Unilateral nodular adrenocortical hyperplasia presenting as Cushing’s syndrome: a case report

Cushing syndrome results from chronic exposure to excess cortisol. Nodular adrenal hyperplasia is usually bilateral and has only a few case reports of unilateral presentation. Biochemically it is presented as hyperaldosteronism or as Cushing’s syndrome. Here, we are reporting a 17-year-old female presenting with weight gain over 5 months and uncontrolled hypertension. Biochemically she was found to have diabetes mellitus, secondary hypothyroidism and hypogonadotrophic hypogonadism due to Cushing’s syndrome of adrenal origin. Unilateral adrenal adenoma/hyperplasia in right adrenal gland was evident by radiology. Histopathological examination was done after laparoscopic adrenalectomy showed nodular adrenocortical hyperplasia in right adrenal mass. Following surgery, clinical features of the patient improved notably. Cushing syndrome due to unilateral nodular adrenocortical hyperplasia is a rare entity. Biochemical evaluation of hypothalamo-pituitary-adrenal axis, radiological evidence and histopathology are the important armaments can guide to final diagnosis. BIRDEM Med J 2022; 12(1): 78-82

Single-cell transcriptome analysis identifies a unique tumor cell type producing multiple hormones in ectopic ACTH and CRH secreting pheochromocytoma

Ectopic Cushing's syndrome due to ectopic ACTH&CRH-secreting by pheochromocytoma is extremely rare and can be fatal if not properly diagnosed. It remains unclear whether a unique cell type is responsible for multiple hormones secreting. In this work, we performed single-cell RNA sequencing to 3 different anatomic tumor tissues and 1 peritumoral tissue based on a rare case with ectopic ACTH&CRH-secreting pheochromocytoma. And in addition to that, 3 adrenal tumor specimens from common pheochromocytoma and adrenocortical adenomas were also involved in the comparison of tumor cellular heterogeneity. A total of 16 cell types in the tumor microenvironment were identified by unbiased cell clustering of single-cell transcriptomic profiles from all specimens. Notably, we identified a novel multi-functionally chromaffin-like cell type with high expression of both POMC (the precursor of ACTH) and CRH, called ACTH+&CRH+ pheochromocyte. We hypothesized that the molecular mechanism of the rare case harbor Cushing's syndrome is due to the identified novel tumor cell type, that is, the secretion of ACTH had a direct effect on the adrenal gland to produce cortisol, while the secretion of CRH can indirectly stimulate the secretion of ACTH from the anterior pituitary. Besides, a new potential marker (GAL) co-expressed with ACTH and CRH might be involved in the regulation of ACTH secretion. The immunohistochemistry results confirmed its multi-functionally chromaffin-like properties with positive staining for CRH, POMC, ACTH, GAL, TH and CgA. Our findings also proved to some extent the heterogeneity of endothelial and immune microenvironment in different adrenal tumor subtypes.

A case of acute exacerbation of chronic hepatitis C during the course of adrenal Cushing's syndrome

A 50-year-old woman with adrenal Cushing’s syndrome and chronic hepatitis C developed an acute exacerbation of chronic hepatitis C before adrenectomy. After administration of Glecaprevir/Pibrentasvir was started, her transaminase levels normalized promptly and a rapid virological response also was achieved. Then laparoscopic left adrenectomy was performed safely.