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Endocrinology›Condition·Updated Jun 26, 2026·v1

Hypothyroidism

Hypothyroidism is a prevalent endocrine disorder characterized by thyroid hormone deficiency. Primary disease (Hashimoto's) is most common, diagnosed by high TSH and low FT4. Treatment with weight-based levothyroxine is highly effective, though special care is needed in the elderly and during pregnancy to avoid cardiovascular and neurodevelopmental risks.

High Evidence281 references·1,163 words·5 min read·v1
endocrinologythyroidhashimotolevothyroxinemyxedema

Quick Reference

RxDrug of choice[[Levothyroxine]] (LT4) 1.6 μg/kg/day
AltAlternatives[[Liothyronine]] (T3) (adjunctive only), Desiccated Thyroid Extract (DTE)
⊘AvoidNon-dihydropyridine CCBs in severe HF-related hypothyroidism; active external rewarming in myxedema coma.
DxTest of choicePaired serum TSH and Free T4
ScKey scoreThyroid Feedback Quantile-based Index (TFQI) for hormone sensitivity
→When to referPregnancy, central hypothyroidism, cardiac disease, or failure to reach TSH target despite >2.0 μg/kg/day LT4
Hypothyroidism is a common, easily treated condition, but requires precise biochemical targeting and awareness of life-threatening decompensation (myxedema coma).
Hypothyroidism is a multisystemic clinical syndrome resulting from thyroid hormone deficiency or impaired peripheral action [20]. It is primarily a biochemical diagnosis, with primary thyroid failure accounting for >99% of cases [20]. Affecting 3% to 5% of pregnancies, it remains a major global health concern and a critical focus for metabolic and cardiovascular risk management [19, 20].

Overview and Recommendations

Background

  • •Hypothyroidism represents a critical failure of the hypothalamic-pituitary-thyroid (HPT) axis to maintain adequate circulating levels of thyroxine (T4) and triiodothyronine (T3), leading to a systemic metabolic deceleration.
  • •Primary hypothyroidism accounts for >99% of cases and is characterized by intrinsic thyroid dysfunction, typically resulting from autoimmune destruction ( ) or iatrogenic loss (post-thyroidectomy or radioactive iodine therapy).
  • •The prevalence of the condition ranges from 4% to 8% in the general population, but incidence rises sharply with age, reaching up to 18% in women over 60 years old.
  • •Iatrogenic and drug-induced causes are major modifiable risk factors; notably, carries a high incidence of hypothyroidism (NNH = 22 over 10 years), and causes dysfunction in approximately 20% of users via the Wolff-Chaikoff effect.
  • •Prognostic stakes are high in specific populations, as untreated maternal hypothyroidism increases the risk of pregnancy loss (OR 1.90) and impaired fetal neurodevelopment, while overt disease in the elderly increases all-cause mortality by 25%.

Evaluation

  • •Suspect hypothyroidism in patients presenting with insidious onset of fatigue, cold intolerance, modest weight gain (2–5 kg), constipation, and dry skin.
  • •Examine for the most specific physical sign: the delayed relaxation phase of deep tendon reflexes (Woltman's sign), which correlates with the severity of the metabolic deficit.
  • •Order a serum TSH as the first-line screening test; because the relationship between TSH and FT4 is inverse-logarithmic, TSH is the most sensitive indicator of primary thyroid status.
  • •Confirm the diagnosis with paired TSH and Free T4 (FT4) levels to differentiate between primary (High TSH, Low FT4) and central (Low/Normal TSH, Low FT4) etiologies.
  • •Measure Thyroid Peroxidase Antibodies (TPOAb) to confirm an autoimmune etiology; positivity predicts a higher rate of progression from subclinical to overt disease.
  • •Evaluate for secondary complications such as hyponatremia (Na < 135 mmol/L), hypercholesterolemia, and macrocytic anemia, which are common metabolic signatures of the disease.
  • •Identify 'Red Flags' for , including altered mental status, hypothermia (<35.5°C), bradycardia, and respiratory failure (FVC < 15 mL/kg).
  • •Perform a pituitary MRI in all confirmed cases of central hypothyroidism to exclude macroadenomas or infiltrative diseases of the sella turcica.
  • •Screen for co-existing autoimmune conditions, particularly and Addison's disease, as autoimmune thyroiditis occurs in nearly 50% of patients with adrenal insufficiency.

Management

  • •Initiate (LT4) monotherapy as the standard of care at a weight-based dose of 1.6 μg/kg/day (ideal body weight) for healthy, non-elderly adults.
  • •Start at a conservative dose of 12.5–25 μg daily in patients over age 65 or those with known coronary artery disease to avoid precipitating myocardial ischemia or arrhythmias.
  • •Administer LT4 on an empty stomach, ideally 30–60 minutes before breakfast or 3 hours after the last meal, to ensure optimal absorption.
  • •Separate LT4 administration from interfering substances (calcium carbonate, ferrous sulfate, proton pump inhibitors) by at least 4 hours.
  • •Titrate the dose every 6–8 weeks based on serum TSH levels, aiming for a target range of 0.4–4.0 mIU/L in most non-pregnant adults.
  • •Increase LT4 requirements by 25–50% immediately upon confirmation of pregnancy, aiming for a TSH < 2.5 mIU/L in the first trimester.
  • •Treat subclinical hypothyroidism (SCH) when TSH is > 10 mIU/L or if the patient is symptomatic with TPOAb positivity and TSH > 4.5 mIU/L.
  • •Manage with immediate IV 100 mg every 8 hours followed by an IV loading dose of 200–400 μg.
  • •Avoid using desiccated thyroid extract (DTE) as first-line therapy due to its high T3:T4 ratio, which may cause supraphysiological T3 levels and cardiotoxicity.
  • •Monitor patients with central hypothyroidism using FT4 levels rather than TSH, aiming for an FT4 in the upper half of the reference range.
  • •Refer to endocrinology for refractory cases, pregnancy, suspected central hypothyroidism, or when cardiac comorbidities complicate titration.

Board Review — High Yield

  • •Woltman's Sign — Delayed relaxation phase of deep tendon reflexes; highly specific for hypothyroidism.
  • •Wolff-Chaikoff Effect — Autoregulatory phenomenon where high iodine levels (e.g., amiodarone) inhibit thyroid hormone synthesis.
  • •Myxedema Coma Triad — Altered mental status, hypothermia, and a precipitating event (e.g., infection, cold).
  • •Subclinical Hypothyroidism — Elevated TSH with a normal Free T4; treat if TSH > 10 or in pregnancy.
  • •Central Hypothyroidism — Low or 'inappropriately normal' TSH with a low Free T4; requires pituitary imaging.
  • •Van Wyk-Grumbach Syndrome — Precocious puberty and multicystic ovaries caused by severe primary hypothyroidism in children.
  • •Levothyroxine Absorption — Impaired by calcium, iron, PPIs, and celiac disease; requires acidic gastric environment.
  • •HPT Axis in Pregnancy — TSH targets are lower (<2.5 mIU/L) and LT4 requirements increase by ~30% by the 4th-6th week.

Deep Dive — Evidence Details

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