A group of diseases caused by excessive synthesis and secretion of thyroid hormone by the thyroid gland
A hypermetabolic state that results from excess thyroid hormone and can occur in the presence or absence of hyperthyroidism. The resulting clinical manifestations are a consequence of the high concentration of thyroid hormone in the tissues
Thyrotoxic crisis/ thyroid storm:
Rare but life-threatening exacerbation of hyperthyroidism, usually precipitated by acute illness or surgery
The most common cause of thyrotoxicosis is Graves’ disease in which thyrotropin receptor antibodies (TRAbs) binds to and stimulates thyroid stimulating hormone receptors (TSHR) on the thyroid cells and results in increased production of T3 and T4.
The following table document causes of thyrotoxicosis and hyperthyroidism.
Assessment of disease severity and underlying cause as determined by history, physical and investigations
Factors that are important to consider in the choice of treatment:
Presence of ophthalmopathy
Obtain CBC and LFTs before the initiation of antithyroid medication.
Regardless of etiology, beta blockers may be started as soon as in laboratory confirmed thyrotoxicosis, except in patients with significant history of asthma; where it is contraindicated.
Note: Calcium channel blockers (verapamil and diltiazem) may be used for rate control in patients intolerant to beta blockers, or in whom it is contraindicated.
Management of overt hyperthyroidism due to Graves’ disease:
Patients should be treated with any of the following modalities i.e.
131I therapy ( radioactive iodine)
Antithyroid drugs (ATDs)
Typically in North America, physicians prefer radioactive iodine, while in Europe and Japan ATD’s/or surgery is preferred. However, the long-term quality of life following any one of the treatment modality is the same.
Management of thyroid nodule in patients with Graves’ disease:
Thyroid nodule larger than 1-1.5 cm should always be evaluated prior to radioactive iodine therapy in GD. The occurrence of thyroid cancer is approximately ≤2% in GD.
Following steps are recommended on discovery of a thyroid nodule:
Any nonfunctioning or hypoactive nodule should be considered for fine needle aspiration
If pathology is suspicious or confirms malignancy, surgery is advised after normalization of thyroid function
Management of thyroid storm associated complication:
Thyroid storm is a life-threatening disorder characterized by involving multiple systems with high mortality if not treated immediately and aggressively.
Criteria for thyroid storm has been defined by Burch- Wartofsky score; is solely based on clinical and physical assessment, which covers the following factors:
Central nervous effects
Hepatic and gastrointestinal symptoms
Treatment comprises of:
Provide immediate IV fluids, oxygen, ventilatory support, and ICU monitoring if needed
Aggressive cooling with cooling blankets; followed by acetaminophen 15 mg/kg every 4 hrs, orally or rectally is administered in hyperthermia
Administer antithyroid drugs to block the synthesis of new hormone; methimazole (MMI) 60-80 mg/day, or propylthiouracil (PTU) 500-1000 mg loading dose, then 250 mg every 4 hourly
Beta-blockers (propranolol 60-80 mg every 4 hrs); it blocks T4 to T3 conversion and also used in patients with congestive cardiac failure (CCF)
Iodine (SSKI) 5 drops (0.25 ml or 250 mg) PO every 6 hrs, to block thyroid hormone release and new hormone synthesis
To further block the conversion of T4-T3, and avoid adrenal insufficiency; administer hydrocortisone 300 mg IV loading dose followed by 100 mg every 8 hrs
Management of overt hyperthyroidism due to TMNG or TA:
Treatment is focused to achieve rapid and sustained euthyroid state, there are two main treatment modalities recommended.
Note: Sometimes lifelong ATDs are the best choice for elderly patients who are in nursing homes, have increased surgical risk and are with limited life expectancy. The treatment requires frequent monitoring (every 3 months).
Subclinical hyperthyroidism is defined by low TSH less than 0.3 mU/L (or undetectable) with normal free T4 estimates and normal total T3 or free T3 estimates.
Usually, an incidental finding during a routine physical or sometimes signs and symptoms suggest the possibility of hyperthyroidism to the physician
Once the results are confirmed by repeating the labs, determine the cause of low TSH by excluding other causes of decrease TSH levels such as:
Pituitary and hypothalamic disease
Euthyroid sick sinus syndrome
Drugs e.g. dobutamine, dopamine and steroids
Pregnancy: First trimester
Factitial TSH suppression e.g. excessive thyroid hormone ingestion
In elderly TMNG is probably the most common cause of SH
Patients with GD rather than a TMNG as the cause of SH may be more likely to spontaneously revert
It is important to diagnose SH; because there is 2.8 folds risk of atrial fibrillation in individuals over the age of 60 yrs, likewise post-menopausal females with SH have increased risk of fractures
Who to Treat according to the age and TSH levels:
Individuals who are >65 years with TSH <0.1 mU/L should be treated; while 0.1-0.5 mU/L should be considered for therapy
Individuals aged <65 years with TSH < 0.1 mU/L with heart disease, osteoporosis and hyperthyroid symptoms should be treated while with TSH 0.1-0.5 mU/L with heart disease, menopausal females and hyperthyroid symptoms should consider treatment
Individuals with aged <65 years and asymptomatic may consider treatment with TSH <0.1 mU/L
Treatment of subclinical hyperthyroidism will depend on its cause. In the case of clinical evidence for underlying Graves’ disease (goiter, ophthalmopathy, positive TSH (receptor antibodies), low-dose thiourea therapy with methimazole could be considered as well as radioiodine.
Management of hyperthyroidism in pregnancy:
If GD is diagnosed during 1st trimester of pregnancy, PTU is recommended treatment. Measure TRAb at diagnosis and if elevated repeat at 22-26 weeks of gestation; if thyroidectomy indicated then perform in 2nd trimester
If it is diagnosed after 1st trimester methimazole is recommended; if surgery indicated it should be done in 2nd trimester
Diagnosed and treated females prior pregnancy; should switch to PTU from methimazole if pregnancy is confirmed
Once in remission after stopping ATDs, TRAb monitoring is not required
If previous treatment with radioiodine or surgery, TRAb are measured initially and if high then repeat 22-26 weeks of gestation
Management of Graves’ ophthalmopathy (GO):
Graves’ ophthalmopathy is defined as an inflammation of the orbital and periorbital soft tissues effecting on the eye; such as pain, itching, chemosis, retraction of the eyelids, and proptosis associated with hyperactivity of thyroid gland.
Approximately 50% of Graves’ hyperthyroidism presents with Graves’ ophthalmopathy, and 5% tend to suffer from severe disease.
Assessment of the disease activity is calculated by a clinical activity score (CAS)**. The score ranges from 0-10 and also predicts response to anti-inflammatory therapy. GO is considered active if the CAS ≥3.
The severity of disease is graded as follows:
Mild GO: Features of GO, having very mild effects on daily life, insufficient to justify treatment
Moderate to severe GO: Features having significant effects on daily life but without sight threatening GO; sufficient to justify treatment with immunosuppressive (inactive disease) or surgical intervention (if inactive disease)
Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: Management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011;17:456-520
Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist Association. Toronto: Webcom Inc. 2012
Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth’s Textbook of Canadian Medical-Surgical Nursing. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6th ed. Toronto: Webcom Inc. 2011
Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 1st ed. New York: McGraw-Hill; 2009
Longo D, Fauci A, Kasper D, et al (eds). Harrison’s Principles of Internal Medicine. 18thed. New York: McGraw-Hill; 2011
Management of thyroid dysfunction during pregnancy and postpartum. An endocrine society clinical practice guidelines. 2007 J Clin Endocrinol Metab:92; S1-S47
Mechanick JI, Pessah-Pollack R, Camacho P, et al. American Association Of Clinical Endocrinologists And American College Of Endocrinology Protocol For Standardized Production Of Clinical Practice Guidelines, Algorithms, And Checklists – 2017 Update. Endocrine Practice:2017, Vol. 23, No. 8, pp. 1006-1021. doi: 10.4158/EP171866.GL
McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49th ed. New York: McGraw-Hill; 2010
Pagana KD, Pagana TJ eds. Mosby’s Diagnostic and Laboratory Test Reference. 9th ed. St. Louis: Elsevier-Mosby; 2009
Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26:1343-1421. DOI: 10.1089/thy.2016.0229
Skidmore-Roth L. ed. Mosby’s drug guide for nurses. 9th ed. St. Louis: Elsevier-Mosby; 2011
Skidmore-Roth L, ed. Mosby’s nursing drug reference. 24th ed. St. Louis: Elsevier-Mosby; 2011
Suwansaksri N, Preechasuk L, Kunavisarut T. Nonthionamide Drugs for the Treatment of Hyperthyroidism: From Present to Future. International Journal of Endocrinology. 2018. 1-10. 10.1155/2018/5794054. https://doi.org/10.1155/2018/5794054
Online Pharmacological Resources:
Assessment of iodine deficiency disorders and monitoring their elimination. A guide for programme managers, (3rd edition). World Health Organization 2007
Aoki Y, Belin RM, Clickner R, Jeffries R, Phillips L, Mahaffey KR. Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002). Thyroid. Dec 2007;17(12):1211-23
Abraham P, Avenell A, Park CM, et al. A systematic review of drug therapy for Graves’ hyperthyroidism. Eur J Endorinol. 2005;153:489-498
Boelaert K, Torlinska B, Holder RL, Franklyn JA. Older subjects with hyperthyroidism present with a paucity of symptoms and signs: a large cross-sectional study J Clin Endocrinol Metab. 2010; 95:2715-26
Bogazzi F, Giovannetti C, Fessehatsion R, et al. Impact of lithium on efficacy of radioactive iodine therapy for Graves’ disease: a cohort study on cure rate, time to cure, and frequency of increased serum thyroxine after antithyroid drug withdrawal. J Clin Endocrinol Metab. 2010;95: 201-208
Collet T-H, Gussekloo J, Bauer DC, et al. Subclinical Hyperthyroidism and the Risk of Coronary Heart Disease and Mortality Archives of Internal Medicine 2012; 172:799-809. doi:10.1001/archinternmed.2012.402
Jumaily JS, Noordzij JP, Dukas AG, et al. Prediction of hypocalcemia after using 1- to 6-hour postoperative parathyroid hormone and calcium levels: an analysis of pooled individual patient data from 3 observational studies. Head Neck. 2010;32:427-434
Kikuchi S, Noguchi S, Yamashita H, et al. Prognosis of small thyroid cancer in patients with Graves’ disease. Br J Surg. 2006; 93:434-439
Mazza E, Carlini M, Flecchia D, et al. Long-term follow-up of patients with hyperthyroidism due to Graves’ disease treated with methimazole. Comparison of usual treatment schedule with drug discontinuation vs continuous treatment with low methimazole doses: a retrospective study. J Endocrinol Invest. 2008;31:866-872
Metso S, Auvinen A, Huhtala H, et al. Increased cancer incidence after radioiodine treatment for hyperthyroidism. Cancer 2007; 109:1972-9
Nakamura H, Noh JY, Itoh K, et al. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease. J Clin Endocrinol Metab. 2007;92:2157-2162
Peters H, Fischer C, Bogner U, et al. Treatment of Graves’ hyperthyroidism with radioiodine: results of a prospective randomized study. Thyroid. 1997;7:247-251
Roh JL, Park CI. Routine oral calcium and vitamin D supplements for prevention of hypocalcemia after total thyroidectomy. Am J Surg. 2006;192:675-678
Ruiz JK, Rossi GV, Vallejos HA, et al. Fulminant hepatic failure associated with propylthiouracil. Ann Pharmacother. 2003;37:224-228
Tajiri J, Noguchi S, Murakami T, et al. Antithyroid drug-induced agranulocytosis. The usefulness of routine white blood cell count monitoring. Arch Intern Med. 1990;150:621-624