exam 2 - Endocrinology Flashcards
inborn errors of metabolism: galactosemia
-Autosomal recessive, incidence of 1:40,000 live births
-Caused by a near total deficiency of galactose-1-phosphate uridyltransferase > accumulation of galactose-1-phosphate > hepatic parenchymal disease and renal Fanconi syndrome
-Neonates: Vomiting, jaundice (direct and indirect), hepatomegaly, liver insufficiency (progressive cirrhosis) after initiation of milk feeding
-Increased risk of speech and language deficits, progressive intellectual disability, tremor, ataxia, and ovarian failure
-Cataracts from untreated cases
-Death occurs within 1 month without treatment (often from E. coli sepsis)
inborn errors of metabolism: galactosemia: dx and tx
-Dx:
-Infants receiving foods containing galactose: Liver dysfunction (PT prolongation), proteinuria, and aminoaciduria
-Elevated galactose-1-phosphate in RBCs
-When suspected, galactose-1-phosphate uridyltransferase should be assayed in RBCs or GALT sequencing pursued
-Newborn screening demonstrating enzyme deficiency in RBCs or increased serum galactose for institution of early treatment
-Tx:
-Galactose-free diet as soon as possible (lifelong)
-Calcium and vitamin D replacement
-DEXA scans
-Monitoring of speech and language development
-Screening for hypergonadotropic hypogonadism during adolescence
inborn errors of metabolism: phenylketonuria
-Autosomal recessive trait, 1:10,000 live Caucasian births
-Disorder of amino acid metabolism caused by decreased activity of phenylalanine hydroxylase (converts phenylalanine to tyrosine)
-Normal diet: Elevated phenylalanine levels > severe intellectual disability!, hyperactivity, seizures, light complexion, eczema
-Dx based on elevated plasma phenylalanine and elevated phenylalanine/tyrosine ratio in a child with a normal diet
-neurotoxic
-Tx: Restriction of phenylalanine as early as possible
inborn errors of metabolism: maple sugar urine ds
-Autosomal recessive
-Deficiency of the enzyme complex that catalyzes the oxidative decarboxylation of the branched-chain ketoacid derivatives of leucine, isoleucine, and valine > accumulated ketoacids cause sweet odor, leucine and corresponding ketoacid cause CNS dysfunction
-Normal at birth, 2-3 days old > irritability/feeding issues, 1 week > seizures and coma (most die within first month of life without intervention)
-Dx: Marked elevation of branched-chain amino acids, genetic testing for confirmation
-Tx:
-Leucine! restriction and avoidance of catabolism
-Infant formulas deficient in branched-chain amino acids must be supplemented with normal foods for growth
-Very high leucine levels require hemodialysis
-Liver transplant corrects the disorder
disturbances of growth
-Disturbances of growth and development are the most common problems evaluated by a pediatric endocrinologist
-Height velocity is most critical parameter in evaluation of growth
-Persistent increase or decrease in height percentiles between 2 years of age and onset of puberty indicates abnormal growth and always warrants evaluation
-Substantial deviations from target height (midparental) may indicate underlying endocrine/skeletal disorders
-Height potential is determined largely by genetic factors
-Target height = Mean parental height (+ 6.5 cm for boys, - 6.5 cm for girls)
-Skeletal maturation/bone age
short stature
-Important to distinguish normal variants of growth (familial short stature and constitutional growth delay) from pathologic conditions
-Endocrine: Maintenance or increase in BMI percentiles
-Pathologic: Low growth velocity, significantly short for their family
-Chronic illness, nutritional deficiencies: Poor linear growth, inadequate weight gain and low BMI
normal short stature: familial short stature (test)
-takes on average of mom and dad (they are both short)
-Normal birth weight and length
-Linear growth velocity decelerates until nearing genetically determined percentile
-Once target percentile reached, child resumes normal linear growth parallel to growth curve
-Skeletal maturation and timing of puberty consistent with chronologic age
-Child grows along own growth percentile and final height is short, but appropriate for family
-growth curve is normal (decelerates briefly) then goes back to normal but just lower than average
-Ba(bone age) = Ca (chronological age) > Ha (height age)
normal short stature: constitutional growth delay (test)
-late bloomers
-born normal ht and wt
-Decline in linear growth velocity, followed by maintenance of normal growth velocity prior to puberty
-Follow growth percentile below what is expected based on parental heights, delayed skeletal maturation compared to chronologic age, delayed onset of puberty
-Late puberty: Exaggerated short stature
-Growth continues beyond the time the average child stops growing, final height appropriate for target height
-17-18yo growth spirt
-Ba = Ha < Ca
short stature: growth hormone deficiency
-Decreased growth velocity and delayed skeletal maturation in absence of other explanations
-May be isolated or coexist with other pituitary hormone deficiencies
-May be congenital, genetic, or acquired
-Idiopathic GHD is MC form
-Infantile GHD: Normal birthweight and slightly reduced length, hypoglycemia (with adrenal insufficiency), micropenis (with gonadotropin deficiency), and conjugated hyperbilirubinemia
-Diagnosis typically combination of clinical and laboratory evidence
-Labs: Serum IGF-1 gives reasonable estimations of GH secretion and action in adequately nourished child
-All patients diagnosed with GHD should have MRI of hypothalamus/pituitary gland to evaluate for tumor
disproportionate short stature: achondroplasia
-dwarfism
-MC form of short-limbed dwarfism
-Autosomal dominant transmission, mutation in fibroblast growth factor receptior-3 gene (80% of time random mutation)
-Upper arms and thighs are proportionately shorter than forearms/legs
-Skeletal dysplasia suspected based on abnormal stature, disproportion, dysmorphism, or deformity
-Height measurements for screening
-Bowing of extremities, waddling gait, limitation of motion of major joints, relaxation of ligaments, short stubby fingers, frontal bossing, midface hypoplasia, otolaryngeal dysfunction, moderate hydrocephalus, depressed nasal bridge, lumbar lordosis
-Imaging:
-Short, thick, tubular bones and irregular epiphyseal plates
-Ends of bones are thick, with broadening and cupping
-Delayed epiphyseal ossification
-Narrowed spinal canal (diminished growth of pedicles)
-Tx: Growth hormone
short stature: SGA/IUGR
-SGA (birth weight and/or length below 3rd percentile for population’s birth weight-gestational age relationship) infants include constitutionally small infants and infants with IUGR
-Most with mild SGA/IUGR exhibit catch-up growth during first 3 years of life
-Have skeletal maturation that corresponds to chronologic age
Short Stature Associated with Syndromes
Turner, Down, Noonan, and Prader-Willi
Psychosocial Short Stature
-Growth impairment associated with emotional deprivation
-Change in environment results in improved growth and improvement of GH secretion, personality, and eating behaviors
short stature work up
-guided by H&P:
-Radiographs of left hand/wrist (bone age)
-Bloodwork: Serum electrolytes (Ca/P - renal tubular ds/metabolic bone disease), CBC (chronic anemia, leukocyte markers of infection), TFTs (T4 and TSH), BUN/Cr, ESR, IGF-1 and/or IGFBP-3 (children younger than 4 years/malnourished)
-Urinalysis
-Stool exam for fat/TTG (malabsorption or celiac disease)
-Karyotyping/Noonan syndrome testing
short stature tx
-Growth Hormone Therapy
-FDA-approved for children with GHD, growth restriction associated with CRF, Turner/Prader-Willi/Noonan syndromes, SGA without catch-up growth by age 2, SHOX gene mutations, those with idiopathic short stature whose current height is 2.25 SDs below normal for age
-Subcutaneous, 6-7 days/week with total weekly dose of 0.15-0.47 mg/kg (dont know)
hypothyroidism
-Congenital occurs in 1:3000-1:4000 infants, mostly sporadic from hypoplasia or aplasia of thyroid gland/failure to migrate to normal anatomic location
-Acquired usually is the result of chronic lymphocytic (Hashimoto) thyroiditis
-Congenital: Most newborns appear normal, jaundice may be present
-Acquired: Poor linear growth, delayed bone age/dental eruption, skin changes (dry, coarse, brittle), hair loss, lateral thinning of eyebrows, neurological findings (hypotonia, slow relaxation of DTRs), physical and mental sluggishness, nonpitting myxedema, constipation, cold temperature intolerance, bradycardia, delayed puberty
-Enzymatic defects/Hashimoto’s: Thyroid enlargement
hypothyroidism dx and tx
-Dx:
-Primary: TSH elevated, total T4/FT4 normal/decreased -> Autoantibodies to thyroid peroxidase and/or thyroglobulin possible
-Central: TSH normal, total T4/FT4 decreased
-Imaging: Thyroid imaging unnecessary, bone age delayed, cardiomegaly common
-Screening: All newborns screened shortly following birth, treatment started asap (otherwise, assoc with intellectual impairment!!)
-Tx:
-Synthetic T4/levothyroxine (75-100 mcg/m^2/day) with monitoring of TFTs for response
hyperthyroidism
-Most cases due to Graves disease (antibodies directed at TSH receptor, which stimulates TH production)
-Other causes: Thyroiditis, thyroid nodules, TSH-producing tumors, McCune-Albright syndrome, exogenous TH excess, acute iodine exposure
-F > M, occurs during adolescence, course may be cyclic
-Poor concentration, hyperactivity, fatigue, emotional lability, personality disturbance, insomnia, weight loss, palpitations, heat intolerance, increased perspiration, increased stool frequency, polyuria, and irregular menses
-Tachycardia, HTN, increased pulse pressure, tremor, proximal muscle weakness, moist/warm skin, accelerated growth/development, diffuse/firm goiter, thyroid bruit/thrill, exophthalmos
-Thyroid storm: Fever, cardiac failure, emesis, and delirium > coma/death
hyperthyroidism dx and tx
-Dx:
-TSH suppressed; T4, FT4, T3, and FT3 are elevated
-TSH receptor-binding antibodies are usually elevated
-Presence of TSI or thyroid eye disease confirms Graves
-Radioactive iodine uptake increased in Graves, decreased in subacute/chronic thyroiditis; autonomous hyperfunctioning nodules take up iodine (hot nodules)
-Advanced bone age, !!premature fusion of cranial sutures!!, osteoporosis (long-standing)
-bad for brain growth!!!
-Tx:
-Avoidance of strenuous physical activity due to concern for cardiovascular instability
-B-Adrenergic blocking agents: Atenolol (B1-specific/cardioselective), propranolol (decreases conversion of T4 to active T3; used in severe cases/thyrotoxicosis)
-Antithyroid agents (methimazole)
-Frequently used in initial management of childhood hyperthyroidism
-Interfere with TH synthesis
-Take several weeks to generate a clinical response
-Initial dose: 10-60 mg/day (0.5-1 mg/kg/day) QD (until FT4 and T4 have normalized and signs/symptoms subside)
-Maintenance of 10-15 mg/day x 2 years with trial of medication thereafter
-If medical therapy unsuccessful, more definitive therapy, such as thyroidectomy or radioiodine ablation considered
diabetes mellitus
-Chronic hyperglycemia caused by defects in insulin secretion, insulin action, or a combination of the two
-Type 1 diabetes (T1D) is characterized by insulin deficiency and is the MC type of DM in those < 20 years of age
-In the U.S., T1D affects ~ 1.6 million people (190,000 < 20 years)
-European > African American > Hispanic; lowest in Asians and Native Americans
-Increased thirst (polydipsia), increased urination (polyuria), and weight loss
-Divided into T1a (autoimmune – 95% of cases) and T1b (idiopathic)
-Type 2 diabetes (T2D) is characterized by resistance to action of insulin
-More common in youth of ethnic and racial minorities – Native American population
-Typically dx in those > 40yo who are obese and initially not insulin dependent
-Increased prevalence of childhood obesity > increased frequency in older children
-Other risks: Female sex, poor diet and sleep, low socioeconomic status
-Monogenic forms of diabetes are caused by single gene defects affecting insulin signaling/secretion (1-2% of childhood diabetes)
-Cystic Fibrosis-Related Diabetes: 20% of adolescents with CF causing insulin resistance
type 1 diabetes mellitus: pathogenesis
-Caused by a combination of genetic factors and unknown environmental factors
-Autoimmune destruction of the insulin-producing B cells of the pancreatic islets begins months to years before onset of clinical symptoms > marked by presence of autoantibodies to islet cell autoantigens (measured in blood)
-Staging of T1D based on concentration of autoantibodies
-Insulin production (fasting/stimulated C-peptide levels) is usually low at diagnosis
->90% of children carry at least 1 of the 2 high-risk HLA halotypes; 40% dx prior to 10 years of age have both
->60 non-HLA genetic variants have also been implicated
-Assoc autoimmune ds: Hashimoto thyroiditis, celiac disease, Addison disease, RA, lupus, psoriasis, scleroderma, vitiligo, dermatomyositis, autoimmune hepatitis, autoimmune gastritis, pernicious anemia, and myasthenia gravis
type 1 DM: dx and tx
-Polyuria, polydipsia, and wt loss
-Heavy diaper in a dehydrated child w/o diarrhea should always raise alarm
-Signs often missed by parents and PCPs
-Frequency of DKA in U.S. kids with newly dx T1D has not decreased in past 20 yes and is ~ 40-50%
-Labs:
-HbA1c does not rule out dx (less sensitive than blood glucose)
-Tx:
-goals -> prevention of acute/long-term complications by reducing chronic hyperglycemia while maximizing quality of life
-Aim for lowest HbA1c that can be sustained w/o severe hypoglycemia or frequent, moderate hypoglycemia
-Pt and family education
-Psychosocial care
-Diet/exercise: At least 60 mins of daily aerobic exercise recommended with bone/muscle strength training at least 3 days/week
type 1 DM: home blood glucose monitoring
-Monitor blood glucose at least 4x/day -> 7-10 checks for optimal management
-Higher monitoring frequencies/CGM -> assoc with lower HbA1c levels
-CGM now routinely available
-Subcutaneous glucose levels measured every 1-5 minutes from sensor placed under the skin (replaced every 6-10 days)
-Transmitter sends glucose levels from sensor to receiver that can be inside an insulin pump, smartphone, or separate receiver device
-Low and high blood glucose alarms can be set
-Subcutaneous glucose levels may lag behind blood glucose levels in times of rapid change, so finger sticks still recommended for treatment and monitoring of recovery from hypoglycemic states
type 1 DM tx: nutritional management
-Monitoring carbohydrate intake is a key component
-Insulin pump and multiple daily injection therapy usually utilize carbohydrate counting in which grams of carbohydrate to be eaten guides insulin dose
-Exchanges/choices may be taught to estimate amounts of foods that = 15 g serving of carbohydrate
