Endocrinology Flashcards
Short stature Generals (not napoleon)
-height 2 SDs below mean.
- normal variant = below 3rd %ile but normal velocity, pathologic if velocity low
-Eval the growth rate! In first 2 YoL, downward shift in %ile means you just a shawty
Kids growing 2 inches/year between age 3 and puberty usualy do NOT have an endocrine disorder
All pts w/ stature 3 SDs below mean or w/ growth <5 cm/ year = pathologic upo
Mid parental height
Use to distinguish a normal variant short stature vs. pathologic
Most kids are within +-4 inches or 2 SDs of MPH
Major diff between MPH %ile and current growth %ile = BAD
Male MPH = Fathers height + mom’s H + 5 inches/2
Female = fathers-5+moms/2
In short stature history look for
Perinatal hx of IUGR. If hypogly, jaundice, cryptorchid or micophallus, think hypopit
Chronic diseases- renal failure, CNS, asthma w/ steroids, sickle cell, IBD
Drug use- roids, stims for ADHD (app suppresion)Fam hx- parental growht/ub histories
social hx- critical- psychosocial dep
ROS- cold, constipation, ab pain, diarrhea, bloody stool, h/a, vom
P/E short stature
Accurate height/weight
Measure U/L body seg- (L = pubic symphysis to heel, upper == rest). Normal = 1.7 @ birth, 1.3 @ 3, 1 at >7. High U:L = rickets, low U:L = marfans
Eyes, thyroid, genetic syndrome check
(Web neck, shield chest, short fourth metacarpal = turners, tanner, scoliosis)
Normal variant short stature
Familial or genetic- hiegh 2 SD below mean with short MPH but NORMAL bone age/onset of puberty + at least 2in/year
constiutional short = 2 SD below + delayed puberty in either/both parentals, delayed bone age, late onset puberty, 2 inc/year
Pathologic short stature
More than 3 SD below w/ low growth velocity
Proportionate = normal u/l ratio, can be pre/postnatal
Prenatal Onset Proportionate SS
Environmental- tobacco/alcohol
Chromosome disorders- downs/turners
Genetic syndromes- russel-silver, prader-willi
Viral infec in prego- CMV/rubella
Postnatal onset proportionate SS
Malnurition, psychosocial causes, or
Organ system disease- Gi = ibd, cardiac = cyanotic congen heart disease, kidney issue, cld, endocrinopathies
Disproportionate short stature
very short legged, increased u/l ratio, rickets/skeletal dysplasia
Rickets = frontal boss, bow leg, low serum phosph, high serum alk phosph
Skeletal dysplasia - short w/ short limbs
To do studies if SS
Lab studies- CBC, ESR, T4, calcium, phosph, Cr, bicarb
IGF-1 (for GH deficiency- check during stage IV non-REM sleep), chromo anlaysis
Radiographic- bone age determine w/ AP of L hand/wrist (look at epiphyses)
AP/lateral skull radiographs to look at pituitary (sella turcica distort/suprasellar calc may be craniopharyngioma)
GH deficiency
Rare. Clin fx= prolonged neonatal jaundice, hypogly, cherubic facies, cnentral obesity, microphallus, cryptorchidism, midline defects
Growth curve w/ poor velocity
Why? - Craniopharyngioma (consider in any kid not going 2/year), prior CNS irrad, CNS vasc issue, AI disease, trauma, congen midline defects. 1 midline incisor + cleft palate
Eval- delayed bone age, MRi of head, Low IGF-1 level, poor esponse to GH stim testing
MGMT = daily subQ recombo GH until max growth potential reached (13-14 in girls, 15-16 males)
Hypothyroidism
Hashimoto’s most common cause
Prsent = increased TSh, low t4, positive antithyroid preoxidase antibodies
Hypercortisolism
Iatrogenic, from prolonged steroid use
Por growth, increasing weight, purpuric strecth marks, dorsal neck fat pad, delayed bone age
Turners
ack of puberty, growth hormone abnormality, GH injections can help
Normal puberty
Prepub- sex steroids supressed by neg feedback at hypothal
Pub begins when reduction in hypothal inhib = > HPG activation
HPGA releases RGnRH, hits pit, FH, GNRH out
Male puberty
@ 9-14 y/o, tesitcular enlargement usually first >4 ml, 75% volume = seminiferous tubules
FSH => sem tubule sperm making
LH = testic Leydig cells make androgens => penile enlarge, axillary, facial, pubic hair
Precocious puberty
Girls- breast dvpt or pubic hair before 7 years agemenarche before 9 yo
boys- testic/penile/pubic changes before 9 years
Premature thelarce
Visible/palapable breast tissue only, nada else, no pubic hair
Very comon bening, usually first 2 years of live
Transient activated HPGA, => trans ovarian follicular stim/release of low estrogen level
NO TX unless pubes/rapid growth spurt
Premature Adrenarche
Just pubic/axillary hair w/out breat tissue/testes
More common in girls
Usually after 5 years, onset of hair + smelly sweat. Growth stays normal, you’re all good
Isosexual precocious puberty/central precocious puberty
Early onset of gonadotropins puberty, just too early, more in girls, see errythang
girls- idiooathic
Boys- tends to be organic, need and MRi
Why? hydrocephalus, CNs infec, CP, benign hypothalamic hamartomas, malig tumors (astorcytoma/glioma), severe head trauma
Also mabes hypothy but poor growth/delayed bone age (not like rest)
Eval of CPP
Elevated FSh, LH, sex steroids
GnRh stim test- inject into patient, LH dramatic increase if CPP.
But with peripheral puberty/inactive HPGA, flat response to injection (b/c periph sex steroids suppress pit gonadotropin secretion)
Do a head MRI in all boys + young girls w/ any neuro sx (h/a or seizure) or rapid pubertal changes
Peripheral Precocious Puberty/Heterosexual Gonadotropin Indep Puberty
Indep of HPGA- caused by periph prod of sex steroids, no FSH/LH mediation, flat respose
Clin fx- boys = feminiation or premature pubic hair. NO testicular enlargement b/c no increase in FSH
Girls = virilization or breast development
Etio- exog exposure, gonadal tumors, adrenal tumors, nonclassic CAH
Boys- think adrenal tumor, Leydig cell tumors (asymm testic enlargement), CAH, BhCG tumor, mccune albright syndrome, testotoxicosis
Girls- adrenal tumors, virilizing ovarian tumors (arrhenoblastomas), feminizing ovarian tumors, nonclassic CAH, Mccune
Mccune Albright syndrome
bony changes (polyostotic fibrous dysplasia)
skin finds- coast of Main cafe-au-lait spots
Endocrinopathies- PPP or hyperthyroidism
Enlarged gonads but secretion of sex steriods indep of HPGA
MGMT- look at fsh, lh, tetoterone, b-hcg
Testoxicosis
Rare, testes enlarge bilaterally indep of HPGA
B-Hcg tumors
Unique to boys
In chest, pineal gland, gonad, or liver (heaptoblastoma)
B-hcg crossreacts w/ Lh, binds too, enlarges testes slightly
Stim Leydig cells and secreting androgens
Delayed puberty
Boys- no testic enlarge by 14, girls no breast by 13, no period by 14
Hypogoadotropic hypogonad inactive hypothal/pit, low FSH/LH, low test/estriol, flat stim test
Hypergonadotropic gonadism- end-organ dysfn, FSH/LH HIGH, low test/estriol (hypothal/pit are fine)
Why hypogonadotropic hypogonad?
Constitutional delay of puberty more common in boys, often fam hx, often w/ delay of growth too
Chronic disease- IBD, arex, renal fil, heart failure
Hypopit- brain tumors
Primary hypothyroid
Prolactinoma
Genetic- Kallman (no gonadotropin or smell), Prader-Willi, Lawrence-Moon-Biedl (obesity, retinitis pigmentosa, hypogonad, polysyndactyly)
Why hypergonadotrop hypogonad?
Chromosomal disorers-
XXY klinefelter in boy,
in girl thing turner/gonadal dysgen
Autoimmune like hashimotos thyroid or addison’s disease
Eval w/ cbc, esr, t4, testosterone, estradiol, fsh, lh, prolactin, bone age
Normal sex differentiation
First 7 week s= undiff gonadal tissue, male sex diff = active, female = absent
Male sex diff
SRY gene on short arm of Y chromo, by 9 weeks diff gonads into fetal testes, makes testosterone + AMH
Internal ducts- test from fetal Leydig cells => development of wolffian ducts (epididymis, vas def, seminal vesicles0 and AMH from sertoli - inhib mullerian development
External genitalia- conversion of testoerone to DHT by 5a reductase in skin of external genitalia. DHT = penile enlargement, scrotal fusion + masculinization of external Genitalia (complete at 12 weeks, then penis keeps growing)
Female sex diff
W/out SRY, gonads become ovaries
Internal ducts- not testicular tissue, no AMH, so wolffian ducts regress, development of mullerian vag 1/3, uterus, fallopian tubes
External genitalia- do not virilize b/c no destosterone/DHT. so labia, clit, lower vag
DDX in undervirilized male (pseudohermaphrodie genetic 46XY/ambigious/1/2testes palpable)
- Inborn testosterone synthesis error
- Gonadal intersex- Mixed gonadal dysgen- 45XO 46XY mosaicism, ambigious genitalia, testis/vas defens one side = streak gonad on other, maybe fallopian tubes
- True hermaphroditism- 46XX usually, but can be xy, have both ovary/testicular gonadal tissue
- Partial androgen insensitivity- some peripheral androgen resistance, defective binding (testic feminization have total insensitivity, look like normal pheno females)
DDX of ambigious genitalia in virilized female- XX genetic w/ ambiguous genitalia/no palpable gonads
- CAH from 21 ydroxylase deficiency = most common cause, 11-BOH and 3hDH also
- Virilizing drug used by momma in prego
- Virilizing tumor of momma in prego
Eval of ambig genitalia
Careful history of fam hx, maternal drugs etc
P.e- gonads? swelling? bifid scrotum, labial fusion, urogen sinus, hypospadias?
Increased BP suggests CAH w/ 11BOH deficiency
Decreased BP suggests adrenal insufficiency
Chromo studies
Radiograph pelvic u/s genitogram
Lab studies- mal DHT/testosterone..if test low, inborn error of anrogen synth maybe? female pseduoherm- serum electro, testost, CAH looking
MGMT- focus on gender assignment asap, uroglogy, hormonal
Adrenal Function
Cortex makes lots of steroids
Medulla makes catecholamines
Major pathways - mineralocorticoids, glucocorts and androgens
Glucocort/androgen synth regulated by neg fb loop via ACTH, but mineralocort = RAAS, indep of it/ACTH
Primary adrenal insufficiency
Destroeyd cortex or enzyme deficiency
Signs of cortisol def (arex, weak, hyponat, hypotn, increased pigment over scars) + aldo deficiency (FTT, salt craving, hyponat, hyperK)
Addion’s disease, CAH, adrenoleukodystrophy (x-linked recessive
Secondary adrenal insufficiency
Any process interfering with CRH in hypothal or ACTH from pit (prob at hypothal or pit level)
Serum potassium may be normal b/ cno aldo deficiency
Examples = pit tumors, carnipharyngioma, langerhands cell histiocytosis. Most common = iatrogenic, after long term glucocort dose
Congen Adrenal Hyperplasia
Enzyme def => underprod of cortisol/aldo + build-up precursors shunt into another path +> more ndrogens
21 Hydroxylase = 90%, three options.
1. Classic salt wasting- girls w/ ambig genitalia, 1-2 weeks boys + girls = FTT, vom, electrolytes eird (cortisol and aldo down)
2. Simple virilizing CAH = only glucocorticoid path is affected => only cortisol def, so ambig genitalia for girls, boys present a 1-4 years w/ tall stature, advancing bone age, pubic hair, penile enlargement
3. Nonclassic CAH- late onset w/ very mild cortisol def, no mineralocorticoid. At 4-5 yo, girls w/ premature adrenarche, clitoromeg, acne, rapid growth, hirsut, infert. Boys = premature adrenarche, rapid growth, premie acne
11B hydroxylase- 5% hypertensive hypokal
3b DHD- salt-wasting crises, glucocorticoid def, ambig genitalia (early block in all three paths)
Dx workup
21hydroxylase def = increased 17 hydroxyprog 17 OHP
11bhydrox def= increased levels of 11-deoxy specific compound S
3B hydroxysteroid DH def = increased DHEA and 17 hydroxypregnelone
MGMT of CAH
Give cortisone to suppress ACTH production so androgen production down but not interfering w/ proper growth
If aldo deficient, mineralocorticoid replacement (fluorocortisol), to normalize plasma renin activity
F/u essential and growth velocity, physical exam, bone age, lab test monitored carefully, compliance super impt, need stress dose steroids sometimes
Acquired Adrenal Inusfficeincy
Why? chornic supraphysio steroid use, or Addisons disease from Ai destruction of adrenal cortex maybe w/ hashimoto’s thyroiditis, T1DM (type I polygland syndrome), or hypoparathy/mucocandidiasis (type II polygland)
Or b/c acute adrenal hemorrhage in neonate/septicemia, or Waterhouse-Friderichsen syndrome
Eval/MGM of acquired AI
High index of suspicison, look a hx of AI or prior steroid use, do ACTH stim tst (measure adrenal cortisol reserve). If blunted response, indicates primary renal insuff. Compare baseline cortisol to 1 hour after.
Random cortisol level not hlepful, but >20 ug/dl in stress excludes AI
Mgmt- Adrenal crisis = EMERGENCY, prompt IVF + 5% dextrose in normal saline + hyponat/prevent hypoglycemia
Give steroids till stabilized
Glucocorticoid excess
Clin- poor growth w/ delayed bone age, central obesity, moon facies, nuchal fad pad, easy bruising, purplish striae, HTN, glucose intol
Why? Iatrogenic from chronic steroid use for asthma/IBG/JRA, or Cushing from benign/malig adrenal tumors, or Cushings disease = ACTH prod by pit tumor
Lab eval- elevated free cortisol in 24 hr urine, absence of expected cortisol suppression in dex supp test.
Cortisol excess can be confused w/ OBESITY. But obesity = fast growth + advanced bone age
T1DM Etiology
Why? Genetic factors, n pattern, 95% HLA haplotypes DR3/4, monozygotics w/ 50% concord, dizyg 30%, _ viral infections maybe (enterovirus and rubella), early intro of cows milk?
AImmune- islet antibodies in 85% pts, ICA in asx pts 10 years before sx, also antibodies against insulin + against glutamic acid GAD, up to 10% pop may have ICA..so nee a combo of factors
More T1DM
Clin fx- polyuria/dip/nocturia, enuresis, then wl/vom/dehy
DKA can be initla pres in 25%, younger pts go more quickly to DKA
Girls w/ monilial vulvovaginitis, adolescents may present in puberty w/ hormones antagonistic to insulin (GH and sex steroids)
Dx- hyperglycemia w/ random bs above 200 + polyur/dip/wl/ornocturia
MGMT of T1DM
Insulin- short acting, int, long, very long
Combo the insulins, or use insulin pup
Monitor- Daily blood glucose before meals + at bedtime
Hgb1Ac- check every 3 months
Wtch for hypogly, have glucagon on hand
Honeymoon period- after initial dx, 75% patients have temp progressive reduction in insulin reqs b/c transient recovery of islet cells => insulin, but only lasts up to 1-2 years
Diet- follow ADA diet, edu/close follow up
Long term- Microvasc, macrovasc in adulthood, DKA when ill
Somogyi phenomenon
evening dose of insulin too high, hypoglycemia in early morning, then epinephrine and glucagon come out..so then high BG/ketones in mroning
tx = lower bedtime insulin dose
T2DM
2-3% of all kids with diabetes, 10x increase b/c of obesity. insulin resistance
VERY strong herediatry comp, peripheral tissue resistance to insulin + decline in insulin secretion
Clin fx- Asx to mild DKKA (less common), obesity, aanthosis nigricans
MGMT with oral hypoglycemic agents if moderate, insulin if high blood sugar
DKA pathophys
Hypergly > 300 mg/dl with ketonuria + serum bicarb < 7.3
Pathophys = insulin deficiency, diminished glucose substrate at cellular level, body make more glucose, hypergly -> osmotic diuresis, and counter reg stress hormones released (glucagon, epi, cortisol, Gh)…
glucagon => free fatty acids convert into ketone bodies (acetone, acetoacetae, b hydroxybutyrate), lipolysis = DKA
MGMT DKA
Present w/ vom/poly/dip/dehydration for MILD,
Severe= severe dehydration, ab pain (like appendicits), rapid and deep respirations (Kussmaul), coma. Fruity breath
Lab = AGMA, hypergly/glucosurine, ketonemia/ketonuria, hyperkal from mets acid (moves out of cells)
MGMT = fluid/electrolytes w/ isotonic saline, gradually decline osmolality (minimze cerebral edema risk), K repletion w/ K acetate/phosphate serum might be normal but cells arent. K phosph => increased 2,3, DPG, shifts o2 dissociation to R, more available for tissues
Regular insulin - continuous infusion
Goal- stop hepatic glucose, reverse ketogen, shut down release of counter-reg hormones, enhance peripheral uptake
Compx- cereral edema 6-12 hours or 24 hours rarely, if younger than 5 pt, faster than 100 mg/dl drop in glucose, or more than 4L /m2 /24 hours, 70% death, also severe hypoK and hypocalc
Thyroid physiology
HPT regu by feedback between t3, t4, TRH and TSH
T4/t3 bind TBPs like TBG and TBPA
unbound = biologically active
Hypothy
Subotimal growth, goiter, myxedema/puffy/orange skin, amenn/oligomenn
Congenital hypothy- why?
Most common mets disorder, 1 in 4K
Why? Thyroid dysgen = most common- 2/3 w/ absent thy gland, 1/3 ectopic anywhere from tongue to chest
Thyroid dyshormonogen- inborn errors of hormone synth, present recessive w/ goiter.
Pendred = organification defect, has sensorineural hearing loss
PTU in pregnancy -> transient hypothy in newborn
Maternal autoimmune can => transient b/c antibodies cross placenta
Clin fx/MGMT hypothy
Asx at birth, unremarkable, but over 2 years
1. prolonged jaundice, poor feeding, lehargy, constipation
large anterior/post fontanelles, protruding tongue, umbilical hernia, myxedema/mottled skin, hypotherm, elayed neuro, poor growth
MGMT- immediately give l-thyroxine! dont delay till symptoms appear bc neuro sequelae :(
Dx- neonatal screening measure TSH, increased TSh = first sign of failure, low t4, or antithyroid antiboides (TAPAB)
Hashimotos CLT (chronic lymphocytic thyroiditis
Most common cause of acquired hypothyroid, more in girls
Etio- thyroid autoabs, thyroid cell cytotox
Clin fx- asx, goiter, short stature, transient hyperthy (Hashitoxicosis)
MGMT- l-thyroxine
Hyperthy Clin Fx
Lid lag exophthalmos
Thyroid enlarged/smooth
Tachy/palpiations/warm flushed skin
Vitiligo/alopecia = maybe autoimmune polyendo (Addisons/DM)
CNS shows nervousness and fine tremors w/ hx of fatigue/school concentration
Pubertal- delayed menarche/gynecomastia in boys
Graves disease
Diffuse toxic goiter, autonomous production of excessive hormone by gland b/c of TSH-like stim ab
Most common cause of hyperthy in childhood, more females
Why? strong genetics, TSI (IgG), see increased t3/t4 with supressed TSH
MGMT = atithryoid PTU and methimazole. Both inhib synth, and PTU also stops periph t4=>t3 convert, first-line
Subtotal thyroidectomy if antithy fails, or radioactive iodine if med compliance issue
Physiology of Calc/Vit D Mets
Vit D/PTH release ca and phosph from bone
PTH maintains normal ca level by releasing calcium from bone/resorbing ca from kids
PTH releases phosph from bone and excretes from kids
K1a hydroxylase vit D made in kidney, converts 25 oh vit D into active 1,25 OH vit D (stim by PTH)
GI - ca absorbed in intestine due to 125OH vit D
Hypocalcemia
less than 8.0 mg, or ionized less than 2.5
Pseudohypo if look slow b/c serum albumin low..so check ionized
Fx- tetany, carpopedal spasm (ankles/wrsts, periph motor nerves too excitable0, laryngospasm, paresthesia, seizures in younger kids
Why hypocalc?
Early neonatal = transient, maybe w/ premature/IUGR/asphyxia/infants of DM mothers, or hypomag => hypocalc
Late neonatal > 4 days =
1. HypoPTH- low calc, elevated phopsh, from asx maternal hyperPTH, mom’s high ca crosses plac, suppresses PTH
2. Di George
3. Hyperphophatemia => hypocalc b/c binds to calcium from uremia or too much formula
Childhood hypoca
1) PTH Failure (genetic/digeorge) 2. PseudohypoPTH- rare dom disorder w/ PTH resistance, short stature, developmental delay, high PTH 3) hypomag- low mag => low ca b/c interferes w/ PTH 4) Vit D def => hypocalc w/ low phosph
Hypoca eval/mgmt
Lab eval- serum ionized ca, phosph, mag
EKG w/ prolonged QT found in hypocalcemia
PTH level to see hypopth vs. pseduo, vit d level, look for rickets
MGMT- milkd asx no tx, if <8, correct to avoid CNS hyperexcitability
Ca supp- oral therapy if no seziures, IV calc gluc if pts sx, 1,25 vit D calitriol if chronic hypoPTH
Rickets why/how
Vit D def => down bone mineralization, normal bone matrix
Why? exclusively breastfed with no sunshine, fad diets, anticonvulsants (phenytoin/phenobarb), interfere w/ liver mets, renal/hep failure
How? Vit D def, GI disorders w/ malabsorb, nutritional, Defective Mets from renal/hep fail => renal osteodystropy
Fx- first 2 years or in adolescence (rapid growth phase), wrists, knees, ribs, knobby, bowed, short, rachitic rosary (costochondral junctios prominent), craniotabes (pingpong ball skull?), bossing, delayed suture closue
X-ray shows end of metaphysis cuppedfrayed, widened,
Lab= low serum phosph, low/normal serum ca, elevated alk phosph, elevated PTH
Vitamin D dep rickets
VERY RARE, autosomal recessive
enzyme def in kidneys of 1ahydroxylas, no 1,25 oh vit D
Increased PTH, low vit D levels, low ca, low phopsh, up alk phosph
Vitam D resistant rickets
Familial hypophophatemia
Most comon form, X-linked dom disorder
Renal tubular phsophorus leak, low serumphosph level
Rickets w/ normal calcium + low phopshorus
Bowed legs but no tetany
Oncogenous rickets
Phsophate-deficient form w/ bone/soft tissue tumor, consider if bone pain/myopathy
Diabetes Insipidus
Can’t concentrate urine b/ low ADH or kidneys not responding
ADH increases permeability of renal collecting ducts to water to water
Central = ADH deficient, b/c of Autoimmune, trauma, hypothal tumors (craniophar, glioma, germinoma), langerhans histiocytosis, granulomatous disease, vasc, genetic
Nephrogenic = x-linked recessive
Fx- nocturia, enuresis, poor weight gain, polydip, polyu
Eval/Dx- if thirst working and kid drinking, electroytes normal, otherwise hypernatremic dehydration w/ inappropriately dilute urine..up serum osmolality
Early morning urine specimen w/ SG > 1/018 r/o DI
Water deprivation test in hospital- rising serum osmolality and low urine! MRI of head, bone scan for Langerhands,
MGMT = DDAVP
Hypoglycemia
Less than 40, whole blood less than 45
Recog early in babies b/c brain needs it!
Newborns/ infants = lethargy, myoclonic jersk, cyanosis, apnea, seizures
Older = like adults, tachy, diaphor, tremors, h/a, seziures
Neonatal hypogly
Transient @ screening for high risk infants- preemie, asphyxia, SGA, fetal distress, LGA
Inappropriate hyperinsulinism in SGA/diabetes mothers
Persistent = hypogly for mroe than 3 days-
1. hyperinsulin from nesidioblastosis (islet hyperplasia) or beckwith-wiedemann- vmegaly of things
2. hereditary defects in carb mets (galactosemia/glycogen storage) AA mets issues
3. hormone deficienes- gGH/cortisol deficiency
Congen hypopit if neonate w/ hypogly, microphallus = midline defects
Hypogly in infancy/kids
Uncommon in older kids, ddx
- Ketotic hypogly- late in morning in presence of ketonuria + low insulin level, can’t adapt to fasting state, kids are thing and hypoglycemic after infection
- Ingestion of alcohol (deplete cofactors for gluconeo), oral hypoglycemic
- IEM
- Hyperinsulinism
