ENDOCRINE EMERGENCIES Jim Holliman M D F

ENDOCRINE 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.

Endocrine Emergencies n. Adrenal –Addisonian Crisis –Pheochromocytoma n. Thyroid –Thyroid Storm –Myxedema Coma n. Miscellaneous –Hypoglycemia –Diabetes Insipidus

General Mechanisms of Endocrine Pathophysiology n. Deficient hormone action n. Excess hormone production or action n. Neoplasia

Mechanisms of Endocrine Pathophysiology n 1. Deficient hormone action –Primary glandular failure ƒ Congenital ƒ Acquired (atrophy, surgery, tumor, druginduced, autoimmune, infectious) –Secondary glandular failure –Disordered hormone release or activation –Accelerated hormone metabolism –Target tissue resistance

Mechanisms of Endocrine Pathophysiology (cont. ) n 2. Excess hormone production or action –Gland autonomy (neoplasia, hyperplasia) –Abnormal stimulation –Ectopic hormone production –Altered hormone metabolism –Target tissue increased sensitivity to hormone action

Mechanisms of Endocrine Pathophysiology (cont. ) n 3. Neoplasia –Benign vs. malignant –Functional vs. nonfunctional –Ectopic hormone production –Sporadic vs. familial syndromes

Multiple Endocrine Neoplasia (MEN) Syndromes n. MEN I (Wermer) –Hyperparathyroid, pituitary adenoma, pancreatic cancer n. MEN IIa (Sipple) –Hyperparathyroid, thyroid medullary ca, pheochromocytoma n. MEN IIb (or III) –Medullary thyroid ca, pheochromocytoma, mucosal neuromas, Marfinoid habitus

Polyendocrine Failure Syndromes n. Type I –Hypoparathyroidism –Hypoadrenalism –Mucocutaneous candidiasis –Other (hypogonadism, autoimmune thyroid disease, JODM) n. Type II –Adrenal insufficiency –Autoimmune thyroid disease –Other (JODM, primary or secondary gonadal failure)

Diseases of the Adrenals n. Adrenocortical insufficiency –Addison's –Hypopituitarism –Iatrogenic ACTH deficiency n. Cushing's Syndrome –Cushing's Disease (cortical hyperplasia) –Pituitary tumor n. Adrenal adenoma or carcinoma –Ectopic ACTH syndrome (from tumors) n. Virilization –Adrenal adenoma or carcinoma –Congenital adrenal hyperplasia (CAH) n. Adrenal-mediated hypertension syndromes –Primary hyperaldosteronism (adenoma vs. hyperplasia), Cushing's syndrome, Pheochromocytomas

Etiologies of Primary Adrenal Insufficiency n. Iatrogenic suppression n. Autoimmune adrenalitis (idiopathic) n. Infections (mycobacteria, fungal, CMV, HIV) n. Sarcoidosis n. Hemorrhage (anticoagulants, meningococcemia, trauma, toxemia, emboli) n. Collagen vascular disease n. Amyloidosis n. Hemochromatosis n. Metastatic malignancy n. Congenital (hypoplasia, adrenogenital syndrome, adrenoleucodystrophy)

CT scan showing bilateral adrenal hemorrhages in a 57 year old female with breast cancer

Etiologies of Secondary Adrenal Insufficiency n. Pituitary insufficiency –Congenital, tumor, infarction, sarcoid, autoimmune n. Hypothalamic dysfunction –Tumor –Vascular malformation

Symptoms of Adrenal Insufficiency n. Weakness, fatigue, lethargy n. Nausea, vomiting n+/- diarrhea n. Anorexia, weight loss n. Mental sluggishness n+/- syncope n. Addisonian Crisis: –Shock –Cardiovascular collapse

Signs of Adrenal Insufficiency n. Hypotension n. Other signs of dehydration n. Hyperpigmentation / vitiligo n. Skin atrophy n. Muscle wasting n. Loss of axillary & pubic hair n+/- fever

Lab Findings in Adrenal Insufficiency n. Hyponatremia n. Hyperkalemia n. Hypoglycemia n. Azotemia (prerenal) n+/- eosinophilia n+/- anemia

Precipitating Factors for Addisonian Crisis n. Acute infection, esp. pneumonia n. Acute MI n. Pulmonary embolus n. Trauma / burns n. Surgery n. Heat exposure n. Vomiting / diarrhea n. Dehydration n. Blood loss n. Rapid cessation or reduction of chronic steroid therapy

Acute Adrenal Crisis Caveats n. Suspect this dx when: –Sudden hypotension in response to procedure or stress, and does not correct with initial IV fluids +/- raising legs n. Patients previously maintained on chronic glucocorticoid Rx may not exhibit severe dehydration or hypotension until preterminal since mineralocorticoid function is usually maintained

Addisonian Crisis Rx n. High flow oxygen n. Aggressive fluid / electrolyte replacement –Initially NS - usually need 4 to 6 liters –Switch to LR when K+ decreases n. IV hydrocortisone – 100 to 250 mg IV bolus – 10 to 20 mg per hr. IV infusion n+/- cortisone acetate 50 mg IM (in case infusion stops) n. Search for precipitating cause

Further Rx of Addisonian Crisis n. Once the patient's condition improves: –Decrease hydrocortisone to 100 mg bid –Halve dose daily till maintenance dose achieved (usually 20 mg hydrocortisone per day) –Add fludrocortisone 0. 1 mg per day when dose of cortisone < 100 mg / day

Prevention of Acute Adrenal Crisis n. For patients on chronic steroid Rx: –Double their normal daily dose before and for at least 2 - 3 days after a stressful procedure or when an active infection is present n. For severe stress: –Consider tripling steroid dose

Dosing Comparisons for Adrenocortical Steroids STEROID t 1/2 (hrs. ) Cortisone 8 - 12 Relative potency 0. 8 Equivalent dose 25 Cortisol 8 - 12 1. 0 20 Prednisone 12 - 36 4. 0 5 Methylprednisolone Dexamethasone 12 - 36 5. 0 4 36 - 72 25 0. 75

Pheochromocytoma n. Tumor of chromaffin cells n. Chromaffin cells produce, store, & secrete catecholamines n. Clinical features of these tumors are due to excessive catechol release ( not usually due to direct tissue extension effects of tumor) n. Cause only 0. 1% of cases of hypertension but represent a curable cause of hypertension

Excised pheochromocytoma (left slice chromium stained)

Excised pheochromocytoma

High power microscopy view of stained pheochromocytoma cells

Familial Syndromes Associated with Pheochromocytomas n. Most are autosomal dominant (variable penetration) n. MEN II (Sipple Syndrome) –Pheos in > 75 % of cases n. MEN III (mucosal neuroma syndrome) –Pheos in > 75 % n. Von Recklinghausen's neurofibromatosis –Pheos in 1 % n. Von Hippel - Lindau Disease –Pheos in 5 to 10 %

Pheochromocytoma Locations n. Adrenal medulla : 90 % n. Abdomen : 8% n. Neck or thorax : 2% n. Multiple sites : 10 % n. Malignant : 10 % n. Associated with familial syndromes : 5 %

Pheochromocytoma Catechol Secretion n. Most secrete both norepi and epi (generally norepi > epi) n. Most extrarenal tumors secrete only norepi n. Malignant tumors secrete more dopamine and HVA n. Predominant catechol secreted cannot be predicted by clinical presentation

Most Common Symptoms of Pheochromocytoma n. Hypertension –Sustained with crises –Paroxysmal n. Headache n. Sweating n. Palpitations > 90 % 30 % 80 % 70 % 65 %

Additional Symptoms of Pheochromocytoma n. Pallor 45 % n. Nausea +/- emesis 40 % n. Nervousness 35 % n. Fundoscopic changes 30 % n. Weight loss 25 % n. Epigastric or chest pain 20 %

Indications to Screen Patients for Pheos n. Hypertension with: –Grade 3 or 4 retinopathy of uncertain cause –Weight loss –Hyperglycemia –Hypermetabolism with nl. thyroid profile –Cardiomyopathy –Resistance to 2 or 3 drug Rx –Orthostatic hypotension (not due to drug Rx) –Unexplained fever n. Marked hyperlability of BP n. Recurrent attacks of sx of pheos

More Indications to Screen Patients for Pheos n. Severe pressor response during or induced by: –Anesthesia or intubation –Surgery –Angiography –Parturition n. Unexplained circulatory shock during: –Anesthesia –Pregnancy, delivery, or puerperium –Surgery (or after surgery) –Use of phenothiazines n. Family history of pheos n. Hyperlabile BP or severe hypertension with pregnancy n. X ray evidence of suprarenal mass

Conditions Causing Increased Urinary Catechol Levels n. Hypoglycemia n. Surgery n. CHF n. Acute MI n. Circulatory shock n. Sepsis n. Acidosis n. Increased ICP n. Spinal cord injury n. Trauma / burns n. Parturition n. Delerium tremens n. Strenuous exercise

Conditions Causing Decreased Urinary Catechol Levels n. Renal insufficiency (oliguria) n. Malnutrition n. Quadriplegia n. Orthostatic hypotension due to adrenergic insufficiency

Localization Techniques for Pheos n. Abdominal CT : most useful –Cannot confirm tissue dx n. Iodine 131 metaiodobenzylguanidine nuclear medicine scanning –Helpful for non-abdominal tumors and to confirm function n. Angiography –Requires medication prep for safety

Bilateral pheochromocytomas (the on the left has a small area of central hemorrhage)

6 cm cystic pheo in the right adrenal of a 29 year old female

Pheochromocytoma at the level of the 7 th rib

Intramyocardial pheo in a patient (who died of CHF from effects of the pheo) known to have a pheo but who never underwent radionuclide scanning to localize it

Meds for Acute Symptom Control for Pheos (also for pre-angio or preop prep) n. Phentolamine 2 to 5 mg IV (alpha block) n. Then propranolol 1 to 2 mg IV (beta block) or labetolol 20 to 40 mg IV (alpha & beta block) n. Use nitroprusside or phentolamine infusion for hypertensive crisis (50 to 100 mg in 250 cc D 5 W) n. For hypotension : norepi infusion n. For arrhythmias : lidocaine bolus & infusion

Meds for Nonemergent or Chronic Sx Control for Pheos n. Phenoxybenzamine 10 to 20 mg tid-qid (alpha block) n. Prazosin 1 to 5 mg bid n. Propranolol 10 to 40 mg qid or labetolol 200 to 600 mg bid (beta block) n. Alpha-methyl-p-tyrosine (metyrosine) 250 mg to 1 gram bid (synthesis inhibitor)

Workup scheme for pheos

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

Thyroid Storm Epidemiology n. Most cases secondary to toxic diffuse goiter (Grave's Disease) –Mostly in women in 3 rd to 4 th decades n. Some cases due to toxic multinodular goiter –Mostly in women in 4 th to 7 th decades n. Very rarely due to : –Factitious –Thyroiditis –Malignancies n. Very rare in children

51 year old male with Graves Disease who presented with urine retention

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

Lag ophthalmos in a patient with Graves Disease

Another patient with Graves Disease

Thyroid scan of patient with Graves Disease Scan of patient with toxic multinodular goiter with hot nodule

Thyroid Storm Prognosis n. Old references quote almost 100% mortality untreated and 20% mortality treated ( but before beta blockers) n. Current mortality ? < 5 % treated (although not well studied or reported due to rarity of cases)

Thyroid Storm Clinical Presentation n. Most important: –Fever –Abnormal mental status (agitation confusion, coma) n. Tachycardia n. Vomiting / diarrhea n+/- jaundice n+/- goiter n+/- exopthalmos

Thyroid Storm CNS Manifestations n. With increasing severity of storm: –Hyperkinesis –Restlessness –Emotional lability –Confusion –Psychosis –Apathy –Somnolence –Obtundation –Coma

Thyroid Storm Cardiovascular Manifestations n. Increased heart rate –Sinus tach or atrial fib n. Increased irritability –First degree AV block, PVC's, PAC's n. Wide pulse pressure n. Apical systolic murmur n. Loud S 1, S 2 n. May develop CHF

"Apathetic" or "Nonactivated" Thyrotoxicosis n. Represents dangerous hyperthyroidism masked by preexistent sx n. Usually age > 70 n. Recent weight loss > 40 lbs. n. May present as seemingly isolated sx: –CHF –Atrial fib –CNS sx ƒ Somnolence, apathy, coma

Thyroid Storm Precipitating Factors n. Infection, esp. pneumonia n. CVA n. CHF n. Pulmonary embolus n. DKA n. Parturition / toxemia n. Trauma n. Surgery n. I 131 Rx n. Iodinated contrast agents n. Withdrawl of antithyroid drugs

Thyroid Storm Initial Lab Studies Needed n. CBC, lytes, BUN, glucose n. T 4, T 3 RU, TSH n. U/A n. ABG n+/- LFT's n+/- serum cortisol

Thyroid Storm Usual Lab Results n. Lab studies do NOT distinguish thyrotoxicosis from thyroid storm n. Usually T 4 & T 3 elevated, but may be only increased T 3 n. Usually plasma cortisol low for degree of physiologic stress present n. Hyperglycemia common

Thyroid Storm Emergent Rx n. High flow O 2 n. Rapid cooling if markedly hyperthermic –Ice packs, cooling blanket, mist / fans, NG lavage, acetominophen (ASA contraindicated) n. IV +/- IV fluid bolus if dehydrated –May need inotropes if already have CHF) n. Propranolol 1 to 2 mg IV & repeat or labetolol 20 to 40 mg IV & repeat prn n+/- digoxin, Ca channel blockers for rate control for atrial fib; +/- diuretics for CHF n. Find & treat precipitating cause

Thyroid Storm Further Rx n. IV hydrocortisone 100 mg n. PTU 600 to 900 mg PO or NG, then 200 to 300 mg qid n. Iodine (> 1 hour after PTU): 1 to 2 gm sodium iodide IV drip, then 500 mg q 12 hr; or 20 gtts SSKI PO tid n+/- Li CO 3 600 mg PO then 300 mg tid n+/- Colestipol (binds T 4 in gut) 10 grams PO tid

Myxedema Coma n. Represents end stage of improperly treated, neglected, or undiagnosed primary hypothyroidism n. Occurs in 0. 1% or less of cases of hypothyroidism n. Very rare under age 50 n 50% of cases become evident after hospital admission n. Mortality 100% untreated, 30 to 60% treated n. Most cases present in the winter

General Causes of Thyroid Failure n. Diseases of the: –Thyroid (primary hypothyroidism) : 95 % –Pituitary (secondary hypothyroidism) : 4% ƒ Pituitary tumor or sarcoid infiltration –Hypothalamus (tertiary hypothyroidism) : < 1 %

Etiologies of Primary Hypothyroidism n. Autoimmune : most common n. Post thyroidectomy n. External radiation n. I 131 Rx n. Severe prolonged iodine deficiency n. Antithyroid drugs (including lithium) n. Inherited enzymatic defect n. Idiopathic

Symptoms of Hypothyroidism n. Cold intolerance n. Dyspnea n. Anorexia n. Constipation n. Menorrhagia or amenorrhea n. Arthralgias / myalgias n. Fatigue n. Depression n. Irritability n. Decreased attention +/- memory n. Paresthesias

Signs Related to Hypothyroidism n. Dry, yellow (carotenemic) skin n. Weight gain (41% of cases) n. Thinning, coarse hair n"Myxedema signs“ : –Puffy eyelids –Hoarse voice –Dependent edema –Carpal tunnel syndrome n. Anemia

Patient with myxedema coma

Hypothyroidism and Myxedema Coma Cardiac Signs n. Hypotension n. Bradycardia n. Pericardial effusion n. Low voltage EKG n. Prolonged QT n. Inverted or flattened T waves

EKG findings in a hypothyroid patient

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

Lab Studies to Order for Suspected Myxedema Coma n. CBC n. Lytes, BUN, glucose, calcium n. T 3, T 4, TSH n. Serum cortisol n. ABG n. LFT's n+/- drug levels

Precipitants of Myxedema Coma n. Cold exposure n. Infection –Pneumonia –UTI n. Trauma n. CNS depressants –Narcotics –Barbiturates –Tranquilizers –General anesthetics n. CVA n. CHF

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

Emergency Treatment of Myxedema Coma n. O 2 +/- intubation / ventilation (if resp. failure) n. Rapid blood glucose check +/- IV D 50 +/- Naloxone n. Hydrocortisone 100 to 250 mg IVP n. Cautious slow rewarming (warm O 2, scalp/groin/axilla warm packs, NG lavage) n. Thyroxine (T 4) 500 micrograms IV, then 50 mcg qd IV n. Add 25 mcg triiodothyronine (T 3) PO or by NG q 12 h if T 4 to T 3 peripheral conversion possibly impaired n. Careful IV fluid rehydration ; watch for CHF n. Follow TSH levels ; should decrease in 24 hrs. & normalize in 7 days of Rx

60 year old male with severe hypothyroid -ism

Same patient as on prior slide 6 months after Rx with T 4

Causes of Hypoglycemia n. Fasting –Insulinoma or extrapancreatic tumors –Extensive hepatic dysfunction –Starvation –Sepsis –Chronic renal failure –Glycogen storage diseases –Diseases with antibodies to insulin or receptor –Hormonal deficiency (steroids, growth hormone, epi) –Drugs (on next slide) n. Postprandial (Alimentary, Reactive, Genetic galactosemia or fructose intolerance) n. Artifactual (leukemia, polycythemia)

Drugs Causing Hypoglycemia n. Insulin n. Oral hypoglycemics n. Ethanol n. Salicylates n. Beta blockers n. Pentamidine n. Diisopyramide n. Quinine n. Isoniazid n. MAO inhibitors n. Various drugs causing decreased liver metabolism of oral hypoglycemic agents

Symptoms and Signs of Hypoglycemia n. Symptoms –Diaphoresis –Palpitations –Headache –Hunger –Trembling –Faintness n. Signs –Hypothermia –Confusion –Amnesia –Seizures –Coma –ANY FOCAL CNS SIGN

Diagnostic Approach to Fasting Hypoglycemia n. Prove that hypoglycemia is directly responsible for sx during attacks by showing: –typical sx –plasma glucose < 50 mg% –prompt relief of sx by glucose ingestion or IV n. Consider checking: –Serum insulin level –Insulin antibodies –Sulfonylurea levels –C-peptide levels –Proinsulin levels

Causes of Polyuria n. UTI n. Osmotic diuresis (e. g. , diabetes mellitus) n. Primary (psychogenic) polydipsia (Compulsive water drinking) n. Nephrogenic diabetes insipidus n. Central diabetes insipidus

Causes of Diabetes Insipidus n. Central –Head trauma –Craniopharyngioma –Infiltrative (sarcoid) –Post neurosurgery –Familial –Vascular –Infectious –Idiopathic n. Nephrogenic –Drugs Demeclocycline ƒ Lithium carbonate ƒ –Acquired Sickle cell anemia ƒ K+ deficiency ƒ Hypercalcemia ƒ Amyloidosis ƒ Sjogren Syndrome ƒ Multiple myeloma ƒ –Familial

Hormone Preparations for Rx of Diabetes Insipidus Medication Aqueous vasopressin Lysine vasopressin Pitressin in oil Desmopressin HCTZ (for nephrogenic) Duration of Action (hrs. ) 2 to 6 Dose Route 5 to 10 u SQ or IV 2 to 6 2 to 4 u Nasal 24 to 48 5 u IM 12 to 24 10 to 20 mcg 12 to 24 50 to 100 mg Nasal PO