Adrenal insufficiency is uncommon in HIV infection, but can occur as a consequence of infections (HIV-1, cytomegalovirus, toxoplasmosis, mycobacterial infections), neoplastic disease (Kaposi’s sarcoma or other malignancies) or, very rarely, autoimmune disease (Addison’s disease). Adrenal insufficiency is more common in the setting of AIDS, with subnormal stimulated cortisol responses in 26% of tested subjects (41).
The symptoms that should alert a clinician to the possibility of adrenal insufficiency include unexplained fatigue, weight loss, nausea, weakness, postural presyncope, myalgias, arthralgias, sweatiness and confusion. Drug therapy can be associated with reduced synthesis of adrenal hormones (e.g. ketoconazole) or induced metabolism of steroids (e.g. rifampicin, phenytoin) (42). A history of recent withdrawal of oral or inhaled corticosteroid drugs should be sought (43). Clinical features of adrenal insufficiency include cachexia, pigmentation of the skin or oral mucosa, or a postural drop in blood pressure. Pigmentation will not be found in adrenal insufficiency of pituitary origin, due to deficiency of adrenocorticotrophin hormone (ACTH), which is rare. Biochemistry tests may show hyponatremia, hyperkalemia, or hypoglycaemia. The diagnostic test for primary adrenal insufficiency is the short synacthen test, where a normal stimulated cortisol response would exceed 550nmol/L. Secondary adrenal insufficiency (due to pituitary disease) will produce a normal response to cosyntropin testing and can be diagnosed by an insulin-induced hypoglycemia test. Pituitary imaging is indicated in this setting to exclude infiltrative or destructive pathology.
Primary adrenal insufficiency is treated with glucocorticoid and mineralocorticoid therapy. Corticosteroid requirements vary and should be individualised to ensure symptomatic improvement, normalisation of electrolytes and alleviation of any postural blood pressure drop. Examples of glucocorticoid replacement types and doses are: prednisone 2.5-5 mg on waking, 1.0-2.5 mg early afternoon; or cortisone acetate 12.5-25 mg on waking, 10-12.5 mg early afternoon; or hydrocortisone 10-20 mg on waking, 4-8 mg early afternoon. Patients will also require mineralocorticoid support with fludrocortisone. 0.05-0.1 mg/d in two divided doses, adjusted to clinical response in blood pressure, aiming for normotension and no postural drop.
Acute adrenal insufficiency may occur in the setting of acute infection, surgery or other physical stress and may manifest with vomiting, hypotension, hemodynamic shock, coma. It is prevented and treated with intravenous glucocorticoids. For example, intravenous hydrocortisone 50-100mg twice daily with acute illness or at surgery and 1-2 days following surgery, for prevention. Higher doses are required with severe illness, such as hydrocortisone 100mg every 6-8 hours.
People with adrenal insufficiency or chronic corticosteroid therapy use who experience acute minor illness should be advised to take double the usual doses of corticosteroids for 2-5 days, until the illness has passed.
An excess of adrenal hormones (Cushing’s syndrome) can occur in patients receiving HIV protease inhibitors. Interference with the cytochrome p450 3A4 enzyme system results in the reduced elimination of oral and inhaled steroids. Cushing’s syndrome can occur rapidly in patients receiving standard doses of oral steroids, in addition to inhaled steroids (for example, fluticasone), with pituitary-adrenal suppression occurring with long term therapy (43). Cushing’s syndrome should be suspected on historical and clinical evidence and diagnosed by detection of low or undetectable plasma cortisol levels in a clinically Cushingoid patient. Treatment is by reduction of oral steroid doses or gradual reduction in inhaled steroids, where the underlying respiratory disease permits. For those patients receiving inhaled steroids, simple strategies will reduce steroid exposure and its side effects. These include using dosing devices with lower oral cavity deposition (eg aerosolised rather than inhalers) with spacers and always rinsing/gargling and spitting (not swallowing). Other strategies may include changing the inhaled steroid therapy to agents that are not predominantly metabolised by the specific cytochrome p450 isoenzymes.