Preventing Cushing Syndrome: Adrenalectomy in PDE11A-Positive Primary Pigmented Nodular Adrenocortical Disease

A 13.5-year-old girl presented with primary amenorrhea, growth plateau, and osteopenia, without overt stigmata of Cushing syndrome. Family history included inherited primary pigmented nodular adrenocortical disease (PPNAD) due to a PDE11A pathogenic variant (c.919C>T, p.R307X), with her mother having undergone bilateral open adrenalectomy at age 19 for severe Cushing syndrome with fragility hip fractures. Biochemical evaluation showed the typical PPNAD paradoxical cortisol rise following an 8-mg dexamethasone suppression test to 15.6 µg/dL (SI: 364 nmol/L), suppressed adrenocorticotropin, mild late night salivary cortisol elevation, and normal urinary free cortisol, indicating mild adrenal hypercortisolism (AHC). Genetic testing confirmed the PDE11A variant. Imaging via adrenal computed tomography was ostensibly normal. To confirm PPNAD and prevent progression to Cushing syndrome, initial unilateral total right mini back scope adrenalectomy (MBSA) was performed, revealing characteristic pigmented nodules (2-5 mm) on histopathology. Completion left total MBSA followed 3 months later and both operations were performed in under 20 minutes. Postoperatively, the patient recovered rapidly, resumed some linear growth and pubertal progression, and is doing well on glucocorticoid replacement. This case highlights the role of early intervention with MBSA to prevent overt Cushing syndrome in germline PDE11A-mutant PPNAD, contrasting the delayed intervention in prior generations.