Endocrinology for the Surgeon

Dr. Jeremy Gilbert Sunnybrook Health Sciences Centre

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

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

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

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)

Uptodate 2012

Sensitive Not Specific

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!

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

Thyroid Storm- Management

Beta-blocker to decrease adrenergic tone
Propanolol 60-80 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
Lugols 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

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

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

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

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

Myxedema Coma- Presentation

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

Myxedema Coma- Diagnosis

Look for thryoid scar or history of RAI Perform thyroid function tests and check cortisol

Adrenal Disorders

Prepared by: Drs Jeannette Goguen, Robert Silver and Jeremy Gilbert

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

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.

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

This differential diagnosis of adrenal insufficiency includes:

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

2. What additional laboratory testing would you order?

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 500-550 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)

TFTs with thyroid antibodies: TSH 10, +++anti-thyroid Ab

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

3. How would you differentiate primary from secondary (pituitary failure) adrenal insufficiency (AI)?
Primary AI Hyperpigmentation? Yes Other autoimmune Often disorders Evidence of pituitary No insufficiency/mass effect Hyponatremia? Yes Hyperkalemia? Yes ACTH level High Secondary AI No Rarely
Maybe

Yes No Low

4. How would you acutely manage this patient?

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

5. What advice for long-term management of AI would you give after discharge?

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

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

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 10-20 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

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

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.

Tapering-alternate days
If prednisone between 20-30 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

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

1. What are your priorities regarding the adrenal mass?

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

2. What do benign adenomas look like on imaging?

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)

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

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

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.

What are you concerned about?

What are you concerned about?

Pheochromocytoma

What genetic syndromes are associated with this disorder?

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)

What should you ask her on history?

What should you ask her on history?

Triad: Spells with the 3 Ps:
Headache (pain), palpitations, perspiration

Symptoms associated with a neck mass (Medullary thyroid cancer)

What would you look for on physical exam?

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, caf au lait markings (NF-1)

What lab tests would you do to confirm Dx?

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

What is definitive therapy and how would you prep her?

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 alphablocker) 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.

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?

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

What is your differential diagnosis?

PTH Mediated
1HPT: PTH adenoma/hyperplasia/carcinoma 3 HPT Familial Hyopcalciuric Hypercalcemia (FHH) Lithium

Non-PTH Mediated

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, Pagets (immobility)

Hypercalcemic Crisis: Rx
1. Volume: IV NS 300-500 cc/h (slower if elderly, cardiac or renal disease) 2. Loop diuretic: Only give if ECFv overloaded. Lasix 20-40 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.)

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 0.3-0.5 mmol/L

Hypercalcemic Crisis: Rx
Bisphosphonates
Pamidronate Ca < 3.0 mM: 30 mg in 500cc NS IV over 4h Ca > 3.0 mM: 60-90 mg in 500cc NS IV over 24h Effect peaks @ 2-4d, lasts 1-6 wk (can retreat q1-6wk) Can also use zoledronic acid
Useful in Vitamin D intoxication, granuloma, lymphoproliferative disorders Prednisone 40-80 mg/d Takes 5-10d to see treatment effect

Steroids

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!

TREATMENT- Summary

FLUIDS FLUIDS FLUIDS FLUIDS FLUIDS FLUIDS

Lasix Other

FLUIDS FLUIDS FLUIDS FLUIDS FLUIDS FLUIDS

FLUIDS FLUIDS FLUIDS FLUIDS FLUIDS FLUIDS

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

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