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Related Concept Videos

Synthesis and Regulation of Thyroid Hormones01:20

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Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
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The thyroid gland is a small, butterfly-shaped gland located in the neck and covers the anterior surface of the trachea. The gland has two lateral lobes connected by a thin tissue mass called the isthmus. Internally, each lobe comprises many small spherical structures known as thyroid follicles, surrounded by a network of blood vessels.
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The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...
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The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
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Two distinct clinical patterns of checkpoint inhibitor-induced thyroid dysfunction.

Anna Olsson-Brown1,2, Rosemary Lord2, Joseph Sacco2,3

  • 1Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.

Endocrine Connections
|March 13, 2020
PubMed
Summary

Immune checkpoint inhibitors (ICI) can cause thyroid dysfunction, often presenting as hyperthyroidism followed by hypothyroidism. Early monitoring and hormone replacement are crucial for managing this side effect in cancer patients.

Keywords:
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Area of Science:

  • Oncology
  • Endocrinology
  • Immunology

Background:

  • Immune checkpoint inhibitors (ICI) are associated with endocrine toxicities, including thyroid dysfunction.
  • Real-world data on the clinical presentation of ICI-induced thyroid dysfunction is limited.
  • Understanding the clinical patterns and associated features is essential for patient management.

Purpose of the Study:

  • To characterize the clinical patterns of thyroid dysfunction in patients receiving ICI therapy.
  • To evaluate demographic, biochemical, and immunological features of this patient cohort.
  • To identify distinct clinical phenotypes of ICI-induced thyroid dysfunction.

Main Methods:

  • Retrospective review of patients treated with anti-PD1 (monotherapy or combination with CTLA-4 inhibitor) at a UK regional cancer centre.
  • Inclusion of patients receiving pembrolizumab, nivolumab, or ipilimumab.
  • Evaluation of toxicity patterns and antibody titres.

Main Results:

  • Thyroid dysfunction occurred in 13/90 patients on anti-PD1 monotherapy and 3/13 on combination therapy.
  • The predominant pattern was hyperthyroidism followed by hypothyroidism (12/16), with 4/16 developing de novo hypothyroidism.
  • All affected patients required thyroid replacement therapy; no correlation was found between dysfunction pattern and thyroid autoantibodies.

Conclusions:

  • Two distinct patterns of ICI-induced thyroid dysfunction exist: transient hyperthyroidism followed by hypothyroidism, and de novo hypothyroidism.
  • Patients with thyroiditis often progress to hypothyroidism.
  • Early detection and hormone replacement are key for managing symptoms and improving outcomes.