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Endocrinology for the Surgeon Dr. Jeremy Gilbert Sunnybrook Health Sciences Centre.

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Presentation on theme: "Endocrinology for the Surgeon Dr. Jeremy Gilbert Sunnybrook Health Sciences Centre."— Presentation transcript:

1 Endocrinology for the Surgeon Dr. Jeremy Gilbert Sunnybrook Health Sciences Centre

2 Objectives By the end of this presentation, participants will be able to: Review diagnosis and treatment of thyroid emergencies Discuss diagnosis and management of adrenal insufficiency – Focus on steroid tapering Review workup for adrenal incidentaloma – Focus on pheochromocytoma Discuss an approach to hypercalcemia diagnosis and management

3 Case #1 66 y.o. woman for elective cholecystectomy Type 1 Diabetes and hypertension Rx: Ramipril 5 mg, Insulin Post Op Day 1 develops Temperature 38.7, HR 125 bpm (sinus), and confusion What is the differential diagnosis, most likely diagnosis and management

4 Differential Diagnosis – Hypoglycemia – Hypoxia – Pulmonary embolism – Myocardial ischemia – Sepsis – Alcohol withdrawal – Atelectasis – Malignant hyperthermia/neuroleptic malignant syndrome

5 Thyroid Storm- Definition Rare, life threatening condition manifesting as exaggeration of thyrotoxicosis Usually patients have underlying hyperthyroidism with an acute precipitant (surgery, trauma, infection) Maybe related to poor compliance and low SES CLINICAL DIAGNOSIS (NOT LABORATORY)

6 Uptodate 2012 Sensitive Not Specific

7 Thyroid Storm- Investigations Clinical exam- goitre, proptosis, tremor Suppressed TSH, elevated FT4 and FT3 Higher BS (catecholamine), Calcium (increased bone metabolism) WBC- elevated or reduced Abnormal liver enzymes Do 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 often Treat comorbidities (eg. infection) Supportive care- tylenol, cooling blanket, fluids or diuretics

9 Thyroid Storm- Management Beta-blocker to decrease adrenergic tone – Propanolol mg q 4-6 h depending on HR, BP 1 mg iv q 10 mins A thionamide to block new hormone synthesis – PTU 200 mg q 4 hrs An iodine solution to block the release of thyroid hormone AT LEAST ONE HOUR AFTER THIONAMIDE – Lugol’s solution 10 drops tid Steroids to reduce T4-to-T3 conversion, promote vasomotor stability, and possibly treat an associated relative adrenal insufficiency – Hydrocortisone 100 mg tid

10 Thyroid Storm Suspect it Review History Complete Physical Exam Appropriate blood work Management

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: 5.1 – Chest clear, HS: distant – Swollen ankles – GCS 9/15 – PERL, face symmetrical, no papilledema – Withdraws all 4 limbs – Plantars downgoing – Neck not stiff

12 Differential Diagnosis “ Metabolic” coma Hypoglycemia, hyperglycemia, hypoxia, Hypotension, hypertension, hypothermia Organ failure (liver, renal, pulmonary, other ???) Drug intoxication / withdrawal Electrolyte abnormalities ([Na], [Ca], [Mg], [PO4], [H+]) Subarachnoid hemorrhage, encephalitis/meningitis Sepsis Postictal Endocrine: hypopit, hypoadrenal, hypothyroid

13 Myxedema Coma Severe hypothyroidism with multiple systems involved Rare, high mortality Usually from chronic untreated hypothyroidism or acute precipitant – Meds (opioids), Infection, MI, Cold exposure Most common in older individuals, especially women

14 Myxedema Coma- Presentation Decreased LOC (often not coma) Hypothermia Hyponatremia Hypotension Hypoglycemia Hypoventilation Bradycardia Puffiness- myxedema- mucin deposits

15 Myxedema Coma- Diagnosis Look for thryoid scar or history of RAI Perform thyroid function tests and check cortisol

16

17 Adrenal Disorders Prepared 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 involuntarily Significant dizziness on arising Retained 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 upright Her JVP is not visible Diffuse abdominal tenderness with no peritoneal signs Large, dark freckles over her cheeks and darkened palmer creases Large patches of vitiligo Preliminary labs: Na=125, K= 5.2, glucose = 2.5.

20 1. What is the likeliest diagnosis? What is in your differential diagnosis?

21 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: Malignancy Endocrine: Diabetes mellitus, thyrotoxicosis Organ failure (liver, kidney) Inflammatory disorders Infections (eg, TB)

22 This differential diagnosis of adrenal insufficiency includes:

23 Autoimmune adrenalitis*** likeliest diagnosis Tuberculosis HIV-related infections including TB, HIV itself, CMV and histoplasmosis Meningococcal septicemia with acute adrenal hemorrhage (Waterehouse-Friedrichson syndrome) Adrenal hemorrhage secondary to anti-coagulant Anti-phospholipid antibody (APLA) Infiltrative disorders Metastatic malignancy Adrenal Leukodystrophy

24 2. What additional laboratory testing would you order?

25 Other baseline labs: – Creatinine 124 – Urea 10 – Hgb 98, increased lymphocytes and eosinophils Baseline 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 and – A 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 2. What additional laboratory testing would you order?

26 3. How would you differentiate primary from secondary (pituitary failure) adrenal insufficiency (AI)?

27 Primary AISecondary AI Hyperpigmentation?YesNo Other autoimmune disorders OftenRarely Evidence of pituitary insufficiency/mass effect NoMaybe Hyponatremia?Yes Hyperkalemia?YesNo ACTH levelHighLow

28 4. How would you acutely manage this patient?

29 IV fluids with normal saline and glucose running wide open until BP has stabilized and hypoglycemia has resolved Administration of 4-8 mg of IV Dexamethasone once baseline ACTH and cortisol drawn, do Cortrosyn Stimulation test DDAVP 1-2 ug iv or sc and sodium load when significantly low baseline plasma Na < 120 Once 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 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 daily Meds 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 steroid Get a Medic Alert bracelet Purchase injectable Dexamethasone for remote travelling

32 Steroids Glucocorticoid dosing equivalences – cortisone acetate 25 mg – hydrocortisone (Solucortef) 20 mg – prednisone 5 mg – methyl-prednisolone (Solumedrol) 4 mg – dexamethasone (Decadron) 0.75 mg

33 Steroid tapering Steroids suppress the H-P-A axis based on duration, potency, dose – Likely if on prednisone 20 mg or its equivalent for more than 3 weeks or who looks Cushingoid – Unlikely if on steroids for < 3 weeks or on alternate day regimens – Uncertain if prednisone mg for < 3 weeks or If uncertain and going for surgery, it may be worth checking their HPA axis via ACTH stim test Individuals vary in how tapering affects them (age, ethnicity- slower in Blacks, elderly) – Consider stability of disease and general health status Too 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 mins If Cortisol > 500 nmol/L at any point, there is no adrenal insufficiency If on steroids, must be dexamethasone Best 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 weeks Decrease alternate day dose by 2.5 mg every 1-2 weeks until the alternate day dose is 0 mg Reduce 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 CT She has a past 1-year history of hypertension, BP today is 165/108 on: – Amlodipine 10 mg daily – Ramipril 10 mg daily

38

39 1. What are your priorities regarding the adrenal mass?

40 Is this a benign or malignant tumor? Is it hormone-secreting? – Catecholamines – Cortisol – Aldosterone – Estrogen or androgen

41 2. What do benign adenomas look like on imaging?

42 Small (typically < 4 cm) Regular shape, no hemorrhage or calcification Lack of growth over time Lipid-rich Advanced answer: on CT, low Hounsfeld units ( 50% in 10 minutes)

43 3. What lifestyle factors can contribute to poorly controlled hypertension?

44 Dietary: salt, alcohol, licorice Lack of exercise Obesity with sleep apnea Over the counter meds: pseudoephedrine, NSAIDs Cocaine, 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.

46 What are you concerned about?

47 Pheochromocytoma

48 What genetic syndromes are associated with this disorder?

49 MEN 2A and 2B Von Hippel Lindau Advanced answer: Neurofibromatosis type 1 Familial paraganglioma syndromes (mutations in SDH genes)

50 What should you ask her on history?

51 Triad: Spells with the 3 P’s: – Headache (“pain”), palpitations, perspiration Symptoms associated with a neck mass (Medullary thyroid cancer)

52 What would you look for on physical exam?

53 BP in both arms, postural hypotension End-organ complications from hypertension Advanced 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)

54 What lab tests would you do to confirm Dx?

55 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/day – Metanephrine normal – Normetanephrine 29.3 (normal 0-3.3) – Epinephrine < 10 (normal) – Norepinephrine 5173 (normal 0-500) Can do plasma metanephrine levels if available Advanced 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 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 factors – Use calcium channel blockers and competitive alpha-blockade (eg, doxazosin) before then Advanced answer: On Phenoxybenzamine: – Increased salt intake to avoid significant postural hypotension – If she becomes tacchycardic, she should receive beta-blockade, once adequately alpha-blocked.

58 Case 5 75 yo M brought by EMS to ED as wife noted patient had decreased LOC O/E dry MM, BP 100/50, HR 110 Chest clear, Normal CVS, abdo Normal Ca+ 3.3, creatinine 125, albumin 29 Management?

59 Symptoms Bones: fractures, osteoporosis, osteitis fibrosa, arthritis Stones: renal stones, polyuria, polydypsia (DI), nephrocalcinosis, renal insufficiency Groans: constipation, nausea, pancreatitis, peptic ulcer disease, abdo pain Moans: lethargy, depression, fatigue, stupor, coma Neuromuscular: proximal muscle weakness, myopathy Cardio: bradycardia, shortened QT, hyperT

60 What is your differential diagnosis? PTH Mediated 1˚HPT: PTH adenoma/hyperplasia/carcinoma 3˚ HPT Familial Hyopcalciuric Hypercalcemia (FHH) Lithium Non-PTH Mediated

61 Hypercalcemia Ddx Non-PTH Mediated Malignancy » PTHrP (SCC) » Osteolysis (myeloma, breast Ca) » 1-alpha hydroxylase of Vitamin D (lymphoma) Granulomatous Disease Drugs » Vitamin D, A » Calcium antacids (milk alkali) » Thiazides Endocrinopathies: Adrenal insufficiency, Pheo, Thyrotoxicosis, Paget’s (immobility)

62 Hypercalcemic Crisis: Rx 1.Volume: IV NS cc/h (slower if elderly, cardiac or renal disease) 2.Loop diuretic: Only give if ECFv overloaded. Lasix mg IV q4-6h. Monitor I/O carefully, keep patient in positive fluid balance 3.Replace electrolyte depletion from saline diuresis as needed (K, Mg, Pi, etc.)

63 Hypercalcemic Crisis: Rx Calcitonin 1 IU SC test dose: skin rxn by 15 min 4 IU/kg SC/IM q12h If no response by 24-48h increase to max dose 8 IU/kg q6h Rapid effect (begins 4-6h) but transient (2-3d) due to tachyphylaxsis Effective in 60-70% of cases, lowers Ca by mmol/L

64 Hypercalcemic Crisis: Rx Bisphosphonates Pamidronate – Ca < 3.0 mM: 30 mg in 500cc NS IV over 4h – Ca > 3.0 mM: mg in 500cc NS IV over 24h Effect 2-4d, lasts 1-6 wk (can retreat q1-6wk) Can also use zoledronic acid Steroids Useful in Vitamin D intoxication, granuloma, lymphoproliferative disorders Prednisone mg/d Takes 5-10d to see treatment effect

65 Hypercalcemic Crisis: Rx Obsolete treatments: Mithramycin: + + N/V & other toxicities Gallium nitrate: nephrotoxic Chelators: IV EDTA, IV or PO phosphate Consider dialysis Identify & Rx underlying cause of hypercalcemia!

66 TREATMENT- Summary FLUIDS FLUIDSFLUIDS Lasix Other

67 Summary of Objectives Review diagnosis and treatment of thyroid emergencies Discuss diagnosis and management of adrenal insufficiency – Focus on steroid tapering Review workup for adrenal incidentaloma – Focus on pheochromocytoma Discuss an approach to hypercalcemia diagnosis and management

68 Thank you!!!! QUESTIONS??????


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