Cushing syndrome in the McCune-Albright syndrome.

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.