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
