Endocrinology (5-10%) Complete

Question 1

In a parathyroid-mediate process, serum calcium and
phosphate go in the __________ direction

Answer 1

In a parathyroid-mediate process, serum calcium and
phosphate go in the opposite direction

Question 2

In a vitamin D-mediated process, serum calcium and phosphate go in the ____________ direction

Answer 2

In a vitamin D-mediated process, serum calcium and phosphate go in the same direction

Question 3

When the calcium, phosphate, and PTH are all high, think of __________

Answer 3

When the calcium, phosphate, and PTH are all high, think of kidney (reduced ability to excrete phosphate)

e.g.
Tertiary Hyperparathyroidism (in long-standing renal failure): ↑Ca, ↑PO4

Question 4

Therefore think of _________ in someone with apparent
hypoparathyroidism (or inappropriately normal PTH).

Answer 4

Therefore think of hypomagnesemia in someone
with apparent hypoparathyroidism (or inappropriately normal PTH).

Magnesium deficiency reduces PTH secretion and causes PTH resistance

Question 5

Indications for surgery in Primary Hyperparathyroidism (PHPT)

Answer 5

Symptomatic PHPT = Surgery
Asymptomatic PHPT= “Stay The Fudge Away U Stupid Calcium”

AT DIAGNOSIS:
Serum total calcium > 0.25 mmol/L above upper limit
T-score <= -2.5 at L-spine, total hip, femoral neck or distal 1/3 radius
Fractures (Vertebral only; by X-ray, CT, MRI or VFA)
Age < 50
Urine calcium >6.25 mmol/d (>250mg/d) in women or >7.5 mmol/d in men (>300mg/d) NEW cutoffs in 2022
Stones or nephrocalcinosis by x-ray, ultrasound, or CT
Creatinine clearance < 60 mL/min (stage 3 CKD)
JBMR 2022

Question 6

If patient NOT a candidate for surgery (e.g. per ENT, or too frail for surgery) -> Medical Mgmt*:
• Calcium intake should be consistent with nutritional guidelines (___________ mg/d)
• Correct vitamin D deficiency/insufficiency: target serum 25OH Vit D to _______ nmol/L
• __________ and __________ are effective at increasing BMD
• __________ is effective in reducing serum Ca and should be considered for symptomatic PHPT if surgery is not an option

Answer 6

If patient NOT a candidate for surgery (e.g. per ENT, or too frail for surgery) -> Medical Mgmt*:
• Calcium intake should be consistent with nutritional guidelines (1000-1200 mg/d)
• Correct vitamin D deficiency/insufficiency: target serum 25OH vit D to >75 nmol/L
• Bisphosphonates and denosumab are effective at increasing BMD
• Cinacalcet ($) is effective in reducing serum Ca and should be considered for symptomatic PHPT if surgery is not an option.
- May combine w Bisphosphonates or denosumab in selected pts (to reduce Ca AND increase BMD).

Question 7

MUST DO A ____________before sending someone
for surgery for primary hyperparathyroidism to rule out ____________

Answer 7

MUST DO A URINE CALCIUM before sending someone
for surgery primary hyperparathyroidism to rule out FHH.

Question 8

Postop Gastic Surgery (ex. gastric bypass/ bilroth/ whipples surgery where a portion of stomach is removed).
For treating hypocalcemia, USE __________ and Why?

Answer 8

use Calcium Citrate

You CANNOT use Calcium Carbonate as a supplement (there is no acidity to absorb this!)

Question 9

Hypercalcemia following a renal transplant or ESRD.
Think?

Answer 9

Tertiary hyperparathyroidism

Question 10

Treatment in tertiary hyperparathyroidism

Answer 10

Cinacalcet (calcimimetics) phosphate binders

Question 11

MEN 1?
MEN 2A?
MEN 2B?

All are autosomal _________ ?

Answer 11

MEN 1
(PPP) PARATHYROID.
PITUITARY ADENOMA
PANCREATIC (insulin, VIP, gastrin)

MEN 2A
(PMP) PARATHYROID
MEDULLARY THYROID CANCER
PHEOCHROMOCYTOMA

MEN 2B
(MMP)
MARFANOID, MUCOSAL NEUROMAS
MEDULLARY THYROID CANCER
PHEOCHROMOCYTOMA

All Autosomal Dominant

Question 12

Hyperthyroidism:
High radioactive iodine uptake (RAIU) (usually >25%) = increased endogenous production of thyroid hormone

Causes?

Answer 12

(e.g. Graves disease, toxic multinodular goiter)

Question 13

Hyperthyroidism:
• Low radioactive iodine uptake = extra
thyroid hormone without increased
endogenous production

Causes?

Answer 13

Exogenous ingestion or inflammatory leak (e.g. acute, sub-acute, post-partum, or amiodarone-induced thyroiditis)*

Question 14

RAIU may be falsely low if _________?

Answer 14

There is an interfering factor (e.g. recent iodine load via IV contrast or amiodarone, use of thionamide medications

Question 15

A big gland (goiter) usually means ________
Think?

Answer 15

The thyroid is being stimulated and think about what is stimulating it

Ø TSH (Hashimoto’s)
Ø Thyroid receptor antibodies (Graves’)
Ø B-hCG (pregnancy)

Question 16

A painful thyroid gland usually means _______?

Answer 16

A painful gland usually means the thyroid is inflamed
Ø Thyroiditis

Question 17

Hyperthyroidism treatment:
Use _________ for symptomatic patients (“especially elderly, those with ________)

Answer 17

Use beta-blockers (e.g. propranolol) for symptomatic patients (“especially elderly, those with resting HR > 90 or CVD”)

Question 18

Hyperthyroidism treatment Medical Management:
Use MMZ instead of PTU because less hepatotoxic EXCEPT in the following situations?

Answer 18

Use MMZ instead of PTU because less hepatotoxic EXCEPT in the following situations:
Ø First trimester of pregnancy (risk of aplasia cutis & cleft palate)
Ø Thyroid storm (PTU Is shorter acting)
Ø Minor MMZ reactions (if severe, then shouldn’t use anti-thyroid drugs at all)

Question 19

Treatment in GRAVES:

• RAI
– _______ dose of ablative radioactive iodine.
– Contraindications: _______, _______, _______, _______
– Adverse effects: Worsened _______, Thyroiditis
– Delay _________ for 6 months after tx
– If giving RAI with orbitopathy, should give _______
– Should be off _______ for at least 2-3 days before radioactive iodine ablation

• Surgery
- Patient should be _______ prior to surgery

Answer 19

• RAI
– Single dose of ablative radioactive iodine.
– Contraindications: Pregnancy, breastfeeding, moderate-severe
orbitopathy, thyroid cancer
– Adverse effects: Worsened Orbitopathy, Thyroiditis
– Delay pregnancy for 6 months after tx
– If giving RAI with orbitopathy, should give steroids
– Should be off methimazole for at least 2-3 days before radioactive iodine ablation

• Surgery
- Patient should be euthyroid prior to surgery

Question 20

Moderate to severe Graves ophthalmopathy treatment?

Answer 20

IV Steroids + mycophenolate is the EUGOGO first-line treatment for those with ACTIVE GO if no contraindications (ie CHF, severe hyperglycemia).

Question 21

Surgery is Graves ophthalmopathy?

Surgery only offered for __________

Answer 21

Surgery only offered for stable INACTIVE GO (must be inactive >6 months)

Question 22

Thyroid Storm?

Answer 22

Think of this with a very sick patient with thyrotoxicosis (tachycardia, confusion, hyperthermia)

Question 23

Thyroid Storm Treatment?
Order of meds?

Answer 23

Thyroid Storm Treatment
• ABCs – get ICU involved early!
• Supportive care

IN THIS ORDER:
• Beta-blockers (careful with hemodynamic status!!) E.g. Propranolol 60-80mg PO q4-6h, if unsure, start at lower Propranolol dose 20-40mg po q4-6hr [the intention is to reduce adrenergic drive]
• PTU (usually 200 mg PO q4h) THEN
• Iodine: Lugol’s iodine 10 drops q8h. Should be given 1 hour after the loading dose of PTU
• Glucocorticoids (often AI co-exists, also help to reduce fT4 -> fT3 conversion)

Question 24

Myxedema Coma?

Answer 24

Life-threatening SLOWING of function in multiple organs

Severe hypothyroidism leading to:
– Altered LOC / lethargy
– Hypothermia
– Hypotension
– Bradycardia
– Hyponatremia
– Hypoventilation

Question 25

Myxedema Coma Treatment

Answer 25

• IV levothyroxine load 200-400mcg x1 followed by 1.6mcg/kg/d (this is the PO dose, multiple by 75% if given IV) • IV glucocorticoids (HC 100mg IV Q8H) until AI ruled out • IV liothyronine load 5-20mcg x1 followed by 2.5-10mcg Q8H • Supportive measures (ICU monitoring, mechanical ventilation, fluids, warming)

Question 26

Subclinical Hypothyroidism in Already Pregnancy? Different scenarios explain?

Answer 26

Question 27

Levothyroxine prepregnancy – preconception guidelines?

Answer 27

Do not treat if TSH is less than 4 regardless of the TPO antibody titers

Question 28

Target TSH? levothyroxine treatment pregnancy

Answer 28

Target TSH ≤ 2.5 throughout pregnancy

Question 29

GTT vs. Thyroid Pathology in pregnancy • Differentiating thyroid pathology from GTT can be hard, but look for: ØOphthalmopathy and/or thyroid bruit (________) ØGoitre (more likely ________) ØThyroid receptor antibody positivity (________) ØNodules (________) ØHistory of hyperemesis (________) ØHistory of thyroid disease (________) ØPossibility of molar pregnancy (________; next step?________)

Answer 29

ØOphthalmopathy and/or thyroid bruit (Graves) ØGoitre (more likely Graves) ØThyroid receptor antibody positivity (Graves) ØNodules (Toxic multinod. goitre or Thyroid Adenoma) ØHistory of hyperemesis (GTT) ØHistory of thyroid disease (not GTT) ØPossibility of molar pregnancy (GTT; get a pelvic U/S!)

Question 30

“Automatic” High-Risk Osteoporosis? * * *

Answer 30

* Both of 1. prior fragility fracture AND 2. prolonged use of glucocorticoids * 1 Hip or Spine fracture * >1 fragility fracture

Question 31

Treatment of osteoporosis?

Answer 31

1. Bisphosphonates 2. Denosumab 3. Teriparatide or Abaloparatide 4. Romosozumab

Question 32

Bisphosphonates: Once on therapy, reassess fracture risk in ___________ – If HIGH-RISK ---> ____________ – If LOW-MODERATE ---> _________

Answer 32

Once on therapy, reassess fracture risk in 3-5 years – If HIGH-RISK ---> continue therapy or switch to another agent – If LOW-MODERATE ---> drug holiday; reassess fracture risk every 2-4 years. Restart therapy if significant bone loss or enters the high risk

Question 33

Denosumab Discontinuation?

Answer 33

• Unlike BPs, denosumab’s benefits on the bone (BMD gains, fracture risk reduction) are LOST within 3-6 months after discontinuation – Drug holiday or treatment interruption is NOT recommended • Discontinuation of denosumab also increases risk of multiple or severe vertebral fractures – Prevent by bridging to IV or PO bisphosphonate

Question 34

When to Use Teriparatide?

Answer 34

• **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**

Question 35

Contraindications to Teriparatide?

Answer 35

• **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

Question 36

Teriparatide: Maximum duration = ___________, longer use *may* ↑risk of ___________ (animal data)

Answer 36

Maximum duration = 24 months, longer use *may* ↑risk of osteosarcoma (animal data)

Question 37

Romosuzumab Most worrisome side effect is _____________ noted in ARCH trial (Romosuzumab vs Alendronate, 2017)

Answer 37

Most worrisome is the increased risk of MACE events noted in ARCH trial (Romosuzumab vs Alendronate, 2017)

Question 38

Thigh pain on bisphosphonates = need to rule out ________ Next Step? ____________, if negative consider _________

Answer 38

Thigh pain on bisphosphonates = need to rule out AFF! (**bilateral femur X-rays**, if these are negative consider bone scan / MRI if high index suspicion

Question 39

OSTEOPOROSIS SUMMARY: ____ risk by FRAX/CAROC ---> start a 1st line therapy ---> Reassess risk at the appropriate interval Bisphosphonate ---> __________ Denosumab ---> __________ Teriparatide ---> __________ Romosuzumab ---> __________ Risk improved to Low/Moderate ---> consider ______ If risk remains HIGH ---> ________ If intolerant to the 4 first-line therapies: ___________

Answer 39

High risk by FRAX/CAROC ---> start a 1st line therapy ---> Reassess risk at the appropriate interval Bisphosphonate ---> 3-5 yrs Denosumab ---> 5-10 yrs Teriparatide ---> 2 yrs Romosuzumab ---> 1 yr Risk improved to Low/Moderate ----> consider drug holiday (if on bisphosphonate) or stepdown to bisphosphonate (if on another agent) If risk remains HIGH ----> continue drug or consider switching to another first-line therapy If intolerant to the 4 first-line therapies: - Consider SERM or Hormone therapy (assumes low VTE Risk) - Ensure adequate Calcium and Vitamin D

Question 40

Diabetes? • Fasting glucose _______ (IFG: _________ - Impaired fasting glycaemia • HbA1c _______ (Prediabetes: ________) • 2h 75g OGTT _________ (IGT: _________) • Random PG _________

Answer 40

• Fasting glucose ≥ 7mmol/L (IFG: 6.1-6.9) • HbA1c ≥ 6.5% (Prediabetes: 6.0-6.4%) • 2h 75g OGTT ≥ 11.1 mmol/L (IGT: 7.8-11.0) • Random PG ≥ 11.1 mmol/L

Question 41

A1C Treatment targets: 1. Almost everyone 2. If functionally dependent (NEW CATEGORY!) 3. if: – Recurrent severe hypoglycemia/hypo unawareness – Limited life expectancy – Frail elderly with dementia 4. Pregnancy planning

Answer 41

1. ≤7% 2. 7.1-8.0% 3. 7.1-8.5% 4. ≤7.0%

Question 42

CGM targets Time in Range Target Range 1. Normal adults 2. Older / High Risk for Hypoglycemia 3. Pregnant T1DM

Answer 42

1. 70% (3.9-10 mmol/L) 2. 50% (3.9-10 mmol/L) 3. 70% (3.5-7.8 mmol/L)

Question 43

Type 1 DM: Benefits of Switching from BBI (Basal Bolus Insulin) to CSII (Insulin Pump)

Answer 43

• Small improvement in A1C • ↑ treatment satisfaction & diabetes-related QOL • ↓ severe hypoglycemia if high baseline rate of severe hypoglycemia

Question 44

Type 1 DM: Benefits of Adding CGM (continuous glucose monitor) to BBI or CSII

Answer 44

• Adding Continuous Glucose Monitoring (CGM) with high sensor adherence can – ↓ A1C with no increase in hypoglycemia – ↑ QOL, diabetes distress, fear of hypoglycemia and treatment satisfaction Note: Benefits of CGM are only seen when patients are actually wearing the sensor/CGM at all times = high sensor adherence (>70% in 14d period)

Question 45

Type 2 diabetes A1c not at target?

Answer 45

Question 46

Don't choose this SGLT2 inhibitor as the answer choice for type 2 diabetes

Answer 46

***Ertugliflozin = no CV benefit, safe, not the best choice for SGLT2i (VERTIS trial NEJM 2020)

Question 47

Indication for Statins in Diabetes?

Answer 47

Cholesterol = Statin therapy. Any of the following: Ø Clinical CVD Ø Age ≥ 40 Ø Age >30 and diabetes duration > 15 years Ø Microvascular disease Ø Other CV risk factors Note: A second-line agent may be used if LDL is not at target with statin therapy alone. In patients with clinical CVD, ezetimibe or evolocumab may be added to reduce CV events (IMPROVE-IT and FOURIER trials)

Question 48

Indication for ACE/ARB in Diabetes?

Answer 48

Ø Clinical CVD Ø Age ≥ 55 with an additional CV risk factor or end-organ damage (albuminuria, retinopathy, LVH) Ø Microvascular disease Note: Should use doses shown to provide CV protection (perindopril 8 mg daily, ramipril 10 mg daily, telmisartan 80 mg daily)

Question 49

Adrenal Insufficiency - Diagnosis First, start with ___________ Ø If < ___________ nmol/L then AI very likely Ø If > ___________ nmol/L then AI unlikely When in between, usually need to do ___________ Ø Expect a rise in ___________ to > ___________ at either ___________ or ___________ min Ø If not, then the diagnosis of AI is made Also, measure ___________ Ø If high, it is ___________ (Check renin and aldosterone levels to assess for mineralocorticoid deficiency) Ø If it is low or inappropriately normal, it is ___________

Answer 49

Adrenal Insufficiency - Diagnosis First start with 8 AM cortisol Ø If < 83 nmol/L then AI very likely Ø If > 500 nmol/L then AI unlikely When in between, usually need to do ACTH stimulation test Ø Expect a rise in cortisol to > 500 at either 30 or 60 min Ø If not, then the diagnosis of AI is made Also, measure ACTH Ø If high, it is the primary AI Ø Check renin and aldosterone levels to assess for mineralocorticoid deficiency Ø If it is low or inappropriately normal, it is central AI

Question 50

Figuring out the etiology of primary adrenal insufficiency First step? ___________ Next step? ___________

Answer 50

First step? 21-OH-Antibody. If positive then autoimmune adrenal sufficiency If negative then next step? CT adrenals (infiltrative disease, adrenal hemorrhage, infections, malignant tumors)

Question 51

Management of Adrenal Crisis?

Answer 51

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

Question 52

How do you screen for Cushing's?

Answer 52

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

Question 53

The etiology of Cushing's syndrome: First Step? Next Step?

Answer 53

Question 54

The gold standard for differentiating pituitary (Cushing's disease) vs. Ectopic ACTH secretion (usually paraneoplastic)

Answer 54

Inferior Petrosal Sinus Sampling (IPSS)

Question 55

Conn’s Syndrome - Hyperaldosteronism Screening test? Confirmatory test?

Answer 55

Screen with Plasma Aldosterone to Renin Ratio (ARR) – check units! Off these before testing: MRA, ACEi/ARB, beta-blocker, clonidine, methyldopa, DHP-CCB Can be on: hydralazine, verapamil, doxazosin Confirmatory Tests (remember the principles): Ø Saline suppression, oral salt load, captopril suppression

Question 56

Pheochromocytoma How to Screen? Confirm with?

Answer 56

A) Biochemical screening test first – **24hr urine total metanephrines and catecholamines(& Cr to ensure adequate collection) – OR plasma-free metanephrines and free normetanephrine** – NOT urinary VMA B) Once Biochemical screen is confirmed: -- Confirm adrenal lesion with MR abdomen or CT abdomen with delayed contrast washout

Question 57

Pheochromocytoma Clinic Management?

Answer 57

• 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_

Question 58

Adrenal Incidentaloma: “A clinically unapparent adrenal mass ____ cm should be investigated further

Answer 58

> 1cm in diameter

Question 59

Adrenal Incidentaloma: Structural evaluation Is it malignant? • Size __________ • Hounsfield Units __________ • __________% delayed contrast washout • Calcifications, extension, adenopathy • History of malignancy Consideration #2: Is it functional? • Screen for __________ in ALL adrenal incidentalomas • Screen for __________ only if HTN +/- Hypokalemia

Answer 59

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

Question 60

Obesity: pharmacotherapy initiation, cut off BMI?

Answer 60

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 (liraglutide 3.0 mg, naltrexone-bupropion combination, orlistat)

Question 61

Obesity: indications for bariatric surgery? BMI cut off

Answer 61

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

Question 62

CCS New Lipid Guidelines: Who to Screen

Answer 62

Question 63

CCS Lipid Guidelines: Who Needs Treatment?

Answer 63

Question 64

LDL targets to remember: 1. The reason to start cholesterol medication was LDL >5, Aim for? 2. Diabetes Mellitus and no ASCVD? or CKD and no ASCVD? 3. ASCVD? 4. AAA? 5. Intermediate FRS or high FRS

Answer 64

1. LDL less than or equal to 2.5 2. LDL less than or equal to 2.0 3. LDL less than or equal to 1.8 4. LDL less than or equal to 1.8 5. LDL less than or equal to 2.0

Question 65

Lipid management in ASCVD: The patient is on a maximally tolerated statin and still, the LDL is greater than 1.8. Next Step? 1. LDL (1.8 - 2.2) 2. LDL (>2.2)

Answer 65

1. Ezetimibe first followed by PCSK9 inhibitor 2. PCSK9 inhibitor first followed by Ezetimibe

Question 66

CCS New Lipid Guidelines: “high PCSK9i benefit”

Answer 66

Question 67

Thyroid Nodule with High-risk features for thyroid cancer = Needs Biopsy What are high-risk features?

Answer 67

– 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

Question 68

TSH goals: Thyroid cancer post thyroidectomy Low-risk = TSH goal of _________________ Intermediate-risk = TSH goal of _________________ High-risk = TSH goal _________________

Answer 68

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

Question 69

Points you to Intermediate-HIGH risk category THYROID CANCER?

Answer 69

Features post-total thyroidectomy of: +LNs +margins +extrathyroidal extension +distant mets +needing RAI (high-risk!)