Ctrl

K

Table of contents

Expand All Topics

Thyroid hormone resistance

Background

Overview

Definition
Resistance to thyroid hormone beta (RTHβ) and resistance to thyroid hormone alpha (RTHα) are autosomal dominant disorders characterized by reduced responsiveness of target tissues to thyroid hormone due to mutations in the THRB and THRA genes, resulting in elevated levels of circulating thyroid hormones with non-suppressed TSH levels (in RTHβ) or low-normal thyroid hormones with inappropriately normal/slightly elevated TSH levels (in RTHα).
1
2
Pathophysiology
Thyroid hormone resistance is most commonly caused by mutations in the THRB or THRA genes. These mutations impair the ability of thyroid hormone receptor to bind thyroid hormone or interact with co-regulators, leading to reduced sensitivity to thyroid hormones in peripheral tissues and a compensatory increase in TSH secretion from the pituitary gland. Consequently, there is impaired action of thyroid hormone in tissues expressing TRα or TRβ, such as the skeletal muscle, heart, and gastrointestinal tract, despite normal or elevated levels of circulating thyroid hormones.
2
3
Epidemiology
The incidence of thyroid hormone resistance is estimated at about 1 case per 40,000 live births.
2
4
Risk factors
Risk factors for thyroid hormone resistance include a family history of the disorder, as it is typically inherited in an autosomal dominant manner. De novo mutations can also occur.
3
Disease course
The clinical course of thyroid hormone resistance varies widely. Some patients remain asymptomatic. Diagnosis is often made in childhood or adolescence when abnormal thyroid function tests are noted. Patients with RTHβ may present with goiter, tachycardia, weight loss, ADHD, growth retardation, and dyslipidemia. The condition is often identified incidentally through abnormal thyroid function tests. In some cases, patients with RTHβ can develop serious cardiovascular complications, such as AF and HF. Patients with RTHα may present growth retardation, developmental delay, constipation, macrocephaly, and skeletal dysplasia. Patients may exhibit mild hypothyroid symptoms despite normal thyroid function tests.
1
5
6
Prognosis and risk of recurrence
Prognosis is generally favorable, with most patients leading normal lives with appropriate management. The presence of serious complications, such as AF and HF, can significantly impact the prognosis and QoL. In patients with RTHβ, there is an increased risk for all-cause mortality, AF, HF, and major adverse cardiovascular events.
7

Guidelines

Key sources

The following summarized guidelines for the evaluation and management of thyroid hormone resistance are prepared by our editorial team based on guidelines from the European Thyroid Association (ETA 2024).
1
2
3
4
5
6
7
8

Screening and diagnosis

Differential diagnosis: as per ETA 2024 guidelines, assess fot potential confounding effects of medications and intercurrent illness carefully when assessing a patient with elevated thyroid hormone concentrations and non-suppressed TSH.
B
Show 2 more
Create free account

Specific circumstances

Patients with resistance to thyroid hormone beta, initial evaluation: as per ETA 2024 guidelines, consider suspecting resistance to thyroid hormone beta in cases with a discordant pattern of thyroid function tests, comprising genuinely elevated, circulating free (or total) T4, elevated free (or total) T3, and non-suppressed TSH.
B
Show 2 more
Create free account

More topics in this section

  • Patients with resistance to thyroid hormone beta (gene sequencing)

  • Patients with resistance to thyroid hormone beta (evaluation for comorbidities)

  • Patients with resistance to thyroid hormone beta (antithyroid drugs and thyroid ablation)

  • Patients with resistance to thyroid hormone beta (management of thyrotoxic symptoms)

  • Patients with resistance to thyroid hormone beta (management of hypothyroidism)

  • Patients with resistance to thyroid hormone beta (developmental assessment)

  • Patients with resistance to thyroid hormone beta (hearing assessment)

  • Patients with resistance to thyroid hormone beta (cardiometabolic assessment)

  • Patients with resistance to thyroid hormone beta (bone density assessment)

  • Patients with resistance to thyroid hormone beta (pregnancy)

  • Patients with resistance to thyroid hormone alpha (initial evaluation)

  • Patients with resistance to thyroid hormone alpha (gene sequencing)

  • Patients with resistance to thyroid hormone alpha (levothyroxine and liothyronine)

  • Patients with resistance to thyroid hormone alpha (monitoring)

  • Patients with MCT8 deficiency (initial evaluation)

  • Patients with MCT8 deficiency (gene sequencing)

  • Patients with MCT8 deficiency (general principles of management)

  • Patients with MCT8 deficiency (thyroid hormone analogs)

  • Patients with MCT8 deficiency (levothyroxine and propylthiouracil)

  • Patients with MCT8 deficiency (symptomatic management)

  • Patients with MCT8 deficiency (nutritional support)

  • Patients with selenoprotein deficiency (initial evaluation)

  • Patients with selenoprotein deficiency (gene sequencing)

  • Patients with selenoprotein deficiency (liothyronine therapy)

  • Patients with selenoprotein deficiency (dietary supplements)

  • Patients with selenoprotein deficiency (monitoring)

  • Patients with iodothyronine deiodinase defects