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Possible Thyroid Hormone Resistance

Last Updated: · Doctors


Your thoughts regarding this generally healthy 65 yo man would be most appreciated.He presented with non-specific but suspicious symptoms: hyperkinetic, emotional irritability, weight loss despite intentional high calorie intake (nickname of “Joe Donuts” by his family). Exam: Equivocal tremor, normal reflexes, no lid lad. Thyroid exam enlarged, consistent with the ultrasound. Lab (all serum results confirmed on multiple determinations over several years): FreeT4=3.3 ng/dl (ARUP) (.8-1.7 ng/dl) FreeT4=2.6 ng/dl (Quest) (.8-1.8 ng/dl) FreeT4 by equilibrium dialysis=3.6 ng/dl (.8-2.7 ng/dl) TotalT3=268 ng/dl (70-175 ng/dl) ESR=15 TSH=1.5-2.5 (.3-5.0 UIU/ml) Thyroid Scan: Mildly enlarged gland; 27% uptake at 24 hours; cold defect. Ultrasound: 2cm nodule; gland 5.4-5.7 cm. bilat. FNA: colloid nodule Bone Density: T score Spine 2004 = -1.6 2007 = -1.5 Rt. Femur 2004 = -1.2 2007 = -1.7 Lt. Femur 2004 = -1.0 2007 = -1.4 The elevated circulating levels of thyroid hormone with a normal TSH appears to support a diagnosis resistance to thyroid hormone. The bone density studies suggest the possibility of accelerated bone loss and the question of whether there could be an organ specific variability in this resistance. Specifically, pituitary resistance and thus the normal TSH, but intact peripheral action and the consequent symptoms and accelerated bone loss. Is this a plausible interpretation of this information? Is there any other study that would confirm or refute the impression of thyroid hormone resistance? Is there any role for anti-thyroid therapy in his care?

Tim Howland


Indeed you are correct that the elevated TH levels and non-suppressed TSH are consistent with Resistance to Thyroid Hormone. RTH TSH secreting pituitary tumor antibodies interfering with measurement of the thyroid hormone levels or TSH. Transient elevations in the TH levels are also seen following certain viral syndromes. Is there any family history of thyroid abnormalities? : -Measurement of the alpha subunit (elevated alpha SU:TSH ratios are seen in the TSHomas) -Measurement of antithyroid antibodies, if negative would make interfering substances less likely -Determination of thyroid hormone function in parents, children, siblings (where possible). If there are other affected individuals it makes the diagnosis of RTH more likely -Obtain an MRI of the pituitary -Measure SHBG in serum (if elevated it would be consistent with a TSHoma) -Send blood for DNA analysis of Thyroid Hormone Receptor beta mutation to Quest Diagnostics The presence of decreased BMD is commonly seen in generalized RTH (GRTH). The reason being that the primary thyroid hormone receptor in bone is the TR alpha. Since it is the TR beta gene which is abnormal in most patients with GRTH, the TR alpha gene is normal and responds to the high thyroid hormone levels dictated by the pituitary. Hence the bone loss. The colloid nodule is likely incidental, as there is no evidence of increase thyroid nodules or thyroid cancer in RTH. Before recommending a specific treatment, it would be best to have a definitive diagnosis which explain the thyroid tests. My recommendations above should help sort this out. Please let me know the results of the testing and if you have any further questions, please feel free to contact me directly.

Roy E. Weiss, MD
University of Chicago