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
type 1 DM tx: pharm
-NEW ONSET:
-Long-acting insulin analog – glargine (Lantus or Basaglar), detemir (Levemir), or degludec (Tresiba) – for “basal” level of insulin
-Rapid-acting analog – lispro (Humalog), aspart (NovoLog), or glulisine (Apidra) – for correction/mealtime dosing
-Above usually suffices for first 12-24 hours preceding systematic diabetes education
-Dose adjusted frequently during first week
-Start low and titrate up based on frequent blood-glucose monitoring or CGM levels
-Higher initial daily dose for ketosis, infection, obesity, or steroid treatment
-Also varies with age, pubertal status, and severity of onset
-Dose peaks approx 1 week after dx and decreases slightly with waning of glucotoxicity and appetite
-Approx 3-6 weeks after dx -> most kids experience initial remission – “honeymoon period” – temporary decrease in insulin dose during this period is necessary to avoid severe hypoglycemia
-LONG TERM INSULIN:
-Rapid-acting insulin to cover food intake or correct high blood glucose and a long-acting insulin to suppress endogenous hepatic glucose production
-used in emergency or before meal
-Regimen using insulin pump or basal-bolus MDI
-3-4 injections (boluses) of rapid-acting before meals and 1-2 injections of long-acting analog per day
-Dose of premeal based on anticipated carbohydrate content + additional insulin for high blood glucose
type 1 DM tx: insulin pump tx
-Receives wireless transmission of test results from glucose meters/CGM
-Patient/caregiver must still manually enter amount of carbohydrate
-Delivers variable, programmed basal rate that corresponds to the diurnal variation in insulin needs
-Pre-pubertal: Higher rate early in night
-Post-pubertal: Higher rates early in morning – “dawn phenomenon”
-Lower rates set for physical activity
-User initiates bolus doses before meals and to correct hyperglycemia
-Stores suggested doses from previously entered parameters – may override suggestion
type 1 DM tx: automated insulin delivery (artificial pancreas)
-Uses CGM sensor input to adjust insulin infusion using control algorithms
-Some systems can react to predicted, rather than current, glucose levels
-Automatic, variable basal dosing, based on CGM input
-Automated correction boluses
-Customization of glycemic targets
-Still requires wearer to give boluses before meals based on carbohydrate consumption
type 1 DM tx: exercise, sick day management
-Exercise:
-Careful monitoring of glucose before, during, and after exercise
-Reducing amount of insulin active during and after exercise
-Reducing bolus, stopping basal, raising glycemic targets
-Extra carbs in forms of snacks
-Sick Day Management
-Must check blood glucose or urine ketone levels during any illness when fasting blood/CGM > 240 mg/dL or randomly measured glucose > 300 mg/dL
-Usually additional 10-20% of total daily insulin dosage given SC as rapid-acting or regular insulin every 2-3 hours until glucose normalizes
type 1 DM: complications: hypogylcemia
-MC acute complication of T1D
-Blood glucose level < 70 mg/dL
-Hunger, weakness, shakiness, tachycardia, sweating, drowsiness, headache, irritability, and confusion
-Severe: LOC, seizures, brain damage, death
-Tx:
-Mild: 10-15 grams of rapidly-absorbed glucose (4 ounces juice, soda, milk), wait 10-15 minutes, repeat if still low
-Moderate (conscious, but incoherent): Half tube of concentrated glucose (Insta-Glucose/cake frosting) between gums and lips and stroking throat to encourage swallowing
-Severe: Glucagon injections
type 1 DM: complications: DKA
-Venous blood pH < 7.30, or bicarbonate < 15 mEq/L and blood B-hydroxybutyrate > 3 mmol/L, or moderate to large ketonuria
-Mild: 7.2-7.29/10-14 mEq/L
-Moderate: 7.10-7.19/5-9 mEq/L
-Severe: < 7.10/<5 mEq/L -> ICU monitoring
-Abdominal pain, nausea, vomiting (flu-like, gastroenteritis, acute abdomen); mild-moderate dehydration (5-10%); Kussmaul respirations; progressively somnolent and obtunded
-Tx:
-Restoration of fluid volume
-Inhibition of lipolysis and return to glucose utilization (insulin)
-Replacement of electrolytes (sodium and potassium)
-Correction of acidosis (spontaneous correction)
type 1 DM complications: hyperosmolar hyperglycemic state (HHS)
-Hyperglycemia > 600 mg/dL and hyperosmolarity > 320 mOsm/kg
-Typically, little to no ketosis and no acidosis
-Profound mental status changes (combativeness to coma), seizures, rhabdomyolysis
-Similar treatment to DKA with close ICU monitoring
-Longer term complications: HTN, lipid abnormalities, nephropathy, retinopathy, neuropathy (more so with T2D)
hypocalcemia
-Imbalance of calcium absorption, excretion, and distribution
-Causes: Nutritional calcium deficiency, hypoparathyroidism, vitamin D deficiency, hyperphosphatemia, activating mutation of calcium-sensing receptor, hypomagnesemia, hypoalbuminemia (nephrotic syndrome), drugs (diuretics, CTX, transfusion products)
-Tetany, photophobia, blepharospasm, and diarrhea
-Tetany: Numbness, muscle cramps, twitching of extremities, carpopedal spasm, and laryngospasm
-Chvostek sign: Tapping of face in front of ear causes facial spasms
-Trousseau’s sign: Inflation of BP cuff above systolic BP causes carpal spasm
-Other symptoms: Headache, vomiting, increased ICP, papilledema; behavioral changes, irritability, LOC, convulsions
-Early infancy: Respiratory distress
-ECG may show prolonged QTc
hypocalcemia dx and tx
-Labs- Serum calcium, phosphate, magnesium, intact PTH, 25-hydroxyvitamin D (occurs in liver), 1,25-dihydroxyvitamin D (occurs in kidney), calcium-creatinine ratio
-Imaging: Skeletal changes similar to/associated with Rickets
-Tx:
-Acute/Severe Tetany
-10% calcium gluconate infusion: 1-2 mL/kg over 5-10 minutes with cardiac monitoring (followed by oral/continuous infusions if hypocalcemia persists in 2-3 hours)
-Maintenance
-Diet: Calcium supplementation at 50-75 mg/kg/day divided TID/QID
-Vitamin D supplementation (ergocalciferol, cholecalciferol)
-Monitoring at 1-3 month intervals to ensure adequate therapy and prevent hypercalcemia/-uria and vitamin D toxicity
hypercalcemia
-Serum calcium > 11 mg/dL (normal 8.8-10.2 mg/dL)
-Hypotonicity, muscle weakness; apathy, mood swings, behavioral changes; N/V, abdominal pain, constipation, weight loss; hyperextensibility of joints; HTN, cardiac irregularities, bradycardia, and shortening of QT interval; calcium deposits in cornea/conjunctiva
-Increased calcium/phosphate excretion: Polyuria, polydipsia, calcium phosphate deposition in renal parenchyma or calculi
-Changes in skeleton: Bone pain, osteitis fibrosa cystica, subperiosteal bone absorption (distal clavicles, phalanges), absence of lamina dura around teeth, spontaneous fractures, moth-eaten appearance of skull
hypercalcemia tx
-Symptomatic:
-Vigorous hydration with normal saline
-Loop diuretic (with caution)
-Glucocorticoids or calcitonin
-Bisphosphonates now more commonly used in refractory pediatric cases
-Chronic: Varies based on cause
-Resection of parathyroid adenoma
-Secondary hyperparathyroidism (from CRD): Phosphate binders, calcitriol (suppress PTH secretion)
-Malignancy treatment
precocious puberty in girls (know this)
-onset of secondary sexual characteristics before 8yo in Caucasian girls
-7 years for African American and Hispanic girls
-Central PP: Idiopathic or 2ndary to a CNS abnormality that disrupts prepubertal restraint on the GnRH pulse generator
-Abnormalities include hypothalamic hamartomas, CNS tumors, cranial irradiation, hydrocephalus, and trauma
-Peripheral PP (GnRH-independent): Ovarian/adrenal tumors, ovarian cysts, late-onset congenital adrenal hyperplasia, McCune-Albright syndrome, or exposure to exogenous estrogen
-starts with breast development, followed by pubic hair growth and menarche
-PPP:
-!Ovarian cysts/tumors usually with signs of estrogen excess: Breast development, vaginal discharge, vaginal bleeding
-!Adrenal tumors and CAH with signs of androgen excess: Pubic hair, axillary hair, acne, and increased body odor
-know the difference
-Accelerated growth/maturation; skeletal maturation quicker than linear growth = compromised adult stature
precocious puberty in girls dx and tx
-Labs:
-CPP: Random FSH and LH concentrations may confirm diagnosis
-PPP: LH response to GnRH is suppressed by autonomously secreted gonadal steroids
-Estradiol levels, androgen levels (testosterone, androstenedione, dehydroepiandosterone sulfate), and 17-hydroxyprogesterone should be measured
-Imaging:
-Bone age (radiographs of L hand and wrist)
-CPP: MRI of brain for CNS lesions
-PPP: Imaging of ovaries and/or adrenal gland
-Tx:
-CPP: GnRH analogues that downregulate pituitary GnRH receptors
-Leuprolide (IM injections), histrelin subdermal implant (replaced annually)
-After stopping therapy, pubertal progression resumes, and ovulation and pregnancy have been documented
-PPP: Dependent on underlying cause
-Regardless of cause, attention to the psychological needs of the patient and family is essential
delayed puberty in girls
-No pubertal signs by age 13 or menarche by 16 years
-MCC is constitutional growth delay
-Primary hypogonadism: Primary abnormality of the ovaries
-MCC is Turner syndrome
-Other causes: Gonadal dysgenesis, galactosemia, autoimmune ovarian failure, radiation, and CTX
-Central hypogonadism: Hypothalamic or pituitary deficiency of GnRH or FSH/LH
-Functional (reversible): Stress, undernutrition, prolactinemia, excessive exercise, or chronic illness
-Permanent: Congenital hypopituitarism, CNS tumors, or cranial irradiation
delayed puberty in girls: clinical eval
-H&P, BONE AGE:
-Low bone age (< 12 years):
-Short stature, normal growth velocity > constitutional growth delay
-Growth rate abnormal > evaluation for causes of growth delay warranted
-Bone age > 12 years:
-FSH/LH distinguishes between primary ovarian failure (elevated FSH/LH) and central hypogonadism (low FSH/LH)
-Karyotyping for elevated gonadotropins
-Cranial MRI for central
-GIRLS W/ ADEQUATE BREAST DEVELOPMENT AND AMENORRHEA:
-Progesterone challenge to determine if sufficient estrogen is being produced and to evaluate for anatomical defects
-Producing estrogen: Withdrawal bleeding 5-10 days of PO progesterone -> MCC of amenorrhea in this case is PCOS
-Estrogen-deficient/anatomical defect: No bleeding
delayed puberty in girls: tx
-Replacement therapy in hypogonadal: Estrogen alone and lowest available dosage
-Doses gradually increased every 6 months, then 18-24 months later; progesterone added cyclically or continuously
-Unopposed estrogen = endometrial hyperplasia
-Stimulates growth rates, close growth plates, and promotes bone mineralization
precocious puberty in boys
-2ndary sexual characteristics before 9yo; also either central or peripheral
-Pubic hair > penile enlargement > scrotal maturation, axillary hair, voice deepening, increased growth velocity
-CPP: Testes enlarge
-PPP: Testes remain much smaller than expected for degree of virilization
-Labs:
-Elevated testosterone levels
-CPP: High LH/FSH
-PPP: Low LH/FSH -> CAH: Adrenal androgens and 17-hydroxyprogesterone will be elevated
-Imaging:
-Bone age
-CPP: Brain MRI
-PPP: Rule out hepatic, adrenal, and testicular tumors
-Tx:
-CPP: GnRH analogues/treatment of underlying cause
-PPP: Steroid synthesis blockers (ketoconazole) or combination of antiandrogens (spironolactone) and aromatase inhibitors (anastrozole or letrozole) that block conversion of testosterone to estrogen
delayed puberty in boys
-No 2ndary sexual characteristics by 14yo or if >5 years since first signs of puberty w/o completion of genital growth
-MCC is constitutional growth delay
-Hypogonadism may be primary or central
-Primary: Testicular insufficiency/anorchia, Klinefelter syndrome/sex chromosome anomalies, enzymatic defects in testosterone synthesis, inflammation/destruction of tests following infection, autoimmune disorders, radiation, trauma
-Central: Deficiencies in pituitary/hypothalamic function (same as girls)
-H&P, bone age:
-Low bone age relative to chronological age + normal growth velocity (prepubertal) > constitutional growth delay
-Bone age > 12 years
-Elevated LH/FSH: Primary hypogonadism or testicular failure
-Low LH/FSH: Central hypogonadism
-Tx:
-4-6-month course of low-dose depot testosterone to promote virilization and possibly “jump-start” endogenous development
