Peds Endocrinology - Endo Flashcards
Growth
Measures
- Length/Height
- Weight
- Head Circumference
Tracking
- Growth Charts
- CDC – birth to 36 mo, 2+, based on actual growth of US kids
- WHO – birth to 5, based on growth of breastfed infants
- Recommend: WHO for 0-2; CDC thereafter
- Available in 5-95%ile, 3-97%ile, various genetic conditions, various languages
Short Stature
History
- Heights of parents and siblings
- Onset of menarche/puberty in parents
- Nutritional history
- Psychosocial history
- PMH: birth weight, congenital infections, syndromes, chronic illnesses, medications (steroids, esp)
PE
- Stadiometer for accurate height measurement; plot
- Weight for height – usually normal in endocrine; reduced in malnutrition
- Congenital abn; dysmorphic
- GI, Cardiac, Pulm, Renal, Goiter
- Pubertal development
- Girls – Consider Turner syndrome (XO): Karyotype or FSH/LH after 9 or 10 yrs reveals ovarian failure
Work Up
- Calculate growth in cm/yr over the longest period available
- Lower limit of normal 4 cm/yr in 5-10 year olds
- Look at growth chart – is growth parallel to normal?
Bone Age
- Normal for chronological age: Familial or primordial short stature
- Delayed and normal growth velocity (>4cm/yr): Delayed for age, but appropriate for height = Constitutional delay
- Delayed and slow growth velocity (<4cm/yr): Assess thyroid (T4/TSH); Consult Ped Endocrine
Target (Midparental) Height
Mean parental height
+ 6.5 cm for boys
- 6.5 cm for girls
Most children achieve adult height within 8 cm of this
Familial Short Stature
- Short parents and relatives
- Usually normal birth weight and length
- Growth velocity decelerates in 1st 2 years as they approach genetic percentile
- Growth normal, parallel by 2-3 yrs
- Skeletal maturation and timing of puberty consistent with chronologic age
- Final height short, but appropriate for family
Constitutional Growth Delay
-Parents not necessarily short
-May have “late bloomer” family history
-Growth pattern similar to familial short stature
BUT
-Delayed skeletal maturation
-Delayed onset of puberty
-Growth continues beyond peers
-Ultimate height appropriate for target height
Growth Hormone Deficiency
- Decreased growth velocity AND delayed skeletal maturation
- May be isolated or accompany other pituitary hormone deficiencies
- May be congenital, genetic, or acquired
- Idiopathic most common 1:4000
- Infants normal birth weight, sl reduced length
- May present with hypoglycemia with central adrenal insufficiency
- May present with micropenis with gonadotropin deficiency
- Isolated GHD and hypopituitarism may present later infancy or early childhood
-Exam :Because GH promotes lipolysis – truncal adiposity
Lab
- GH is VARIABLE, pulsatile – big overlap between normal and GHD
- Serum IGF-1 (Insulin-like growth factor) gives estimate of GH secretion and action
Because tests are difficult to interpret, GH trial can clarify
- 0.15-0.3mg/kg/week SQ divided and given 7 days/week recombinant GH
- SEs – rare benign intracranial hypertension (optic disc), SCFE (slipped capital = knee pain)
Growth Hormone Uses
- Growth Hormone Deficiency
- Chronic renal failure
- Turner Syndrome
- Prader-Willi and Noonan’s syndromes
- Small for Gestational Age who fail catch-up by age 4
- Idiopathic Short stature >2.25 SDs below norm for age
- Controversial
- Gets an extra 5-7 cm
Small for Gestational Age/Intrauterine growth retardation (IUGR)
- Definition: below 10th %ile for population’s birth-weight/gestational age
- Includes both constitutionally small and intrauterine growth retardation
Due to
- Poor maternal environment
- Intrinsic fetal abnormalities (primordial short stature)
- Congenital infections
- Fetal malnutrition
- If no intrinsic abnormalities – catch up growth in first 3 years
- Earlier insult – less likely full catch up
- Normal skeletal maturation
Turner Syndrome
- Chromosomal abnormality (XO)
- Micrognathia
- Webbed neck
- Low posterior hairline
- Edema of hands and feet
- Multiple pigmented nevi
- Increased carrying angle
- FOR SOME, SHORT STATURE is the only obvious manifestation
Psychosocial Short Stature
- Growth retardation associated with emotional deprivation
- Undernutrition probably also contributes in some
Other symptoms
- Bizarre eating and drinking habits
- Bowel and bladder incontinence
- Social withdrawal
- Delayed speech
- Growth hormone is diminished, but replacement not helpful
- Foster home or change in psychosocial environment is effective
Tall Stature
- Excessive GH rare
- Functioning pituitary adenoma
- Leads to gigantism if epiphyses are open
- Leads to acromegaly if epiphyses are closed
Diagnosis
-Elevated GH and IGF-1 and Failure of GH suppression with oral glucose tolerance test
Fetal Development of Thyroid
- Fetal thyroid synthesizes thyroid hormone by 10th week of gestation
- Fetal pituitary-thyroid axis independent of maternal because TSH does not cross the placenta
- BUT maternal thyroid hormone does in small part
- At birth, TSH surge within 60 minutes
- Thyroid hormone increases as a result
- TSH decreases to normal by a few weeks
- Normal TSH surge can produce false-positive newborn hypothyroidism screen if collected on 1st day of life
Congenital Hypothyroidism
- Incidence 1:3000 – 1:4000
- Untreated – SEVERE NEUROCOGNITIVE IMPAIRMENT
- Most case sporadic hypoplasia or aplasia of thyroid gland
- Numerous other causes
- Antithyroid drugs PTU and methimazole cross the placenta
- Hyperthyroid moms on these drugs may have goiterous hypothyroid babies
- Severe maternal iodine deficiency – both mom and baby T4 deficient, baby with irreversible brain damage
- Even if thyroid is absent, appear normal at birth
- Gain weight normally first few months
- But intellectual impairment is progressing unnoticed
Symptoms, if present
- Jaundice, associated with unconjugated hyperbilirubinemia
- Thick tongue, Hypotonia, Large fontanelles
- Constipation, Umbilical hernia, Hoarse cry, Dry skin
- Newborn screen essential to early intervention
- Confirm abnormals immediately with T4 and TSH
- Rx: Levothyroxine 10-15 mcg/kg/day
Juvenile Hypothyroidism
- Short stature, abnormal weight gain
- Delayed epiphyseal development
- Delayed closure of the fontanelles
- Retarded dental eruption
- Skin: Dry, thick, scaly, coarse, pale, yellow, cool, or mottled
- Hair: Dry, coarse, or brittle; lateral thinning of the eyebrows
- Hypotonia, slow relaxation component of DTRs (ankles)
- Transient deafness
- Delayed puberty
- Occasionally pseudopuberty and galactorrhea in girls
- Rx: Levothyroxine 75-100 mcg/m2/day
Conditions associated with Acquired Autoimmune Hypothyroidism
Low threshold for thyroid screening
- Down
- Turner
- Celiac
- Vitiligo
- Alopecia
- T1DM
Disorders of Sexual Development
Ambiguous Genitalia at birth: Consult
- Ped Endocrine
- Urology
- Psychiatry/psychology
- Genetics
- Complete family history – afffected offspring, neonatal deaths, consanguinity, maternal exposures
- Exam – dysmorphic features, hyperpigmentation of nipples/scrotum/labia,
- Workup – Karyotype and FISH studies for SRY (Transcription factor on Y chromosome)
Gonadal Dysgenesis
- XY dysgenesis
- Mosaicism involving the Y, XX sex reversal, true hermaphoditism
- Streak gonads (don’t produce testosterone)
- Normal female external and internal genitalia
- Present as girls with delayed puberty and amenorrhea
- 45, X/46, XY mosaicism
- Normal male external genitalia
- OR ambiguity due to abnormal testicular formation
Disorders of Steroidogenesis
- Missing enzymes in the biosynthesis of testosterone
- Lack of virilization in XYs
- Gonads and adrenals share common enzymes, so
- Cortisol and aldosterone production also affected
- In XX, most common is congenital adrenal hyperplasia
- Secondary to 21-hydroxylase deficiency
- Classic salt-losing form
- Genital ambiguity but normal uterus and ovaries
Precocious Puberty in Girls
- Definition: Onset of secondary sexual characteristics before 8 in Caucasian, 7 in African-American and Hispanic
- 6-8 years: Most benign, slowly-progressing
- Age of pubertal onset advanced by obesity
Central GnRH-dependent precocious puberty
- Activation of the normal hypothalamic GnRH pulse generator
- Generally idiopathic
- May be due to CNS abnormality
- Hypothalamic hamartomas, CNS tumors, cranial irradiation, hydrocephalus, trauma
- Breast development – pubic hair - menarche
Peripheral (GnRH-independent)
- Caused by ovarian or adrenal tumors, ovarian cysts, CAH, exposure to exogenous estrogen
- Estrogen excess sx – breast development, vag bleeding
- Adrenal tumors – signs of adrenarche – pubic hair, axillary hair, acne, body odor
- All have accelerated growth and skeletal maturation
- Temporarily tall, but end up shorter due to rapid maturation
Work up -Bone age – If advanced, further work up -Estradiol – reveals excess estrogen -Andrenarche signs – androgen levels and 17-hydroxyprogesterone If central precocious puberty -MRI brain (not usually necessary in 6-8 year olds) If peripheral -US of ovaries and adrenal glands
Treatment
- GnRH analogues for central
- Variable for peripheral, dependent on cause
Benign Variants of Precocious Puberty
Benign Premature Thelarche (breast development)
- Girls younger than 2
- Isolate, no other signs or growth concerns
- Usually present since birth and waxes and wanes
- Unilateral or bilateral
- Probably from greater ovarian hormone production in infancy
- Treatment: Reassurance
Benign Premature Adrenarche (pubic/axillary hair, acne, body odor)
- Normal linear growth, normal bone age
- Timing of true puberty unaffected, no treatment required BUT
- 15% at risk for PCOS
Delayed Puberty in Girls
- No pubertal signs by 13 or no menarche by 16
- Failure to complete pubertal development to Tanner V within 4 years of onset
- Most common cause – constitutional growth delay
- Timing of menarche is commensurate with BONE AGE, not chronological age
- Anything that delays growth (GHD, hypothyroidism)
- Work up: Start with H&P, bone age, growth records
- Primary amenorrhea – pelvic US
Precocious Puberty in Boys
- Secondary sexual characteristics before age 9
- Less common than in girls
- More likely to have CNS abnormality
- Increased linear growth rate + pubic hair
- Testicular size
- Enlarged – central precocity
- Small - Gonadotropin independent, like CAH
Work up
- Elevated testosterone levels – don’t differentiate source
- Central – cranial MRI
- Peripheral – CAH work up
Delayed Puberty in Boys
- No secondary sex characteristics by age 14 OR
- More than 5 years have elapsed since onset of puberty without completion of genital growth
- Most common cause: Constitutional growth delay
- Hypogonadism : Primary – absence or destruction of testicular tissue, Klinefelter Syndrome (47, XXY)
- Central – pituitary or hypothalamic insufficiency: Prader-Willi
- Work up – H&P, growth analysis, bone age
Congenital Adrenal Hyperplasia
Pathophysiology
- Autosomal recessive mutations in the enzymes of adrenal steroidogenesis in the fetus, causes
- Abnormal cortisol biosynthesis
- Increased ACTH secretion, which results in
- Adrenal hyperplasia
- Increased adrenal hormone precursors – conveyed thru androgen pathway, resulting in
- Increased androgen production
- Increased pigmentation scrotum, labia majora, nipples (excessive ACTH secretion)
Symptoms and signs
Girls
-Genital virilization
-Pubic hair (before age 2), acne, deep voice
-Labial fusion, Urogenital sinus, Enlargement of the clitoris
-Signs of adrenal insufficiency (salt loss) in 2nd or 3rd week
Boys
-Salt-losing crisis in infant males
-Isosexual precosity in older males with infantile testes
Both
-Increased linear growth and advanced skeletal maturation
-tx: Replace deficient steroids with smallest dose needed to produce normal growth