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

Demographics

• 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 ...