Adrenal insufficiency common in people with HIV, often unrecognised

Adrenal insufficiency – a reduced ability to produce cortisol and other hormones critical for regulating many bodily processes – is common in people with HIV or tuberculosis and needs to be considered as the cause of a host of symptoms, researchers from Uganda report in the journal Open Forum Infectious Diseases.

Adrenal insufficiency, or Addison’s disease, occurs when the adrenal glands that sit above the kidneys make too little of the hormones cortisol and aldosterone. Cortisol helps the body turn food into energy and plays a role in the body’s response to stress. Aldosterone helps the body balance levels of sodium and potassium to keep blood pressure at a healthy level.

Symptoms of adrenal insufficiency can include weight loss, loss of appetite, salt craving, extreme tiredness, dark patches on the skin, fainting, dehydration, nausea, vomiting or abdominal pain. Many of these symptoms are non-specific and could indicate other common conditions, making early diagnosis difficult. Loss of libido and darkening of the skin (especially in sun-exposed areas or around the knees, elbows, palms or the mouth) should increase clinical suspicion of adrenal insufficiency.

In some cases, adrenal insufficiency results in an acute adrenal crisis, which is a medical emergency. Very low cortisol levels can lead to severe weakness and dizziness, tiredness, confusion, severe abdominal and lower back pain, as well as other symptoms seen in cases of ongoing adrenal insufficiency. As a form of shock that can lead to reduced blood flow and organ damage, an acute adrenal crisis needs to be diagnosed quickly and treated with a hydrocortisone injection.

Checking blood levels of cortisol alone may not provide accurate results because levels vary during the day. Adrenal insufficiency is usually diagnosed by several methods that test the body’s ability to make ACTH, the hormone that triggers the adrenal glands to make cortisol:

• Giving a dose of ACTH to check whether the body is able to mount a normal cortisol response (ACTH stimulation test)
• Giving a dose of insulin sufficient to lower blood sugar and then testing glucose, cortisol and ACTH levels
• Giving a dose of the hormone CRH to check whether the body can make ACTH in response to it.

But in cases of acute adrenal crisis, there won't be time to carry out these tests, so doctors need to make decisions on treatment on the basis of symptoms.

Adrenal insufficiency is more common in people with HIV or tuberculosis, but it is unclear how much more common it is in people with HIV than in the rest of the population. General population studies find it affects about six out of one million people in any given year.

Researchers in Uganda carried out a systematic review of studies which had assessed the prevalence, clinical features and predictors of adrenal insufficiency in people with HIV or tuberculosis. To aid diagnosis, they wanted to establish whether adrenal insufficiency has distinctive symptom patterns in people with HIV or tuberculosis and whether any factors raise the risk of developing adrenal insufficiency in these two groups.

The researchers identified 47 studies, 21 in people with tuberculosis and 26 in people with HIV. Most (38) were cross-sectional, although there were four case-control studies involving people with HIV.

Most studies on adrenal insufficiency in people with tuberculosis were carried out in Africa (n=10) or Asia (n=8). Studies in people with HIV were mainly conducted in Asia (n=10), North America (n=6) and Africa (n=5).

The systematic review found seven studies that reported on significant clinical features and predictors in people with HIV. No clinical feature or predictor was common to all studies; CMV antigenemia positivity, low blood sugar (hypoglycemia) and low potassium levels (hypokalemia), eisonophilia >3% and rifampicin treatment were significantly associated with adrenal insufficiency in some studies, as was advanced HIV with symptomatic illness (WHO stage 4 disease).

Eight studies reported on significant clinical features and predictors in people with tuberculosis. Again, no clinical feature or predictor was common to all studies. In some studies, multidrug-resistant TB, abdominal pain, salt craving, muscle pain and an absence of nausea predicted the presence of adrenal insufficiency in people with tuberculosis.

A meta-analysis of studies was carried out to define the global and regional prevalences of adrenal insufficiency. The study populations totalled 1599 people with TB and 2445 people with HIV.

The global pooled prevalence in people with HIV was 28%. Prevalence was highest in studies carried out in Africa (38%) and Asia (29%) and lowest in North America (21%) and Europe (12%). Age and CD4 count were not associated with the pooled prevalence of adrenal insufficiency, but an increased duration since HIV diagnosis was associated with higher prevalence.

In people with tuberculosis, the global pooled prevalence was 33%. Prevalence was highest in studies carried out in Asia (40%) and Africa (23%).

The researchers did not report on the prevalence in people with HIV and TB coinfection.

The study investigators say that the high prevalence of adrenal insufficiency in people with HIV or tuberculosis should raise the suspicion of adrenal insufficiency when doctors encounter patients with HIV or tuberculosis who have non-specific symptoms such as weight loss, muscle or joint pain, abdominal pain, low blood pressure or low blood sugar.