Detection of new potentially pathogenic mutations in two patients with primary pigmented nodular adrenocortical disease (PPNAD) — case reports with literature review


Katarzyna Pasternak-Pietrzak, Constantine A. Stratakis, Elżbieta Moszczyńska, Agnieszka Lecka-Ambroziak, Michał Staniszewski, Urszula Wątrobińska, Charalampos Lyssikatos, Monika Prokop-Piotrkowska, Wiesława Grajkowska, Maciej Pronicki, Mieczysław Szalecki


Primary pigmented nodular adrenocortical disease (PPNAD) is a rare form of ACTH-independent Cushing’s syndrome (CS). Half of patients with PPNAD are sporadic cases and the other half familial.

Material and methods:
We present two patients with PPNAD confirmed by genetic analysis.

In both patients there were no abnormal findings on diagnostic imaging of both adrenals and heart. Patients underwent bilateral two-stage adrenalectomy. Histopathological examination confirmed PPNAD. Genetic testing showed the following mutations in the PRKAR1A gene coding for the regulatory subunit type 1A of the protein kinase A enzyme: c.125dupG (patient 1) and c.15dupT (patient 2). Both these defects lead to inactivation of the PRKAR1A protein and are consequently causative of PPNAD in these patients. Conclusions: The novel mutations presented in this article are considered to be pathogenic for PPNAD.

Key words: Cushing’s syndrome; nodular adrenocortical disease; Carney complex; PPNAD

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