ESPE Abstracts

Introduction: Cushing's syndrome(CS) is rare in the pediatric population, and the cause vary with age. Primary pigmented nodular adrenocortical disease (PPNAD) is one of the causes of CS, though it is a rare disorder. It has been proposed that in children with CS, PPNAD should be suspected. Here we report a young boy with CS due to PPNAD associated with a somatic mutation of the PRKACA.

Case Presentation: The child was marked by growth arrest and weight gain for 6 months. No family history or chronic diseases in the past. Physical examination showed: height 112.6 cm （-2.2SD）, wight 39.1kg(+2.9SD), moon face and obesity, hirsutism but no abdominal striae. BP 90/69 mmHg. 8 Am cor 20.10 mg /dl, 0Am Cor 18.50 mg /dl, 8Am ACTH ﹤0.22 pmol/L. A 2 days sequential Liddle’s test revealed the paradoxically increased urinary cortisol levels from baseline(576.60 mg /24h to 1423.36 mg /24h). Magnetic resonance imaging (MRI) showed bilateral adrenal enlargement, mainly on the left side. Thyroid fuction was normal. Thyroid nodular(TR2) was found by thyroid ultrasound. Laparoscopic unilateral adrenalectomy was performed. CS remission was achieved after operation. And the Histological examination showed nodules in the adrenal cortex. Lipofuscin pigment in the cytoplasm was found in some cells. DNA analysis revealed a copy number duplication mutation in the PRKACA in the adrenal. However, genetic testing including the PRKACA and carney complex was negative of the boy and his parents. So a somatic mutation chimera was speculated. According to literature search, the most common PPNAD-related gene mutations reported are PRKAR1A, PDE11A, PDE8B in peripheral blood. Recently, a case of somatic mutation of PRKAR1A leading to PPNAD was reported, which suggested that somatic mutation may be the genetic background of sporadic PPNAD. PRKACA mutation is a rare cause of PPNAD. So far, only several cases of germline mutation have been reported, while somatic mutation has not been reported.

Conclusion: PPNAD should be considered as one of the reasons of CS in young children, though it is rare. This article is the first to report a rare case of PPNAD in children caused by somatic mutation of PRKACA, which enriches the datas on the relationship between clinical phenotype and genotype in such rare diseases, having guiding significance for the diagnosis and treatment of PPNAD.

Keywords: Non ACTH dependent Cushing's syndrome; primary pigmented nodular adrenocortical disease; PRKACA; protein kinase A(PKA)