Coexistence of Familial Acromegaly and Genetic Diabetes Mellitus Linked to Mitochondrial Dysfunction

Abstract

Acromegaly is a rare chronic endocrine disorder caused by excessive secretion of growth hormone (GH), usually from a pituitary adenoma, leading to characteristic somatic changes and multiple systemic complications. A substantial proportion of patients with acromegaly develop endocrine comorbidities, most notably impaired glucose metabolism and diabetes mellitus, due to GH-induced insulin resistance and β-cell dysfunction. We present a clinical case of a 37-year-old male, referred for diagnostic clarification in a specialized endocrine clinic due to an enlarged thyroid gland and distinct acromegaloid features, prompting further investigation. Biochemical testing confirmed the presence of hypersomatotropism, and magnetic resonance imaging (MRI) identified a pituitary macroadenoma, measuring 21 × 13 mm. The patient underwent successful transsphenoidal biportal adenomectomy. Given the positive family history - a sister previously diagnosed with acromegaly, genetic testing was initiated. The patient tested negative for common syndromic causes, including familial isolated pituitary adenomas (FIPA), multiple endocrine neoplasia type 1 and 4 (MEN1, MEN4). Whole exome sequencing revealed pathogenic variants in genes MT-ND5 and MT-ND4, associated with a genetic form of diabetes mellitus. While hyperglycemia may resolve in some patients after successful treatment of acromegaly, persistent diabetes mellitus was observed in our case, likely due to the alterations in MT-ND5 and MT-ND4 genes. This clinical case provides initial evidence suggesting a novel link between familial forms of acromegaly and mitochondrial diabetes, offering new perspectives on shared genetic pathways.