Hyperthyroidism encompasses a spectrum of conditions united by excess circulating thyroid hormone, but the underlying pathophysiology determines both the pharmacological approach and the expected response to treatment. Graves’ disease, the dominant cause in younger patients, is driven by thyroid-stimulating immunoglobulins that autonomously activate the thyroid-stimulating hormone (TSH) receptor and are amenable to immunological remission with prolonged thionamide therapy. Toxic multinodular goiter and solitary toxic adenomas, more common in older patients and iodine-deficient populations, represent clonal follicular autonomy that does not remit with thionamides and requires definitive ablation. This module covers the pharmacology of thionamide drugs in depth including their mechanisms, ADME, adverse effect profiles, and the evidence base for selecting propylthiouracil (PTU) versus methimazole in specific clinical situations, followed by adjunctive pharmacotherapy with beta-blockers and iodide, and the pharmacological management of thyroid storm, the most dangerous acute manifestation of thyroid hormone excess.
Graves’ disease is an autoimmune disorder in which thyroid-stimulating immunoglobulins (TSIs), also called thyroid-stimulating antibody (TSAb) or TSH receptor antibody (TRAb), bind and chronically activate the TSH (thyroid-stimulating hormone) receptor on thyroid follicular cells, producing unregulated thyroid hormone synthesis and secretion that is independent of pituitary TSH control. Thyroid-stimulating immunoglobulin (TSI) binding activates the Gs-cyclic adenosine monophosphate (cAMP) pathway with the same downstream consequences as TSH binding, but unlike TSH, TSIs are not subject to negative feedback suppression by thyroid hormone, which is why the hyperthyroid state perpetuates until immunosuppression, ablation, or spontaneous remission intervenes. TSIs also stimulate follicular cell proliferation, accounting for the diffuse goiter that characterizes Graves’ disease. The autoimmune pathogenesis involves T-helper (CD4+) cell sensitization to thyroid antigens, B-cell production of TSIs, and a complex genetic susceptibility landscape involving HLA-DR3 (human leukocyte antigen DR3), CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), and PTPN22 (protein tyrosine phosphatase non-receptor type 22) gene variants; environmental triggers including smoking, iodine excess, stress, and pregnancy are implicated in disease precipitation.1,2
The extrathyroidal manifestations of Graves’ disease are unique to this autoimmune etiology and do not occur in toxic nodular hyperthyroidism, because they are driven by TSH receptor expression in non-thyroidal tissues rather than by thyroid hormone excess per se. Graves’ ophthalmopathy, occurring in approximately 25–50% of patients, results from TSH receptor-expressing orbital fibroblasts being targeted by the same autoimmune response that drives thyroid disease; fibroblast activation leads to glycosaminoglycan deposition, orbital fat expansion, and extraocular muscle enlargement producing proptosis, diplopia, and in severe cases corneal exposure and compressive optic neuropathy. Ophthalmopathy can worsen after radioactive iodine (RAI) treatment, particularly in smokers, and this risk must factor into definitive therapy selection. Graves’ dermopathy (pretibial myxedema) and thyroid acropachy are rare extrathyroidal manifestations sharing the same fibroblast-mediated pathogenesis.1,2
Toxic multinodular goiter (TMNG) and toxic adenoma (TA) represent a different pathophysiological substrate. In TMNG, multiple follicular nodules acquire somatic mutations in the TSH receptor or in downstream signaling components (particularly Gs alpha subunit, encoded by GNAS) that constitutively activate cAMP production, driving autonomous thyroid hormone secretion independent of TSH. Unlike Graves’ disease, TMNG does not have an autoimmune basis, TRAb are negative, and there is no risk of spontaneous immunological remission. Thionamides effectively suppress thyroid hormone synthesis in TMNG but cannot induce remission; they are used primarily for pre-procedural control before definitive RAI or surgical ablation. The distinction between Graves’ disease and TMNG is established by TRAb measurement and thyroid scintigraphy: Graves’ disease shows diffuse homogeneous uptake, while TMNG shows patchy heterogeneous uptake with hot nodules suppressing surrounding normal tissue.1,3
TRAb (TSH receptor antibodies) measured as thyroid-stimulating immunoglobulins (TSIs) or inhibitory immunoglobulins (TBAb) serve three clinical roles: (1) confirming Graves’ disease diagnosis when scintigraphy is unavailable or contraindicated; (2) predicting relapse risk after thionamide discontinuation — persistently elevated TRAb at 12–18 months predicts high relapse risk; and (3) predicting neonatal Graves’ disease when measured in pregnant women, since maternal TSIs cross the placenta and can stimulate the fetal thyroid at concentrations above 3x the upper reference limit.
Thionamide drugs, comprising methimazole (MMI) and propylthiouracil (PTU), inhibit thyroid hormone biosynthesis by blocking thyroid peroxidase (TPO)-mediated iodide organification and iodotyrosine coupling within the thyroid follicular lumen. Methimazole is approximately 10 times more potent than PTU on a milligram basis and is the preferred thionamide for most clinical situations. PTU has a second pharmacodynamic action not shared by methimazole: inhibition of type 1 deiodinase (D1) in peripheral tissues, reducing the conversion of thyroxine (T4) to the more potent triiodothyronine (T3) by approximately 40%. This peripheral conversion blockade makes PTU theoretically preferable in thyroid storm, where rapid reduction of T3 availability is therapeutically important, and it accounts for why PTU produces a faster reduction in serum T3 despite slower normalization of T4 compared with methimazole. Thionamides do not block release of preformed thyroid hormone already stored in the follicular colloid, which is why a 2–4 week lag before significant clinical improvement is expected even after adequate dosing is established.2,4
Two dosing strategies are used in clinical practice for Graves’ disease. The titrate-to-block approach begins at a moderately high starting dose and reduces the dose progressively as thyroid function normalizes over weeks to months, ultimately reaching a low maintenance dose that suppresses residual autonomous thyroid hormone secretion. This strategy minimizes the risk of iatrogenic hypothyroidism but requires more frequent laboratory monitoring and dose adjustments. The block-and-replace strategy uses a high fixed dose of thionamide to fully suppress endogenous thyroid hormone synthesis while simultaneously administering levothyroxine to maintain euthyroidism. This approach simplifies monitoring by eliminating the need for dose titration, produces more stable free T4 levels throughout treatment, and may reduce the risk of fluctuation between hypothyroid and hyperthyroid states, but exposes the patient to higher cumulative thionamide doses and carries increased adverse effect risk in pregnancy because methimazole and PTU cross the placenta more readily than levothyroxine at the doses required. Block-and-replace is therefore contraindicated in pregnancy.1,4
Remission rates after 12–18 months of thionamide therapy in Graves’ disease range from 40–60%, with higher remission rates in patients who have small goiters, mild biochemical hyperthyroidism, and TRAb that normalize during treatment. Patients with large goiters, high initial TRAb titers, and persistent TRAb at the end of treatment have high relapse rates (60–70% within one year of discontinuation) and should be counseled toward definitive therapy with radioactive iodine (RAI) or thyroidectomy after thionamide control is established. A prolonged treatment course of 18–24 months versus the traditional 12 months does not substantially improve remission rates in most patients, though a small subgroup with declining TRAb may benefit from extension. When relapse occurs, a second course of thionamide therapy rarely achieves remission; definitive therapy should be recommended.1,4
Thionamides block new hormone synthesis but do not release preformed T4 and T3 from the follicular colloid. The thyroid gland stores 2–3 months’ supply of thyroid hormone as thyroglobulin. Clinical improvement depends on depletion of this store through ongoing secretion while new synthesis is blocked. Initiating beta-blockade simultaneously provides symptomatic relief during this lag period. Patients who improve dramatically within days of thionamide initiation may have had a destructive thyroiditis component rather than Graves’ disease.
Methimazole has superior pharmacokinetics for routine outpatient use. Oral bioavailability is approximately 93%, the elimination half-life is 4–6 hours, and the drug concentrates in thyroid tissue where intrathyroidal half-life is substantially longer, allowing once-daily dosing despite the relatively short plasma half-life. Standard starting doses range from 10–40 mg/day depending on hyperthyroid severity; doses above 40 mg/day rarely provide additional benefit because thyroid peroxidase (TPO) inhibition is nearly complete at lower doses. Methimazole crosses the placenta and is present in breast milk, but at standard doses the risk of fetal hypothyroidism is low with appropriate monitoring. Propylthiouracil (PTU) has lower and more variable oral bioavailability (50–75%), a shorter plasma half-life of 1–2 hours requiring three-times-daily dosing, higher plasma protein binding (approximately 80%), and lower placental transfer per milligram than methimazole, which is the pharmacokinetic basis for its first-trimester preference in pregnancy. Standard PTU doses are 100–200 mg three times daily for moderate hyperthyroidism, scaling to 200–300 mg three times daily for severe disease or storm.2,4,5
Agranulocytosis is the most feared adverse effect of thionamide therapy, occurring in 0.1–0.5% of treated patients. It presents as an abrupt onset of fever and pharyngitis, typically within the first 90 days of treatment, caused by immune-mediated destruction of granulocyte precursors. The reaction is idiosyncratic rather than dose-dependent for most patients, though higher doses (methimazole above 40 mg/day) may carry marginally higher risk. Routine complete blood count (CBC) monitoring has not been shown to prevent mortality because agranulocytosis can develop between monitoring intervals; the clinically important intervention is patient education. Every patient starting a thionamide must be instructed to stop the drug immediately and seek urgent evaluation if fever or sore throat develops. Granulocyte-colony stimulating factor (G-CSF) accelerates neutrophil recovery in established agranulocytosis and reduces the duration of severe neutropenia. Thionamide-induced agranulocytosis is a class effect: patients who develop agranulocytosis on one thionamide should not be rechallenged with the other.5,6
Hepatotoxicity has distinct patterns for the two thionamides with sharply divergent severity profiles. Methimazole produces a cholestatic pattern with elevated alkaline phosphatase and bilirubin, which is generally mild and reversible on drug discontinuation. PTU produces an idiosyncratic fulminant hepatic necrosis pattern with hepatocellular injury; the FDA issued a black box warning for PTU in 2010 after cases of liver failure, liver transplantation, and death, predominantly in pediatric patients. This hepatotoxicity risk is the primary reason PTU is no longer recommended as a first-line agent except in the first trimester of pregnancy, thyroid storm, and patients with a confirmed allergy to methimazole but not PTU. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, manifesting as glomerulonephritis, pulmonary hemorrhage, or cutaneous vasculitis, occurs more commonly with PTU (reported prevalence up to 4% in long-term users) than with methimazole, making PTU a poor choice for patients requiring prolonged therapy.5,6
The PTU versus methimazole selection decision is governed by four clinical rules. Rule 1: methimazole is preferred for all non-pregnant adults and for hyperthyroid children. Rule 2: PTU is preferred in the first trimester of pregnancy because methimazole embryopathy (aplasia cutis congenita, choanal atresia, esophageal atresia, and the methimazole embryopathy syndrome) occurs during organogenesis at weeks 6–10; PTU carries no equivalent teratogenic risk profile in the first trimester. Rule 3: at 16 weeks gestation, after organogenesis is complete, the patient should be switched from PTU back to methimazole to reduce the risk of PTU-associated fulminant hepatitis during the longer second and third trimester exposure. Rule 4: PTU is preferred in thyroid storm because its inhibition of peripheral type 1 deiodinase (D1) reduces triiodothyronine (T3) production, which methimazole cannot accomplish. These four rules cover the overwhelming majority of clinical decisions regarding thionamide selection.5,6,7
Every patient starting methimazole or PTU must be told explicitly: if you develop fever or sore throat, stop the drug immediately and go to the emergency department for an urgent complete blood count. Do not wait for an office appointment. Do not self-treat with antibiotics. Agranulocytosis resolves in most patients if the drug is stopped promptly; unrecognized continued exposure in the setting of agranulocytosis carries mortality risk. This education must be documented and repeated at each visit.
Beta-adrenergic receptor blockers are the mainstay of symptomatic management in hyperthyroidism, providing rapid relief of palpitations, tremor, anxiety, heat intolerance, and exercise intolerance while thyroid hormone levels decline over weeks on thionamide therapy. Propranolol, a non-selective beta-blocker, is the most widely used agent and has the additional advantage of inhibiting type 1 deiodinase (D1) at high doses (80–160 mg/day), reducing peripheral thyroxine (T4)-to-T3 (triiodothyronine) conversion and lowering circulating T3 by approximately 10–20%; this dual action makes it particularly useful in thyroid storm. Atenolol and metoprolol are cardioselective alternatives preferred in patients with reactive airway disease, though cardioselectivity is relative and all beta-blockers should be used with caution in asthma. The target resting heart rate in hyperthyroid patients on beta-blockade is below 90 beats per minute. Beta-blockers do not affect thyroid hormone synthesis, secretion, or the underlying autoimmune process, and must be tapered gradually as thionamide control is established and thyroid hormone levels normalize to avoid rebound tachycardia.1,4
Iodide in pharmacological doses exploits two distinct physiological mechanisms. The Wolff-Chaikoff effect, in which excess iodide transiently inhibits thyroid peroxidase (TPO)-mediated organification within hours of administration, reduces ongoing thyroid hormone synthesis. Additionally, pharmacological iodide reduces thyroid gland vascularity and firmness over 7–14 days by an incompletely understood mechanism that is distinct from its effect on synthesis, making the gland more technically manageable at surgery. Lugol’s iodine solution (approximately 8 mg iodide per drop, usually given as 5–10 drops three times daily) and saturated solution of potassium iodide, abbreviated SSKI (approximately 38 mg iodide per drop, given as 1–5 drops three times daily) are the two available preparations. Iodide must never be given before thionamide loading in thyroid storm, because the iodide substrate could paradoxically increase thyroid hormone synthesis until the Wolff-Chaikoff effect is established; thionamide must precede iodide by at least one hour. The thyroid gland escapes from Wolff-Chaikoff inhibition within days to weeks by downregulating NIS (sodium-iodide symporter), so iodide is not a durable antithyroid therapy and should not be used as sole long-term treatment.2,4
Cholestyramine, a bile acid sequestrant, binds thyroid hormone in the intestinal lumen and interrupts enterohepatic recirculation, reducing the effective pool of circulating T4 and T3. At doses of 4 g four times daily, cholestyramine can accelerate the decline of thyroid hormone levels and is used as an adjunct in thyroid storm or when rapid control is needed before surgery in patients with contraindications to other agents. Glucocorticoids, particularly hydrocortisone or dexamethasone, reduce thyroid hormone secretion by inhibiting glandular release of preformed hormone and additionally inhibit peripheral D1 activity, lowering T3 levels. In thyroid storm, dexamethasone 2 mg every 6 hours or hydrocortisone 100 mg every 8 hours is used as part of the comprehensive multi-drug protocol. Glucocorticoids are also indicated prophylactically when radioactive iodine (RAI) is given to patients with significant Graves’ ophthalmopathy, where RAI-associated immunological flares can worsen orbital disease; oral prednisone 0.4 mg/kg/day started at the time of RAI and tapered over 3 months substantially reduces the risk of ophthalmopathy progression.1,4
Iodide must be given at least one hour after thionamide loading in thyroid storm. If iodide is given first, the sudden excess of iodide substrate reaches a TPO enzyme that is not yet inhibited; this can transiently increase thyroid hormone synthesis before the Wolff-Chaikoff effect is established (the Jod-Basedow phenomenon in reverse). The correct sequence: PTU 500–1000 mg PO/NG load → wait 1 hour → Lugol’s iodine or SSKI → propranolol IV/PO → hydrocortisone IV → supportive care.
Thyroid storm is a life-threatening decompensation of thyrotoxicosis in which the systemic effects of excess thyroid hormone overwhelm compensatory mechanisms, producing multi-organ dysfunction with mortality rates of 10–25% even with aggressive treatment. The Burch-Wartofsky Point Scale (BWPS) provides a semi-quantitative scoring system based on thermoregulatory, cardiovascular (heart rate, atrial fibrillation, congestive heart failure), central nervous system (CNS), and gastrointestinal-hepatic manifestations; a score above 45 is highly suggestive of thyroid storm and above 25 suggests impending storm. Precipitating factors include infection, surgery, trauma, iodine loading (contrast agents, amiodarone), and abrupt thionamide discontinuation, and the precipitant must be aggressively identified and treated concurrently with anti-thyroid pharmacology. Thyroid hormone levels in storm are often only modestly elevated above baseline hyperthyroid levels, reflecting the fact that storm is a systemic decompensation rather than simply a quantitative excess of hormone; the degree of decompensation depends on adrenergic hyperactivation and end-organ susceptibility as much as on thyroid hormone concentrations per se.1,8
The pharmacological management of thyroid storm is a multi-drug protocol with mandatory sequencing. The first priority is thionamide loading: propylthiouracil (PTU) 500–1000 mg by mouth or by nasogastric (NG) tube as a loading dose, followed by 200–250 mg every 4 hours, is preferred over methimazole in storm because of PTU’s type 1 deiodinase (D1) inhibitory activity reducing peripheral triiodothyronine (T3) generation. In patients with established methimazole allergy who cannot receive PTU, methimazole 60–80 mg/day divided every 6 hours remains an acceptable alternative. Propranolol is the preferred beta-blocker in storm: given intravenously (IV) at 0.5–1 mg every 5 minutes under cardiac monitoring (maximum 5 mg) or orally at 60–80 mg every 4–6 hours, it controls the adrenergic hyperactivation driving tachycardia and high-output hemodynamic compromise while simultaneously inhibiting peripheral D1 at the doses used. In patients with bronchospasm or hemodynamic instability, short-acting IV esmolol provides more titratable adrenergic blockade. Glucocorticoids (hydrocortisone 100 mg IV every 8 hours or dexamethasone 2 mg IV every 6 hours) are mandatory in storm for three reasons: they inhibit thyroid hormone secretion, inhibit peripheral D1 reducing T3 levels, and cover the possibility of relative adrenal insufficiency in a patient under extreme physiological stress.8,9
Iodide administration follows thionamide by at least one hour as described in Section 4. Bile acid sequestrants such as cholestyramine 4 g four times daily accelerate fecal elimination of thyroid hormone by interrupting enterohepatic recirculation and should be added in refractory or severe cases. Lithium carbonate 300 mg every 6–8 hours is an alternative iodide-blocking agent that inhibits thyroid hormone secretion and can be used when iodide is contraindicated or when escape from the Wolff-Chaikoff effect is anticipated; it is reserved for refractory cases due to toxicity concerns. Cooling measures (acetaminophen preferred; salicylates avoided because they displace thyroid hormone from binding proteins and may worsen hormonal excess), IV fluid resuscitation for dehydration and fever-associated losses, thiamine supplementation, and intensive monitoring of cardiac rhythm and hemodynamics complete supportive care. In patients failing maximal medical therapy, plasmapheresis removes circulating thyroid hormone and thyroid-stimulating immunoglobulins (TSIs) and can serve as a bridge to definitive therapy; emergency thyroidectomy during the acute episode has been performed at specialized centers when pharmacological control cannot be achieved.8,9
Aspirin and other salicylates displace T4 and T3 from plasma binding proteins (thyroxine-binding globulin, transthyretin, and albumin), acutely raising free hormone concentrations at a time when end-organ stress is already maximal. Use acetaminophen exclusively for fever and pain management in thyroid storm. This pharmacological interaction, well recognized but still encountered in clinical practice, can transiently worsen the storm at a physiologically critical moment.
Radioactive iodine (RAI, iodine-131, I-131) ablation is the most commonly used definitive therapy for Graves’ disease and toxic nodular hyperthyroidism in North America. I-131 is concentrated in thyroid follicular cells via NIS (sodium-iodide symporter) by the same mechanism as stable iodide; once intracellular, it emits beta particles (primary tissue-destructive effect, range 1–2 mm in tissue) and gamma radiation (used for imaging). The goal in Graves’ disease is complete thyroid ablation producing permanent hypothyroidism, which is then managed with levothyroxine; attempts to achieve euthyroidism with a smaller RAI dose produce higher rates of treatment failure and are not recommended by current guidelines. Dose is typically calculated based on estimated thyroid weight and 24-hour RAI uptake, with commonly used fixed doses of 10–15 mCi for Graves’ disease and 15–30 mCi for toxic multinodular goiter (TMNG). Pre-treatment with methimazole for 4–8 weeks normalizes thyroid hormone levels before RAI, reducing the risk of radiation thyroiditis precipitating thyroid storm, though methimazole must be stopped 5–7 days before I-131 administration because its presence impairs RAI uptake and efficacy.1,3
Graves’ ophthalmopathy is the most important contraindication to modifying RAI versus non-RAI therapy selection. RAI is associated with new development or worsening of ophthalmopathy in 15–20% of patients, particularly smokers, compared with 3–5% in thionamide-treated patients; the mechanism involves RAI-induced release of thyroid antigens that trigger a surge in TRAb and orbital fibroblast activation. In patients with mild ophthalmopathy, glucocorticoid prophylaxis (oral prednisone 0.4 mg/kg/day starting on the day of RAI, tapered over 3 months) reduces the ophthalmopathy progression risk to near that of thionamide therapy, as established in EUGOGO (European Group on Graves’ Orbitopathy) guidelines.1,3,10
Total or near-total thyroidectomy is preferred over RAI in several clinical situations: large goiters (above 80 g) where RAI efficacy is reduced; coexisting thyroid nodules requiring pathological evaluation; patients with significant ophthalmopathy, especially if TRAb are highly elevated; women planning pregnancy within the next 6–12 months (because RAI requires 6–12 months of contraception post-treatment due to radiation safety concerns); and patients who decline RAI. A linked-record cohort study demonstrated that primary treatment of Graves’ disease with thyroidectomy was associated with lower cardiovascular morbidity and mortality compared with RAI, raising the threshold for RAI in younger patients with significant cardiovascular risk factors.1,3,12
Pre-operative preparation requires achieving biochemical euthyroidism with methimazole and adding iodide (Lugol’s solution 5–10 drops three times daily for 7–10 days immediately pre-operatively) to reduce gland vascularity and intraoperative blood loss. Beta-blockade should be continued perioperatively and tapered post-operatively. Bilateral total thyroidectomy by an experienced surgeon carries low rates of permanent hypoparathyroidism (approximately 1–2%) and recurrent laryngeal nerve injury (approximately 1%), with outcomes substantially better at high-volume thyroid surgery centers. Post-surgical levothyroxine is initiated at full replacement dosing on the first post-operative day. The diagnostic classification of Graves’ disease rests on the combination of clinical features, TRAb positivity, and scintigraphic pattern; the Menconi classification framework integrates these elements for systematic diagnosis.1,3,11,13
RAI preferred: uncomplicated Graves’, older patient, no significant ophthalmopathy, not planning pregnancy imminently, prior thionamide failure or intolerance. Surgery preferred: large goiter, coexistent suspicious nodule, significant ophthalmopathy, planning pregnancy within 6 months, patient preference for cure without radiation. Thionamide continuation: patient preference, first episode with good remission predictors (small goiter, mild disease, normalizing TRAb), pregnancy (where definitive therapy is deferred). All three options are acceptable; patient preference and clinical context determine final selection.
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(10):1343–1421.
doi:10.1089/thy.2016.0229Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association guideline for the management of Graves’ hyperthyroidism. Eur Thyroid J. 2018;7(4):167–186.
doi:10.1159/000490384Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1–133.
doi:10.1089/thy.2015.0020Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352(9):905–917.
doi:10.1056/NEJMra042972Bahn Chair 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. Thyroid. 2011;21(6):593–646.
doi:10.1089/thy.2010.0417Watanabe N, Narimatsu H, Noh JY, et al. Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves’ disease. J Clin Endocrinol Metab. 2012;97(1):E49–E53.
doi:10.1210/jc.2011-2221Alexander EK, Pearce EN, Brent GA, et al. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27(3):315–389.
doi:10.1089/thy.2016.0457Akamizu T. Thyroid storm: a Japanese perspective. Thyroid. 2018;28(1):32–40.
doi:10.1089/thy.2017.0243Satoh T, Isozaki O, Suzuki A, et al. 2016 guidelines for the management of thyroid storm from the Japan Thyroid Association and Japan Endocrine Society (first edition). Endocr J. 2016;63(12):1025–1064.
doi:10.1507/endocrj.EJ16-0336Bartalena L, Baldeschi L, Boboridis K, et al. The 2016 European Group on Graves’ Orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2016;174(2):G1–G22.
doi:10.1530/EJE-15-0813Pearce SH, Brabant G, Duntas LH, et al. 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J. 2013;2(4):215–228.
doi:10.1159/000356507Okosieme OE, Taylor PN, Evans C, et al. Primary therapy of Graves’ disease and cardiovascular morbidity and mortality: a linked-record cohort study. Lancet Diabetes Endocrinol. 2019;7(4):278–287.
doi:10.1016/S2213-8587(19)30059-2Menconi F, Marcocci C, Marinò M. Diagnosis and classification of Graves’ disease. Autoimmun Rev. 2014;13(4–5):398–402.
doi:10.1016/j.autrev.2014.01.013