Endo Flashcards
(26 cards)
DMT1 definition and DKA
90% autoimmune – pancreatic β cells fail to respond to stimuli & undergo autoimmune destruction
Onset: usually <30 (3/4 diagnosed in childhood)
*peaks at 4-6y then again at 10-14y
*NOT associated w/ obesity
Type 1A: autoimmune (MC); HLA-DR3 & HLA-DR4 association
Type 1B: non-autoimmune β cell destruction
Main RF: family hx (first-degree relative)
Diabetic Ketoacidosis (DKA):
*infection MCC – others: D/C or inadequate insulin therapy, undiagnosed DM, MI, CVA, pancreatitis
DMT1 sx
3 initial presentations:
*Classic new onset: polydipsia, polyuria, & weight loss + hyperglycemia & ketonemia (or kentonuria)
*DKA
*Silent (asymptomatic) incidental discovery
*perineal candidiasis – common in young children/girls
*acute visual disturbances
DKA: sxs evolve rapidly over 24h
Child appears acutely ill & suffers from moderate to profound dehydration
*polyuria, polydipsia
*fatigue, HA, AMS
*N/V, abdominal pain
PE: tachycardia, tachypnea, hypotension, ↓ skin turgor
*fruity (acetone) breath
*Kussmaul respirations (deep, labored breathing)
DM1 Associations & Solutions:
Dawn Phenomenon: normal glucose until 2-8am when it rises; results from ↓ insulin sensitivity & a nightly surge of counter-regulatory hormones during nighttime fasting
TX: bedtime injection of NPH to blunt morning hyperglycemia; avoid carbs late at night
Somogyi Effect: nocturnal hypoglycemia followed by rebound hyperglycemia d/t surge in growth hormone
TX: ↓ nighttime NPH dose or give bedtime snack
Insulin Waning: a progressive rise in glucose from bed to morning
TX: change of insulin dose to bedtime
DMT1 dx
Criteria: one of the following
1) Fasting plasma glucose ≥126mg/dL on >1 occasion
2) Random plasma glucose ≥200mg/dL + classic s/sxs of hyperglycemia
3) OGTT – plasma glucose ≥200mg/dL after 2hr
4) HbA1C ≥6.5% confirmed by repeat testing
Autoantibodies: GAD65, IA2, insulin
*any (+) autoantibodies 🡪 assume DM1
LOW insulin & C-peptide
*urine: glucose, ketones
DKA:
*BG >250mg/dL (usually <800mg/dL)
*acidic pH <7.3, anion gap usually >20mEq/L
*bicarb <15-18
*(+) urine/serum ketones
Potassium: total body K is depleted, but serum K is normal/elevated (K shift from intracellular fluid to extracellular fluid)
DMT1 tx
INSULIN THERAPY!!
*Multiple Daily Injections (MDI): long-acting insulin injections 1-2x/d + rapid or short-acting insulin before each meal/snack
*Insulin Pump: delivers continuous SC infusion of rapid or short-acting insulin + supplemented boluses before each meal/snack
DKA: SIPS – saline, insulin (regular), potassium repletion, search for underlying cause
Saline: isotonic 0.9% (normal saline) until hypotension & orthostasis resolves
*then switch to ½ NS (0.45%)
*once serum glucose reaches ~200-250, add dextrose (to prevent hypoglycemia from insulin)
Insulin: for pts w/ K ≥3.3mEq/L – regular insulin continuous infusion; 2 regimens
*0.1units/kg IV bolus then continuous IV infusion 0.1units/kg/h
*NO BOLUS, start continuous IV infusion 0.14units/kg/h
*if serum glucose doesn’t fall by at least 50-70mg/dL in the first hour, DOUBLE rate of insulin infusion
Potassium: regardless of serum K, pts have a large total body K deficit
*K <3.3mEq/L – HOLD INSULIN; give IV KCl 20-40mEq/L until K above 3.3mEq/L
*K 3.3-5.3mEq/L – give KCl 20-30mEq/L IV fluid
*maintain SERUM K 4-5mEq/L
*K >5.3mEq/L – DO NOT GIVE K; check serum K q2h & delay KCl admin until serum K <5.3mEq/L
Sodium Bicarbonate: ONLY GIVEN TO PTS W/ pH <6.90 (admin associated w/ complications of overcorrection & increased cerebral edema)
DMT2 definition, RF and HHS
Combination of insulin insensitivity (resistance) & relative impairment of insulin secretion
Risk Factors: obesity greatest RF, decreased physical activity, family hx, metabolic syndrome
Hyperosmolar Hyperglycemic State (HHS): seen in older patients, associated w/ more severe dehydration; no ketosis or acidosis
DMT2 sx
3 Ps: polyuria, polydipsia, polyphagia
*poor wound healing
*increased infections
HHS: s/sxs develop more insidiously
*polyuria, polydipsia, weight loss, profound dehydration
*NEURO SXS – mental obtundation, coma, seizures
*fatigue, weakness, N/V
PE: tachycardia, hypotension, ↓ skin turgor, ↑ capillary refill time
DMT2 dx
Criteria: one of the following
1) Fasting plasma glucose ≥126mg/dL on >1 occasion
2) Random plasma glucose ≥200mg/dL + classic s/sxs of hyperglycemia
3) OGTT – plasma glucose ≥200mg/dL after 2hr
4) HbA1C ≥6.5% confirmed by repeat testing
HIGH insulin & C-peptide
HHS:
*BG >600mg/dL, often >1000mg/dL
*Plasma osmolality >320
*pH >7.3, bicarb >18
*ketones: small
DMT2 tx
Initial: diet, exercise, lifestyle changes
Asymptomatic:
*metformin MC initial
*intolerance/CI: GLP-1 receptor agonists, SGLT2 inhibitors
Symptomatic: insulin indicated as initial therapy
HHS: fluids most important management!!
*start IV fluids – 0.9% NaCl at 1L/h
*once glucose ~300mg/dL 🡪 5% dextrose w/ 0.45% NaCl at 150-250mL/h
Insulin: 0.1units/kg bolus then 0.1units/kg/h continuous IV infusion
Potassium: same guidelines as in DM1
Glucose monitoring and target goals
Glucose Monitoring: finger sticks 4x/d or continuous glucose monitoring
Targets for Glycemia Control: A1C <7% (check q3mo), blood glucose 80-130mg/dL before meals, 80-140mg/dL at bedtime & overnight
Other Monitoring: q4-6mo 🡪 hx/physical, diabetic foot exam, CV risk assessment; annually 🡪 fasting lipids, urine albumin to creatinine ration, EYE EXAM
Rapid acting insulin meds, onset, peak and duration
Aspart, Lispro, Glusilin
onset: 10-20
peak: 30-90
duration: 3-5
Long acting insulin meds, onset, peak, duration
detemir, glargine, degludec
onset: 1-4 hours
peak: 6-14 hours
duration: 16-42 hours
Biguanides meds, MOA, ADRs
- metformin
MOA: Decreased hepatic glucose production
First line oral for DM II
- weight loss
- decreased TGs
- decreased CV risk
ADR:
- GI MC
- B12 deficiency
- lactic acidosis
Severe renal or hepatic impairment
- held before giving iodinated contrast, resumed 48hrs after
Sulfonylureas meds, MOA, ADRs
Sulfonylureas
- 2nd gen: glipizide, glyburide, glimepiride
- 1st gen: tolbutamide, chlorpropamide
MOA
Stimulates pancreatic beta cell insulin release
ADRs
- hypoglycemia
Chlorpropamide:
- hyponatremia, disulfiram reaction
Thiazolidinediones med, MOA, ADR
- pioglitazone
- rosiglitazone
MOA:
Increases insulin sensitivity at peripheral receptor sites
ADR
- peripheral edema, fluid retention, CHF
- hepatotoxicity
CI: Heart failure, pregnancy, DMT1
GLP-1 meds, MOA, ADR, CI
- liraglutide, semaglutide, dulaglutide
MOA: Increased glucose-dependent insulin secretion
ADR: GI, pancreatitis
CI: Hx of gastroparesis or pancreatitis, Medullary thyroid cancer
DPP4 Inhibitors meds, MOA, ADR
- sitagliptin
- linagliptin
- saxagliptin
MOA: Increases GLP-1 levels
ADR: acute pancreatitis
SGLT-2 Inhibitors meds, MOA, ADR, CI
- empagliflozin
- canagliflozin
- dapagliflozin
MOA: Lowers renal glucose threshold, leading to increased urinary glucose excretion
ADR:
- transient N/V
- UTI, yeast infections
CI: DMT1
Hyperthyroidism: congenital vs graves
Congenital Hyperthyroidism: usually due to maternal Graves
*occurs in <2% of infants of mothers w/ Graves due to low incidence of thyrotoxicosis in pregnancy; affects males/females equally
PATHO: transplacental passage of maternal TRSAb or TSI leads to excessive thyroid hormone production in offspring; concomitant transplacental passage of TRBAb or TBII &/or antithyroid medications can affect the onset, severity, & course
Graves: autoimmune disease that affects thyroid, orbital tissue, & skin; MCC of hyperthyroidism in children w/ peak incidence in adolescence; more common in females; often associated w/ other autoimmune disorders & family hx of autoimmune thyroid disease
PATHO: TRSAb/TSI bind to/stimulate TSH receptors in thyroid gland, resulting in excessive thyroid hormone synthesis & release & follicular-cell hyperplasia; these effects may be counterbalanced by TRBAb/TBII
Hyperthyroidism: sx of graves vs congenital vs thyroid storm
Congenital Hyperthyroidism:
Prenatal: fetal tachycardia, intrauterine growth retardation, goiter
Postnatal:
*irritability, hyperactivity, anxiety, flushing, diaphoresis
*voracious appetite, ↓ SQ fat, goiter, exophthalmos
*elevated temperature, elevated BP/HR/RR
*advanced bone age, craniosynostosis, frontal bossing
*triangular facies, microcephaly, ventriculomegaly
*severe cases 🡪 hepatosplenomegaly, jaundice, cardiac failure, death
Long-term effects: growth retardation, intellectual & developmental impairments, secondary central hypothyroidism
Graves:
*goiter of varying degrees, exophthalmos, lid lag
*tachycardia, palpitations, cardiomegaly, systolic HTN
*widened pulse pressure, heat-intolerance
*tachypnea, diarrhea, tremors
*proximal muscle weakness, tongue fasciculations
*emotional lability, hyperactivity
*difficulty concentrating, difficulty sleeping
*↑ appetite w/o change in weight or w/ weight loss
*linear growth acceleration, bone maturation
Thyroid Storm: acute onset of hyperthermia & severe tachycardia that can progress rapidly to delirium, coma, & death
Hyperthyroidism congenital vs graves: dx and tx
dx
Congenital Hyperthyroidism:
*TRAb (TSH receptor antibody b) – may be blocking or stimulatory
*if (-) but suspicion is high, TSI can
be ordered
*↑ T4/T3, ↓ TSH
Graves:
*↑ T4/free T4, T3/free T3, thyroglobulin
*↓ TSH
*(+) TSI or TRAb – presence of TPO or TgAb does not r/o Graves
tx
Congenital Hyperthyroidism:
*ADMIT to NICU w/ endocrinology consult
*Methimazole or PTU
*SSKI 1 drop/d (48mg iodide) or Lugol solution 1-3 drops/d – accelerates ↓ in circulating thyroid hormone
*beta-blockers
*decompensation 🡪 consider digoxin, IV fluids, corticosteroids
Monitoring:
*TSH, T4, T3 frequently – remission gradual as maternal TRAb is degraded; usually euthyroid by 3-4mo of age
Graves:
Antithyroid drugs: methimazole, PTU
Methimazole 0.25-1mg/kg/d divided 1-3x daily
PTU 5-10mg/kg/d divided 2-3x daily
*MOA: inhibit TPO; PTU also inhibits 5’-deiodinase in peripheral tissues, thus inhibiting T4-to-T3 conversion
*Rare ADRs: hypersensitivity reactions, agranulocytosis; PTU used ONLY as second-line treatment because of a black box warning about liver dysfunction & death
*beta-blockers: propranolol generally used for acute thyrotoxicosis; atenolol used for symptomatic relief of catecholamine-mediated s/sxs until pt is euthyroid
*radioiodine (I-131) thyroid ablation: alternative or adjunct to medical/surgical therapy; results in hypothyroidism, necessitating lifelong thyroid hormone replacement
*total thyroidectomy: indicated if failure of medical therapy/coexisting carcinoma; only performed after euthyroid state achieved medically (SSKI or Lugol)
Monitoring: TSH, T4/T3, TSI
Hypothyroidism congenital vs acquired definition
Congenital Hypothyroidism: MC congenital endocrine disorder; leading cause of preventable mental retardation
PATHO:
*Thyroid Dysgenesis: defects in follicular-cell differentiation or survival results in thyroid-gland hypoplasia, complete agenesis, or ectopic location; ~85% of cases, MC in females
*Thyroid Dyshormonogenesis: due to defects in thyroid hormone biosynthesis; ~15% of cases
Acquired Hypothyroidism: Hashimoto thyroiditis (autoimmune thyroiditis) MCC of acquired hypothyroidism in children
*female to male ratio 2:1; 40-50% of pts have + family hx of autoimmune thyroid disease
*can be associated w/ other autoimmune disorders; more common in pts w/ certain chromosomal disorders (Downs, Turner)
PATHO: consequence of antibody-mediated destruction of thyroid tissue resulting in low thyroid hormone levels; absence of thyroid hormone feedback on hypothalamus/pituitary results in increased levels of TRH/TSH; TSH stimulation of thyroid gland results in goiter
Hypothyroidism congenital acquired sx
Congenital Hypothyroidism:
Birth: mild phenotype, postmaturity, macrosomia, large fontanels
Early infancy: ↓ tone, lethargy, poor feeding, prolonged jaundice, hoarse cry
Childhood: delayed linear growth, delayed bone age, fatigue, constipation, dry skin, cold intolerance, goiter in 2/3 of pts
Acquired Hypothyroidism (Hashimoto):
*fatigue, cold intolerance, constipation
*nontender goiter, bradycardia
*delayed DTRs, proximal muscle weakness
*irregular menses
*linear growth failure w/ preservation of normal weight gain
Hypothyroidism congenital vs acquired dx and tx
dx
Congenital Hypothyroidism:
*↑ TSH, ↓T4 – newborn screening now routine, preferably at 48-72h of life; TSH threshold 20-25mclU/mL
Acquired Hypothyroidism (Hashimoto):
*↑ TSH, ↓ T4/free T4
*(+) thyroglobulin & TPO antibodies
In subclinical primary hypothyroidism, there will be a mildly elevated TSH w/ normal T4
In a child w/ central hypothyroidism, TSH can be low, normal, or even elevated, & T4 will be low
tx
Congenital Hypothyroidism:
*levothyroxine 37.5-50mcg/d in term, normal-sized infants (10-15mcg/kg/d); only tablets should be used, even in neonates & infants
Monitoring: TSH (goal is lower end of normal, 0.5-2mU/L) & T4
Acquired Hypothyroidism (Hashimoto):
Levothyroxine tablets, not suspension
*0-3mo: 10-15mcg/kg/d
*3-6mo: 8-10mcg/kg/d
*6-12mo: 6-8mcg/kg/d
*1-5y: 5-6mcg/kg/d
*6-12y: 4-5mcg/kg/d
*>12y: 2-3mcg/kg/d
Monitoring
*TSH, T4/free T4 q6-8wks after initiating tx or w/ dose adjustments
*thyroid function q6mo until growth is complete, then q12mo
*goal of tx is to keep TSH/T4 within the normal range
Obesity definition, sx, dx, tx
All children >2yrs should have their BMI calculated at least annually to determine percentile
*underweight: BMI <5th%
*normal weight: BMI 5th - <85th%
*overweight: BMI ≥85th - <95th%
*obese: BMI ≥95th%
*severe obesity: BMI 120% of the 95th percentile values or a BMI ≥35kg/m2 (whichever is lower)
Screening: USPSTF recommended screening for all ≥6yo
sx
Complications:
*↑ risk of coronary disease, DM II, breast & colon cancers
*about 50% of pts experience binge eating episodes
dx
*lipids, BP, A1C, fasting glucose
*ALT for ages 9-11 to evaluate for fatty liver disease
Additional testing:
*PCOS, OSA, Cushing’s, hypothyroidism
tx
*limit sugar intake, particularly sweet beverages
Plates:
*1/2 vegetables & fruits
*1/4 whole grains
*1/4 protein
*antidepressants
*Orlistat, Lorcaserin
Surgery:
*gastric bypass
*gastric sleeve
*gastric banding
*bariatric surgery
