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

17. Prepared by: Drs Jeannette Goguen, Robert Silver and Jeremy Gilbert
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
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:
Malignancy
Endocrine: Diabetes mellitus, thyrotoxicosis
Organ failure (liver, kidney)
Inflammatory disorders
Infections (eg, TB)

22. This differential diagnosis of adrenal insufficiency includes:

23. This differential diagnosis of adrenal insufficiency includes:
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. 2. What additional laboratory testing would you order?
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

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 AI
Secondary AI
Hyperpigmentation?
Yes No
Other autoimmune disorders
Often
Rarely
Evidence of pituitary insufficiency/mass effect
Maybe
Hyponatremia?
Hyperkalemia?
ACTH level
High
Low

28. 4. How would you acutely manage this patient?

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 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. 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 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

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?
Catecholamines
Cortisol
Aldosterone
Estrogen 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 calcification
Lack of growth over time
Lipid-rich
Advanced 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, 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. What are you concerned about?
Pheochromocytoma

48. What genetic syndromes are associated with this disorder?

49. What genetic syndromes are associated with this disorder?
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. What should you ask her on history?
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. What would you look for on physical exam?
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. 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/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. 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 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 Granulomatous Disease
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
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 balance
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 FLUIDS FLUIDS
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??????