Wednesday, March 3, 2010

Cushing Syndrome in the McCune-Albright Syndrome

Rebecca J. Brown, Marilyn H. Kelly,  and Michael T. Collins*

Clinical Endocrinology Branch (R.J.B.), National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20814; and Skeletal Clinical Studies Unit (M.H.K., M.T.C.), Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892

* To whom correspondence should be addressed. E-mail: mc247k@nih.gov.

Context: Cushing syndrome (CS) is a rare but potentially fatal feature of McCune-Albright syndrome (MAS). Optimal management, prognostic features, and long-term follow-up of this disorder have not been described.

Setting: The study was conducted at an academic tertiary care center.

Patients: A total of 112 patients participating in a natural history study at the National Institutes of Health (NIH) were evaluated, and 21 published cases were reviewed.

Interventions: Subjects received observation, medical management, or bilateral adrenalectomy.

Main Outcome Measures: We measured prevalence, prognostic factors, and natural history.

Results: The prevalence of CS among NIH patients was 7.1%. The median age at diagnosis was 3 months. Clinical features included "Cushingoid facies" (66.7%), failure to thrive (60.0%), low birth weight (50.0%), liver disease (36.7%), and heart disease (26.7%). Six patients (20.0%) died, four after adrenalectomy. Death was more likely in patients with comorbid heart disease (odds ratio, 13.3; P < 0.05). Of 23 survivors, 13 underwent adrenalectomy, and 10 exhibited spontaneous resolution. Two patients with spontaneous resolution who were tested later in life (3 and 15 yr after resolution) continued to have low-level, autonomous adrenal function with biochemical adrenal insufficiency. Compared to MAS patients without CS, patients with CS were more likely to have a cognitive/developmental disorder (44.4 vs. 4.8%; P < 0.001; odds ratio, 8.8).

Conclusions: Comorbid heart and liver disease were poor prognostic markers and may indicate the need for prompt adrenalectomy. The high incidence of cognitive disorders indicates a need for close developmental follow-up and parental counseling. Patients with spontaneous resolution of CS may develop adrenal insufficiency, and they require long-term monitoring.

 

From http://jcem.endojournals.org/cgi/content/abstract/jc.2009-2321v1