[A combination of endogenous hypercortisolism and primary hyperparathyroidism: clinical and genetic characteristics].

backgroundA combination of endogenous hypercortisolism and primary hyperparathyroidism (PHPT) occurs rarely, few clinical cases are described in the literature. The causes of the development of such combination are poorly investigated.

aimTo study clinical and genetic characteristics of a combination of endogenous hypercortisolism and PHPT. MATERIALS AND

methodsA retrospective, single-center, cross-sectional, observational study was performed. Clinical characteristics of patients with a combination of endogenous hypercortisolism and PHPT were analyzed. All patients had previously undergone genetic testing as follows: MEN1 Sanger sequencing (n=10), next-generation sequencing of a panel of genes including MEN1 and CDKN1B (n=3), whole-exome sequencing (n=8).

results21 patients (17 females, 4 males) were included in the study: 17 with Cushing's disease (CD) and PHPT, 3 patients with Cushing's syndrome (CS) and PHPT, and one patient with ACTH-ectopic syndrome (ACTH-ES) and PHPT. Among patients with CD and PHPT ten had MEN1 mutations (multiple endocrine neoplasia type 1 syndrome (MEN1)), and seven did not have MEN1 mutations (MEN1 phenocopies). In patients with MEN1 the debut of both CD and PHPT occurred at younger age in comparison to MEN1 phenocopies (p=0,015 and p=0,0006). In 60% of MEN1 CD occured in infancy, and in all children CD was the first manifestation. In 75% of adult MEN1 patients CD was diagnosed after PHPT, whereas in all MEN1 phenocopies PHPT was diagnosed after or during investigation with regard to CD. The majority of MEN1 patients also had gastro-entero- pancreatic neuroendocrine tumors (NETs), and some had lung NETs, whereas patients with MEN1 phenocopies did not have NETs. One patient with CS (bilateral lesions) and PHPT had ARMC5 mutation. In a patient with ACTH-ES and PHPT no mutations were found.

conclusionA combination of endogenous hypercortisolism and PHPT occurs more frequently in females. In children with MEN1 and in MEN1 phenocopies the first manifestation is more frequently CD, while PHPT is diagnosed accidentally during evaluation, whereas in adults with MEN1 the first manifestation is more frequently PHPT. MEN1 mutations can be the cause of a combination of these two endocrine tumor diseases, and, possibly, ARMC5 mutations in cases of CS and PHPT, though in the majority of cases the cause remains unknown. Identification of causes of endogenous hypercortisolism and PHPT co-occurrence can expand our understanding of the mechanisms of endocrine tumor development.