SAT-329 - Frequent recurrence of Graves’ disease in patient with MODY5

Title: Frequent recurrence of Graves’ disease in patient with MODY5
Authors: Nishant Kumar, Avin Pothuloori
Division of Endocrinology, Creighton University Medical Center

Background: MODY5 is a rare form of diabetes resulting from mutation in the HF1B gene. Cases of Graves disease in patients with MODY5 have not been previously reported.
Clinical case: A 29-year-old man with past medical history of MODY 5 diabetes and graves’ disease presented to endocrine for follow up on 9/1/23 clinically euthyroid at time of visit. He had been treated for Graves’ disease from 8/16/22 to 1/5/23 in the past by endocrine with resolution of symptoms at a prior facility. 9/1/23 labs resulted TSH < 0.0008, (0.550 – 4.780 UIU/ml), free t4 1.96 (0.70 – 1.45 ng/dl). He was started on 5 mg of methimazole. Repeat TSH 1/8/24 showed TSH 0.008 (0.550 – 4.780 UIU/ml), free t4 1.65 (0.70 – 1.45 ng/dl). Thyroid function tests normalized 4/2/24, showing TSH 0.916 (0.550 – 4.780 UIU/ml) and free t4 1.18 (0.70 – 1.45 ng/dl). Methimazole was continued until 8/16/24 and discontinued. He biochemically remained in remission until April 2025. 4/2/25 labs showed TSH < 0.01(0.550 – 4.780 UIU/ml), and free T4 2.6(0.70 – 1.45 ng/dl). He was asymptomatic. Methimazole 5 mg was restarted. Next set of labs drawn 9/4/25 showed TSH 0.01(0.550 – 4.780 UIU/ml), free T4 1.8918 (0.70 – 1.45 ng/dl). Following set of labs drawn 2/16/26 showed TSH 1.119(0.550 – 4.780 UIU/ml) and free T4 1.50 (0.70 – 1.45 ng/dl. Methimazole was continued.

Discussion: MODY 5 is a rare form of diabetes resulting from deletions in the HF1B gene on chromosome 17q12. MODY5 accounts for less than 2% of cases of MODY. The estimated prevalence of MODY is 108/ 1 million. As of 8/2023, University of Chicago had 4000 participants with all forms MODY enrolled.
Graves’ disease is typically genetically associated with genes for thyroid receptor, thyroglobulin and genes involved in immunomodulation such as HLA, CD25, CD40, CTLA4, and PTPN22. However, these genes likely do not account for more than 10% of Graves disease and many undetected loci are hypothesized to contribute. Rapid recurrence of Graves’ disease exacerbations may be related to underlying genetic mutation responsible for MODY5. To our knowledge, no case of Graves disease in a patient with MODY5 has ever been reported.

Conclusion: More research is required to make definitive association between MODY5 and Graves’ disease. Though not yet known, underlying genetic correlation may exist between MODY5 and Graves’ disease.

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