Screening for an Endocrine Disorder

A medical history and physical examination directed towards eliciting any symptoms or signs of hyperan-drogenism should be performed. Screening tests for hyperandrogenism include serum DHEAS, total testosterone, free testosterone, and luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio. In some cases additional information can be gained from a serum level of 17-hydroxypregnenolone. These tests should be obtained in the luteal phase of the menstrual cycle (within 2 weeks prior to the onset of menses). If a patient is taking oral contraceptives, any underlying hyperandrogenism would be masked. Therefore, it is required that the patients dis continue oral contraceptives 4-6 weeks prior to the endocrine evaluation.

In women there are three possible sources of androgen production:

(1) The ovary, where androgens are produced under the influence of follicle stimulating hormone (FSH) and luteinizing hormone (LH), which are secreted by the pituitary gland. LH causes the theca cells of the ovary to make androstenedione, which can be converted into testosterone. Testosterone in turn can then be released into the circulation or converted into estrogens by the aromatase enzyme present in the follicular cells of the ovary.

(2) The adrenal gland, which is acted upon by adreno-corticotrophic hormone (ACTH), also secreted by the pituitary, to produce dehydroepiandrosterone (DHEA) that can then be metabolized into more potent androgens such as androstenedione and testosterone.

(3) Within the skin itself, where all the necessary enzymes exist to convert compounds such as DHEA into more potent androgens such as DHT [47].

An elevated level of DHEAS would indicate that the source of androgens is the adrenal gland. Patients with a serum DHEAS greater than 800 ^g/dl may have an adrenal tumor and should be referred to an endocrinologist for further evaluation. Values of DHEAS in the range of 400800 ^g/dl may be associated with congenital adrenal hyperplasia which is most commonly a partial deficiency in the 21-hydroxylase or 11-hydroxylase enzyme in the adrenal gland. Such an enzyme deficiency results in the shunting of steroids into the pathway resulting in increased androgen production.

If the ovary is the source of androgens, this is most commonly indicated by an elevation in testosterone. Serum total testosterone in the range of 150-200 ng/dl or an increased LH/FSH ratio (greater than 2-3) can be found in cases of polycystic ovary disease which can be characterized by irregular menstrual periods, reduced fertility, obesity, insulin resistance and hirsutism (fig. 4). Greater elevations in serum testosterone may indicate an ovarian tumor and appropriate referral should be made. However, an elevated testosterone level does not necessarily preclude an adrenal abnormality. In this case, an additional test, the LH/FSH ratio, can be performed, and an elevated serum level of 17-hydroxyprogesterone would also be indicative of a congenital adrenal hyperplasia, thus enabling an identification of an adrenal source of androgens. There is a significant amount of variation in an individual's serum androgen levels. In cases where abnormal results are obtained, it is recommended to repeat the test before proceeding with therapy or a more extensive work-up.

In the majority of cases of women with acne, serum androgens are completely normal, yet it may nonetheless seem clear that there is a hormonal component to the acne. That is, the acne becomes worse prior to menstruation, for example, and it does in fact respond if treated with hormonal therapy. This dilemma has led to studies that have found that, as a group, women with acne will have higher levels of serum DHEAS, testosterone, and DHT, than those without acne [11, 47]. However, the laboratory values may still be within the normal range. Worth noting is that these values are at the high end of the normal range and that clinical and laboratory data support the use of hormonal therapy in this group in that their acne does respond to the therapy [47].

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