Thyroid Storm

1. Intern P.D.Chen 1 Thyroid Storm ???? ??? Thyrotoxicosis and Thyroid Storm Bindu Nayak, MD, Kenneth Burman, MD, Endocrinol Metab Clin N Am 35(2006) 663-686 Harrison's Principles of Internal Medicine Perioperative management of the thyrotoxic patient Roy W. Langley, MD, Henry B. Burch, MD, Endocrinol Metab Clin N Am 32 (2003) 519–534

2. Intern P.D.Chen 2 Thyroid Storm Exacerbation of hyperthyroidism Acute, life-threatening, hypermetabolic state Thyroid storm may be the initial presentation of thyrotoxicosis Less than 10% of hospitalized thyrotoxicosis Mortality: 20-30%

3. Intern P.D.Chen 3 Thyroid Storm – underlying cause Graves’ disease Solitary, multinodular goitor Hypersecretory thyroid carcinoma Axis related tumor Hyperthyroidism aggravated by iodine exposure (radiocontrast, Amiodarone)

4. Intern P.D.Chen 4 Thyroid Storm – precipitating event Systemic insults Discontinuation of antithyroid drug Pseudoephedrine, salicylate use Most common: infection Systemic insults: Systemic insults:

5. Intern P.D.Chen 5 Thyroid Storm – pathophysiology I Patients with thyroid storm have relatively higher levels of free thyroid hormones(THs) than patients with uncomplicated thyrotoxicosis, even though total TH levels may not be increased. Adrenergic receptor activation is a hypothesis. Sympathetic nerves innervate the thyroid gland, and catecholamines stimulate TH synthesis. In turn, increased THs increase the density of beta-adrenergic receptors, thereby enhancing the effect of catecholamines.

6. Intern P.D.Chen 6 Thyroid Storm – pathophysiology II Another theory suggests a rapid rise of hormone levels as the pathogenic source. A drop in binding protein levels, which may occur postoperatively, might cause a sudden rise in free hormone levels. In addition, hormone levels may rise rapidly when the gland is manipulated during surgery, during vigorous palpation during examination, or from damaged follicles following RAI therapy. Other proposed theories include alterations in tissue tolerance to THs, the presence of a unique catecholaminelike substance in thyrotoxicosis, and a direct sympathomimetic effect of TH as a result of its structural similarity to catecholamines.

7. Intern P.D.Chen 7 Thyroid Storm – presentation I Heat intolerance and diaphoresis are common in simple thyrotoxicosis -> hyperpyrexia in thyroid storm. Extremely high metabolism increases oxygen and energy consumption. Cardiac findings in thyrotoxicosis -> accelerated tachycardia, hypertension, high-output cardiac failure, and a propensity to develop cardiac arrhythmias.

8. Intern P.D.Chen 8 Thyroid Storm – presentation II irritability and restlessness in thyrotoxicosis -> severe agitation, delirium, seizures, and coma. mild elevations of transaminases and simple enhancement of intestinal transport in thyrotoxicosis -> diarrhea, vomiting, jaundice, and abdominal pain

9. Intern P.D.Chen 9 Thyroid Storm- diagnosis A score of 45 or more is highly suggestive of thyroid storm; a score of 25 to 44 supports the diagnosis; and a score below 25 makes thyroid storm unlikely.Adapted from Burch, HB, Wartofsky, L, Endocrinol Metab Clin North Am 1993; 22:263.

10. Intern P.D.Chen 10 Thyroid Storm - prognosis The mortality rate due to cardiac failure, arrhythmia, or hyperthermia is as high as 30%, even with treatment. Thyrotoxic crisis is usually precipitated by acute illness, surgery (especially on the thyroid), or radioiodine treatment of a patient with partially treated or untreated hyperthyroidism.

11. Intern P.D.Chen 11 Thyroid Storm – treatment I Medications to halt the synthesis, release, and peripheral effects of thyroid hormone. Controlling adrenergic symptoms and systemic decompensation with supportive therapy Management requires intensive monitoring and supportive care, identification and treatment of the precipitating cause, and measures that reduce thyroid hormone synthesis.Management requires intensive monitoring and supportive care, identification and treatment of the precipitating cause, and measures that reduce thyroid hormone synthesis.

12. Intern P.D.Chen 12 Thyroid Storm  – treatment II

13. Intern P.D.Chen 13 Thyroid Storm – treatment III Thionamides interfere with thyroperoxidase-catalyzed coupling, and inhibitory effect on thyroid follicular cell function and growth Thiouracil (propylthiouracil) v.s. imidazoles (methimazole, carbimazole) SE: abnormal taste, pruritus, urticaria, fever, arthralgia; agranulocytosis, hepatotoxicity, vasculitis MMI 4-6hrs, PTU1.5hr PTU inhibit T4->T3MMI 4-6hrs, PTU1.5hr PTU inhibit T4->T3

14. Intern P.D.Chen 14 Thyroid Storm – treatment IV Thionamides interfere with thyroperoxidase-catalyzed coupling, and inhibitory effect on thyroid follicular cell function and growth Thiouracil (propylthiouracil) v.s. imidazoles (methimazole, carbimazole) SE: abnormal taste, pruritus, urticaria, fever, arthralgia; agranulocytosis, hepatotoxicity, vasculitis

15. Intern P.D.Chen 15 Thyroid Storm – treatment V Large doses of propylthiouracil (600mg loading dose and 200 to 300 mg every 6 h) orally or per rectum; One hour after the first dose of propylthiouracil, stable iodide is given to block thyroid hormone synthesis via the Wolff-Chaikoff effect : saturated solution of potassium iodide (5 drops SSKI every 6 h), or ipodate or iopanoic acid (0.5 mg every 12 h), may be given orally. (Sodium iodide, 0.25 g intravenously every 6 h is an alternative but is not generally available.) the propylthiouracil inhibitory action on T4 T3 conversion makes it the antithyroid drug of choice. Wolff-Chaikoff effect (the delay allows the antithyroid drug to prevent the excess iodine from being incorporated into new hormone). Although other -adrenergic blockers can be used, high doses of propranolol decrease T4 T3 conversion, and the doses can be easily adjusted. the propylthiouracil inhibitory action on T4 T3 conversion makes it the antithyroid drug of choice. Wolff-Chaikoff effect (the delay allows the antithyroid drug to prevent the excess iodine from being incorporated into new hormone). Although other -adrenergic blockers can be used, high doses of propranolol decrease T4 T3 conversion, and the doses can be easily adjusted.

16. Intern P.D.Chen 16 Thyroid Storm – treatment VI Propranolol should also be given to reduce tachycardia and other adrenergic manifestations (40 to 60 mg orally every 4 h; or 2 mg intravenously every 4 h). Additional therapeutic measures include glucocorticoids (e.g., dexamethasone, 2 mg every 6 h), antibiotics if infection is present, cooling, oxygen, and intravenous fluids.

17. Intern P.D.Chen 17 Thyroid Storm – operation consideration 8%-20% mortality in the past 1% with pre-op inorganic iodine

18. Intern P.D.Chen 18 Thyroid Storm – operation consideration

19. Intern P.D.Chen 19 Thyroid Storm  – pre-operation consideration A combination of targets in the thyroid hormone synthetic, secretory and peripheral action pathways. Concurrent treatment to reverse any decompensation of normal homeostatic mechanisms

20. Intern P.D.Chen 20 Thyroid Storm  – pre-operation rapid preparation

21. Intern P.D.Chen 21 Thyroid Storm  – post-operation consideration Keep regimen after resolution of thyrotoxicity Monitor thyroid hormones To render the patient as close as possible to clinical and biochemical euthyroidism

22. Intern P.D.Chen 22 Thyroid Storm- Take home message A score of 45 or more is highly suggestive of thyroid storm

23. Intern P.D.Chen 23 Thanks you for attention