eMedicine Specialties > Obstetrics and Gynecology > Reproductive Endocrinology and Infertility
Androgen Excess: Differential Diagnoses & Workup
Updated: Aug 18, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Cushing Syndrome
Polycystic Ovarian Syndrome
Other Problems to Be Considered
Congenital adrenal hyperplasia
Adrenal tumor
Ovarian tumor
Hyperprolactinemia
Idiopathic
Factitious
Workup
Laboratory Studies
- In premenopausal women with hirsutism, clinical practice guidelines from The Endocrine Society recommend basing the decision whether to test for elevated androgen levels on the results of the history and physical examination.3
- In women with isolated mild hirsutism, the guidelines suggest against testing for elevated androgen levels because there is little likelihood of identifying a medical disorder that would change management or outcome.
- The guidelines recommend testing for elevated androgen levels in women with moderate or severe hirsutism and in women with hirsutism of any degree that is sudden in onset; rapidly progressive; or associated with menstrual irregularity or infertility, central obesity, acanthosis nigricans, or clitoromegaly.
- The selection of a laboratory with expertise in androgen determination is crucial. The laboratory must have a reliable reference range and quality control to ensure reproducible androgen determination over a long period, as long-term therapy for hyperandrogenism is often necessary.
- The purpose of laboratory tests is to detect the specific androgens involved, the degree of hypersecretion, and the origin of the androgens. The following are markers of androgen production:
- Adrenal glands: Virtually all DHEAS is produced by the adrenal glands.
- Ovaries: Two thirds of circulating testosterone originates from the ovaries.
- Peripheral production: 3 α -androstanediol glucuronide is a metabolite of DHT and indicates the level of activity of target tissue conversion of testosterone and androstenedione to DHT.
- Follicle-stimulating hormone (FSH), total and free testosterone, 17-hydroxyprogesterone (17-OHP), DHEAS, SHBG, and prolactin should be tested during the initial assessment.
- The test should be performed during the early follicular phase of the menstrual cycle. Test samples should be obtained in the morning because of the diurnal rhythm of adrenal steroids.
- An elevated LH or LH/FSH ratio greater than 2.5 is demonstrable in two thirds of women with PCOS; however, it is not useful in the workup of hirsutism (see Polycystic Ovarian Syndrome).
- Testosterone levels between the upper limit of the reference range and 2 ng/mL (8.92 nmol/L, 200 ng/dL) or 2.5 times the upper range are consistent with PCOS. Values within the reference range may indicate end-organ sensitivity or genetically determined hirsutism.
- Serum testosterone level greater than 2 ng/mL (8.92 nmol/L) or 2.5 times the upper limit of the reference range for the laboratory suggests an ovarian tumor. Adrenal tumors that secrete testosterone have been reported, and markedly elevated adrenal androgens can be converted peripherally to testosterone.
- Not all women with a testosterone level greater than 2 ng/mL have a tumor. To avoid unnecessary surgery and radiographic testing, several samples should be elevated.
- Testing for free testosterone should be limited to those patients who have a sign of hyperandrogenism in the presence of normal levels of testosterone and DHEAS (idiopathic hirsutism).
- Obese women may have relatively high testosterone levels because of reduced SHBG due to hyperinsulinemia.
- 17-OH-progesterone is elevated in the luteal phase, hence the rationale of testing in early follicular phase. CAH due to 21-hydroxylase defect can be screened by measuring 17-OH-progesterone. Tests revealing levels above 2 ng/mL (6.05 nmol/L) need to be repeated and, if elevated, an ACTH stimulation test with 0.25 mg of ACTH (Cortrosyn) must be performed. Levels above 10 ng/mL (30.02 nmol/L) at 1 hour are diagnostic.
- Elevated DHEAS levels indicate an adrenal cause for androgen excess. An adrenal tumor should be suspected if the value is greater than 7 µg/mL (18 µmol/L), and radiographic studies should be undertaken. If no tumor is suspected, then Cushing syndrome should be ruled out, if clinically indicated; see Cortisol studies. Media file 2 is an algorithm that outlines the workup of an elevated DHEAS level.
Algorithm for workup of a dehydroepiandrosterone sulfate (DHEAS) value exceeding 7 mg/mL.
- Prolactin is occasionally elevated in hirsutism. When other test results are normal, prolactin testing is recommended to determine whether bromocriptine might be useful.
- Fasting glucose and insulin should be tested in women who are obese or have PCOS. An elevated insulin level or, even better, a fasting glucose/insulin ratio less than 4.5 indicates insulin resistance.
- Cortisol studies are indicated if the physical examination is consistent with Cushing syndrome and no other explanation can be found for hirsutism in the patient. A 24-hour urinary free cortisol level or an overnight dexamethasone suppression test should be completed.
- Testing for androstanediol glucuronide is useful when testosterone and DHEAS levels are in the reference range. Androstanediol glucuronide levels are frequently elevated in patients with hirsutism who have normal testosterone levels. This test is most useful when considering the use of finasteride.
The following outlines the clinical conclusion for various combinations of testosterone and DHEAS levels.
- Testosterone level greater than 200 ng/d; DHEAS level normal
- Possible diagnoses
- Ovarian neoplasm
- Hyperthecosis
- Workup
- CT scan of adrenals
- Pelvic ultrasonography
- Ovarian and adrenal venous sampling
- Possible diagnoses
- Testosterone level variable; DHEAS level greater than 7µg/mL
- Possible diagnoses
- Adrenal tumor
- Cushing syndrome
- Workup
- Adrenal CT scan
- Dexamethasone suppression test
- Possible diagnoses
- Testosterone level greater than 70 ng/dL; DHEAS level elevated but less than 7µg/mL
- Possible diagnoses
- PCOS
- Adrenal hyperplasia
- Cushing syndrome
- Workup
- No further workup
- Rule out Cushing syndrome
- Rule out CAH
- Possible diagnoses
- Testosterone level normal; DHEAS level normal
- Possible diagnoses
- End-organ sensitivity
- Decreased SHBG
- Workup
- Free testosterone
- 3 α -androstanediol glucuronide
- Possible diagnoses
Imaging Studies
- Ultrasonography allows an accurate evaluation of the ovaries.
- Polycystic ovaries (PCO) are defined on ultrasonography as having 12 or more follicles measuring 2–9 mm in diameter, and/or increased ovarian volume (>10 cm3). The presence of PCO in 1 ovary is sufficient to make a diagnosis. About 20% of healthy patients can have ultrasonographic evidence of PCO and patients with PCOS can have normal looking ovaries.
- Color-flow Doppler is helpful for tumor detection and localization but small hilar cell tumors can be missed. Ultrasonography helps the diagnosis of ovarian hyperthecosis.
- CT scans help in the diagnosis of adrenal androgen – secreting tumors. CT scans are rarely useful or necessary for ovarian tumors.
- MRI can detect some ovarian tumors, although it is more useful for adrenal lesions. Because CT scans and ultrasonography are less expensive, they should be performed first.
- Radionuclide studies: Iodomethyl-norcholesterol (NP-59) can light up steroid-secreting areas of the adrenal gland or ovary. If available, these studies help to differentiate and locate a tumor when other radiographic studies fail to show a tumor.
Other Tests
Functional tests are used in clinical scenarios when the androgen excess origins cannot be attributed.
- 2-day dexamethasone suppression test
- DHEAS, testosterone, and cortisol are measured before and after administration of 8 doses of 0.5 mg of dexamethasone given over a period of 48 hours.
- Adrenal source: Following administration of dexamethasone, testosterone is suppressed more than 40% and DHEAS is suppressed more than 60%.
- Ovarian source: Following administration of dexamethasone, testosterone is not suppressed while DHEAS and cortisol are suppressed.
- Combined source: Following administration of dexamethasone, testosterone suppression is less than 40%.
- If androgens and cortisol fail to suppress following administration of dexamethasone, Cushing syndrome or adrenal cancer must be the cause.
- Synthetic ACTH (Cosyntropin) adrenal stimulation test
- This test is indicated only if a morning early follicular phase 17-OHP is elevated.
- This test helps detect enzyme deficiencies (eg, 21-hydroxylase deficiency) of the adrenal gland.
- Gonadotrophin-releasing hormone (GnRH) stimulation test
- This test is useful to confirm the ovarian origin of the hyperandrogenemia.
- Dexamethasone is used to suppress the adrenal glands while the GnRH analogue stimulates the ovaries.
- Hypersecretion of 17-hydroxyprogesterone confirms the ovarian origin of androgen excess.
- GnRH antagonist (Cetrolix) suppression test
- This test helps determine if the androgen production is gonadotrophin dependent.
- This test is used in the diagnosis of ovarian-secreting tumor.
Procedures
- Ovarian and adrenal vein sampling
- Ovarian and adrenal vein sampling is used when laboratory values indicate a tumor but no tumor can be identified by imaging studies.
- Sampling of blood from the ovarian and adrenal veins helps determine the source of elevated androgen levels and whether 1 or both glands are involved. Involvement of a single gland is highly suggestive of a tumor.
More on Androgen Excess |
| Overview: Androgen Excess |
 Differential Diagnoses & Workup: Androgen Excess |
| Treatment & Medication: Androgen Excess |
| Follow-up: Androgen Excess |
| Multimedia: Androgen Excess |
| References |
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References
Boyd-Woschinko G, Kushner H, Falkner B. Androgen excess is associated with insulin resistance and the development of diabetes in African American women. J Cardiometab Syndr. Fall 2007;2(4):254-9. [Medline].
Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. Nov 1961;21:1440-7. [Medline].
[Guideline] Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, et al. Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. Apr 2008;93(4):1105-20. [Medline]. [Full Text].
[Guideline] The evaluation and treatment of androgen excess. Fertil Steril. Nov 2006;86(5 Suppl 1):S241-7. [Medline].
Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ. Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril. Dec 3 2008;[Medline].
Ibanez L, Lopez-Bermejo A, del Rio L, Enriquez G, Valls C, de Zegher F. Combined low-dose pioglitazone, flutamide, and metformin for women with androgen excess. J Clin Endocrinol Metab. May 2007;92(5):1710-4. [Medline].
Arowojolu AO, Gallo MF, Lopez LM, Grimes DA, Garner SE. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. Jul 8 2009;CD004425. [Medline].
Azziz R, Sanchez LA, Knochenhauer ES, et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab. Feb 2004;89(2):453-62. [Medline].
Balfour JA, McClellan K. Topical eflornithine. Am J Clin Dermatol. 2001;2(3):197-201; discussion 202. [Medline].
Barbieri RL. Hyperandrogenic disorders. Clin Obstet Gynecol. Sep 1990;33(3):640-54. [Medline].
Carmina E. Mild androgen phenotypes. Best Pract Res Clin Endocrinol Metab. Jun 2006;20(2):207-20. [Medline].
Carmina E, Lobo RA. Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab. Jun 1999;84(6):1897-9. [Medline].
Falsetti L, De Fusco D, Eleftheriou G. Treatment of hirsutism by finasteride and flutamide in women with polycystic ovary syndrome. Gynecol Endocrinol. Aug 1997;11(4):251-7. [Medline].
Falsetti L, Gambera A. Comparison of finasteride and flutamide in the treatment of idiopathic hirsutism. Fertil Steril. Jul 1999;72(1):41-6. [Medline].
Friedman CI, Schmidt GE, Kim MH. Serum testosterone concentrations in the evaluation of androgen- producing tumors. Am J Obstet Gynecol. Sep 1 1985;153(1):44-9. [Medline].
Goodman NF, Bledsoe MB, Futterweit W, et al. American Association of Clinical Endocrinologists medical guidelines for the clinical practice for the diagnosis and treatment of hyperandrogenic disorders. Endocr Pract. Mar-Apr 2001;7(2):120-34. [Medline].
Guido M, Romualdi D, Giuliani M, et al. Drospirenone for the treatment of hirsute women with polycystic ovary syndrome: a clinical, endocrinological, metabolic pilot study. J Clin Endocrinol Metab. Jun 2004;89(6):2817-23. [Medline].
Hock DL, Seifer DB. New treatments of hyperandrogenism and hirsutism. Obstet Gynecol Clin North Am. Sep 2000;27(3):567-81, vi-vii. [Medline].
Liepa GU, Sengupta A, Karsies D. Polycystic ovary syndrome (PCOS) and other androgen excess-related conditions: can changes in dietary intake make a difference?. Nutr Clin Pract. Feb 2008;23(1):63-71. [Medline].
Meyer-Bahlburg HF, Dolezal C, Baker SW, New MI. Sexual orientation in women with classical or non-classical congenital adrenal hyperplasia as a function of degree of prenatal androgen excess. Arch Sex Behav. Feb 2008;37(1):85-99. [Medline].
Moghetti P, Toscano V. Treatment of hirsutism and acne in hyperandrogenism. Best Pract Res Clin Endocrinol Metab. Jun 2006;20(2):221-34. [Medline].
Moghetti P, Tosi F, Tosti A. Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a randomized, double blind, placebo-controlled trial. J Clin Endocrinol Metab. Jan 2000;85(1):89-94. [Medline].
Moran C, Knochenhauer ES, Azziz R. Non-classic adrenal hyperplasia in hyperandrogenism: a reappraisal. J Endocrinol Invest. Nov 1998;21(10):707-20. [Medline].
Muderris II, Bayram F, Sahin Y. A comparison between two doses of flutamide (250 mg/d and 500 mg/d) in the treatment of hirsutism. Fertil Steril. Oct 1997;68(4):644-7. [Medline].
New MI. An update of congenital adrenal hyperplasia. Ann N Y Acad Sci. Dec 2004;1038:14-43. [Medline].
Rao S, Malik MA, Wilder L, Mott T. Clinical inquiries. What is the best treatment for mild to moderate acne?. J Fam Pract. Nov 2006;55(11):994-6. [Medline].
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. Jan 2004;81(1):19-25. [Medline].
Seifer DB. Daya S, ed. Evidence-based Obstetrics & Gynecology. Vol 1. 1999:112.
Serafini P, Ablan F, Lobo RA. 5 alpha-Reductase activity in the genital skin of hirsute women. J Clin Endocrinol Metab. Feb 1985;60(2):349-55. [Medline].
Smith SR, Piacquadio DJ, Beger B, Littler C. Eflornithine cream combined with laser therapy in the management of unwanted facial hair growth in women: a randomized trial. Dermatol Surg. Oct 2006;32(10):1237-43. [Medline].
Stanczyk FZ. Diagnosis of hyperandrogenism: biochemical criteria. Best Pract Res Clin Endocrinol Metab. Jun 2006;20(2):177-91. [Medline].
Steinberger E, Rodriguez-Rigau LJ, Smith KD. The prognostic value of acute adrenal suppression and stimulation tests in hyperandrogenic women. Fertil Steril. Feb 1982;37(2):187-92. [Medline].
Thielitz A, Krautheim A, Gollnick H. Update in retinoid therapy of acne. Dermatol Ther. Sep-Oct 2006;19(5):272-9. [Medline].
Van der Spuy ZM, le Roux PA. Cyproterone acetate for hirsutism. Cochrane Database Syst Rev. 2003;(4):CD001125. [Medline].
Wild RA. Obesity, lipids, cardiovascular risk, and androgen excess. Am J Med. Jan 16 1995;98(1A):27S-32S. [Medline].
Witkowski JA, Parish LC. The assessment of acne: an evaluation of grading and lesion counting in the measurement of acne. Clin Dermatol. Sep-Oct 2004;22(5):394-7. [Medline].
Further Reading
Keywords
androgen excess, excessive androgen production, adrenal glands, ovary, endocrine glands, testosterone, dihydrotestosterone, DHT, dehydroepiandrosterone sulfate, DHEAS, dehydroepiandrosterone (DHEA), androstenedione, androstenediol luteinizing hormone, LH, adrenocorticotropic hormone, ACTH, 11-androstenedione, adrenal androgen secretion, albumin, sex hormone-binding globulin, SHBG, congenital adrenal hyperplasia, CAH, enzyme defect, adrenal steroid hormone, cortisol, aldosterone, hyperandrogenism, deoxycorticosterone, DOC, hypertension, hypokalemia, hydroxylase deficiency, 3α-hydroxy-steroid dehydrogenase deficiency, pregnenolone, 17-hydroxy-pregnenolone, cardiovascular disease, CVD, acanthosis nigricans, hirsutism, polycystic ovarian syndrome, PCOS, hyperthecosis, Sertoli-Leydig cell tumor, hilus cell tumor, lipoid cell tumor
