Endocrine Abstracts

Introduction: MODYs are being identified more frequently but the rarity of some types still precludes in-dept knowledge of their natural course of disease. One of this rare forms is MODY 5, the result of a mutation on the hepatocyte nuclear factor 1 beta (HNF-1B) gene that associates with genitourinary and pancreatic malformations/dysfunction.

Case report: A 24-year-old female was referred to the Endocrinology clinic due to hyperglycaemia identified on pre-operative evaluation for lung lobectomy (Carcinoid tumour). She had also history of ureteropelvic junction stenosis that required surgical intervention at the age of 12 months. Laboratory records from preceding years showed wondering 8h-fasting glycaemia 106–142 mg/dl and maximal A1c of 5.8%, without hemoglobinopathies. Despite recurrent measurements of fasting glycemia 126–142 mg/dl, the OGGT tuned out normal (fasting 88 mg/dl, 2h 90 mg/dl). Family history of Diabetes was denied, apart from the gestational diabetes of her mother. Physical examination did not reveal acanthosis, cushingoid nor acromegaloid features and her BMI was 20.6 kg/m². Anti-islet-cell and glutamate decarboxylase autoantibodies were negative, C-peptide levels were low-normal (0.9–1.8 ng/ml), fasting insulin levels and HOMA-IR did not suggest insulin resistance. Creatinemia, proteinuria, magnesemia and uricemia were normal. Renal US showed the known unilateral hydronephrosis plus bilateral microlithiasis, one simple cyst and a mass suggestive of angiomyolipoma. Despite the absence of family history, the suspicion of a MODY form of diabetes was confirmed by genetic testing and identification of a deletion on the HNF1B gene. Systematic revision of common associated anomalies further identified a bicornuate uterus. She complied with a regimen of diet and regular exercise that was able to maintain euglycemia for 4 years. Today she is medicated with metformin with good glycaemic control and well-preserved renal and retinal function. Her father and grandfather had undiagnosed diabetes.

Messages: Despite de AD inheritance of MODY, family history is not always reported. There is double benefit from MODY diagnosis for both patients and family members, concerning early diabetes management and precocious identification of associated malformations. Diabetes and developmental genitourinary malformations should always raise suspicion of MODY 5. The magnitude of hyperglycaemia in MODY 5 reports is highly variable and though there is progressive pancreatic failure, initially, hyperglycaemia may present intermittently. Progression to renal dysfunction is also heterogeneous but strict surveillance is mandatory once renal function may be highly compromised due to the combination of diabetes, ureteric malformations, renal cysts, urate stones and recurrent urinary infections.