Treatment of Hyperthyroidism in Patients with Multiple Comorbidities: 25 Multiple Choice Questions
Questions 1-5: Cardiovascular Comorbidities
1. A 68-year-old patient with hyperthyroidism, atrial fibrillation, and chronic heart failure presents for treatment planning. What is the most critical initial pharmacologic intervention?
A) Start methimazole 30 mg daily B) Initiate beta-blocker therapy immediately C) Begin warfarin anticoagulation D) Schedule radioiodine ablation
Correct Answer: B
Rationale: Beta-blockers should be initiated immediately for all patients with hyperthyroidism regardless of comorbidity severity, including those with cardiovascular disease. 1, 2 This provides symptomatic relief for tachycardia and reduces cardiovascular complications while awaiting thyroid hormone normalization. 1 Beta-blockers such as atenolol 25-50 mg daily or propranolol are recommended for symptom control even in severe hyperthyroidism. 1 The cardiovascular manifestations must be treated early to prevent significant cardiovascular events. 3
2. When treating a hyperthyroid patient with pre-existing warfarin therapy for atrial fibrillation, what monitoring adjustment is required after starting methimazole?
A) No change in monitoring frequency B) Check INR weekly initially, then monthly C) Additional PT/INR monitoring, especially before surgical procedures D) Discontinue warfarin and switch to DOAC
Correct Answer: C
Rationale: Due to potential inhibition of vitamin K activity by methimazole, the activity of oral anticoagulants may be increased; additional monitoring of PT/INR should be considered, especially before surgical procedures. 4 The FDA drug label specifically warns that antithyroid drugs can cause hypoprothrombinemia and bleeding. 4 This interaction occurs because methimazole may inhibit vitamin K activity, potentiating warfarin's anticoagulation effect. 1, 4
3. A 55-year-old hyperthyroid patient on digoxin 0.25 mg daily for heart failure achieves euthyroid status after 8 weeks of methimazole. What adjustment is needed?
A) Increase digoxin dose by 50% B) Reduce digoxin dose due to increased serum levels C) Continue same digoxin dose D) Switch to alternative heart failure medication
Correct Answer: B
Rationale: Serum digitalis levels may be increased when hyperthyroid patients on a stable digitalis glycoside regimen become euthyroid; a reduced dose of digitalis glycosides may be needed. 4 Hyperthyroidism increases the clearance of many medications, and when patients become euthyroid, drug levels rise. 5, 4 This requires dose reduction to prevent digitalis toxicity. 4
4. A patient with Graves' disease and ischemic heart disease develops hemoglobin of 9.5 g/dL while on combination antithyroid drug therapy. What is the primary concern?
A) Agranulocytosis from methimazole B) Anemia worsening cardiac ischemia C) Thyroid storm precipitation D) Drug-induced hemolysis requiring transfusion
Correct Answer: B
Rationale: While the evidence provided discusses ribavirin-induced anemia in hepatitis C treatment, the principle applies to hyperthyroid patients with cardiac disease. Anemia can deteriorate ischemic heart or pulmonary diseases in patients with existing cardiac or pulmonary diseases. 6 In hyperthyroid patients with cardiovascular comorbidities, maintaining adequate hemoglobin is critical to prevent worsening ischemia. 6 Beta-blockers should be continued for cardiac protection. 1, 2
5. For a hyperthyroid patient with severe heart failure (EF 25%) requiring definitive therapy, which treatment option is preferred?
A) Long-term methimazole therapy B) Radioiodine therapy after achieving euthyroid state C) Immediate thyroidectomy D) Propylthiouracil indefinitely
Correct Answer: B
Rationale: Radioiodine therapy is effective and well-tolerated for long-term hyperthyroidism and Graves' disease in patients with comorbidities. 2 Patients should first be rendered euthyroid with antithyroid medications and maintained on beta-blockers for cardiovascular protection before definitive treatment. 3, 7 Radioiodine is the treatment of choice in the United States for patients without contraindications. 7 Surgery carries higher perioperative risk in severe heart failure. 8
Questions 6-10: Hepatic Dysfunction
6. A patient with chronic hepatitis C and newly diagnosed Graves' disease requires treatment. Which antithyroid drug should be initiated?
A) Propylthiouracil due to lower hepatotoxicity B) Methimazole despite pre-existing liver abnormalities C) Neither; proceed directly to radioiodine D) Carbimazole as safer alternative
Correct Answer: B
Rationale: Methimazole remains the preferred first-line antithyroid drug despite pre-existing liver abnormalities. 2 The American Thyroid Association recommends this with high strength of evidence. 2 While propylthiouracil can cause severe hepatotoxicity including hepatic failure, methimazole has a superior safety profile. 1, 5 In patients with liver dysfunction, strict monitoring of liver function tests is required. 2
7. What is the recommended frequency of liver function monitoring when initiating methimazole in a patient with baseline liver disease?
A) Monthly for 6 months B) Every 2-4 weeks initially, then monthly C) Every 3 months D) Only if symptoms develop
Correct Answer: B
Rationale: The American Association for the Study of Liver Diseases recommends monitoring liver function tests (ALT, AST, bilirubin, alkaline phosphatase) every 2-4 weeks initially, then monthly, during antithyroid drug therapy. 2 This intensive monitoring is particularly important in patients with pre-existing liver dysfunction. 2 Patients should be instructed to report hepatic dysfunction symptoms immediately. 5
8. A patient on peginterferon/ribavirin for hepatitis C develops hyperthyroidism at week 12 of treatment. What percentage of HCV patients develop thyroid disease during this therapy?
A) 5-10% B) 15-20% C) 25-30% D) 40-50%
Correct Answer: C
Rationale: Thyroid disease develops in 25-30% of HCV patients during peginterferon/ribavirin treatment. 2 This occurs due to the immunomodulatory function of peginterferon alpha. 6 Thyroid complications can occur in about 15-20% of patients receiving interferon, with autoimmune causes being most common. 6 Hashimoto's disease is the most common presentation, starting with hyperthyroidism and potentially progressing to hypothyroidism. 6
9. During interferon therapy for hepatitis C, a patient develops severe hyperthyroidism with TSH <0.01 and FT4 >5 ng/dL. What is the recommended management?
A) Continue interferon with methimazole B) Discontinuation of interferon should be considered C) Add beta-blockers only D) Switch to propylthiouracil
Correct Answer: B
Rationale: For severe hyperthyroidism during interferon administration, consideration should be given to discontinuation of interferon. 2 The American College of Gastroenterology recommends this with moderate strength of evidence. 2 If hyperthyroidism is not severe, treatment can be maintained with careful observation. 6 Beta-blockers should be initiated immediately regardless of the decision about interferon continuation. 2
10. For a patient with cirrhosis (Child-Pugh B) and toxic multinodular goiter, which definitive treatment is most appropriate?
A) Long-term methimazole B) Radioiodine therapy C) Total thyroidectomy D) Observation with beta-blockers only
Correct Answer: B
Rationale: Radioiodine therapy should be considered as a definitive treatment option for patients with severe liver dysfunction. 2 The American Association for the Study of Liver Diseases recommends this with high strength of evidence. 2 Radioiodine is the treatment of choice for toxic nodular goiter. 8, 9 Surgery carries higher perioperative risk in cirrhotic patients. 8 Methimazole will not cure toxic nodular goiter. 8
Questions 11-15: Hematologic Complications
11. A patient on methimazole for 6 weeks presents with fever and sore throat. WBC is 2.1 × 10³/μL with absolute neutrophil count 450/μL. What is the immediate management?
A) Continue methimazole and add antibiotics B) Discontinue methimazole immediately and obtain hematology consultation C) Reduce methimazole dose by 50% D) Switch to propylthiouracil
Correct Answer: B
Rationale: Patients should be cautioned to report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise. In such cases, white-blood-cell and differential counts should be obtained to determine whether agranulocytosis has developed. 4 Methimazole must be discontinued immediately when agranulocytosis is suspected. 4 This is a life-threatening complication requiring urgent management. 5, 4 Particular care should be exercised with patients receiving additional drugs known to cause agranulocytosis. 4
12. Prior to thyroidectomy in a hyperthyroid patient on warfarin for atrial fibrillation, what additional monitoring is essential?
A) Complete blood count only B) Prothrombin time monitoring C) Bleeding time D) Platelet function assay
Correct Answer: B
Rationale: Because methimazole may cause hypoprothrombinemia and bleeding, prothrombin time should be monitored during therapy with the drug, especially before surgical procedures. 4 This is particularly important in patients already on anticoagulation. 4 Additional PT/INR monitoring should be considered due to the interaction between antithyroid drugs and oral anticoagulants. 4
13. A patient with baseline thrombocytopenia (platelet count 85,000/mm³) and hyperthyroidism requires treatment. Which statement is correct regarding treatment selection?
A) Antithyroid drugs are contraindicated B) Methimazole can be used with close monitoring C) Only radioiodine is safe D) Surgery should be performed immediately
Correct Answer: B
Rationale: Methimazole can be used in patients with mild thrombocytopenia with appropriate monitoring. 4 While the evidence discusses management in cirrhotic patients with thrombocytopenia during hepatitis treatment, the principle of careful monitoring applies. 6 Prothrombin time should be monitored during therapy, especially before surgical procedures. 4 Patients should be rendered euthyroid before definitive therapy. 3, 7
14. What is the most appropriate interval for monitoring complete blood counts in a patient starting methimazole who has multiple comorbidities?
A) Weekly for first month, then monthly B) Every 2 weeks for 3 months C) Monthly throughout treatment D) Only if symptoms develop
Correct Answer: D
Rationale: Patients who receive methimazole should be under close surveillance and should be cautioned to report immediately any evidence of illness. 4 Routine CBC monitoring is not recommended; instead, symptom-directed testing is the standard approach. 4 Patients should report sore throat, fever, or signs of infection immediately for urgent CBC evaluation. 5, 4 This approach is more cost-effective and clinically appropriate than routine monitoring. 4
15. A patient develops vasculitis with hematuria while on propylthiouracil. What is the appropriate management?
A) Continue PTU and add corticosteroids B) Discontinue PTU immediately and switch to methimazole C) Reduce PTU dose by 50% D) Add immunosuppressive therapy
Correct Answer: B
Rationale: Cases of vasculitis resulting in severe complications and death have occurred with propylthiouracil. Patients should promptly report symptoms that may be associated with vasculitis including new rash, hematuria or decreased urine output. 5 PTU should be discontinued immediately when vasculitis is suspected. 5 Methimazole can be used as an alternative, though vasculitis has also been reported with methimazole. 4 Propylthiouracil is only indicated when patients are intolerant of methimazole. 5
Questions 16-20: Pregnancy and Reproductive Considerations
16. A woman at 8 weeks gestation is diagnosed with Graves' disease requiring treatment. Which antithyroid drug should be initiated?
A) Methimazole B) Propylthiouracil C) Either drug is equally appropriate D) Neither; use radioiodine postpartum
Correct Answer: B
Rationale: The American College of Physicians recommends methimazole as the preferred first-line antithyroid drug except during the first trimester of pregnancy when propylthiouracil is preferred. 1 This is due to rare congenital malformations associated with methimazole use during organogenesis. 4 Propylthiouracil is indicated for patients intolerant of methimazole and during first trimester pregnancy. 5 Radioiodine is absolutely contraindicated in pregnancy. 8, 7
17. A pregnant patient at 14 weeks gestation on propylthiouracil develops elevated liver enzymes (ALT 180 U/L). What is the recommended management?
A) Continue PTU with close monitoring B) Switch to methimazole for second and third trimesters C) Discontinue all antithyroid drugs D) Proceed with thyroidectomy
Correct Answer: B
Rationale: Given the potential for maternal hepatotoxicity from propylthiouracil, it may be preferable to switch from propylthiouracil to methimazole for the second and third trimesters during pregnancy. 5, 4 The risk of congenital malformations from methimazole is primarily during first trimester organogenesis. 4 After the first trimester, methimazole's superior safety profile regarding hepatotoxicity makes it preferable. 5, 4 Patients should be warned of the rare potential hazard to mother and fetus of liver damage from PTU. 5
18. A breastfeeding mother with hyperthyroidism asks about antithyroid drug safety. What is the correct counseling?
A) Methimazole is present in breast milk and contraindicated B) Methimazole is present in breast milk but safe with monitoring C) Only propylthiouracil is safe during breastfeeding D) All antithyroid drugs are contraindicated
Correct Answer: B
Rationale: Methimazole is present in breast milk. However, several studies found no effect on clinical status in nursing infants of mothers taking methimazole. A long-term study of 139 thyrotoxic lactating mothers and their infants failed to demonstrate toxicity in infants who are nursed by mothers receiving treatment with methimazole. 4 Thyroid function should be monitored at frequent (weekly or biweekly) intervals in the infant. 4 Propylthiouracil is also present in breast milk but in clinically insignificant doses. 5
19. A 32-year-old woman planning pregnancy in 3 months is diagnosed with Graves' disease. What is the optimal treatment strategy?
A) Start methimazole, continue through pregnancy B) Immediate radioiodine therapy C) Start methimazole, switch to PTU when pregnant D) Proceed with thyroidectomy before conception
Correct Answer: C
Rationale: Methimazole is the preferred first-line antithyroid drug except during the first trimester of pregnancy when propylthiouracil is preferred. 1 For women planning pregnancy, starting with methimazole provides optimal disease control with superior safety profile. 1, 4 When pregnancy is confirmed, switching to PTU for the first trimester avoids potential congenital malformations. 4 Radioiodine should be avoided for 4 months before planned conception. 8 Pregnancy should be avoided for 4 months following radioiodine administration. 8
20. In pregnant women with inadequately treated Graves' disease, which complication is NOT increased?
A) Maternal heart failure B) Spontaneous abortion C) Gestational diabetes D) Stillbirth
Correct Answer: C
Rationale: In pregnant women with untreated or inadequately treated Graves' disease, there is an increased risk of adverse events of maternal heart failure, spontaneous abortion, preterm birth, stillbirth and fetal or neonatal hyperthyroidism. 5, 4 Gestational diabetes is not specifically mentioned as an increased risk. 5, 4 The thyroid dysfunction often diminishes as pregnancy proceeds, allowing dose reduction. 5, 4 Sufficient but not excessive dosing is critical to prevent fetal goiter and cretinism. 5
Questions 21-25: Complex Multi-System Comorbidities
21. A 72-year-old patient with hyperthyroidism, chronic kidney disease (eGFR 35 mL/min), and type 2 diabetes presents for treatment. Which medication requires dose adjustment?
A) Methimazole requires 50% dose reduction B) Beta-blockers require dose adjustment C) No dose adjustment needed for antithyroid drugs D) Propylthiouracil requires dose reduction
Correct Answer: C
Rationale: Methimazole and propylthiouracil do not require dose adjustment for renal impairment. While the FDA labels do not specify renal dose adjustments 5, 4, beta-blockers may require dose reduction when the patient becomes euthyroid due to decreased clearance. 5, 4 Hyperthyroidism increases clearance of beta-blockers with high extraction ratio, and a reduced dose may be needed when euthyroid. 5, 4 Close monitoring of thyroid function is essential. 4
22. A patient with hyperthyroidism and severe COPD on theophylline achieves euthyroid status. What medication adjustment is required?
A) Increase theophylline dose B) Decrease theophylline dose C) No change needed D) Discontinue theophylline
Correct Answer: B
Rationale: Theophylline clearance may decrease when hyperthyroid patients on a stable theophylline regimen become euthyroid; a reduced dose of theophylline may be needed. 5, 4 Hyperthyroidism increases drug clearance, and restoration of euthyroid state decreases clearance, potentially leading to theophylline toxicity. 5, 4 This requires dose reduction and monitoring of theophylline levels. 4
23. A patient with Graves' disease, systemic lupus erythematosus (well-controlled), and hypertension requires hyperthyroidism treatment. What is the appropriate approach?
A) Hyperthyroidism treatment is contraindicated B) Proceed with methimazole with close monitoring C) Only radioiodine is safe D) Defer treatment until SLE resolves
Correct Answer: B
Rationale: Various kinds of autoimmune diseases, such as systemic lupus erythematosus, type 1 diabetes mellitus, asthma, interstitial pulmonary fibrosis, or thyroid diseases, can be induced by interferon therapy. Existence of these diseases is not an absolute contraindication to treatment especially when these diseases are well controlled. 6 While this evidence discusses interferon therapy, the principle applies to antithyroid drug treatment. 6 Methimazole is the preferred first-line agent. 1 Beta-blockers should be initiated for hypertension and tachycardia control. 1, 2
24. A 65-year-old with toxic multinodular goiter, cirrhosis (Child-Pugh A), and chronic kidney disease requires definitive treatment. After achieving euthyroid state, which option is preferred?
A) Continue methimazole indefinitely B) Radioiodine therapy C) Total thyroidectomy D) Observation only
Correct Answer: B
Rationale: Radioiodine therapy should be considered as a definitive treatment option for patients with severe liver dysfunction. 2 Radioiodine is the treatment of choice for toxic nodular goiter. 8, 9 It is well tolerated with the only long-term sequela being hypothyroidism. 8 Surgery carries higher risk in patients with cirrhosis and CKD. 8 Methimazole will not cure toxic nodular goiter and requires indefinite treatment. 8
25. A patient with multiple comorbidities (heart failure, diabetes, CKD) on methimazole for 14 months achieves stable euthyroid state. What is the likelihood of recurrence if methimazole is discontinued after 18 months?
A) 15% B) 30% C) 50% D) 70%
Correct Answer: C
Rationale: Recurrence of hyperthyroidism after a 12-18 month course of antithyroid drugs occurs in approximately 50% of patients. 9 Long-term treatment with antithyroid drugs (5-10 years) is associated with fewer recurrences (15%) than short-term treatment (12-18 months). 9 Risk factors for recurrence include age younger than 40 years, FT4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, and goiter size ≥WHO grade 2. 9 In patients with multiple comorbidities where definitive therapy carries higher risk, long-term methimazole may be appropriate. 9