Adrenal insufficiency in HIV/AIDS: a review

ABSTRACT

Introduction

Adrenal insufficiency (AI) is one of the most common potentially life-threatening endocrine complications in people living with human immunodeficiency virus (PLHIV) infection and acquired immunodeficiency syndrome (AIDS).

Areas covered

In this review, the authors explore the definitions of relative AI, primary AI, secondary AI and peripheral glucocorticoid resistance in PLHIV. It also focuses on the pathophysiology, etiology, diagnosis and management of this endocrinopathy in PLHIV. A literature review was conducted through Medline and Google Scholar search on the subject.

Expert opinion

Physicians need to be aware of the endocrinological implications of HIV infection and its treatment, especially CYP3A4 enzyme inhibitors. A high index of clinical suspicion is needed in the detection of AI, especially in PLHIV, as it may present insidiously with nonspecific signs and symptoms and may be potentially life threatening if left untreated. Patients with overt primary and secondary AI require glucocorticoid replacement therapy. Overt primary AI also necessitates mineralocorticoid replacement. On the other hand, the management of relative AI remains controversial. In order to reduce the risk of adrenal crisis during periods of stress, the short-term use of glucocorticoids may be necessary in relative AI.

KEYWORDS:

• Acquired Immunodeficiency Syndrome
• Adrenal Insufficiency
• Glucocorticoid Resistance
• Human Immunodeficiency Virus
• Relative Adrenal Insufficiency

Article highlights

• Adrenal insufficiency (AI) is one of the most common potentially life-threatening endocrine complications in people living with HIV infection and AIDS.

• Whilst clinicians need to exhibit a high level of clinical suspicion for adrenal insufficiency, diagnosing adrenal insufficiency in HIV infection/AIDS may not always be clear cut. This is due to the pathophysiological changes that take place in this subset of patients’ hypothalamic-pituitary-adrenal (HPA) axis.

• Based upon a thorough assessment of the patient’s clinical presentation together with hormonal and biochemical investigations, one may be able to rule out adrenal insufficiency or categorize patients into relative adrenal insufficiency, primary adrenal insufficiency, secondary adrenal insufficiency or peripheral glucocorticoid resistance. This is important as the correct diagnosis will determine management.

• Patients with HIV infection/AIDS suspected of having adrenal insufficiency should have their current and previous drug history rigorously assessed for cytochrome P450 enzyme inducers, 11-β hydroxylase enzyme inhibitors and CYP3A4 enzyme inhibitors especially when such patients are taking glucocorticoids.

• Relative adrenal insufficiency or critical illness-related corticosteroid insufficiency may become apparent in patients with subclinical adrenal insufficiency since there is an inadequate cortisol response in proportion to the degree of stress present. Glucocorticoid replacement therapy during such periods of stress may be beneficial.

• Adrenal insufficiency is characterized by persistently low serum cortisol levels (<100nmol/L) or failure to achieve a post-ACTH stimulated cortisol level of >500nmol/L. A plasma ACTH twice the upper limit of the reference range is consistent with primary AI, whereas an inappropriately low or normal ACTH level is indicative of secondary AI. Patients with overt primary and secondary AI require glucocorticoid replacement therapy. Overt primary AI also necessitates mineralocorticoid replacement.

• Peripheral glucocorticoid resistance is defined by an elevated basal cortisol level (>938nmol/L) and a cortisol increment of >250nmol/L following ACTH stimulation. It is also characterized by an elevated ACTH level and resistance of the HPA axis to dexamethasone suppression. AIDS patients with glucocorticoid resistance mainly present with symptoms of AI and usually do not have symptoms of mineralocorticoid and androgen excess. Thus, AIDS patients probably do not need treatment in this regard, however, this matter needs to be evaluated further in future studies.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.