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

Key Features

Essentials of Diagnosis

  • Autoimmune (Hashimoto) 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.

  • FT4 is usually low.

  • TSH elevated in primary hypothyroidism

General Considerations

  • 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

  • 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

  • Chemotherapeutic agents that can cause silent thyroiditis include

    • Tyrosine kinase inhibitors

    • Denileukin diftitox

    • Alemtuzumab

    • Interferon-α

    • Interleukin-2

    • Thalidomide, lenalidomide

    • Immune checkpoint inhibitors

  • Radiation therapy to the head-neck-chest-shoulder region can cause hypothyroidism with or without goiter or thyroid cancer many years later

Clinical Findings

Symptoms and Signs

  • Common manifestations

    • Weight gain, fatigue, lethargy, depression

    • Weakness, dyspnea on exertion

    • Arthralgias or myalgias, muscle cramps, paresthesias

    • Cold intolerance

    • 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 the tongue

    • Hard pitting edema

    • Effusions into the pleural and peritoneal cavities as well as into joints

    • Galactorrhea may also be present

    • Cardiac enlargement ("myxedema heart") and pericardial effusions may occur

    • Psychosis ("myxedema madness") may occur

Differential Diagnosis

  • Conditions and drugs that cause a low serum T4 or T3 or high serum TSH in the absence of hypothyroidism


Laboratory Tests

  • Serum TSH is increased in primary hypothyroidism

  • Serum FT4 may be low or low normal

  • Other laboratory abnormalities include

    • Hypoglycemia

    • Anemia (with normal or increased mean corpuscular volume)

  • Hyponatremia due to SIADH or decreased glomerular filtration rate is common

  • Additional findings frequently include increased serum levels of

    • LDL cholesterol, triglycerides, lipoprotein (a)

    • Liver enzymes

    • Creatine kinase

    • Prolactin

  • During pregnancy in women with hypothyroidism taking replacement thyroxine, check serum TSH frequently (eg, every 4–6 weeks) to ensure adequate replacement


  • Radiologic imaging is usually not necessary

  • CT or MRI

    • Chest CT or MRI may show a goiter in the neck or in the mediastinum ...

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