Hirsutism Clinical Presentation

Updated: Mar 24, 2017
  • Author: George T Griffing, MD; Chief Editor: Michel E Rivlin, MD  more...
  • Print
Presentation

History

An accurate history of the patient's onset of hirsutism and developmental milestones can be helpful in the etiologic diagnosis.

  • Age of onset
    • Idiopathic hirsutism and the other less-serious causes of hirsutism usually begin at puberty.
    • Conversely, hirsutism that occurs in middle-aged or older women should suggest an adrenal or ovarian tumor.
  • Family history: A patient with a family history of hirsutism is consistent with congenital adrenal hyperplasia (CAH); however, idiopathic hirsutism and polycystic ovary syndrome (PCOS) can also be familial. See presentation in the image below.
    The photograph depicts familial hirsutism in a Pak The photograph depicts familial hirsutism in a Pakistani woman.
  • Hirsutism severity and rate of progression
    • The history of a benign form of hirsutism is usually characterized by pubertal onset with slow progression over many years. This is often true of hirsutism with PCOS.
    • When a history of rapid severe hirsutism or other signs of virilization are obtained, an androgen-secreting tumor is a possibility.
  • Adrenarche and puberty
    • Because the development of pubic hair depends on adrenal androgens, early development points toward CAH.
    • In contrast, ovarian hyperandrogenism is associated with normal adrenarche and delayed menarche or irregular menses.
Next:

Physical

The most important goal in the clinical evaluation of a patient with hirsutism is to rule out significant underlying disease. To do this, seek to understand the cause of hyperandrogenism, if this is present.

  • Excess androgens can be from either an exogenous or an endogenous source.
    • An exogenous source of androgens can usually be elicited by history findings; however, surreptitious androgen use has been reported in female athletes, especially those at a high level of competition.
    • Endogenous androgens originate from either the adrenal cortex or the ovary. Therefore, the evaluation of androgen excess can focus on disorders of these 2 glands. The principal possibilities are tumors of the ovary or the adrenal cortex, Cushing syndrome, CAH, and PCOS. Idiopathic hirsutism is the most common etiology, but it is a diagnosis of exclusion. Therefore, seek other causes first.
  • The initial task in the evaluation of hirsutism via the physical examination is to quantitate the disorder. [7] This task requires that terminal hair, which depends on androgen, be differentiated from vellus hair, which is androgen-independent.
    • Vellus hair is fine, soft, and lightly pigmented. An excess of vellus hair (hypertrichosis) is usually idiopathic, but may be associated with metabolic disorders (eg, hyperthyroidism, anorexia nervosa, porphyria) and with some medications (eg, phenytoin, diazoxide, minoxidil, glucocorticoids, cyclosporine, hexachlorobenzene).
    • By contrast, terminal hair is coarse, curly, and pigmented. Because small amounts of terminal hair are normal in women, quantitation is important.
  • The most widely accepted method of quantitation uses the Ferriman and Gallwey scale. However, use care because this method has significant interobserver variability. In this approach, hair growth is judged in each of 11 androgen-sensitive areas.
    • The grade for each area ranges from 0 (no terminal hair) to 4 (frankly virile).
    • The body areas used to grade hirsutism are (1) the upper lip, (2) chin, (3) chest, (4) leg, (5) thigh, (6) upper arm, (7) forearm, (8) upper back, (9) lower back, (10), upper abdomen, and (11) lower abdomen.
    • Areas such as the axilla and pubis are not included because terminal hair grows in these places at normal androgen levels in women.
    • The total score correlates roughly with the elevation of androgen levels. A woman with a score of 8 or higher is considered to have hirsutism. Most women who seek medical attention for the disorder have scores of 15 or higher. Normal scores have also been established for Turkey (up to 11) and Thailand (up to 3 on the modified Ferriman and Gallwey scale).
  • In women with moderate-to-severe hirsutism (score >15), seek additional signs of hyperandrogenism, including (1) temporal hair recession, (2) oily skin, (3) masculine voice, (4) well-developed musculature, (5) enlargement of the clitoris (>35 mm 2 in surface area), (6) irregular menses, and (7) psychological changes (eg, heightened libido, aggressiveness).
  • The degree to which these clinical factors are present suggests the level of androgen overproduction and, thus, helps to determine the degree of concern for the presence of an underlying disease.
  • The extent of the evaluation for the cause of hirsutism is greater in women who have more severe clinical evidence of masculinization.
  • A thorough abdominal and pelvic examination is important in patients with hirsutism because more than half of androgen-secreting adrenal and ovarian tumors are palpable.
  • Examine the skin for acanthosis nigricans, a manifestation of insulin resistance.
  • Women with hirsutism are usually obese, with increased waist-hip ratios, and are thought to be at an increased risk for atherosclerosis and coronary heart disease. They also have increased bone mineral density scores at the hip and spine. These increases correlate with higher levels of serum free testosterone and estrogen.
Previous
Next:

Causes

Multiple diseases can cause hyperandrogenism and hirsutism. The etiologic forms of hirsutism include endocrine-related, idiopathic, medication-related, and miscellaneous. Endocrine-related causes include adrenocortical disorders and ovarian disorders.

Tumors, Cushing syndrome, and CAH are the adrenocortical causes. Tumors (malignant or benign) and PCOS are the ovarian causes of hirsutism.

Adrenal tumors

Adrenocortical tumors are almost always malignant in patients who present with hirsutism. These tumors are usually large and are associated with a very poor prognosis.

Cushing syndrome

In most instances, Cushing syndrome is caused by glucocorticoid therapy. Because pure glucocorticoids have no androgenic activity, the treatment rarely produces hirsutism. Instead, glucocorticoid therapy is one of the causes of hypertrichosis (see Physical), resulting in vellus hair growth, especially on the face. Thus, excess growth of terminal hair in a patient with the clinical stigmata of Cushing syndrome suggests that the syndrome has an endogenous origin, ie, a pituitary tumor that secretes adrenocorticotropin hormone (ACTH), an adrenal tumor that secretes both cortisol and androgens, or an ectopic tumor that secretes ACTH. The pituitary tumor is the most likely possibility. Cushing syndrome, as a cause of hirsutism, is diagnosed based on the presence of dexamethasone that fails to suppress both androgens and cortisol.

CAH

CAH is actually a family of defects in 1 of 5 enzymes that are responsible for the biosynthesis of cortisol. The resulting cortisol deficiency heightens the secretion of ACTH and thereby leads to adrenal cell proliferation. However, only 3 of these defects can produce hirsutism—21-hydroxylase (most frequent), 3β-hydroxysteroid dehydrogenase (less frequent), and 11-β-hydroxylase deficiency (least frequent).

If CAH is considered, an ACTH-stimulation test is indicated, which is a search for exaggerated quantities of the precursors of cortisol. The stimulation test is required because baseline elevation of these steroids may be in the reference range.

Hyperandrogenism in CAH can cause infertility, but dexamethasone therapy in this setting may induce ovulation. Two important reasons for the diagnosis of CAH are that specific therapy is available and genetic counseling may be necessary. Women with both CAH (21-hydroxylase deficiency) and Cushing syndrome. Have been described with particularly severe hirsutism.

Ovarian tumors

Ovarian tumors may be malignant, and the threat can be serious. Androgen-secreting ovarian tumors are a less-serious threat. The most common among them is arrhenoblastoma, which accounts for less than 1% of all ovarian tumors. In patients with this neoplasm, the serum testosterone level is always elevated, and most patients have amenorrhea and a palpable ovarian mass.

Gonadoblastomas

Gonadoblastomas usually develop in younger persons (aged 10-30 y) who are genetic males with female external genitalia. Nearly half of these tumors are malignant, and many are bilateral. Pelvic examination findings are abnormal because internal female genitalia are absent.

Lipoid cell tumors

Lipoid cell tumors are of 2 histologic types: adrenal-like cells (in younger patients) and hilar or Leydiglike cells (in older patients). These tumors are usually palpable but are seldom malignant. Ovarian tumors, which are even less frequently encountered, include dysgerminomas, Brenner tumors, and cystic granulosa-theca cell tumors.

PCOS

PCOS is the most common ovarian disorder associated with hirsutism. Although the cause of PCOS is not known, the etiology is speculated to be multifactorial. By definition, polycystic ovaries have 20 or more subcapsular follicles, which range from approximately 1-15 mm in diameter. The follicles are at various states of atresia, and hyperplasia of the theca interna, the anatomic source of ovarian androgens, is present. However, the basic abnormalities in PCOS are functional, rather than anatomic, in nature. In particular, levels of luteinizing hormone (LH) are tonically elevated (with LH levels higher than those of follicle-stimulating hormone [FSH]).

Many women with PCOS have insulin resistance, manifested by acanthosis nigricans and elevated plasma insulin levels. Increased insulin levels have been speculated to stimulate androgen production from the ovarian theca interna cells. An experiment in nature supports this hypothesis; women with PCOS who have a specific genetic mutation that lowers insulin resistance have lower hirsutism scores. In addition, the importance of insulin resistance is emphasized by the therapeutic effect of insulin-sensitizing medications (eg, metformin, thiazolidinediones), which restore normal ovarian androgen production and ovulation. [8]

PCOS usually begins at puberty. The incidence has been estimated to be approximately 5% among adolescent girls and adult women in the United States. As noted, the characteristic endocrine abnormality is an elevation in levels of plasma free testosterone that is not suppressed by dexamethasone; however, as many as 50% of patients also show abnormal adrenal androgen secretion.

A study by Villarroel et al indicated that in adolescent girls, hirsutism and oligomenorrhea (persistent menstrual cycles >45 days) have a strong association with the presence of biochemical hyperandrogenism and polycystic ovarian morphology and are therefore useful in the diagnosis of PCOS. [9]

A study by Turan et al indicated that in patients with PCOS, hyperandrogenism contributes to the elevation of hearing thresholds. Among the study’s subjects, the investigators found that increased free testosterone index values and hirsutism scores were associated with a greater extended high-frequency threshold. [10]

Idiopathic hirsutism

Idiopathic hirsutism is a diagnosis of exclusion.

The patient's hirsutism is not caused by well-defined abnormalities such as an androgen-secreting tumor or CAH.

The spectrum of clinical presentations ranges from normal menses and mild hirsutism to amenorrhea and signs of virilization, and testosterone levels range from normal to frankly elevated.

The hirsutism usually begins at puberty.

The disorder is often familial and may be associated with obesity and insulin resistance.

Some classification schemes distinguish patients with elevated adrenal androgen levels (dehydroepiandrosterone sulfate [DHEAS]); in these cases, the disorder is called idiopathic adrenal hyperandrogenism.

Some patients with idiopathic hirsutism have normal plasma androgen levels. As noted above, the underlying mechanism in these patients may be an increase in androgen sensitivity or in 5-alpha-reductase activity in the skin. Increased activity of the enzyme has been demonstrated based on skin biopsy findings and by a finding of elevated urinary levels of dihydrotestosterone metabolites; however, presently, tests for 5-alpha-reductase activity have been used only in research.

Previous