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 15yr 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.