Pharmacology of Thyroid Hormones and Antithyroid Drugs

Introduction/Overview

The thyroid gland, through the synthesis and secretion of thyroid hormones, exerts a profound influence on metabolic rate, thermogenesis, growth, and development. Disorders of thyroid function, namely hypothyroidism and hyperthyroidism, are among the most prevalent endocrine conditions encountered in clinical practice. The pharmacological management of these disorders is a cornerstone of endocrinology, relying on two principal therapeutic strategies: replacement with exogenous thyroid hormones in deficiency states and suppression of hormone synthesis or action in excess states. A thorough understanding of the pharmacology underlying these agents is essential for safe and effective therapeutic decision-making.

The clinical relevance of this topic is underscored by the high prevalence of thyroid dysfunction. Hypothyroidism, often managed with lifelong hormone replacement, requires precise dosing to mimic physiological levels and avoid both under-treatment and iatrogenic thyrotoxicosis. Conversely, hyperthyroidism, particularly Graves’ disease, necessitates the use of antithyroid drugs that carry risks of significant adverse effects, including agranulocytosis, requiring vigilant monitoring. The narrow therapeutic index of these agents and their impact on fundamental physiological processes demand a detailed pharmacological knowledge base from clinicians.

Learning Objectives

• Describe the biosynthesis and physiological roles of endogenous thyroid hormones, triiodothyronine (T₃) and thyroxine (T₄), as a foundation for understanding pharmacotherapy.
• Compare and contrast the mechanisms of action, pharmacokinetic profiles, and clinical applications of synthetic thyroid hormone preparations used for replacement therapy.
• Explain the molecular targets and mechanisms by which thioamide antithyroid drugs, ionic inhibitors, and radioactive iodine suppress thyroid hormone synthesis and secretion.
• Analyze the major adverse effect profiles, drug interactions, and special population considerations for both thyroid hormone and antithyroid medications to optimize therapeutic outcomes and minimize risk.
• Formulate appropriate monitoring parameters and treatment goals for patients receiving pharmacotherapy for hypothyroidism and hyperthyroidism.

Classification

Agents affecting thyroid function are classified into two broad categories: those that replace or supplement thyroid hormone activity and those that inhibit thyroid hormone synthesis or action.

Thyroid Hormone Preparations

• Synthetic Hormones:
  • Levothyroxine sodium (L-T₄, T₄): The synthetic sodium salt of thyroxine. It is the preparation of choice for most clinical indications.
  • Liothyronine sodium (L-T₃, T₃): The synthetic sodium salt of triiodothyronine.
  • Liotrix: A fixed-ratio combination of synthetic T₄ and T₃ (typically 4:1 ratio by weight).
• Natural Desiccated Thyroid: Derived from porcine thyroid glands, containing both T₄ and T₃ in a non-human, variable ratio (approximately 4:1 by weight, but content is not standardized).

Antithyroid Drugs

• Thioamides (Thionamides): These drugs inhibit the synthesis of thyroid hormones.
  • Methimazole (Thiamazole)
  • Propylthiouracil (PTU)
• Ionic Inhibitors: Agents that block the uptake of iodide by the thyroid gland.
  • Potassium Perchlorate (ClO₄^–): Rarely used clinically due to toxicity.
  • Potassium Thiocyanate (SCN^–): Of historical interest.
• Radioactive Iodine (¹³¹I): A radioactive isotope used for ablative therapy of the thyroid gland.
• Iodine and Iodide Solutions: High doses have a paradoxical inhibitory effect on thyroid hormone release and synthesis (Wolff-Chaikoff effect and its escape).
  • Lugol’s Solution (5% iodine, 10% potassium iodide)
  • Potassium Iodide (SSKI – Saturated Solution of Potassium Iodide)
• Adjunctive Agents: Used to manage symptoms of thyrotoxicosis.
  • Beta-Adrenergic Antagonists (e.g., propranolol, atenolol)
  • Iodinated Radiocontrast Agents (e.g., iopanoic acid): Inhibit peripheral conversion of T₄ to T₃.
  • Glucocorticoids (e.g., dexamethasone): Also inhibit T₄ to T₃ conversion and have immunosuppressive effects.

Mechanism of Action

Endogenous Thyroid Hormone Synthesis and Physiology

Understanding drug mechanisms requires a foundation in thyroid physiology. The thyroid follicular cell synthesizes thyroglobulin (Tg), a large glycoprotein, and secretes it into the follicular lumen. Iodide (I^–) is actively transported into the cell via the sodium-iodide symporter (NIS) and oxidized to iodine (I₂) by thyroid peroxidase (TPO). TPO then catalyzes the iodination of tyrosine residues on Tg to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). Subsequently, TPO mediates the coupling of two DIT molecules to form thyroxine (T₄), or one MIT and one DIT to form triiodothyronine (T₃). Thyroglobulin, stored as colloid, is endocytosed back into the cell and proteolyzed to release T₄ and T₃ into the circulation. The majority of circulating T₃, the more biologically active hormone, is produced by peripheral deiodination of T₄ by 5′-deiodinase enzymes (types I and II).

Thyroid hormones exert their effects by binding to nuclear thyroid hormone receptors (TRs), which are ligand-dependent transcription factors. TRs form heterodimers with retinoid X receptors (RXRs) and bind to thyroid hormone response elements (TREs) in the promoter regions of target genes. Hormone binding induces a conformational change, leading to recruitment of coactivators and stimulation of gene transcription. This genomic action, responsible for most physiological effects, has a latency of hours to days. Non-genomic actions, occurring within minutes, have also been described and involve activation of secondary messenger systems like PI3K and MAPK.

Mechanism of Synthetic Thyroid Hormones

Levothyroxine (T₄) is a prohormone. Its therapeutic effect is primarily mediated through its conversion to the active hormone, liothyronine (T₃), in peripheral tissues via deiodinases. Therefore, levothyroxine replacement aims to restore physiological levels of both T₄ and, through conversion, T₃. It binds to and activates the same nuclear TRs as endogenous hormone. Liothyronine (T₃) directly binds to and activates TRs, bypassing the need for peripheral conversion. This results in a more rapid onset of action but also a more fluctuating serum level due to its shorter half-life.

Mechanism of Antithyroid Drugs

Thioamides (Methimazole and Propylthiouracil): These drugs share a common mechanism but have distinct pharmacological profiles. Both are concentrated in the thyroid gland and act as substrates for TPO. They inhibit the oxidation and organification of iodide, as well as the coupling of iodotyrosines (MIT and DIT) to form T₃ and T₄. Propylthiouracil has an additional, extrathyroidal mechanism: it inhibits the peripheral conversion of T₄ to T₃ by type I 5′-deiodinase, which can be advantageous in severe thyrotoxicosis or thyroid storm. Methimazole does not possess this property but is approximately 10 times more potent in inhibiting thyroid hormone synthesis within the gland.

Radioactive Iodine (¹³¹I): The ¹³¹I isotope is administered orally as sodium iodide. It is avidly taken up by thyroid follicular cells via the NIS, identical to stable iodide. The emitted beta radiation (with a penetration range of about 0.8 mm) causes extensive cellular damage and necrosis, leading to ablation of thyroid tissue over a period of weeks to months. The goal is to destroy overactive tissue, resulting in a hypothyroid state that is subsequently managed with levothyroxine replacement.

Iodine and Iodide: In pharmacological doses (≥ 6 mg/day), iodide has complex, transient effects. Acutely, it inhibits thyroid hormone release (possibly by inhibiting thyroglobulin proteolysis) and, via the Wolff-Chaikoff effect, inhibits iodide organification and hormone synthesis. This effect is self-limiting, as the gland “escapes” inhibition within 1-2 weeks due to downregulation of NIS activity, making iodine unsuitable for long-term therapy. Iodine also decreases the vascularity and size of the gland, which is useful preoperatively.

Beta-Adrenergic Antagonists: These agents do not alter thyroid hormone levels. They ameliorate the peripheral sympathetic manifestations of thyrotoxicosis (tachycardia, tremor, anxiety, heat intolerance) by competitive blockade of β-adrenoceptors. Propranolol may also weakly inhibit peripheral T₄ to T₃ conversion.

Pharmacokinetics

Thyroid Hormone Preparations

Levothyroxine (T₄): Absorption from the gastrointestinal tract is variable and incomplete, averaging approximately 70-80% under optimal fasting conditions. Absorption occurs primarily in the jejunum and ileum and is significantly impaired by food, coffee, fiber, calcium, iron, and proton pump inhibitors. It is highly protein-bound (>99.9%) to thyroxine-binding globulin (TBG), transthyretin, and albumin. The volume of distribution is relatively small (≈0.1-0.2 L/kg), reflecting its extensive plasma protein binding. Levothyroxine undergoes sequential deiodination in peripheral tissues (liver, kidney, muscle) to form T₃ and reverse T₃ (rT₃). A small fraction is conjugated and excreted in bile. Its elimination half-life is long, approximately 7 days in euthyroid individuals, allowing for once-daily dosing. Steady-state serum levels are achieved after 4-5 weeks of consistent dosing.

Liothyronine (T₃): Absorption is nearly complete (95%) but can also be affected by food and other agents. Protein binding is slightly less extensive than T₄ (≈99%). It is not a prohormone and is active upon administration. The volume of distribution is larger than T₄ (≈0.5 L/kg). It is metabolized primarily by deiodination. The elimination half-life is short, approximately 1-2 days, but its biological effect persists longer. Due to its rapid absorption and short half-life, serum levels can peak 2-4 hours after dosing, potentially causing transient symptoms of hyperthyroidism, and trough before the next dose, leading to fluctuating tissue levels.

Antithyroid Drugs

Methimazole: Well absorbed orally (≈80-95%). It is concentrated in the thyroid gland, where its half-life is prolonged (estimated >20 hours). Plasma half-life is 4-6 hours, but its antithyroid effect lasts much longer due to thyroidal accumulation, permitting once-daily dosing in mild to moderate disease. It crosses the placenta readily and is excreted in breast milk.

Propylthiouracil (PTU): Oral absorption is rapid but variable (≈80-95%). It is also concentrated in the thyroid. Plasma half-life is shorter (1-2 hours), necessitating more frequent dosing (typically every 6-8 hours). Protein binding is minimal. PTU crosses the placenta less readily than methimazole but is still present in fetal circulation. It is excreted in breast milk, though in lower concentrations than methimazole.

Radioactive Iodine (¹³¹I): Orally administered ¹³¹I is rapidly and almost completely absorbed. Approximately 20-40% of the administered dose is taken up by the thyroid gland within 24 hours, with the remainder excreted primarily in urine. The effective half-life within the thyroid is about 5-7 days, combining physical decay (8-day half-life) and biological elimination. Radiation exposure to other tissues is minimal due to the short range of beta particles.

Iodide Solutions: Orally administered iodide is rapidly absorbed and distributed in the extracellular fluid. Renal excretion is the primary route of elimination, with a half-life of approximately 8 hours. Thyroidal uptake is competitive and can be blocked by prior administration of ionic inhibitors or thioamides.

Therapeutic Uses/Clinical Applications

Thyroid Hormone Replacement Therapy

• Primary Hypothyroidism: The most common indication for levothyroxine. This includes autoimmune (Hashimoto’s) thyroiditis, post-ablative hypothyroidism (after ¹³¹I or surgery), and congenital hypothyroidism. Levothyroxine is the standard of care.
• Secondary (Central) Hypothyroidism: Due to pituitary or hypothalamic disease. Treatment is with levothyroxine, but it must not be initiated until coexistent adrenal insufficiency is ruled out or treated with glucocorticoids first, to avoid precipitating an adrenal crisis.
• Subclinical Hypothyroidism: Treatment with levothyroxine may be considered in patients with TSH levels >10 mIU/L, or in those with symptoms and TSH levels between 4.5-10 mIU/L, especially in the presence of positive thyroid antibodies or cardiovascular risk factors.
• Suppression Therapy: Levothyroxine in supraphysiological doses is used to suppress TSH secretion in patients with a history of differentiated thyroid cancer (papillary or follicular) to reduce the risk of recurrence. It is also used in the management of nontoxic goiter to reduce gland size.
• Myxedema Coma: A life-threatening emergency of severe hypothyroidism. Intravenous levothyroxine is the mainstay, often supplemented with intravenous liothyronine (T₃) due to its rapid onset. Supportive care with glucocorticoids and warming is critical.
• Special Considerations for T₃: Liothyronine use is generally restricted to specific situations: myxedema coma, in combination with T₄ in thyroid cancer suppression protocols where a rapid TSH suppression is needed, and occasionally in patients with persistent hypothyroid symptoms despite normal TSH on T₄ monotherapy (a controversial and off-label use).

Antithyroid Therapy

• Graves’ Disease: The primary indication for thioamides. They are used to induce a euthyroid state prior to definitive therapy (radioiodine or surgery) or as long-term (12-18 month) primary therapy aiming for remission. Methimazole is preferred in most cases except during the first trimester of pregnancy and in thyroid storm.
• Toxic Nodular Goiter (Toxic Adenoma or Multinodular Goiter): Thioamides can be used to achieve euthyroidism before definitive therapy with radioiodine or surgery. Long-term medical management is less successful than in Graves’ disease.
• Preparation for Thyroidectomy: Patients are rendered euthyroid with a thioamide, often with the addition of iodide (Lugol’s solution) for 7-10 days preoperatively to reduce gland vascularity and fragility.
• Thyroid Storm: A medical emergency. Aggressive therapy includes high-dose PTU (preferred due to its inhibition of T₄ to T₃ conversion), iodide given 1-2 hours after the first dose of PTU, beta-blockers (propranolol), glucocorticoids, and supportive care.
• Radioactive Iodine (¹³¹I): Used as definitive ablative therapy for Graves’ disease, toxic nodular goiter, and toxic adenoma. It is the most common treatment for Graves’ disease in adults in many countries. It is contraindicated in pregnancy and breastfeeding.
• Adjunctive Beta-Blockers: Used in all forms of thyrotoxicosis for rapid symptomatic relief of adrenergic symptoms while awaiting the effects of specific antithyroid treatments.

Adverse Effects

Thyroid Hormone Preparations

Adverse effects are almost exclusively due to excessive dosing, resulting in symptoms of iatrogenic hyperthyroidism or thyrotoxicosis.

• Common (Dose-Related): Tachycardia, palpitations, arrhythmias (atrial fibrillation), weight loss, increased appetite, heat intolerance, sweating, tremors, anxiety, insomnia, headache, and menstrual irregularities.
• Serious: Excessive doses, particularly in elderly patients or those with underlying cardiovascular disease, can precipitate angina pectoris, myocardial infarction, or heart failure. Osteoporosis can occur with long-term supraphysiological TSH-suppressive doses.
• Allergic Reactions: Rare. Hypersensitivity to color dyes or inactive ingredients in some formulations has been reported.

No black box warnings exist for synthetic thyroid hormones when used appropriately. The risk lies in improper use, such as for weight loss, which is dangerous and contraindicated.

Antithyroid Drugs

Thioamides (Common to both Methimazole and PTU):

• Minor, Dose-Dependent: Skin rash (maculopapular), urticaria, arthralgias, fever, gastrointestinal upset, abnormal taste sensation (dysgeusia).
• Major, Idiosyncratic:
  • Agranulocytosis: The most feared adverse effect, occurring in 0.1-0.5% of patients. It is an immune-mediated, rapid-onset neutropenia (absolute neutrophil count <500/mm³) that typically presents with fever and sore throat. It requires immediate drug discontinuation, hospitalization, and supportive care. The risk is higher with higher doses and may be slightly greater with PTU. Patients must be instructed to report any fever or sore throat immediately.
  • Hepatotoxicity: PTU carries a risk of severe, sometimes fatal, hepatocellular necrosis and acute liver failure, leading to a black box warning from regulatory agencies. Hepatitis can also occur with methimazole but is more often cholestatic in pattern and generally less severe.
  • Vasculitis: Anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis, resembling polyarteritis nodosa or lupus-like syndrome, is more strongly associated with PTU.

Radioactive Iodine (¹³¹I):

• Early (within 2 weeks): Radiation thyroiditis, causing transient neck pain and tenderness, and a potential rise in serum thyroid hormone levels that may exacerbate thyrotoxicosis.
• Late: The intended effect is hypothyroidism, which occurs in the majority of Graves’ patients within 6-12 months and is essentially universal over time, requiring lifelong levothyroxine replacement. There is no conclusive evidence for an increased risk of secondary malignancies, teratogenicity (if administered to non-pregnant patients), or genetic damage to offspring.

Iodine and Iodide:

• Iodism: Metallic taste, burning mouth, sore teeth and gums, increased salivation, coryza, skin eruptions.
• Hypersensitivity: Angioedema, cutaneous hemorrhages, fever, arthralgia, lymph node enlargement.
• Thyroid Dysfunction: Can induce hyperthyroidism (Jod-Basedow phenomenon) in susceptible individuals with autonomous nodules or in areas of iodine deficiency, or hypothyroidism (Wolff-Chaikoff effect) in others.

Drug Interactions

Interactions with Thyroid Hormones

Many drugs and conditions can alter the absorption, metabolism, protein binding, or requirement for thyroid hormone.

• Impaired Absorption: Calcium carbonate, iron salts, aluminum hydroxide (antacids), sucralfate, cholestyramine, colesevelam, sevelamer, proton pump inhibitors, and high-fiber diets can bind levothyroxine in the gut, reducing its bioavailability. Administration should be separated by at least 4 hours.
• Altered Protein Binding: Drugs that displace T₄ from TBG (e.g., salicylates, furosemide, phenytoin) can transiently increase free T₄ but also accelerate its metabolism.
• Increased Hepatic Metabolism: Enzyme inducers such as phenytoin, carbamazepine, phenobarbital, rifampin, and sertraline can increase the clearance of thyroid hormones, potentially necessitating a dose increase.
• Altered Thyroid Hormone Requirements: Estrogen therapy (including oral contraceptives) increases TBG levels, increasing the total T₄ pool and often requiring a slight increase in levothyroxine dose. Androgens and glucocorticoids have the opposite effect. Amiodarone, due to its high iodine content and direct effects on deiodinases, can cause both hypothyroidism and hyperthyroidism.

Interactions with Antithyroid Drugs

• Anticoagulants (Warfarin): Thyrotoxicosis increases the catabolism of vitamin K-dependent clotting factors, potentiating warfarin’s effect. As antithyroid drugs take effect and the patient becomes euthyroid, the warfarin dose must be carefully reduced to avoid over-anticoagulation.
• Beta-Blockers: Used adjunctively; no significant pharmacokinetic interactions, but additive bradycardia may occur as thyrotoxicosis resolves.
• Other Bone Marrow Suppressants: Concomitant use of other drugs causing neutropenia (e.g., clozapine, some chemotherapies) may increase the risk of agranulocytosis, though this is primarily theoretical.
• Iodine-Containing Agents: Administration of iodine (e.g., in contrast media, amiodarone) can interfere with the efficacy of thioamides and alter the uptake of radioactive iodine.

Contraindications

• Levothyroxine: Contraindicated in patients with untreated adrenal insufficiency, untreated thyrotoxicosis, and acute myocardial infarction (unless severe hypothyroidism is contributing to the cardiac event).
• Thioamides: Contraindicated in patients with a prior history of major adverse reactions (agranulocytosis, severe hepatitis, vasculitis) to the drug. Relative contraindications include significant liver disease (especially for PTU).
• Radioactive Iodine: Absolute contraindications include pregnancy and breastfeeding. It is generally avoided in women planning pregnancy within 4-6 months, in patients with active thyroid ophthalmopathy (may worsen), and in children under 5 years, though it is used in older children and adolescents in certain contexts.
• Iodide: Contraindicated in patients with known hypersensitivity to iodine.

Special Considerations

Pregnancy and Lactation

Hypothyroidism in Pregnancy: Adequate maternal thyroid hormone is critical for fetal neurodevelopment, especially in the first trimester. Levothyroxine requirements often increase by 25-50% during pregnancy, necessitating close monitoring with TSH levels (goal trimester-specific ranges) and dose adjustments. Preconception TSH optimization is ideal.

Hyperthyroidism in Pregnancy: Graves’ disease is the most common cause. Propylthiouracil is preferred during the first trimester due to a possibly lower risk of teratogenic effects (methimazole has been associated with rare embryopathies, including aplasia cutis and choanal atresia). After the first trimester, consideration is often given to switching to methimazole due to PTU’s risk of hepatotoxicity. The goal is to use the lowest effective dose to maintain maternal free T₄ at or slightly above the upper limit of normal. Radioactive iodine is absolutely contraindicated. Thyroid function in the neonate must be monitored due to transplacental passage of maternal TSH receptor antibodies and antithyroid drugs.

Lactation: Both levothyroxine and antithyroid drugs are excreted in breast milk. Levothyroxine is considered safe. For antithyroid drugs, methimazole at doses ≤20-30 mg/day is generally considered compatible with breastfeeding, with monitoring of the infant’s thyroid function recommended. PTU is also considered an option but carries its own maternal hepatotoxicity risk.

Pediatric Considerations

Congenital Hypothyroidism: Requires immediate and aggressive levothyroxine replacement (dose: 10-15 mcg/kg/day) to prevent irreversible intellectual disability. Doses are weight-based and require frequent monitoring and adjustment during growth.

Childhood Graves’ Disease: Antithyroid drugs (methimazole preferred) are typically the first-line treatment, often for longer durations than in adults. Radioactive iodine may be used in older children and adolescents who fail drug therapy, with careful consideration of long-term risks. Surgery (thyroidectomy) is also an option.

Geriatric Considerations

Elderly patients with hypothyroidism are more sensitive to thyroid hormone. Levothyroxine therapy should be initiated at low doses (e.g., 25-50 mcg/day) and titrated slowly to avoid precipitating cardiac ischemia or arrhythmias. The target TSH range may be relaxed to the upper half of the reference range (e.g., 4-6 mIU/L) in the very elderly or frail. In hyperthyroidism, elderly patients often present with “apathetic thyrotoxicosis,” lacking typical adrenergic symptoms but presenting with weight loss, atrial fibrillation, or heart failure. Antithyroid drug doses may need adjustment for age-related changes in renal and hepatic function.

Renal and Hepatic Impairment

Renal Impairment: No significant dose adjustment is typically required for levothyroxine, though the half-life may be slightly prolonged in severe renal failure. Antithyroid drugs do not require renal dose adjustment. Radioactive iodine is excreted renally; severe impairment may alter dosimetry calculations.

Hepatic Impairment: Levothyroxine metabolism may be reduced in severe liver disease, potentially requiring a lower dose. Propylthiouracil is contraindicated in significant hepatic impairment due to its risk of hepatotoxicity. Methimazole, which can also cause cholestatic injury, should be used with extreme caution and close monitoring in patients with pre-existing liver disease.

Summary/Key Points

• Thyroid hormone pharmacology involves two main classes: replacement hormones (levothyroxine, liothyronine) for hypothyroidism and antithyroid agents (thioamides, ¹³¹I) for hyperthyroidism.
• Levothyroxine (T₄) is a prohormone with a long half-life (~7 days); it is the standard for hypothyroidism treatment due to stable serum levels. Liothyronine (T₃) has a rapid onset but short half-life, limiting its routine use.
• Thioamide antithyroid drugs (methimazole, PTU) inhibit thyroid peroxidase, blocking hormone synthesis. Methimazole is preferred in most settings due to once-daily dosing and a better safety profile, except in the first trimester of pregnancy and thyroid storm, where PTU is favored for its additional inhibition of peripheral T₄ to T₃ conversion.
• The most serious adverse effect of thioamides is idiosyncratic agranulocytosis, mandating patient education to report fever/sore throat. PTU carries a black box warning for severe hepatotoxicity.
• Radioactive iodine (¹³¹I) is a definitive ablative therapy for hyperthyroidism, with hypothyroidism as its intended outcome in most cases, requiring subsequent lifelong levothyroxine replacement.
• Numerous drug interactions affect thyroid hormone therapy, primarily through impaired absorption (e.g., calcium, iron) or altered metabolism (e.g., enzyme inducers). Dosing of levothyroxine should be on an empty stomach, separated from interacting agents by at least 4 hours.
• Special population management is critical: thyroid hormone requirements increase in pregnancy; antithyroid drug choice is influenced by trimester; therapy in the elderly must be initiated cautiously to avoid cardiac complications; and congenital hypothyroidism requires urgent, high-dose treatment.

Clinical Pearls

• The goal of levothyroxine therapy is to normalize the serum TSH level (for primary hypothyroidism), not to achieve a specific total T₄ level. Dose adjustments should be made in 12.5-25 mcg increments every 6-8 weeks based on TSH.
• Persistent symptoms or abnormal TSH on a stable levothyroxine dose should prompt an evaluation for non-adherence, improper administration (with food/other drugs), malabsorption, or drug interactions before changing the dose.
• In hyperthyroidism, a baseline complete blood count with differential should be obtained before starting a thioamide, and patients must be counseled on the signs of agranulocytosis. Routine monitoring of white blood cell counts in asymptomatic patients is not recommended.
• When switching from antithyroid drugs to radioactive iodine, a “washout” period (stopping methimazole 3-5 days prior, PTU 5-7 days prior) is often recommended to maximize thyroidal radioiodine uptake, though practices vary.
• In thyroid storm, remember the “Block and Replace” concept is not used; instead, high-dose PTU is given to block new synthesis and peripheral conversion, followed by iodide to block release.

References

1. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.
2. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.
3. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill Education; 2023.
4. Trevor AJ, Katzung BG, Kruidering-Hall M. Katzung & Trevor's Pharmacology: Examination & Board Review. 13th ed. New York: McGraw-Hill Education; 2022.
5. Katzung BG, Vanderah TW. Basic & Clinical Pharmacology. 15th ed. New York: McGraw-Hill Education; 2021.
6. Golan DE, Armstrong EJ, Armstrong AW. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 4th ed. Philadelphia: Wolters Kluwer; 2017.
7. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.
8. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.