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

Diagnosis

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

Imaging

• Radiologic imaging is usually not necessary

• CT or MRI

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