Normal growth In Utero mediated by?
Post-natal grown mediated by?
In Utero - Insulin
Post-Natal - GH
(GH deficient born normal and dont see problems until later on in life)
What are the 3 tall stature Overgrowth Syndromes and Buzzwords with each?
1) Beckwith-Wiedemann = Macroglossia, Hypoglycemia, Macrosomia
- Abdominal wall defects and Ear Creases
- Wilms Tumor
2) Sotos Syndrome = Cerebral Gigantistm - BIG HEADS! normal adult height
3) WEavver's Syndrome
fetal and childhood overgrowth dysmorphism
When do you need to evaluate short kids?
Crossing percentiles or below 3rd percentile
outside genetic expecations
What are some genetic diseases to consider in kids w/ short stature?
PRADER WILLI or Russel-silver, Osteogenesis imperfecta, Down syndrome, Noonan
Inborn errors of metabolism
What is Turner Syndrome? Features?
Chromosome 45 X
Webbed neck, broad spaced nipples and increased carrying angles of arms
Low posterior hair line
Lymphedema of feet
SHORT and break off around puberty
What is PRader-Willi Syndrome?
Deletion or Uniparental Disomy of Chromosme 15q
Hypotonic at birth, FTT, delayed motor skills, low muscle mass
ages 3-4 Hyperphagia but don't grow
Hypogonadism and developmental delay
Define "small for gestational Age" and what is significant about that
Birthweight or length at least 2 SD below mean for Age
Most catch up by ages 2-3 and don't have GH resistance
Children can be GH resistant BUT will grow in response to higher than normal doses of GH bc releated to haplotype variations in IGF1 receptor
Increased risk for Insulin resistance, T2DM and obesity
What is LAron Dwarfism? Treatment?
GH resistance bc of receptor
Tx: skip a step and just give IGF1
What are SHOX genes? PResentation? What other conditions is it implicated in?
Short Stature Homeobox containing genes - isoform of homeodomain TF for limb development
Implicated in Turner Syndrome, Idiopathic short stature, Leri-Weill Dyschondrosteosis
SEE MADELUNGS DEFORMITY
What are the clinical features of PEdiatric GH deficiency? Causes/Associations?
Diagnosis and Treatment?
Normal size at birth but growth failure after 6 months (nutrition responsible for growth before that)
See Excessive ADiposity +/- Hypoglycemia
Cause: Either Idiopathic OR Multiple Putuitary hormone deficiency - seen w/ cleft palate, midline defect, craniopharyngioma etc
DX: GH STIMULATION TEST - stimulate w/ Arginine, Clonidine, Hypoglycemia and should reach > 10 GH
Treatment - GH!!!
What do you see in adults w/ GH deficiency?
poor lean body mass
GH treatment may increase risk of Cancer and Diabetes
Ages and staging for normal puberty?
Girls breast buds ages 8-13 and Menarche within 5 years
Boys - testicular enlargement > 9 yo and by age 14
Girls can be earlier especially AA girls
Tanner Staging based on breast/testicular size and pubic hair
BONE AGE EVALUATIONS!
Differential Dx for delayed puberty in a girl? Which occurs at what age?
Delayed = no onset by 13 yo
Primary Gonadal Failure - Estradiol low but LH/FSH high
Hypothalamus problems - anorexia or Kallmans!!!
Androgen Insensitivity Syndrome
Androgen Insensitivity Syndrome presentation
Testes make testosterone but no receptors for them
sometimes breasts develop
Whats the DDX for delayed puberty in boys?
Primary Gonadal Failure:
- Kleinfelter syndrome 47 XXY
- XY gonadal dysgenesis / cryptochordism
Hypothal probs- Kallman's Syndrome
Treatment of delayed puberty
Treat underlying problem
start low dose E in girls then increase and start cycling
start low dose T in boys and increase over time
What is True Precocious Puberty?
True PP: Gonadotropin dependent - breasts + Pubes or Testes + pubes
Thelarche - BReasts only
Adrenarche - pubes only
Workup that you need to do for preciocious puberty?
BONE AGE!!! determine how aggressive process is
Determine if Gonadotropin-depend or independent
via 8 am labs or GnRH stimulation test
What are some causes of Central Precocious Puberty?
10x more common in females and 85% idiopathic
Males - TUMOR RISK!!!! 20%
CNS lesions - trauma, hypothalamic Hamartoma, cranial irradiation, Craniopharyngioma, meningitis
sometimes Peripheral PP can push pituitary to start central PP (ex high adrenal levels then hypothal responds)
Causes of Gonadotropin-Independent Peripheral PP in girls?
Exocenous sex steroids
Ovarian Hypersecretion --> McCune-Albright Syndrome
McCune Albright Syndrome - Presentation and caues
TRIAD: Ovarian hypersecretion, Polyostotoic Fibrous Dyspasia, Coast of Main Cafe Au Lait spots (dont cross midline and has jagged edges)
caused by Gs protein mutations so genes always on
Thyroid and ovary thing that they are on without stimulation
What happens in precocious puberty due to Hypothyroidism?
ELEVATED TSH!!! -lkike ALOT
Subunit same as FSH to appears to ovaries like FSH and triggers secretion of Estrogen
does NOT spontaneously reverse when treat hypothyroid and TSH goes down
What are some Gonadotropin-independent Peropheral causes of PP in boys?
Testicular Hypersecretion - Familial Male PP where LH receptors always on
Ectopic tumor - Androgen of HCG secreting
Treatment of PP in Gonadotropin-dependent process?
GnRH Agonists to block receptors and no pulsing action (which normally release is puslatile) and stops pituitary signals
Leuprolide Depot - IM shot q3 months
Histrelin implant that lasts 1 year
Treatment of PP in Gonadotropin Independent processes?
Stoired blockers - Ketoconazole
ARBs - Spironolactone
ERBs - Tamoxifen
Premature Thelarche - causes? Dx?
can be idiopathic and benign in toddler girls
LOOK AT BONE AGE!!!
PRemature Adrenarche - causes?
NON-CLASSICAL CAH = higher androgens
also see hirsuitism, acne, and altered fertility
could also be adrenal or gonadal tumor
What are the 4 disorders of sexual development we discuss? Which is most common?
1) CAH - MOST COMMON
2) Ovotesticular DSD - both ovarian and testicular tissue - True HErmaphroditism
3) Androgen Insensitivity Syndrome - complete and partial
conmplete - female phenotype
Partial - ambiguous
4) 5-alpha reductase deficiency and T cant be converted to DHT
- typically overcomes in puberty and then get virilization so girl becomes boy at puberty
MOst common CAH? Presentation?
21-Hydroxylase most common form of CAH
Salt-wasting bc hypo-Aldo
Virilization of XX females
46XX females look virilized 46XY males have typical phenotype but adrenal crisis
What is Thyroid Congenital Hypothyroidism? Presentation?
occurs AT BIRTH so do newborn screening
Thyroid helps cns myelination and so if dont have it then get Mental retardation
Large Fontanelle and Coarse features
What do you see in DiGeorge's Syndrome?
Thymic Aplasia - infections
Deletion on Chromosome 22