Altered Leptin Signalling in Adrenal Tumours - Preliminary Study

Leptin and its receptor (LepR) are implicated in tumour biology, but their role across adrenal diseases remains incompletely defined. This study characterised leptin and LepR immunoreactivity in adrenal pathologies and compared these findings with transcript-level data in adrenocortical carcinoma (ACC). Immunohistochemistry was performed on an adrenal tissue microarray including ACC, adrenocortical adenoma (ACA), pheochromocytoma, adrenal hyperplasia, and normal adrenal cortex. Automated digital image analysis quantified staining intensity and the proportion of positive cells. Public datasets were used to compare LEP mRNA expression between ACC and normal adrenal tissue, while exploratory analyses examined associations with sex and age. Leptin immunoreactivity in ACC was lower than in several benign and reference adrenal groups, depending on the quantification readout. ACC showed lower staining intensity than ACA, pheochromocytoma, adrenal hyperplasia, and cancer-adjacent tissue. The proportion of leptin-positive cells was lower in ACC than in normal cortex, cancer-adjacent tissue, adrenal hyperplasia, and pheochromocytoma, but not ACA. LepR staining intensity was lower in ACC than in ACA and pheochromocytoma, but not lower than in normal cortex or adrenal hyperplasia. LEP mRNA was lower in ACC than in normal adrenal tissue; however, expression was very low in both groups, and adipose-lineage content explained about half of the difference. Females showed higher leptin staining intensity than males. In ACC, the proportion of leptin-positive cells was inversely associated with age, whereas in normal cortex it was positively associated with age; LepR showed no sex effect. These findings indicate altered leptin-axis immunoreactivity in malignant adrenocortical disease. As whole tissue cores were analyzed without adjustment for adipose or stromal content, the results should be considered hypothesis-generating and require validation in prospectively characterized cohorts.