Endocrinology Flashcards
Paget’s Disease presentation and workup
Pt: Hearing loss, compressive neuropathy, OA, osteosarcoma
Ix: elevated ALP +/- bone specific ALP w/o other abnormalities
1) XR symptomatic area
2) If asymptomatic –> skeletal survey
3) Once dx confirmed: bone scan for extent of dz
Indications for parathyroidectomy in primary hyperPTH
Symptoms or
Asx + SCUBA
S: Serum Ca >0.25 above ULN
C: CrCl <60 (stage 3 CKD)
U: urine Ca >10mmol/d (400mg/d) OR nephrocalcinosis / stones
B: Bones (Osteoporosis by Tscore or vertebral fractures)
Age<50
Indications for parathyroidectomy in tertiary hyperPTH
- Refractory hyperPTH despite VitD analogues / calcimemetics
- Severe symptomatic hyperCa –> bone dz, calciphylaxis
MEN1 (autosomal dominant)
Diamond:
Pituitary adenoma
Parathyroid
Pancreas (Insulinoma, VIP, gastrinoma etc)
MEN2a (autosomal dominant)
Square:
Parathyroid
Medullary thyroid CA
Pheochromocytoma
MEN2b (autosomal dominant)
Triangle:
Marfanoid, mucosal neuromas
Medullary thyroid CA
Pheochromocytoma
Treatment Grave’s Disease & C/Is
- BB for symptoms (esp if elderly, CVD, HR>90, planned for RAI ablation) unless C/I like asthma *can cause IUGR, fetal brady, and neonatal hypoglyc
- Anti-thyroid meds: MMZ > PTU bc less hepatotox (except in T1 preg, thyroid storm, past minor reaction to MMZ)
- Radioactive iodine (C/I preg, breastfeed, thyroid ca, mod-sev orbitopathy) - pre-tx with MMZ if at high risk of complications with post-op thyroiditis (hold 2 days pre), and can resume 3-7d after RAI if high risk
- Surgery - need to be euthyroid 1st
*If preg check TSH R AB titer in T2, if v high (3x) = increased fetal monitoring of fetal graves
Side effects anti-thyroidal drugs (PTU, MMZ)
Hepatitis/Liver ailure (PTU>MMZ): MMZ cholestatic elevation, PTU hepatic necrosis (stop if LFT>3xULN)
Rash –> antihistamine +/- pred
Agranulocytosis (monitor fever/sore throat) –> GCS, steroids, abx (if febrile) +/- suppotive cae
GI symptoms
Leukocytoclastic vasculitis
*STOP and cannot switch unless minor rash, GI, myalgia, arthralgia
Hints to gestational transient thyrotoxicosis
*HCG also stim TSH R to decrease TSH and increase T4 eg choriocharcinoma, mult gestational preg
Thyroid binding globulin and T4 increase GA 7-16 wks, (improves by 14-18wks)
Hyperemesis gravidarum
Resolves spontaneously
Possibility molar pregnancy (GET PELVIC US)
No features suggestive of grave’s: thyroid bruit, opthalmopathy, goitre, thyroid R AB pos
No history past thyroid dz
TSH Targets in pregnancy
+how to adjust thyroxine
If TPO Ab +: Initiate tx if TSH >2.5
If TPO Ab - : Initiate tx if TSH >10, consider in 4-10
If starting on thyroxine, or on pre-existing, target TSH <=2.5 in pregnancy (increase pre-preg dose by 2 pills/week)
Starting L-thyroxine dose
1.6mcg/kg
Start at 25/50 and go up slowly in elderly/CVD/afib
Def’n high and very high risk osteoporosis
High risk:
1+ past vertebral fracture or hip fracture
2+ prior fragility fracture
1+ fragility fracture + prolonged steroids (>7.5 x3mo)
Moderate risk + fragility fracture over 40yo
Moderate risk + prolonged steroids
CAROC>20%, FRAX > 20%
Very high risk: Multiple vertebral fractures Fracture in last 12 months Fracture on OP treatment or steroids History/High risk falls T-score < -3 FRAX >=30%
OP Tx options, duration
1st line: Bisphosphonate, Denosumab, Teriperitide (PTH analog), Romo (antisclerostin AB promotes bone formation)
- r/a at: 3-5 yrs if BP, 5-10 yrs prolia, 2 yrs teri, 1 yr romo
If failed one 1st line, try 2nd; if improved BMD, drug holiday from BP or step down to BP from others
2nd line: If intol or failed all 1st lines:
- If >60: SERM > HRT > calcitonin > Ca+VitD
- If <60 or <10y past menopause and low VTE risk: SERM (if breast ca risk) or HRT (if vasomotor symptoms)
*Raloxifene no hip/non-vertebral coverage;
Teri = no hip coverage
OP and CKD
Alendronate and Zoledronic Acid: Stop at eGFR 35
Risedronate, Pami, Teri: eGFR 30
Denosumab: Down to any GFR
Romo - not studied
Diabetes Diagnosis
A1c >=6.5% Random glucose >= 11.1 2hr OGTT >= 11.1 FPG >= 7 *Need 2 positive tests (separate times) *If symptomatic, only 1 of these tests
“Pre-diabetes” Diagnosis
vs Diabetes Diag
A1c 6-6.4% (>6.5)
FPG 6.1-6.9 (impaired fasting glucose) (>=7)
2 hr OGTT 7.8-11 (impaired glucose tolerance) (>=11.1)
Factors that increase HbA1c
Decreased production: Fe/B12 deficiency, Aplastic anemia, Splenectomy
Increased glycation: EtOH, CKD
Factors that decrease HbA1c
Increased production: Fe/B12 use, EPO use, hemolytic anemia, chronic liver disease
Increased destruction: Splenomegaly, CKD, Hemoglobinopathies, RA, Dapsone, HAART
Decreased glycation: ASA, Vit C, Vit E
HbA1c targets
<=7% for most
<= 6.5% if low risk hypos and pre-pregnancy
7.1-8% if functionally dependent
7.1-8.5% if short life expectancy, frail elderly w/ dementia, recurrent severe hypos/unaware
T2DM: When to initiate treatment and with what?
Sx/Metabolic decompensation: Insulin +/- metformin until glycemic control (then taper insulin while adding OAC)
A1c >1.5% above target: Metformin + 2nd agent
A1c within 1.5% of target: Metformin OR Lifestyle x3 months–> metformin if A1C still elevated after 3 mo
*symptomatic/ decompensation: polyuria, polydipsia, blurry vision. wt loss, ketosis, hypovolemic, HHS/DKA
T2DM: Add on agents and compelling indications
CKD: SGLT-2
CHF: SGLT-2
Established CVD: GLP-1 or SGLT-2
>60 + >=1 CVD RF: GLP-1 (wt loss, lower A1c >basal insulin - not basal +MDI; stroke benefit vs SGLT2)
Obesity: GLP-1
No compelling indications: SGLT-2, GLP1, DPP4 (if frail)
- If still above target on 2nd agent, add 3rd (GLP1 if on SGLT-2 and vice versa).
- If not on target despite 3rd, insulin (basal –> MDI)
CVD RF: smoking, HTN , DLPD, obesity
Anti-glycemics and CKD (eGFR cutoffs)
SGLT2s: Dose reduce to 15, STOP if on HD
GLP1s: No dose change to 15, limited data below
Metformin: avoid if <15 (dose reduce below 15-60)
DPP4: Lina/sitagliptin at any GFR (caution <15 and dose adjust), normal dose to 45 and dose reduce 30-45
Glyburide: avoid in CKD below 60
Gliclazide or repaglinide: dose reduce below 45
Insulin: Normal dose to 30, dose reduce <30
Side effects / Contraindications GLP-1
Side effects:
GI upset (abdo pain, dyspepsia N/V/D)
Retinopathy (semaglutide)
Contraindications:
PMHX or FHX MEN2
PMHX or FHX Thyroid CA
PMHX pancreatitis or pancreatic CA
DM: Indications for ACEi at CV protective doses (perindopril 8, ramipril 10, *telmisartan 80)
- 55yo+ and 1 additional CV RF or end organ dmg (eg LVH, retinopathy, albuminuria)
- Microvascular dz (retino-, neuro-, nephropathy - ACR>20 or >2 i GFR<60, autonomic dysfcn, gastroparesis)
- Established CVD
- does not reduce nephropathy in T1DM w/o microalbuminuria or HTN
DM: Indications and target for Statin
-what is 2nd, 3rd line
- Age >40
- Age >30 and DM duration >15 years
- Established CVD
- CV RFs
- Microvascular disease
target LDL<2.0 or >50% reduction
+ezetimibe or evolocumab to reduce CV events if LDL not at target w/ statin alone
DM Targets in Pregnancy
-which meds ok in preg
A1C <7, ideally 6.5%
FPG <5.3
1 hr post-prandial <7.8
2 hr post-prandial <6.7
*Insulin, metformin, glyburide okay
GDM Screening (@24-28 weeks)
50 g 1hr OGTT: >=11.1 = GDM, <7.8 = Normal, between = borderline –>
75g 2hr OGTT: GDM = FPG >=5.3, 1hr >=10.6, 2hr>=9
or in COVID: A1c >=5.7%, random plasma glucose >=11.1
Pituitary adenoma - workup:
1) Assess structure: MRI sella
2) Assess function: GH (IGF1/glucose), LH/FSH (T, E2), TSH/T4, ACTH (cortisol), Prolactin
Pituitary adenoma: Treatment
+features of mass effect
Prolactinoma (even if mass effect): DA Ag (Cabergoline > Bromocriptine - more S/E: nausea, H/A, nasal stuffiness)
All other tumor (Not prolactinoma): Surgery (transphenoidal resection) if mass effect (H/A, cranial nerve, visual field, hemorrhage, hyper/hypofunctioning), otherwise clinically monitor
Diagnosing Diabetes Insipidus
- Water deprivation test: If serum [Na] increases with no change in urine Osm (dilute, ie <300) = confirmed DI
- DDAVP Rescue:
- If Na decreases and Urine Osm increases (>600) = Central DI
- If no significant change = Nephrogenic DI
Thyroid nodules - threshold to biopsy
> 2cm - all nodules except purely cystic
> 1.5 cm with low suspicion sonographic features (iso/hyper-echoic, part cystic/solid)
> 1cm with intermed/high suspicion features
- mod risk: hypoechoic, no other high risk feats
- high risk: microcalcification, HYPOechoic , irreg margins, tall>wide, extrathyroid extension, LND, interrupted rim calcifications, >20% increase in 2 dimensions)
<=1cm or purely cystic or hot nodule - don’t biopsy, follow with repeat US in 1-2 years
TSH Targets post-op thyroidectomy for thyroid CA
High risk <0.1 (if extra-thyroid extension, incompl resection, LND, distant mets, + margins, need post-op RAI)
Intermed: 0.1-0.5
Low risk: 0.5-2 (<=5 LN micromets)
Differentiate Insulinoma from Exogenous Insulin from Secretagogue Use
Insulinoma: Glucose Low, Insulin High, C-peptide High
Secretaogue: Glucose Low, Insulin High, C-peptide High
Exogenous Insulin: Glucose low, Insulin high, C-pep low
Adrenal Insufficiency: Screening, diagnosis, determining etiology
Screening: 8am cortisol (<83 = AI likely, >500 unlikely, between need further testing)
Diagnostic Test = ACTH Stimulation test (Positive if cortisol fails to rise to >500)
Determine Etiology:
A) If ACTH low/N = secondary/central –> Image pituitary
B) If ACTH high = primary
i) 21-OH Ab + = Addison’s
ii) 21-OH Ab - = infiltrat/bleed/ infxn/ Ca vs genetic –> CT adrenals and if neg send genetic testing
Cushing’s: Screening, Diagnosis, Determine etiology
Screening: 1mg DST (<=50 - N, >140 abn)
Dx: 2/3 of: 1mg DST, 24hr urine free cortisol, midnight salivary cortisol
Determine Etiology:
A) ACTH low=primary (adenoma/carcinoma)-> CT/MRI abdo
B) If ACTH high/N = secondary vs ectopic-> 8mg DST
i) If cortisol suppresses: Pituitary adenoma –> MRI sella
ii) if cortisol does not suppress: Ectopic. Review meds. CT chest r/o SCLC or neuroendocrine
Adrenal Incidentaloma: Work-up and f/u
Work-up if >1cm
1) non-con-CT or MRI to assess structure and malignancy risk
2) Functional Screening:
- 1mg DST (For Cushing’s)
- 24 hrs urine total metanephrines and catecholamines (For Pheo)
- Plasma renin:aldo (for Conn’s) - only if HTN or hypokalemic (<3 with diuretic, <3.5 spont)
If normal, FU in 1 year and r/o pheo, hypercortisol (not for aldo)
- Image mass - surgery if abN, if N: only 1 addtnl FU
Adrenal Nodule/ Hyperfunction Mx
Adrenalectomy if:
1) >4 cm nodule or high risk features (pre-tx with alpha-B x2 wks for pheo)
2) Pheo or symptomatic cushings
3) Unilateral Conn’s on b/l adrenal sampling. If bilateral –> MRA
Indications for Bariatric surgery
BMI >=40
BMI >=35 with DM2 or HTN or CAD
Paget’s Disease Indication for Tx and meds used
Indications:
- Symptoms (pain, #, compression)
- Active disease w/ high fracture risk
- Hypercalcemia
- ALP >2x ULN
- Prior to orthopedic surgery involving nearby bone
Tx = Zoledronic acid 5mg IV q1year, PO can be used but diff dose and DAILY
2nd: calcitonin
Indications to screen for primary Hyperaldosteronism (Conn’s)
Adrenal Incidentaloma with HTN or hypoK
Refractory HTN to 3+ meds
Unexplained hypoK (<3.5 without diuretic, <3 with)
Screening test for Primary HyperAldo
Plasma renin:aldo ratio
*MRA, diuretic, OCP should be held 4-6 wks prior
If non-diagnostic, ACE/ARB/BB/CCB should also be held
Diagnostic tests for primary hyperaldo
PRA >1400 with aldo >440
Saline loading test
Captopril suppression test
Approach to primary hyperaldo
1 - screen for condition if indicated
2- diagnostic test (saline loading, captopril suppression)
3- CT/MRI to localize the lesion (if present)
4- Bilateral adrenal vein sampling to determine if unilateral or bilateral hypersecretion
Treatment of primary hyperaldosteronism
If bilateral hypersecretion: MRA
If unilateral hypersecretion: Adrenalectomy
Indications to screen for Pheochromocytoma
- Adrenal incidentaloma
- MEN2A/B, NFL-1, VHL
- Symptoms: Paroxysmal headache, palpitations, sweating, panic attacks,
- Labile/severe HTN >180/110 refractory to meds or triggered by MAOi, BB, micturition, surgery, anesthesia
Screening Test for Pheochromocytoma
24 hr urine total metanephrines and catecholamines or
Plasma free metanephrines and normetanephrines
*NOT urinary VMA
Screen + –> MR/CT abdo with delayed contrast washout to confirm adrenal lesion
Treatment for Pheochromocytoma
Surgical resection after 14 days Alpha-blockade (doxazocin or phenoxybenzamine) with liberal salt and fluid intake
*BB only after high dose alpha blockade
Periop: Phentolamine IV prn, pressors prn
Postop: caution hypotension, hypoglycemia, consider MEN
Treatment of patient with profound hyperthyroidism requiring contrast CT
PTU Pre-treatment
Treatment of hypoglycemia
Mild/mod: 15g glucose/sucrose tabs
Severe (req assistance): 20g glucose as tablets
Unconscious: 1mg glucagon IM (less effective in liver dz or alcoholics) or 10-25g Dextrose if IV access
*If acarbose related, needs to be dextrose/glucose, NO SUCROSE (ie. glucose tabs or honey or milk or IV D50W)
Other: 15ml of sugar packets dissolved in water 5 cubes sugar 150 ml of juice/pop 15ml honey 6 lifesavers IV D50W
Medications that do not interfere with plasma renin:aldo ratio
Alpha blocker
Verapamil
Hydralazine
Treatment of primary hyperparathyroidism
Surgery - if meets criteria (STFAUSC)
Otherwise: bisphosphonate, cinecalcet, observe (if mild)
Treatment thyroid storm
Propranolol (60-80 PO Q6hr, 1mg IV Q3hr)
PTU (200 mg PO/PR Q4 hrs) THEN Lugol’s Iodine (10 drops PO/IV - started >=1 hr post PTU)
Hydrocortisone (100 mg IV Q8hrs) prev T4–>T3 conversion
Cholestyramine 4g PO QID
Treatment of DKA
1) Fluids:
1-2L NS up front then 500 cc/hr x2 hrs –> 250/hr x4
If rpt Na or Osm high: Change to 1/2 NS
If rpt Na low or normal: Continue NS
*Add D5W or D10W once gluc <14 to maintain bw 12-14
2) K:
- If <3.3 - 40mmol KCl before insulin
- If 3.3-5.5 - 40 mmol KCl with insulin
- >5.5 - no KCl
3) AGMA
- Start insulin 0.1U/kg/hr IV once K >3.3
- Continue until AG closed
- Transition to SC insulin (give 1/2 basal needs = 24 hr insulin req / 2 /2) and overlap x2-4 hrs
Thyroid Nodules: Timeline to repeat US
High risk features: 6-12 months
Intermediate risk features: 12-24 months
Low risk or very low risk features: 2 years
<1cm + very low suspicion or pure cyst - never
Hypo/HyperMg association
HypoMg –> PTH resistance (inappropriately normal PTH in someone with apparent hypoPTH)
HyperMG can happen in FHH
Secondary HyperPTH
-how to replace in CKD and gastric sx
HypoCa or Vit D Deficiency
- After gastric sx (bypass, bilroth, whipples) - use Ca citrate (no acid to absorb Ca carbonate)
- In CKD: treat w/ vit D, PO4 restrict, non-Ca PO4 binders, cinacalcet
HypoPTH ddx
Acquired: HypoMg, thyroidectomy, radiation, infiltrative (sarcoid, amyloid, mets), autoimmune polyglandular syndrome type 1 (whitaker’s triad: chronic mucocutaneous candidiasis, Addison’s, hypoPTH)
Congenital: pseudohypoPTH, Digeorge (agenesis)
Falsely low RAIU
CT scan (iodinated contrast) Amiodarone (iodine load) Iodine intake (eg kelp, seaweed)
Goiter (big thyroid) ddx
TSH (Hashimotos)
Thyroid R AB (Graves)
B hCG (preg)
Thyroid Storm: features and precipitants
- Fever
- Neuro sx
- GI/hepatic dysfunction
- Tachy
- Afib
- -HF
- Precipitants: infxn, surg, trauma, iodine load, preg, nonadherence to meds
When/How to Tx subclinical Hypothyroid
- TSH>10
- Consider if symptomatic, goiter, preg/planning, +anti TPO AB
OP Meds S/E
BP: flu like sx, reflux sx, jaw ON (higher in Ca, DM, steroids, dental procedures), AFF, ?esophageal Ca
Prolia: ?increased cellulitis, hypoCa, AFF, jaw ON, BMD decline + # if stopped
Raloxifene/HRT: VTE
Teri: HyperCa, Hypercalciuria
ROMO: MACE events, AFF, jaw ON, OK for eGFR<30 but risk of hypoCa
OP Med Failure Def’n
Fracture or BMD decreased despite >80% adherence to therapy for 1 year
- Maj insuff # (spine, femur, wrist, prox humeral) OR
- Multiple minor insuf # OR
- BMD decease > least signifc change after 5 yrs or earlier in pt w/ minor #
AFF Prev and Tx
Prev: drug holiday if LOW risk on BP x5y (or IV BP x3y)
Tx: Ortho consult (IM nail insertion)
- Image contralateral femur for asymptomatic
- Stop BP, ensure Vit D and Ca
- START teriparatide
Non Pharm OP
Exercise: resistance, core, balance (tai chi)
Hip protectors if elderly in LTC
Smoking cessation + EtOH moderation
Falls prevention via PT/OT
Vit D (800-2000U if >50yo; 400-1000 if <50yo and low risk deiciency) to target >75nmol/L
1200mg Ca/d (ideally from diet)
T1DM Tx
Basal bolus (BBI), Continuous SC Insulin infusion (pump) +/- continuous gluc monitoring (CGM) - benefits if adherent >70% in 14d No recommendation for non-insulin antihyperglycemic
Continuous glucose monitoring targetes
Glycemic variability <36% (less hypos)
Time in range (3.9-10) >70%
Time below range (<3.9) <4%
Time above range (>10.1) <25%
In elderly: TIR (3.9-10) >50%, TBR <1%, TAR (>13.9) <10%
CGM<3.9 may not be true/clinically signif hypo if not on insulin or sulfonylurea
In preg: TIR (btwn 3.5-7.8) >70%, TBR (<3.4) <4%, TAR (>7.8) <25%
If T2DM NOT on insulin: measure fasting, pre/2h post prandial qAC, qhs q1-3 mo if not hitting A1C target
Do not need to test daily except illness or risk of hyperglycemia (if not on insulin/sulfonylurea or hitting A1C)
DM drugs and weight
Loss: GLP1 (-lutide), SGLT2 (-flozin)
Neutral: DPP4i (-liptins; saxagliptin risk of HF), acarbose
Gain: Sulfonylurea, meglitinides, insulin, thiazolidinediones (risk of HF)
SGLT2 Benefits and RIsks
Benefits: BG control w/o hypo, wt loss, BP reduction, less MACE/HF/CV mort, better renal outcomes, PO tab
Risks:
- GU infxn: UTI, yeast infxn, possible nec fasc (Fournier’s gangrene) - tx normally and continue SGLT2
- Toe amputations (cana)
- Euglycemic DKA (caution in low carb diet, hold for major surg, caution w extreme EtOH/exercise)
- Vol depletion / AKI - hold for sick days
- Worsening OP - fractures
C/I: Dapa in bladder Ca
Adrenal Incidentaloma High Risk Features
Size >4cm Hounsfield units >10 (>20 v suspicious) Delayed contrast washout <50% Calcifications, extension, adenopathy History of malignancy
Bariatric Surgery Complications
Post-prandial hypoglycemia, dumping syndrome
Malabsorption: Fe, B12, folate, Ca, vit ADEK, thiamine
General surgical risks, stomal obstruction, gastric perf
Biliary stone disease, hernia
Obesity increases risk of which cancers
Colon Kidney Esophagus Endometrium Postmenopausal breast
Obesity therapies
Psych: behaviour modification, manage sleep/ time/ stress, CBT
Meds (if BMI>30 or BMI>27 w/ T2DM, NAFLD, gallbladder dz, gout) to maintain weight loss: 1st Liraglutide, 2nd Naltrexone/Buproprion, 3rd Orlistat
- r/a in 3 mo then switch or add
- can use Naltrexone/buproprion as 1st line if depression, smoking, food cravings
Surgery (if BMI>40, or >35 w/ complications or >30 w/ poorly controlled T2DM): sleeve gastrectomy, Roux en Y gastric bypass, biliopancreatic diversion +/- duodenal switch
Non diabetic meds causing weight Gain
Neuroleptics: olanzapine, QTP, risperidone, clozapine, haldol
TCAs: amitriptyline, nortriptyline
SSRIs: paroxetine, citalopram
Anti-depressants: mirtazapine, Li, phenelzine
Anticonvulsants: Valproate, carbamazepine, gabapentin
Antihyperglycemic: Insulin, sulfonylurea, TZDs
Antihistamines: 1st gen
Beta blockers: propanolol
Steroid hormones: contraceptives, glucocorticoids
Dyslipidemia - who to screen
Age> 40 or postmenopausal, earlier if south asians or indigenous
- Clinical/Preclinical atherosclerotic CV dz (coronary artery score or carotid US abN), stigmata of DLPD
- AAA
- Smoker
- DM, HTN, CKD (ACR>3, eGFR<60), Obesity (BMI>30), ED
- Chronic dz: COPD, HIV, Inflamm dz (Ra, SLE, PSA, AS, IBD)
- Preg related complication (GDM, HTN, preterm birth, low BW) - screen in LATE post partum using CV age over 10y risk calculator
- Fam Hx of premature CVD or DLPD
How to screen for dyslipidemia
Lipoprot(a) ONCE in pt's lifetime Lipid profile: TC, LDL-C, HDL-C, nonHDL-C, TG H&P FPG or A1c eGFR
Optional: ApoB, urine ACR (if eGR<60, HTN, DM)
- Use non-HDL C or ApoB instead of LDL to screen if TG>1.5
- Lp(a)>100nmol/L needs earlier/more intense behav change +/- statin
Dyslipidemia Therapies
Lower LDL-C
- Statin - decrease chol production, upreg LDL-R; high potency (rosuva, atorva, simva), low (fluva-, lova-, prava-)
- Bile acid sequestrant (eg cholestyramine, colesevelam): upreg LDL-R and reduce bile acid circulation
- Cholesterol absorption inhibitor (from food): eg ezetimibe - reduced CVD when in combo with statin
- PCSK9 (Alirocumab, Evolocumab) - recycles LDL-R
Lower TG
-Fibrate (eg -fibrate, gemfibrozil
Statin indicated conditions, target, and add on drugs
Conditions:
-LDL>5
–> TARGET LDL<2.5 or 50% reduction or ApoB<0.85 or nonHDL-C<3.2
add on: ezetimibe, pcsk9
*also qualifies: familial or if TG>1.5: ApoB>=1.45 or nonHDL-C>=5.8)
-DM (40+ or 30+ w/ 15y DM or microvascular dz), OR CKD (50+ and GFR<60 or ACR>3) OR Intermed/High (<20%) FRS
–> TARGET LDL<2.0 or ApoB<0.8 or nonHDL-C<2.6
add on: ezetimibe, bile sequestrant
ASCVD or AAA (3cm or prev sx)
- -> TARGET LDL<1.8 or ApoB<0.7 or nonHDL-C<2.4
a) If LDL >2.2 or ApoB>0.8, or nonHDL>2.9 or high PCSK9 benefit patient –> PCSK9i +/- ezetimibe
b) otherwise : ezetimibe +/- PCSK9i
Other conditions:
-FRS 5-9% (low) w/ LDL >=3.5 or nonHDL-C >=4.2 or ApoB>=1.05 w/ FHx, Lp(a) >100, CAC>0AU
Dx of Familial Hypercholesterolemia
1) LDL>5
2) R/O 2ndary causes: anorexia, nephrotic syndrome, hypothyroid, obstructive liver dz
3) Diagnosed if:
a) 1st deg rel w/ LDL >5, OR
b) Early CAD: <65F, <55M OR
c) Xanthelasma, arcus corneus, xanthomas
High PCSK9i benefit
Recent ACS within 1y
ASCVD +any of:
-DM, metabolic syndrome
-Symptomatic PAD, or vascular dz in 2+arterial beds
-MI in past 2 yr, recurrent MI, previous CABG
-LDL-C>2.6 or lipoprot(a) >120nmol/L
When to use icosapent ethyl 2000mg BID
ASCVD + TG >1.5 to 5.6
Consider if DM >50yo + 1 CV RF:
- M>55, F>65
- HDLc < 1.04 (M) or 1.3 (F)
- HTN >140/90, ABI<0.9 without symptoms
- Smoker or quit w/i 3 mo
- Microvascular dz: GFR >30 and <60, Micro/macroalbuminuria, Retinopathy
Transgender care
- Offer fertility referral
- Counsel smoking cessation
- Must be on gender affirming hormone therapy if gonadectomy bc risk of OP
Transwoman increased VTE and Br Ca than Cis-men
Transmen increased erythrocytosis, metabolic syndrome, OSA, and PCOS prior to GAHT
Amenorrhea Defn
No menses at 16
No sexual characteristics at 13
Amenorrhea workup
Ultrasound:
- Mullerian structures present: anatomic obstruction, XO karyotype, OR endocine problem (BHCG, FSH, LH, PCOS, pituitary)
- Mullerian structures absent: karyotype ?XY with androgen insensitivity, 5a reductase deficiency, check testosterone
Secondary amenorrhea Def’n and DDX
No cycles >3mo when previously regular, or >6mo when previously irregular
- Hypothalamic: functional (eg female athelete, eating disorder, high stress, chronic illness) –> low FSH/LH and estradiol
- Pituitary: pituitary adenoma (Prl), other sellar mass, infiltration (hemochromatosis), Sheehan’s, etc
- Ovarian: PCOS (ovarian insulin resistance), Primary ovarian insufficiency (age <40)
- Pregnancy
- Structural: bicornuat uterus, endometriosis, Asherman’s
PCOS Defn, features, workup + tx
*red flags NOT PCOS
2/3 of:
- Menstrual irreg
- Biochemical of clinical hyperandrogenism
- US findings of polycystic ovaries
Exam: BMI, hyperandrogen (alopecia, hirsutism, acne), acanthosis nigricans
Ix: Prl, TSH, DHEAS, LH>FSH, estradiol, fasting BG, 2hr OGTT, lipid profile
-sleep study
-US pelvis
*virilization (increased muscle bulk, voice, clitoromegaly) = red flags = NOT PCOS, look for tumor causing adrenal corticocarcinoma
Tx: OCP (1st line), Metformin (endometrial protection, anovulation), Spironolactone (hirsutism), Clomiphene (fertility), Weight loss
Primary ovarian insufficiency cause, workup, Tx
Etiology: Autoimmune, Radiation, Chemo, Fragile x (family hx intellectual disability, ataxia)
Ix: Karyotype, fragile X, Anti-adrenal AB, screen BMD
Tx: hormone replacement until age of usual menopause (age 51)
Hyperandrogenism in women H&P, Ix
H&P:
- Acne, voice change, mood, hirsutism,
- Clitoromegaly, menstrual abnormalities,
- Hypothyroid, liver dz, anabolic steroids?
Ix:
- Total/free T: Image ovaries and adrenals if testosterone very high (>5moml/L)
- DHEAS (if normal = NOT adrenal problem)
- FSH, LH, Prl, TSH
- 17OH Prog - increased in CAH, nonclassic CAH (>6mmol/L warrants ACTH stim testing)
Ddx Hyperandrogenism
- PCOS
- Non classic CAH
- Virilizing tumor
- Cushings
- Acromegaly
- Hypothyroid
- HyperPrl (rare)
- Exogenous androgens/ anabolic steroids, valproic acid
Premenopausal Hirstism Dx and Tx
Dx:
- Random total testosterone - if abN hirsutism score
- Morning 17OH Prog to assess for NCCAH in women w/ high T or high risk for CAH
- Do not measure androgen lvl if normal hirsutism score and normal menses
Tx:
- Local hair removal: electrolysis, photoepilation, pluck, wax
- Weight loss if obese or PCOS
- OCP, spironolactone
- Antiandrogens NOT recommended bc teratogenic, ok if sterilized or using contraception or not sexually active
Hypogonadism approach
- Measure fasting total T (and free T if altered SHBG or borderline total T near lower limit of N)
- If low tot or free T: repeat morning fasting total and free T. If still low –> confirmed dx –> Measure LH/FSH:
- LH/FSH high = primary hypogonadism: Klinefelter (XXY), chemo, trauma, mumps, AI, systemic illness
- LH/FSH low or inappropriately normal = 2ndary hypogonadism: measure PrL, Tsat +/- other pituitary hormones +/- pituitary MRI
Tx: Replace T UNLESS:
- Planning fertility
- BCa or PCa/ high PSA / prostate nodule
- Untreated OSA, high hematocrit
- Uncontrolled HF, MI/stroke in last 5 mo
- Thrombophilia
- Severe LUTS
Monitor: sx, T lvls, Hct, PSA
Klinefelter’s syndrome
- Small firm testes
- Increased LH, FSH, decreased T
- Arm span> height +5cm
- Leg length > upper body +2cm
- Comorbid: NHL, bronchiectasis, SLE, DM, osteopenia, BCa
- Dx: Karyotype (XXY)
Factors affecting sex hormone binding globulin level
Decrease SHBG: obesity, DM, acromegaly, hypothyroid, steroid use, nephrotic syndrome
Increase SHBG: aging, HIV, liver (hepatitis/cirrhosis), hyperthyoid, E2 use, anticonvulsant use
Hyperprolactinemia ddx
Drugs (eg antipsychotics)
Hypothyroid
Stalk effect (tumor)
Prolactinoma
Acromegaly: Pt, Screening, Dx, Tx
Macrognathia, macroglossia, increased ring / shoe/ collar/ glove size, OSA, coarse facial features, gap between incisors, carpal tunnel, visual field defects, cranial neuropathies
Screen: IGF-1
Dx: 75g glucose suppression of GH
Tx: Surgical
Approach to thyroid nodule
TSH –> RAIU if TSH <0.5
US (to r/o cystic)
FNA
- tx each nodule individually if multiple nodules
- If nodule is “hot” –> look for Graves ,toxic adenoma, multi nodular goitre
Graves Orbitopathy Tx
Mild: monitor, selenium +/- steroids if QoL impaired
Mod/Severe: active/inflamm –> steroids then rehab, if inactive = rehab
Sight threatening: steroids (2nd: cyclosporine or ritux) –> decompression if no response by 2 weeks, if response = rehab
Surgery only for STABLE INACTIVE GO
DM Complication Screening schedule
- 5y after T1DM dx after age 15
- At dx of DM2
- Retinopathy: dilated fundoscopy, fundus photography q1h T1DM, q1-2y T2DM
- Neuropathy: 10g monofilament or 128H vibration
- Nephropathy: Random UACr >20
DM meds and benefits
MACE or 60+ and 2+ CV rf: GLIP1 (lira, dula, sema), SGLT2 (empa, cana)
HHF or nephropathy : SGLT2 (empa, cana, dapa) - if GFR>30
*Give even if at A1c target
Driving and diabetes
Rules for insulin / secretagogue:
- Q2y exam for fitness to drive
- BG measurement before driving and q4h (q2h if recurrent/unaware hypos) or wear CGM
- No driving if BG<4.0
- No driving at least 40 min after tx of hypoglycemia (BG must be 5+)
Report if:
- Severe hypo driving in last 12mo
- Severe hypo not driving in past 6mo for private or 12 mo for commercial
Hypoglycemia WORKUP
72h fast w/ capillary glucose monitoring until glucose <3.3, increase to q1h BW
If venous glucose <2.5, send for :
-Insulin
-Proinsulin and Cpeptide (produced with endogenous insulin)
-B hydroxybutyrate (high in normal hypoglyc and noninsulin mediated hypoglyc)
-Glucose lvl after glucagon response
-Insulin AB
GFR Cutoffs for antihyperglycemics
<60: Avoid glyburide, reduce Metformin by half at each interval until <15
<45: Reduce SGLT2, DPP4, Gliclazide, Repaglinide
<30: Reduce Insulin
<15: Avoid metformin, GLP1
Teriperitide C/I
C/I:
- Primary hyperparathyroid
- Paget’s, HyperCa, Stones
- CKD
- Extensive skeletal radiation
Don’t use in: children, young adults, preg, gout, hyperuricemia, longer than 2 years (osteosarcoma)
Teriparatide Indications
- Severe OP and mult vertebral fractures
- Fracture on bisphosphonate
- OP on prolonged steroids
- Jaw osteonecrosis or AFF
ZES features, Dx
Multiple refractory ulcers
Dx: Fasting gastrin levels
-Secretin stim test to differentiate gastrinoma from other hypergastrin causes when serum gastrin concentration and pH not diagnostic
Osteomalacia Pt and labs
Pt: may be asymptomatic with radiologic osteopenia +/- diffuse bone and joint pain, muscle weakness and difficulty walking.
Labs: HypoCa, hypoPO4, ALP elevation, PTH elevation, low urinary Ca and low calcidiol
Dyslipidemia findings
Tendon Xanthoma (Cholesterol) Arcus Senilis (cholesterol w age) Scleral lipemia (TGs) Eruptive xanthomas (TGs)
