Endocrinology (5-10%) Complete Flashcards
In a parathyroid-mediate process, serum calcium and
phosphate go in the __________ direction
In a parathyroid-mediate process, serum calcium and
phosphate go in the opposite direction
In a vitamin D-mediated process, serum calcium and phosphate go in the ____________ direction
In a vitamin D-mediated process, serum calcium and phosphate go in the same direction
When the calcium, phosphate, and PTH are all high, think of __________
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
Therefore think of _________ in someone with apparent
hypoparathyroidism (or inappropriately normal PTH).
Therefore think of hypomagnesemia in someone
with apparent hypoparathyroidism (or inappropriately normal PTH).
Magnesium deficiency reduces PTH secretion and causes PTH resistance
Indications for surgery in Primary Hyperparathyroidism (PHPT)
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
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
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).
MUST DO A ____________before sending someone
for surgery for primary hyperparathyroidism to rule out ____________
MUST DO A URINE CALCIUM before sending someone
for surgery primary hyperparathyroidism to rule out FHH.
Postop Gastic Surgery (ex. gastric bypass/ bilroth/ whipples surgery where a portion of stomach is removed).
For treating hypocalcemia, USE __________ and Why?
use Calcium Citrate
You CANNOT use Calcium Carbonate as a supplement (there is no acidity to absorb this!)
Hypercalcemia following a renal transplant or ESRD.
Think?
Tertiary hyperparathyroidism
Treatment in tertiary hyperparathyroidism
Cinacalcet (calcimimetics) phosphate binders
MEN 1?
MEN 2A?
MEN 2B?
All are autosomal _________ ?
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
Hyperthyroidism:
High radioactive iodine uptake (RAIU) (usually >25%) = increased endogenous production of thyroid hormone
Causes?
(e.g. Graves disease, toxic multinodular goiter)
Hyperthyroidism:
• Low radioactive iodine uptake = extra
thyroid hormone without increased
endogenous production
Causes?
Exogenous ingestion or inflammatory leak (e.g. acute, sub-acute, post-partum, or amiodarone-induced thyroiditis)*
RAIU may be falsely low if _________?
There is an interfering factor (e.g. recent iodine load via IV contrast or amiodarone, use of thionamide medications
A big gland (goiter) usually means ________
Think?
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)
A painful thyroid gland usually means _______?
A painful gland usually means the thyroid is inflamed
Ø Thyroiditis
Hyperthyroidism treatment:
Use _________ for symptomatic patients (“especially elderly, those with ________)
Use beta-blockers (e.g. propranolol) for symptomatic patients (“especially elderly, those with resting HR > 90 or CVD”)
Hyperthyroidism treatment Medical Management:
Use MMZ instead of PTU because less hepatotoxic EXCEPT in the following situations?
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)
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
• 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
Moderate to severe Graves ophthalmopathy treatment?
IV Steroids + mycophenolate is the EUGOGO first-line treatment for those with ACTIVE GO if no contraindications (ie CHF, severe hyperglycemia).
Surgery is Graves ophthalmopathy?
Surgery only offered for __________
Surgery only offered for stable INACTIVE GO (must be inactive >6 months)
Thyroid Storm?
Think of this with a very sick patient with thyrotoxicosis (tachycardia, confusion, hyperthermia)
Thyroid Storm Treatment?
Order of meds?
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)
Myxedema Coma?
Life-threatening SLOWING of function in multiple organs
Severe hypothyroidism leading to:
– Altered LOC / lethargy
– Hypothermia
– Hypotension
– Bradycardia
– Hyponatremia
– Hypoventilation
Myxedema Coma Treatment
• 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)
Subclinical Hypothyroidism in Already Pregnancy?
Different scenarios explain?
Levothyroxine prepregnancy – preconception guidelines?
Do not treat if TSH is less than 4 regardless of the TPO antibody titers
Target TSH?
levothyroxine treatment pregnancy
Target TSH ≤ 2.5 throughout pregnancy
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?________)
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!)
“Automatic” High-Risk Osteoporosis?
*
*
*
- Both of
1. prior fragility fracture AND
2. prolonged use of glucocorticoids - 1 Hip or Spine fracture
- > 1 fragility fracture
Treatment of osteoporosis?
- Bisphosphonates
- Denosumab
- Teriparatide or Abaloparatide
- Romosozumab
Bisphosphonates:
Once on therapy, reassess fracture risk in ___________
– If HIGH-RISK —> ____________
– If LOW-MODERATE —> _________
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
Denosumab Discontinuation?
• 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
When to Use Teriparatide?
• 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
Contraindications to Teriparatide?
• 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
Teriparatide:
Maximum duration = ___________, longer use may ↑risk of ___________ (animal data)
Maximum duration = 24 months, longer use may ↑risk of osteosarcoma (animal data)
Romosuzumab
Most worrisome side effect is _____________ noted in ARCH trial (Romosuzumab vs Alendronate, 2017)
Most worrisome is the increased risk of MACE events noted in ARCH trial (Romosuzumab vs Alendronate, 2017)
Thigh pain on bisphosphonates = need to rule out ________
Next Step? ____________, if negative consider _________
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
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:
___________
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
Diabetes?
• Fasting glucose _______ (IFG: _________ - Impaired fasting glycaemia
• HbA1c _______ (Prediabetes: ________)
• 2h 75g OGTT _________ (IGT: _________)
• Random PG _________
• 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
A1C Treatment targets:
1. Almost everyone
- If functionally dependent (NEW CATEGORY!)
- if:
– Recurrent severe hypoglycemia/hypo unawareness
– Limited life expectancy
– Frail elderly with dementia - Pregnancy planning
- ≤7%
- 7.1-8.0%
- 7.1-8.5%
- ≤7.0%
CGM targets
Time in Range
Target Range
- Normal adults
- Older / High Risk for Hypoglycemia
- Pregnant T1DM
- 70%
(3.9-10 mmol/L) - 50%
(3.9-10 mmol/L) - 70%
(3.5-7.8 mmol/L)
Type 1 DM: Benefits of Switching from BBI (Basal Bolus Insulin) to CSII (Insulin Pump)
• Small improvement in A1C
• ↑ treatment satisfaction & diabetes-related QOL
• ↓ severe hypoglycemia if high baseline rate of
severe hypoglycemia
Type 1 DM: Benefits of Adding CGM (continuous glucose monitor) to BBI or CSII
• 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)
Type 2 diabetes
A1c not at target?
Don’t choose this SGLT2 inhibitor as the answer choice for type 2 diabetes
***Ertugliflozin = no CV benefit, safe, not the best choice for SGLT2i (VERTIS trial NEJM 2020)
Indication for Statins in Diabetes?
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)
Indication for ACE/ARB in Diabetes?
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)
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 ___________
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
Figuring out the etiology of primary adrenal insufficiency
First step? ___________
Next step? ___________
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)
Management of Adrenal Crisis?
• Hydrocortisone 100mg IV load followed by 50mg IV Q6H
• IV hydration
• Identify precipitating cause
• Educate patients on sick day rules
– advise MedicAlert bracelet
How do you screen for Cushing’s?
*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
The etiology of Cushing’s syndrome:
First Step?
Next Step?
The gold standard for differentiating pituitary (Cushing’s disease) vs. Ectopic ACTH secretion (usually paraneoplastic)
Inferior Petrosal Sinus Sampling (IPSS)
Conn’s Syndrome - Hyperaldosteronism
Screening test?
Confirmatory test?
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
Pheochromocytoma
How to Screen?
Confirm with?
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
Pheochromocytoma
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
Adrenal Incidentaloma:
“A clinically unapparent adrenal mass ____ cm should be investigated further
> 1cm in diameter
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
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
Obesity: pharmacotherapy initiation, cut off BMI?
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)
Obesity: indications for bariatric surgery? BMI cut off
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
CCS New Lipid Guidelines: Who to Screen
CCS Lipid Guidelines: Who Needs Treatment?
LDL targets to remember:
1. The reason to start cholesterol medication was LDL >5, Aim for?
- Diabetes Mellitus and no ASCVD? or CKD and no ASCVD?
- ASCVD?
- AAA?
- Intermediate FRS or high FRS
- LDL less than or equal to 2.5
- LDL less than or equal to 2.0
- LDL less than or equal to 1.8
- LDL less than or equal to 1.8
- LDL less than or equal to 2.0
Lipid management in ASCVD:
The patient is on a maximally tolerated statin and still, the LDL is greater than 1.8. Next Step?
- LDL (1.8 - 2.2)
- LDL (>2.2)
- Ezetimibe first followed by PCSK9 inhibitor
- PCSK9 inhibitor first followed by Ezetimibe
CCS New Lipid Guidelines: “high PCSK9i benefit”
Thyroid Nodule with High-risk features for thyroid cancer = Needs Biopsy
What are 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
TSH goals: Thyroid cancer post thyroidectomy
Low-risk = TSH goal of _________________
Intermediate-risk = TSH goal of _________________
High-risk = TSH goal _________________
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
Points you to Intermediate-HIGH risk category THYROID CANCER?
Features post-total thyroidectomy of:
+LNs
+margins
+extrathyroidal extension
+distant mets
+needing RAI (high-risk!)
