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Thyroid Emergencies Jim Holliman, M.D., F.A.C.E.P. Professor of Military and Emergency Medicine Uniformed Services University of the Health Sciences Clinical.

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Presentation on theme: "Thyroid Emergencies Jim Holliman, M.D., F.A.C.E.P. Professor of Military and Emergency Medicine Uniformed Services University of the Health Sciences Clinical."— Presentation transcript:

1 Thyroid Emergencies Jim Holliman, M.D., F.A.C.E.P. Professor of Military and Emergency Medicine Uniformed Services University of the Health Sciences Clinical Professor of Emergency Medicine George Washington University Bethesda, Maryland, U.S.A.

2 Thyroid Emergencies Lecture Goals Review pathophysiology of thyroid related illnesses Present information on recognition and management of medical emergencies related to thyroid diseases

3 The Thyroid Emergencies Previously undiagnosed hyperthyroidism "Apathetic thyrotoxicosis" Thyroid Storm Myxedema coma Airway compression or superior vena cava syndrome from goiter or tumor

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5 Ancient Greek and Roman coins showing goiters

6 Maria de Medici, wife of King Henry IV of France in 1625, with a goiter

7 Thyroid gland secretes 2 hormones : –Thyroxine (tetraiodothyronine or T4) –Triiodothyronine (T3) –Secretion ratio T4 to T3 is 15:1 –Iodine is attached to tyrosine amino acid residues of thyroglobulin in the gland (organification) –Coupling of these residues then produces T4 & T3 Thyroid Physiology

8 Thyroid Physiology (cont.) T4 & T3 released by the gland are bound & transported by serum proteins : –Thyroxine-Binding Globulin (TBG) : 75 % –Thyroxine-Binding Prealbumin (TBPA) –Albumin The free (or unbound) hormone levels are the levels which are maintained constant by feedback & regulate thyroid function Total measured serum T4 includes bound & unbound

9 Variations in Thyroxine Binding Proteins Causes of increased TBG levels : –Pregnancy, estrogens, cirrhosis, hepatitis, porphyrias Causes of decreased TBG levels : –Protein malnutrition, nephrotic syndrome, hepatic failure, androgenic steroids, high dose glucocorticoids Free T4 (FT4) usually constant in the above conditions

10 Thyroid Hormone Action in the Tissues T4 deiodonated in periphery to T3 –This is 80 % of T3 produced Other metabolite of T4 is reverse T3 (rT3) which is metabolically inactive T3 enters cells & binds to group of nuclear receptors, then affects wide range of cellular metabolic functions Thyroid hormone required for normal cell metabolism

11 Feedback Regulation of Thyroid Hormone Levels Normal regulation requires intact hypothalamic- pituitary system Hypothalamus secretes Thyrotropin-Releasing Hormone (TRH) TRH then stimulates synthesis & release of thyrotropin (Thyroid Stimulating Hormone or TSH) by the anterior pituitary TSH then stimulates the thyroid gland to uptake iodine, synthesize & release T4 & T3 T4 & T3 levels feedback to both hypothalamus & pituitary affecting TRH & TSH release

12 Thyroid Function Tests Radioimmunoassay for T4 (T4RIA) is most useful single test of thyroid function –Normal levels 4 to 12 mcg / dl Free thyroid homone difficult to measure directly, so "indirect" tests developed –T3 Resin Uptake (T3RU) measures amount of radioactive T3 unbound when added to patient's serum –Reflects # of sites available for binding T4 &T3 –Is indirect measure of level of circulating T4 –Normal is 25 to 35 %

13 Other Thyroid Function Tests Free T4 Index (FT4I) –Correlates with level of Free T4 –Is the product of T4RIA & T3RU T3 radioimmunoassay (less useful) –Normal 75 to 195 ng / dl Serum TSH –Normal is 0.3 to 5.0 mcU / ml TRH Stimulation Test –Measures TSH response to TRH IV injection –Normal is increase in TSH to 30 mcU / ml

14 Clinical Interpretation of Thyroid Function Tests T3RU : –Low in hypothyroidism & high TBG states –High in hyperthyroidism & low TBG states –T4RIA & the T3RU go in same direction with thyroid disease & in opposite directions with TBG level abnormalities TSH –Elevated in primary hypothyroidism –If patient hypothyroid & TSH is low, then lesion is in hypothalamic-pituitary axis, and TRH Stimulation Test should be done

15 Directional Changes in Thyroid Function Tests Clinical State Total T4 T3RU FT4I Free T4 TSH Euthyroid N N N N N Hyper- thyroid Hypothyroid High TBG N N N Low TBG N N N Nonthyroid Illness N or (N = Normal)

16 Medications Which May Cause "Euthyroid Hyperthyroxinemia" Oral contraceptives Narcotics (methadone, heroin) Perphenazine Clofibrate 5-flurouracil Heparin Amiodarone Iodine contrast agents

17 Disorders of Thyroid Hormone Excess "Thyrotoxicosis" is the term for all disorders with increased levels of circulating thyroid hormones "Hyperthyroidism" refers to disorders in which the thyroid gland secretes too much hormone Radioactive iodine uptake test (RAUI) distinguishes hyperthyroidism from other forms of thyrotoxicosis

18 The Radioactive Iodine Uptake Test (RAIU) Quantitates the fraction of a dose of radioiodine I-123 taken up by the thyroid gland within 24 hours Normal is 5 to 30 % Elevated when thyroid gland is overstimulated Decreased when thyroid gland is suppressed (as by ectopic production of T4 or T3) Is decreased falsely by recent iodine load (as from contrast computed tomography scan)

19 Thyroid scans Graves Disease Toxic multinodular goiter with hot nodule

20 Causes of Thyrotoxicosis with Elevated RAUI Graves' Disease Pituitary tumor secreting excess TSH Pituitary insensitivity to feedback Hydatidiform mole Choriocarcinoma Testis embryonal carcinoma Toxic multinodular goiter Toxic uninodular goiter

21 Causes of Thyrotoxicosis with Decreased RAUI Acute autoimmune thyroiditis (may later lead to hypothyroidism) Infectious thyroiditis Postpartum thyroiditis Factitious (taking PO excess thyroid hormone) Metastatic thyroid cancer Struma ovarii (dermoid tumors or teratomas of the ovary)

22 Medications Which Can Induce Hyperthyroidism Iodine Amiodarone Lithium Also rarely due to ground beef contaminated with bovine thyroid glands

23 Features of Graves' Disease (Toxic Diffuse Goiter) Most common cause of hyperthyroidism (70 to 85 % of all cases) Caused by thyroid stimulating immunoglobulins Mainly in young adults ages 20 to 50 5 times more frequent in women Half of cases have infiltrative ophthalmopathy with exopthalmos (not seen with other causes of hyperthyroidism) 5 % have pretibial myxedema

24 51 year old male who presented with urinary retention and proved to have Graves Disease

25 Pretibial myxedema and “square toes” in the same patient on the prior slide

26 Ophthalmo- pathy associated with Graves Disease

27 Asymmetric ophthalmo- pathy with lag ophthalmos in Graves Disease

28 Features of Toxic Multinodular Goiter Second most common cause of hyperthyroidism Most cases in women in 5th to 7th decades Often have long standing goiter Symptoms usually develop slowly

29 Symptoms Suggestive of Thyrotoxicosis Nervousness, restlessness,shortened attention span, emotional lability, difficulty sleeping Increased appetite Weight loss Heat intolerance, perhaps low fever Diaphoresis Weakness Menstrual irregularities

30 Signs Suggestive of Thyrotoxicosis Sinus tachycardia, PVC's, PAC's, atrial fibrillation Tremor, hyperreflexia, muscle wasting Warm, erythematous, moist skin Alopecia, nail friability & separation from bed Hyperventilation Eyelid retraction, lid lag, persistent stare Hyperactive bowel sounds With Graves' : may have exopthalmos, tender enlarged thyroid, & pretibial myxedema

31 Patient with thyrotoxicosis from Graves Disease

32 Onycholysis (irregular separation of nail plate from nail bed near distal end) in the same patient on the prior slide

33 Possible Complications of Thyrotoxicosis at Presentation High output congestive heart failure Dehydration Electrolyte imbalance (from diarrhea) Corneal lesions from exopthalmos Worsening of preexistent angina

34 Syndrome of "Apathetic" or "Nonactivated" Thyrotoxicosis Represents potentially dangerous degree of hyperthyroidism masked by other preexistent chronic conditions or illnesses High mortality if not recognized & patient has surgery or another new illness Most cases in elderly or patients with compromised communication ability

35 Clinical Features of Apathetic Thyrotoxicosis May present with any of these seemingly isolated symptoms : –Congestive heart failure –Atrial fibrillation –Recent weight loss > 20 kg –Somnolence, apathy –Irritability and uncooperative behavior If not recognized and treated, patients may slip into coma and die

36 Thyroid Storm, A True Medical Emergency Exact pathogenesis not understood No clear cut clinical feature separation from thyrotoxicosis Represents diffuse life-threatening decompensated dysfunction of the body's metabolism Cases now very rare and sporadic

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38 Thyroid Storm Definitions "Exaggerated or florid state of thyrotoxicosis" "Life threatening, sudden onset of thyroid hyperactivity" May represent end stage of a continuum : –Thyroid hyperactivity to thyrotoxicosis to thyrotoxic crisis to thyroid storm "Probably reflects the addition of adrenergic hyperactivity, induced by a nonspecific stress, into the setting of untreated or undertreated hyperthyroidism"

39 Thyroid Storm Background Etiology Most cases secondary to Graves' disease Some due to toxic multinodular goiter Rare causes : –Acute thyroiditis –Factitious –Malignancies (most do not efficiently produce thyroid hormones) Very rare in children

40 Thyroid Storm Prognosis Old references quote almost 100 % mortality untreated, and 20 % treated (but these reports were before use of beta blockers) Current mortality ? should be < 5% (although not well studied or reported due to rarity of cases)

41 Thyroid Storm Clinical Presentation 2 most important defining features : –High fever (usually over 40 degrees C) –Significantly abnormal mental status ƒ Agitation, confusion, psychosis, coma May also exhibit : –Marked tachycardia –Vomiting, diarrhea –Jaundice (in 20 %) –Associated signs of Graves' disease

42 Thyroid Storm Precipitating Factors Infection, especially pneumonia Cerebrovascular accident Acute coronary syndrome, Congestive heart failure Pulmonary embolus Diabetic ketoacidosis Parturition / toxemia Major trauma Surgery Iodine 131 Rx or iodine contrast agents Rapid withdrawl of antithyroid medications

43 Thyroid Storm Differential Diagnosis Environmental heatstroke Cocaine, amphetamine, or phencyclidine toxicity Neuroleptic malignant syndrome Meningitis or encephalitis Intracranial hemorrhage Malignant hyperthermia Falciparum cerebral malaria

44 Progression of Neurologic Findings in Thyroid Storm Emotional lability Restlessness Hyperkinesis Confusion Psychosis Lethargy Somnolence Obtundation Coma

45 Cardiovascular Findings in Thyroid Storm Marked tachycardia –Sinus tach or atrial fibrillation Increased myocardial irritability –PVC's, PAC's, first degree AV block Wide pulse pressure Apical systolic murmur Loud S1 and S2 valve sounds Some have high output CHF

46 Case Reports of Unusual Presentations of Thyroid Storm Coma without prominent cardiovascular findings Status epilepticus Nonembolic cerebral infarction Abdominal pain and fever Acute renal failure / rhabdomyolysis

47 Usual Indicated Initial Lab Studies for Thyroid Storm Glucose (stat fingerstick because of altered mental status) Pulse oximetry (+/- ABG) CBC, electrolytes, BUN, creatinine T4RIA, T3RU, TSH, +/- T3RIA Urinalysis Liver function tests Serum cortisol

48 Thyroid Storm Usual Lab Results Lab studies do NOT distinguish thyrotoxicosis from thyroid storm Usually T4 and T3 are elevated, but may only be elevated T3 Usually plasma cortisol is low for degree of stress present Hyperglycemia common

49 Thyroid Storm Emergent Rx High flow O2 Rapid cooling if markedly hyperthermic –Ice packs, cooling blanket, mist / fans, nasogastric tube lavage, acetominophen (Salicylates contraindicated because cause peripheral deiodination to T3) IV fluid bolus if dehydrated –May need inotropes instead if in CHF Propranolol 1 mg doses or labetolol 10 to 20 mg doses IV & repeat doses as needed

50 Thyroid Storm Further Rx IV diltiazem +/- digoxin for rate control for atrial fib IV diuretics if in CHF IV hydrocortisone (or equivalent) 100 mg Propylthiouracil (PTU) 600 to 1200 mg PO or by NG Sodium iodide 1 gram IV one hour after the PTU Find and treat the precipitating cause

51 Thyroid Storm Additional Optional Meds Lithium carbonate 600 mg PO –Follow-on dose 300 mg PO tid Colestipol (resin which binds T4 in the gut) 10 grams PO –Follow-on dose 10 grams PO tid Consider sedatives such as benzodiazepines (but beta blockers are the mainstay of therapy)

52 Actions of Antithyroid Meds for Thyroid Storm Rx PTU inhibits hormone synthesis by the thyroid gland & also inhibits T4 to T3 conversion peripherally (this is why it is preferred over methimizole which just acts at the thyroid) Iodine inhibits secretion of T4 & T3 from the thyroid (it must be given AFTER synthesis block from PTU or else it may provide more substrate for gland hormone synthesis) Lithium can be used in patients alergic to iodine but can cause relapse when stopped

53 Follow-on Doses of Meds for Thyroid Storm PTU 100 to 300 mg PO tid –Monitor for later agranulocytosis or liver dysfunction –Or Methimizole 20 mg PO tid to qid Sodium iodide 500 mg IV q 12 hours –Or SSKI 5 to 20 gtts PO tid 50 to 100 mg hydrocortisone IV daily till stable, then wean as appropriate Propranolol or labetolol or metoprolol (same daily doses as for hypertension)

54 Additional Rx for Thyroid Storm Not Responding to Initial Rx Plasma exchange or plasmapheresis Peritoneal dialysis or charcoal hemoperfusion Emergency surgery for partial or total thyroidectomy

55 Myxedema Coma : The Other Thyroid Emergency Represents end stage of improperly treated, neglected, or undiagnosed primary hypothyroidism Occurs in 0.1 % or less of cases of hypothyroidism Very rare under age % of cases become evident after hospital admission Mortality is 100 % untreated, 50 % even if treated Most cases present in winter (cold exposure)

56 General Causes of Thyroid Failure Diseases of the : –Thyroid (primary hypothyroidism) : 95 % –Pituitary (secondary hypothyroidism) : 4 % –Hypothalamus (tertiary hypothyroidism) : < 1% Can be associated with the multiple endocrine failure syndromes

57 Etiologies of Primary Hypothyroidism Autoimmune : most common –Some have lymphocytic infiltration variant Post surgical thyroidectomy External radiation Iodine 131 Rx for hyperthyroidism Severe prolonged iodine deficiency Antithyroid meds (such as lithium) Inherited enzymatic defects True idiopathic

58 Symptoms of Hypothyroidism Cold intolerance Dyspnea Anorexia Constipation Menorrhagia or amenorrhea Arthralgias, myalgias Fatigue Depression Irritability Decreased attention & memory Paresthesias

59 Signs Related to Hypothyroidism Dry, yellow (carotenemic ) skin Weight gain (41 % of cases) Thinning, coarse hair Myxedema signs (mucopolysaccharide deposition in tissues) : –Puffy eyelids –Hoarse voice –Dependent edema –Carpal tunnel syndrome Anemia

60 Signs of advanced hypothyroidism

61 60 year old male who presented with fatigue and alopecia ; his FTI was 0.2 and his TSH was > 75

62 Same patient on prior slide after 6 months treatment with T4

63 Hypothyroidism and Myxedema Coma : Cardiac Signs Hypotension Bradycardia Pericardial effusion Low voltage EKG Prolonged QT interval Inverted / flattened T waves

64 EKG of 52 year old female presenting with fatigue and weight gain ; her T4 was 2.7 and her TSH was 40

65 EKG of same patient on prior slide after treatment with T4

66 Precipitants of Myxedema Coma Cold exposure Infection –Pneumonia –Urinary tract infection Trauma CNS depressants ƒ Narcotics ƒ Barbiturates, Tranquilizers ƒ General anesthetics Cerebrovascular accident Congestive heart failure

67 Myxedema Coma Typical Presentation Usual symptoms & signs of hypothyroidism, plus : –Hypothermia (80 % of cases) ƒ If temp. is normal, consider infection present –Hypotension / bradycardia –Hypoventilation / respiratory failure –Ileus –Depressed mental status / coma

68 Patient with myxedema coma

69 Contributing Factors to Coma in Myxedema Coma Hypothyroidism itself Hypercapnia Hypoxia Hypothermia Hypotension Hypoglycemia Hyponatremia Drug (sedative) side effect +/- sepsis

70 Lab Studies to Order for Suspected Myxedema Coma Stat glucose (because of altered mental status) Pulse oximetry (ABG usually indicated) CBC, Lytes, BUN, creat., calcium T4RAI, T3RU, TSH Serum cortisol Liver function tests Relevant drug / alcohol levels

71 Emergency Treatment of Myxedema Coma O2 +/- intubation / ventilation if resp. failure Rapid blood glucose check +/- IV D50 +/- naloxone Hydrocortisone 100 to 250 mg IV Cautious slow rewarming (warm O2, scalp, groin, & axilla warm packs, +/- NG lavage) Thyroxine (T4) 500 mcg IV, then 50 mcg IV q day Add 25 mcg T3 PO or by NG q 12 h (if T4 to T3 peripheral conversion possibly impaired) Careful IV fluid rehydration (watch for CHF)

72 Other Aspects of Treatment for Myxedema Coma Search for and treat precipitating cause Use lower doses of most other meds (drug metabolism is impaired & decreased until T4 physiology is restored) Follow TSH levels –Should decrease in 24 hours and normalize by day 7 of Rx

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74 "Mechanical " Symptoms Associated with Goiter Frequent : –Dyspnea, dysphagia –Fullness, choking or pressure sensation in neck Less common : –Acute respiratory failure –Superior vena cava syndrome –Esophageal varices Uncommon but reported : –New onset asthma, phrenic nerve paralysis, Horner's syndrome, chylothorax, neck abscess, sleep apnea

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76 70 year old male with a substernal goiter causing tracheal compression

77 Surgical excision of a goiter

78 Causes of Airway Distress Due to Thyroid Disease Preoperative : –Direct tracheal deviation & compression –Intrathyroid bleeding causing tracheal compression –Tracheal invasion by anaplastic cancer –Bleeding into trachea –Resp. failure from pulmonary metastases of thyroid cancer Postoperative : –Wound hematoma –Laryngeal edema –Bilateral vocal cord paralysis –Tracheomalacia

79 Thyroid Emergencies Summary Important to remember interpretation of thyroid function tests to avoid overdiagnosis Keep high index of suspicion for "apathetic thyrotoxicosis" in the elderly Usual "ABC" care & correction of temperature are important aspects of emergency care for both thyroid storm & myxedema coma Consider thyroid disease in differential Dx for upper airway symptoms


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