Chemistry, toxicology & urinalysis

Organ specific


Hypothyroidism-lab diagnosis

Topic Completed: 1 March 2011

Minor changes: 8 October 2021

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PubMed Search: Hypothyroidism [title] thyroid

Nat Pernick, M.D.
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Cite this page: Pernick N. Hypothyroidism-lab diagnosis. website. Accessed December 3rd, 2021.
Definition / general
  • See also Hypothyroidism in Thyroid chapter
  • May initially have transient hyperthyroidism
  • May cause macrocytic, nonmegaloblastic anemia with normal RDW
Primary hypothyroidism
  • Due to:
    • Destruction or ablation of thyroid gland (surgery, radiation, Hashimoto thyroiditis, developmental)
    • Interference with thyroid hormone synthesis (idiopathic, genetic J Med Genet 2005;42:379)
    • Drugs (lithium, iodide, methimazole, PTU)
    • Iodine ingestion or iodine deficiency (Intern Med 2007;46:391)
    • T4 is low causing high TSH
  • Other causes:

Secondary hypothyroidism
  • Pituitary disorder causes reduced TSH secretion

Tertiary disease
  • Hypothalamic lesion causes reduced TRF secretion

Subclinical hypothyroidism

  • Hypothyroidism developing during infancy/childhood
  • May be due to maternal hypothyroidism (maternal T3/T4 crosses placenta and is critical to fetal brain development before fetal thyroid gland develops)
  • Now rare due to newborn testing and iodine supplementation (Pediatrics 2006;117:2290)

  • Chronic hypothyroidism in older child or adult
Thyrotropin releasing hormone
Definition / general
  • Also called thyrotropin releasing factor
  • Produced by hypothalamus
  • Enhances TSH synthesis and stimulates its secretion
  • Also affects prolactin and other pituitary hormones to a lesser extent
  • Also produced in pancreatic beta cell, where it colocalizes with insulin, highest levels in neonates (Acta Biomed 2007;78:216)
  • Feedback inhibition due to circulating T3 and T4
  • Regulated also by leptin, which mediates food appetite
  • Resistance occurs rarely (OMIM: TRHR [Accessed 8 October 2021])

  • Methodology:
    • Can measure by RIA but specimen must be frozen
    • TRH stimulation test:
      • Measure baseline TSH
      • Give IV bolus of TRH
      • Measure TSH (should rise within 5 minutes, peak in 20 minutes)
        • Fold increase is a better measure of response than absolute increase

  • Exaggerated: primary hypothyroidism
  • Suppressed: hyperthyroid patients (including Graves disease), also multinodular goiter, renal failure, Cushing syndrome, depression, drugs
  • No response: pituitary disorder (may not be necessary for diagnosis) (J Clin Endocrinol Metab 2003;88:5696)
Thyroid binding globulin
Definition / general
  • Deficiency does not cause thyroid disease by itself
  • Increases / decreases cause increase / decrease in total T3 and T4
  • However, free T3 and T4 are unchanged

  • Produced in liver
  • Major carrier protein for T3 and T4
  • Has highest affinity but lowest concentration of the carrier proteins
  • Other thyroid carrier proteins are transthyretin and albumin, which have lower affinity but higher concentration

  • Indications:
    • Interpreting T3 and T4 levels that do not match clinical findings or other laboratory results
      • For example, total T3 and T4 levels are very low, TSH is normal, free T3 and T4 are normal, patient is clinically euthyroid
    • Methodology:
      • Chemiluminescence immunoassay
    • Reference range:
      • 13 - 39 μg/dL (150 - 360 nmol/L)
    • High values:
      • Inherited abnormalities, drugs (clofibrate, estrogens, 5-FU, heroin / methadone), hepatitis, pregnancy, idiopathic)
    • Low values:
      • Inherited abnormalities, drugs (androgens, glucocorticoids), liver failure, malnutrition, nephrotic syndrome, idiopathic)
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