Isolated ACTH deficiency in adult age – presentation of four new cases

Isolated ACTH deficiency in adults is a rare and highly heterogeneous disorder. Autoimmune involvement or loss of hypothalamic control may play a role, although pathogenesis remains undefined in most cases. Awareness of this disorder is important to avoid potentially fatal consequences for the patient.

Here we present 4 new cases of isolated ACTH deficiency in adult women. Diagnosis was established by low basal concentrations of ACTH and cortisol, and failure of CRH 100µg IV to stimulate these parameters. Detailed examination of other pituitary axes revealed no relevant abnormalities. Other potential causes of ACTH deficiency such as pituitary tumors were excluded. Apart from increased tiredness which was present in all patients symptoms widely varied and included severe fasting hypoglycemia, electrolyte disturbances, gastrointestinal discomfort, hypotonia, muscle and joint pain, and axillary hair loss. Symptoms were accompanied by various endocrine abnormalities that appeared to be secondary to ACTH and glucocorticoid deficiency. These were mainly reversible after hydrocortisone replacement therapy was started. No spontaneous remission from isolated ACTH deficiency was observed.

We propose that the differential diagnosis of isolated ACTH deficiency should be considered in adults presenting with unexplained fatigue. Normal function of other pituitary axes is an unreliable markers for the exclusion of ACTH deficiency.