Treatment refractory hypothyroidism as a result of excessive donation of plasma has not been previously reported in the literature. A 43-year-old woman with past medical history of Grave’s disease and post thyroidectomy hypothyroidism was evaluated for treatment refractory hypothyroidism. She weighed 90 kg and was started on levothyroxine (150 mcg) 3 months after thyroidectomy. Two months after starting levothyroxine her thyroid profile rapidly improved toward normal (TSH 6.99 lU/mL, T4 1.52 ng/dL) and subsequently, her TSH began to rise and levothyroxine was gradually increased to 225 mcg over eleven months, however, her thyroid profile did not normalize (TSH 30.4 lU/mL, T4 0.79 ng/dL). Her other medication included Aspirin, Ergocalciferol, Pantoprazole, Calcium carbonate, and Diltiazem. Poor medication adherence, ineffective timing of medication with meals and concomitant use of medication with Calcium carbonate and Pantoprazole were ruled out as causes for sub-optimal treatment. Basic metabolic profile, complete blood count and urinalysis were within normal limits. Total protein and Albumin were low (6.1 and 3.1 g/dL) respectively and antimicrosomal and thyroglobulin antibodies were negative. She had no symptoms of diarrhea or food intolerance to suggest malabsorption. At this point the etiology of her persistently elevated TSH level was a mystery. Exploration of her ideas, concerns, and expectations revealed that she was going through a divorce, and was having financial difficulty, so she resorted to donating plasma for income. She wondered if donating plasma was somehow responsible for her lack of response to treatment. Further enquiry revealed that she was donating plasma twice weekly at different sites. She was advised to stop donating plasma for 6 months and repeat her TSH/T4 before her next appointment. Her thyroid hormone levels had normalized by the next appointment three months later with a trend toward over treatment at 5 months (Fig. 1) and her dose of levothyroxine was appropriately reduced. Persistently elevated TSH in patients on thyroxine replacement therapy can result from medication non-adherence, inadequate dosing, concomitant use of levothyroxine with meals, coffee, competing medications, coexisting medical conditions such as celiac disease, autoimmune gastritis, and rarely, interference of the TSH/T4 laboratory assay by rheumatoid factor and heterophil antibodies [1]. The recommended frequency of plasma donation by the American Red Cross is every 28 days and hypothyroid patients on replacement therapy can donate blood products if feeling well and euthyroid on thyroxine for 6 months [2]. In contrast, our patient was donating plasma every 4 days which was clearly in excess of the recommended frequency of donation. We postulate that the likely pathophysiological mechanism of reduced efficacy of levothyroxine in our patient is via rapid removal of levothyroxine which is bound to plasma proteins. This is analogous to what happens in patients with hypothyroidism secondary to nephrotic syndrome [3]. In the latter, patients become hypothyroid secondary to excessive urinary losses of binding proteins, such as thyroxine binding globulin, prealbumin, and albumin, resulting in a reduction of serum total thyroxine (T4) and, sometimes triiodothyronine (T3) A. T. Abegunde (&) B. Mba Department of Internal Medicine, John H. Stroger Jr. Hospital of Cook County, 1900 W, Polk Street, Chicago, IL 60612, USA e-mail: abegs@doctors.org.uk
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