SUN-549 Erratic Medication-Related Malabsorption of L-T4 Associated with Highly Elevated TSH Levels in a Patient with Renal Tubular Acidosis, Thyrotroph Hyperplasia, and Hashimoto's Thyroiditis

Case: A 30-yr-old pregnant woman presented with hypothyroidism at 19 weeks. She had been diagnosed with hypothyroidism 15 years ago and was treated with L-T4. She was told 1-1/2 yr ago that her thyroid levels had normalized and L-T4 was discontinued. Shortly thereafter she became pregnant. Labs then included TSH-37 mU/L (NL: 0.358-3.74) and Free T4 (FT4)-0.52 ng/dL (NL: 0.76-1.46) with elevated Anti-Peroxidase and Anti-Thyroglobulin antibody levels. She was started on L-T4, 25 mcg/d. During the pregnancy, her FT4 levels (0.52 - 1.27) were commensurate with her associated L-T4 dosages (25 - 150 mcg/day), consistent with a mid-FT4 level in accord with her calculated Ideal Body Weight dosage of 94 mcg/day. Likewise, her TSH levels (37 - 1.13) were inversely commensurate with her FT4 levels and L-T4 dosages. She delivered a normal baby, and since has been treated with L-T4, 150-175 mcg/d, and remained clinically euthyroid. Because of renal failure (GFR-36.3) with Type I Renal Tubular Acidosis, she was started on a urine alkalizing agent, sodium citrate/citric acid (SC/CA), 20 mg orally every 6 hrs. Since delivery, the patient’s FT4 levels have been very erratic and non-commensurate with her L-T4 dosages. In the past 14 mos. she has been on L-T4 dosages of 150-175 mcg/d (aver: 172 mcg/d). Her FT4 levels (ranging from 0.17 to 1.51 [aver: 0.89]), however, have continued to correlate very closely with her TSH levels (0.397 to 373 [aver: 68.7]). Notably, her four highest TSH levels were 373, 177, 134 and 122. She credibly insists on full compliance with her L-T4 therapy, never taking the medication within an hour of having breakfast or taking her other medications, which included ferrous sulfate and SC/CA. Interestingly, the highest TSH level recorded before starting SC/CA was only 24.9, associated with a low FT4 level of 0.66. Discussion: Evaluation focused on (1) the high levels of TSH, and (2) the postpartum lack of correlation of her FT4 levels and her L-T4 dosages. Regarding the former, extensive thyrotroph hyperplasia was not evident on pituitary MRI (though not ruling out lesser hyperplasia) and very high TSH levels are occasionally observed in patients hypothyroid for years. Resistance to Thyroid Hormone and TSH-producing pituitary adenoma were not likely in view of the close correlation of her TSH and FT4 levels, and her occasional near-normal TSH and FT4 levels. Human Anti-Mouse Antibodies (HAMA) and Macro-TSH were ruled out by assay. TSH Receptor Resistance to TSH could not be ruled out for lack of available assays and genetic analysis. Her normal absorption of L-T4 during pregnancy argues against chronic intrinsic malabsorption. Conclusion: Malabsorption of L-T4 relating to drug interference from ferrous sulfate and/or GI alkalinization from use of SC/CA, in a patient with thyrotroph hyperplasia from long-term Hashimoto’s hypothyroidism would appear to be the most likely, though complex, explanation.