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For further information, see CMDT Part 26-08: Hypothyroidism & Myxedema

Key Features

Essentials of Diagnosis

  • Hashimoto autoimmune thyroiditis is the most common cause of hypothyroidism

  • Fatigue, cold intolerance, constipation, weight change, depression, menorrhagia, hoarseness

  • Dry skin, bradycardia, delayed return of deep tendon reflexes

  • Free thyroxine (FT4) is usually low

  • TSH elevated in primary hypothyroidism

General Considerations

  • Thyroid hormone deficiency affects almost all bodily functions and ranges from unrecognized and mild hypothyroid states to striking myxedema

  • Autoimmune thyroiditis is the most common cause of hypothyroidism

  • Primary hypothyroidism is due to thyroid gland disease

  • Secondary hypothyroidism is due to deficiency of pituitary TSH

  • Maternal hypothyroidism during pregnancy results in cognitive impairment in child

  • Goiter (thyroid enlargement) may be present with

    • Thyroiditis

    • Iodide deficiency

    • Genetic thyroid enzyme defects

    • Food goitrogens in iodide-deficient areas

    • Peripheral resistance to thyroid hormone or infiltrating diseases (rare)

  • Goitrogenic medications include

    • Iodide

    • Propylthiouracil (PTU) or methimazole

    • Sulfonamides

    • Amiodarone; its high iodine content can cause significant hypothyroidism in 15–20% of patients as well as thyrotoxicosis

    • Interferon-α

    • Interferon-β

    • Interleukin-2

    • Lithium (~50% of patient taking lithium long term have goiter)

  • Chemotherapeutic agents that can cause silent thyroiditis include

    • Tyrosine kinase inhibitors

    • Denileukin diftitox

    • Alemtuzumab

    • Interferon-α

    • Interleukin-2

    • Thalidomide, lenalidomide

    • Immune checkpoint inhibitors

  • Some malignancies (eg, large hemangiomas) cause "consumptive hypothyroidism"

  • Goiter is also usually absent when hypothyroidism is due to destruction of the gland by head-neck or chest-shoulder radiation therapy or 131I therapy

  • Myxedema crisis

    • Severe, life-threatening manifestation of hypothyroidism with high mortality rate

    • Primarily affects elderly women

    • Affected patients have

      • Impaired cognition, ranging from confusion to somnolence to coma (myxedema coma)

      • Convulsions and abnormal CNS signs

      • Profound hypothermia, hypoventilation, hyponatremia, hypoglycemia, hypoxemia, hypercapnia, and hypotension

      • Rhabdomyolysis and acute kidney injury

    • Can be induced by

      • Prolonged exposure to cold with resultant hypothermia

      • Stroke, heart failure, infection, or trauma

      • Administration of sedatives, antidepressants, hypnotics, anesthetics, or opioids


  • Hypothyroidism is common, affecting > 1% of the general population and 5% of individuals > 60 years of age

  • ~85% of affected individuals are women

  • Congenital hypothyroidism occurs in ~1 in 4000 births

Clinical Findings

Symptoms and Signs

  • Common manifestations

    • Weight gain, fatigue, lethargy, depression

    • Weakness, dyspnea on exertion

    • Arthralgias or myalgias, muscle cramps, paresthesias

    • Cold intolerance, Raynaud syndrome

    • Constipation

    • Dry skin

    • Headache

    • Carpal tunnel syndrome

    • Menorrhagia

    • Bradycardia; diastolic hypertension

    • Thin, brittle nails

    • Thinning of hair

    • Peripheral edema, puffy face and eyelids

    • Skin pallor or yellowing (carotenemia)

    • Delayed relaxation of deep tendon reflexes may be present

    • Palpably enlarged thyroid (goiter) that arises due to elevated serum TSH levels or the underlying thyroid pathology

  • Less common manifestations

    • Diminished appetite and weight loss

    • Hoarseness

    • Decreased sense of taste and smell and diminished auditory acuity

    • Dysphagia or neck discomfort

    • Menorrhagia, scant menses, or amenorrhea

    • Loss of eyelash and eyebrow hairs

    • Thickening of ...

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