1. Thyroid storm DR KH. ELMIZADEH GYNE-ONCOLOGIST

2. Thyroid storm is a rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis incidence of thyroid storm in hospitalized patients was 0.20 per 100,000 per year the mortality rate of thyroid storm is substantial (10 to 30 percent)

3. RISK FACTORS Although thyroid storm can develop in patients with long-standing untreated hyperthyroidism (Graves’ disease, toxic multinodular goiter, solitary toxic adenoma), it is often precipitated by an acute event such as thyroid or nonthyroidal surgery, trauma, infection, or parturition. In addition, irregular use or discontinuation of antithyroid drugs is a commonly reported precipitant of thyroid storm The advent of appropriate preoperative preparation of hyperthyroid patients undergoing surgery for hyperthyroidism has led to a dramatic reduction in the prevalence of surgically-induced thyroid storm.

4. Why certain factors result in the development of thyroid storm. Hypotheses include : -A rapid increase in serum thyroid hormone levels -Increased responsiveness to catecholamines -Enhanced cellular responses to thyroid hormone. -The degree of thyroid hormone excess elevation of T4 and T3 and suppression of TSH typically is not more profound than that seen in patients with uncomplicated thyrotoxicosis. However, one study found that while the total T4 and T3 levels were similar, the free T4 and free T3 concentrations were higher in patients with thyroid storm

5. CLINICAL FEATURES Patients with severe and life-threatening thyrotoxicosis typically have an exaggeration of the usual symptoms of hyperthyroidism. Cardiovascular symptoms in many patients include tachycardia to rates that can exceed 140 beats/minute and congestive heart failure. Hypotension, cardiac arrhythmia, and death from cardiovascular collapse may occur. Hyperpyrexia to 104 to 106°F is common. CNS symptoms :Agitation, anxiety, delirium, psychosis, or coma are also common and are considered by many to be essential to the diagnosis. GI symptoms: Severe nausea, vomiting, diarrhea, abdominal pain, or hepatic failure with jaundice can also occur.

6. Physical examination : may reveal goiter, ophthalmopathy,lid lag, hand tremor, and warm and moist skin.

7. Laboratory findings All patients have low TSH and high free T4 and/or T3 concentrations. The degree of thyroid hormone excess typically is not more profound than that seen in patients with uncomplicated thyrotoxicosis. Other nonspecific laboratory findings may include mild hyperglycemia, mild hypercalcemia, abnormal liver function tests, leukocytosis, or leukopenia.

8. Diagnosis The diagnosis of thyroid storm is based upon the presence of severe and life- threatening symptoms (hyperpyrexia, cardiovascular dysfunction, altered mentation) in a patient with biochemical evidence of hyperthyroidism (elevation of free thyroxine [T4] and/or [T3] and suppression of [TSH]). There are no universally accepted criteria or validated clinical tools for diagnosing thyroid storm.

9. This system is probably best used as a clinical guideline rather than a strict formula to include or exclude thyroid storm as a diagnosis. Thermoregulatory Temp. (°F) Points 99-100 5 100-101 10 101-102 15 102-103 20 103-104 25 >104 30

10. CNS Alteration Points mild (agitation) 10 moderate (delirium, psychois) 20 Congestive Heart Failure Symptom Points mild (pedal edema) 5 Moderate (bibasilar rales) 10 Severe (pulmonary edema) 15 Atrial fibrillation 10

11. Gastrointestinal Symptom Points Moderate (n/v/d, abd pain) 10 severe (jaundice) 20 Precipitant History absent 0 present 10

12. Scores greater than 45 are indicative of thyroid storm Scores 25-45 suggest thyroid storm Scores less than 25 are unlikely to be thyroid storm.

13. Thyroid function tests (TSH) should be assessed in all patients in whom there is a clinical suspicion of thyroid storm. If the TSH is below normal, free T4 and T3 should be measured. The degree of hyperthyroidism is not a criterion for diagnosing thyroid storm.

14. Radioiodine uptake is not necessary for the diagnosis of thyroid storm, and treatment should not be delayed for scanning in patients with clinical manifestations of thyroid storm.

15. TREATMENT The therapeutic options for thyroid storm are expanded from those used for uncomplicated hyperthyroidism, with additional drugs often used such as glucocorticoids and an iodine solution. The standard drugs are given in higher doses and with more frequent dosing. In addition, full support of the patient in ICU is essential, since the mortality rate of thyroid storm is substantial.

16. The principles of treatment outlined below are based upon clinical experience and case studies, since there are no prospective studies. They are frequently also applied to patients with severe hyperthyroidism who do not fully meet the criteria for thyroid storm. The therapeutic regimen typically consists of multiple medications, each of which has a different mechanism of action.

17. ●A beta blocker to control the symptoms and signs induced by increased adrenergic tone ●A thionamide to block new hormone synthesis ●An iodine solution to block the release of thyroid hormone ●An iodinated radiocontrast agent (if available) to inhibit the peripheral conversion of (T4) to (T3) ●Glucocorticoids to reduce T4-to-T3 conversion, promote vasomotor stability, and possibly treat an associated relative adrenal insufficiency ●Bile acid to decrease enterohepatic recycling of thyroid hormones

18. For patients with clinical features of thyroid storm or with severe thyrotoxicosis who do not fully meet the criteria for thyroid storm), we begin immediate treatment with a beta blocker (propranolol in a dose to achieve adequate control of heart rate, typically 60 to 80 mg orally every four to six hours, with appropriate adjustment for heart rate and blood pressure)propranolol and either propylthiouracil (PTU) 200 mg every four hours or methimazole (20 mg orally every four to six hours).propylthiouracilmethimazole

19. PTU is favored over methimazole because of PTU’s effect to decrease T4 to T3 conversion. However, for severe but not life-threatening hyperthyroidism, methimazole (20 mg every six hours) may be preferred because of its longer half life, lower risk of hepatic toxicity, and because it ultimately restores euthyroidism more quickly than PTU. Patients initially treated with PTU should be transitioned to methimazole before discharge from the hospital.

20. One hour after the first dose of thionamide is taken, we administer iodine (saturated solution of potassium iodide [SSKI], five drops orally every six hours, or Lugol's solution, 10 drops every eight hours). The administration of iodine should be delayed for at least one hour after thionamide administration to prevent the iodine from being used as substrate for new hormone synthesis.

21. For patients with clinical features of thyroid storm, we also administer glucocorticoids (hydrocortisone, 100 mg intravenously every eight hours) and cholestyramine (4 g orally four times daily) to reduce enterohepatic circulation of thyroid hormone.hydrocortisonecholestyramine In addition, supportive therapy and recognition and treatment of any precipitating factors (eg, infection), in addition to specific therapy directed against the thyroid, may be critical to the final outcome.

22. Many patients require substantial amounts of fluid, while others may require diuresis because of congestive heart failure. Digoxin and beta blocker requirements may be quite high because of increased drug metabolism as a result of hyperthyroidism. Infection needs to be identified and treated, and hyperpyrexia should be aggressively corrected. Acetaminophen should be used instead of aspirin, since the latter can increase serum free T4 and T3 concentrations by interfering with their protein binding.DigoxinAcetaminophenaspirin

23. ● After the clinical manifestations of thyroid storm are improved, long- term therapy is required to prevent a recurrence of severe thyrotoxicosis. For definitive therapy of patients with hyperthyroidism secondary to Graves’ disease, toxic multinodular goiter, or toxic adenoma, we suggest radioiodine therapy as our first choice, given its lower cost and lower complication rate than surgery (Grade 2B). Surgery is an option for patients with hyperthyroidism due to a very large or obstructive goiter.Grade 2B

24. THANKS FOR YOUR ATTENTION