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.

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.

6

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

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.

9

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

Hyperactivity/Irritable/Dysphoria Heat Intolerance/Sweating Palpitations Fatigue/Weakness Weight loss/Hyperphagia

Signs

Tachycardia/A. fib in elderly Tremor Goiter Warm, moist skin Muscle Weakness/Proximal Myopathy Diarrhea Polyuria Lid retraction/Lag Gynecomastia Oligomenorrhea/Dec. Libido Harrison’s Principles of Internal Medicine 16 th Ed. p2113

Causes of Thyrotoxicosis

Causes of Thyrotoxicosis

Toxic Diffuse Goiter (Graves ’ Disease) Toxic Multinodular Goiter Toxic Uninodular Goiter Factitious Thyrotoxicosis (external supplementation) T 3 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 –

I 131 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

1 6

“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 FT 4 or FT 3 • 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 T 4 • Propylthiouracil (PTU) • Dexamethasone 2mg IV q6h • Propranolol to T 3 – 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.

2 2

“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,

complete paralysis

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) 3 0

Post Partum Thyroiditis

• Laboratory Findings – FT 4 >> T 3 – 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 3 5

• CT head: normal • CXR: normal • Urine normal • CT abdo/pelvis:probable ovarian mass, no diverticulitis or pancreatic abscess/pseudocyst, small bilat effusions 3 6 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 3 8

Hypothyroidism

Subclinical Disease Myxedema Coma • Primary disease most common – Autoimmune – Iatrogenic • Elderly Obese Females

Signs/Symptoms of Hypothyroidism

Symptoms Signs

Fatigue/Weakness Dry Skin Cold intolerance Hair Loss Difficulty Concentrating/Poor Memory Dry /Cool Skin Puffy face, hands, feet (myxedema) Diffuse alopecia Bradycardia Peripheral Edema Constipation Weight Gain/Poor Appetite Dyspnea Hoarse Voice Delayed DTRs Carpal Tunnel Syndrome Serous Cavity Effusion Menorrhagia Paresthesia Impaired Hearing Harrison ’s Principles of Internal Medicine 16 th 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 T 4 – Note: Dopamine, Glucocorticoids, and Somatostatin suppress TSH at pharmacologic doses.

• Low/Normal TSH and Low Free T 4 ?

– 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 – D 5 W 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!!!

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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

Case 3: “The Disappearing Tan Lines ”

• Review of Systems – Low BP (states at time as low as 85 systolic), wt loss of 20lbs over past year, Tingling and muscle weakness, shortness of breath on exertion, no chest pain, denies any drug or EtOH abuse – Previously treated for depression – Family hx of hypothyroid and diabetes

Case 3: “The Disappearing Tan Lines ”

• Exam – HEENT: normal – CVS: S1 S2, no murmurs – RESP: clear – NEURO: no focal – ABDO: benign – DERM: Bronze skin, no tan lines – MSK: muscle wasting

Case 3: “The Disappearing Tan Lines ”

• Labs: all normal in ED • However, outpt lab work one month ago shows: – Na 131, K: 5.8, Cl: 99, CO2: 23, CK: 410, Ferritin 364, Fe: 7, TSH 3.3

Adrenal Insufficiency

• An absolute or relative deficiency of adrenal hormones – Cortisol, Aldosterone, Androgen

Adrenal Physiology

Steroid Hormone Synthesis

Steroid Hormone Synthesis

17 α-Hydroxylase

Steroid Hormones

• Cortisol: – Intermediary metabolism (carbs,protein,fat,NA) – Immune response (depressed) Hypothalamus CRH Anterior Pituitary ACTH Negative Feedback Negative Feedback Adrenal Cortex (Cortisol)

Steroid Hormones

• Aldosterone – Blood Pressure – Vascular Volume – Electrolytes • Regulation – Primarily by Renin-Angiotensin-Aldosterone Axis • Small role by ACTH

Steroid Hormones

• Androgens – Male sex steroids • Secondary sexual characteristics in females • Small proportion of total androgen in males – Minimal effect of males • Regulation: – ACTH stimulates release – Does NOT feedback to decrease ACTH

Etiologies of Adrenal Insufficiency

• Primary – Idiopathic – autoimmune, idiopathic – Infectious – granulomatous, viral, fungal – Infiltrative – neoplasm, amyloidosis, sarcoidosis – Iatrogenic – post-adrenalectomy – Hemorrhage – CAH – lack of 21β-Hydroxylase deficiency – Congenital Unresponsiveness to ACTH

Etiologies

• Secondary – Pituitary Insufficiency • Infarction, Hemorrhage, Tumour/Infiltration, ACTH deficiency – Hypothalamic Insufficiency – Head Trauma • Functional Disease – Exogenous glucocorticoids

Acute Adrenal Insufficiency

• Acute illness on Chronic Adrenal Insufficiency

Precipitants of Acute Adrenal Insufficiency

Exogenous Steroids Infection Vascular Event (MI, CVA) Trauma Surgery Hypoglycemia Pain Psychiatric Event

Special Cases

• Adrenal Hemorrhage – Waterhouse-Friedrickson Syndrome • Sepsis from meningococcemia with associated adrenal hemorrhage (amongst hypotension,shock,DIC) • Can also occur from Pseudomonas sepsis – Acute, severe illness + anticoagulation/coagulopathy • Pituitary Infarction – Sheehan Syndrome • Delayed effect of intrapartum/post-partum hemorrhage leading to pituitary infarction

The Usual Suspects

Symptom/Sign

Weakness Pigmentation of Skin Weight Loss Anorexia/Nausea/Vomiting Hypotension (<110/70) Pigmentation of mucous membranes

Frequency (%)

99 98 97 90 87 82 Abdominal Pain Salt Craving Diarrhea Constipation Syncope Vitiligo 34 22 20 19 16 9

Hyperpigmentation

Adrenal Crisis

• Hypotension – Decreased myocardial contractility – Decreased responsiveness to catecholamines – Hypovolemia (Na wasting, N/V) • Hypoglycemia – Decreased gluconeogenesis – Increased peripheral glucose use

Treatment

• Correct the greatest threats to life!

– Hypotension: Fluid resuscitate ± pressors – Hypoglycemia: D 5 W or D 5 0.9% saline • Glucagon 1-2mg IM/SC – Correct hormone deficiency: • Cortrosyn Stimulation Test – 0.25mg (25U) cosyntropin IV/IM – Serum cortisol at time: 0, 30 mins, 60 mins – Normal: cortisol >500nmol/L or >200nmol/L over baseline • Dexamethasone 4mg IV q6-8h (during test) • Hydrocortisone 100mg IV/IM q6-8h • Treat the Precipitating Factor!

Case 3: “The Disappearing Tan Lines ”

• DX: Primary Adrenal Insufficiency/Addison ’s Disease • Referral made to Urgent Internal Medicine/Endo – Cosyntropin stim test performed – Started on Decadron – Marked improvement within 48hrs

Prevention

• Cortisol: – Acute Illness • Double dose of hydrocortisone – Severe Illness • 75-150mg hydrocortisone/day • Aldosterone: • Fludrocortisone 0.05-0.1mg

• Increase salt in diet

Adrenal Medulla

Norepinephrine Epinephrine

Catecholamine Effects

• Norepinephrine/Epinephrine: – α and β effects • Increased CV contractility, excitability, heart rate – Increased gluconeogenesis/glycogenolysis – Increased metabolic rate – Increased alertness/anxiety/fear

Pheochromocytoma

• Catecholamine secreting tumour – Adrenal or Extra-adrenal – Rare! – Young to Mid-Adult Life • Clinical Presentation: – Hypertension – most common – Paroxysms • Hypertension, Headache, Sweating, Palpitations, Apprehension, Sense of impending doom, Chest Pain, Abdo Pain, N/V, pallor/flushing

Differential Diagnosis

• Sympathomimetic Intoxication • MAOI Crisis • Withdrawal of Clonidine therapy • Seizures • Intracranial Lesions – posterior fossa tumours • SAH

Pheochromocytoma

• Cardiovascular – Hypertension (DBP >120) – ECG • Sinus tachycardia, SVT, VT, V.Fib.

• Non-specific ST changes, U-waves (hypoK) • Ventricular Strain • RBBB, LBBB • Prolonged QT • Endocrine – Impaired glucose tolerance

Diagnosis

• 24 Hour Urine Studies – Catecholamines and Metabolites • Free Catecholamines • Free Metanephrines • Vanillylmandelic acid (VMA) – Provocative and Adrenolytic Tests obsolete

Treatment

• α-adrenergic Blockade – Phentolamine 1-2mg IV q5mins – Phenoxybenzamine 10mg PO q12h (long term) • β-blockade – ONLY AFTER stable α-blockade achieved – usually reserved for tachydysrrhythmias – Propranolol 10mg PO q6-8h • Nitroprusside, CCB, ACEi

Pituitary Gland

Growth Hormone ACTH Prolactin TSH LH FSH ADH Oxytocin

Pituitary Apoplexy

• Infarction or Hemorrhage of Pituitary Gland – Pre-existing tumour – Head trauma – Pregnancy – Anti-coagulation – Hypertension – DKA – Irradiation – Estrogen – Diuretic use – Bromocriptine

Clinical Presentation

• Sudden onset headache • Visual abnormalities • Oculomotor abnormalities • Meningeal irritation • Altered mental status • Pituitary Insufficiency • Adrenal Insufficiency

Diagnosis

• MRI – gold standard • CT

• Treatment

• Dexamethasone 4mg IV q6-8h • Hydrocortisone 100mg IV/IM q6-8h • ±Emergent Neurosurgery

Conclusion

• Endocrine emergencies are RARE! – High index of suspicion in certain patient populations • Most diagnoses are

CLINICAL!!!!!

• Search for precipitating causes!!

Questions?