Chapter 4 Adrenal Insufficiency
Definition and Epidemiology
Primary adrenal insufficiency occurs when the adrenal glands fail to produce enough corticosteroids to meet the body’s needs. Approximately 90% of adrenal mass must be lost before this condition occurs.
Primary adrenal insufficiency is a rare condition, with a prevalence of 40 to 60 cases per million. Historically, tuberculosis accounted for the majority of cases. Currently, autoimmune adrenalitis accounts for approximately 80% of cases, tuberculosis accounts for less than 20%; the remaining 1% of cases are due to other miscellaneous causes (Box 4-1).
Secondary adrenal insufficiency is caused by failure of the pituitary gland to produce enough ACTH to maintain cortisol production by the adrenal glands. Exogenous administration of glucocorticoids is the most common cause of secondary adrenal insufficiency. Non-iatrogenic causes, such as pituitary apoplexy, infarction, hemorrhage, or tumors, are uncommon.
Etiology
We will briefly discuss a few of the more common causes of primary adrenal insufficiency (see Box 4-1).
Autoimmune Adrenalitis
Evidence of autoimmune attack against all three zones of the adrenal cortex is present. Antibodies to 17 alpha hydroxylase and 21 hydroxylase are present in 65% of patients, although the role of these auto-antibodies is unclear. There is an association between autoimmune adrenalitis and other autoimmune diseases, which will be discussed.
Polyglandular Autoimmune Syndrome Type I (PAS I)
The classic triad of PAS I is hypoparathyroidism, chronic mucocutaneous candidiasis, and adrenal insufficiency. PAS I usually presents by age 5, with clinical manifestations complete by age 15.
Box 4-2 Medications That Increase Glucocorticoid Metabolism
Patients treated with these medications may need higher replacement doses of glucocorticoids
Typically, hypoparathyroidism or candidiasis occurs first, with adrenal insufficiency presenting in the early teens.
In some patients, PAS I is also associated with gonadal failure, autoimmune thyroiditis, and type 1 diabetes mellitus. There is no HLA association. PAS I is commonly associated with other autoimmune diseases, such as pernicious anemia, vitiligo, and alopecia. Siblings of the proband should be screened for PAS I at regular screenings.
Polyglandular Autoimmune Syndrome Type II (PAS II)
PAS II is the more common form of polyglandular autoimmune syndrome, and occurs mainly in adults between the third and fifth decades of life. There is at least a 2:1 female predominance. The classic triad is adrenal insufficiency, autoimmune thyroid disease, and type 1 diabetes mellitus.
PAS II is not usually associated with other auto-immune diseases except vitiligo.
Other Causes
Although clinical adrenal insufficiency is rare, the adrenals are involved in up to 85% of cases of terminal tuberculosis. In patients with HIV, atypical mycobacteria, such as mycobacterium avium-intracellulare, may cause adrenal insufficiency. Cytomegalovirus infection is another cause of adrenal insufficiency in patients with HIV.
Disseminated histoplasmosis results in adrenal insufficiency in up to 50% of cases. Other fungal infections, such as paracoccidioidomycosis, blastomycosis, coccidioidomycosis, and cryptococcus cause adrenal insufficiency much less frequently.
Metastatic tumors are a rare cause of adrenal insufficiency, because 90% of total adrenal mass must be destroyed before symptoms develop.
Special Cases
Exogenous glucocorticoid administration is the most common cause of adrenal insufficiency. The administration of greater than 5 mg of prednisone (or equivalent) for longer than three weeks may result in suppression of the hypothalamic–pituitary–adrenal axis, and result in adrenal insufficiency during times of stress or medication non-compliance. These patients should be treated with supplemental glucocorticoids during stressful periods (Box 4-3).
