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thyrotoxicosis

A term that encompasses all forms of thyroid hormone excess, as distinguished from hyperthyroidism that relates specifically to excess thyroid hormone production by the thyroid gland. Etiology: 1) Graves disease 2) toxic multinodular goiter 3) thyroiditis 4) medications - iodine-induced thyrotoxicosis - iodinated contrast - amiodarone [1] - pharmaceutical lithium - interferon-alfa - interleukin-2 - tyrosine kinase inhibitors - immune checkpoint inhibitors 5) thyrotoxicosis facticia: exogenous thyroid hormone - levothyroxine may be found in weight-loss supplements [6] 6) hCG-mediated: pregnancy, trophoblastic disease, germ cell tumor 7) struma ovarii: autonomously functioning thyroid tissue within an ovarian teratoma 8) metastases of follicular thyroid cancer 9) TSH-secreting pituitary adenoma (rare) 10) immune reconstitution inflammatory syndrome Pathology: - excess thyroid hormone production by the thyroid - T3 thyrotoxicosis - thyroiditis resulting in release of preformed thyroid hormone Clinical manifestations: - tachycardia, fine tremor, hyperreflexia, lid lag, proximal muscle weakness - nervousness, anxiety, emotional lability - hyperhidrosis, heat intolerance - palpitations - increased defecation, diarrhea - weight loss - menstrual irregularity - symmetrically enlarged thyroid gland is consistent with Graves disease - also see hyperthyroidism Laboratory: - decreased or undetectable serum TSH - high serum free T4 &/or serum free T3 - if serum TSH is low, but serum free T4 is normal, high serum free T3 diagnoses T3 toxicosis (rare) [1] - serum thyroglobulin* - high with hyperthyroidism & thyroiditis - low with serruptitious thyroid hormone use [1] - thyroid auto-antibodies - anti-thyroid peroxidase Ab - anti-thyroglobulin Ab - thyrotropin (TSH)-receptor antibody (thyroid-stimulating immunoglobulin) is associated with Graves disease - elevated erythrocyte sedimentation rate supports diagnosis of thyroiditis * TSH receptor Ab in serum is the next test to order if low TSH & high free T4 &/or high total T3 (MKSAP20 anchors on Graves disease) [1] * MKSAP20 algorithm uses thyroid scintigraphy rather than serum thryoglobulin to assess exogenous thyroxine [1] Special laboratory: - color-flow doppler ultrasonography distinguishes hyperthyroidism (high flow) from thyroiditis (low flow)* [1] * distinguishes type 1 from type 2 amiodarone-induced thyrotoxicosis [1] * thyroid scintigraphy is test of choice for thyroid nodule(s) with low serum TSH & normal or high serum free T4 [1] * thyroid ultrasound generally not helpful for thyrotoxicosis [5] Radiology: - thyroid scintigraphy - radioactive iodine uptake (iodine-123 uptake) - high with hyperthyroidism & thyroiditis - low with serruptitious thyroid hormone use [1] - radionuclide scanning with iodine-123 or Tc-99m [5] - indicated vs ultrasound if serum TSH is low & serum free T4 is normal or high - contraindicated during pregnancy - not useful if patient has recently received iodinated contrast - diffuse increased uptake in Graves disease - patchy areas of increased uptake with decreased uptake in other areas in toxic multinodular goiter - focal area of increased uptake with decreased uptake in other areas with thyroid adenoma - decreased or no iodine I-123 uptake with - increased iodine load (IV contrast or amiodarone) - thyroiditis during thyrotoxic phase - serruptitious ingestion of thyroid hormona Differential diagnosis: - hyperthyroidism Complications: - increased risk of mild cognitive impairment or dementia in elderly >= 65 years [7] - thyroid storm is a life-threatening form of thyrotoxicosis Management: 1) thyroiditis a) painful inflammatory thyroiditis - non-steroidal anti-inflammatory agents (NSAIDs) - prednisone may be useful - not unless thyroid is tender to palpation (even if ESR elevated) [1] - NOT for infectious thyroiditis b) beta blockers for symptoms of hyperthyroidism 2) prednisone indicated for type 2 amiodarone-induced thyrotoxicosis 3) methimazole + propranolol if contrast-induced thyrotoxicosis [1] - methimazole contraindicated 1st trimester of prognancy & during lactation [1] 4) radioactive I-131 ablation 5) thyroid surgery 3) also see hyperthyroidism

Related

thyroiditis

Specific

factitious hyperthyroidism; factitious thyrotoxicosis; thyrotoxicosis facticia hyperthyroidism T3 thyrotoxicosis thyroid storm

General

endocrine disease sign/symptom

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025
  2. Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006 Dec;35(4):663-86 PMID: 17127140
  3. Vaidya B, Pearce SH. Diagnosis and management of thyrotoxicosis. Review. PMID: 25146390
  4. Bogazzi F, Bartalena L, Martino E. Approach to the patient with amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab. 2010 Jun;95(6):2529-35. Review. PMID: 20525904
  5. NEJM Knowledge+ Question of the Week. March 8, 2022. https://knowledgeplus.nejm.org/question-of-week/1666/ - Ross DS et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016 Oct; 26:1343 PMID: 27521067
  6. NEJM Knowledge+ Endocrinology
  7. Adams R, Oh ES, Yasar S et al Endogenous and Exogenous Thyrotoxicosis and Risk of Incident Cognitive Disorders in Older Adults. JAMA Intern Med. Published online October 23, 2023 PMID: 37870843 PMCID: PMC10594176 (available on 2024-10-23) https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2811088 - Papaleontiou M, Brito JP. Disentangling the association between excess thyroid hormone and cognition in older adults. JAMA Intern Med 2023 Oct 23; [e-pub] PMID: 37870840 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2811093