1. A Dyspnoeic Lady Author Dr Tang Chung Leung Dec 2013

2. Case ▪ Triaged as Cat. 3 ▪ A 37 years old female ▪ C/O: dizziness and chest discomfort 1 day ago, severe back pain today, unable to walk ▪ BP 107/86 pulse 156/min ▪ Temperature and SaO2 not documented

3. History of Present Illness ▪ Sudden onset of back pain and limb pain in MTR for one day ▪ SOB for 2 weeks ▪ No chest pain ▪ No fever ▪ No cough Add your first bullet point here ▪ Add your second bullet point here ▪ Add your third bullet point here Past Medical History Tourist guide FU OLMH for thyroid problem Not taking any medication

4. Physical Examinations ▪ General conditions fair ▪ No pallor, jaundice, no LN palpable ▪ No neck mass noted ▪ Ankle edema noted ▪ No sweating ▪ Temperature not documented Respiratory:  Respiratory rate not documented  Bilateral basal crepitations CVS:  BP 107/86 mmHg, HR 156/min.  Distended neck veins  Heart sound normal, no murmur noted Abdomen:  soft

5. Investigations ▪ ECG – fast AF Rate ~ 150/min ▪ CXR: cardiomegaly, right pleural effusion ▪ Blood send for CBP, L/RFT, cardiac enzyme, thyroid function.

6. Summary of Clinical Findings ▪ Low back pain ▪ Fast AF ▪ Neck mass ▪ Borderline blood pressure reading ▪ Cardiomegaly/pleural effusion

7. Differential diagnoses ▪ ?Sepsis ▪ ?Heart failure/pericardial effusion/ tamponade ▪ ?Surgical emergency (Boerhaave ’ s Sx) ▪ ?Orthopaedics emergency ▪ ?Endocrine emergency (thyroid crisis) Provisional diagnoses ▪ Thyroid storm ▪ Atrial fibrillation ▪ Heart failure

8. Treatment ▪ High flow O2 ▪ Lasix 40mg ivi x2 ▪ Betaloc 5mg ivi x2 ▪ Carbimazole 20mg po ▪ Iodine (not available in AED) ▪ After treatment, ▪ BP 119/91 pulse 145/min ▪ She was admitted into medical ward. ▪ ? ICU

9. Progress ▪ D1 admission 21:20 ▪ On call medical MO, ▪ Found generalized hypotonia esp. lower limbs (grade 4/5) ▪ Right pleural effusion and back pain ▪ ? Cord compression ▪ ? Rupture esophagus ▪ ? Aortic dissection ▪ ? Any more

10. Progress ▪ Urgent CT thorax and x-ray LS spine ordered ▪ No aortic dissection, right pleural effusion ▪ X-ray LS spine were normal (assessed by orthopaedics colleagues) ▪ Orthopaedic opinion: ▪ Unlikely to be cord compression. ▪ Surgeon opinion: ▪ Unlikely ruptured esophagus (because patient was not in severe chest pain and not very septic) ▪ (? Sequence of events for Boerhaave ’ syndrome)

11. Progress ▪ D1 admission 23:10 ▪ Urgent echocardiogram: ▪ Impaired LVEF (45%), functional MR and TR ▪ D2 admission 14:15 ▪ Chest drain inserted with 1.5 litre pleural fluid drained. (transudative) Blood Results ▪ WBC 12.3 ▪ Hb = 10.9 ▪ Free T4 > 100 ▪ TSH < 0.01 ▪ ESR 1 ▪ CRP <1 ▪ CK. Troponin T - normal ▪ PTU 200mg QID added

12. Progress ▪ D3 admission 13:00 ▪ Patient developed shock ▪ BP 68/24 pulse 66 SaO2 91 ▪ Drowsy, shallow breathing and cold extremities ▪ GCS 3/15 ▪ No active bleeding and PR showed no malaena ▪ Intubated and transferred to ICU

13. Progress ▪ Persistent hypotension ▪ Multiple doses of volume expander and inotrope started ▪ Developed DIC ▪ INR up to 4.03 ▪ Multiple doses of FFP, platelet concentrate given ▪ Developed multiple organ failure and treated conservatively. ▪ D8 admission ▪ Persistent coma ▪ Bedside EEG showed depressed EEG activities ▪ D10 admission ▪ CT brain ▪ SAH, cerebral edema ▪ NS opinion: not for surgical intervention

14. Causes of death ▪ D17 admission: succumbed Causes ▪ Thyroid storm ▪ Septicemia ▪ Multiple organ failure ▪ Intracerebral hemorrhage

15. DISCUSSIONS

16. Terminology ▪ Hyperthyroidism: ▪ thyroid gland hyperfunction ▪ Increased thyroid hormone synthesis and release ▪ Thyrotoxicosis ▪ Increased metabolic and sympathetic nervous state as a result of elevated serum free thyroid hormone ▪ Thyroid storm ▪ Emergent multisystem disorder ▪ Extreme manifestation of thyrotoxicosis

17. Thyroid storm ▪ Thyroid storm is a rare complication( 1- 2 % hyperthyroidism patients) ▪ Precipitated by a physiologically stressful events such as trauma, myocardial infarction, pulmonary embolism, diabetic ketoacidosis, sepsis, partuition, surgery, excessive ingestion of iodine, and incorrect discontinuation of antithyroid drugs

18. Thyroid physiology ▪ Thyroid function is controlled by negative feedback loop that is regulated by circulating TSH and thyroid hormones (T4 and T3) ▪ Thyroid gland mainly produces T4 and smaller amount of T3 ▪ ≈80% of T3 is formed by conversion of T4 to T3 in periphery ▪ Over 99.5% of T4 and T3 are protein bound ▪ Bound hormone is metabolically inactive ▪ Serum free T3 (FT3) and T4(FT4) provide more valuable clinical information ▪ In thyrotoxicosis/ thyroid storm states, TSH concentration is very depressed with elevations of FT4 and FT3

19. Pathogenesis ▪ FT4 and FT3 are taken into the cells whereas T4 is converted into its active form ▪ Conversion of T4 to T3 is accomplished by deiodination in the outer ring of T4 ▪ Normally deiodination of T4 to T3 provides only 20% to 30% of T3 ▪ In thyrotoxic state, it can provide more than 50% ▪ Increase in amount of free thyroid hormone ▪ Increase in target cell beta- adrenergic receptor density ▪ Increase post receptor modifications in signaling pathways

20. Causes of Hyperthyroidism ▪ Circulating thyroid stimulators ▪ Graves’ disease ▪ Pituitary adenoma ▪ Choriocarcinoma ▪ Hyperemesis gravidarum ▪ Thyroid autonomy ▪ Toxic nodular goitre ▪ Toxic solitary adenoma ▪ Iodine-induced hyperthyroidism ▪ Exogenous thyroid hormone ▪ Excess ingestion of thyroid hormone ▪ Destruction of thyroid follicles (thyroiditis) ▪ Subacute thyroiditis ▪ postpartum ▪ Amiodarone induced ▪ Infectious ▪ Ectopic thyroid tissue ▪ Struma ovarii ▪ Metastatic follicular thyroid cancer

21. Symptoms ▪ CNS ▪ Emotional lability ▪ Anxiety ▪ Confusion ▪ GI ▪ Diarrhoea ▪ CVS ▪ Palpitations ▪ Chest pain ▪ Dyspnoea ▪ Ophthalmologic ▪ Diplopia ▪ Reproductive ▪ Oligomenorrhoea ▪ Loss of libido ▪ Dermatologic ▪ Hair loss ▪ Thyroid gland ▪ Neck fullness

22. Laboratory ▪ free T4 is elevated and TSH is decreased ▪ diagnosis must be made on the basis of the clinical examination

23. Thyroid storm- diagnostic criteria SCORE: ≥ 45: HIGHLY SUGGESTIVE OF THYROID STORM; 25-44: SUGGESTIVE OF IMPENDING STORM; BELOW 25: UNLIKELY TO REPRESENT THYROID STORM BURCH HB, WARTOFSKY L. LIFE-THREATENING THYROTOXICOSIS. THYROID STORM ENDOCRINOL META CLIN NORTH AM 1993;22(2):263-77 Diagnostic parametersScoring points Thermoregulatory dysfunction Temperature 99-99.9 100-100.9 101-101.9 102-102.9 103-103.9 ≥ 104 5 10 15 20 25 30 CNS effects Absent Mild (agitation) Moderate (delirium, psychosis, extreme lethargy) Severe (seizure, coma) 0 10 20 30 GI-hepatic dysfunction Absent Moderate (diarrhoea, nausea/ vomiting, abdominal pain) Severe (unexplained jaundice) 0 10 20 Cardiovascular dysfunction Tachycardia 90-109 110-119 120-129 ≥ 140 Congestive heart failure Absent Mild (pedal edema) Moderate (bibasilar rales) Severe (pulmonary edema) Atrial fibrillation Absent Present Precipitating event Absent present 5 10 15 25 0 5 10 15 0 10 0 10

24. Management If untreated, thyroid storm may be fatal Thyroid storm often must be recognized and treated on clinical grounds

25. Management ▪ Multiple targets ▪ Inhibition of new hormone synthesis within thyroid gland ▪ Inhibition of thyroid hormone release ▪ Preventing conversion of T4 to T3 ▪ Controlling the adrenergic symptoms ▪ Supportive therapy ▪ Deal with underlying precipitants

26. Management ▪ Inhibition of new hormone production ▪ Propylthiouracil (extra effect of decreases T4 to T3 conversion) ▪ Carbimazole ▪ Inhibition of thyroid hormone release ▪ Lugol’s solution ▪ Potassium iodide/ SSKI ▪ (administer at least 1 hour after anti-thyroid medication)

27. Management ▪ Beta-adrenergic blockade ▪ Propranolol (extra effect of decrease T4 to T3 conversion) ▪ Atenolol (cardioselective) ▪ Metoprolol (cardioselective) ▪ Esmolol (intravenous) ▪ Supportive ▪ Acetaminophen (for hyperthermia) ▪ Glucocorticoids, e.g. hydrocortisone/ dexamethasone (decreases T4 to T3 conversion) ▪ External cooling: ice packs, cooling blankets ▪ IV fluid

28. Management ▪ Alternative therapies ▪ Lithium carbonate ▪ when anti-thyroid drugs or iodide therapy is contraindicated ▪ Decrease thyroid hormone secretion directly ▪ Potassium perchlorate ▪ in combination of anti-thyroid medication in treatment of Amiodarone induced thyrotoxicosis

29. Thank you