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New Treatments for Excessive Facial Hair and Hirsutism

The first step in the biochemical evaluation of such a patient is to measure serum testosterone and DHEAS. If testosterone is over 2 nanograms, again keep in mind that the upper normal limit is about more than 2 times the upper normal limits of testosterone, then an androgen-producing ovarian tumor should be suspected. Many of these tumors can be palpated on pelvic exam. The majority of these tumors are unilateral and are of sufficient size. If the pelvic exam is negative, then you have to resort to vaginal probe ultrasound and if that is negative, then you have excessive facial hair.

The point is that when you have a patient with severe hirsutism of late onset and rapid progression, you have to make the diagnosis as early as you can. If the level of DHEAS is over 7000 - again, more than two times upper normal limits - you have to entertain the possibility.

There are basically two types of androgen-producing adeno-tumors; you might have an adenoma, which tends to be smaller and well circumscribed; or you might have an adrenal cancer. Adrenal cancers usually have irregular borders and they are usually large - about 5.

6 cm in diameter. CT scan is the preferred method for making the diagnosis of adrenal tumors. Cancers of the adrenal are highly malignant and metastases are very common. It is urgent to make the diagnosis as early as you can so you can subject these patients.

As far as the treatment for ovarian androgen-producing tumors are concerned, the extent of surgery would depend on the age of your patient and the desire for future fertility. If your patient is younger and desires future fertility, then you have to limit surgery to unilateral oophorectomy. However, if the patient is older and doesn't desire future fertility, then it would be safer to perform bilateral salpingo-oophorectomy.

The vast majority of patients you are going to see are going to have a non-neoplastic cause for their androgen excess. Many of your patients, maybe sixty-five to eighty-five percent, will have androgen excess. About two to five percent of your patients may have late onset congenital adrenal hyperplasia. Others - maybe fifteen to twenty-five percent, will have idiopathic hirsutism. Here again, the first step in evaluating such a patient is to get serum testosterone, DHEAS and 17-hydroxyprogesterone. Moderate elevations in the level of testosterone - 1 to 1.5 - is an indication of polycystic ovary syndrome. But you also have to remember that as much as forty percent of patients with polycystic ovary syndrome.

Polycystic ovary syndrome occurs in about five to ten percent of reproductive-age females. If you are talking about millions of women, maybe two to three million of women in this country are afflicted with polycystic ovary syndrome.

A number of years ago, Gulzier reported on the frequency of symptoms and signs in patients with proven polycystic ovary syndrome - obesity, hirsutism, dysfunctional uterine bleeding and infertility. These are the types of problems that would bring these patients to you for treatment. Hirsutism is of the midline type; facial hirsutism - sideburns, chin, upper lip, chest, below the umbilicus. The ovaries are usually enlarged - about eighty percent of the time - bilaterally.

10 mm in diameter. If you look at these under a microscope, you can appreciate the scarcity of granulosa cells - there are one or two layers of granulosa cells. The most striking feature of these ovaries is the hyperplasia of the thecal cells. The thecal cells respond to an increasing amount of luteinizing hormone and they would be producing androgens. They produce androstenedione.

The pathogenesis of polycystic ovary syndrome has been debated for years. A number of years ago, it was thought that maybe these patients had exposed to an exaggerated adrenarche; they had been under stress. And because of the increased ACTH, the androgen production by the adrenals had increased and part of that androgen would be converted to estrogen and this is acyclic, extraglandular estrogen production. This would be a steady state of anovulation.

Recently, it has been appreciated that many patients with polycystic ovary syndrome would also have insulin resistance. We know that the insulin would augment the reaction of thecal cells to respond to luteinizing hormone by producing more and more androgen. At the same time, insulin would also reduce testosterone-binding globulin so that the free fraction of testosterone would be elevated. Insulin also would reduce IGF binding proteins, so IGF would be more available.

If you have a patient with an increasing level of 17-hydroxyprogesterone, over 8 nanograms per milliliter, then you make the diagnosis of congenital adrenal hyperplasia. Congenital adrenal hyperplasia, in classical form, would be diagnosed in the presence of ambiguous external genitalia. In partial form of enzymatic deficiency, the patient might escape androgen excess in utero; they would escape androgen excess during childhood.

21-hydroxylase deficiency is the most common enzymatic deficiency in these patients. Because of the decrease in the synthesis of cortisol, ACTH would be unrestrained, ACTH would over-stimulate the adrenals, and all of the steroids prior to this block would be increased, including 17-hydroxyprogesterone, and through the 17,20 desmolase activity, that would be converted.

Another virilizing congenital adrenal hyperplasia which is much less common than 21-hydroxylase is 11-hydroxylase deficiency. Through the same mechanism, there would be unrestrained ACTH; there would be over-production of 17-hydroxyprogesterone and androgens in the adrenals, but at the same time, there is over-production of 11-deoxycortisol and 11-desoxycorticosterone. These patients are not only hyperandrogenic, but they could also be hypertensive.

Some of your patients with late onset congenital adrenal hyperplasia might have such a mild enzymatic deficiency that if you measure the level of 17-hydroxyprogesterone in basal condition, when you send the patient to lab at 8:00 or 9:00, that would be within normal limits. But if these patients would be subjected to stress, the increase in the level of 17-hydroxyprogesterone could not be processed adequately because of the limitations of enzyme to cortisol. These are the patients that will show androgen excess. We can't subject the patient to stress, but we can challenge them with ACTH in order to find out about this kind of problem. Basically, you would give them a bolus of Cortrosyn, 0.25 milligrams, and you would measure the 17-hydroxyprogesterone after 60 minutes. If the level of 17-hydroxyprogesterone goes above 12 nanograms, you have made the diagnosis of late onset congenital adrenal hyperplasia.

At times, you may want to rule out the possibility of Cushing's syndrome. The patient may be hirsute and may be obese. There are some practical and very simple methods to rule out the possibility of Cushing's syndrome. One of the methods would be overnight dexamethasone suppression; you would give the patient 1 milligram of dexamethasone the night before and run the cortisol level the next morning at 8:00. If the cortisol is less than 5 micrograms percent, you have to rule out the possibility of Cushing's syndrome.