Endocrine Abstracts

The treatment of hypothyroidism is straightforward,replacing with orally L-thyroxine(LT4).However,some factors including malabsorption,pancreas and liver disorders,drug interactions,etc.,may impair the absorption of LT4,and cause therapy failures.In these circumstances,high doses of different oral formulae or parenterally given LT4 may be a solution. Here,we present a case of primary hypothyroidism,resistant to high doses of oral LT4 replacement but,responsive parenteral LT4 administration.

Case: A thirty-eight years old female patient with effort precipitated fatigue,constipation and hair loss was admitted to endocrinology clinic in Jan. 2019. History revealed that she had bilateral total thyroidectomy for papillary thyroid cancer in May 2018. She was given radioactive iodine,100 mCi, in July 2018. Physical exam showed that she had a puffy face,dry skin,decreased hair,and bilateral nonpitting pretibial edema. She was not given any other medications that interact with LT4. At the admission,serum levels of her thyroglobulin,anti-thyroglobulin antibody,freeT4, and TSH were 0.20 ng/ml,3.79 IU/ml, < 0.40 ng/dl and 175 mIU/ml,respectively. She has been given high doses of oral LT4, 1000 mg/day. Antibodies against endomysium and tissue transglutaminases were also negative. Endoscopic examination of upper gastrointestinal tract and biopsies of the duodenum also showed no abnormality. Echocardiographic examination revealed pericardial effusion but normal cardiac output. Dose of LT4 was increased to 1500 mg/day,and added 25 mg T3 thrice a day. A few days later, serum levels of thyroid hormones and TSH were repeated,still showing high TSH and low T4, and pointing therapy failure. Hence, we decided to begin intravenous LT4 therapy. Intravenously,1000 mg/day LT4 was applied and observed no unwanted effects. Thereafter,400 mg/day LT4 was given for three days. Therapy, then, was switched to another regime consisting of 200 mg/day LT4 intramuscularly once a week. This approach resulted in normalization of serum TSH and T4 levels. Abnormalities on physical exam at the admission also improved significantly.

Discussion: Our case is refractory hypothyroidism since unresponsive to very high doses of oral thyroid hormone replacement,approaching totally 1500 mg/day T4 + 75 mg/day T3. We were not able to find such a case report, requiring so high doses in the literature. Currently LT4 is available in tablet, soft gel, liquid and ampul formulations,being mostly used oral tablets. However,this treatment is not sufficient in some patients due to a variety of conditions such as autoimmune gastritis,malabsorption,pancreatic and liver diseases,drug interactions,noncompliance to the prescription,etc. In such situations, in which oral liquid or gel formulations are ineffective,parenteral forms of LT4 should be undertaken. Parenteral form of LT4 is, however,not available in every country. Though it is a very rare condition,it causes great challenges for both the patients and the care providers. Therefore,the health authorities of every country should provide parenteral form of LT4.