Presentation on theme: "Endocrinology for the Surgeon"— Presentation transcript:
1 Endocrinology for the Surgeon Dr. Jeremy GilbertSunnybrook Health Sciences Centre
2 ObjectivesBy the end of this presentation, participants will be able to:Review diagnosis and treatment of thyroid emergenciesDiscuss diagnosis and management of adrenal insufficiencyFocus on steroid taperingReview workup for adrenal incidentalomaFocus on pheochromocytomaDiscuss an approach to hypercalcemia diagnosis and management
3 Case #1 66 y.o. woman for elective cholecystectomy Type 1 Diabetes and hypertensionRx: Ramipril 5 mg, InsulinPost Op Day 1 develops Temperature 38.7, HR 125 bpm (sinus), and confusionWhat is the differential diagnosis, most likely diagnosis and management
5 Thyroid Storm- Definition Rare, life threatening condition manifesting as exaggeration of thyrotoxicosisUsually patients have underlying hyperthyroidism with an acute precipitant (surgery, trauma, infection)Maybe related to poor compliance and low SESCLINICAL DIAGNOSIS (NOT LABORATORY)
7 Thyroid Storm- Investigations Clinical exam- goitre, proptosis, tremorSuppressed TSH, elevated FT4 and FT3Higher BS (catecholamine), Calcium (increased bone metabolism)WBC- elevated or reducedAbnormal liver enzymesDo not wait for imaging (u/s, RAIU and scan) to make diagnosis!
8 Thyroid Storm- Management Monitored Setting (10-30% mortality rate)Same as for hyperthyroidism, except meds given in higher doses, more oftenTreat comorbidities (eg. infection)Supportive care- tylenol, cooling blanket, fluids or diuretics
9 Thyroid Storm- Management Beta-blocker to decrease adrenergic tonePropanolol mg q 4-6 h depending on HR, BP1 mg iv q 10 minsA thionamide to block new hormone synthesisPTU 200 mg q 4 hrsAn iodine solution to block the release of thyroid hormone AT LEAST ONE HOUR AFTER THIONAMIDELugol’s solution 10 drops tidSteroids to reduce T4-to-T3 conversion, promote vasomotor stability, and possibly treat an associated relative adrenal insufficiencyHydrocortisone 100 mg tid
10 Thyroid Storm Suspect it Review History Complete Physical Exam Appropriate blood workManagement
11 Case #2 83 yo F found at home with decreased LOC Very drowsy BP 100/60, P 48, Temp 34.3, O2 sat 96% RA, BG: 5.1Chest clear, HS: distantSwollen anklesGCS 9/15PERL, face symmetrical, no papilledemaWithdraws all 4 limbsPlantars downgoingNeck not stiff
13 Myxedema Coma Severe hypothyroidism with multiple systems involved Rare, high mortalityUsually from chronic untreated hypothyroidism or acute precipitantMeds (opioids), Infection, MI, Cold exposureMost common in older individuals, especially women
14 Myxedema Coma- Presentation Decreased LOC (often not coma)HypothermiaHyponatremiaHypotensionHypoglycemiaHypoventilationBradycardiaPuffiness- myxedema- mucin deposits
15 Myxedema Coma- Diagnosis Look for thryoid scar or history of RAIPerform thyroid function tests and check cortisol
17 Prepared by: Drs Jeannette Goguen, Robert Silver and Jeremy Gilbert Adrenal DisordersPrepared by: Drs Jeannette Goguen, Robert Silver and Jeremy Gilbert
18 Case 3 A 25 yo woman is brought to ER: c/o vomiting, diarrhea and abdominal pain x 24 hrs.Decreased appetite, lost 5 kgs involuntarilySignificant dizziness on arisingRetained her “suntan” from the previous summer
19 Case 3 continued . . . O/E: she looks chronically unwell HR120/minute; BP is 90/60 supine and 60/30 uprightHer JVP is not visibleDiffuse abdominal tenderness with no peritoneal signsLarge, dark freckles over her cheeks and darkened palmer creasesLarge patches of vitiligoPreliminary labs: Na=125, K= 5.2, glucose = 2.5.
20 1. What is the likeliest diagnosis 1. What is the likeliest diagnosis? What is in your differential diagnosis?
21 1. What is the likeliest diagnosis 1. What is the likeliest diagnosis? What is in your differential diagnosis?The likeliest diagnosis:acute on chronic adrenal insufficiency presumably precipitated by an acute viral gastroenteritis.The differential of weight loss and malaise is very broad, and includes:MalignancyEndocrine: Diabetes mellitus, thyrotoxicosisOrgan failure (liver, kidney)Inflammatory disordersInfections (eg, TB)
22 This differential diagnosis of adrenal insufficiency includes:
23 This differential diagnosis of adrenal insufficiency includes: Autoimmune adrenalitis*** likeliest diagnosisTuberculosisHIV-related infections including TB, HIV itself, CMV and histoplasmosisMeningococcal septicemia with acute adrenal hemorrhage (Waterehouse-Friedrichson syndrome)Adrenal hemorrhage secondary to anti-coagulantAnti-phospholipid antibody (APLA)Infiltrative disordersMetastatic malignancyAdrenal Leukodystrophy
24 2. What additional laboratory testing would you order?
25 2. What additional laboratory testing would you order? Other baseline labs:Creatinine 124Urea 10Hgb 98, increased lymphocytes and eosinophilsBaseline cortisol = 88 nmol/L (next day)Baseline ACTH = 100 (normal < 20) (1 month later)Formal Cortrosyn stim test: 1 hr cortisol= 120 (next day)Cortisol level over nmol/L at either baseline or 60 minutes post-injection of Cortrosyn andA rise in Cortisol of 250 nmol/L above baseline. (baseline cortisol > 500 nmol/L rules out adrenal insufficiency)TFT’s with thyroid antibodies: TSH 10, +++anti-thyroid Ab
26 3. How would you differentiate primary from secondary (pituitary failure) adrenal insufficiency (AI)?
27 3. How would you differentiate primary from secondary (pituitary failure) adrenal insufficiency (AI)?Primary AISecondary AIHyperpigmentation?YesNoOther autoimmune disordersOftenRarelyEvidence of pituitary insufficiency/mass effectMaybeHyponatremia?Hyperkalemia?ACTH levelHighLow
29 4. How would you acutely manage this patient? IV fluids with normal saline and glucose running wide open until BP has stabilized and hypoglycemia has resolvedAdministration of 4-8 mg of IV Dexamethasone once baseline ACTH and cortisol drawn, do Cortrosyn Stimulation testDDAVP 1-2 ug iv or sc and sodium load when significantly low baseline plasma Na < 120Once hemodynamically stable and able to eat, stress dose steroid coverage can be aborted and oral administration of Hydrocortisone can begin
30 5. What advice for long-term management of AI would you give after discharge?
31 5. What advice for long-term management of AI would you give after discharge? Hydrocortisone- 25 mg daily in split doses, try to reduce to lowest tolerated dose, typically 10 mg QAM, 5 mg QPM (dose is weight-dependent)Florinef- 0.1 mg dailyMeds must be taken every day.For a mild febrile illness, double the dosage of Hydrocortisone for 3 days then see doctor if still unwell.If persistently nauseated or vomiting, go immediately to a local emergency room for intravenous glucocorticoid steroidGet a Medic Alert braceletPurchase injectable Dexamethasone for remote travelling
33 Steroid taperingSteroids suppress the H-P-A axis based on duration, potency, doseLikely if on prednisone 20 mg or its equivalent for more than 3 weeks or who looks CushingoidUnlikely if on steroids for < 3 weeks or on alternate day regimensUncertain if prednisone mg for < 3 weeks orIf uncertain and going for surgery, it may be worth checking their HPA axis via ACTH stim testIndividuals vary in how tapering affects them (age, ethnicity- slower in Blacks, elderly)Consider stability of disease and general health statusToo expensive and not practical to be following cortisols
34 ACTH Stimulation test 250 mcg or 1 mcg of cosyntropin (ACTH) given iv Measure cortisol before test, 30 mins and 60 minsIf Cortisol > 500 nmol/L at any point, there is no adrenal insufficiencyIf on steroids, must be dexamethasoneBest done in am when cortisol should be highest
35 Tapering- paucity of evidence 5 to 10 mg/day every one to two weeks from an initial dose above 40 mg of prednisone or equivalent per day.5 mg/day every one to two weeks at prednisone doses between 40 and 20 mg/day.2.5 mg/day every two to three weeks at prednisone doses between 20 and 10 mg/day.1 mg/day every two to four weeks at prednisone doses between 10 and 5 mg/day.0.5 mg/day every two to four weeks at prednisone doses from 5 mg/day down. This can be achieved by alternating daily doses, eg, 5 mg on day 1 and 4 mg on day 2.
36 Tapering-alternate days If prednisone between mg, can try alternate days at 10 mg by reducing by 5 mg every 1-2 weeksDecrease alternate day dose by 2.5 mg every 1-2 weeks until the alternate day dose is 0 mgReduce the other dose as you would on a daily regimen
37 Case 4:Mrs S is a 55 yo woman with kidney stones who has been found to have a right 4 cm adrenal mass on routine CTShe has a past 1-year history of hypertension, BP today is 165/108 on:Amlodipine 10 mg dailyRamipril 10 mg daily
39 1. What are your priorities regarding the adrenal mass?
40 1. What are your priorities regarding the adrenal mass? Is this a benign or malignant tumor?Is it hormone-secreting?CatecholaminesCortisolAldosteroneEstrogen or androgen
41 2. What do benign adenomas look like on imaging?
42 2. What do benign adenomas look like on imaging? Small (typically < 4 cm)Regular shape, no hemorrhage or calcificationLack of growth over timeLipid-richAdvanced answer: on CT, low Hounsfeld units (< 10); rapid wash out of contrast (>50% in 10 minutes)
43 3. What lifestyle factors can contribute to poorly controlled hypertension?
44 3. What lifestyle factors can contribute to poorly controlled hypertension? Dietary: salt, alcohol, licoriceLack of exerciseObesity with sleep apneaOver the counter meds: pseudoephedrine, NSAIDsCocaine, amphetamines
45 Case Continued. . .Mrs S has a family history of “dangerous tumors” in the adrenal gland: both her father, paternal uncle and cousin had these removed. It had been recommended to her that she get her urine tested for adrenaline and that she consider genetic testing, but she has felt well overall and has been too busy with her law practice to get the testing done.
53 What would you look for on physical exam? BP in both arms, postural hypotensionEnd-organ complications from hypertensionAdvanced answer:Thyroid mass (MEN 2 A and B)Mucosal neuromas on lips, Marfanoid habitus (MEN 2B)Retinal, cerebellar findings (hemangioblastomas with vHL)Neuromas, café au lait markings (NF-1)
55 What lab tests would you do to confirm Dx? 24 hour urine catecholamines, metanephrines and creatinine (if negative, repeat with symptoms if gets spells, but asymptomatic with first collection)Results: volume 2.5 L, creatinine 8 mmol/dayMetanephrine normalNormetanephrine 29.3 (normal 0-3.3)Epinephrine < 10 (normal)Norepinephrine 5173 (normal 0-500)Can do plasma metanephrine levels if availableAdvanced answer:MIBG nuclear scan can be used to localize tumors of no masses on adrenal imaging, or if suspect multiple tumors (if familial condition)Genetic counseling/genetic testing/screen for other associated tumors if suspect genetic disorder
56 What is definitive therapy and how would you prep her?
57 What is definitive therapy and how would you prep her? Surgery to remove the tumor.She will need adequate control of her blood pressure prior to surgery with Phenoxybenzamine (non-competitive alpha-blocker) to avoid surges in blood pressure during surgery.Only for the 2 weeks before surgery, because of cost factorsUse calcium channel blockers and competitive alpha-blockade (eg, doxazosin) before thenAdvanced answer:On Phenoxybenzamine:Increased salt intake to avoid significant postural hypotensionIf she becomes tacchycardic, she should receive beta-blockade, once adequately alpha-blocked.
58 Case 575 yo M brought by EMS to ED as wife noted patient had decreased LOCO/E dry MM, BP 100/50, HR 110Chest clear, Normal CVS, abdo NormalCa+ 3.3, creatinine 125, albumin 29Management?
60 What is your differential diagnosis? PTH Mediated1˚HPT: PTH adenoma/hyperplasia/carcinoma3˚ HPTFamilial Hyopcalciuric Hypercalcemia (FHH)LithiumNon-PTH Mediated
61 Hypercalcemia Ddx Non-PTH Mediated Malignancy Granulomatous Disease PTHrP (SCC)Osteolysis (myeloma, breast Ca)1-alpha hydroxylase of Vitamin D (lymphoma)Granulomatous DiseaseDrugsVitamin D, ACalcium antacids (milk alkali)ThiazidesEndocrinopathies: Adrenal insufficiency, Pheo, Thyrotoxicosis, Paget’s (immobility)
62 Hypercalcemic Crisis: Rx Volume: IV NS cc/h (slower if elderly, cardiac or renal disease)Loop diuretic: Only give if ECFv overloaded. Lasix mg IV q4-6h. Monitor I/O carefully, keep patient in positive fluid balanceReplace electrolyte depletion from saline diuresis as needed (K, Mg, Pi, etc.)
63 Hypercalcemic Crisis: Rx Calcitonin1 IU SC test dose: skin rxn by 15 min4 IU/kg SC/IM q12hIf no response by 24-48h increase to max dose 8 IU/kg q6hRapid effect (begins 4-6h) but transient (2-3d) due to tachyphylaxsisEffective in 60-70% of cases, lowers Ca by mmol/L
64 Hypercalcemic Crisis: Rx BisphosphonatesPamidronateCa < 3.0 mM: 30 mg in 500cc NS IV over 4hCa > 3.0 mM: mg in 500cc NS IV over 24hEffect 2-4d, lasts 1-6 wk (can retreat q1-6wk)Can also use zoledronic acidSteroidsUseful in Vitamin D intoxication, granuloma, lymphoproliferative disordersPrednisone mg/dTakes 5-10d to see treatment effect
65 Hypercalcemic Crisis: Rx Obsolete treatments:Mithramycin: + + N/V & other toxicitiesGallium nitrate: nephrotoxicChelators: IV EDTA, IV or PO phosphateConsider dialysisIdentify & Rx underlying cause of hypercalcemia!
67 Summary of ObjectivesReview diagnosis and treatment of thyroid emergenciesDiscuss diagnosis and management of adrenal insufficiencyFocus on steroid taperingReview workup for adrenal incidentalomaFocus on pheochromocytomaDiscuss an approach to hypercalcemia diagnosis and management