Resistance to Thyroid Hormones: A Case-Series Study

Abstract

The aim of the study is to describe the clinical features of two unrelated patients with resistance to thyroid hormones (RTH), the first, a total thyroidectomized patient, and the second, a pregnant woman. We report the features found in her newborn who also showed RTH. Patient 1 is a 38-year-old man with total thyroidectomy managed for excessive thyroid stimulating hormone (TSH) production, which poorly responded to the replacement therapy. He was found with a THRβ c.1378G>A p.(Glu460Lys) heterozygous mutation, which was also present in other members of his family (son, brother, and father). Interestingly, Patient 1 had hypertension, dyslipidemia, and hepatic steatosis, which have been recently suggested as RTH-related comorbidities. Patient 2 is a 32-year-old pregnant woman with multinodular goiter, and the THRβ heterozygous variant c.959G>C, that, to the best of our knowledge, has been reported in literature only once. Her newborn had tachycardia and increased thyroid hormone levels, and showed the same mutation. After delivery, high parathyroid hormone (PTH) and calcium serum levels were found in Patient 2 and the scintigraphy showed the presence of adenoma of a parathyroid gland. This case-series study provides a practical example of the management of RTH in a thyroidectomized patient, a pregnant woman, and a newborn. A novel RTH pathogenic mutation is described for the second time in literature. Furthermore, the importance of metabolic assessment in patients with RTHβ has been highlighted and the possible correlation between RTH and primary hyperparathyroidism is discussed.

Atrial Fibrillation with Heart Failure in a Case with Resistance to Thyroid Hormone Due to a Rare Thyroid Hormone Receptor β Gene Mutation

“…Nowadays, the terms GRTH and PRTH are no longer used to classify RTH. In addition to R320L, mutations at codon 320 of the THRβ gene with different nucleotides have also been reported, such as R320H, R320C, and R320P [ 7 , 8 , 9 , 10 ]. Manifestations of those other codons 320 mutations were not all clearly recorded in the previous pieces of literature, and the age of these patients if mentioned, were all in the 30 s. Among them, a 31-year-old Japanese male with R320P mutation [ 9 ], such as our proband, had a history of atrial fibrillation status post cardiac catheter ablation when he was 21 and 25 years old.…”

Thyroid Hormone Resistance Syndrome: From Molecular Mechanisms to Its Potential Contribution to Hypertension

“…Goiter is the most common symptom, while sinus tachycardia, short stature, developmental delays, hair loss, ear infections, and abnormalities in the nose, throat, and psychological function are also frequently observed. In children, growth delays, delayed bone maturation, and cognitive impairments, along with hyperactivity and tachycardia, may coexist [ 23 ]. THR can cause both hypothyroidism and hyperthyroidism in different tissues, depending on which TRs are most prevalent in each organ, which could be TRβ (liver, adipose tissues) or TRα (skeletal and cardiac muscles, vascular endothelium) [ 24 ].…”