P-63 PREVENTION OF POSSIBLE ABORTIONS IN PREGNANT WOMEN WITH REFETOFF SYNDROME USING METFORMIN AND THUS ACHIEVING A HEALTHY BIRTH
Authors: Cesur Mustafa , Gül Elif Zeynep , Erkol Alperen , Demirci Ibrahim 
Published: January 2025

Introduction

Refetoff syndrome (RS) is an autosomal dominantly inherited rare disease (1/40,000), characterized by thyroid hormone resistance (THR) mostly caused by Thyroid Hormone Receptor Beta (THR-B) gene defect. In the pregnancy period of female RS patients, the probability of live birth may decrease to 15%.

It has been reported in the literature that metformin has effects on the thyroid hormone metabolism. Two female patients with RS being followed up in our center had pregnancy period that resulted in healthy deliveries with the use of metformin. This observation led us to question that metformin treatment may have positive effects in pregnancy of these patients by unknown mechanism of THR. We could not find any case reports or studies in the literature about the pregnancy periods in patients with RS, so we wanted to share our follow-up experience.

Clinical Case

Patient A and B were siblings with genetically proven THR-B mutation (figure 1). Patient A was on metformin treatment for insulin resistance before pregnancy. Her previous two pregnancies resulted in miscarriage following metformin discontinuation in pregnancy. In her third pregnancy under our follow-up, metformin treatment was continued. She completed the pregnancy without any problem and gave birth to healthy twins. Patient B, sister of Patient A, had two pregnancies. She used metformin in both pregnancies because of the favorable outcome in her sister. There were no problems in her pregnancies.

The use of metformin has been shown to decrease TSH levels in patients with prediabetes and diabetes. The studies emphasize that metformin leads to a decrease in TSH values in individuals with subclinical or overt hypothyroidism, but this effect is not seen in healthy euthyroid patients. There are also reports that the effect of metformin leads to a decrease in thyroid hormone levels as well as thyroid gland and nodule size.

In the literature search, we could only find a case report about metformin use in RS. In the report, metformin was started in a 28-year-old male RS patient due to a diabetic picture that developed over time. THR improved after metformin, but after a while metformin was discontinued due to dyspeptic complaints. Following the cessation of metformin THR became severe again.

Although the exact mechanism of the thyroid suppressive effects of metformin is not clearly known, it is hypothesized that metformin, a compound that can cross the blood-brain barrier, increases the number and affinity of thyroid hormone receptors in the pituitary and hypothalamus, causes an increase in central dopaminergic activity, and as a result increases the pituitary feedback effect of peripheral thyroid hormones.

Conclusion

The incidence of healthy births in patients with RS is low. When we combine the limited literature data with our experience, we suggest that metformin treatment may contribute positively to a healthier pregnancy outcome in patients with RS.Figure 1:The pedigree of the family with Refetoff syndrome  Table 1:Summary of pregnancies  Table 2:Blood and genetic results of patients and* The records of two patients with Refetoff syndrome who were followed up in our center were obtained from the electronic health records.