Endocrine Disorders

Endocrine dysfunction has not been prominent in HIV infection. Nonetheless, all glands of the endocrine system may be infiltrated with opportunistic infections or malignancies or may be affected by drugs used to treat HIV-related disorders. More recently, hyperlipidemia and lipodystrophy have been associated with the use of highly active antiretroviral therapy, especially with certain protease inhibitors. The specific etiology of these disorder remains unclear. The subtle presentations of endocrine diseases create difficult diagnostic challenges.

Adrenal Gland Dysfunction

The adrenal gland is the endocrine gland most commonly affected in AIDS patients examined at autopsy, although clinical evidence of adrenal insufficiency is observed in <8% of AIDS patients. Widespread lipid depletion and varying degrees of adrenal necrosis are the most prevalent pathologic findings in postmortem examinations. Adrenal invasion by CMV is noted in up to 50% of patients with adrenal pathology. Mycobacterium avium complex, Kaposi's sarcoma, C. neoformans, and Histoplasma capsulatum involve the adrenal glands in 5 to 12% of cases. Drug therapy, with agents such as ketoconazole (adrenal dysfunction) or rifampin (increased clearance of cortisol) may also result in adrenal insufficiency. Fatigue, anorexia, nausea, vomiting, orthostatic hypotension, and hyponatremia are symptoms frequently noted in many HIV-infected patients; however, only a few with these symptoms are actually adrenal insufficient when evaluated using standard laboratory criteria.

Basal 8 _A.M. plasma cortisol levels are usually higher in patients with advanced HIV disease than in asymptomatic patients and uninfected healthy controls. However, other ACTH-dependent steroids, such as desoxycorticosterone (DOC), compound B, and 18-hydroxy-DOC, are not elevated and show a blunted response to corticotropin (ACTH) stimulation, implying subnormal adrenal reserves. Patients who fail to achieve plasma cortisol levels >20 mug per deciliter 60 minutes after ACTH stimulation should be considered to have, or be at high risk of developing, adrenal insufficiency. Plasma ACTH levels are frequently normal or subnormal even when plasma cortisol levels are depressed, suggesting that adrenal insufficiency in some HIV-infected patients is due to a primary pituitary or CNS disorder. Treatment of adrenal insufficiency in HIV-infected patients is the same as in other individuals with abnormal adrenal function.

Hypogonadism

The most common abnormality of endocrine function noted clinically is hypogonadism. Decreased libido occurs in over one half of male patients with AIDS, and impotence, usually associated with low serum testosterone levels, is reported in up to 30% of AIDS patients. Serum gonadotropin levels may be below normal or inappropriately within normal limits in hypogonadal men with AIDS. When pituitary responsiveness to gonadotropin-releasing hormone is assessed in these hypogonadotropic males, normal release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) has been observed, suggesting a hypothalamic basis for the central hypogonadotropism.