Familial Combined Hyperlipidemia (FCHL) is a common primary dyslipidemia with a complex polygenic inheritance pattern, influenced by metabolic and environmental factors. Long term glucocorticoid therapy may exacerbate dyslipidemia and suppress the hypothalamic–pituitary–adrenal (HPA) axis, resulting in tertiary adrenal insufficiency. This case illustrates a young woman with juvenile gout arthritis who developed severe mixed dyslipidemia and glucocorticoid induced adrenal suppression, highlighting how genetic susceptibility (USF1 and ADIPOQ variants) and chronic steroid exposure interact to drive metabolic dysfunction.

A 20-year-old woman with a six-year history of juvenile gout arthritis was evaluated for refractory dyslipidemia following prolonged oral glucocorticoid use. Clinical and biochemical assessments included fasting lipid profile, uric acid, liver function tests, morning cortisol, and ACTH levels. Imaging comprised hepatic ultrasonography and bone densitometry. Targeted genotyping of USF1 rs3737787 and ADIPOQ rs2241766 was performed. A multidisciplinary management plan involved endocrinology, rheumatology, and ophthalmology teams.

Initial investigations showed LDL-C 263 mg/dL, triglycerides 1163 mg/dL, uric acid 14.4 mg/dL, morning cortisol <1.0 µg/dL, and ACTH 3.5 pg/mL, confirming tertiary adrenal insufficiency. Hepatic ultrasound revealed steatosis, bone densitometry demonstrated osteopenia, and ophthalmologic evaluation identified secondary glaucoma ODS (oculus dexter et sinister). Genetic analysis detected USF1 rs3737787 AG and ADIPOQ rs2241766 TG polymorphisms, suggesting hereditary predisposition compatible with the polygenic nature of FCHL and adipokine-mediated insulin resistance. Therapy included atorvastatin 40 mg/day, fenofibrate 300 mg/day, omega-3 fatty acids 3×1 capsule, allopurinol 300 mg/day, colchicine 0.5 mg/day, and physiologic hydrocortisone 15 mg/day with stress-dose education. After three months, LDL-C improved to 109 mg/dL, triglycerides to 531 mg/dL, and uric acid to 8.4 mg/dL, accompanied by normalization of liver enzymes and improved metabolic stability.

This case highlights the complex interaction between genetic susceptibility (USF1, ADIPOQ) and chronic glucocorticoid exposure leading to extreme dyslipidemia, secondary glaucoma, adrenal suppression, and metabolic dysfunction associated steatotic liver disease (MASLD). Early recognition of gene environment interactions and comprehensive, multidisciplinary management are essential to prevent long-term endocrine and cardiometabolic complications in patients receiving chronic corticosteroids.