Late-onset isolated ACTH deficiency

Late-onset isolated ACTH deficiency (also known as isolated adrenocorticotropic hormone deficiency or isolated corticotropin deficiency) is a rare endocrine disorder characterized by insufficient production of adrenocorticotropic hormone (ACTH) by the anterior pituitary gland, occurring in adulthood without deficiency of other pituitary hormones. ACTH is the primary hormone that stimulates the adrenal glands to produce cortisol, a vital stress hormone. When ACTH secretion is impaired, the adrenal glands fail to produce adequate cortisol, leading to secondary adrenal insufficiency. Unlike congenital forms, this condition manifests later in life, often in middle-aged or elderly adults, and may be associated with autoimmune mechanisms, including lymphocytic hypophysitis targeting corticotroph cells. An association with anti-pituitary antibodies has been reported in some patients. Key symptoms include profound fatigue, generalized weakness, anorexia, weight loss, nausea, vomiting, hypotension, and hyponatremia (low blood sodium). Patients may present with acute adrenal crisis triggered by physiological stress such as infection, surgery, or trauma, which can be life-threatening if not promptly recognized and treated. Hypoglycemia may also occur. Unlike primary adrenal insufficiency (Addison's disease), hyperpigmentation is typically absent because ACTH levels are low rather than elevated, and aldosterone production is generally preserved since it is primarily regulated by the renin-angiotensin system rather than ACTH. Diagnosis is established through laboratory findings of low morning serum cortisol with inappropriately low or undetectable ACTH levels, confirmed by stimulation tests such as the insulin tolerance test or CRH stimulation test. MRI of the pituitary is performed to exclude structural lesions. Treatment consists of lifelong glucocorticoid replacement therapy, typically with oral hydrocortisone administered in divided doses to mimic the physiological cortisol rhythm. Patients must be educated about stress dosing — increasing their glucocorticoid dose during illness, injury, or surgery — and should carry emergency identification and injectable hydrocortisone for adrenal crisis prevention. With appropriate hormone replacement and patient education, individuals with this condition can lead relatively normal lives.

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