS Jr, Wand GS. Diabetes insipidus. Crit Care Med. 1992;20:69-79.

   From http://yassermetwally.wordpress.com/2010/10/08/acquired-hypopituitarism-2/

Cushing's Disease in Children: Report of Three Cases

Ping-Yi Hsua, Yi-Ching Tungb, Cheng-Ting Leeb, Fu-Sung Loc, Mu-Zon Wud, Wen-Yu Tsaib, Yong-Kwang Tue

Received 12 November 2009; received in revised form 8 April 2010; accepted 1 May 2010.

Cushing's disease is rare in children and adolescents. We report the clinical presentations of three children with Cushing's disease. All three exhibited the typical symptoms and signs of weight gain and growth retardation.

Two also demonstrated personality changes, hypertension and hypokalemia, the last of these being rarely reported in patients with Cushing's disease. Lack of diurnal changes in serum cortisol levels was the most common biochemical finding. Serum cortisol levels were suppressed by low-dose dexamethasone in one patient, which is not typical for patients with Cushing's disease. Imaging studies are essential for localizing the tumor.

Transsphenoidal surgery remains the treatment of choice, and pituitary irradiation should be considered for those patients whose tumors cannot be totally removed. Careful follow-up of these patients with awareness of the possibilities of relapse and the complications of hypopituitarism is indicated.

Key Words:  Cushing's syndrome , Cushing's disease , hypokalemia

Read the article here.

a Department of Pediatrics, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan

b Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan

c Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan

d Department of Pathology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan

e Department of Surgery National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan

Corresponding author. Department of Pediatrics, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan

PII: S1875-9572(10)60059-9

doi:10.1016/S1875-9572(10)60059-9

© 2010 Taiwan Pediatric Association. Published by Elsevier Inc. All rights reserved.

From http://www.pediatr-neonatol.com/article/S1875-9572%2810%2960059-9/abstract

Treatment of Cushing disease: overview and recent findings

Authors: Tatiana Mancini, Teresa Porcelli, Andrea Giustina

Published Date October 2010 , Volume 2010:6 Pages 505 - 516 DOI 10.2147/TCRM.S12952

Tatiana Mancini¹, Teresa Porcelli², Andrea Giustina^2
1Department of Internal Medicine and Medical Specialties, San Marino Hospital, San Marino, Republic of San Marino, ²Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy

Abstract:

Endogenous Cushing syndrome is an endocrine disease caused by excessive secretion of adrenocorticotropin hormone in approximately 80% of cases, usually by a pituitary corticotroph adenoma (Cushing disease [CD]). It is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management.

The goals of treatment of CD include the reversal of clinical features, the normalization of biochemical changes with minimal morbidity, and long-term control without recurrence. Generally, the treatment of choice is the surgical removal of the pituitary tumor by transsphenoidal approach, performed by an experienced surgeon. Considering the high recurrence rate, other treatments should be considered.

Second-line treatments include more radical surgery, radiation therapy, medical therapy, and bilateral adrenalectomy. Drug treatment has been targeted at the hypothalamic or pituitary level, at the adrenal gland, and also at the glucocorticoid receptor level. Frequently, medical therapy is performed before surgery to reduce the complications of the procedure, reducing the effects of severe hypercortisolism.

Commonly, in patients in whom surgery has failed, medical management is often essential to reduce or normalize the hypercortisolemia, and should be attempted before bilateral adrenalectomy is considered. Medical therapy can be also useful in patients with CD while waiting for pituitary radiotherapy to take effect, which can take up to 10 years or more.

So far, results of medical treatment of CD have not been particularly relevant; however, newer tools promise to change this scenario. The aim of this review is to analyze the results and experiences with old and new medical treatments of CD and to reevaluate medical therapies for complications of CD and hypopituitarism in patients with cured CD.

Keywords: ketoconazole, somatostatin analogs, dopamine agonists, rosiglitazone, Cushing disease, glucocorticoids, hypopituitarism

From http://www.dovepress.com/treatment-of-cushing-disease-overview-and-recent-findings-peer-reviewed-article-TCRM