Androgens in Health and Disease.pdf - E Library

126 Legro
Virilization presents with a variety of peripheral effects. Acne and hirsutism are
invariably present. In virilization balding in women tends to present with centripetal
balding and frontal recession more characteristic of androgenic alopecia in men, as
opposed to the more indolent presentation of androgenic alopecia in women with a
generalized thinning of the crown region (3). A deepening of the voice has been reported
in women with androgen-secreting tumors or undergoing exogenous androgen treatment
(this does not necessarily improve after removal of the androgen excess). Increase in the
size of the larynx is one factor in the voice change. Clitoromegaly is defined as a clitoral
index greater than 35 mm 2 (the clitoral index is the product of the sagittal and transverse
diameters of the glans of the clitoris) (4). In normal women, these diameters are in the
range of 5 mm each. The degree of clitoral enlargement correlates with the degree of
androgen excess. Androgens can lead to body composition changes especially in the
upper body, with increased muscle mass and decreased fat mass. This is accompanied
by breast atrophy.
Differential Diagnosis
The differential diagnosis of androgen excess leading to virilization, especially combined
with a sudden onset and rapid progression will always begin and end with tumors
or dysfunctional states, usually of the ovary and, less commonly, of the adrenal. The most
common androgen-producing tumor in a premenopausal woman is a Sertoli–Leydig cell
tumor. Any large ovarian tumor can produce androgens indirectly by causing hyperplasia
of the surrounding normal stroma (i.e., benign cystic teratomas, dysgerminomas,
epithelial tumors). The vast majority of ovarian androgen-secreting tumors are benign.
Adrenal tumors are rare, with an estimated incidence of two cases per one million
persons per year, these are equally divided among adenomas and carcinomas. The age
of onset in adults peaks in the fifth decade. Virilization can accompany both tumors
primarily producing androgens and tumors primarily producing cortisol (Cushing’s
syndrome). A long history of symptoms, as in the case with an ovarian tumor does not
exclude the presence of an adrenocortical neoplasm.
Dysfunctional states of the ovary, primarily hyperthecosis may also result in marked
androgen excess. In stromal hyperthecosis, most of the ovarian androgen overproduction
results from hyperplasia of the ovarian stroma and not from the accumulation of
small follicles, as is the case with PCOS. Most women with stromal hyperthecosis have
severe hyperinsulinemia, which may be the stimulus for stromal androgen overproduction.
It has been reported in both premenopausal and postmenopausal women,
often with coexisting sequelae of the insulin-resistance syndrome such as dyslipidemia
and glucose intolerance. Surgery, consisting of oophorectomy, usually results in restoration
of both normal insulin levels and androgen levels in the acquired late presentations
of stromal hyperthecosis.
Extreme elevations in insulin levels occur in individuals with insulin-receptor defects.
A substantial number of such defects have now been identified although their overall
prevalence is low. In such individuals, the elevated insulin levels may stimulate excess
ovarian androgen production, resulting in what has been described as the HAIR-AN
syndrome, which represents the coexistence of hyperandrogenism, insulin resistance,
and acanthosis nigricans (5). Also in the differential of androgen excess in an adult
female are the use of exogenous androgens, anabolic steroids in a bodybuilder for
example, or an overdose of androgens in postmenopausal women. Severe hirsutism and