Challenging Diagnostic Workup of a 22-year-old Patient With Primary Pigmented Nodular Adrenocortical Disease

Abstract

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome (CS), presenting diagnostic challenges due to its rarity and its difficult clinical differentiation from other causes of CS. Here, we report the case of a 22-year-old female who developed classical symptoms of hypercortisolism including progressive weight gain, moon facies, and various skin manifestations. Despite biochemical screening confirming ACTH-independent CS, imaging modalities including computed tomography and magnetic resonance imaging showed normal adrenal gland morphology, complicating the localization of cortisol hypersecretion. Subsequent nuclear imaging methods were not indicative of ectopic cortisol production until adrenal vein sampling (AVS) conclusively identified the adrenal glands as the only possible source of cortisol hypersecretion. Eventually, bilateral adrenalectomy led to a significant improvement in symptoms. Pathological examination confirmed the diagnosis of PPNAD, and genetic testing revealed a mutation in the PRKAR1A gene associated with the Carney complex. This case highlights the importance of considering rare etiologies in hypercortisolism diagnosis and describes their challenging diagnostic workup and the utility of AVS in localizing cortisol hypersecretion in PPNAD patients.

Keywords: PPNAD; adrenal vein sampling; carney complex; hypercortisolism; primary pigmented nodular adrenocortical disease.

Figure 1.

(A) Our patient at first examination presenting herself with truncal obesity, abdominal striae, and multiple hematomas. (B) The truncal obesity contrasts with the slim legs of the patient.

Figure 2.

(A) The patient presented herself with moon facies and severe acne. (B) A closer look reveals growth of hair on the upper lip and other parts of the face indicative of hirsutism.

Figure 3.

Adrenalectomy specimen (formalin fixed) showing multiple micro-nodules (< 1 cm diameter) in the adrenal cortex on cut surface. This is the typical macroscopic appearance of primary pigmented nodular adrenocortical disease.

Figure 4.

(A) Histology of the adrenalectomy specimen (hematoxylin and eosin stain). On low power, one can recognize multiple micro-nodules in the adrenal cortex; most of them are associated with the islands of fat tissue. (B) On high power, the cells within the nodules show pronounced anisokaryosis, variable enlargement of the cytoplasm, and marked accumulation of pigment.