THYROID STORM Catherine Barrett PGY4 Endocrinology September 24, 2014.

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THYROID STORM Catherine Barrett PGY4 Endocrinology September 24, 2014 Slide 2 OBJECTIVES Brief overview of thyroid hormone synthesis and metabolism Review the signs and symptoms of thyrotoxicosis and apply this to the clinical manifestations of thyroid storm Discuss the diagnostic challenges of patients presenting with severe thyrotoxicosis Develop an approach to the management of patients with thyroid storm Slide 3 Slide 4 THYROID HORMONE Slide 5 Synthesis of thyroid hormone requires uptake of iodide into the thyrocyte via a sodium-iodide symporter (NIS) Iodide is transferred to the colloid by Pendrin Thyroid peroxidase (TPO) catalyses iodide oxidation and covalent linkage of iodine to the tyrosine residues of thyroglobulin (Tg) Slide 6 Colloid is engulfed in vesicles by pinocytosis and absorbed into the thyrocyte Lysosomes fuse with the vesicle releasing T4 and T3 along with inactive peptides DIT and MIT are deiodinated and their iodide conserved Slide 7 THYROID HORMONE T4 and T3 are poorly water soluble 99% of circulating T4 and T3 is bound to: Thyroid binding globulin Transthyretin Albumin TBG has a higher affinity for T4 and T3 10-20% of circulating T3 comes from direct secretion by the thyroid gland 80-90% is produced by peripheral conversion of T4 T3 5-deiodination of T4 occurs in the liver, kidney and skeletal muscle D1 is the most abundant deiodinase and is the major converter of T4 to T3 Slide 8 Slide 9 ENTEROHEPATIC CIRCULATION Thyroid hormone is metabolized in the liver Conjugated to glucurunides and sulfates Conjugated products are excreted in the bile A fraction of free thyroid hormones are released in the intestine and reabsorbed THYROID HORMONE FUNCTION Bone bone turnover (resorption > formation) Cholesterol cholesterol synthesis and degradation Slide 14 HYPERTHYROIDISM 20 million people worldwide have some form of thyroid disease Hyperthyroidism is more likely in people older than 60 years of age are 2 to 10 times more likely than to develop hyperthyroidism Graves disease is the most common cause of hyperthyroidism Slide 15 CASE 38 year old Vietnamese PMHX: Microcytic anemia Thrombocytopenia HPI: Seen in ER June 14, 2014 for throat swelling, difficulty swallowing and weight loss (29 pounds) TSH supressed Started on Atenolol 25mg OD Seen in urgent endocrine clinic June 20, 2014 Tremor, palpitations, racing thoughts, frequent bowel movements, heat intolerance and fatigue Thyroid visibly enlarged and hands tremulous EOM normal and no evidence of lid lag Atenolol increased to 50mg OD Methimazole started at 10mg OD Slide 16 Slide 17 THYROTOXICOSIS Basal rate Chronic caloric and nutritional deficiency Weight loss despite appetite Muscle wasting Proximal muscle weakness Heat Intolerance Central nervous system Nervousness Emotional lability Hyperkinesia Insomnia Tremor Hyperreflexia Slide 18 THYROTOXICOSIS Cardiovascular system circulatory demands HR (sympathetic tone > vagal tone) cardiac output peripheral vascular resistance Widened pulse pressure Waterhammer pulse, Quinckes sign Palpitations, SOBOE, CHF Respiratory system vital capacity (weakness of respiratory muscles) Slide 19 THYROTOXICOSIS Gastrointestinal system: frequency of bowel movements Hepatic dysfunction, hypoproteinemia and ALT, ALP Skin, hair and nails Warm, moist skin Cutaneous dilation and excessive sweating Palmar erythema Fine, friable hair Onycholysis Typically 4 th and 5 th fingers Vitiligo Slide 20 THYROTOXICOSIS Eyes Retraction of upper or lower eyelids Lid lag Globe lag Bone excretion of calcium and phosphorous in urine and stool Demineralization of bone T3 accelerates osteoclast activity Serum calcium may be Hematopoietic System erythropoiesis and plasma volume Thymus, spleen and lymph nodes can enlarge Slide 21 THYROTOXICOSIS Reproductive System Intermenstrual interval may be prolonged or shortened Menses may stop Fertility is reduced risk of miscarriage SHBG conversion of androstenedione testosterone, estrone and estradiol conversion of testosterone dihydrotestosterone Slide 22 THYROTOXICOSIS Diagnosis: Supressed TSH Elevated free T3 and T4 Thyroid uptake and scan TBII Slide 23 CASE Investigations: TSH < 0.02 Free T4 > 100 Free T3 49.2 TBII > 40 Follow up clinic visit August 5, 2014 Tapazole 10mg OD and Atenolol 25mg OD Goiter decreased in size Swallowing improved Weight increased by 3kg July 30, 2014: TSH3.0mg/dl (51.3 mol/L) (32.3% vs 10.5%) Slide 37 Thyroid, 2012(2):661-672 Slide 38 CLINICAL FEATURES CHF Leg edema and pleural effusions common signs of CHF but in the Japanese study was not a significant determinant of TS NYHA functional class tends to be higher in TS Thyroid, 2012(2):661-672 Slide 39 Slide 40 DIAGNOSIS 1. History of thyroid disease 2. Trigger 3. Typical signs and symptoms 4. Undetectable TSH, FT4 & FT3 Slide 41 DIAGNOSIS Mazzaferri et al. 1969 Temperature 37.8C Marked tachycardia Accentuated signs and symptoms of thyrotoxicosis Organ dysfunction in one ore more of: CNS Cardiovascular Gastrointestinal systems Slide 42 DIAGNOSIS Burch and Wartofsky 1993 Scoring system for identifying thyroid storm 45 is highly suggestive of thyroid storm 25-44 suggestive of impending storm < 25 makes thyroid storm unlikely Slide 43 Slide 44 JAPANESE CRITERIA Akamizu et al. diagnostic criteria based on Japanese Nationwide surveys CNS manifestations Temperature 38C Tachycardia 130bpm CHF GI-hepatic manifestations Definite TS (TS1) and suspected TS (TS2) Slide 45 Thyroid, 2012(2):661-672 Slide 46 Front Endocrinol (Lausanne) 2014 Slide 47 DIAGNOSIS Other laboratory findings include: bilirubin blood glucose total cholesterol WBC calcium urea Markers of DIC ( LDH, haptoglobin, INR, PTT, fibrinogen) Electrolyte imbalances Slide 48 Burch and Wartofksy score on admission to CTU 55. Slide 49 Burch and Wartofksy score on admission to the ICU 85. Slide 50 MANAGEMENT PRINCIPLES: (1) Make the diagnosis sufficiently early (2) Determine etiology and treat the underlying precipitant or trigger (3) Resuscitate, initiate supportive care and specific thyroid storm treatment Oxygen Intubation and mechanical ventilation Electrolyte replacement Cooling blankets Treat infections Reduce thyroid hormone excess in the blood stream and its peripheral effects Slide 51 Hampton et al. Advanced Critical Care 2013:326-332 Slide 52 ANTI-THYROID TREATMENT Beta Blockers Blocks Beta adrenergic receptors Propranolol reduces peripheral T4 T3 conversion Dosing: Propranolol 1-2mg IV or 40-80mg PO q4h Glucocorticoids Block thyroid hormone release Decreased peripheral T4 T3 conversion Dosing: Hydrocortisone 100mg IV q6-8h Dexamethasone 2mg IV q6h Slide 53 Propylthiouracil (PTU) Blocks synthesis of thyroid hormones T4 to T3 conversion in the thyroid and periphery Loading dose of 500-1000mg followed by 250mg PO/NG q4h, 20-40mg PR q6-8h Methimazole Blocks synthesis of thyroid hormones 15-20mg PO/NG q6h Can be given IV 400-600mg PR q6 h Thionamides have no effect on the release of preformed thyroid hormone. Cooper DS. N Engl J Med 2005;352:905-917. Slide 54 ANTI-THYROID TREATMENT Iodine Blocks thyroid hormone release within hours Should start no sooner than 1h after anti- thyroid drug administration to prevent the iodine from being used as a substrate for new hormone synthesis Dosing: Lugol solution 10 drops TID Saturated K+ iodide solution 5 drops TID-QID Sodium iodine 500-1000mg IV daily Slide 55 ANTI-THYROID TREATMENT Lithium Used for the treatment of thyrotoxicosis since 1970s thyroid hormone synthesis and release Impaired response to TSH Alteration in tubulin polymerisation Altered thyroglobulin structure Impaired iodine uptake and iodination of tyrosine peripheral deiodination Dosing: 300mg q6-8 hours Target level 0.6-1.2 Slide 56 ANTI-THYROID TREATMENT Toxicity (rare if level