Hypothyroidism: Diagnosis and Management

Educational Objectives

The goal of this program is to improve management of hypo- and hyperthyroidism. After hearing and assimilating this program, the clinician will be better able to:

1. Recognize signs and symptoms of hypothyroidism.

2. Differentiate between primary and secondary hypothyroidism.

3. Prescribe appropriate replacement therapy for patients with hypothyroidism.

Summary

Epidemiology: hypothyroidism is more common after age 65 yr and in women; risk is elevated among residents of skilled nursing facilities; risk factors include previous irradiation or surgery involving the thyroid, family history of thyroid disease, recent pregnancy, Turner syndrome, and presence of other autoimmune conditions

Signs and symptoms: generally nonspecific, with few pathognomonic signs; common symptoms — include fatigue, difficulty concentrating, weight gain, dry skin, depression, intolerance of cold, and hair loss, especially in the outer third of the eyebrows (pathognomonic for hypothyroidism); women may experience menorrhagia, amenorrhea, or irregular periods; patients with thyroiditis may have discomfort or pain over the lower neck and a diffusely enlarged thyroid; goiter is more common with severe disease and in longstanding hypothyroidism; goiter is also common in patients with Riedel struma, most of whom are euthyroid; common physical findings — include bradycardia and low blood pressure (BP); general hair loss and nonpitting peripheral edema are possible; physical examination is typically normal, other than vital signs

Evaluation: levels of thyrotropin (TSH), free triiodothyronine (T3), and thyroxine (T4) levels are key; an elevated TSH level with low T4 or T3 level is overt hypothyroidism; mildly elevated TSH with normal T4 and T3 is subclinical hypothyroidism; TSH is elevated in patients with primary hypothyroidism but low in secondary hypothyroidism; peroxidase antibody titers may help identify Hashimoto thyroiditis but have little or no value in treatment or prognosis; there is no role for imaging unless nodules are present; in cases of secondary hypothyroidism, assess for other pituitary abnormalities

Hashimoto thyroiditis: the most common type of thyroiditis that leads to permanent, overt long-term hypothyroidism; autoimmune thyroiditis that progresses slowly over time; symptoms manifest when patients are in their late 30s or 40s; typically, patients do not seek care until thyroid function is significantly impaired; exacerbated by iodine supplements and foods high in iodine

Hypothyroidism secondary to acute thyroiditis: eg, DeQuervain thyroiditis; patients may become transiently hyperthyroid due to the release of existing thyroid hormone stored in the gland; subsequently, levels usually decrease to a euthyroid or hypothyroid state lasting a few weeks to months (permanent in 10% patients)

Iatrogenic disease: secondary to irradiation or surgery for Graves disease, Riedel struma, or chronic fibrocytic thyroiditis (associated with large, nontender goiter)

Other causes: include medications (eg, amiodarone, lithium, interferon alpha), infiltrative disorders (amyloidosis or sarcoidosis), or iodine insufficiency

Congenital hypothyroidism (CH): usually caused by agenesis or hypoplasia of the thyroid gland; also caused by ingestion of antithyroid medications by mothers early in pregnancy, particularly methimazole; propylthiouracil does not cross the blood-placenta barrier; signs in infants include large, thick tongues, abnormally enlarged fontanelles, delayed closure of the posterior fontanelle, hoarse cry, abdominal distention, difficulty feeding, constipation, poor muscle tone, and persistent newborn jaundice; infants may be deficient in several pituitary hormones; hypopituitarism should be suspected in infants with issues maintaining blood glucose, persistent hyperbilirubinemia, or micropenis

Treatment: L-thyroxine is used for replacement; the typical daily requirement for a patient with complete absence of thyroid function is between 113 and 137 µg; for older patients or those at risk for or having existing heart disease, start with 25 to 50 µg, then increase by 25 µg every 4 to 6 wk, based on TSH levels; patients with mild thyroid dysfunction typically require 50 to 100 µg and annual surveillance; a study by Dong BJ et al (1997) showed similar efficacy of generic and brand-name formulations

Desiccated thyroid (Armour Thyroid) vs purified thyroid: desiccated thyroid is ground and dried animal thyroid tissue; contains all thyroid components; safe to prescribe but has no advantage over L-thyroxine for most patients

Missed doses: in a study of ≈50 patients, the investigators compared daily dosing vs 7 times the daily dose once weekly; daily measurements of metabolic indicators of thyroid function showed no differences between groups; findings suggest catch-up doses are not harmful

Treatment using T3: some studies have shown that, among patients >65 yr of age exhibiting neurocognitive deficits despite euthyroid replacement of thyroid hormone, 12.5 µg of T3 with a concomitant 50-µg reduction in the T4 dose may be beneficial; in studies of patients <45 yr of age, supplemental T3 was not associated with cognitive benefits

Monitoring thyroid hormone levels: 97% of T4 and 99.7% of T3 is protein bound; changes in serum protein levels require changes in dosage to maintain free T4 and T3 levels; starvation for weight loss or related to chemotherapy, malnutrition, or nephrotic syndrome require reduced doses; patients who are pregnant or initiate estrogen therapy may require increased doses; pregnant women — need close monitoring throughout gestation; replacement requirements may increase 25% to 50%; L-thyroxine should not be taken within ≈4 hr of taking iron or prenatal vitamins because iron and calcium decrease absorption

Treatment of CH: L-thyroxine is crushed and mixed with formula or breast milk at a dose of 10 to 15 µg/kg per day; thyroid medication should not be mixed with soy-based formula because soy proteins combine with thyroxine and reduce absorption levels

Subacute hypothyroidism: common in older adults, women, and persons of European ancestry; over time, there is a low risk for progression to overt hypothyroidism (≈5% over a 3-yr period); patients with TSH levels >10 mIU/mL and those with positive antithyroid antibodies are at higher risk; treatment is not recommended unless patients become symptomatic; follow up annually with TSH and T4 levels to monitor for progression; Leiden 85-plus Study — compared euthyroid individuals with patients who had subclinical hypothyroidism; no differences were found in decline in cognitive function, need for support in activities of daily living, or development of other clinical problems; patients with subclinical hypothyroidism had a lower mortality rate over the next 5 yr

Complications of hypothyroidism: associated with elevated lipid levels, including the low-density lipoproteins, which increase risk for heart disease; severe hypothyroidism can lead to myxedema, myxedema coma, and neuropsychiatric problems, such as depression and confusion; CH can result in severe and irreversible intellectual disability if not recognized early in life; however, because of universal screening in most developed countries, this is now uncommon

Recommendations for screening: in 2015, the US Preventive Services Task Force reaffirmed their previous recommendation against routine screening for thyroid disease in healthy adults; this is consistent with the 2004 jointly issued guidelines from the American Thyroid Association, the American Association of Clinical Endocrinologists, and the Endocrine Society

Readings

Chaker L et al. Hypothyroidism. Lancet. 2017;390(10101):1550-1562. doi:10.1016/S0140-6736(17)30703-1; Duntas LH, Jonklaas J. Levothyroxine dose adjustment to optimise therapy throughout a patient’s lifetime. Adv Ther. 2019;36(Suppl 2):30-46. doi:10.1007/s12325-019-01078-2; Garber JR et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association [published correction appears in Thyroid. 2013 Feb;23(2):251] [published correction appears in Thyroid. 2013 Jan;23(1):129]. Thyroid. 2012;22(12):1200-1235. doi:10.1089/thy.2012.0205; Gosi SKY, Garla VV. Subclinical hypothyroidism. StatPearls Publishing. 2021 Jan 26; Gussekloo J et al. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004;292(21):2591-2599. doi:10.1001/jama.292.21.2591; Khandelwal D, Tandon N. Overt and subclinical hypothyroidism: who to treat and how. Drugs. 2012;72(1):17-33. doi:10.2165/11598070-000000000-00000; Ladenson PW et al. American Thyroid Association guidelines for detection of thyroid dysfunction [published correction appears in Arch Intern Med 2001 Jan 22;161(2):284]. Arch Intern Med. 2000;160(11):1573-1575. doi:10.1001/archinte.160.11.1573; Ralli M et al. Hashimoto’s thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Autoimmun Rev. 2020;19(10):102649. doi:10.1016/j.autrev.2020.102649; Roberts CG, Ladenson PW. Hypothyroidism. Lancet. 2004;363(9411):793-803. doi:10.1016/S0140-6736(04)15696-1; Safer JD. Thyroid hormone action on skin. Dermatoendocrinol. 2011;3(3):211-215. doi:10.4161/derm.3.3.17027.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Hueston was recorded on March 29, 2021, exclusively for Audio Digest, using virtual teleconference software, in compliance with current social-distancing guidelines during the COVID-19 pandemic. Audio Digest thanks Dr. Hueston for his cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

FP692401

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.