Delayed Puberty/Precocious Flashcards
infant with Y chromosome
expression of transcription factor SRY initiates cascade gene expression that directs formation of testes without SRY ovaries develop
Sexual differentiation is complete at
12 weeks
disorders of sexual development
arise from 3 main process; gonadal differentiation, steroidogensis, androgen action
DSD
often visible during newborn period; some arise during abnormal pubertal development
Gonadal Differentiation
testes/ovaries don’t develop-ambiguous genitalia or sex reversal
Deficiency of 21 hydroxylase
enzyme in cortisol and aldosterone- overproduction of adrenal androgens- most common form of congenital adrenal hyperplasia
Disorder of androgen action
androgen insensitivity syndrome (AIS) caused by inactivating mutation in androgen receptor gene- individuals have normal appearing female external genitalia with a short vagina, absent mullerian structures, absent wolffian structures, gonads located either intra abd or in inguinal canal, tx surgery for inguinal hernia reveals testis in hernia sack
Precocious puberty in girls- definded
pubertal development occurring below the age limit set for normal onset of puberty
Precocious puberty in girls- dx
if onset of sex characteristics occurs before 8 in caucasian girls, 7 years in AA and hispanics
Precocious puberty in girls- prevalence
more common in girls than boys, age of onset may be advanced by obesity
Precocious puberty in girls is either
Central or Peripheral
Central PP
activation of hypothalamic GnRH pulse generator, increase in gonadotropin secretin, and resultant increase in production in sex steroids; sequence of hormonal/ physical events is identical to normal puberty, generally idiopathic or secondary to CND abn that disrupts prepubertal restraint on GnRH pulse generator
Peripheral PP
LH response to GnRH stimulation is suppressed by feedback inhibition of the hypothalamic-pituitary axis
Girls with ovarian tumors/cysts
estradiol levels with be markedly elevated
Girls who present with pubic and/or axillary hair but no breast development
obtain androgen levels and 17 hydroxyprogesterone
Precocious puberty in girls- S&S
begins with breast development- pubic hair growth and menarche
accelerated growth and skeletal maturation- may temp be tall for age b/c skeletal maturation advances at more rapid rate than linear growth, final adult stature may be compromised
Precocious puberty in girls- Labs
estradiol level- draw to r/o ovarian tumor or cyst
if bone age is advanced- further lab tests are warranted
random FSH/LH may still be prepubertal range- stimulation of GnRH
Precocious puberty in girls- causes Central
Idiopathic, CNS abn- acquired, congenital, tumors
Precocious puberty in girls- causes Peripheral
congenital adrenal hyperplasia, adrenal tumors, McCune- Albright Syndrome, Familial male limited gonadotropin independent precocious puberty, gondal tumors, exogenous estrogen, ovarian cyst, HCG secreting tumors
Imaging- Precocious puberty in girls
xray of hand and wrist to determine skeletal maturity
Central PP- Imgaing
MRI of brain to evaluate for CNS lesions
IF labs suggest PP- Imaging
US of ovaries and/or adrenal gland
Central PP- Tx
tx with GnRH analogues that down-regulate pituitary GnRH receptors- decrease gonadotropin secretion- Leuprolide (IM once a month) histrelin (sub-dermal implant); projected final heights often increase as a result of slowing skeletal maturation- after stopping tx pubertal progression resumes- ovulation and pregnancy are possible
Peripheral PP-TX
dependent on underlying cause- cyst intervention normally not necessary, surgical resection and chemo indicated for rare adrenal ovarian tumor
Bengin Variants of precocious puberty
Benign Premature Adrenarche and Benign premature thelarche
Benign Premature Adrenarche
early development of pubic hair, acne, body odor, normal linear growth and non or no minimal bone age advancement; lan tests: differentiate benign premature adrenarche from late-onset CAH and adrenal tumors; 15% of girls with BPA will go on to develop PCOS
Benign Premature Thelarche
most commonly in girls younger than 2 years; presents with isolated breast development without other signs of puberty; typically presents since birth, often waxes and wanes in size, unilateral or bilateral, ex parental reassurance regarding self-limited nature of condition; observations of child every few months is indicated; onset of thelarche after 36m or in association with other signs of puberty- REQUIRES REFERAL
Delayed Puberty in girls required evaluation if??
no puberty sign by 13yr or no menarche by 16
Primary Amenorrhea
absence of menarche
Secondary Amenorrhea
absence of menses for at least 6mo after regular menses has been established
Delayed Puberty in girls- most common cause
constitutional growth delay
Delayed Puberty in girls- Causes
Growth pattern
Short stature, normal growth velocity, delay in skeletal maturation
Delayed Puberty in girls- Causes
Timing of Puberty
commensurate to the bone age not the chronologic age
Delayed Puberty in girls- Causes
Other
hypothyroidism and GHD
Delayed Puberty in girls- Causes
Primary hypogonadism
primary abn of ovaries, most common is turner syndrome- missing/abn secondary x chromosomes; signs of adrenarche is generally present
Delayed Puberty in girls- Causes
Central Hypogondism
hypothalamic or pituitary deficiency of GnRH or FSH/LH can be functional (reversible) caused by stress, undernutrition, prolactinemia, excessive exercise, chronic illness, signs of adrenarche are generally present.
Clinical evaluation- Pertinent hx- Delayed Puberty in girls
whether and when puberty started, level of exercise, nutritional intake, stressors, sense of smell, symptoms of chronic illness and family hx of delayed puberty
Clinical evaluation- Past growth records- Delayed Puberty in girls
assess appropriateness of height/weight velocity
Clinical Evaluation- Physical exam- Delayed Puberty in girls
body proportions, breast/genital development, and stigmata of turner syndrome
Delayed Puberty in girls- When should pelvic exam or pelvic us be considered
Primary amenorrhea
Clinical Evaulation- Bone age Xray- Delayed Puberty in girls
obtain this first!
Delayed Puberty in girls- Bone age xray- Bone age attained <12 year with pubertal onset
focus on finding cause of bone age delay, if short stature and normal growth velocity then Constitutional growth delay is likely
Delayed Puberty in girls- Bone age xray- Abnormal growth rate
Eval for causes of growth delay is warranted- measure of FSH and LH may not be helpful in the setting of delayed bone age since prepubertal levels are normally low
Delayed Puberty in girls- Bone age xray- Bone age >12 years + minimal /no signs of puberty on physical exam
Obtain FSH/LH
Primary ovarian failure- increased FSH/LH
Central Hypogonadism- decreased FSH/LH
Elevated gondotropins- karyotype should be performed to evaluate for turner syndrome
Central Hypogondaism- Clinical Evaluation-
Low gonadotropin levels- Determine if functional or permanent hypogondism
Labs- Identify chronic disease & hyperprolactienemia
Imagining- Cranial MRI may be helpful
Adequate breast development + amenorrhea
Progesterone challenge to determine if sufficient estrogen is being produced and to evaluate for anatomical defects
Progesterone Challenge-
Producing estrogen- withdrawal bleeding occurs 5-10 days of oral progesterone
Estrogen-deficient/Anatomical defect- have little to no bleeding, evaluation is similar to those with delayed puberty
Most common cause of amenorrhea with sufficient estrogen is PCOS
Delayed Puberty in girls- Treatment
Estrogen alone at lowest dose available- oral or topical
Gradually increase dose every 6months
18-24hours- add progesterone
May change to COC or patch if desired
Why is progesterone therapy needed- Delayed Puberty in girls-
counteract effects of estrogen on the uterus which can promote endometrial hyperplasia
Why is the estrogen component necessary - Delayed Puberty in girls-
required to promote bone mineralization and prevent osteoporosis
Precocious Puberty in Boys- Defined
secondary sexual characteristics appear before age 9
Precocious Puberty in Boys- Prevalence
frequency of central PP is much lower in boys than girls, boys are much more likely to have associated CNS abn and require medial attention
Precocious Puberty in Boys
several types of fonadotropin-independent (peripheral) PP occur in boys
Precocious Puberty in Boys- Dx testing- Central PP
Cranial MRU should be obtained to evaluate for Cranial abn
Precocious Puberty in Boys- Dx testing- Peripheral PP
lab studies are not consistant with CAH: imaging may be useful to detect hepatic, adrenal and testicular tumors.
Precocious Puberty in Boys- S&S
Appearance of pubic hair- most common sign
exam of testes is critical component of evaluation
Precocious Puberty in Boys- S&S- Central Precocity- testes size
testes enlarge >2cm
Precocious Puberty in Boys- S&S- Gonadotropin- independent causes- testes size
usually remain small
Precocious Puberty in Boys- S&S- Tumors of the testes- testes size
asymmetrical or unilateral testicular enlargement
Precocious Puberty in Boys- Lab Studies- testosterone
increase testosterone concentrations confirm the presence of puberty but doesn’t differentiate the source
Precocious Puberty in Boys- Lab Studies- LH/FSH
Central PP- pubertal range
Peripheral (gonadotropin-independent)- decreased
Precocious Puberty in Boys- Lab Studies- Leuprolide stimulation test (GnRH analogue)-
distinguish central from gondaotropin- independent puberty- as the LH response with differ
Precocious Puberty in Boys- Lab Studies- abn plasma adrenal androgens-
Peripheral PP due to congenital adrenal hyperplasia- CAH
Precocious Puberty in Boys- Lab Studies– Serum B HCG concentrations
PP + testes enlargement but suppressed gonadotropins after GnRH analogue testing- HCG- producing tumor (CNS dysgerminoma or hepatoma)
Precocious Puberty in Boys- Lab Studies- Genetic Testing
dx other forms of Peripheral PP- Familial Male PP & mcCune ALbright Syndrome
Delayed Puberty in Boys- Definded
no secondary sexual characteristics by 14 years of age or if >5yr have elapsed since the 1st sign of puberty without completion of genital growth
Delayed Puberty in Boys- Most common cause
Constitutional growth delay
True Hypogonadism can be
Primary or central
Primary Hypogonadism
due to absence, malfunction, or destruction of testicular tissue
Causes of primary hypogonadism
Ancorchia, klinefelter syndrome, Enzymatic defects in testosterone synthesis, inflammation or destruction of the testes after infection, autoimmune disorders radiation trauma or tumor
Central Hypogonadism
due to pituitary of hypothalamic insufficiency
Central Hypogonadism causes-
May accompany multiple pituitary hormonedeficiency or due to isolated hypogonadotropic hypogonadism with Kallmann syndrome or without abn in smell
Other causes of Hypogonadism-
Hyperprolactinemia, isolated LH or FSH deficiency, destruction lesion in or near the anterior pituitary, infection, prader willi syndrome and Laurence moon syndrome
Functional or reversible gonadotropin deficiency-
Chronic illness, malnutrition, hyperprolactinemia, hypothyroidism, anorexia nervosa, excessive exercise- athlete triad
Genetic forms of idiopathic hypogonadotropic hypogonadism
reversible after tx with gonadal steroids
Delayed Puberty in Boys- Clinical evaluation- patient history
whether and when puberty started, testicular descent abn, symptoms of chronic illness, nutritional intake, sense of smell and family hx of delayed puberty
Delayed Puberty in Boys- Clinical evaluation- Physical Exam
body proportions, height and weight, pubertal stage, testicular location, size, and consistency, symmetric testes >2.5 cm or >4ml indicate on of puberty
Delayed Puberty in Boys- Clinical evaluation- xray
left wrist to assess bone age- this should be the 1st step in evaluating a boy with delayed puberty; if bone age is delayed relative to chronological age and growth velocity is normal for a prepubertal boy- constitutional growth delay is the most likely cause
Delayed Puberty in Boys- Lab studies-
LH and FSH
increase gonadotropins for bone age- primary hypogonadism or testicular failure
decreased gonadotropins for bone age- possible central hypogonadism- requires further evaluation to assess for pituitary hormone deficiencies, chronic disease, undernutrition, hyperprolactinemia, CNS abn
Delayed Puberty in Boys- Treatment- Simple Constitutional delay + troubled by stature and or prepubertal apppearance
4-6m of low dose depot testosterone (50-100mg/m) - Promote virilization and possibly jump-start their endogenous development
Delayed Puberty in Boys- Treatment- adolescent boys + permanent hypogonadism
tx with depot testosterone in initiated with 50-100mg IM each month- increase over 3-4 years to adult dose 200mg every 2-3 weeks,
Alternative- Gel- applied daily
Cryptorchidism
Undescended testes
Cryptorchidism- Prevealance
affects 2-4% of full term newborns- up to 30% if preterm infants- after 6m spontaneous descent is very rare- intervention is considered beginning at this time
Cryptorchidism- Major risks
infertility ( 33%- 66% after unilateral and bilateral) and testicular malignancy- 5-10% higher than normal chance
Cryptorchidism- Etiology
Unkwn,
Cryptorchidism- Predispose
abn in hypothalamic pituitary gondola axis, intrinsic testicular development defects, and androgen biosynthesis or receptor defects
Cryptorchidism- Labs- Infants 2-6 m
measure LH/FSH, inhibin B and testosterone to determine if testes are present
Cryptorchidism- labs after 6m
obtain HCG stimulation test to confirm the presence or absence of functional abdominal testes
Cryptorchidism- dx imaging
US- CT scan- MRI- detect testes in inguinal regions
Cryptorchidism- diff dx
During PE- cremasteric reflex may cause testis to retract in inguinal canal or abd to prevent retraction place fingers across abd ring and upper portion of inguinal canal, examination in squatting position or in warm bath may be helpful- no treatment for retractile testes
Cryptorchidism- Dx b/l normal male only if
possibility child is a fully virilized female with potentially fatal salt-losing CAH HAS BEEN RULED OUT
Cryptorchidism- Treatment
surgical orchidopexy should be performed if descent has not happened by 6-12 months
Gynecomastia
common- self limiting condition that occurs in up to 75% of pubertal boys
more common in obese boys
occurs in make hypogonadism (klinefelter syndrome) and SE of some meds
Gynecomastia- patho
typically resolves within 2 years but may bot totally resolve if the degree of gynecomastia is extreme >2 cm of tissue
Gynecomastia- Treatment
anti-estrogen and/or aromatase inhibitors if started early
surgical
