1. Thyroid Emergencies Heidi Chamberlain Shea, MD Endocrine Associates of Dallas

2. Thyroid Trivia Largest endocrine gland –20 grams in adult –Each lobe 2-2.5cm in width and thickness 4cm in height –Isthmus 0.5cm thick 2cm height and width Named for the relationship to the laryngeal thyroid cartilage –Resembles a Greek shield

3. Thyroid Hormone Synthesis Iodide trapping Oxidation of iodide and iodination of thyroglobulin Coupling of iodotyrosine molecules within thyroglobulin (formation of T3 and T4) Proteolysis of thyroglobulin Deiodination of iodotyrosines Intrathyroidal deiodination of T4 to T3

4. Thyroid Hormones  T4 ( Tetraiodothyronine )  T3 ( Triiodothyronine ), Reverse T3 T3T4

5. Goals of Discussion Hypothryoidism –Clinical symptoms –Myxedema Coma Definition Treatment Hyperthryoidism –Clinical symptoms –Thyroid Storm Definition Treatment

6. Hypothyroidism Symptoms Nervous system –Forgetfulness and mental slowing –Paresthesias –Carpal tunnel –Ataxia and decreased hearing –Tendon jerk slowed with prolonged relaxation phase Cardiovascular –Bradycardia –Decreased cardiac output –Pericardial effusion –Reduced voltage on EKG and flat T waves –Dependent edema

7. Hypothyroidism Symptoms Gastrointestinal –Constipation –Achlorhydria with pernicious anemia –Ascitic fluid with high protein Renal –Reduced excretion of water load Hyponatremia –Decreased renal blood flow and glomerular filtration Pulmonary –Responses to hypoxia and hypercapnia are decreased –Pleural effusions high protein Musculoskeletal –Arthralgia –Joint effusions –Muscle cramps –CK can be elevated Anemia –Normochromic normocytic –Megaloblastic Pernicious anemia

8. Hypothyroidism Symptoms Skin and hair –Loss of lateral eye brows –Dry, cool skin –Facial features Coarse and puffy –Orange skin Carotene Reproductive system –Menorrhagia from anovulatory cycles –Hyperprolactinemia No inhibition of thyroid hormone Metabolism –Hypothermia –Intolerance to cold –Increased cholesterol and triglyceride Decreased lipoprotein receptors –Weight gain

9. Myxedema Coma Diagnosis Altered mental status –Decreased orientation –Increased lethargy –Confusion/psychosis –May be secondary to Stroke Medication effect Sepsis CO 2 narcosis

10. Myxedema Coma Diagnosis Defective thermoregulation –Normal body temperature with sepsis Age –Most are elderly Decreased ability to compensate Precipitating illness or event –Exclude pulmonary or urinary tract source –Trauma –Stroke –Hypoglycemia –Hypothermia –CO 2 narcosis –Diuretics –Sedatives –Tranquilizers –Drug overdose

11. Myxedema Coma Management When in doubt, treat –Mortality 30-40% ICU setting Lab tests –TSH, T4, T3-uptake, Cortisol, CBC with diff and routine chemistries –Blood, sputum and urine cultures –WBC may not be elevated Bands present of other concerning finding, empiric treatment is appropriate

12. Myxedema Coma Management Body temperature support –Poikilothermic –No aggressive warming Vasodilatation= vascular collapse –Passive warming Respiratory support –Intubation may be needed –If HCT <30%, transfuse Provide adequate perfusion and oxygen carrying capacity

13. Myxedema Coma Management Cardiovascular support –Fall in blood pressure is ominous Look for GI bleed, MI, over diuresis or iatrogenic vasodilatation Endocrine support –Hydrocortisone 100 mg Q8 hrs Treat possible coexisting primary or secondary adrenal insufficiency Stop once cortisol level is confirmed to be normal

14. Myxedema Coma Management Thyroid hormone therapy –300-500 ug IV Levothyroxine x1 –50-100 ug IV Qday Lower doses for smaller people or older at risk for cardiac events IV to bypass poor absorption in the bowel –Alternately give T4 and T3 due to decreased T3 conversion 200-300 ug T4 then 50 ug/day 5-20 ug T3 then 2.5-10 ug Q8 hrs

15. Myxedema Coma Management Addition of Levothyroxine causes –Increase in cardiac index 1-2 days –TSH falls 32% in 24 hrs –Serum T3 levels increased on 3 rd day –Reversal of blunted ventilatory responses 7 days

16. Myxedema Coma Management Obtain Free T4- 3 days after initiation of therapy to make sure it is increasing –Adjust to normalize value Once tolerating PO can change to oral therapy –Increase IV dose by 40% for oral dosing ie: IV 100 mcg then 140 mcg PO

17. Hyperthyroidism

18. Hyperthyroidism Symptoms Nervousness/Anxiety Weight loss Increased hunger Heat intolerance Cardiac –Atrial fibrillation –Palpitations Increased stool frequency Decreased concentration Weakness Fatigue Decreased sleep Irritablity Change in menstrual patterns Infiltrative orbitopathy –Exopthalmos Goiter –20% elderly no goiter –3% normal size

19. Hyperthyroidism Cardiac –Sinus tachycardia –15% atrial fibrillation –Increased cardiac output 2-3 times normal Nervous system –Diaphoresis –Tremor

20. Hyperthyroidism Increased metabolic rate –Increased blood flow to tissues by vasodilatation T3 affects smooth muscle tone –Systemic vascular resistance is decreased by 50% Decreased diastolic blood pressure Increased rate and force of cardiac contraction –Increased erythropoietin = increased blood volume

21. Hyperthyroidism Lab Tests TSH Free T4 –If done by RIA can be falsely elevated –Gold standard equilibrium dialysis T4 and T3 uptake T3 Thyroid stimulating immunoglobulin (TSI AB) TSH suppressed with increase in T3 and T4

22. Thyroid Storm Diagnosis Decompensation of function due to symptoms –Hyperthermia –CNS effects Delirium, psychosis, coma, seizure –Cardiac Tachycardia Heart failure Abnormal rhythm –GI/Liver dysfunction Jaundice Diarrhea, nausea, vomiting and abdominal pain

23. Hyperthyroidism Treatment B-adrenergic blockade –Use cautiously in asthmatics and diabetics –Improves Tachycardia Widens pulse pressure Decreases palpitations Anxiety Sweating –Propranolol Some decrease in T4 to T3 conversion 20-40 mg Q4-6hrs –Atenolol or Metoprolol Longer acting

24. Hyperthyroidism Treatment Thionamide medications –Block the thyroid hormone synthesis by blocking organification of iodine Propylthiouracil (PTU) –Blocks peripheral conversion of T4 to T3 in liver and kidney –300-600 mg Q8 hrs Methimazole (Tapazole) –30-60 mg Q8hrs, BID or QD

25. Thyroid Storm Management ICU setting Mortality of 20-30% Obtain thyroid function tests Load PTU oral 1000 mg x1 then 200-250 Q4 hrs. –Rectal administration Use Tapazole 30 mg Q6hrs –Rectal administration Side Effects –Rash, arthralgia, serum sickness, abnormal liver function tests and agranulocytosis Sodium ipodate and iopanoic acid –Radiographic contrast agents –Potent inhibitors of T4 to T3 conversion –Structurally similar to thyroxine –1 gram daily Decrease T3 in 24-48 hours Continue for 7-14 days

26. Thyroid Storm Management Inorganic iodine –Blocks thyroid hormone release –Lugol’s solution (8 drops) or saturated solution of potassium iodide (SSKI) (6 drops) Q6 hrs. Can dilute and give as a retention enema –Give iodine one hour after thionamides Lithium –Patient’s with iodine allergy –300 mg Q6 hrs –Titrate to level of 1 mEq/L –Renal and neurological toxicity impair lithium’s usefulness

27. Thyroid Storm Management Corticosteroids –Decrease secretion of thyroid hormone and decrease T4 to T3 conversion –Hydrocortisone 100 mg Q8 hrs –Dexamethasone 2 mg Q6 hrs –Use for 2 weeks

28. Thyroid Storm Management B-adrenergic blockade –Need higher doses –Propranolol 0.5 to 1.0 mg initially with monitoring up to 2-3 mg in 1 minutes 60-80 mg oral every 4 hours –Esmolol loading 250-500 μg/kg 50-100 μg/kg/minute –Can use diltiazem and guanethidine Asthma and heart failure With tachyarrhythmia can use loading propranolol

29. Thyroid Storm Management Hyperthermia –Cooling blankets –Acetaminophen –Avoid aspirin Can displace thyroid hormones from binding proteins –Fluids 3-5 liters per day Include glucose and thiamine –Depletion of liver glycogen and thiamine deficiency –Congestive heart failure Diuretics Digoxin –Requires higher doses in thyroid storm

30. Thyroid Storm Management Look for precipitating event –All febrile patients should be cultured –Unless source found, no empiric treatment needed Once stable and T4 levels are decreasing can decrease dosing of thionamides

31. Hyperthyroidism Limit activity –In patients with heart disease Increased risk of heart failure –Young patients High output failure –Increased circulating volume –During exercise not able to increase LVEF Not able to further decrease SVR

32. Conclusion Myxedema coma –Critical samples –Passive warming –Load Synthroid Daily IV –Start Hydrocortisone –Look for inciting event Thyroid storm –Critical samples –Control heart rate B-blockade Calcium channel blockade –Thionamide therapy –Look for inciting event