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hyperthyroidism

Classification: - thyrotoxicosis describes high levels of thyroid hormone (T4 & T3) from any cause - hyperthyroidism is caused by excessive endogenous thyroid hormone production by the thyroid gland [3] Etiology: 1) Graves' disease (most common cause) 2) thyroid neoplasm a) thyroid adenoma (uncommon) b) hyperfunctioning thyroid carcinoma, esp. metastatic 3) postpartum (uncommon, transient) 4) neonatal hyperthyroidism due to maternal Graves' disease 5) TSH-secreting pituitary tumor 6) hypersecretion of hypothalamic TRH 7) genetic defects in thyrotropin receptor (TSHR) * also see Differential diagnosis (below) Epidemiology: - affects ~ 0.2-1.4% of people worldwide [12] Pathology: 1) skeletal muscle: myopathy (normal serum creatine kinase) [3] 2) cardiac a) increased heart rate b) increased stroke volume c) increased cardiac output d) decreased peripheral vascular resistance e) widened pulse pressure f) acute heart failure [3] 3) morphology: a) cardiomegaly b) atrophy & fatty infiltration of skeletal muscle c) focal interstitial lymphocytic infiltration d) minimal fatty changes in liver e) osteoporosis f) generalized lymphoid hyperplasia & lymphadenopathy Genetics: - may be associated with defects in thyrotropin receptor (TSHR) Clinical manifestations: Symptoms: - alertness, emotional lability, irritability, nervousness, proximal muscle weakness, palpitations, hyperphagia, weight loss, diarrhea, heat intolerance, dyspnea, arthralgias, menstrual irregularity Signs: - hyperkinesia, rapid speech, quadriceps weakness, fine tremor, abundant fine hair, moist skin, increased sweating, osteopenia, onycholysis, lid lag, stare, chemosis, periorbital edema, proptosis, extraocular muscle palsy, accentuated heart sound, tachycardia, atrial fibrillation, wide pulse pressure, systolic ejection murmur, midsystolic click, bounding pulse, forceful apical pulse, goiter, bilateral pretibial edema, vitiligo Elderly patients: a) sympathetic manifestations may be absent b) may present only with weight loss, anorexia, CHF, palpitations or atrial fibrillation Laboratory: 1) increased total serum T4, serum free T4, serum T4 index 2) increased serum total T3 or serum free T3 if serum T4 is normal (T3 toxicosis) 3) suppressed serum TSH (primary hyperthyroidism) - levels generally < 0.005 mU/mL 4) elevated serum TSH, serum T4 & serum free T3 suggest TSH-secreting pituitary tumor 5) low serum TSH; normal serum T4 & serum free T3 suggest subclinical hyperthyroidism 5) thyroid-stimulating immunoglobulin in serum 6) thyroid peroxidase antibody in serum to identify Hashimoto's thyroiditis 7) elevated serum thyroglobulin & ESR distinguish thyroiditis from serreptitious ingestion of thyroxine (suppressed serum thyroglobulin & normal ESR) 8) serum creatine kinase is normal [3] * serum T4, serum free T4 & serum TSH initial diagnostic tests [3] Special laboratory: - color-flow doppler ultrasonography distinguishes hyperthyroidism (high flow) from thyroiditis (low flow)* [3,4] * distinguishes type 1 from type 2 amiodarone-induced thyrotoxicosis [3,4] Radiology: 1) thyroid scan (radioactive iodine-123 uptake) a) contraindicated in pregnancy b) propylthiouracil, methimazole & iodides interfere, stop at least 1 week prior to scan; propranolol is OK c) radioactive iodine uptake is increased in - Graves disease - toxic multinodular goiter - solitary thyroid adenoma d) radioactive iodine uptake is suppressed in - thyroiditis: - Hashimoto's thyroiditis - subacute thyroiditis - factitious hyperthyroidism - recent iodine load (contrast) 2) 99m-Tc-pertechnate scan (technesium scan) identifies a) autonomously functioning thyroid nodule or b) multinodular goiter Differential diagnosis: - euthyroid sick syndrome - low serum TSH; normal serum T4 & serum free T4 - thyrotoxicosis - toxic multinodular goiter - most common cause in older patients - iodine from contrast agents or amiodarone can precipitate thyrotoxicosis - iodide-induced (uncommon, transient) i.e. amiodarone, contrast agents - subacute thyroiditis (uncommon, transient) - factitious or iatrogenic exogenous T4 - choriocarcinoma or hydatidiform mole - chorionic gonadotropin - TSH-like molecule - struma ovarii (ovarian teratomatous thyroid) Complications: - osteoporosis [3], increased risk of fractures - thyroid storm is severe life-threatening hyperthyroidism Management: 1) see thyroid storm, severe life-threatening hyperthyroidism 2) radioactive I-131 ablation a) 100 to 200 uCi/g of tissue b) maximal effect in 2-3 months c) hypothyroidism eventually occurs in 80% of patients - thyroid hormone replacement as needed d) exacerbation of ophthalmopathy (controversial) - ref [2] does not mention any controversy - use methimazole if symptomatic Graves ophthalmopathy 3) subtotal thyroidectomy 4) pharmacologic a) thionamides -inhibit thyroid hormone synthesis 1] methimazole 15 mg QD or BID [5] a] preparation for thyroidectomy b] severe Graves disease ophthalmopathy c] reluctance to take radioiodine d] contraindicated in 1st trimester of pregnancy 2] propylthiouracil a] also inhibits peripheral T4 -> T3 conversion b] 1st trimester of pregnancy or lactating women (ok) [7,9] 3] methimazole better than propylthiouracil - except during 1st trimester of pregnancy [5] - methimazole for 2nd & 2rd trimester of pregnancy 4] not useful for thyroiditis resulting in release of preformed thyroid hormone [3] - de Quervain thyroiditis (anticedent URI) b) beta-adrenergic receptor antagonists - propranolol 20-40 mg PO QID a] control of palpitations, tremor, anxiety b] also inhibits peripheral T4 -> T3 conversion c) iodide inhibits release of hormone from thyroid gland 1] saturated solution of KI (SSKI) 2] Lugol's solution 3] not recommended in pregnant women [3] - safe for fetus, but less effective than propylthiouracil d) other iodide-containing agents 1] sodium ipodate (Oragrafin) 2] iopanoic acid (Telepaque) 3] amiodarone 4] these agents also inhibit T4 -> T3 conversion e) thyrotoxicosis can masquerade as hyperthyroidism - amiodarone iodide-induced thyrotoxicosis (see amiodarone) - treat with moderate to high-dose prednisone tapered over 1-3 months [3] f) NSAIDs or glucocorticoids for painful thyroiditis [3] 5) treat depression if present in apathetic variant of hyperthyroidism [4] 6) anticoagulation for atrial fibrillation unnecessary if no other thromboembolic risk factors - anticoagulation prior to cardioversion if thromboembolic risk factors (CHA2DS2-VASc score > 1 men, > 2 women) - direct-oral anticoagulant for rate controlled atrial fibrillation 7) screening not recommended: insufficient data to recommend for or against screening for thyroid disease in non-pregnant adults [8]

Related

Graves disease (Basedow's disease, exothalmic goiter) thyroidectomy toxic multinodular goiter (Plummer's disease)

Specific

factitious hyperthyroidism; factitious thyrotoxicosis; thyrotoxicosis facticia hashitoxicosis hyperthyroidism during pregnancy selective pituitary thyroid hormone resistance (PRTH); familial hyperthyroidism due to inappropriate thyrotropin secretion subacute lymphocytic thyroiditis subclinical hyperthyroidism thyrotoxic hypokalemic periodic paralysis

General

thyroid disease thyrotoxicosis

Database Correlations

OMIM correlations MORBIDMAP 603372

References

  1. DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin, McGraw Hill, New York 1994
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 54, 205
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Solomon DH, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  5. Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by graves' disease. J Clin Endocrinol Metab. 2007 Jun;92(6):2157-62. Epub 2007 Mar 27. PMID: 17389704
  6. Bahn Chair RS et al Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011 Jun;21(6):593-646 PMID: 21510801 (corresponding NGC guideline withdrawn Nov 2016)
  7. De Groot L et al Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab August 1, 2012 97(8):2543 PMID: 22869843 http://jcem.endojournals.org/content/97/8/2543.abstract (corresponding NGC guideline withdrawn Feb 2018) - Stagnaro-Green A Optimal Care of the Pregnant Woman with Thyroid Disease J Clin Endocrinol Metab August 1, 2012 97(8):2619 PMID: 22869845 http://jcem.endojournals.org/content/97/8/2619.full
  8. LeFevre ML et al Screening for Thyroid Dysfunction: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. Published online 24 March 2015 PMID: 25798805 http://annals.org/article.aspx?articleid=2208599
  9. Lazarus JH Management of hyperthyroidism in pregnancy. Endocrine. 2014 Mar;45(2):190-4 PMID: 24174179
  10. De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016 Aug 27;388(10047):906-918. Review. PMID: 27038492 Free PMC Article
  11. McDermott MT. Hyperthyroidism. Ann Intern Med. 2020;172:ITC49-ITC64. PMID: 32252086
  12. Lee SY, Pearce EN Hyperthyroidism. A Review. JAMA. 2023;330(15):1472-1483. PMID: 37847271 https://jamanetwork.com/journals/jama/fullarticle/2810692