Endocrinology Flashcards

Question

Clinical Pearl Regarding Imaging hyper/hypo thyroidsm

Answer 1

only image thyroid if thyroid nodule felt or seen on carotid imaging

Answer 2

Severe hypothyroidism leading to: – Altered LOC / lethargy – Hypothermia – Hypotension – Bradycardia – Hyponatremia – Hypoventilation Life-threatening SLOWING of function in multiple organs! Diagnosis is clinical – but often see very low/undetectable FT4, high TSH

Answer 3

IV levothyroxine load 200-400mcg x1 followed by 1.6mcg/kg/d (this is the PO dose, multiple by 75% if given IV) – Lower dose should be considered if cardiac history or elderly – PO levothyroxine ~75% as potent as IV form * IV glucocorticoids (HC 100mg IV Q8H) until AI ruled out * IV liothyronine (T3) load 5-20mcg x1 followed by 2.5-10mcg Q8H * Supportive measures (ICU monitoring, mechanical ventilation, fluids, warming)

Answer 4

see chart in notes -Pregnant women with TSH >2.5 mU/L should be evaluated for TPOAb -Once on treatment, target TSH ≤ 2.5 throughout the pregnancy -In Canada, we do not routinely screen TSH in asymptomatic pregnant women

Answer 5

Need ~30-35% more LT4 as soon as pregnant = take an extra LT4 pill on Saturdays and Sundays (two extra pills/week = 9 pills/week) as soon as they are pregnant Need ~30-35% more LT4 as soon as pregnant = take an extra LT4 pill on Saturdays and Sundays (two extra pills/week = 9 pills/week) as soon as they are pregnant -Upon delivery, go back to pre-pregnancy dose -Target TSH ≤ 2.5 throughout pregnancy

Answer 6

1. Anti-thyroidal medications are teratogenic. a) Use PTU in the first trimester (conversion ~1mg MMZ:20mg PTU), MMZ after that (or discontinue all ATDs if possible!) - Patients on MMZ <10mg/d or PTU <200mg/d may try discontinuing b) Use the lowest possible dose (aim for T4 at high-normal range) 2. TSH-R Ab can cross the placenta. a) Check Ab titer in second trimester. If very high (3x ULN), need increased fetal monitoring for fetal Graves’. 3. Long-term treatment with β-blockers has been associated with intrauterine growth restriction, fetal bradycardia, and neonatal hypoglycemia. 4. Watch for post partum exacerbations a) Could also be post partum thyroiditis

Answer 7

In normal pregnancy, Thyroid Binding Globulin and total T4 increase by 7 wks GA and peak at 16 wks GA * hCG stimulates the TSH receptor on the thyroid gland causing ↑thyroid hormone & ↓TSH * The hCG effect may be even more pronounced in: -Hyperemesis gravidarum -Molar pregnancy -Multiple gestation -Choriocarcinoma Generally self-limited, improves by 14-18 weeks * Treat hyperemesis if present * Use B-blockers if really necessary for symptoms * Do NOT give PTU or methimazole

Answer 8

A) Fragility fracture OR B) Bone mineral density of 2.5 or more standard deviations (SD) below the peak bone mass for young adults (T-score ≤ –2.5) on dual-energy x- ray absorptiometry (DEXA)

Answer 9

How do we risk stratify? * History: identify signs of “automatic high risk” * CAROC or FRAX tools BMD * 50–64 yr with a previous osteoporosis-related fracture or ≥ 2 clinical risk factors * ≥ 65 yr with 1 clinical risk factor for fracture * ≥ 70 yr Spine x-ray / vertebral fracture assessment * ≥ 65 yr with T-score ≤ –2.5 (femoral neck, total hip or lumbar spine) * 10-yr major osteoporotic fracture risk between 15% and 19.9% (moderate) * Clinical signs: vertebral tenderness, height loss (historical 6 cm, prospective 2cm), occiput to wall > 5 cm, rib-pelvis < 2 fingers

Answer 10

When to Treat: High Risk * Hip, vertebra or ≥ 2 osteoporosis-related fractures * 10-yr major osteoporotic fracture risk ≥ 20% * ≥ 70 yo and have a T-score ≤ –2.5 (femoral neck, total hip or lumbar spine) Before initiating pharmacotherapy, assess for secondary causes of osteoporosis: ALP (Paget's), PTH, Calcium/Alb/PO4 (parathyroid), Cr/eGFR (renal disease), TSH (hyperthyroidism), 25OH vitamin D (deficiency, malabsorption), Meds/Alcohol SPEP – vertebral #, anemia (MM), Eating disorders, Bariatric Surgery Hx, testosterone (hypogonadism), CRP (IBD), tTG-IGA (Celiac) etc. Suggest Treatment: Moderate Risk * 10-yr major osteoporotic fracture risk between 15% and 19.9% * < 70 yr and have a T-score ≤ –2.5 (femoral neck, total hip or lumbar spine) Other treatment decision factors to consider: * a fracture in the last 2 years (risk of subsequent fracture highest) * ongoing risk factors

Answer 11

See Chart 1. Oral Bisphosphonates (First line in consideration of cost and access) 2. IV Zolendronic Acid (If GI effects on oral bisphosphonates) 3. Denosumab (If intolerant to bisphosphonates) * 4. Romosozumab or Teriparatide (If vertebral body height loss >40% OR > 1 vertebral fracture AND a T-score ≤ –2.5) 5. HRT (if female < 60, within 10 yr of menopause start, with goals to treat menopause symptoms Ω) 6. Raloxifene (Over no treatment in postmenopausal females who cannot tolerate any other therapies) 7. Off Label Bisphosphonate Dose/frequency reduction, Denosumab, collaborative decision making with nephro & endo (If CKD, eGFR<30) Length of treatment Bisphosphonates: initial therapy for 3–6 yr, Reassess during drug holiday with BMD/FRAX in 3 years (or sooner if clinical indication) * Denosumab: long-term uninterrupted therapy (should not delay Q6month dosing by more than 1 mo) may be re-assessed after 6–10 yr * If stop at ≤ 4 doses, transition to bisphosphonate 6 mo after the last dose of denosumab (reduces risk of rapid bone loss. Bisphosphonate therapy for 1 yr and then reassessing). * If stop at ≥ 5 doses (risk of rapid bone loss or vertebral fractures is high): refer to OP expert * Teriparatide (24 mos)/Romo (12 mos): one course then transitionto antiresorptive agent to maintain bone density gains

Answer 12

BP effects on bone persist for several years after discontinuation *it should be FIRST LINE for most patients with OP* * Atypical femur fracture (AFF) and Osteonecrosis of Jaw (ONJ) risks rise sharply after 3-5 years, and can be reduced by taking a drug holiday * Drug holiday = temporarily stopping BP for up to 5 years – Restart therapy within 5 years if significant BMD decline, interval fracture, or other risk factors that increase risk * Once on therapy, reassess fracture risk in 3-5 years – If HIGH-RISK à continue therapy or switch to another agent – If LOW-MODERATE à drug holiday; reassess fracture risk every 2-4 years * Restart therapy if significant bone loss or enters high risk BMD Monitoring Frequency * Not a candidate for pharmacological treatment: – 5–10 yr: if risk of major osteoporotic fracture (MOF) is < 10% – 5 yr if risk of MOF is 10%–15% – 3 yr if the risk of MOF is > 15% * Those on Therapy: – 3 yr after starting Rx * Those on Bisphosphonate Drug Holiday: – 3 yrs after stopping *BMD measurement may be repeated sooner/more frequently in people with new fracture, secondary causes of osteoporosis, or new clinical risk factors associated with rapid bone loss

Answer 13

Severe osteoporosis (T-score <-2.5) with multiple vertebral fractures *look for contraindications to bisphosphonates and denosumab when considering* * Fractures despite prolonged bisphosphonate use * High fracture risk and low bone formation * Osteoporosis and prolonged steroid use * Osteonecrosis of the Jaw * Atypical Femoral Fracture

Answer 14

Renal insufficiency (not well-studied) * Renal stones * Primary hyperparathyroidism/hypercalcemia * Extensive skeletal radiation * Paget’s disease Don’t use in: * children or young adults * women who are pregnant or nursing * gout or hyperuricemia Maximum duration = 24 months, longer use *may* ↑risk of osteosarcoma (animal data)

Answer 15

Monoclonal anti-sclerostin antibody – Sclerostin is produced by osteocytes and inhibits bone formation. – Anti-sclerostin promotes bone formation and bone remodeling. * SC injection given monthly for up to 12 months – Can be used in eGFR <30 but risk of hypocalcemia * Benefits: – reduced vertebral, non-vertebral, *hip fractures – very low risk of atypical femoral fractures or osteonecrosis of jaw *not powered adequately but signal towards less hip # * Side Effects: – Most worrisome is increased risk of MACE events noted in ARCH trial (Romosuzumab vs Alendronate, 2017) – Most common side effect were injection site reactions or hypersensitivity reactions – Very low risk of AFF and ONJ but still possible

Answer 16

**Thigh pain on bisphosphonates = need to rule out AFF! (bilateral femur X-rays, if these negative consider bone scan / MRI if high index suspicion)** * Proximal femoral shaft fracture * Atraumatic * Chronic bisphosphonate use (risk increases as early as 3 years) * Asian women * prodromal thigh pain (in up to 70%) -can also occur with denosumab and romosozumab PREVENTION * Consider drug holiday in low or moderate-risk patients on oral bisphosphonate for 5 years (or IV bisphosphonate for 3 years) (NOT in high-risk patients) TREATMENT * Orthopedic surgery consult (for IM nail insertion) * Make sure contralateral femur is imaged (early fractures may be asymptomatic) * Stop bisphosphonate * Ensure adequate vitamin D and calcium intake * Start teriparatide (if still meet OP treatment criteria= still High Risk)

Answer 17

> 1 fracture or substantial bone density decline (e.g. ≥ 5%) * adherence to an adequate course of treatment (typically >1 yr) * Consider : secondary causes of osteoporosis, falls, BMD imprecision errors * Do not use bone turnover markers or FRAX/CAROC for monitoring What to do: * extend or switch therapy * reassess for secondary causes and refer to OP expert

Answer 18

If GFR <30 and low BMD but no history of fragility fracture, no treatment is recommended If high risk based on fractures (not BMD alone) and osteomalacia / adynamic bone disease excluded, may consider pharmacotherapy * – Consult with specialists in MBD (Endo and Nephro) * – Lower dose bisphosphonate (e.g. risedronate every other week is suggested but this is off-label use) * If GFR <15, consider bone biopsy and only treat if clear that risk of mortality from recurrent fracture is high if untreated

Answer 19

Pathophysiology: focal ↑ in bone resorption by very large osteoclasts, then ↑ osteoblastic activity producing a high rate of bone formation/turn-over. * Initial Labs: ↑ serum total alkaline phosphatase (ALP) +/- bone specific ALP, without other abnormalities * Imaging: do plain film XRs first of suspicious areas, if asymptomatic do skeletal survey/series (look for thickened cortices with tunnelling & accentuated trabeculae) * If the diagnosis is confirmed - bone scan shouldbe done to determine the extent of the disease. * Associated illness: – Hearing loss, compressive neuropathies, osteoarthritis, osteosarcoma

Answer 20

Indications for Treatment: – Symptoms – pain, compression, fracture – Evidence of active disease with impending symptoms (high risk for fracture) – Hypercalcemia (usually should only happen if immobile) – ALP >2x ULN – Pre-orthopedic surgery at or near site (i.e. femoral Paget’s lesion for hip replacement) * First Line Treatment: IV zoledronic acid 5mg IV q1yr is treatment of choice or Oral bisphosphonate can be used **NOTE DOSING** – alendronate 40 mg/day x 6 months – Risedronate 30mg/day x 2 months * 2nd Line Agent (if intolerant to bisphos) is : Calcitonin

Answer 21

T2DM diagnosis should be made by any one of being abnormal -Fasting glucose ≥ 7mmol/L -HbA1c ≥ 6.5% -2h 75g OGTT ≥ 11.1 mmol/L -Random PG ≥ 11.1 mmol/L Type of Diabetes: * Type1: insulin deficiency (pancreatic β cell destruction), DKA prone, Usually Anti-GAD/Anti-Islet Cell + * Type 2: insulin resistance (tissue resistance, secretory defect), metabolic syndrome * Latent autoimmune diabetes in adults (LADA): type 2 diabetes who also have immune-mediated loss of pancreatic β cells * Monogenic: familial autosomal dominant mutation leading to beta cell defects, neonatal or <25 yo * GDM: glucose intolerance during pregnancy

Answer 22

(IFG: 6.1-6.9) (Prediabetes: 6.0-6.4%) (IGT: 7.8-11.0)

Answer 23

* ≤6.5% in some with T2DM if low-risk of hypoglycemia * ≤7% for almost everyone – corresponds to FBG 4.0-7.0 and 2h post meal 5.0-10.0 * 7.1-8.0% if functionally dependent (NEW CATEGORY!) * 7.1-8.5% if: – Recurrent severe hypoglycemia/hypo unawareness – Limited life expectancy – Frail elderly with dementia * Pregnancy planning – ≤7.0% (≤6.5% if possible and safe)

Answer 24

Type 2 but not on insulin: - When A1C targets are not being reached, structured CBG testing should be instituted (including a 7-point profile; fasting, preprandial/2-h postprandial at eachmeal, bedtime; every 1-3 months) to improve A1C If achieving A1C targets or receiving anti-hyperglycemic medications not associated with hypoglycemia, daily CBG testing is not recommended except during illness or at risk of hyperglycemia. Type 2 ON basal-bolus-insulin: -rtCGM may be used to reduce A1C and duration of hypoglycemia -isCGM may be used as an alternative to CapBG testing to reduce frequency and duration of hypoglycemia -In pregnant women with type 1 diabetes, rtCGM should be used to increase TIR and reduce TAR

Answer 25

* Non-pharmacological management (refer to Diabetes Education Centre, Set A1C target, assess CV status) * Diet/Lifestyle changes for all * Metformin if A1C ≧ 1.5% above target at diagnosis – Insulin + Metformin if symptomatic hyperglycemia and/or metabolic decompensation * Reassess in 3-6 months

Answer 26

non-fatal stroke

Answer 27

Suggests a state of relative or absolute insulin deficiency. * Polyuria * Polydipsia * Blurry Vision * Unintentional Weight loss * Volume depletion * Ketosis * HHS/DKA SHOULD BE STARTED ON INSULIN +/- metformin until glycemic control is achieved! (then you back off insulin if you can, while adding on oral agents)

Answer 28

Risk of euglycemic DKA (look out for relatively OK sugars with metabolic acidosis on SGLT2i drugs, caution if very low carb diet!) GU infections * Yeast infection * Possible perineal necrotizing fasciitis (Fournier’s Gangrene) * CKD patients: Glycemic lowering less at lower GFR (but cardiorenal protection preserved) Dapagliflozin -Avoid if active bladder cancer

Answer 29

GI side effects : dyspepsia, anorexia, nausea, vomiting, abdo pain, diarrhea Contraindicated with personal/family history of medullary thyroid cancer or MEN2 Caution if history of pancreatitis or pancreatic cancer Semaglutide- Worsening retinopathy:SUSTAIN-6 trial **note worsening retinopathy may be from rapid glucose lowering**

Answer 30

Cholesterol = Statin therapy -Clinical CVD -Age ≥ 40 -Age >30 and diabetes duration > 15 years -Microvascular disease -Other CV risk factors ACEi/ARB -Clinical CVD -Age ≥ 55 with an additional CV risk factor or end organ damage (albuminuria, retinopathy, LVH) -Microvascular disease Note: Should use doses shown to provide CV protection (perindopril 8 mg daily, ramipril 10 mg daily, telmisartan 80 mg daily) ASA -Established CV disease only -We no longer recommend ASA for primary prevention of CVD in people with diabetes (10). **2020 UPDATE**

Answer 31

Autoimmune thyroid disease develops in 10% (up to 30% of females) – Check TSH, anti-TPO Ab at diagnosis and q2-5 years thereafter Thyroid peroxidase antibodies (TPOAb)- hashimotos/hypothyroid Autoimmune adrenal insufficiency is rare – Screen if symptoms, unexplained hypoglycemia * Celiac disease in about 5%, asymptomatic – Screen if any symptoms, including iron deficiency, unexplained hypoglycemia, vitamin D deficiency, osteoporosis

Answer 32

Screening: T1D: Start 5 years after diagnosis after age 15 T2D: Start at diagnosis for all patients Dilated fundoscopy, fundus photography 1. If present: Further monitoring and treatment as determined by ophthalmology. 2. If not present: Rescreen q1yr (T1DM), q1-2yr (T2DM) TX; Tight BG + BP control. Laser therapy, intraocular therapy (anti-VEGF), surgery (vitrectomy).

Answer 33

Annual Screening: Start after 5 years’ duration of post-pubertal Type 1 diabetes All patients with Type 2 diabetes- at diagnosis 10g monofilament test OR 128 Hz Vibration annually Treatment: 1. Intensify glycemic control 2. Anticonvulsants > Antidepressants > Opioid > topical

Answer 34

Annual Screening: 5 years after diagnosis of Type 1 Diabetes At diagnosis of Type 2 Diabetes Dx: Random Urine ACr >20, OR 2 of 3 >2mg/mmol and/or eGFR <60 Treatment: ACE inhibitor or ARB Refer if: chronic progressive loss of renal function, ACR persistently >60, eGFR <30, inability to continue on ARB/ACE, unable to achieve target BP

Answer 35

Patients treated with insulin or a secretagogue should: -Have a medical exam at least q2 yrs to assess fitness to drive -Measure BG immediately before driving and at least q4h (q2h if history of recurrent severe hypoglycemia or hypoglycemic unawareness) while driving, or wear a CGM - Not drive if BG <4.0 -Not drive for at least 40 min after successful treatment of hypoglycemia, and BG should be at least 5.0 “FIVE TO DRIVE!” Health care professionals should instruct patients not to drive and should report to the appropriate driving licensing body if: -Any episode of severe hypoglycemia while driving in the past 12 months -More than 1 episode of severe hypoglycemia while awake (but not driving) in the past 6 months for private drivers and 12 months for commercial drivers

Answer 36

* Basal-Bolus Injection (BBI) * Continuous Subcutaneous Insulin Infusion (CSII, also known as insulin pump therapy) * +/- Continuous Glucose Monitoring (CGM) * No recommendations for non-insulin antihyperglycemic agents in T1DM (metformin, SGLT2 inhibitors, GLP-1 receptor agonists)

Answer 37

*Arterial pH is ≤7.3 * serum bicarbonate is ≤15 mmol/L and the anion gap is >12 mmol/L *positive serum and/or urine ketones *BG is usually ≥14.0 mmol/L Transition: *2-3 h overlap to subcut insulin and make sure they're eating Don't forget to manage the precipitant! *MI, infection, trauma, thyrotoxicosis, insulin omission etc vs. HHS: * Usually BG≥34.0 mmol/L * Increased plasma osmolality >320 mOsm/kg * greater ECFV contraction, minimal to no acidosis * Neuro: more decreased LOC, seizures

Answer 38

If you think the hormone is high, diagnosis is made by: Trying to measure it when it should be low Trying to suppress it If you think the hormone is low, diagnosis is made by: Trying to measure it when it should be high Trying to stimulate it

Answer 39

Weakness, lethargy, GI symptoms – not very specific Hyponatremia, HYPERKALEMIA Orthostatic hypotension, hypoglycemia, uremia Hyperpigmentation – 1o AI only

Answer 40

First start with 8 AM cortisol - If < 80 nmol/L then AI very likely -If > 500 nmol/L then AI unlikely When in between, usually need to do ACTH stimulation test - Expect a rise in cortisol to > 500 at either 30 or 60 min -If not, then diagnosis of AI is made -doesn't rise in primary does in secondary Also measure ACTH -If high, it is primary AI -Check renin and aldosterone level to assess for mineralocorticoid deficiency -If it is low or inappropriately normal, it is central AI

Answer 41

* Hydrocortisone 100mg IV load followed by 50mg IV Q6H * IV hydration * Identify precipitating cause * Educate patients on sick day rules – advise MedicAlert bracelet

Answer 42

The loss of adrenal function may be from a variety of etiologies,and may be sudden/acute with multiple presentations. The most common cause in the US is autoimmune adrenalitis; it’s TB worldwide. In the setting of sepsis there may be bilateral adrenal destruction from hemorrhage (Waterhouse-Friderichsen). Weirddeposition disease can also compromise the adrenals (amyloid,sarcoid, and hemochromatosis). In primary failure (loss of cortisol, maintenance of ACTH) the symptoms will be hypotension, fatigue, N/V of cortisol loss, as well as the hyperpigmentation and hyperkalemia. Hyperpigmentation is a result of ACTH production trying to increase cortisol while hyperkalemia is from deficient aldosterone. In secondary failure,no ACTH is produced so hyperpigmentation is absent. Because aldosterone production is intact there’s also no hyperkalemia. Prednisone for all types and fludrocortisone for primary only (it’s a synthetic aldo)

Answer 43

3 Screening Tests – 2 out of 3 needed to establish CS 1mg dex suppression test -A post-dexamethasone cortisol level (<50 nmol/L) is considered “normal” because it suppresses appropriately and excludes cortisol excess in most patients. - Cortisol levels (>140 nmol/L) confirms hypercortisolemia. 24hr urine free cortisol (UFC) - Positive if abnormal on 2 separate collections Late-night salivary cortisol -Positive if abnormal on 2 separate collections ACTH high = pituitary ACTH low = adrenal

Answer 44

Inferior Petrosal Sinus Sampling (IPSS): -Gold standard for differentiating pituitary (CD) vs. ectopic ACTH secretion (usually paraneoplastic) -Measures ACTH level both at the inferior petrosal sinus (vascular drainage system of pituitary gland) and peripheral venous system -Uses a central-to-peripheral ACTH ratio to distinguish pituitary vs. ectopic source -Invasive, only offered at specialized centres

Answer 45

A disease of excess cortisol, it’s caused by one of four conditions: 1) Iatrogenic (most common, taper off to fix), 2) Pituitary tumor (Cushing’s disease), 3) Adrenal Tumor, or 4) Ectopic ACTH. The patient will present with a “Cushingoid appearance”: central obesity, moon facies, extremity wasting, a buffalo hump, glucose intolerance or diabetes, and hypertension.

Answer 46

Screen for hyperaldosteronism in hypertensive patients with: - refractory hypertension (high BP despite ≥3 drugs) -spontaneous hypokalemia (K <3.5) or severe diuretic-induced hypokalemia (K<3) -adrenal incidentaloma Note: Screen with Plasma Aldosterone to Renin Ratio (ARR) – check units! Off: MRA, ACEi/ARB, beta-blocker, clonidine, methyldopa, DHP-CCB Can be on: hydralazine, verapamil, doxazosin Confirmatory Tests (remember the principles): -Saline suppression, oral salt load, captopril suppression

Answer 47

Aldosterone causes resorption of Na and H2O producing an expanded vascular volume and hypertension by ↑ENa in the collecting tubules, trading Na for K. This produces a refractory HTN or a Diastolic HTN and Hypokalemia. Differentiate between: primary (a tumor or adenoma called Conn’s Syndrome) where aldosterone production is independent of Renin, secondary (renovascular disease, edematous states of CHF, Cirrhosis, Nephrotic Syndrome) where the production of aldosterone is dependent on renin and is an appropriate response to ↓ renovascular flow, and mimickers (CAG, Licorice, or exogenous mineral corticosteroids). When suspected, perform 8am levels for Aldosterone, Renin, and Aldo:Renin Ratio. Ensure any hypertension medication is discontinued (ACE, CCB, Diuretics confound the test). If elevated (>20 Aldo and >20 Aldo:Renin), it’s likely primary. Confirm with the salt suppression test (where aldo will not decrease after a 200g Na load).

Answer 48

* Who to Screen – Paroxysmal, unexplained, labile, and/or severe (≥ 180/110) sustained HTN refractory to usual therapy – HTN + symptoms of PCC (palpitations, head aches, sweating, panic attacks) – HTN triggered by beta-blockers, MAO-Is, changes in abdominal pressure, surgery, anesthesia, micturition – Adrenal incidentaloma – Genetic condition – such as Von-Hippel-Lindau, MEN 2A or 2B, neurofibomatosis type 1 How to Screen A) Biochemical screening test first – 24hr urine total metanephrines and catecholamines(& Cr to ensure adequate collection) – OR plasma free metanephrines and free normetanephrines – NOT urinary VMA B) Once Biochemical screen confirmed: -- Confirm adrenal lesion with MR abdomen or CT abdomen with delayed contrast washout

Answer 49

Clinic Management * Alpha blockade: Phenoxybenzamine or Doxazosin * Beta blockade ONLY AFTER high dose alpha blockade * Avoid surgery until at least two weeks of adequate alpha blockade, with liberal salt and fluid intake Perioperative * Phentolamine IV if necessary * Practical recommendations: Pre-op Anesthesia Consult (they need to have bags of vasopressors ready to go as soon as adrenal gland manipulated!), ICU bed postop Postoperative * Watch for hypotension, hypoglycemia * Consider familial syndromes [MEN]

Answer 50

An overproduction of catecholamines produces either a sustained refractory HTN or Paroxysmal Five P’s which are 1) Pressure (HTN), 2) Pain (Headache or Chest Pain), 3) Pallor (vasoconstriction), 4) Palpitations (tachycardia, tremor), and 5)Perspiration.

Answer 51

* Women ≥40 years of age (or postmenopausal) * Men ≥40 years of age * Consider earlier in ethnic groups at increased risk such as South Asians or Indigenous individuals * In women with pregnancy-related complication (GDM, HTN, Pre-term birth, LowBW), screen with complete lipid profile in late postpartum period (incr. risk of premature CVD and stroke 10-15yr post-delivery) * Counsel all women with pregnancy related complication for incr. lifetime risk of ASCVD and reinforce healthy lifestyle behaviours. * To assist in lipid-lowering pharmacotherapy decisions in this specific patient population, use CV age over 10yr risk calculators – CV age calculator: myhealthcheckup.com CCS New Lipid Guidelines: Who to Screen * ALL patients with any of the following conditions regardless of age - pls see chart in slides

Answer 52

Non-fasting acceptable as long as TG ≤4.5 mmol/L (otherwise, do fasting) Non-HDL: an alternative to LDL or apo B alternative to screening vs LDL-C if tricylcerides >1.5mmol/L

Answer 53

* Examples: Alirocumab, Evolocumab * Mechanism of Action: PCSK-9 is a protein which tags LDL-R for recycling. Inhibition causes decreased degradation of LDL-R, and therefore more hepatic uptake of LDL * Effect: ~50-60% reduction in LDL-R, regardless of LDL or background therapy * Current indications: – Heterozygous Familial Hypercholesterolemia – Clinical atherosclerotic cardiovascular disease – Homozygous Familial Hypercholesterolemia

Answer 54

Fasting TG ≥1.5-5.6 AND – ASCVD on maximally tolerated statin (with LDL >1 ) OR – DM on max tolerated statin with ≥1 CV risk factor * Men ≥ 55y and Women ≥65y * Smoker currently or within 3 mos * HTN * HDL <1.04 men or <1.3 women * hsCRP >3 * eGFR 30-60 ml/min * Retinopathy * Albuminuria * ABI <0.9 * What? Icosapent Ethyl 2g BID (VASCEPA) – $3500/ year

Answer 55

Definition: * Absent menses at age 16 * Absent sexual characteristics at age 13 * Most common cause is a chromosomal abnormality Ultrasound Mullerian Structures Present Anatomic obstruction Endocrine workup – BHCG, FSH, LH, pituitary, PCOS Check karyotype (XO) Mullerian Structures Absent Karyotype (?XY) with androgen insensitivity, 5a reductase deficiency Check testosterone Mullerian Agenesis The Mullerian ducts create the tubes, uterus, and the upper third of the vagina. If they fail to form the girl will still be genetically female (X,X), so will have normal primary and normal secondary sex characteristics (the ovaries are working great), but she’ll have no uterus. She can never have children and will never bleed. To increase satisfaction with sex elevate the vagina to increase the length. This is considered a Breast positive and Uterus negative disease. This is differentiated from testicular feminization based on the karyotype (X,X) and testosterone level (normal). Androgen Insensitivity / Testicular Feminization A male genotype expresses mullerian inhibitory factor as well as testosterone. In this disease testosterone is made fine, but there’s an insensitvity to testosterone by the body. Thus, despite having testes, the primary and secondary sex characteristics are as if there was no testosterone - she appears totally female.MIF works perfectly and inhibits the mullerian ducts (see above). She’ll never have children or ever bleed. It’s imperative to elevate the vagina in this patient as we did in mullerian agenesis. There’s also the issue of the testes – perform an orchiectomy to prevent testicular cancer. Do this after age 20 (i.e. after puberty) to allow her to develop normally. This is considered a Breast Uterus disease. This is differentiated from Mullerian Agenesis by the karyotype (XY) and testosterone level (elevated). Turner Syndrome A genetic abnormality (X,O) that causes the production of streak ovaries. Patients are female with intact primary sex characteristics and mullerian structures ( uterus). But, in the absence of estrogen she’ll never develop secondary sex characteristics. She’ll also have a broad, shield-shaped chest with wide spaced nipples and a webbed neck. Lacking both Estrogen and Progesterone, treat by giving them what they don’t have (estrogen and progesterone) to induce puberty. Also investigate for cardiac abnormalities with an Echo (coarctation of bicuspid aorta). In this disease, the FSH and LH will be high as the normal pituitary tries to drive the production of estrogen and progesterone. Karyotype confirms. Craniopharyngioma and Kallman Syndrome In both conditions the axis is broken. The anatomy is fine and intact (she’s female on the outside as well as inside), but the absence of endocrine effects leaves the girl without secondary sex characteristics. Kallman syndrome is a defunct hypothalamus (so low FSH and LH) associated with anosmia and primary amenorrhea. Craniopharyngioma and other anterior pituitary tumors turn off the FSH and LH production. There is no anosmia, and an MRI will separate the diseases.

Answer 56

1. Hypothalamic – Functional hypothalamic amenorrhea * FSH, LH are low * Estradiol low * Phenotype = when the body can’t support a pregnancy – High performance female athlete – Eating disorder – High stress environment – Chronic illness 2. Pituitary – hyperprolactinemia from prolactinoma or other sellar mass causing stalk effect, infiltration (hemochromatosis), Sheehan’s, Cushing’s 3. Thyroid - hyperthyroidism 4. Ovarian – PCOS (#1), POI *PCOS is insulin resistance at the level of the ovary, this is why metformin may help regularize cycles* PCOS – Diagnosis – 2/3 of the Rotterdam criteria: * Menstrual irregularity * Biochemical or clinical hyperandrogenism (hirsutism, acne, androgenic alopecia) * Ultrasound findings of polycystic ovaries – Exam: BMI, Ferriman-Gallwey score, alopecia, acne, acanthosis nigricans – Investigations: Prl, TSH, 17OHP, testosterone, DHEAS, LH, FSH, estradiol, US pelvis, fasting BG, 2hr OGTT, lipid profile, sleep study – Issues: hyperandrogenism, fertility, metabolic health 5. Pregnancy Definition: No cycles for >3 months in those with regular periods, or >6 months in those with irregular periods Other structural considerations: bicornuate uterus, endometriosis, Asherman’s syndrome

Answer 57

Primary Ovarian Insufficiency (loss of ovarian activity at age <40) – High FSH, Low Estradiol – History: Autoimmune, Radiation, Chemotherapy, Fragile X (FHx intellectual disability/ataxia) – Tests: Karyotype (for Turner syndrome), Fragile X, Anti-adrenal antibodies, Anti-TPO antibodies – Screening: BMD – Rx: HRT until age of usual menopause (52) for CV and bone protection

Answer 58

Diagnosis – random total testosterone in women with an abnormal hirsutism score – morning 17-hydroxyprogesterone to assess for non-classical congenital adrenal hyperplasia (NCCAH) in women with high testosterone or high risk for CAH – Do not measure androgen levels in women with a normal hirsutism score and normal menses Therapy – Cosmetic measures (plucking, tweezing, waxing) – Local hair removal methods (photoepilation, electrolysis) – Lifestyle changes (if obese or PCOS) – First Line Pharmacotherapy: oral contraceptive pill – Second Line Pharmacotherapy: anti-androgen (spironolactone) in combination with OCP if no improvement after 6 months of monotherapy – Anti-androgens not recommended as monotherapy due to teratogenic potential * unless a woman is not sexually active, has undergone permanent sterilization, or is using long-acting reversible contraception

Answer 59

Diagnosis: signs and symptoms of hypogonadism PLUS unequivocally and consistently low total and/or free testosterone concentrations – screen with morning fasting TT – if any conditions that alter SHBG, screen with FT using equilibrium dialysis assays or calculations that involve TT, SHBG, and albumin (other FT assays are inaccurate) – when low T confirmed, measure LH and FSH to determine if the cause is primary (testicular) or secondary (pituitary) When to measure Free T vs Total T: 1. Conditions that decrease SHBG - obesity, diabetes, steroid use, nephrotic syndrome, hypothyroidism, acromegaly, polymorphisms in the SHBG gene 2. Conditions that increase SHBG - aging, HIV disease, cirrhosis, hepatitis, hyperthyroidism, use of estrogens, use of anticonvulsants, polymorphisms in the SHBG gene 3. Borderline total testosterone levels (i.e. near the lower limit of normal)

Answer 60

Primary: High FSH/LH -Klinefelter (XXY), chemotherapy, testicular ,trauma, mumps, autoimmune, systemic illness * Secondary: Low FSH/LH à pituitary adenoma, hyperprolactinemia, hemochromatosis, anabolic steroids, obesity, opioids, DM2. Klinefelter’s Syndrome – Small firm testes – Increased LH, FSH, decreased testosterone – Arm span > Height + 5cm – Leg length > upper body + 2cm – Comorbid: NHL, bronchiectasis, SLE, diabetes, osteopenia, breast cancer – Diagnosis: Karyotype

Answer 61

Therapy – Recommended to maintain secondary sex characteristics and to correct symptoms of testosterone deficiency – Not recommended if planning fertility in the near term, breast or prostate cancer, prostate nodule/induration, high PSA, high hematocrit, untreated OSA, severe LUTS, uncontrolled heart failure, MI or stroke in the last 6 months, or thrombophilia – Caution in older men à discuss risks and benefits * Monitoring – Symptoms, testosterone levels, hematocrit, PSA – Several times during the first year then annually

Answer 62

Differential Diagnosis: * Multinodular goiter, Toxic nodule, Benign non-functional nodule, Cyst * Thyroid cancer (Papillary 90%, Follicular, Medullary, Anaplastic) * Lymphoma WORKUP: 1. History and physical examination 2. TSH a) Do RAI Uptake/Scan if TSH <0.5 *don’t stick a needle in a hot nodule* 3. Ultrasound *because if it’s 3cm but purely cystic, you wouldn’t biopsy* 4. FNA

Answer 63

Determined based on TIRADS scoring (don’t memorize, know the high-risk features): 1. High suspicion sonographic features (TR5): >1cm 2. Moderate suspicion sonographic features (TR4): >1.5cm 3. Mild suspicion sonographic features (TR3): >2.5cm 4. Do not biopsy if TR1-2: Purely cystic nodules High risk features: – Hypoechoic – Irregular margins – Microcalcifications *highest specificity feature for thyroid ca on U/S* – Taller than wide – Extrathyroidal extension – Peripheral (rim) calcifications – Lymphadenopathy – >20% increase in 2 dimensions *Note if TSH is suppressed <0.1, and/or the nodule is “hot” do not biopsy it,this is a LOW risk feature and warrants investigation for Graves, toxic adenoma, and multi-nodular goitre*

Answer 64

Look at the initial TSH goal. Features post-total thyroidectomy of: +LNs +margins +extrathyroidal extension +distant mets +needing RAI (high-risk!) - Point you to Intermediate-HIGH risk category. Low-risk = TSH goal of 0.5-2.0mU/L Intermediate-risk = TSH goal of 0.1-0.5mU/L High-risk = TSH goal <0.1mU/L

Answer 65

ASK: would it be all right if we discussed your weight today? ASSESS: goals that matter to the patient, obesity history, obesity classification [BMI, physical exam], functional assessment [Edmonton obesity staging system – see BONUS slides] ADVISE: referred to dietitian, exercise 30 to 60 minutes most days, obesity therapies including psychotherapy, weight loss medication, know indications for referral for bariatric surgery AGREE: agree on goals, collaborate on sustainable action plan ASSIST with drivers and barriers

Answer 66

* Pharmacotherapy for weight loss can be used for persons with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with adiposity-related complications (Type 2 diabetes, Gallbladder disease, Nonalcoholic fatty liver disease, Gout), in conjunction with medical nutrition therapy, physical activity and psychological interventions Options include: – semaglutide 2.4mg SC weekly (Wegovy) * – liraglutide 3.0mg SC daily (Saxenda) – naltrexone/bupropion 16mg/180mg PO BID (Contrave) – orlistat 120mg PO TID (Xenical) * Pharmacotherapy may be used to maintain weight loss that has been achieved by health behaviour changes, and to prevent weight regain Level 2a, grade B. * For people living with type 2 diabetes and a BMI ≥ 27 kg/m2, pharmacotherapy can be used in conjunction with health behaviour changes for weight loss and improvement in glycemic control: liraglutide 3.0 mg (level 1a, grade A), naltrexone-bupropion combination (level 2a, grade B), orlistat (level 2a, grade B) * Bariatric surgery should be considered in patients with poorly controlled type 2 diabetes and class I obesity (BMI between 30 and 35 kg/m2) despite optimal medical management (Level 1a, grade A). Referral indications: BMI 35-40 AND 1 serious comorbidity (DM2, DLD, CAD, HTN, pseudotumor cerebri, obesity hypoventilation syndrome, debilitating OA, NAFLD, OSA, severe GERD) BMI >= 40 without comorbidity Complications: General surgical risks Stomal obstruction, gastric perforation, GI bleed, biliary stone disease, hernia, dumping syndrome, post-prandial hypoglycemia Malabsorption: iron, B12, folate, calcium, vitamin ADEK, thiamine * We suggest that the choice of bariatric procedure (sleeve gastrectomy, gastric bypass or duodenal switch) be decided according to the patient’s need, in collaboration with an experienced interprofessional team (Level 4, grade D (consensus).

Answer 67

Consideration #1: Is it malignant? * Size >4cm * Hounsfield Units >10 (>20) * <50% delayed contrast washout * Calcifications, extension, adenopathy * History of malignancy Consideration #2: Is it functional? * Screen for hypercortisolism or MACS (by 1mg DST) and pheochromocytoma (by 24hr urine or plasma metanephrines) in ALL adrenal incidentalomas * Screen for hyperaldosteronism (by ARR) only if HTN +/- Hypokalemia

Answer 68

* Mild autonomous cortisol hypersecretion (MACS) refers to when incidentalomas produce enough cortisol to result in an abnormal 1mg DST but screen normal on 24hr UFC and late night salivary cortisol testing. * MACS alone, without overt Cushings, is associated with increased hypertension, hyperglycemia, obesity, dyslipidemia and vertebral fractures. * Consensus recommendations support the use of the 1mg DST as having the highest sensitivity for screening for MACS in all cases of adrenal incidentaloma; with low ACTH +/- low DHEAS as markers of support. *note this differs from CS screening as any of 1mg DST, 24hr UFC, or late night salivary cortisol can be used for CS*

Answer 69

Hyperprolactinemia differential – Disruption of the stalk à decreased dopamine; Prl rarely >100 – Lactotroph adenoma (prolactinoma); if ~1cm in size, Prl ~100 – Anti-dopaminergic drugs -antipsychotics especially – Hypothyroidism, renal failure – Physiologic stimuli – nipple, chest wall trauma, sex – Estrogen effect on lactotrophs->OCP Symptoms: amenorrhea, infertility, galactorrhea, hypogonadism, mass effect – ++ Symptoms, not very high prolactin? à Hook effect * Hook effect – lab peculiarity where very high levels of prolactin are read as low levels. If you dilute the sample, you can get a more accurate reading – ++ Prolactin, not very many symptoms à Macroprolactin * Macroprolactin – a type of prolactin multimer which is biologically inactive. It can be in the serum in very high levels and cause no symptoms. It only sticks around because its clearance is slow. * Need to rule out stalk effect and other pituitary dysfunction

Answer 70

1) Prolactinoma A benign tumor that autonomously secretes Prolactin will causea prolactinemia. Prolactinemia presents differently in men than women. They’re caught early in women as microadenomas,because women tend to notice galactorrhea and amenorrhea. There’s been no time for the tumor to grow; it’s small and presents without field cuts. In men, who don’t lactate or haveperiods, there’s nothing to tip them off that something’s wrong (decreased libido may be the only symptom). Thus, the tumor grows. As it becomes a macroadenoma it digs into the optic chiasm to produce a bitemporal hemianopia. In the case of field cuts it’s easy to be pretty sure there’s a tumor. But in the case of a microadenoma other causes of prolactinemia must be ruled out. For example, dopamine antagonists (antipsychotics) disinhibit Prolactin while ↑↑TRH (from hypothyroidism) stimulates its production. So, before getting an MRI test, get Prolactin levels and a TSH after looking over their med list. Treat by using dopamine agonists (cabergoline > bromocriptine). Consider surgery only after medical therapy fails; unlike most tumors Prolactinomas are very sensitive to medical therapy. Follow prolactinomas with prolactin levels q3months and an MRI annually until stable.

Answer 71

If drug / hypothyroid: reverse * If stalk effect: manage the primary tumor * If prolactinoma – treat with dopamine agonist, EVEN IF MASS EFFECT – Cabergoline: more effective, better tolerated, not well studied in pregnancy – Bromocriptine: older, more side effects, cheaper – Side effects: nausea, nasal stuffiness, headache

Answer 72

Syndrome of growth hormone excess * Examination: macrognathia, macroglossia, increased ring shoe/collar/glove size, OSA, coarsened facial features, gap between incisors, carpal tunnel, osteoarthritis, type 2 diabetes, visual field defects, cranial neuropathies * Screening Test: IGF-1 level * Diagnostic Test (remember principles): 75 g glucose suppression * Treatment: Surgical 2) Acromegaly A benign tumor that autonomously secretes Growth Hormonewill cause things that can grow to grow. In a child, before the closure of the growth plates, that means the long bones - resulting in gigantism. But in an adult it means the hands, feet, face, and visceral organs. It also induces gluconeogenesis and causes the patient to present with glucose intolerance or even frank diabetes. The thing that kills these patients is the cardiomegaly and subsequent diastolic heart failure. The diagnosis is made biochemically. However, GH is pulsatile, and so it can’t be used to make the diagnosis. Instead, because GH exacts its effects through the liver via ILGF-1 (somatomedin); the diagnosis begins there. A failure to suppress GH levels in a glucose tolerance test (next page) is a finding and should prompt the confirmatory MRI. The only treatment is surgery. However, radiation or medical therapy with octreotide (somatostatin) can be used for residual tissue to ↓GH production which will ↓ILGF effects.

Answer 73

* Absence of ADH leads to inability to concentrate urine * Presentation is polydipsia and polyuria, usually post-neurosurgery Remember that the other possibility is dumping fluids from the OR! Can tell the difference by comparing urine osmolality to serum osmolality. If urine osm > serum osm it is not DI. * Diagnosis: – Hypernatremia, hyperosmolar plasma, inappropriately dilute urine – 24 hour urine to confirm polyuria – Water deprivation test * Usually presents in post-sellar surgical patients – Can be triphasic (or have some or none of): * 1. Transient Diabetes insipidus – Pituitary stunning post-operatively * 2. SIADH – release of stored ADH * 3. Permanent Diabetes insipidus – loss of posterior pituitary function