Non Diabetic Endocrine Emergencies Ping-Wei Chen Dr. Stefan DaSilva December 18th 2008
Objectives Brief review of HPA axis physiology Thyroid Storm Thyrotoxicosis Myxedema Coma Adrenal Insufficiency/Crisis Pheochromocytoma Pituitary Apoplexy
Thyroid Physiology • Hypothalamus • Thyroptropin releasing hormone (TRH) • Anterior Pituitary • Thyroid stimulating hormone (TSH) • Thyroid • T3 and T4 Hypothalamic-Pituitary-Thyroid Axis
Thyroid Hormone Synthesis bloodstream lumen T3 T4
Case 1: Cranked!! 60 yr old female presents to PLC ED concerned because she might have a “clot in the veins”. States feels heart beating fast and very sweaty. HR 140, BP 180/90, 98% RA, Temp 37.6, glucose 11. 5 5
Cranked!! Review of Systems 5 days ago had radioactive iodine therapy. No fevers/chills/malaise “Thyroid disorder for years” States hx of previous DVT Hyperactive Remainder of review unremarkable.
Cranked!! Exam Hyperactive, speaking fast, restless Tremulous No tenderness to thyroid (why is this important??) Normal cardiopulmonary exam Hyperreflexive otherwise normal neurological examination 6
Cranked!! LABS: All normal. TSH sent Doppler U/S legs normal Cardiac markers negative CXR normal. ECG: sinus tachycardia 7 7
Cranked!! Treatment In ED gave Propranolol 2mg IV q10minutes x 3 ---> heartrate decreased to 70 - 80 During the day so discussed case with her primary endocrinologist. Wished her started back on Propanolol and Tapazole (methimazole). Agreed to see her the next day in clinic.
Hyperthyroidism/Thyrotoxicosis/Thyroid Storm Non-synonymous terms But no consensus on definitions Hyperthyroidism: the result of excessive thyroid function Thyrotoxicosis: a state of thyroid hormone excess Thyroid Storm: acute, life-threatening exacerbation of thyrotoxicosis Rosen’s: “They refer to the continuum of disease that results from thyroid hyperfunction”.
Symptoms/Signs of Hyperthyroidism Symptoms Signs Hyperactivity/Irritable/Dysphoria Tachycardia/A. fib in elderly Heat Intolerance/Sweating Tremor Palpitations Goiter Fatigue/Weakness Warm, moist skin Weight loss/Hyperphagia Muscle Weakness/Proximal Myopathy Diarrhea Lid retraction/Lag Polyuria Gynecomastia Oligomenorrhea/Dec. Libido Harrison’s Principles of Internal Medicine 16th Ed. p2113
Causes of Thyrotoxicosis Causes of Thyrotoxicosis Toxic Diffuse Goiter (Graves’ Disease) Toxic Multinodular Goiter Toxic Uninodular Goiter Factitious Thyrotoxicosis (external supplementation) T3 Toxicosis Thyrotoxicosis associated with Thyroiditis (eg: Hashimoto’s, de Quervain’s) Iodine Loads (eg: amiodarone) Metastatic Follicular Carcinoma Malignancies with circulating thyroid stimulators TSH – producing pituitary tumours Struma Ovarii with hyperthyroidism Hypothalamic hyperthyroidism
Precipitant of Thyroid Storm V – vascular accidents, PE, infarction I – infection T – trauma, surgery, burns A - *** M – hypoglycemia, DKA, HONK I – I131 therapy, thyroid hormone, contrast N - ***
Thyroid Storm Exaggerated hyperthyroidism + Fever + Altered LOC Cardiovascular: hyperdynamic + excitable Sinus tachycardia/Atrial tachycardia (A. fib) CHF (±underlying heart disease) Chest pain, Dyspnea, Palpitations, Inc. Pulse Pressure, “Water Hammer” pulse Gastrointestinal: Diarrhea, N/V, Abdominal pain Liver dysfunction
Thyroid Storm Neurological/Behavioural: Proximal myopathy/Weakness Tremor Agitation/Anxiety/Restlessness/Delirium
“Apathetic Hyperthyroidism” Elderly Fatigue and Weight Loss Multinodular Goiter Apathetic Thyroid Storm? Exaggerated Hyperthyroidism + Fever + Altered LOC NOT agitated/restless/anxious CV, GI, Neuro signs/symptoms still present
Diagnosis Low TSH, High FT4 or FT3 Differential Diagnosis: Sepsis – CXRay, Blood, Urine, Skin Intoxication (Cocaine, Amphetamines) – toxidrome? Withdrawal (EtOH, benzodiazapene) Heat Stroke - history Hypothyroidism
Treatment of Thyroid Storm 5 Goals of Treatment: 1) Inhibit Hormone Synthesis Propylthiouracil (PTU) 600-1000mg PO/NG, then 200-250mg q4-6h 2) Block Hormone Release (>1 hr post PTU) Saturated Solution of KI (SSKI) 5 drops PO/NG q6h Iodine Anaphylaxis: Lithium Carbonate 300mg PO q6h Iodine Overload Hyperthyroidism: Potassium Perchlorate 500mg PO OD.
3) Prevent Peripheral Conversion of T4 to T3 Propylthiouracil (PTU) Dexamethasone 2mg IV q6h Propranolol 4) Peripheral Adrenergic Blockade Propranolol 1-2mg IV bolus q10-15mins until effect 5) Supportive Care Treat fever: Acetaminophen (Not ASA) Treat CHF (digitalis, diuretics, oxygen) Stress dose steroids (Hydrocortisone 100mg IV q8h) Treat Precipitating Factors
Case 2: “I Can’t Move!” 21 yr old male woke up at 0300 hrs feeling unwell. Progressive weakness migrating from lower extremities to upper extremities. Now unable to move. Has had similar episodes in the past but not as severe and always resolved on their own.
“I Can’t Move!!” Vitals: 130/75, 105HR, 96% RA, 18RR, glucose 7.6, Temp 36.4 Recent URTI, no chest pain, shortness of breath, difficulty swallowing, back pain or bowel or bladder dysfunction. Recently immigrated from Mexico. Denies any medications or any medical history. Denies any drug or EtOH abuse.
“I Can’t Move!!” HEENT: no palpable lymph nodes, normal oropharynx CVS: S1S2, no murmurs RESP: Clear ABDO: soft, non-tender, no organomegaly NEURO: Cranial nerve exam normal, completeparalysis both upper and lower extremities, markedly hyporeflexia bilaterally (upper and lower), sensation and proprioception remained intact, rectal tone normal
Labs Arterial Blood Gas Na: 144, K: <1.5, Cl: 109, CO2: 16, Cr: 61, gluc: 8.0 WBC: 15.1, Ca: 2.57, Mg: 0.77, Phos: 0.15, Urea: 7.5 TSH: <0.01A, Free T4: 37, CK: 218 CXR: normal, CT head: normal
Thyrotoxic Periodic Paralysis Asian Males most common Native Americans/African Americans/South Americans Vigorous exercise/high carb meal Flaccid, ascending paralysis (proximal > distal) Spares facial and respiratory muscles Depressed/Absent DTR Due to weakness
Thyrotoxic Periodic Paralysis Low serum potassium Shift
Thyrotoxic Periodic Paralysis Management: 1) Block β-adrenergic stimulation of Na/K ATPase Propranolol 60mg PO q6h 2) Replete Potassium ORAL potassium (given not decreased total stores) 3) Treat Hyperthyroidism AVOID: IV glucose, β-agonists
Case 1: “I Can’t Move!” DX: Thyrotoxic Periodic Paralysis Improvement in ED with Potassium Replacement and B-blocker therapy Admitted to Internal Medicine During Admission diagnosed with 1st Presentation Graves Disease.
Post Partum Thyroiditis “Silent/Painless” thyroiditis 5% postpartum cases 3-4 months post-delivery 27
Clinical Features: Transient hyperthyroid followed by transient hypothyroid Triphasic course Non-tender thyroid, Normal ESR (cf. subacute thyroiditis) No eye findings (cf. Graves’ Disease)
Post Partum Thyroiditis Laboratory Findings FT4 >> T3 – leakage of hormone from gland Treatment (if needed) Propranolol 20mg-40mg q6-8h 28
Case 2: “I Can’t Warm Up!” 70 yr old non-english speaking female brought by EMS because of decline in LOC and function of past few days. Multiple recent ED visits for hyponatremia. Complaints of malaise, fatigue, weakness and confusion.
Case 2: “I Can’t Warm Up!” Vitals 35.2, 45-55HR, 10RR, 150/74 (initial), glucose 5.7 Past Medical History: HTN, RA, Shingles, Bilateral Hip Replacement Meds: BP med(water pill), acyclovir
Case 2: “I Can’t Warm Up!” Collateral History from son states multiple visits over past months for low salt, confusion and lethargy. Had been referred to Outpatient Internal Med Clinic. EXAM: puffy face, dry mm, tender epigastrium, tremelous, depressed reflexes, initial GCS 14/15, remainder of exam unremarkable.
LABS: Hgb: 109, WBC 3.9, Plts 100, ESR 111, Na 132, K 5.0, Glucose 4.1, Lipase 410, Urea 10.8, CK pending, TnT normal Initial ABG 7.43/38/78/25 lactate 0.6 TSH: not back in ED
CT head: normal CXR: normal Urine normal CT abdo/pelvis:probable ovarian mass, no diverticulitis or pancreatic abscess/pseudocyst, small bilat effusions seen.
Case 2: “I Can’t Warm Up!” In ED declining GCS to 8/15 profoundly bradycardic, borderline hypotensive, hyponatremia and hypoglycemia hypothermic (31.4C despite external re-warming techniques) decreased RR --> increasing CO2 on ABG Intubated and lined in ED After induction agents and paralytics had worn off pt made no respiratory effort on own, nor response to painful stimuli
DX: ?Myxedema Coma Given steroids and thyroxine (also given dose of abx after cultures drawn) Sent to ICU
Hypothyroidism Primary disease most common Autoimmune Iatrogenic Elderly Obese Females Subclinical Disease Myxedema Coma
Signs/Symptoms of Hypothyroidism Symptoms Signs Fatigue/Weakness Dry /Cool Skin Dry Skin Puffy face, hands, feet (myxedema) Cold intolerance Diffuse alopecia Hair Loss Bradycardia Difficulty Concentrating/Poor Memory Peripheral Edema Constipation Delayed DTRs Weight Gain/Poor Appetite Carpal Tunnel Syndrome Dyspnea Serous Cavity Effusion Hoarse Voice Menorrhagia Paresthesia Impaired Hearing Harrison’s Principles of Internal Medicine 16th Ed. p2109
Myxedema Coma Most dramatic of untreated/inadequately treated dz Rarely first presentation of hypothyroidism Most common: Thyroid hormone discontinuation Precipitating event Misnomer! ±Coma Myxedema Coma: Severe Hypothyroidism + Hypothermia + Altered LOC
Myxedema Coma Precipitants of Myxedema Coma Cold Exposure Infection (usually pulmonary) CHF Trauma Drugs Iodides CVA Hemorrhage (esp. GI) Hypoxia Hypercapnea Hyponatremia Hypoglycemia
Myxedema Coma Cardiovascular: Sinus bradycardia BP variable Leaky capillaries Effusions Respiratory: Depressed respiratory drive (hypoxic + hypercapneic) Airway obstruction (from edema)
Myxedema Coma Gastrointestinal: Decreased peristalsis Abdominal pain, distension, constipation Neurological: Paresthesias Cerebellar-Like Symptoms Due to increased muscle tone/prolonged contraction Coma
Diagnosis High TSH and Low Free T4 Note: Dopamine, Glucocorticoids, and Somatostatin suppress TSH at pharmacologic doses. Low/Normal TSH and Low Free T4? Hypothalamic/Pituitary Disease
Differential Diagnosis Sepsis Accidental Hypothermia Nephrotic Syndrome/Renal Failure Apathetic Hyperthyroidism Hyperglycemia Intoxication (sedatives)
Treatment of Myxedema Coma 4 Goals: 1) Thyroid Hormone Replacement Levothyroxine 500µg PO/IV, then 100µg/day 2) Correct Metabolic Abnormalities Hypoventilation – Intubate + Ventilate Hyponatremia – water restriction Hypoglycemia – D5W IV 3) Identify/Correct Precipitating Factors Infection? CHF?
4) Supportive Care Hypotension – Fluids, Pressors Hypothermia – GENTLE Rewarming Stress Dose Steroids – Hydrocortisone 300mg IV, then 100mg q6-8h.
Some Pearls ***beware when giving IV thyroxine and pressors together as may result in VF/VT (should stop pressor when giving IV thyroxine) ***try to avoid use of ASA in setting of storm as may worsen disease. ***can use CK as poor man’s TSH in setting of presumed myxedema coma. ***be diligent re: searching for precipitating causes!!! 43
Case 3: “The Disappearing Tan Lines” 29 yr old male with fatigue, heart palpitations, vomiting and lightheadness for 1yr. Presented to ED because of frustration and multiple physician visits for similar. Vitals: 36.6, 67HR, 14RR, 112/65, 99% RA, gluc 8.0