Selective Pituitary Resistance to Thyroid Hormone: Clinical Hyperthyroidism with High TSH on Levothyroxine Administration in I-131 Ablated “Graves Disease”

Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause clinically distinguishable patient presentations. In PRTH, typically only the pituitary gland is resistant to thyroid hormone (TH) while the rest of the body maintains sensitivity. Selective pituitary resistance to thyroid hormone results in dysregulation of thyroid hormone homeostasis with clinical presentation as either euthyroid or hyperthyroidism. PRTH is characterized by elevated thyroid hormone levels with an elevated or inappropriately normal TSH concentration. Herein we describe a case report of a 70-year-old woman who complained of weight loss of over 35 lbs., palpitations, jitters, hair loss, diarrhea, fatigue, muscle weakness, etc. over 6 months, thus, indicating the presence of iatrogenic hyperthyroidism while receiving levothyroxine 175 ug daily prescribed by her primary care provider because of a reported history of “Graves disease” treated by radioactive iodine ablation of the thyroid several years ago. The daily dose of levothyroxine had been increased gradually at an interval of 3 months over a year because of persistent elevation of serum TSH level. Laboratory tests revealed markedly elevated Free T4, Free T3 and TSH levels, along with low concentrations of all lipid fractions, serum creatinine and urea nitrogen levels, indicating TSH induced hyperthyroidism or PRTH. Further testing documented a mutation of thyroid hormone receptor beta gene 2 confirming presence of PRTH. We believe that the initial diagnosis of Graves Disease was erroneous and I-131 ablation further confounded and missed the diagnosis of PRTH. Thus, the purpose of this report is to report a patient with PRTH and describe potential pitfalls in diagnosis and management of this rare disorder.

Low Reverse T3: A Reliable, Sensitive and Specific in Diagnosis of Central Hypothyroidism*

Background: Low free T4 and normal/low TSH concentrations are often noted in clinical practice and denote presence of “Euthyroid Sick Syndrome” or Central Hypothyroidism. However, accurate diagnosis is difficult even with determination of free T3 being low/normal in both. Repeated determination of these tests may help differentiate between these disorders. Objective: Evaluation of reverse T3 to differentiate between “Euthyroid Sick Syndrome” and Central Hypothyroidism. Subjects and Methods: Free T3 and Reverse T3 were determined as “add on” tests using previously drawn blood samples of 78 consecutive adults showing low free T4, 0.80 ± 0.02 and low/normal TSH, 1.29 ± 0.40 [normal ranges, 0.89 - 1.70 mcg/dl;0.45 - 4.67 uU/ml]. Free T4, free T3, TSH and reverse T3 levels were also determined in age-matched 35 healthy volunteers and reassessed in study group. Statistical analyses for comparisons were conducted between groups. All data are reported as Mean ± SEM. Results: Reverse T3 established two distinct groups: 1) subnormal concentrations, 8.31 ± 0.52 [range, 11 - 14 ng/dl];2) supernormal levels;32 ± 4 [normal Range 12 - 26]. Free T3 concentrations were subnormal or normal, 1.6 - 2.9 [normal range, 2.3 - 4.2 ng/ml] in individuals amongst both groups. On reassessment after 3 - 6 weeks, free T4, free T3, TSH and reverse T3 normalized in group with normal or elevated reverse T3 indicating recovery from “Euthyroid Sick Syndrome” whereas free T4 and reverse T3 remained subnormal in the other group suggesting presence of Central Hypothyroidism. Conclusion: Reverse T3 is a reliable laboratory test differentiating between Central Hypothyroidism and “Euthyroid Sick Syndrome” in subjects with low free T4 and low/normal TSH levels.