Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 26-08: Hypothyroidism & Myxedema + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Autoimmune (Hashimoto) thyroiditis is the most common cause of hypothyroidism Weakness, cold intolerance, constipation, depression, menorrhagia, hoarseness Dry skin, bradycardia, delayed return of deep tendon reflexes Free tetraiodothyronine (FT4) low Thyroid-stimulating hormone (TSH) elevated in primary hypothyroidism +++ General Considerations ++ Primary hypothyroidism is due to thyroid gland disease Secondary hypothyroidism is due to lack of pituitary TSH Maternal hypothyroidism during pregnancy results in cognitive impairment in child Hypothyroidism with goiter is caused by Hashimoto thyroiditis Subacute (de Quervain thyroiditis) (after initial hyperthyroidism) Riedel thyroiditis Iodine deficiency Genetic thyroid enzyme defects Hepatitis C Medications: Iodide, propylthiouracil or methimazole, sulfonamides, amiodarone, interferon-alpha, interferon-beta, interleukin-2, and lithium Food goitrogens in iodide-deficient areas Peripheral resistance to thyroid hormone Infiltrating diseases Hypothyroidism without goiter is caused by Thyroid surgery, irradiation, or radioiodine treatment Deficient pituitary TSH Severe illness Radiation therapy to the head-neck-chest-shoulder region can cause hypothyroidism with or without goiter or thyroid cancer many years later TSH may be mildly elevated in some euthyroid individuals, especially elderly women (10% incidence) Amiodarone, due to high iodine content, causes clinical hypothyroidism in 15–20% High iodine intake from other sources may also cause hypothyroidism, especially in those with underlying lymphocytic thyroiditis Myxedema is caused by interstitial accumulation of hydrophilic mucopolysaccharides, leading to fluid retention and lymphedema Euthyroid sick syndrome Functional hypothyroidism that occurs in serious nonthyroidal disease e.g. severe illness, caloric deprivation, or major surgery Patients without known thyroid disease have a low serum FT4 and a serum TSH that is not elevated Does not require treatment with levothyroxine + Clinical Findings Download Section PDF Listen +++ +++ 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 Thinning of the outer halves of the eyebrows 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 Download Section PDF Listen +++ +++ Laboratory Tests ++ Serum TSH is the single best screening test for hypothyroidism 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 (retrosternal goiter) An enlarged thymus is frequently seen in the mediastinum in cases of autoimmune thyroiditis On head MRI, the pituitary is often quite enlarged in primary hypothyroidism due to hyperplasia of TSH-secreting cells, which is reversible following thyroid therapy + Treatment Download Section PDF Listen +++ +++ Medications ++ Levothyroxine (T4) Synthetic levothyroxine is the preferred preparation for hypothyroidism Intestinal absorption can vary by up to 15% with different levothyroxine preparations, so ideally, the patient should receive a consistent manufacturer's preparation For young and middle-aged adults with hypothyroidism who are otherwise healthy Initial average dose is about 1.6 mcg/kg/day Lower doses can be used for very mild hypothyroidism, while full doses are given for more symptomatic hypothyroidism Patients with stable coronary artery disease or those who are over age 60 years Initial dose: 25–50 mcg orally daily; higher initial doses may be used if such patients are severely hypothyroid Dose can be increased by 25 mcg every 1–3 weeks until the patient is euthyroid For patients with active coronary artery disease or recurrent atrial fibrillation, Ideally, patients with hypothyroidism and unstable coronary artery disease or uncontrolled atrial fibrillation should begin levothyroxine replacement following medical or interventional therapy of their cardiac disease May be prudent to administer lower doses of levothyroxine to keep the serum TSH in the high-normal or even slightly elevated range For most other patients, a high serum TSH indicates underreplacement with levothyroxine Myxedema crisis Requires larger initial doses of levothyroxine intravenously, since myxedema itself can interfere with intestinal absorption of oral levothyroxine Levothyroxine sodium 500 mcg is given intravenously as a loading dose, followed by 50–100 mcg intravenously daily The lower dose is given to patients with suspected coronary artery disease In patients with severe myxedema crisis, liothyronine (T3, Triostat) can be given intravenously with a loading bolus of 10–20 mcg, followed by 10 mcg intravenous boluses every 8-12 hours for the first 48 hours Pregnant women with overt hypothyroidism or myxedema Should be treated immediately with levothyroxine at full replacement doses of 1.6 mcg/kg/day (about 100–150 mcg daily) For initial titration, the dosage may be increased according to clinical response and serum TSH, measuring serum TSH every 4–6 weeks and trying to keep the serum TSH level in the lower half of the reference range (0.4–2.0 milli-international units/L) during pregnancy Pregnancy Usually increases the levothyroxine dosage requirement; an increase in levothyroxine requirement has been noted as early as the fifth week of pregnancy Adequate levothyroxine is critical to the health of the fetus Therefore, dosages should be increased by approximately 20–30% as soon as pregnancy is confirmed By mid-pregnancy, women require an average of 47% increase in the dosage Postpartum, levothyroxine replacement requirement usually returns to prepregnancy level Increased levothyroxine dosage requirements (low serum T4 levels) can occur with drugs that increase the hepatic metabolism of levothyroxine (Table 26–3) Oral estrogen therapy may necessitate increased doses of levothyroxine Proton pump inhibitors interfere slightly with the absorption of levothyroxine Gastrointestinal disorders can interfere with levothyroxine absorption, including Celiac disease Inflammatory bowel disease Lactose intolerance Helicobacter pylori gastritis Atrophic gastritis Nephrotic syndrome can increase the required dose of oral levothyroxine ++Table Graphic Jump LocationTable 26–3.Factors that may cause aberrations in laboratory tests that may be mistaken for primary hypothyroidism.1View Table||Download (.pdf) Table 26–3. Factors that may cause aberrations in laboratory tests that may be mistaken for primary hypothyroidism.1 Low Serum T4 or T3 High Serum TSH Acute psychiatric illness Cirrhosis Familial thyroid-binding globulin deficiency Laboratory error Nephrotic syndrome Severe illness Drugs Androgens Antiseizure drugs Carbamazepine Phenobarbitol Phenytoin Asparaginase Carbamazepine (T4) Chloral hydrate Corticosteroids Diclofenac (T3), naproxen (T3) Didanosine Fenclofenac 5-Fluorouracil Halofenate Imatinib Mitotane Nicotinic acid Oxcarbazepine Phenobarbital Phenytoin Salicylates in large doses (T3 and T4) Sertraline Stavudine T3 therapy (T4) Acute psychiatric illness (transient) (14%) Amiodarone Anti-mouse antibodies Antithyrotropin (TSH) antibodies Anti-TSH receptor antibodies Autoimmune disease (assay interference) Drugs Amphetamines Atypical antipsychotics Dopamine agonists Heroin Phenothiazines Elderly (especially women) Exercise before testing Following prolonged primary hypothyroidism Heterophile antibodies Laboratory error Macro-thyrotropin Nonadherence to thyroid replacement therapy Pituitary TSH hypersecretion Recovery from acute nonthyroidal illness (transient) Strenuous exercise (acute) Sleep deprivation (acute) TSH resistance 1True primary hypothyroidism may coexist.T4, levothyroxine; T3, triiodothyronine; TSH, thyroid-stimulating hormone. + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ Continue T4 for life; reassess dosage requirements periodically by clinical examination and by serum TSH Surveillance for atrial arrhythmias and for osteoporosis, especially in patients who require high doses of T4 Monitor patients with subclinical hypothyroidism for subtle signs (eg, fatigue, depression, hyperlipidemia) Clinical hypothyroidism later develops in ~18% +++ Complications ++ Cardiac complications may occur as a result of preexistent coronary artery disease and heart failure, which may be exacerbated by levothyroxine therapy Increased susceptibility to infection Megacolon in long-standing hypothyroidism Organic psychoses with paranoid delusions ("myxedema madness") Adrenal crisis precipitated by thyroid replacement Rhabdomyolysis may occur and cause kidney dysfunction Infertility (rare), miscarriage in untreated hypothyroidism Sellar enlargement and TSH-secreting tumors in untreated cases +++ Prognosis ++ Excellent prognosis with early treatment, but relapses may occur if treatment is interrupted Mortality rate for myxedema coma is high +++ When to Refer ++ Difficulty titrating T4 replacement to normal TSH or clinically euthyroid state Any patient with significant coronary artery disease needing T4 +++ When to Admit ++ Suspected myxedema coma Hypercapnia + References Download Section PDF Listen +++ + +Bekkering GE et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019 May 14;365:l2006. [PubMed: 31088853] + +Biondi B et al. Subclinical hypothyroidism: a review. JAMA. 2019 Jul 9;322(2):153–60. [PubMed: 31287527] + +Burch HB. Drug effects on the thyroid. N Engl J Med. 2019 Aug 22;381(8):749–61. [PubMed: 31433922] + +McAninch EA et al. Systemic thyroid hormone status during levothyroxine therapy in hypothyroidism: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2018 Dec;103(12):4533–42. [PubMed: 30124904] + +Okosieme O et al. Management of primary hypothyroidism: statement by the British Thyroid Association executive committee. Clin Endocrinol (Oxf). 2016 Jun;84(6):799–808. [PubMed: 26010808] + +Peeters RP. Subclinical hypothyroidism. N Engl J Med. 2017 Jun 29;376(26):2556–65. [PubMed: 28657873]