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Thyroid hormone resistance syndromes

M T McDermott1, E C Ridgway

  • 1Endocrinology Service, Fitzsimons Army Medical Center, Aurora, Colorado 80045-5001.

The American Journal of Medicine
|April 1, 1993
PubMed
Summary
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Thyroid hormone resistance syndromes involve tissues resisting thyroid hormone effects. These conditions, often misdiagnosed, include generalized, pituitary, and peripheral resistance, with varying clinical presentations and genetic causes.

Area of Science:

  • Endocrinology
  • Molecular Genetics
  • Hormone Physiology

Background:

  • Thyroid hormone resistance syndromes (THRS) are a group of disorders characterized by impaired tissue response to thyroid hormones.
  • These syndromes present with diverse clinical manifestations, ranging from euthyroid to thyrotoxic or hypothyroid states, despite altered thyroid hormone levels.
  • Accurate diagnosis and management are often challenging due to their complexity and potential for misdiagnosis.

Purpose of the Study:

  • To delineate the characteristics of different types of thyroid hormone resistance syndromes.
  • To explore the underlying genetic basis and molecular mechanisms of these disorders.
  • To highlight the diagnostic challenges and therapeutic considerations for patients with THRS.

Main Methods:

Related Experiment Videos

  • Review of clinical and biochemical profiles of patients with generalized resistance to thyroid hormone (GRTH), selective pituitary resistance to thyroid hormone (PRTH), and selective peripheral resistance to thyroid hormone (PerRTH).
  • Analysis of genetic mutations, particularly in the thyroid hormone receptor beta (TRβ) gene, associated with GRTH.
  • Discussion of diagnostic criteria and therapeutic strategies based on affected tissues and hormone levels.

    • Main Results:

    • GRTH is characterized by resistance in both pituitary and peripheral tissues, leading to elevated thyroid hormones and normal/elevated TSH, usually without overt symptoms.
    • PRTH involves pituitary resistance only, resulting in thyrotoxicosis despite elevated thyroid hormones and TSH.
    • PerRTH affects peripheral tissues, with one described case presenting as hypothyroidism despite normal thyroid hormone and TSH levels.
    • GRTH is frequently caused by mutations in the TRβ gene affecting the hormone-binding domain.

    Conclusions:

    • Thyroid hormone resistance syndromes are likely underdiagnosed and often mismanaged.
    • Understanding the specific type of resistance (generalized, pituitary, or peripheral) is crucial for appropriate clinical management.
    • Further research is needed to elucidate the genetic causes of PRTH and PerRTH and to develop optimal therapeutic approaches.