An immunoglobulin G complexed form of thyroid-stimulating hormone (macro thyroid-stimulating hormone) is a cause of

Francesca Mills1, Jinny Jeffery, Paul Mackenzie

  • 1Department of Clinical Biochemistry, Derriford Hospital, Plymouth, UK. francesca.mills@nhs.net

Insights

Macro-thyroid-stimulating hormone (TSH) can elevate TSH levels, causing diagnostic confusion. A study found macro-TSH in 0.6% of samples, highlighting the need for awareness in clinical laboratories.

Area of Science:

  • Clinical Chemistry
  • Endocrinology
  • Laboratory Medicine

Background:

  • Macrocomplexes can cause elevated serum hormone concentrations, leading to diagnostic confusion.
  • Polyethylene glycol (PEG) precipitation is a common screening method for macroprolactin, but less familiar for macro-thyroid-stimulating hormone (TSH).
  • Elevated TSH levels may be misinterpreted without considering the possibility of macro-TSH.

Purpose of the Study:

  • To determine the prevalence of macro-TSH in routine thyroid function testing.
  • To establish a screening method for macro-TSH in the Roche Elecsys assay.
  • To alert laboratories to macro-TSH as a potential cause of assay interference.

Main Methods:

  • Samples with TSH >10 mU/L were analyzed for macro-TSH using the Roche Elecsys assay.
  • Polyethylene glycol (PEG) precipitation was employed as a screening method.
  • Gel filtration chromatography was used for confirmation of macro-TSH.

Main Results:

  • Out of 495 samples tested, 3 (0.6%) exhibited macro-TSH.
  • A PEG precipitation recovery cut-off of <25% was identified for detecting samples with macro-TSH.
  • The study confirmed macro-TSH as a cause of elevated TSH concentrations.

Conclusions:

  • The prevalence of elevated TSH due to macro-TSH is 0.6%.
  • Laboratories should be aware of macro-TSH as a cause of assay interference in thyroid function tests.
  • Implementing screening methods for macro-TSH is recommended for accurate TSH measurement.
Abstract

Related Concept Videos

Hyperthyroidism I: Introduction01:25

Hyperthyroidism I: Introduction

Hyperthyroidism is a type of thyrotoxicosis characterized by the thyroid gland's overproduction of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). This hormone excess increases the basal metabolic rate and enhances sensitivity to catecholamines.DiagnosisDiagnosis is based on clinical features and biochemical testing. It typically shows suppressed thyroid-stimulating hormone (TSH) levels below 0.4 mIU/L, with elevated free T3 and/or T4. Additional tests, including thyroid...
Synthesis and Regulation of Thyroid Hormones01:20

Synthesis and Regulation of Thyroid Hormones

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.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
Hyperthyroidism II: Pathophysiology01:27

Hyperthyroidism II: Pathophysiology

Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...
Goiter01:27

Goiter

Goiter refers to an abnormal enlargement of the thyroid gland that may appear as a diffuse goiter (uniform enlargement) or nodular (single or multiple nodules). Functionally, it is classified as nontoxic (normal/low hormone levels) or toxic (excess hormone production).PathophysiologyDiffuse thyroid enlargement typically results from prolonged stimulation by thyroid-stimulating hormone (TSH) or TSH-like agents, commonly seen in hypothyroidism or iodine deficiency. In contrast, in hyperthyroid...
Graves' Disease I: Introduction01:28

Graves' Disease I: Introduction

Graves' disease is an autoimmune disorder that causes hyperthyroidism, or overactivity of the thyroid gland. It results from autoantibodies called thyroid-stimulating immunoglobulins (TSIs), which bind to thyroid-stimulating hormone (TSH) receptors, leading to overstimulation of hormone production and a hypermetabolic state.EtiologyAlthough considered idiopathic, Graves’ disease has well-established contributing factors. There is a strong genetic component, with increased prevalence in...
Graves Disease II: Pathophysiology01:24

Graves Disease II: Pathophysiology

Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...