Pituitary and adrenal gland dysfunction in HIV-infected patients
- Melissa Weinberg, MD
Melissa Weinberg, MD
- Assistant Clinical Professor of Medicine
- University of California, San Francisco
- Morris Schambelan, MD
Morris Schambelan, MD
- Professor Emeritus of Medicine
- University of California San Francisco
In the early AIDS epidemic, the diverse endocrine manifestations of HIV infection were more often a consequence of opportunistic infections (OIs), neoplasms, or concomitant systemic illness. The widespread use of potent antiretroviral therapy (ART) has led to a decline in the incidence of glandular infiltration by OIs and neoplasms and has generated increased attention toward the metabolic complications of HIV therapy, including insulin resistance, dyslipidemia, and alterations in body fat distribution.
This topic review will address the assessment and management of pituitary and adrenal disorders in patients with HIV/AIDS. Issues related to insulin resistance, bone and calcium disorders, and thyroid dysfunction are discussed elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy" and "Treatment of HIV-associated lipodystrophy" and "Bone and calcium disorders in HIV-infected patients" and "Thyroid gland dysfunction in HIV-infected patients".)
In general, the diagnosis and treatment of a specific endocrinopathy in a patient with HIV infection does not differ from that in an immunocompetent individual. There are, however, some special considerations. HIV infection may cause changes in pituitary and adrenal function that are adaptive and do not require treatment. Furthermore, many of the signs and symptoms of pituitary and adrenal dysfunction are nonspecific and can overlap with other non-endocrine disorders that are common in HIV-infected patients. Finally, many medications that are used to treat HIV infection and its complications can induce endocrine dysfunction (table 1), including affecting pituitary and adrenal hormones.
GLANDULAR INFECTION AND INFILTRATION
Infection by a diverse array of organisms, as well as HIV-associated malignancies (ie, Kaposi's sarcoma and lymphoma), have been detected in the pituitary and adrenal glands (table 2). Such occurrences were far more common prior to the widespread introduction of potent ART, although they may still be observed in patients not receiving ART or who have antiretroviral drug resistant infection.
Tissue is generally required for a definitive diagnosis. When technically feasible, fine needle aspiration (FNA) biopsy of the adrenal gland provides a less invasive alternative to open biopsy. Pheochromocytoma must always be excluded before FNA biopsy of the adrenal gland is performed. Standard functional testing should also be performed since clinically significant endocrine dysfunction may accompany glandular infection or infiltration of the pituitary or adrenal glands.
- Dobs AS, Dempsey MA, Ladenson PW, Polk BF. Endocrine disorders in men infected with human immunodeficiency virus. Am J Med 1988; 84:611.
- Raffi F, Brisseau JM, Planchon B, et al. Endocrine function in 98 HIV-infected patients: a prospective study. AIDS 1991; 5:729.
- Hommes MJ, Romijn JA, Endert E, et al. Hypothyroid-like regulation of the pituitary-thyroid axis in stable human immunodeficiency virus infection. Metabolism 1993; 42:556.
- Wilson LD, Truong MP, Barber AR, Aoki TT. Anterior pitutiary and pitutiary-dependent target organ function in men infected with the human immunodeficiency virus. Metabolism 1996; 45:738.
- Poretsky L, Can S, Zumoff B. Testicular dysfunction in human immunodeficiency virus-infected men. Metabolism 1995; 44:946.
- Graef AS, Gonzalez SS, Baca VR, et al. High serum prolactin levels in asymptomatic HIV-infected patients and in patients with acquired immunodeficiency syndrome. Clin Immunol Immunopathol 1994; 72:390.
- Croxson TS, Chapman WE, Miller LK, et al. Changes in the hypothalamic-pituitary-gonadal axis in human immunodeficiency virus-infected homosexual men. J Clin Endocrinol Metab 1989; 68:317.
- Chernow B, Schooley RT, Dracup K, et al. Serum prolactin concentrations in patients with the acquired immunodeficiency syndrome. Crit Care Med 1990; 18:440.
- Gorman JM, Warne PA, Begg MD, et al. Serum prolactin levels in homosexual and bisexual men with HIV infection. Am J Psychiatry 1992; 149:367.
- Collazos J, Ibarra S, Martínez E, Mayo J. Serum prolactin concentrations in patients infected with human immunodeficiency virus. HIV Clin Trials 2002; 3:133.
- Ram S, Acharya S, Fernando JJ, et al. Serum prolactin in human immunodeficiency virus infection. Clin Lab 2004; 50:617.
- Agarwal A, Soni A, Ciechanowsky M, et al. Hyponatremia in patients with the acquired immunodeficiency syndrome. Nephron 1989; 53:317.
- Heijligenberg R, Sauerwein HP, Brabant G, et al. Circadian growth hormone secretion in asymptomatic human immune deficiency virus infection and acquired immunodeficiency syndrome. J Clin Endocrinol Metab 1996; 81:4028.
- Frost RA, Fuhrer J, Steigbigel R, et al. Wasting in the acquired immune deficiency syndrome is associated with multiple defects in the serum insulin-like growth factor system. Clin Endocrinol (Oxf) 1996; 44:501.
- Rietschel P, Hadigan C, Corcoran C, et al. Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy. J Clin Endocrinol Metab 2001; 86:504.
- Koutkia P, Canavan B, Breu J, Grinspoon S. Growth hormone (GH) responses to GH-releasing hormone-arginine testing in human immunodeficiency virus lipodystrophy. J Clin Endocrinol Metab 2005; 90:32.
- Hutchinson J, Murphy M, Harries R, Skinner CJ. Galactorrhoea and hyperprolactinaemia associated with protease-inhibitors. Lancet 2000; 356:1003.
- Membreno L, Irony I, Dere W, et al. Adrenocortical function in acquired immunodeficiency syndrome. J Clin Endocrinol Metab 1987; 65:482.
- Villette JM, Bourin P, Doinel C, et al. Circadian variations in plasma levels of hypophyseal, adrenocortical and testicular hormones in men infected with human immunodeficiency virus. J Clin Endocrinol Metab 1990; 70:572.
- Lortholary O, Christeff N, Casassus P, et al. Hypothalamo-pituitary-adrenal function in human immunodeficiency virus-infected men. J Clin Endocrinol Metab 1996; 81:791.
- Verges B, Chavanet P, Desgres J, et al. Adrenal function in HIV infected patients. Acta Endocrinol (Copenh) 1989; 121:633.
- Mayo J, Collazos J, Martínez E, Ibarra S. Adrenal function in the human immunodeficiency virus-infected patient. Arch Intern Med 2002; 162:1095.
- Bricaire F, Marche C, Zoubi D, et al. Adrenocortical lesions and AIDS. Lancet 1988; 1:881.
- Welch K, Finkbeiner W, Alpers CE, et al. Autopsy findings in the acquired immune deficiency syndrome. JAMA 1984; 252:1152.
- Eledrisi MS, Verghese AC. Adrenal insufficiency in HIV infection: a review and recommendations. Am J Med Sci 2001; 321:137.
- Kalin MF, Poretsky L, Seres DS, Zumoff B. Hyporeninemic hypoaldosteronism associated with acquired immune deficiency syndrome. Am J Med 1987; 82:1035.
- Schambelan M, Stockigt JR, Biglieri EG. Isolated hypoaldosteronism in adults. A renin-deficiency syndrome. N Engl J Med 1972; 287:573.
- Henderson E, Yang JY, Schwartz A. Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication. AIDS Res Hum Retroviruses 1992; 8:625.
- Yang JY, Schwartz A, Henderson EE. Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA. AIDS Res Hum Retroviruses 1993; 9:747.
- Yang JY, Schwartz A, Henderson EE. Inhibition of 3'azido-3'deoxythymidine-resistant HIV-1 infection by dehydroepiandrosterone in vitro. Biochem Biophys Res Commun 1994; 201:1424.
- Jacobson MA, Fusaro RE, Galmarini M, Lang W. Decreased serum dehydroepiandrosterone is associated with an increased progression of human immunodeficiency virus infection in men with CD4 cell counts of 200-499. J Infect Dis 1991; 164:864.
- Mulder JW, Frissen PH, Krijnen P, et al. Dehydroepiandrosterone as predictor for progression to AIDS in asymptomatic human immunodeficiency virus-infected men. J Infect Dis 1992; 165:413.
- Laudat A, Blum L, Guéchot J, et al. Changes in systemic gonadal and adrenal steroids in asymptomatic human immunodeficiency virus-infected men: relationship with the CD4 cell counts. Eur J Endocrinol 1995; 133:418.
- Piketty C, Jayle D, Leplege A, et al. Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease. Clin Endocrinol (Oxf) 2001; 55:325.
- Abrams DI, Shade SB, Couey P, et al. Dehydroepiandrosterone (DHEA) effects on HIV replication and host immunity: a randomized placebo-controlled study. AIDS Res Hum Retroviruses 2007; 23:77.
- Rabkin JG, McElhiney MC, Rabkin R, et al. Placebo-controlled trial of dehydroepiandrosterone (DHEA) for treatment of nonmajor depression in patients with HIV/AIDS. Am J Psychiatry 2006; 163:59.
- Lo JC, Mulligan K, Tai VW, et al. "Buffalo hump" in men with HIV-1 infection. Lancet 1998; 351:867.
- Yanovski JA, Miller KD, Kino T, et al. Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. J Clin Endocrinol Metab 1999; 84:1925.
- Samaras K, Pett S, Gowers A, et al. Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. J Clin Endocrinol Metab 2005; 90:4394.
- Kedem E, Shahar E, Hassoun G, Pollack S. Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient. J Asthma 2010; 47:830.
- Gray D, Roux P, Carrihill M, Klein M. Adrenal suppression and Cushing's syndrome secondary to ritonavir and budesonide. S Afr Med J 2010; 100:296.
- Yombi JC, Maiter D, Belkhir L, et al. Iatrogenic Cushing's syndrome and secondary adrenal insufficiency after a single intra-articular administration of triamcinolone acetonide in HIV-infected patients treated with ritonavir. Clin Rheumatol 2008; 27 Suppl 2:S79.
- Dort K, Padia S, Wispelwey B, Moore CC. Adrenal suppression due to an interaction between ritonavir and injected triamcinolone: a case report. AIDS Res Ther 2009; 6:10.
- Hyle EP, Wood BR, Backman ES, et al. High frequency of hypothalamic-pituitary-adrenal axis dysfunction after local corticosteroid injection in HIV-infected patients on protease inhibitor therapy. J Acquir Immune Defic Syndr 2013; 63:602.
- Cooper OB, Brown TT, Dobs AS. Opiate drug use: a potential contributor to the endocrine and metabolic complications in human immunodeficiency virus disease. Clin Infect Dis 2003; 37 Suppl 2:S132.
- Grinspoon SK, Biller BM. Clinical review 62: Laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab 1994; 79:923.
- Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med 2004; 350:1629.
- GENERAL PRINCIPLES
- GLANDULAR INFECTION AND INFILTRATION
- PITUITARY GLAND
- Alterations in pituitary function
- The somatotropic axis
- Effects of antiretroviral therapy on pituitary gland function
- Clinical manifestations
- Assessment and treatment of pituitary gland dysfunction
- ADRENAL GLAND
- Alterations in adrenal function
- Dehydroepiandrosterone replacement therapy
- Effects of medications on adrenal function
- - Antiretroviral agents
- - Protease inhibitors with inhaled or injected corticosteroids
- - Other medications frequently used among HIV-infected patients
- Assessment and treatment of adrenal dysfunction
- SUMMARY AND RECOMMENDATIONS
- Pituitary gland
- Adrenal gland