The document discusses various endocrine emergencies including diabetic ketoacidosis (DKA), hypoglycemia, and thyroid storm. It provides details on the causes, symptoms, diagnostic criteria and treatment approaches for each condition. DKA results from lack of insulin and needs urgent treatment including rehydration, insulin administration, and electrolyte correction. Hypoglycemia can be caused by too much insulin or too little food intake and requires glucose administration. Thyroid storm is a life-threatening exacerbation of hyperthyroidism that requires treatments to correct the hyperthyroidism and address any precipitating factors.

1. Endocrine Emergencies Professor Ikram S Ismail PhD (Wales) FRCP (Edin) FAMM FACE

2. Endocrine Emergencies Diabetic Coma Hypoglycaemia Diabetic Ketoacidosis Hyperosmolar nonketotic coma Thyroid storm

4. Diabetic Ketoacidosis Results from lack of insulin Occurs in people with type 1 diabetes. Can also occur in type 2 DM in severe stress. Medical emergency that needs urgent hospitalization Accounts for approximately 5% mortality

5. Causes of DKA A. Absolute Insulin Deficiency: Omission or reduction of insulin Undiagnosed diabetes

6. Causes of DKA B. Relative Insulin Deficiency: (excess catabolic hormone secretion with fixed insulin dosage) Acute illness: Infection Myocardial infarction Stroke Trauma Severe emotional disturbance Endocrine Disorders Steroid therapy Adrenergic agonists Phaeochromocytoma Thyroid storm

7. DKA: Pathophysiology

8. DKA: Pathophysiology

9. DKA - Symptoms Symptoms develop over several hours Thirst, Polyuria Osmotic Diuresis Fatigue Dehydration, protein loss Weight loss Protein loss, catabolism, dehydration Nausea, vomiting ?Ketosis, gastric stasis Abdominal pain ?ileus, gastric stasis, K deficit Muscle cramps ?K deficiency

10. DKA - Signs Dehydration Osmotic Diuresis, vomiting Tachycardia Dehydration Hypotension Dehydration, acidosis Warm skin Acidosis (peripheral vasodilatation) Hyperventilation Ketosis, acidosis Coma, drowsiness Hyperosmolality

11. DKA - Diagnosis Diagnostic procedures Determine blood glucose level and test for ketones Send blood to laboratory for estimation of glucose, urea, electrolytes,arterial pH, pO 2 , pCO 2, Hb, and WBC Send for culture of blood, urine and lung secretions

12. Blood Ketone Testing Indications Asymptomatic patients with glucose > 16.70 mM Symptomatic patients with possible DKA Monitoring in established DKA To assist in making decision on admission To assist in making decisions for intensive medical therapy

13. Established DKA >3.0 If concurrent stress and poor compliance - admit >1.5 Retest glucose and ketones in 2-4hrs 0.6 – 1.5 Check clinical status <0.6

14. DKA – Investigations Hyperglycaemia, hyperketonaemia Insulin deficiency Decreased pH, PCO2, bicarbonate Increased ketogenesis Hyponatraemia Hyperglycaemia Variable K Insulin deficiency, acidosis, urine loss Raised WCC Hyperketonaemia Raised haematocrit Dehydration

15. DKA - Deficits Water 5 to 8 liters Sodium 400-700 mmol Chloride 300-500 mmol Potassium 300-1000 mmol Calcium 100 mmol Magnesium 50 mmol Phosphate 50 mmol Bicarbonate 350 to 400 mmol

16. Treatment of ketoacidosis Initiation of treatment must be immediate Treatment includes Rehydration Insulin administration Electrolyte correction Stabilization of cardiovascular and and renal function

17. Treatment of ketoacidosis Fluids Most urgent and first line treatment Rehydration alone will cause fall in glucose Increase urine flow Allow perfusion Saline given rapidly 1 L in 30min, then hourly for 3 hrs CVP monitoring in elderly/CVS disease

18. Treatment of ketoacidosis Insulin Aim to switch off gluconeogenesis, lipolysis, ketogenesis Insulin regimens Intramuscular: 20 units stat, then 5U/hr Children: 0.25 U/kg stat, then 0.1 U/kg/hr Intravenous infusion Adults: 6 U/hr Children 0.1 U/kg/hr Once glucose fallen to below 15 mmol/L, replace saline with 10%Dextrose with 20-40 mmol K, reduce insulin to 3 U/hr

19. Treatment of ketoacidosis Potassium Hypokalemia most common cause of death Potassium will fall during therapy: Move into cells resulting from insulin, correction of acidosis, and restoration of volume Haemodilution Urinary loss Begin with insulin treatment: 20 mmol/h

20. Treatment of ketoacidosis Acid-base Hazards of acidosis pH<7 Hazards of alkali therapy Negative inotropism Peripheral vasodilatation Cerebral depression Insulin resistance Enzyme depression Hypokalaemia Increased anaerobic glycolysis Impaired tissue oxygen delivery Paradoxical fall in CSF pH Rebound alkalosis Sodium overload

21. Treatment of ketoacidosis Acid-base Give 100 mmoL with KCl 200 mmol when pH < 7, repeat until pH  7 Symptomatic relief: 50 mmoL with KCl 10 mmol

22. Treatment of ketoacidosis Clinical measures Gastric stasis: NG suction in drowsy pts Infection: Usual signs lacking Hyperglycaemia increases risk of sepsis Use broad spectrum antibiotics after cultures Risk of thrombosis Prophylactic SC Heparin 5000 units q6-8hrly in the unconscious, elderly, hyperosmolar Hypotension: use plasma expanders Clinical monitoring

23. Complications of treatment ARDS Sudden dyspnoea, hypoxaemia, diffuse pulmonary infiltrates Younger pts, fatal Mechanisms: Use of crystalloids Alveolar defect caused by acidosis snf hyperventilation Cerebral oedema High mortality Use of hypotonic replacement fluids Abdominal pain Can mimic acute abdomen

24. Hyperosmolar Non-ketotic Hyperglycaemia Accounts for 5-10% of hyperglycemic comas Mortality 30-50%, usually from arterial or venous thrombosis Occurs mainly in elderly persons with type 2 diabetes When compared with DKA, it has: Higher mortality Higher hyperglycemia More severe dehydration

25. HONK: Treatment Rehydration is the most important treatment Is performed under close observation of circulatory status Insulin concentration is usually low Blood glucose will drop in parallel with rehydration Patients should be monitored in a special intensive care unit

26. Hypoglycaemia Defined as blood glucose below 3 mmol/l Some people with diabetes develop hypoglycaemic symptoms even when BG > 3 mmol/l Some persons with diabetes do not have symptoms even at very low BG Hypoglycaemic unawareness

27. Causes of Hypoglycaemia Administration of too much insulin. Insufficient intake of carbohydrate. Delay or omission of a snack or main meal. Performing more exercise than usual. Overdosing of sulphonylureas. Over-indulgence in alcohol.

28. Hypoglycaemia : Symptoms and Signs

29. Hypoglycaemia : Classification Mild hypoglycaemia Activation of the autonomic nervous system Symptoms: tremors, palpitations, sweating, hunger The patients are able to treat themselves Severe hypoglycaemia Very low blood glucose level Symptoms : confusion, drowsiness, coma, seizure Help is needed from others or consciousness is lost Acute professional assistance may be needed

30. Nocturnal Hypoglycaemia Usually occurs between 2 and 4 am Diagnosis through : Symptoms in the night and next morning Blood glucose testing at the time of occurrence Treatment Add a snack before bedtime Reduce dose of insulin Adjust timing of insulin injection Change the type of insulin

31. Hypoglycaemia Caused by Sulphonylureas More common with longer acting sulphonylureas Chlorpropamide Glibenclamide Treatment with glucose Hospitalisation with severe hypoglycaemia Alternative diabetic treatment Shorter acting sulphonylureas Metformin

32. Hypoglycaemic Unawareness Low blood glucose without symptoms Associated with Long duration of diabetes Condition requires frequent blood glucose monitoring

33. Treatment of Mild Hypoglycaemia Relieved by 1 glass of fruit juice or soft drink 3 heaped teaspoon of sugar, honey or 3-5 sweets Dextrose tablets of 5 g Repeat if symptoms are not relieved after 5 to 10 minutes If next meal not immediately due, take 30 g of complex carbohydrate i.e. an apple or a slice of bread after recovery

34. Treatment of Severe Hypoglycaemia Confirm diagnosis with a portable meter Administer 1 mg of glucagon intramuscularly for adults and for children >25 kg (children < 25kg, give 0.5 mg or 0.02 mg/kg body weight) If next meal not immediately available, give 30 g complex carbohydrate If the patient does not recover consciousness within 5-10 minutes, admit to hospital

35. Thyroid Storm Life threatening exacerbation of hyperthyroid state with evidence of decompensation in one or more organ systems. Incidence : 10% of patient hospitalized for thyrotoxicosis Fatal if not treated Mortality 20-30%

36. Pathophysiology: Levels of thyroid hormones Rate of rise of thyroid hormone Development of tissue intolerance Role of adrenergic activation

37. Pathophysiology Levels of thyroid hormones Most older studies found no difference in thyroid hormone levels Newer studies measuring free hormone levels showed higher levels of free T4 in thyroid storm

38. Pathophysiology Rate of rise of thyroid hormone Related to the change in levels of binding proteins noted in systemic illness and postoperatively Production of T4 binding inhibitors resulting in decreased binding affinity of T4 and increase free T4 levels Rapid release of T4 into the circulation could saturate binding capacity

39. Pathophysiology Development of tissue intolerance Homeostatic decompensation despite similar hormone levels. Role of adrenergic activation Normal plasma levels of adrenaline noted But T 4 causes increased  receptors in some tissues Post receptor action to alter responsiveness to catecholamine

40. Clinical presentation All of usual features of thyrotoxicosis - usually exaggerated and severe History of previous thyroid disease partially treated or a history of symptoms suggestive of thyrotoxicosis Fever typically present Sweating profuse initially, later dry when become dehydrated Pulse pressure widened

41. Atrial arrhythmias Nausea, vomiting, diarrhea Increase motor and psychic restlessness  confusion, delirium, agitation Unusual presentation reported acute abdomen status epilepticus, coma stroke Clinical presentation

42. Clinical Presentation Occasionally few or no thyrotoxic features  GI, cardiovascular or neurologic features predominate May be impossible to distinguish between severe hyperthyroidism with concurrent illness and thyroid storm. Usually thyroid storm, the fever and tachycardia tends to be out of proportion to the illness

43. Precipitating events Infection Surgery Radioactive iodine Withdrawal of anti-thyroid drugs Amiodarone, thyroid hormone ingestion DKA, CCF, Hypoglycemia PET, parturition Vigorous palpation of the thyroid gland

44. Diagnosis Mainly clinical Diagnostic criteria to aid clinical diagnosis Thermoregulatory Dysfunction

45. Diagnosis Central Nervous system Effects

46. Diagnosis Gastrointestinal-hepatic Dysfunction

47. Diagnosis Cardiovascular dysfunction

48. Diagnosis Clinical Diagnostic Criteria A score of 45 or more is highly suggestive of a storm A score of 25-44 is suggestive of impending storm A score below 25 is unlikely to represent storm

49. Laboratory Criteria No lab criteria for a storm Biochemical evidence of thyrotoxicosis i.e.  T 3 , T 4 ,  TSH Free T 4 tends to be higher but no criteria as yet Do not wait for lab confirmation If diagnosis not clear and no known history of hyperthyroidism, 2 hour RAI uptake useful Other suggestive features include hyperglycemia, leukocytosis, hypercalcemia,  AST,  LDH.

50. Treatment Correct hyperthyroidism Block synthesis of additional hormones Block release of thyroid hormones Inhibit peripheral conversion Direct measures to reduce levels of hormones Definitive treatment Normalizing homeostatic decompensation Treat precipitating event

51. Treatment Correct hyperthyroidism Block synthesis of additional hormones PTU, carbimazole orally, NG. Block iodine incorporation within 1 hour PTU loading dose 600-1000 mg, then 200-250 mg q4hr Carbimazole 20 mg Q4H Block release of thyroid hormones Inorganic iodine only after carbimazole. Orally or nasogastric. Lugol’s iodine 30 drops daily Ipodate (Oragrafin) 1 g tds. Also inhibit T4 conversion Lithium only if allergic to iodine

52. Treatment Inhibit peripheral conversion PTU Ipodate  blockers with MSA e.g. propanolol steroids Direct measures to reduce levels of hormones Plasmapheresis, PD, exchange transfusion Definitive treatment Radioiodine must be delayed 6 months as iodine can inhibit uptake

53. Treatment Normalizing homeostatic decompensation IV Fluids to rehydrate Glucose for calories and restore glycogen storage Multivitamins Treatment of arrhythmias, CCF. Pressors/invasive monitoring if indicated Supplemental oxygen

54. Treatment Treat hyperthermia Central thermoregulation Paracetamol. Aspirin can displace T4 from binding proteins Peripheral measures icepacks, cooling blanket Glucocorticoids Relative adrenal insufficiency due to increased degradation of cortisol Absolute adrenal insufficiency associated with Graves Disease Inhibit T4 to T3 conversion

55. Treatment Cardiac failure CCF usual treatment Arrhythmias: most common AF Large doses of digoxin needed Significant risk of embolism: anticoagulate if no contraindications Anti adrenergic agents Propanolol result in dramatic improvement 20-40 mg Q6h  1 selective, esmolol (short acting during perioperative period).

56. Treatment Treat precipitating event Identify and treat aggressively Infections

57. Treatment Response Clinical response within 12-24 hours - defervesence, reduced pulse. Full recovery in 7-8 days Mental status good marker for recovery.