How best to approach endocrine evaluation in patients with HIV in the era of combined antiretroviral therapy?

Abstract

SummaryEndocrine and metabolic dysfunction has been documented throughout the history of clinical experience with HIV and AIDS. Opportunistic infections such as CMV and TB adrenalitis, tumours affecting endocrine organs, and cachexia and wasting can still be seen, particulary in severely immunocompromised individuals who may be noncompliant with, resistant to, or without access to effective antiretroviral therapy (ART). However, in those with good control of their HIV infection, the profile of endocrinopathy in HIV has largely changed with the advent of highly effective combination ART. The problems that we now more frequently see in people living for many years with low viral loads and good CD4 counts relate to side effects or interactions of therapy. These included adverse metabolic effects of antiretrovirals, most notably dyslipidaemia and lipodystrophy with protease inhibitors, drug-drug interactions, including marked CYP3A4 inhibition with protease inhibitors and autoimmune endocrinopathy as part of an immune reconstitution syndrome after initiation of antiretrovirals. In addition, chronic endocrine and metabolic disorders, including hypogonadism and osteoporosis, occur at higher levels than in the background population, associated with chronic illness, lower body weight and use of both prescribed and nonprescribed drugs. To illustrate my approach to endocrine evaluation in HIV, I will describe a recent patient as the differential diagnoses considered cover the commoner endocrine complications seen. He was 34 years old, had been diagnosed with HIV 4 years previously, had regularly attended follow-up and had been started on antiretrovirals in a planned fashion 4 months previously. His antiretroviral regimen was ritonavir, darunavir and truvada (tenofovir/emtricitabine). He had a good response from an HIV point of view with undetectable viral load and improvement in his CD4 count from 319 to 382 cells/ll (normal range 300-1400) but attended his next HIV clinic appointment feeling unwell with tiredness, erectile dysfunction, loss of libido and general malaise. His thyroid function was normal, TSH 0Á59 mU/l (NR 0Á3-4Á2), fT4 15Á9 pM (NR 9-26), and he had a low testosterone 4Á5 nM, then 7Á2 nM 4 weeks later (NR 10-30 nM) with SHBG 31 nM and nonelevated gonadotrophins. Most worryingly, he had an undetectable 9am cortisol. The HIV unit rapidly arranged a short Synacthen test, which showed baseline cortisol <20 nM, 30-min cortisol of 75 nM and 60-min cortisol of 110 nM. Electrolytes were normal with potassium of 4Á0 mM.Further history in endocrine clinic revealed recent mild headaches and transient increase in appetite which had since resolved. He spontaneously volunteered that his face was fatter with fullness around his neck and weight gain, particularly around the middle. He had noted reduction in libido and erectile dysfunction with loss of morning erections over the last few months, but this was spontaneously resolving. He had some hair loss on his legs but not reduced shaving frequency. He felt tired with red...

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