Intermittent Cushing's disease in hirsute women

Abstract

Clinical symptoms of Cushing's syndrome were recognized in approximately 23 of 97 successive hirsute women attending the Endocrinological Department of the Women's Hospital. Endocrine and radiological examinations ultimately confirmed Cushing's syndrome caused by pituitary microadenomas (Cushing's disease) in only 2 women. In 17 of the remaining 21 patients suspected of having Cushing's disease hypercortisolism could not be diagnosed by classical endocrine tests. Thus further endocrinologial tests as corticotrophin releasing hormone (CRH)-tests (100 micrograms i.v.) and insulin tolerance tests were initiated including serum and stress-free salivary cortisol profiles during the day. Diurnal cortisol profiles showed higher values in the morning than during the night, but intermittent elevated cortisol concentrations could be detected. Finally, seven patients could be classified as suffering from a special form of pituitary ACTH-dependent hypercortisolism, named intermittent Cushing's disease (ICD). It is characterized by severe Cushingoid symptoms like marked central adiposity, purple striae, hirsutism and acne, intermittently increased cortisol concentrations, no cortisol response to hypoglycaemia, but preservation of some diurnal variation of serum or saliva cortisol. Three of these seven patients had diagnostic transsphenoidal neurosurgery and pituitary ACTH-producing microadenomas were removed in two women. Repeated determinations of the circadian rhythm of cortisol in saliva samples in combination with an overnight 1 mg dexamethasone suppression and an insulin stimulation test, are recommended to diagnose patients with suspicion on ICD even in an outpatient clinic.