Secondary adrenal insufficiency

Secondary adrenal insufficiency is hypofunction of the adrenal glands caused by a lack of ACTH. Symptoms are similar to those of Addison's disease. Diagnosis is based on clinical and laboratory findings, including low ACTH and plasma cortisol levels. Treatment depends on the cause, but generally involves hydrocortisone.

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Causes secondary adrenal insufficiency.

Secondary adrenal insufficiency may occur with panhypopituitarism, isolated ACTH deficiency, in patients taking glucocorticoids, or after glucocorticoid withdrawal. Insufficient ACTH production may also be caused by a lack of hypothalamic stimulation of ACTH production, which is sometimes called tertiary adrenal insufficiency.

Panhypopituitarism may be secondary to pituitary tumors, craniopharyngiomas in young people, various tumors, granulomas, and, less commonly, infections or trauma that destroy pituitary tissue. Patients taking glucocorticoids for more than 4 weeks may develop insufficient ACTH production, which, during metabolic stress, does not provide sufficient stimulation of the adrenal glands and the production of sufficient glucocorticoids, or these patients may develop adrenal atrophy with no response to ACTH stimulation. These problems may persist for more than 1 year after the end of glucocorticoid therapy.

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Symptoms secondary adrenal insufficiency.

Symptoms and signs are similar to those of Addison's disease. Distinctive clinical and general laboratory features include absence of hyperpigmentation, relatively normal electrolytes and blood urea; hyponatremia, if present, is due to dilution.

Patients with panhypopituitarism experience suppression of thyroid and sexual function, hypoglycemia, and coma may develop in secondary adrenal insufficiency with severe symptoms. Adrenal crisis is most likely in patients receiving treatment for replacement of the function of one endocrine gland, especially when treated with thyroxine without hydrocortisone replacement.

Tests to differentiate primary from secondary adrenal insufficiency are discussed under Addison's disease. Patients with confirmed secondary adrenal insufficiency should undergo CT or MRI of the brain to detect a pituitary tumor or atrophy. The adequacy of the hypothalamic-pituitary-adrenal axis during chronic glucocorticoid therapy can be determined by giving 250 mcg of a synthetic ACTH analog intravenously. At 30 minutes, the plasma cortisol level should be greater than 20 mcg/dL (> 552 nmol/L). The gold standard for testing the hypothalamic-pituitary-adrenal axis is the insulin stress test, which induces hypoglycemia and an increase in cortisol.

The corticotropin-releasing hormone (CRH) test can be used to differentiate between hypothalamic and pituitary variants, but is rarely used in clinical practice. After intravenous administration of 100 μg (or 1 μg/kg) of CRH, the normal response is an increase in plasma ACTH by 30-40 pg/ml; patients with hypothalamic insufficiency usually respond, but not those with pituitary insufficiency.

Treatment secondary adrenal insufficiency.

Glucocorticoid replacement therapy is similar to that in Addison's disease. Each case varies depending on the type and degree of specific hormone deficiency. Fludrocortisone is not required because intact adrenal glands produce aldosterone.

During acute illness or after injury, patients receiving glucocorticoids for non-endocrinological disorders may require additional doses to increase endogenous hydrocortisone production. In panhypopituitarism, other types of pituitary insufficiency must be adequately treated.