Endocrinol Metab.  2019 Jun;34(2):95-105. 10.3803/EnM.2019.34.2.95.

Human Immunodeficiency Virus Infection and the Endocrine System

Affiliations
  • 1Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel. Yonagr@tlvmc.gov.il
  • 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abstract

In the current era of effective antiretroviral therapies (ARTs), human immunodeficiency virus (HIV) infection became a chronic disorder that requires long term follow-up. Among other medical issues, these patients may develop endocrine problems, specific to HIV infection and its treatment. The purpose of this review is to give an overview of common endocrine complications associated with HIV infection, and to propose diagnostic and therapeutic strategies. HIV can affect the endocrine system at several levels. Adrenal and gonadal dysfunction, osteoporosis with increased fracture risk, dyslipidemia with increased cardiovascular risk, are some of the endocrine disorders prevalent in HIV-infected patients that may negatively influence quality of life, and increase morbidity and mortality. While ARTs have dramatically increased life expectancy in the HIV-infected population, they are not devoid of adverse effects, including endocrine dysfunction. Physicians caring for HIV-infected patients should be knowledgeable and exercise a high index of suspicion for the diagnosis of endocrine abnormalities, and in particular be aware of those that can be life threatening. Endocrine evaluation should follow the same strategies as in the general population, including prevention, early detection, and treatment.

Keyword

HIV; Anti-retroviral agents; Endocrine system diseases; HIV-associated lipodystrophy syndrome; Diabetes mellitus; Hyperlipidemias; Osteoporosis

MeSH Terms

Anti-Retroviral Agents
Diabetes Mellitus
Diagnosis
Dyslipidemias
Endocrine System Diseases
Endocrine System*
Follow-Up Studies
Gonads
HIV Infections
HIV*
HIV-Associated Lipodystrophy Syndrome
Humans*
Hyperlipidemias
Life Expectancy
Mortality
Osteoporosis
Quality of Life
Anti-Retroviral Agents

Reference

1. Avert. Global HIV and AIDS statistics [Internet]. Brighton: Avert;c2017. cited 2019 Mar 26. Available from: http://www.avert.org/worldstats.htm.
2. Raffi F, Brisseau JM, Planchon B, Remi JP, Barrier JH, Grolleau JY. Endocrine function in 98 HIV-infected patients: a prospective study. AIDS. 1991; 5:729–733.
3. 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; 45:738–746.
4. Poretsky L, Can S, Zumoff B. Testicular dysfunction in human immunodeficiency virus-infected men. Metabolism. 1995; 44:946–953.
Article
5. Graef AS, Gonzalez SS, Baca VR, Ramirez ML, Daza LB, Blanco FF, et al. High serum prolactin levels in asymptomatic HIV-infected patients and in patients with acquired immunodeficiency syndrome. Clin Immunol Immunopathol. 1994; 72:390–393.
Article
6. Ram S, Acharya S, Fernando JJ, Anderson NR, Gama R. Serum prolactin in human immunodeficiency virus infection. Clin Lab. 2004; 50:617–620.
7. Heijligenberg R, Sauerwein HP, Brabant G, Endert E, Hommes MJ, Romijn JA. Circadian growth hormone secretion in asymptomatic human immune deficiency virus infection and acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1996; 81:4028–4032.
Article
8. Rietschel P, Hadigan C, Corcoran C, Stanley T, Neubauer G, Gertner J, et al. Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy. J Clin Endocrinol Metab. 2001; 86:504–510.
Article
9. Rochira V, Guaraldi G. Growth hormone deficiency and human immunodeficiency virus. Best Pract Res Clin Endocrinol Metab. 2017; 31:91–111.
Article
10. Hutchinson J, Murphy M, Harries R, Skinner CJ. Galactorrhoea and hyperprolactinaemia associated with protease-inhibitors. Lancet. 2000; 356:1003–1004.
Article
11. Membreno L, Irony I, Dere W, Klein R, Biglieri EG, Cobb E. Adrenocortical function in acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1987; 65:482–487.
Article
12. Glasgow BJ, Steinsapir KD, Anders K, Layfield LJ. Adrenal pathology in the acquired immune deficiency syndrome. Am J Clin Pathol. 1985; 84:594–597.
Article
13. Grinspoon S, Corcoran C, Stanley T, Rabe J, Wilkie S. Mechanisms of androgen deficiency in human immunodeficiency virus-infected women with the wasting syndrome. J Clin Endocrinol Metab. 2001; 86:4120–4126.
Article
14. Villette JM, Bourin P, Doinel C, Mansour I, Fiet J, Boudou P, 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; 70:572–577.
Article
15. Kalin MF, Poretsky L, Seres DS, Zumoff B. Hyporeninemic hypoaldosteronism associated with acquired immune deficiency syndrome. Am J Med. 1987; 82:1035–1038.
Article
16. Mirza FS, Luthra P, Chirch L. Endocrinological aspects of HIV infection. J Endocrinol Invest. 2018; 41:881–899.
Article
17. Elliot ER, Theodoraki A, Jain LR, Marshall NJ, Boffito M, Baldeweg SE, et al. Iatrogenic Cushing's syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies. Clin Med (Lond). 2016; 16:412–418.
Article
18. Hyle EP, Wood BR, Backman ES, Noubary F, Hwang J, Lu Z, 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; 63:602–608.
Article
19. Rochira V, Zirilli L, Orlando G, Santi D, Brigante G, Diazzi C, et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011; 6:e28512.
Article
20. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95:2536–2559.
Article
21. Bannister P, Handley T, Chapman C, Losowsky MS. Hypogonadism in chronic liver disease: impaired release of luteinising hormone. Br Med J. 1986; 293:1191–1193.
Article
22. Clark RA, Mulligan K, Stamenovic E, Chang B, Watts H, Andersen J, et al. Frequency of anovulation and early menopause among women enrolled in selected adult AIDS clinical trials group studies. J Infect Dis. 2001; 184:1325–1327.
Article
23. Dube MP, Parker RA, Mulligan K, Tebas P, Robbins GK, Roubenoff R, et al. Effects of potent antiretroviral therapy on free testosterone levels and fat-free mass in men in a prospective, randomized trial: A5005s, a substudy of AIDS Clinical Trials Group Study 384. Clin Infect Dis. 2007; 45:120–126.
Article
24. Wunder DM, Bersinger NA, Fux CA, Mueller NJ, Hirschel B, Cavassini M, et al. Hypogonadism in HIV-1-infected men is common and does not resolve during antiretroviral therapy. Antivir Ther. 2007; 12:261–265.
25. Bourdoux PP, De Wit SA, Servais GM, Clumeck N, Bonnyns MA. Biochemical thyroid profile in patients infected with the human immunodeficiency virus. Thyroid. 1991; 1:147–149.
Article
26. Grinspoon SK, Bilezikian JP. HIV disease and the endocrine system. N Engl J Med. 1992; 327:1360–1365.
Article
27. Madge S, Smith CJ, Lampe FC, Thomas M, Johnson MA, Youle M, et al. No association between HIV disease and its treatment and thyroid function. HIV Med. 2007; 8:22–27.
Article
28. Hoffmann CJ, Brown TT. Thyroid function abnormalities in HIV-infected patients. Clin Infect Dis. 2007; 45:488–494.
29. Chen F, Day SL, Metcalfe RA, Sethi G, Kapembwa MS, Brook MG, et al. Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease. Medicine. 2005; 84:98–106.
Article
30. Madeddu G, Spanu A, Chessa F, Calia GM, Lovigu C, Solinas P, et al. Thyroid function in human immunodeficiency virus patients treated with highly active antiretroviral therapy (HAART): a longitudinal study. Clin Endocrinol (Oxf). 2006; 64:375–383.
Article
31. Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med. 1995; 332:305–311.
32. Hellman P, Albert J, Gidlund M, Klareskog L, Rastad J, Akerstrom G, et al. Impaired parathyroid hormone release in human immunodeficiency virus infection. AIDS Res Hum Retroviruses. 1994; 10:391–394.
Article
33. Brown TT, Hoy J, Borderi M, Guaraldi G, Renjifo B, Vescini F, et al. Recommendations for evaluation and management of bone disease in HIV. Clin Infect Dis. 2015; 60:1242–1251.
Article
34. Perrot S, Aslangul E, Szwebel T, Caillat-Vigneron N, Le Jeunne C. Bone pain due to fractures revealing osteomalacia related to tenofovir-induced proximal renal tubular dysfunction in a human immunodeficiency virus-infected patient. J Clin Rheumatol. 2009; 15:72–74.
Article
35. Brown TT, McComsey GA. Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D. Antivir Ther. 2010; 15:425–429.
Article
36. Yin MT, Brown TT. HIV and bone complications: understudied populations and new management strategies. Curr HIV/AIDS Rep. 2016; 13:349–358.
Article
37. Hellerstein MK, Grunfeld C, Wu K, Christiansen M, Kaempfer S, Kletke C, et al. Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. J Clin Endocrinol Metab. 1993; 76:559–565.
Article
38. Grunfeld C, Pang M, Doerrler W, Shigenaga JK, Jensen P, Feingold KR. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992; 74:1045–1052.
Article
39. Riddler SA, Smit E, Cole SR, Li R, Chmiel JS, Dobs A, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003; 289:2978–2982.
Article
40. Hadigan C, Meigs JB, Corcoran C, Rietschel P, Piecuch S, Basgoz N, et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis. 2001; 32:130–139.
Article
41. Myerson M. Lipid management in human immunodeficiency virus. Endocrinol Metab Clin North Am. 2016; 45:141–169.
Article
42. Rasmussen LD, Mathiesen ER, Kronborg G, Pedersen C, Gerstoft J, Obel N. Risk of diabetes mellitus in persons with and without HIV: a Danish nationwide population-based cohort study. PLoS One. 2012; 7:e44575.
Article
43. Carper MJ, Cade WT, Cam M, Zhang S, Shalev A, Yarasheski KE, et al. HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus. Am J Physiol Endocrinol Metab. 2008; 294:E558–E567.
Article
44. Pedersen KK, Pedersen M, Troseid M, Gaardbo JC, Lund TT, Thomsen C, et al. Microbial translocation in HIV infection is associated with dyslipidemia, insulin resistance, and risk of myocardial infarction. J Acquir Immune Defic Syndr. 2013; 64:425–433.
Article
45. Fleischman A, Johnsen S, Systrom DM, Hrovat M, Farrar CT, Frontera W, et al. Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults. Am J Physiol Endocrinol Metab. 2007; 292:E1666–E1673.
Article
46. Grunfeld C, Kotler DP, Hamadeh R, Tierney A, Wang J, Pierson RN. Hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med. 1989; 86:27–31.
Article
47. Mulligan K, Parker RA, Komarow L, Grinspoon SK, Tebas P, Robbins GK, et al. Mixed patterns of changes in central and peripheral fat following initiation of antiretroviral therapy in a randomized trial. J Acquir Immune Defic Syndr. 2006; 41:590–597.
Article
48. Hammond E, McKinnon E, Nolan D. Human immunodeficiency virus treatment-induced adipose tissue pathology and lipoatrophy: prevalence and metabolic consequences. Clin Infect Dis. 2010; 51:591–599.
Article
49. Jacobson DL, Knox T, Spiegelman D, Skinner S, Gorbach S, Wanke C. Prevalence of, evolution of, and risk factors for fat atrophy and fat deposition in a cohort of HIV-infected men and women. Clin Infect Dis. 2005; 40:1837–1845.
Article
50. Addy CL, Gavrila A, Tsiodras S, Brodovicz K, Karchmer AW, Mantzoros CS. Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. J Clin Endocrinol Metab. 2003; 88:627–636.
Article
51. Sweeney LL, Brennan AM, Mantzoros CS. The role of adipokines in relation to HIV lipodystrophy. AIDS. 2007; 21:895–904.
Article
52. Nagy GS, Tsiodras S, Martin LD, Avihingsanon A, Gavrila A, Hsu WC, et al. Human immunodeficiency virus type 1-related lipoatrophy and lipohypertrophy are associated with serum concentrations of leptin. Clin Infect Dis. 2003; 36:795–802.
Article
53. Ranade K, Geese WJ, Noor M, Flint O, Tebas P, Mulligan K, et al. Genetic analysis implicates resistin in HIV lipodystrophy. AIDS. 2008; 22:1561–1568.
Article
Full Text Links
  • ENM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr