Pregnancy-induced Cushing’s Syndrome: A Case Report

 

Cushing’s syndrome(CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature. Adrenal adenomas were found to be the commonest cause.The other causes include tumors in hypothalamus and pituitary. Ectopic ACTH secretion has been reported to cause CS.

There is a very rare condition. Cushing’s syndrome develops in pregnancy and resolving after delivery. The mechanisms underlying these conditions are poorly understood.

There are non-significant differences in the clinical features of pregnant and non-pregnant women with CS.The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, The normal gestational changes in the HPA axis alter these parameters and complicate the screening process for CS.

Comparing with non-pregnant women with CS, the treatment is different in Cushing’s syndrome during pregnancy.

We described here the case of a 25-year-old woman with CS during her forth [sic] pregnancy. Hypertension, diabetes, hypopotassaemia, purple striae and acne are present. Cushing’s syndrome in the patient resolved within four weeks of artificial termination. Eight months after artificial termination, the patient became pregnant again and rapidly developed Cushing’s syndrome with typical clinical symptoms and signs and laboratory results.

Title: Pregnancy-induced Cushing’s Syndrome: A Case Report

Category: Tumor Biology

Filename: Pregnancy-induced Cushing’s Syndrome: A Case Report.pdf

Pages: 101

Price: US$48.00

Buy this pater at http://www.tumorres.com/tumor-biology/25201.htm

 

Diabetes in Cushing syndrome: basic and clinical aspects

Diabetes mellitus is a frequent complication of Cushing syndrome (CS) which is caused by chronic exposure to glucocorticoid excess, either endogenous or exogenous, and that is characterized by several clinical symptoms such as central obesity, purple striae, proximal muscle weakness, acne, hirsutism and neuropsychological disturbances.

Diabetes occurs as a consequence of an insulin-resistant state together with impaired insulin secretion which are induced by glucocorticoid excess. The management of patients with CS and diabetes mellitus includes the treatment of hyperglycemia and, when possible, the correction of glucocorticoid excess.

This review focuses on the disorders of glucose metabolism in patients exposed to glucocorticoid excess, addressing both the pathophysiological aspects and the clinical and therapeutic implications.

Read the entire article at http://www.cell.com/trends/endocrinology-metabolism/abstract/S1043-2760(11)00138-X

Archived Interviews with MaryO, Cushing's Help Founder

From August 10, 2011

Listen to internet radio with CushingsHelp on Blog Talk Radio

 

The Co-Hosts also provided a TweetChat Transcription

#TCK_-_Healthcare_Social_Media_Transcript.pdf Download this file

:

 

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From January 3, 2008

Interview with Mary O'Connor (MaryO), founder of Cushings-Help.com and 20-year pituitary Cushing's Survivor. Robin (staticnrg) hosts.

Listen to internet radio with CushingsHelp on Blog Talk Radio

 

These episodes and many more are also available on iTunes podcasts

Read MaryO's bio

Cushing's Awareness Day passes but disease lingers for reader

Dear Dr. Gott: Would you please mention that April 8 was Cushing's Awareness Day

I was a healthy woman until the age of 55. After more a year, I was diagnosed with Cushing's disease. I have had two brain surgeries, Graves' disease, recurring Cushing's and 25 radiation treatments to the pituitary. Eight years later, I still live with the effects of this monster. Thank you, Dr. Gott.

Dear Reader: Unfortunately, I was not able to print your letter on April 8, having only received it on April 6. It takes about three weeks before any letter appears in the newspaper.

Cushing's syndrome is a rare endocrine disorder. It occurs when the body produces or receives too much cortisol over an extended period of time.

Cortisol is a vital component in the body. It helps the body respond to stress, maintain blood pressure and cardiovascular function, regulates carbohydrate, fat and protein metabolism, reduces the inflammatory response of the immune system, and balances the effects of insulin.

The most common symptoms include a rounded face and upper body (abdomen, upper back, neck and between the shoulders ("buffalo hump"), obesity and relatively slender arms and legs.

Other symptoms can include acne, slow-healing cuts, bites or infection, bone loss, muscle weakness, fatigue, cognitive difficulties, high blood pressure, high blood glucose levels, headaches, thin skin with easy bruising, purple/red stretch marks, depression and/or anxiety, abnormal menstruation and excess body and facial hair in women, and erectile dysfunction and a decrease in libido and fertility in men. Children typically present with obesity and slowed growth.

Write to Dr. Gott, c/o NEA-United Media, 200 Madison Ave., Fourth Floor, New York, NY 10016.

From http://amarillo.com/news/local-news/2011-05-23/dr-gott-rare-cushings-causes-multiple-problems

Be Your Own Health Advocate: 5 Body Signs Women Should Heed

Having persistent pain, fever or bleeding are usually wake-up calls that something's medically wrong and we should see a doctor. But we sometimes write off subtle or unsightly signs as mere annoyances or cosmetic concerns that we can cover up or ignore. Here are five body signs that women shouldn't overlook:

1. Too Much Facial or Body Hair
Hair sprouting in undesirable places, especially on the face and chest (hirsutism), often signals a hormonal imbalance from such conditions as Cushing's syndrome and polycystic ovarian syndrome (PCOS). In fact, PCOS affects 6 to 8 percent of women of childbearing age, and is a major cause of infertility. Other signs of PCOS include acne and being overweight.

Cushing's is a much rarer condition that usually strikes women (and sometimes men) between the ages of 20 and 50. Weight gain, fat on the upper back (aka buffalo hump) with thin arms and legs, round face, irregular periods and fatigue are other common signs. Depending on the cause, various treatments can help correct the hormonal imbalances for both PCOS and Cushing's. Having some facial hair is also fairly common during menopause, when estrogen decreases and androgen increases. However, a lot of facial or body hair in postmenopausal women can signal ovarian cysts or even ovarian cancer.

2. Feeling Cold All the Time
If you often are cold when others aren't, you may be suffering from an under-active thyroid (hypothyroidism), one of the most under-diagnosed conditions in women. Indeed, more than half of the cases of go undiagnosed. This is very unfortunate since an under-active thyroid causes a plethora of unpleasant signs including weight gain, bags under the eyes or droopy eyelids, constipation, and dry hair, skin and nails. Hypothyroidism is much more common in women than men and usually affects those over the age of 50. It can be treated hormonally.

3. Dry Eyes, Mouth and Skin
In winter, many women notice that their eyes and skin are dry and their mouths are parched due to low humidity and over-heated rooms. Mucous membranes can also become dry as a side effect of various medications, as well as from the loss of estrogen that normally accompanies aging. But dry eyes, mouth and other mucous membranes including the vagina, can also signal Sjorgren's syndrome, a potentially serious autoimmune disease that primarily affects women in their 40s and 50s.

Joint inflammation or tenderness is another common sign. Although Sjorgren's is not rare, it often goes undiagnosed or misdiagnosed for years. Unfortunately it's a progressive disease that, without treatment, can cause eye damage, dental decay and gum disease, as well as damage to the digestive and reproductive systems. There is no cure, but early detection and treatment can help alleviate the symptoms and help stop the progression of the disease.

4. Abdominal Bloating
Occasional abdominal bloating can be due to a number of digestive conditions such as lactose intolerance and other food sensitivities. However, abdominal bloating or a distended abdomen that lasts more than a few weeks can be an early -− and sometimes the only −- warning sign of ovarian cancer, one of the deadliest cancers in women. Other signs may include difficulty eating or feeling full quickly after eating or having frequent or urgent needs to urinate. About 80 percent of ovarian cancers have spread (metastasized) before they're diagnosed, but if detected and treated early the prognosis can be good.

5. A Discolored, Swollen Breast
Many women get swollen breasts before their periods and when they're pregnant. But if you have one swollen breast that's red or discolored and feels warm, it may be a warning sign of inflammatory breast cancer (IBC), a rare but very aggressive form of breast cancer. Unfortunately, IBC is often misdiagnosed by doctors as an infection or even an insect bite. And, unlike with other forms of breast cancer, most women with IBC do not have a breast lump. Their breast may also be dimpled like the skin of an orange, and may be tender, itchy, or achy. With early diagnosis and treatment, more women are now surviving this deadly form of breast cancer.

If you notice any of these or other disturbing signs, be sure to mention them to your doctor as soon as possible. He or she can determine whether it's something you can safely ignore or something that warrants further diagnosis or treatment.

From http://www.huffingtonpost.com/joan-liebmannsmith-phd-and-jacqueline-nardi-egan/be-your-own-health-advoca_b_657944.html

Update on the management of hirsutism

doi: 10.3949/ccjm.77a.08079    Cleveland Clinic Journal of Medicine  June 2010   vol. 77  6  388-398 

   1.  SHANNON HARRISON, MBBS, MMed, FACD*

   1.  NAJWA SOMANI, MD

   1.  WILMA F. BERGFELD, MD?

ADDRESS: Wilma F. Bergfeld, MD, Dermatology and Plastic Surgery Institute, A61, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail bergfew@ccf.org.

EDUCATIONAL OBJECTIVE: Readers will recognize signs of androgen excess and will consider current treatment options for hirsutism

 

Abstract

Hirsutism is a source of significant anxiety in women. While polycystic ovary syndrome or other endocrine conditions are responsible for excess androgen in many patients, other patients have normal menses and normal androgen levels (“idiopathic” hirsutism). The goal of the evaluation is to rule out any underlying pathology. The goals of therapy are to treat any underlying condition and to remove the excess hair. Current options for hair removal are discussed. Educating patients so they have reasonable treatment expectations is essential, as significant improvement may take weeks or months, and treatment may need to be repeated on an ongoing basis.

Key points

The finding of polycystic ovaries is not required for the diagnosis of polycystic ovary syndrome, nor does their presence prove the diagnosis. Gonadotropin-dependent functional ovarian hyperandrogenism is believed to cause this syndrome; however, mild adrenocorticotropic-dependent functional adrenal hyperandrogenism also is a feature in many cases.

Even women with mild hirsutism with subtle symptoms and signs of hyperandrogenism can have elevated androgen levels, and thus, they deserve a laboratory evaluation.

Laser treatment does not result in complete, permanent hair reduction, but it is more effective than shaving, waxing, and electrolysis, producing partial hair reduction for up to 6 months.

• ↵* Dr. Harrison received funding in 2008 from the F.C. Florance Bequest, administered through the Australasian College of Dermatologists.

Hirsutism causes significant anxiety and lack of self-esteem in women. Although it is itself a benign condition, it is often the sign of an underlying and possibly serious endocrine condition.

As we will discuss, the diagnosis begins with a detailed history and physical examination, with laboratory testing and imaging as needed to confirm or rule out underlying causes. Management begins with patient education and support and includes hair removal and drug treatment of any underlying metabolic derangement.

PREVALENCE AND IMPACT

Hirsutism is a common disorder of excess growth of terminal hair in an androgen-dependent male distribution in women, including the chin, upper lip, breasts, upper back, and abdomen.¹ It affects 5% to 10% of women of reproductive age.^1,2

Hirsutism should be differentiated from hypertrichosis, which can be hereditary or acquired, and which is defined as increased general hair growth in androgen-independent areas.¹

Excess hair is cosmetically concerning for women and can significantly affect self-esteem. ³ Normal or acceptable hair growth depends on a woman’s ethnicity and her perception of familial, cultural, and societal norms for the quantity and distribution of hair. Mediterranean women generally have a medium amount of body and facial hair, whereas Asian women have a minimal amount.^1,4,5

Hirsutism can be clinically graded according to the Ferriman-Gallwey scale^2,6 and is defined as a Ferriman-Gallwey score of 8 or higher.¹

HOW CIRCULATING ANDROGENS AFFECT HAIR FOLLICLES

In androgen-dependent areas, circulating androgens influence hair follicle characteristics. Androgens increase the size and diameter of the hair fibers in certain androgen-dependent sites, as seen in puberty with the transformation of vellus hairs (small, nonpigmented hairs) into terminal hairs (large, pigmented hairs) in the pubic and axillary regions in women, as well as the beard area in men.^2,7 Interestingly, the same circulating androgens cause miniaturization of the susceptible hair follicles of the central scalp.⁷ The susceptibility of the hair follicle to the effects of the androgens may be genetically determined.^7,8

Hirsutism is a sign of hyperandrogenism and increased action of androgens on hair follicles. In women, about half of circulating testosterone arises from the ovaries and adrenal glands; the rest originates from peripheral conversion of weaker androgens (such as androstenedione produced by the adrenals and ovaries) into testosterone.⁹ Dehydroepiandrosterone sulfate (DHEAS) originates mainly in the adrenal glands.^9,10 Testosterone is converted to the more potent dihydrotestosterone (DHT) by type II 5-alpha reductase in the skin, which can then act on susceptible hair follicles.^7,11 Therefore, hirsutism can be a consequence of endogenous androgen over-production from the ovaries or the adrenal glands (or both), of exposure to an exogenous source of androgen such as a drug, or of heightened hair follicle sensitivity and metabolism of normal circulating androgen levels (target end-organ dysfunction).¹

‘IDIOPATHIC’ HIRSUTISM: A MISLEADING DIAGNOSIS

Many women with hirsutism are found to have polycystic ovary syndrome as the underlying cause, but hirsutism is also commonly labeled as idiopathic when it occurs without an obvious cause, eg, in women with regular menses and normal androgen levels and without features suspicious for other causes of hirsutism. ^1,2,12,13 But while this term is commonly used,^1,12 it may be misleading, especially if the diagnosis of idiopathic hirsutism is based on standard laboratory tests, which do not always detect androgen excess.^2,13 Minor ovarian or adrenal functional hyperandrogenism,¹⁴ increased peripheral activity of 5-alpha reductase in the hair follicle, or abnormalities in the androgen receptor have been implicated in the pathogenesis of so-called idiopathic hirsutism. ^2,15

HIRSUTISM AND POLYCYSTIC OVARY SYNDROME

Polycystic ovary syndrome, a metabolic syndrome, presents clinically with menstrual irregularities such as oligomenorrhea or amenorrhea, infertility, and signs of hyperandrogenism such as hirsutism, acne, or androgenetic alopecia.^16,17 Metabolic disturbances including insulin resistance, impaired glucose tolerance, hyperlipidemia, and obesity (body mass index > 30 kg/m²) also can occur, thus increasing cardiovascular risk.^16–18

The finding of polycystic ovaries is not required to make the diagnosis of polycystic ovary syndrome, and their presence does not prove the diagnosis.^16,19 Gonadotropin-dependent functional ovarian hyperandrogenism is believed to cause this syndrome; however, mild adrenocorticotropic-dependent functional adrenal hyperandrogenism also is a feature in many cases. In rare cases, polycystic ovary syndrome presents with an isolated elevation of DHEAS.^16,20

OTHER CONDITIONS OF EXCESS ANDROGEN

The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans, abbreviated as HAIR-AN, is separate from polycystic ovary syndrome; it characterizes a group of inherited syndromes associated with severe metabolic abnormalities of insulin and glucose metabolism and with marked clinical signs of hyperandrogenism.¹²

The syndrome of seborrhea, acne, hirsutism, and acanthosis nigricans, abbreviated as SAHA, while not itself a diagnosis, is a clinical spectrum of dermatologic signs and symptoms also associated with hyperandrogenism. These are signs that may present with the HAIR-AN syndrome or with another cause of excess androgens, such as idiopathic, ovarian, adrenal, or hyperprolactinemic hyperandrogenism.²¹

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FIGURE 1.

A modification of the Ferriman-Gallwey scoring system. A score of 8 or more indicates hirsutism.

Thyroid disease, hyperprolactinemia, acromegaly, Cushing syndrome, exogenous factors such as androgenic drugs, and nonclassical congenital adrenal hyperplasia can also produce hirsutism.¹² In nonclassical congenital adrenal hyperplasia, which is typically caused by a deficiency of 21-hydroxylase, patients present with premature pubarche, hirsutism in the prepubertal years, and menstrual irregularities including primary amenorrhea.^22,23

Important rare causes of hirsutism include benign and malignant androgen-secreting tumors of adrenal or ovarian origin. In such cases, hirsutism can have an acute onset or rapid progression and may be associated with features of virilization, such as deepened voice, increased muscle mass, androgenetic alopecia, clitoromegaly, and increased libido.¹²

A THOROUGH HISTORY IS CRITICAL TO DIAGNOSIS

A thorough medical history can provide important diagnostic clues in women with hirsutism. The clinician should elicit details about the onset and progression of the hair growth,^12,15 previous treatments, and any cutaneous signs of hyperandrogenism, such as acne, seborrhea, acanthosis nigricans, or patterned hair loss.

Also important are the menstrual history and a history of infertility. Primary amenorrhea is defined as failure to menstruate by 16 years of age if secondary sexual characteristics have developed, or by 14 years of age if no secondary sexual characteristics have developed, and it can indicate nonclassical congenital adrenal hyperplasia.

The clinician should also try to determine if the patient has a history of galactorrhea or symptoms of virilization (eg, deepened voice, clitoromegaly, increased muscle mass); a family history of hirsutism, polycystic ovary syndrome, HAIR-AN syndrome, metabolic conditions such as type 2 diabetes mellitus, or cardiovascular disease^12,15; or a history of symptoms of any condition known to produce hirsutism, such as Cushing disease, acromegaly, or a thyroid disorder. Also important is a drug history to determine if the patient has taken drugs such as androgens, anabolic steroids, or valproic acid (Depakote).²⁰

THE PHYSICAL EXAMINATION

The physical examination involves use of the Ferriman-Gallwey hirsutism scoring system or a modified Ferriman-Gallwey scoring system (FIGURE 1), which helps categorize the severity and distribution of excess hair growth. A Ferriman-Gallwey score of 8 to 15 (out of a possible 36) indicates moderate hirsutism, whereas a score above 15 indicates severe hirsutism.^2,15

Another proposed predictor of hirsutism is that terminal hair on the chin or the lower abdomen (Ferriman-Gallwey score ≥ 2) is nearly 100% sensitive and 27% specific at predicting total-body hirsutism.²⁴

As part of the physical examination, the clinician should also look for other cutaneous signs of hyperandrogenism, such as acne, androgenetic alopecia, and seborrhea. Acanthosis nigricans is a sign of insulin resistance. Height and weight should be measured and the body mass index calculated. Blood pressure should be recorded, as high blood pressure may be seen in Cushing syndrome and is an important cardiovascular risk factor. Signs of virilization should be identified. Indicators of Cushing disease such as striae, moon facies, fat redistribution, fragile skin, and proximal myopathy should be noted as well as signs of thyroid disease, such as textural skin changes, goiter, and hair loss. Expressible or spontaneous galactorrhea suggests hyperprolactinemia. Acromegaly is associated with coarse facies and enlarged hands and feet. Many of the endocrinopathies can be caused by a pituitary adenoma, which can manifest as a visual field defect, so visual fields should be examined.²⁵ The examination should also exclude any palpable ovarian or adrenal mass.¹²

WHEN IS ADDITIONAL TESTING NEEDED?

Laboratory and radiologic testing in patients with hirsutism may be needed to confirm the diagnosis of a suspected underlying condition or to exclude serious underlying pathology (TABLE 1).^{1,12,15–18,20,22,23,25–28}

The current Endocrine Society guidelines²⁰ recommend obtaining an early-morning testosterone blood level in the following patients:

• Women with moderate or severe hirsutism

• Women with hirsutism of any degree with sudden onset or rapid progression, or accompanied by signs or symptoms suggesting malignancy or polycystic ovary syndrome: eg, menstrual irregularity, infertility, central obesity, clitoromegaly, or acanthosis nigricans.^15,20

Testing androgen levels in mild, isolated hirsutism has not been proven to be useful or to alter management.²⁰

Free testosterone level

An early-morning total or free testosterone level is the initial test in the laboratory evaluation of hirsutism.^12,15 Additional specialized laboratory testing may be needed to determine the free testosterone level,¹⁵ as the free testosterone test is not available at all laboratories. A normal total testosterone level does not exclude hyperandrogenism but can suggest the diagnosis of idiopathic hirsutism.¹⁵

Further testing is needed if the total testosterone level is normal or only slightly elevated, or if there is a strong clinical suspicion of an underlying condition such as endocrinopathy or tumor. It is also useful in patients whose hirsutism responds poorly to medical treatments¹⁵ (see discussion below).

If the total testosterone level is elevated, if the hirsutism is moderate to severe, if there are associated symptoms, or if hirsutism is acute or progressive, a further endocrinologic workup is needed,¹⁵ possibly including measurement of free testosterone, sex hormone-binding globulin, DHEAS, and androstenedione.¹⁵ Free testosterone, unbound to sex hormone-binding globulin, is the biologically active fraction, with the levels of binding globulin increased by drugs such as oral contraceptives¹⁵ and decreased by high insulin levels in insulin resistance.²⁵

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TABLE 1

Tests suggested in the workup of hirsutism

Test in patients with mild hirsutism?

Although the guidelines suggest that no additional workup is necessary for women with mild hirsutism, we evaluate all patients with hirsutism and those with the SAHA clinical spectrum by measuring free and total testosterone and DHEAS. In our experience, even women with mild hirsutism with subtle symptoms and signs of hyperandrogenism and mild hirsutism often have elevated androgen levels.

Test in women with idiopathic hirsutism?

In women with idiopathic hirsutism, minor forms of functional ovarian and adrenal hyperandrogenism are believed to play a role and are thought to be undetectable with conventional testing.²⁵ The gonadotropin-releasing hormone (GnRH) analogue stimulation test may uncover occult hyperandrogenism in this setting, but it is used as a research tool and does not currently have application in routine clinical practice.¹⁴

It is important to remember that some women with apparent idiopathic hirsutism and a history of regular menstrual cycles are actually oligo-ovulatory or anovulatory. In these instances, another diagnosis should be considered,¹³ and referral to an endocrinologist for further evaluation of ovulatory function is recommended.¹³

CURRENT USE OF DIAGNOSTIC IMAGING

When malignancy is suspected

A testosterone level above 200 ng/dL suggests an ovarian tumor, and a DHEAS level above 700 μg/dL suggests an adrenal tumor.²⁶ However, not all tumors present with such high androgen levels, and sudden onset of hirsutism, rapid progression of hirsutism, or signs of virilization suggest a tumor.¹⁵ In such cases, transvaginal ultrasonography, computed tomography, or magnetic resonance imaging (MRI) of the abdomen can exclude an ovarian or adrenal tumor.

When polycystic ovary syndrome is suspected

The diagnosis of polycystic ovary syndrome is confirmed by two out of three criteria:

• Oligo-ovulation or anovulation

• Clinical or laboratory signs of hyperandrogenism

• Ultrasonographic evidence of polycystic ovaries, with exclusion of other causes of hyperandrogenism.

ADDITIONAL LABORATORY TESTING

Tests for polycystic ovary syndrome

Assessment of polycystic ovary syndrome involves transvaginal ultrasonography, but ultrasonographic evidence of a polycystic ovary is not necessary for the diagnosis.¹⁶ A fasting lipid profile and fasting serum glucose are recommended, and if the fasting serum glucose is normal, an oral glucose tolerance test is recommended. ¹⁷

Some have reported measuring the ratio of luteinizing hormone to follicle-stimulating hormone in the workup of polycystic ovary syndrome, and a ratio greater than 2 has been considered indicative but not diagnostic.^16,25 The individual levels of luteinizing hormone, follicle-stimulating hormone, and estradiol are more important in the evaluation of infertility and ovulatory dysfunction. In patients with elevations of these hormones or with these symptoms, referral for infertility screening with an endocrinologist or gynecologist is recommended. ²⁵

Additional testing and referral for Cushing syndrome, other conditions

Cushing syndrome can be tested for with a 24-hour urine cortisol, overnight low-dose dexamethasone suppression test, and late-night salivary cortisol.^27,28 Referral to an endocrinologist for further testing can differentiate between corticotropin-dependent or corticotropin-independent Cushing syndrome.²⁵ Cushing syndrome is often associated with hyperandrogenism, particularly in those cases caused by adrenal tumors.²⁹

The prolactin level and the level of somatomedin C (insulin-like growth factor 1) can be used to rule out hyperprolactinemia and acromegaly, respectively.¹² If Cushing syndrome, hyperprolactinemia, or acromegaly is diagnosed by endocrinologic testing, pituitary MRI should be performed.^12,25

Referral to specialist centers with experience with these conditions is essential. Nonclassical congenital adrenal hyperplasia can be screened for by a serum 17-hydroxyprogesterone level measured in the follicular phase.¹² Measurement of thyroid-stimulating hormone, free thyroxine, and thyroid peroxidase antibodies screens for thyroid disease.¹² Hirsutism has been reported with the commencement of L-thyroxine therapy.³⁰

THE PRINCIPLES OF TREATMENT

Patient education regarding the cause of hirsutism and reasonable treatment expectations and emotional support are important in the management of hirsutism. Also important is regular follow-up to measure and document the response to treatment; this can include repeating Ferriman-Gallwey scoring, taking photographs of affected areas, and retesting androgen levels after 3 to 6 months.¹²

Treatment must be continued for an ongoing effect, and most pharmacologic treatments can take up to 3 to 6 months to produce significant improvement.¹

When an underlying condition is diagnosed, treatment of the condition is essential. Androgen-secreting tumors require surgical management.¹² Cushing disease, hyperprolactinemia, and acromegaly should be clinically apparent from examination and testing, and appropriate referral and standard management should be instigated. Exogenous sources of androgen such as androgenic progestins or anabolic steroids should be discontinued. Lifestyle management is important, and weight loss in obese patients with polycystic ovary syndrome can improve hirsutism as well as mitigate cardiovascular risk factors.³¹

In classic congenital adrenal hyperplasia, glucocorticoid therapy manages both ovulation induction and hirsutism.²⁰ However, in nonclassical congenital adrenal hyperplasia, glucocorticoid therapy supports ovulation induction, but hirsutism usually requires both systemic antiandrogen and hair removal.²⁰

CURRENT OPTIONS FOR HAIR REMOVAL

The mainstay of treatment of hirsutism is removing the excess hair. Options (TABLE 2) include inexpensive, home-based, self-care methods such as plucking, shaving, waxing, using depilatory creams, and bleaching, and more expensive clinic-based treatments such as clinic-based waxing, electrolysis, and laser hair removal. These methods can also be combined with drug therapy.¹

The choice of method depends on patient preference, adverse effects, the degree of hirsutism, the level of distress, previous treatments, and cost.^1,15,32

Self-care methods

Self-care methods offer only temporary reduction of excess hairs.

Plucking removes the entire hair, including the root, but it is painful and time-consuming, and it is only practical for areas where few hairs exist, such as on the face.¹

Shaving is an easy, inexpensive, and painless choice for hair removal. Although a common belief is that shaving causes faster or thicker hair regrowth, shaving affects neither the diameter nor the rate of growth of the hair.³² Given its masculine association, shaving is not acceptable to most women except perhaps for use on the legs and axillae.^1,32 Shaving can cause irritation, folliculitis, pseudofolliculitis, and infection.¹

Waxing removes the entire hair. While it is more expensive than plucking, regrowth is slower, occurring over weeks. It is painful and can cause thermal burns, irritation, folliculitis, scarring, and postinflammatory dyspigmentation.¹

Chemical depilatories, usually thioglycollic acid preparations, are inexpensive, painless, and easy to use. However, the resulting hair reduction is of short duration because the hair shafts are only removed at the level of the skin surface.¹ They can also cause irritant dermatitis. ¹

Bleaching with hydrogen peroxide is inexpensive and can camouflage dark facial hair, but it can also cause skin discoloration and irritation. ¹

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TABLE 2

Hair removal methods and their potential side effects

Clinic-based methods

Electrolysis often results in a permanent reduction in hair growth.^1,32 A fine needle is placed into the hair follicle and an electrical current is applied. Each follicle is treated individually. ^1,32 Best results are seen on darker hairs in patients with lighter skin, but it can be used on all skin types and hair colors.^1,32

Electrolysis is operator-dependent, and there are US Food and Drug Administration (FDA) regulations regarding electrolysis techniques. It requires multiple treatments, and it is painful and can cause erythema, folliculitis, pseudofolliculitis, infection, scarring, and postinflammatory dyspigmentation.^1,32 Some reports suggest that prior waxing and plucking of hairs damages the hair by twisting the hair shaft, making electrolysis more difficult.³²

Laser treatment uses light of certain wavelengths to damage the hair follicles. While laser hair removal does not result in complete or persistent hair removal, it is more effective than shaving, waxing, and electrolysis, producing partial hair reduction for up to 6 months; the effect is enhanced with multiple treatments.^33,34 The number of treatments required depends on the laser type and on the nature of the patient’s hair follicles.³⁵

Laser systems for hair removal are of various wavelengths and also include intense pulsed light systems. The choice of system depends on the patient’s skin type and hair color. Women with fair skin and dark hair are ideal candidates; longer-wavelength lasers are preferred for darker or tanned skin types.

Adverse effects of laser hair removal include pain, erythema, burns, dyspigmentation, and scarring. Laser cooling devices can prevent or minimize some of these effects. Laser treatment has also been known to cause a paradoxical increase in hair growth.^1,33,34

DRUG THERAPIES FOR HIRSUTISM

Another option for hair removal in patients with hirsutism is drug therapy (TABLE 3).^{1,12,15,20,31,32,36–42} Several meta-analyses have studied drug treatments for hirsutism and treatment guidelines have been published. ^20,36–38 However, the studies are limited by the heterogeneity of patients with hirsutism, small sample sizes, limited methodology, and failure to distinguish between the types of hirsutism.

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TABLE 3

Possible side effects of drug treatments for hirsutism

The drugs most commonly used for hirsutism are oral contraceptives (off-label use) and antiandrogenic drugs (off-label use). Topical eflornithine cream (Vaniqa) is FDA-approved for hirsutism but is less commonly used. Insulin sensitizers, GnRH analogues, and other drugs are occasionally used (off-label) to treat hirsutism.

Topical eflornithine cream

Topical eflornithine cream treats facial hirsutism by slowing the rate of hair growth; it does this by irreversibly inhibiting ornithine decarboxylase, an enzyme essential for hair growth.^39,40 Studies showed that twice-daily application reduced unwanted facial hair in women after 24 weeks of treatment.^39,40 Treatment must be continuous, since hair growth rapidly returns to the pretreatment rate by 8 weeks after discontinuing eflornithine.^39,40 White women have been shown to respond better than black women.³⁹ Adverse effects include a mild burning sensation, acne, pseudofolliculitis barbae, irritation, and allergic contact dermatitis.^39,40 Improved outcomes have been suggested when eflornithine cream is combined with laser hair removal.⁴¹

Oral contraceptives

Oral contraceptives are commonly used off-label for the management of hirsutism.²⁰ Oral contraceptives suppress the secretion of luteinizing hormone and, hence, the synthesis of ovarian androgen, thereby increasing levels of sex hormone-binding globulin and decreasing free plasma testosterone.^1,20 Adrenal androgen production is also slightly reduced.²⁰

Oral contraceptives usually combine a synthetic estrogen and a progestin. Certain progestins are more androgenic and should be avoided.¹

For treating hirsutism, oral contraceptives should be used that contain low-androgenic progestins such as cyproterone acetate (not available in the United States), drosperinone (eg, in Yasmin), norgestimate (eg, in Ortho Tri-Cyclen), or desogestrel (eg, in Mircette).^1,20

Side effects of oral contraceptives include breast tenderness, gastrointestinal upset, headache, loss of libido, hypertension, and the potential risk of venous thromboembolism.^1,15,32,36

Antiandrogenic drugs

Several antiandrogenic drugs are used off-label to treat hirsutism.

Spironolactone (Aldactone), a competitive inhibitor of the androgen receptor and 5-alpha reductase activity,²⁰ can be effective in the treatment of hirsutism. Monotherapy with spironolactone, without an oral contraceptive or other reliable form of contraception, is not recommended because of the teratogenic potential of all antiandrogens to feminize a developing male fetus.²⁰ Thus, reliable contraception should be used in females of childbearing age when starting antiandrogen therapy.

The dosage of spironolactone for hirsutism is usually 100 mg to 200 mg daily.^1,20 Hyperkalemia, polyuria, postural hypotension, irregular menses, and liver abnormalities are among the possible adverse effects (TABLE 3). Spironolactone was found to be tumorigenic in animal studies, although this has unknown relevance in humans.³⁶

Cyproterone, an antiandrogen not available in the United States,⁴² competitively inhibits the androgen receptor and 5-alpha-reductase activity.^1,20,36 It can be used for only the first 10 days of the menstrual cycle (50-mg or 100-mg dose) with an oral contraceptive pill, or in a low dose in a combined oral contraceptive pill (Diane-35 in Canada and the United Kingdom).¹

Side effects are similar to those of oral contraceptives and include fatigue, mood change, risk of venous thromboembolism, and decreased libido.^1,15,36 Importantly, in woman of childbearing age, there is the potential risk of feminization of a male fetus, so reliable contraception must be used.^15,36

Flutamide, an investigational antiandrogen, has shown promise in the treatment of hirsutism.²⁰ Flutamide is a nonsteroidal competitive inhibitor of androgen receptor binding. It carries a significant risk of hepatotoxicity. ^1,15

Finasteride (Propecia) 1 mg is only occasionally used in the treatment of hirsutism (off-label usage). It inhibits type II 5-alphareductase to suppress dihydrotestosterone levels. ³² It carries a risk of gastrointestinal disturbance, decreased libido, hepatotoxicity, and feminization of a male fetus (pregnancy category X), so reliable contraception is required in all females of childbearing age, as with all antiandrogens¹ (TABLE 3).

Dutasteride (Avodart), a type I and II 5-alpha-reductase inhibitor, has not been studied for the treatment of hirsutism (pregnancy category X).

Insulin sensitizers

Metformin (Glucophage) and other insulin sensitizers are less effective than antiandrogens at reducing hirsutism.^20,38 However, metformin is effective at inducing ovulation in patients with polycystic ovary syndrome.³⁸ Gastrointestinal upset is a common side effect; lactic acidosis is a serious but rare adverse effect.¹

Gonadotropin-releasing hormone analogues

GnRH analogues are an option only if oral contraceptives and antiandrogen drugs are unsuccessful in patients with severe hyperandrogenism. ²⁰ They suppress secretion of luteinizing hormone and the synthesis of ovarian androgen.^1,20 These drugs are given as monthly intramuscular injections, usually with some form of estrogen-progestin replacement, since GnRH analogues cause estrogen levels to fall to menopausal levels.¹

Side effects include signs and symptoms of menopause including hot flushes, atrophic vaginitis, and osteoporosis.^1,15 These drugs completely inhibit ovulation, and some endocrinologists and gynecologists do not suggest further contraception in women of childbearing years for this reason. However, GnRH analogues are not approved as a contraceptive and are pregnancy category X.

Other drugs

Other drugs with antiandrogen activity include cimetidine and ketoconazole.¹² Cimetidine (Tagamet) is not effective for the treatment of hirsutism, and ketoconazole (Nizoral) is associated with significant risk for adrenocortical suppression¹² and hepatotoxicity in addition to multiple drug interactions, given its effect on the hepatic P450 enzyme system.

Acknowledgments

Many thanks to Rebecca Tung, MD, dermatologic surgeon, Cleveland Clinic, for her advice on lasers.

• Copyright© 2010 The Cleveland Clinic Foundation

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From http://www.ccjm.org/content/77/6/388.full

Cushing's Syndrome

Medical Codes

ICD-9-CM:
255, 255.0

255 -
Disorders of Adrenal Glands

255.0 -
Disorders of Adrenal Glands, Cushings Syndrome; Adrenal Hyperplasia Due to Excess ACTH Cushings Syndrome NOS, Iatrogenic, Idiopathic, Pituitary-Dependent, Ectopic ACTH Syndrome, Iatrogenic Syndrome of Excess Cortisol, Overproduction of Cortisol

Definition

Cushing's syndrome is a condition caused by excess corticosteroids in an individual's body. These steroids can be produced by the body itself or can result from high doses of medical steroids being administered to the individual. Cushing's syndrome is characterized by a large, round face and a thick torso with comparatively thin arms and legs. Muscle weakness, depression, hallucinations, thin skin that bruises easily and heals slowly, and purple streaks on the abdomen are also common signs and symptoms of this condition.

The adrenal glands located on top of the kidneys produce cortisol. Under normal conditions, the release of cortisol is controlled by the pituitary gland and the hypothalamus in the brain. The hypothalamus sends a hormone (corticotropin-releasing hormone or CRH) to the pituitary gland. CRH causes the pituitary gland to secrete a hormone called ACTH (adrenocorticotropic hormone). ACTH is the signal for the adrenal gland to produce cortisol.

A common cause of Cushing's syndrome is the administration of glucocorticoid drugs (such as prednisone) or ACTH for various medical reasons. This is called exogenous Cushing's syndrome. Individuals with any disease requiring prolonged use of corticosteroid medications are at increased risk of developing Cushing's syndrome. Examples of some medical conditions that are often treated with glucocorticoids or ACTH and may increase one's risk of developing Cushing's syndrome include rheumatoid arthritis, lupus, asthma, or other chronic inflammatory diseases.

When a tumor (adenoma) of the pituitary gland produces excessive amounts of ACTH, there is a subsequent release of excess cortisol by the adrenal glands. This condition is called Cushing's disease (hypercortisolism), and it accounts for about 70% of the naturally occurring (endogenous) cases of Cushing's syndrome. Another 15% of the naturally occurring cases of Cushing's syndrome are caused by release of cortisol from noncancerous (benign) or cancerous (malignant) tumors of the adrenal gland (adrenal adenoma and adrenal carcinoma). The remaining 15% of cases are caused by the production of ACTH by a tumor (either benign or malignant) located elsewhere in the body (ectopic ACTH syndrome) (Adler).

 

Risk: Cushing's syndrome most commonly affects adults between the ages of 20 and 50, although it can strike at any age. Although Cushing's syndrome is not inherited, some people have an inherited predisposition to tumors of the hormone-secreting glands. This predisposition places these individuals at a higher risk for Cushing's syndrome than the general population.

Cushing's disease more commonly affects women of reproductive age, but it can occur in men and women at any age (Kirk). Women are five times more likely than men to have Cushing's syndrome caused by a pituitary or an adrenal tumor (Adler).

Ectopic ACTH syndrome is caused by lung tumors (usually carcinoid) in 50% of cases. Other ACTH-producing tumors include thymomas, pancreatic islet cell carcinomas, and medullary carcinomas of the thyroid. Ectopic ACTH syndrome affects men more often than women because lung cancer occurs more frequently among men (Adler).

 

Incidence and Prevalence: Cushing's syndrome is relatively rare, affecting about 13 of every million individuals each year (Adler).

Diagnosis

History: Frequent complaints include weight gain, fatigue, muscle weakness (especially of the upper arms and thighs), easy bruising, poor wound healing, thinning scalp hair, abnormal growth of body hair and purple streaking (striae) of the breasts, buttocks, lower abdomen and thighs. Individuals may also complain of excessive thirst and frequent urination. Psychiatric symptoms include mood swings, depression, and personality changes (steroid psychosis). Women may notice changes in the menstrual flow (oligomenorrhea or amenorrhea), and men may complain of decreased sex drive (libido) and inability to achieve or maintain an erection (erectile dysfunction). Often, individuals will report that routine bending, lifting, or rising from a chair has become difficult or painful.

 

Physical exam: High blood pressure (hypertension) is seen in over 80% of cases. There are some striking physical changes in Cushing's syndrome. The face is round and unusually red. Acne may be present. Obesity is common; 50% of individuals gain weight in the abdomen and buttocks while the arms and legs are normal. Fat pads appear over the collarbones and upper spine.

 

Tests: If it has been determined from the history and physical exam that the individual is not showing the signs of Cushing's syndrome from prescribed medications, further testing is carried out at two levels. First, it must be determined whether the individual has elevated levels of cortisol. A 24-hour urine collection is taken, and the amount of cortisol in the urine is measured. The cortisol level will be elevated in individuals with Cushing's syndrome. Another test is the overnight dexamethasone suppression test. Dexamethasone is a steroid medication that suppresses ACTH release and lowers the early morning levels of blood cortisol in normal individuals but has no effect in individuals with Cushing's syndrome. A newer means to detect Cushing's syndrome uses a combination of the CRH stimulation test with the dexamethasone suppression test. Cortisol levels exceeding 1.4 µg per L would be diagnostic for Cushing's syndrome. This method is reported to have a very high rate of diagnostic accuracy.

Once the diagnosis of Cushing's syndrome is established, a second level of testing is carried out to determine the cause of the disease: a tumor of the pituitary gland or adrenal glands or a tumor that stimulates the adrenal glands through ectopic ACTH secretion. A test called the CRH stimulation test is often performed to help distinguish individuals with Cushing's syndrome due to pituitary adenomas from those with ectopic ACTH syndrome or cortisol-secreting adrenal tumors.

In the CRH stimulation test, individuals are given an injection of CRH. Those with a pituitary adenoma usually experience a rise in blood levels of ACTH and cortisol. This response is rarely seen in people with ectopic ACTH syndrome and practically never in those with cortisol-secreting adrenal tumors.

Routine chest x-rays are done, along with CT of the chest in suspected cases of ectopic ACTH production. A CT of the adrenal glands can show an adrenal tumor, or in the case of a pituitary tumor that stimulates both glands, enlarged adrenal glands. MRI of the pituitary gland is done in cases of suspected pituitary tumors. Pituitary adenomas are only seen on 50% of MRI tests, so it is important that the biochemical testing is thorough before surgery (Kirk).

Blood tests may also show high levels of sugar (hyperglycemia), fat (hyperlipidemia), or potassium (hyperkalemia) and abnormal numbers of certain white blood cells (neutrophilia, lymphopenia).

Treatment

If the condition is caused by overmedication, it is treated by reducing the dosage of glucocorticoids or changing the medication. When the underlying cause is a benign or malignant tumor of the adrenal gland, the tumor must be surgically removed.

The treatment of choice for tumors of the pituitary gland is surgical removal. Irradiation of the pituitary gland has a lower success rate and a higher rate of complications, and notable improvement may not be noted for a year or more. Hormone replacement therapy usually follows surgery and, in some cases, must be continued for life.

Medical treatment (chemotherapy) is usually not recommended as the primary treatment for Cushing's syndrome but is an alternative if surgery is not possible and may be used with radiation treatments to hasten better results. If the cause of Cushing's syndrome is ectopic ACTH, treatment is directed at the underlying disease.

 

Prognosis

Before the introduction of effective therapy approximately 50% of patients with untreated Cushing's syndrome died within 5 years. Now with appropriate medical intervention, the outcome of endogenous Cushing's is generally good. Cushing's secondary to ACTH-producing tumors of the adrenal gland are often treated by surgical removal of the adrenal gland, which has a 100% cure rate. However, Cushing's secondary to ACTH-producing tumors of the lung generally has a poor outcome (Stewart 522).

 

Complications

Cushing's syndrome is complicated by high blood pressure, diabetes, increased susceptibility to infections, emotional disturbances, and metastasis of cancerous tumors. The bones become fragile (osteoporosis), and compression fractures of the spine are common.

 

Return to Work (Restrictions / Accommodations)

No restrictions or accommodations should be necessary once the individual returns to work.

 

Failure to Recover

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.

 

Regarding diagnosis:

• On exam, are symptoms present such as hypertension, red, round face, acne, and weight gain in the abdomen and buttocks or fat pads over the collarbones and upper spine? Does individual have a thick torso with comparatively thin arms and legs?
• Does individual also have muscle weakness, thin skin that bruises easily and heals slowly, and purple streaks on the abdomen, breasts, buttocks and thighs?
• Does individual have a pituitary tumor, adrenal tumor, small cell lung cancer, thymomas, pancreatic islet cell carcinomas, or medullary carcinomas of the thyroid?
• Is individual being treated with glucocorticoid drugs for another condition?
• Does individual have a family history of tumors of the hormone-secreting glands?
• Does individual complain of weight gain, fatigue, thinning scalp hair, excessive body hair, excessive thirst, and frequent urination?
• Does individual have mood swings, depression, hallucinations, and personality changes?
• Does individual have oligomenorrhea or amenorrhea? Decreased libido? Impotence? Does individual report that routine bending, lifting, or rising from a chair is difficult or painful?
• Were cortisol levels tested? Was individual tested for the presence of cortisol-secreting tumors?
• Was an overnight dexamethasone suppression test done? Was a combination CRH stimulation and dexamethasone suppression test done to confirm the diagnosis? CT or MRI? Comprehensive blood testing? Was inferior petrosal sinus sampling done?
• Were conditions with similar symptoms ruled out?

 

Regarding treatment:

• Is the condition caused by overmedication? Is the dosage of glucocorticoids reduced or the medication changed?
• Is the condition caused by a tumor? Was it surgically removed? Is individual on hormone replacement therapy?

 

Regarding prognosis:

• Does individual have any conditions that may affect ability to recover?
• Have any complications developed, such as high blood pressure, diabetes, infections, emotional disturbances, metastasis of tumors, osteoporosis, and compression fractures of the spine?

 

Cited References

Adler, Gail. "Cushing Syndrome." eMedicine. Eds. William Chiang, et al. 17 Aug. 2004. Medscape. 28 Sep. 2004 http://emedicine.com/emerg/topic117.htm.

 

Kirk, Lawrence F., et al. "Cushing's Disease: Clinical Manifestations and Diagnostic Evaluation." American Academy of Family Physicians. 28 Sep. 2004 http://www.aafp.org/afp/20000901/1119.html.

 

Stewart, Paul M. "Therapeutic Corticosteroids." Williams Textbook of Endocrinology. Eds. R. H. Williams and Reed P. Larsen. 10^th ed. Philadelphia: Elsevier, Inc., 2003. 508-525. MD Consult. Elsevier, Inc. 28 Sep. 2004 http://home.mdconsult.com.

 

From http://www.mdguidelines.com/cushings-syndrome

Cushing's: Bleaching is alive and well in sunny Jamaica

BY DR NEIL PERSADSINGH

Monday, June 29, 2009

THE phenomenon of skin bleaching is alive and well in Jamaica. The recent seizure by customs of goods containing a selection of bleaching creams only proves the point.

 

Bleaching is the application of chemicals to the skin to obtain a fairer colour. It may also be referred to as toning.

 

Usually the chemicals used contain hydroxyquinone or cortisone, eg Bethamethasone, R Triamcinilone, Clobetasol or Mercury. Usually the chemicals are obtained by illicit means and as that customs bust proved, not even the government is able to collect tax revenues on these drugs.

 

So much can be said for government's control of these chemicals. Every wholesale in Kingston has these drugs for sale. At every street corner in downtown Kingston these drugs are available. Men are bleaching, women are bleaching, boys and girls are bleaching. At every Passa Passa fete you will see a lot of girls who are bleaching, or just take a drive into the ghetto and you will see girls, their faces covered with a white cream busily bleaching.

 

The question naturally arises, what can be done? We need a new educational policy. Last year we had a drive that was put on by the pharmacy board at the Ministry of Health, where we went to the schools and to the libraries and spoke to the kids. I believe that it was successful but it was discontinued. We need to get back to the drawing board and get a new strategy to deal with this problem.

 

We approve of the ad shown on national TV showing a lady saying that she would never bleach her skin, but the usual response from our patients is, "She nuh know nuttin, she a eediat", completely dismissing the message that bleaching will damage their skin.

 

The preparations containing mercury are illegal because mercury is a toxic chemical which accumulates in the body and leads to some serious problems like liver disease. Mercury products are therefore banned worldwide but still find themselves unto our streets.

 

Hydroxyquinine products are used in medicine by dermatologist and by doctors. They should not be used carelessly as they may have the effect of causing onchynerosis in which there is the development of ugly dark spots on the skin caused by the deposition of melanin - the pigment of the skin deep in the second layer of the skin.

Cortisione preparations are used again by dermatologists and in medicine but these preparations should be obtainable only with a doctor's prescription. They should only be used for a week or at the most two weeks before their use is assessed by a doctor to ensure that they are not causing any harm.
If these products are used for a long time they can cause the appearance of stretch marks.

Thinning of the skin, a severe form of acne called steroid acne and the appearance of a lump of fat at the back of the neck called cushings syndrome are also results. The face can also become round and moon like and there can also be wasting of the limbs.

If enough of the steroid is absorbed we can get high blood pressure and diabetes and if the creams are used around the eyes we can develop glaucoma. In fact we expect to see more cancers of the skin as the melanin is removed by the bleaching and the skin is exposed to the harmful effects of the sun.

 

Despite all of this our people continue to bleach and the sales of these creams continue to flourish. As soon as we crack down on one product it resurfaces under another name and in a different packaging.

 

It is hard to believe that in the 21st Century in Jamaica the country which is the heart of black pride - a country which gave the world Garvey and Marley and Rastafari - is still bleaching.

 

From http://www.jamaicaobserver.com/magazines/AllWoman/html/20090628T210000-0500_154347_OBS_BLEACHING_IS_ALIVE_AND_WELL_IN_SUNNY_JAMAICA.asp