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1
Endocrine Emergencies
Maude LatulippeDr. Arun Abbi
January 21st 2010
2
Objectives
• Thyroid Storm• Thyrotoxicosis• Myxedema Coma• Adrenal Insufficiency/Crisis• Pheochromocytoma
3
Thyroid Physiology
• Hypothalamus– Thyrotropin releasing
hormone (TRH)
• Anterior Pituitary– Thyroid stimulating
hormone (TSH)
• Thyroid – T3 and T4
Hypothalamic-Pituitary-Thyroid Axis
4
Thyroid Hormone Synthesis
T3 T4
bloodstream
lumen
55
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
66
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.
76
Cranked!!
• Exam– Hyperactive, speaking fast, restless– Tremulous– No tenderness to thyroid (why is this
important??)– Normal cardiopulmonary exam– Hyperreflexive otherwise normal
neurological examination
87
Cranked!!
• LABS: All normal. TSH sent• Doppler U/S legs normal• Cardiac markers negative• CXR normal.• ECG: sinus tachycardia
7
99
Cranked!!
• Treatment– In ED gave Propranolol 2mg IV
q10minutes x 3 ---> heart rate 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.
10
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
11
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
12
Causes of ThyrotoxicosisCauses 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
13
Precipitant of Thyroid Storm
• V – vascular accidents, PE, infarction• I – infection• T – trauma, surgery, burns, palpation• A - ***• M – hypoglycemia, DKA, HONK• I – I131 therapy, thyroid hormone,
contrast, amiodarone, iodine, Li, withdrawal thyroid meds• N - ***
14
Thyroid StormThyrotoxicosis + altered mental status +
fever
• Temp > 37.8 oC• Tachycardia out of proportion to fever• CNS sx (excitation early, depress later)• Cardiovasc or GI signs and sx-dysrythmias -severe Do
-PVCs -No ,Vo
-AV block -Cramps20-30% surgical
emerg!!
15
“Apathetic Hyperthyroidism”
• Elderly (>70yo)– Lethargy, Slow mentation, Apathetic
facies– Goiter– Blepharoptosis– Excessive weight loss (average=40lbs)– Prox muscle weakness–Masked thyrotoxicosis by cardiovasc sx:
a fib with CHF
16
Diagnosis• Low TSH, High FT4 or FT3
• Differential Diagnosis:– Sepsis – CXRay, Blood, Urine, Skin– Intoxication (Cocaine, Amphetamines) –
toxidrome?–Withdrawal (EtOH, benzo)– Heat Stroke – history–Malignant hyperthermia– Neuroleptic malignant syndrome– Hypoglycemia or DKA
17
Treatment of Thyroid Storm• 5 Goals of Treatment:– 1) Inhibit Hormone Synthesis• Propylthiouracil (PTU) 600-1200mg PO/NG,
then 200-250mg q4-6h• Methimazole 20mg PO q4h
– 2) Block Hormone Release (>1 hr post PTU)• Iodine: Saturated Solution of KI (SSKI) 5 drops
PO/NG q6h (iopanoic acid, Lugol’s iodine), • Iodine Anaphylaxis: Lithium Carbonate
300mg PO q6h
18
– 3) Prevent Peripheral effectsConversion of T4 to T3 • Propylthiouracil (PTU)• Propranolol• Dexamethasone 10mg
Peripheral Adrenergic Blockade• Propranolol 1-2mg IV bolus q5mins until effect• Alternative: esmolol, guanethidine,
reserpine
– 4) Supportive Care• Treat fever: Acetaminophen (Not ASA)• Treat CHF (diuretics, oxygen)• Stress dose steroids
5) Treat Precipitating factors
19
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.
2020
“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.
21
“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
22
23
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
24
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
25
Thyrotoxic Periodic Paralysis
• Low serum potassium– Shift
26
Thyrotoxic Periodic Paralysis
• Management:– 1) Block β-adrenergic stimulation of Na/K
ATPase• Propranolol 60mg PO q6h
– 2) Replete Potassium– 3) Treat Hyperthyroidism
• AVOID: IV glucose, β-agonists
27
Case 1: “I Can’t Move!”
• DX: Thyrotoxic Periodic Paralysis
• Improvement in ED after K+ 10mEqK IV B-blocker therapy
• Admitted to Internal Medicine
• During Admission diagnosed with 1st Presentation Graves Disease.
28
Post Partum Thyroiditis• “Silent/Painless” thyroiditis• 5-10% postpartum cases• 6 wks to 6 months months post-
delivery• Transient hyperthyroid followed by
transient hypothyroid then euthyroid • Propranolol if needed
27
29
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.
30
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
31
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, tremulous, depressed reflexes, initial GCS 14/15, remainder of exam unremarkable.
3232
• 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
3333
• CT head: normal
• CXR: normal
• Urine normal
• CT abdo/pelvis: probable ovarian mass, no diverticulitis or pancreatic abscess/pseudocyst, small bilat effusions seen.
34
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
3535
• DX: ? Myxedema Coma• Given steroids and thyroxine (also
given dose of Abx after cultures drawn)
• Sent to ICU
36
Hypothyroidism
• Primary disease most common– Autoimmune– Iatrogenic
• Elderly Obese Females
Subclinical Disease Myxedema Coma
37
Medications associated with hypothyroidismDecreased TSH secretionDopamineGlucocorticoidsOctreotideDecreased thyroid hormone secretionLithiumIodideAmiodaroneDecreased T4 absorptionColestipolCholestyramineAluminum hydroxideFerrous sulfateSucralfateIncreased thyroid hormone metabolismPhenobarbitalRifampinPhenytoinCarbamazepine
38
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
Seizures 25% cases(low Na+, low glycemia)
Harrison’s Principles of Internal Medicine 16th Ed. p2109
Signs/Symptoms of Hypothyroidism
39
Myxedema Coma
• Most dramatic of untreated/inadequately treated dz– Rarely first presentation of hypothyroidism– Most common:
• Thyroid hormone discontinuation• Precipitating event
• Misnomer! ±Coma ±Myxedema
• Myxedema Coma:– Severe Hypothyroidism + Hypothermia +
Altered LOC
40
Myxedema ComaPrecipitants of Myxedema ComaCold Exposure
Infection (usually pulmonary)
CHF
Trauma
Drugs
Iodides
CVA
Hemorrhage (esp. GI)
Hypoxia
Hypercapnea
Hyponatremia
Hypoglycemia
41
Myxedema Coma
• Cardiovascular:– Sinus bradycardia– BP variable– Leaky capillaries• Effusions
• Respiratory:– Depressed respiratory drive (hypoxic +
hypercapneic)– Airway obstruction (from edema)– Muscle weakness
42
• Gastrointestinal:– Decreased peristalsis• Abdominal pain, distension, constipation
• Neurological:– Paresthesias– Cerebellar-Like Symptoms • Due to increased muscle tone/prolonged
contraction
– Coma
43
• Mortality 15%
• Predictors– Age– temp < 34– HR < 40 – large amounts of T4 iv
44
Investigation
• Hyponatremia• Blood glucose N to low• ↑CPK/AST/LDH• ABG: resp acidosis (Hypoventilation)• Urinalysis: source infection• CXR• +- Abdo XR• +- Head CT• +- Echo
45
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– Critically ill patients
46
Differential Diagnosis
• Sepsis• Accidental Hypothermia• Nephrotic Syndrome/Renal Failure• Apathetic Hyperthyroidism• Hyperglycemia• Intoxication (sedatives)• CHF• Electrolytes imbalance• Depression• Hepatic encephalopathy
47
Treatment of Myxedema Coma
• ABC• 4 Goals:– 1) Thyroid Hormone Replacement• Levothyroxine 300µg slow IV, then 100µg/day
– 2) Correct Metabolic Abnormalities• Hypoventilation – Intubate + Ventilate• Hyponatremia – water restriction
• Hypoglycemia – D5W IV
– 3) Identify/Correct Precipitating Factors• Infection? CHF?
48
– 4) Supportive Care• Hypotension – Fluids• Hypothermia – GENTLE Rewarming• Stress Dose Steroids – Hydrocortisone 100mg
IV q8h
4943
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 if TSH not available in setting
of presumed myxedema coma.• ***be diligent re: searching for precipitating
causes!!!
50
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
51
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
52
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
53
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
54
Adrenal Insufficiency
• An absolute or relative deficiency of adrenal hormones– Cortisol, Aldosterone, Androgen
55
Adrenal Physiology
56
Steroid Hormones• Cortisol:– Intermediary metabolism (carbs,protein,fat,NA)– Immune response (depressed)– Fonction of catecholamines on cardiac muscle
and arterioles Hypothalamus
CRH
Anterior Pituitary
ACTH
Adrenal Cortex
(Cortisol)
Negative Feedback
Negative Feedback
57
Steroid Hormones
• Aldosterone– Blood Pressure– Vascular Volume– Electrolytes
• Regulation– Primarily by Renin-Angiotensin-
Aldosterone Axis• Small role by ACTH
58
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
59
Etiologies of Adrenal Insufficiency
• BIG CAUSE TODAY: HIV-RELATED• Primary– Idiopathic – autoimmune, idiopathic– Infectious – granulomatous, viral, fungal– Infiltrative – neoplasm, amyloidosis,
sarcoidosis– Iatrogenic – post-adrenalectomy, RX– Hemorrhage– CAH – lack of 21β-Hydroxylase deficiency– Congenital Unresponsiveness to ACTH
60
Etiologies
• Secondary– Pituitary Insufficiency• Infarction, Hemorrhage, Tumour/Infiltration,
ACTH deficiency
– Hypothalamic Insufficiency– Head Trauma
• Functional Disease– Exogenous glucocorticoids
61
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
62
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
63
The Usual SuspectsSymptom/Sign Frequency (%)
Weakness 99
Pigmentation of Skin 98
Weight Loss 97
Anorexia/Nausea/Vomiting 90
Hypotension (<110/70) 87
Pigmentation of mucous membranes
82
Abdominal Pain 34
Salt Craving 22
Diarrhea 20
Constipation 19
Syncope 16
Vitiligo 9
64
Hyperpigmentation
65
Adrenal Crisis
• Hypotension– Decreased myocardial contractility– Decreased responsiveness to
catecholamines– Hypovolemia (Na wasting, N/V)
• HypoNa, HyperK, HyperCa• Hypoglycemia– Decreased gluconeogenesis– Increased peripheral glucose use
66
Treatment• Correct the greatest threats to life!– Hypotension: Fluid resuscitate ± pressors– Correct hyper K (hyper Ca, hypo Na)– Hypoglycemia: D5W or D50.9% saline– Correct hormone deficiency:
• Corticotropin Stimulation Test– Baseline cortisol– 250mcg cosyntropin IV/IM– Serum cortisol at time: 0, 30 mins, 60 mins– Normal: cortisol baseline or after test >550nmol/L or
2xbaseline• Dexamethasone 4mg IV q6-8h (during test)• Hydrocortisone 100mg IV/IM q6-8h
• Treat the Precipitating Factor!
67
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
68
Prevention
• Cortisol:– Acute Illness• Double dose of hydrocortisone
– Severe Illness• 75-150mg hydrocortisone/day
• Aldosterone:• Increase salt in diet • Fludrocortisone 0.05-0.2mg
69
Adrenal Medulla
NorepinephrineEpinephrine
70
Precipitants!!ExerciceStressNaloxoneGlucagon, Metoclopramide5-HTBBRocuronium
If those drug precipitate HTN crise = pheo!!
71
Catecholamine Effects
• Norepinephrine/Epinephrine:– α and β effects• Increased CV contractility, excitability, heart
rate
– Increased gluconeogenesis/glycogenolysis
– Increased metabolic rate– Increased alertness/anxiety/fear
72
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
73
Differential Diagnosis
• Sympathomimetic Intoxication• MAOI Crisis• Withdrawal of Clonidine therapy• Seizures• Intracranial Lesions – posterior fossa
tumours• SAH
74
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
75
Diagnosis
• 24 Hour Urine Studies– Catecholamines and Metabolites• Free Catecholamines • Free Metanephrines• Vanillylmandelic acid (VMA)
76
Treatment
• α-adrenergic Blockade– Phentolamine 5 mg IV q1-2min– Phenoxybenzamine 10mg PO q12h (long
term)
• β-blockade– ONLY AFTER stable α-blockade achieved – usually reserved for tachydysrrhythmias– Propranolol 10mg PO q6-8h
• Mg, Nitroprusside, CCB, ACEi
77
Conclusion
• Endocrine emergencies are RARE! – High index of suspicion in certain patient
populations
• Most diagnoses are CLINICAL!!!!!• Search for precipitating causes!!
78
Questions?