The past medical history was notable for major depressive disorder treated with trazadone and aripiprazole, asthma treated with ventolin inhaler and advair, and hypercholesterolemia treated with atorvastatin. The patient denied taking any nutritional supplements, including biotin, which can interfere with certain thyroid hormone assays. The patient had smoked half a pack of cigarettes per day for the past thirty years. Family history was remarkable for mother who had died at age 88 years and suffered with hyperthyroidism and atrial fibrillation, an identical twin sister previously diagnosed with RTH (case 2; figure 1), three adult children (ages 41, 33 and 28 years old) alive and in good health, and five grandchildren (ranging in age from 7-14 years old) who were all reportedly asymptomatic (figure 1), i.e. no hyperthyroidism, goiter or cardiac ailment.
Physical examination revealed an anxious older woman with resting tremor and pressured speech. Height 63 inches, weight 159 lbs. Seated blood pressure was 122/87 mm hg, resting heart rate was 77 bpm (irregularly irregular), respirations were 14 breaths per minute (non-labored), and the patient was a febrile. After the patient stood up, walked a few steps and sat down on the examining table, her heart rate increased suddenly to 170 bpm. The skin was warm and dry. There was no proptosis or exophthalmos, and the visual fields were normal to confrontation testing. There was no jugular venous distension at 15 degrees. The thyroid was symmetrically enlarged, approximately 25 grams, and there were two palpable (1-2 cm) nodules, one in each lobe. Lung exam revealed scattered wheezes, decreased breath sounds at the right base and no rales. Cardiac examination was remarkable for rapid, irregular rate and rhythm, no s4, s3 gallop or rub was appreciated. There was no edema of the lower extremities. Neurologic exam was non-focal and deep tendon reflexes were brisk.
Magnetic resonance imaging of the brain was performed and it was negative for a pituitary mass lesion. Thyroxine binding globulin (TBG) was within the normal assay range (Table 1). Antithyroid autoantibody levels: thyroid stimulating immunoglobulin (TSI), anti-thyroglobulin and anti-thyroid peroxidase (TPO) were within the normal assay ranges: TSI 97% (0-139%); Thyroglobulin Ab < 1 (0-0.9)IU/ml, Anti-TPO Ab 13 (0-34) IU/ml. An iodine-123 radioactive thyroid uptake and scan revealed an enlarged gland with two cold nodules. The four-hour radioactive iodine uptake was 23.2%, normal range (3-10%); the 24 hour uptake 67.3%, normal range (10-40%). Serum albumin and total cholesterol were both within the normal ranges, and alkaline phosphatase was elevated at 174 (39-117) U/L. A blood sample was drawn and sent out for resistance to thyroid hormone mutational analysis testing.
Owing to the patients' refractory congestive heart failure requiring frequent hospitalizations, and the unexpectedly long delay in obtaining the results of thyroid hormone resistance mutational analysis, a 'modified L-T3 suppression test' (without serial I131 thyroid uptake determination) was performed to substantiate a working clinical diagnosis of resistance to thyroid hormone. Low-dose cytomel (L-T3) 25 micrograms was given once daily in the morning to evaluate suppressibility of TSH. After three weeks' L-T3 treatment, repeat thyroid function tests demonstrated a 22% decline in the free T4 level, unchanged total T3 level and a 50% decline in TSH level compared to basal levels (T+171 vs T+115 days; Table 1; Figure 2). During the treatment interval, the patient reported a reduction in her symptoms of dyspnea and dizziness and was not hospitalized. After discontinuation of L-T3, however, free T4 and TSH levels reverted to their pre-treatment levels (T+ 201 days; Table 1; Figure 2), and dizziness and dyspnea also recurred requiring the patient to be hospitalized again and treated for congestive heart failure.