Diagnosis and complications of Cushing's disease: gender-related differences.

Objective: Cushing's disease (CD) presents a remarkable preponderance in female gender, with a female-to-male ratio of 3-8:1. The aim of this study was to evaluate gender-related differences in the presentation of CD, as regards: biochemical indices of hypercortisolism; sensitivity of diagnostic tests; clinical features and complications of disease.

Methods: We retrospectively studied 84 adult patients with CD, 67 women and 17 men, evaluated at diagnosis. We compared the features of the disease between the sexes and analysed the effect of gender on CD complications, adjusted for potential confounders (age, gonadal status, BMI, urinary free cortisol values).

Results: We observed no differences between males and females as regards age at diagnosis, disease duration and BMI. Men, compared with women, presented higher urinary free cortisol values (P < 0·001) and ACTH values (P < 0·05). As regards diagnostic tests, men presented a lower ACTH response to DDAVP stimulation (P < 0·05). The pituitary tumour itself was less easily visualized by pituitary MRI in males compared with females (P < 0·05). Furthermore, some complications of disease were more frequent or more severe in men, in particular hypokalaemia (P < 0·05), hypercoagulable state and osteoporosis at lumbar spine (P < 0·01), with consequent higher risk of vertebral fractures. Male gender was found to be an independent risk factor for dyslipidaemia, severity of hypertension, lumbar osteoporosis and fractures.

Conclusions: Although CD is less frequent in male patients, in this gender, it presents with more florid clinical manifestations and may imply more diagnostic difficulties.