Endo

Question 1

DMT1 definition and DKA

Answer 1

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

Question 2

DMT1 sx

Answer 2

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

Question 3

DMT1 dx

Answer 3

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)

Question 4

DMT1 tx

Answer 4

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)

Question 5

DMT2 definition, RF and HHS

Answer 5

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

Question 6

DMT2 sx

Answer 6

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

Question 7

DMT2 dx

Answer 7

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

Question 8

DMT2 tx

Answer 8

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

Question 9

Glucose monitoring and target goals

Answer 9

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

Question 10

Rapid acting insulin meds, onset, peak and duration

Answer 10

Aspart, Lispro, Glusilin

onset: 10-20
peak: 30-90
duration: 3-5

Question 11

Long acting insulin meds, onset, peak, duration

Answer 11

detemir, glargine, degludec

onset: 1-4 hours
peak: 6-14 hours
duration: 16-42 hours

Question 12

Biguanides meds, MOA, ADRs

Answer 12

• 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

Question 13

Sulfonylureas meds, MOA, ADRs

Answer 13

Sulfonylureas
- 2nd gen: glipizide, glyburide, glimepiride
- 1st gen: tolbutamide, chlorpropamide

MOA
Stimulates pancreatic beta cell insulin release

ADRs
- hypoglycemia
Chlorpropamide:
- hyponatremia, disulfiram reaction

Question 14

Thiazolidinediones med, MOA, ADR

Answer 14

• pioglitazone
• rosiglitazone

MOA:
Increases insulin sensitivity at peripheral receptor sites

ADR
- peripheral edema, fluid retention, CHF
- hepatotoxicity

CI: Heart failure, pregnancy, DMT1

Question 15

GLP-1 meds, MOA, ADR, CI

Answer 15

• liraglutide, semaglutide, dulaglutide

MOA: Increased glucose-dependent insulin secretion

ADR: GI, pancreatitis

CI: Hx of gastroparesis or pancreatitis, Medullary thyroid cancer

Question 16

DPP4 Inhibitors meds, MOA, ADR

Answer 16

• sitagliptin
• linagliptin
• saxagliptin

MOA: Increases GLP-1 levels

ADR: acute pancreatitis

Question 17

SGLT-2 Inhibitors meds, MOA, ADR, CI

Answer 17

• empagliflozin
• canagliflozin
• dapagliflozin

MOA: Lowers renal glucose threshold, leading to increased urinary glucose excretion

ADR:
- transient N/V
- UTI, yeast infections

CI: DMT1

Question 18

Hyperthyroidism: congenital vs graves

Answer 18

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

Question 19

Hyperthyroidism: sx of graves vs congenital vs thyroid storm

Answer 19

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

Question 20

Hyperthyroidism congenital vs graves: dx and tx

Answer 20

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

Question 21

Hypothyroidism congenital vs acquired definition

Answer 21

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

Question 22

Hypothyroidism congenital acquired sx

Answer 22

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

Question 23

Hypothyroidism congenital vs acquired dx and tx

Answer 23

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

Question 24

Obesity definition, sx, dx, tx

Answer 24

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

Question 25

Short Stature (familial vs constitutional) definition, sx, dx, tx

Answer 25

Familial Short Stature: children establish growth curves at or below the 5th% by the age of 2
*otherwise completely healthy, normal PE
*normal bone age, puberty occurs on time

Constitutional Delay: children grow & develop at or below the 5th% at normal growth velocities
*results in a curve parallel to the 5th%
*puberty delayed = delay in bone age

sx
Pathologic causes:
Disproportionate Short Stature: short limbs, avg. trunk
*Rickets
*Achondroplasia (dwarfism)

Proportionate Short Stature: person small, but all parts in their usual proportions
*Prenatal – IUGR, placental dysfunction, intrauterine infections, teratogens, trisomy 21, Turner’s syndrome
*Postnatal – malnutrition, chronic systemic disease, psychosocial deprivation, drugs, hypothyroidism, GH deficiency, glucocorticoid excess, precocious puberty

dx
Bone age (AP x-ray of the left wrist)
*advanced 🡪 precocious puberty
*normal 🡪 familial short stature
*delayed 🡪 constitutional delay

*TFTs 🡪 r/o hypothyroidism
*UA, renal function tests 🡪 r/o chronic renal dz
*CBC & SED rate 🡪 chronic systemic infection
*albumin, total protein 🡪 determine nutritional status
*IGF-1, IGF-BP3 🡪 GH deficiency
*karyotype 🡪 chromosomal anomaly
*head MRI 🡪 hypothalamic or pituitary process that is resulting in decreased GH secretion from the pituitary

tx
Females:
*low dose estrogen, switch to OCPs

Males:
*testosterone

Question 26

Hypercalcemia definition, sx, dx, tx

Answer 26

<1y: 8.7-11mf/dL
1-17y: 9.3-10.6mg/dL
≥18y: 8.6-10mg/dL

Hypercalcemia: ~11.5mg/dL or above

Etiologies: hyperparathyroidism, vitamin D intoxication, subcutaneous fat necrosis, Williams syndrome, granulomatous disease (sarcoidosis), familial hypocalciuric hypercalcemia, immobilization, malignancy

sx
“stones, bones, abdominal groans, psychiatric moans”

*nephrolithiasis
*bone pain & fractures
*ileus, constipation
*depression, anxiety, cognitive dysfunction

*weakness, irritability, lethargy
*seizures, coma
*abdominal cramps, anorexia, N/V
*polyuria/polydipsia, pancreatitis

dx
Labs: serum calcium, serum phosphorus, fractional excretion of calcium, PTH, PTHrP, 25(OH)D, 1,25(OH)2D

Imaging: KUB
EKG: shortened QT interval

tx
*IV NS w/ maintenance K
*Furosemide

Malignancy, granulomatous disease, vitamin D toxicity: consider steroids

Severe/persistently elevated Ca: consider calcitonin or bisphosphonates + endocrine consult

Parathyroid: surgery to remove parathyroid