Dr Clutter has no financial conflicts to disclose. Or does he?

Endocrine Emergencies Learning objectives: understand the diagnosis and treatment of major endocrine emergencies: Diabetic ketoacidosis Hyperosmolar coma Severe hypercalcemia Adrenal crisis Hyperthyroidism Hypothyroidism

Diabetic ketoacidosis: pathogenesis INSULIN DEFICIENCY + COUNTERREGULATORY HORMONES HYPERGLYCEMIA KETOACIDOSIS

Diabetic ketoacidosis: pathogenesis HYPERGLYCEMIA PRERENAL AZOTEMIA GLYCOSURIA - OSMOTIC DIURESIS WATER > Na DEPLETION K DEPLETION HYPOTENSION

Diabetic ketoacidosis: pathogenesis NAUSEA ABDOMINAL PAIN KETONURIA OSMOTIC DIURESIS HYPERCHLOREMIC ACIDOSIS

Diabetic ketoacidosis: pathogenesis HYPERGLYCEMIA WATER DEPLETION HYPEROSMOLARITY STUPOR & COMA

Diabetic ketoacidosis: causes In Type 1 diabetes new onset inadequate insulin dose illness: Infection, inflammation MI, stroke surgery, trauma

Hyperosmolar Nonketotic Coma Older, type 2 diabetics Pre-existing renal failure More severe volume depletion Drugs as precipitants Steroids Thiazides Phenytoin

Diabetic ketoacidosis: presentation Thirst, polyuria Nausea, vomiting, abdominal pain Somnolence (coma in 10%) Tachycardia, hypotension Kussmaul respiration Abdominal tenderness (no rebound) Signs of triggering illness (eg fever)

Diabetic ketoacidosis: Rx goals Correct volume & potassium deficits Find & treat cause Avoid complications Correct acidosis & hyperglycemia

Diabetic ketoacidosis: management Rapid diagnosis IV saline & potassium IV insulin Monitor VS, I&O [K], glucose, AG Insulin & K infusions Find cause Watch for complications Prevent recurrence Pay attention!

Diabetic ketoacidosis: lab evaluation Rapid diagnosis Blood glucose by meter Ketones (urine or blood) or Direct b-hydroxybutyrate Initial lab BMP (potassium, anion gap) CBC & routine admission labs CXR if febrile, other signs of pneumonia ABG if respiratory failure suspected

Diabetic ketoacidosis: lab evaluation Calculate anion gap AG = [Na] - [Cl] - [HCO3] (normal: 8-16) If comatose, calculate plasma osmolarity pOsm = 2[Na] + [glucose]/20 + [urea]/3 Follow: Blood glucose by meter Q 1 hr BMP & anion gap Q 2-4 hr (not serum ketones, ABG)

Diabetic ketoacidosis: IV fluid Normal saline >1 liter/hr until hypovolemia improved (VS, urine output), then Half-normal saline until BG <300 mg/dl, then D5/half-normal saline Bladder catheter if comatose or unable to void remove ASAP

Diabetic ketoacidosis: potassium Initial [K] normal or increased [K] rapidly falls with therapy KCl 10 mEq/hr follow [K] Q 2-4 hr & adjust rate Cardiac monitor If oliguria or severe renal failure present: initial rate 5 mEq/hr

Diabetic ketoacidosis: insulin Regular insulin 10 units IV push Regular insulin 5-10 units/hr IV until AG normal If no decrease in anion gap in 2 hr: check IV double insulin infusion rate IV glucose to keep BG 150-250 ng/dl Insulin glargine 1-2 hr before stopping IV insulin 1/2 usual dose or 10-15 units

Diabetic ketoacidosis: find the cause Continuing clinical evaluation If INFECTION suspected: cultures empiric antibiotics for clinical infection fever is not due to DKA leukocytosis is usual in DKA If ABDOMINAL PAIN present: treat DKA follow abdominal exam, labs

Diabetic ketoacidosis: complications Hypoglycemia Hypokalemia Coma seek other causes if pOsm <330 mOsm/L cerebral edema may occur in children Aspiration

Diabetic ketoacidosis: common management errors Too little fluid Too little insulin IV dose reduced No insulin glargine Reliance only on sliding scale insulin Too little clinical evaluation Too much attention to trivia (eg phosphate)

Severe hypercalcemia: signs Renal: polyuria, dehydration renal failure Gastrointestinal: nausea, vomiting, constipation abdominal pain Neurologic: fatigue, confusion coma

Severe hypercalcemia: causes Malignancy: Breast carcinoma Squamous carcinoma (lung, head & neck, esophagus) Myeloma Renal carcinoma Primary hyperparathyroidism Miscellaneous: vitamin D intoxication milk-alkali syndrome (calcium carbonate) sarcoidosis

Severe hypercalcemia: evaluation Evidence of cancer Evidence of primary hyperparathyroidism Hypercalcemia for >6 months h/o renal stones Plasma PTH, 25-OH vitamin D Other labs as needed: SPEP, UPEP 1,25-OH D chest & abdomen CT bone scan (PTH-rP)

Severe hypercalcemia: Principles of therapy Expand ECF volume Increase urinary calcium excretion Decrease bone resorption Indications for emergent therapy Symptoms of hypercalcemia Plasma [Ca] >12 mg/dl

Severe hypercalcemia: therapy Restore ECF volume / saline diuresis Normal saline rapidly Positive fluid balance >2 liters in first 24 hr, then Normal saline 100-200 ml/hr (replace potassium) Zoledronic acid 4 mg IV over 15 min or Pamidronate 60 mg IV over 4 hr Monitor plasma calcium QD Myeloma or vitamin D toxicity: prednisone 30 mg BID Optional: Calcitonin 4-8 units/kg IM or SC Q12h

Adrenal failure: causes Primary (cortisol & aldosterone deficient) AUTOIMMUNE tuberculosis, fungal infections Bilateral hemorrhage, sepsis, etc Secondary (ACTH & cortisol deficient) GLUCOCORTICOID THERAPY hypothalamic or pituitary lesions

Adrenal failure: signs In both primary & secondary adrenal failure Weakness & fatigue Anorexia & weight loss Nausea & vomiting Lethargy, stupor Hyponatremia Hypotension Shock & death Only in primary adrenal failure: Hyperkalemia Hyperpigmentation

Adrenal failure: emergency evaluation Dexamethasone 10 mg IV Cortrosyn stimulation test: Cortrosyn 250 mcg IV Plasma cortisol @ 30 min Normal: >18-20 mcg/dl

Adrenal failure: emergency therapy Indications: Hypotension Stupor Severe hyperkalemia or hyponatremia Hydrocortisone 50-100 mg IV Q 8 hr D5/normal saline

Hyperthyroidism: indications for emergency management Acute coronary syndrome Severe heart failure “Thyroid storm” fever agitation or stupor severe concomitant illness

Hyperthyroidism: emergency management Confirm hyperthyroidism (free T4, TSH) Methimazole 60 mg QD po or per tube or PTU 300 mg Q6 hr po Iodine (SSKI) 2 gtt (80 mg) po Q 12 hr Beta- adrenergic antagonist if not in CHF propranolol 40 mg Q 6 hr adjust dose to HR <100/min

Hyperthyroidism: emergency management Intensive therapy of concomitant disease Follow free T4 Q 4-6 days When free T4 normal, schedule RAI therapy stop iodine >2 weeks before stop methimazole 3 days before

Hypothyroidism: emergent therapy Indications: Hypoventilation Bradycardia Hypotension Stupor Confirm diagnosis: FT4, TSH T4 50-100 mg IV Q 6 hr x 24 hr, then T4 75-100 mg IV Q 24 hr Monitor cardiac rhythm, evidence of myocardial ischemia

Any questions?