Transcript puberty

Puberty Disorders
Dr. Sarar Mohamed
MBBS, FRCPCH(UK), MRCP (UK), MRCPCH(UK), DCH(Ire), CCST(Ire), CPT(Ire), MD
Consultant Pediatric Endocrinologist & Metabolic Physician
Assistant Professor of Pediatrics
King Saud University
Definition of puberty
• What is puberty?
– It is the transitional period of development during
which an individual mature from childhood to
physical, psychosocial, sexual & reproductive
maturity.
PUBERTY
Gonadal maturation with acquisition of
secondary sexual characteristics and
associated growth spurt
FERTILITY AND FINAL HEIGHT
Endocrine Regulation
• Negative feedback:
– Inhibits GnRH from
hypothalamus.
– Inhibits anterior pituitary
response to GnRH.
• Inhibin secretion inhibits
anterior pituitary release of
FSH.
• Female:
– Estrogen and progesterone.
• Male:
– Testosterone.
Insert fig. 20.9
Onset of puberty
• The age of onset of puberty
– Females 8-13
– Males 9-14
• Average age of onset:
– GIRLS 10 to 11 years (range 8 to 13 years)
– BOYS 11 to 12 years (range 9 to 14 years)
• 1st sign of puberty in females is breast development, and testicular
enlargement in males. Axiliary and pubic hair follows along with
other 2ndary sexual characteristics.
• The maximum growth velocity occurs at 12 years.
• The age of menarche has decreased over the last 3-4
decades due to improved nutrition, general health & life style.
• Menarche marks the attainment of reproductive maturity.
Duration of puberty
• The time from onset to completion of puberty
– Average 4.2 years
– Range 1.5-6 years
Factors That Affect Puberty
• Genetics
• Race/Ethnicity (blacks before white)
• Previous nutrition ,malnourished they go to puberty
later.
• Subcutaneous fat (overweight reach puberty faster)
• Obesity
– Increased leptin and estrogen production
– Insulin stimulation of ovaries & uterus
• Birth weight
Initial signs of puberty
• GIRLS – Breast Development
• BOYS – Testicular Enlargement
– Volume > 3.0 cm³
– Length > 2.5 cm
Growth in puberty
• Female enter
growth spurt
before males
because females
(around 10 years)
enter puberty
before males
(around 12 years).
Insert fig. 20.10
Evaluation of disorder of puberty
• CLINICAL ASSESSMENT
– History
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Behavioural changes
Pubertal staging
Skin examination
Height measurement / Growth velocity
Bone age assessment
Hormone study if needed
Assessment of Puberty
• History
– Parents
• onset of puberty
– Menarche
– Male Age of first shaving regularly
• Parental heights (mid-parental height)
• prenatal and perinatal (exposure to exogenous sex steroids in
intrauterine period; birth weight; perinatal asphyxia)
• Concomitant illnesses, postnatal exposure to sex steroids
• Time of first sign of puberty
– Thelarche (galactorrhea) development of breast, testicles
– Adrenarche/pubarche (body odor, axillary & pubic hair, acne)
development of pubic and axillary hair.
– Menarche menstruation
– Gonadarche
• Premature thelarche is different the precocious puberty.
Premature thelarche is when there is breast or testicular
enlargement before the age of 8 or 9 years in females and
males respectively.
• In premature thelarche the X-ray images and hormonal levels
are normal with no other signs of puberty.
History
• Important to include:
– Past medical history (history of brain tumor, radiation,
chemotherapy, known genetic disorder, chronic
disease affecting growth)
– Eating habits
• Any evidence of disordered eating
– Activity level
• Is exercise excessive or is this an athlete with a high level of
training
– Growth history
• Previous growth chart can be extremely helpful
History
• Review of Systems
– CNS: visual changes/visual field abnormalities,
headaches, anosmia
– Cardiac: congenital anomaly
– Respiratory: asthma
– Renal:
– GI: diarrhea, blood in stools
Physical Examination
• Examination of Growth
– Height
– Weight
• Pubertal Assessment (Tanner staging)
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Axillary hair
Pubic hair & staging
Breast development & staging
Genital development & staging
• skin, hair, thyroid
• Neurological assessment
Growth charts
Staging of pubertal development in
girls (Tanner)
Staging of pubertal development in
bpys (Tanner)
G1-5, Pu 1-5, A 1-5, testicular volum > 4 ml – first sign of male puberty
Its used to measure the testicular size and development.
Prader orchidometer along with tanner staging is used to
asses puberty in males.
Diagnostic evaluation
• Laboratory
– gonadotropins (FSH, LH) basal and peak after LHRH
stimulation (prepubertal LH/FSH<1)
– estradiol
– testosteron (basal value and value after LH stimulation)
– adrenal androgens (17-OHP, A-dion,...) and ACTH
– bone age by hand X-ray.
– Pelvic US (ovarian and uterine size)
– CT or MRI of adrenals, Brain to exclude tumors.
– Vaginoscopy
– Genetic – karyotype, DNA analysis
Bone age
2 yrs 6 m.
10 yrs
12 yrs
Summary:Variants of puberty
• Premature thelarché
– Only premature breast development, with normal hormones.
– exclude the start of precocious puberty!
• Premature adrenarché
– Only premature axillary and pubic hair, with normal hormones.
– exclude simple virilising form of CAH!
• Premature menarché
– exclude vaginal bleeding due to trauma of vagine or rare ovarian cyst!
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Bone age is not accelerated!
FSH and LH levels after LH-RH are normal
Gonadal and adrenal steroid levels are normal
Pelvic and adrenal ultrasonography is normal
Reassurance & f/u
PRECOCIOUS PUBERTY
Landmark Case of Precocious Puberty
• 5 year old Lina Medina of Peru
– Menses onset age 8 months
– Breast development age 4
– Advanced bone maturation age 5
– Was evaluated for abdominal tumor due to
increasing abdominal size at age 5
– On 5/14/1939 gave birth to a 2.9 kg baby boy
Definition of Precocious Puberty
• ONSET OF PUBERTY BEFORE
– Females 8 years
– Males 9 years
• Lawson Wilkins Pediatric Endocrine Society
recommended 7 for white girls/ 6 for black
• Prevalence
– is estimated to be between one in 5,000 to 10,000
children annually in the United States.
• They can conceive.
Classification
• Central (true), gonadotropin-dependent
– Early stimulation of hypothalamic-pituitary-gonadal axis.
– Idiopathic.
• Peripheral resistance, GnRH independent
(precocious pseudopuberty)
– The source of sex steroid may be endogenous or
exogenous, gonadal or extragonadal, independent of
gonadotropins stimulation.
– Look for ovarian tumor.
True precocious puberty
(central, GnRH dependent)
• Idiopatic, constitutional sporadic or familial (common)
• CNS abnormalities
– Congenital (hydrocephalus, arachnoid cysts, ...)
– Acquired pathology (posttraumatic, infections, radiation,..
– Tumors (LH secreting pituitary microadenoma, glioma – may be
associated with neurofibromatosis, hamartoma,..
– Reversible forms - space occuping or pressure-associated lesion
(abscess, hydrocephalus,...)
• Adopted children or children emigrating from developping
countries
– Improved nutrition, environmental stability and psychosocial
support
True precocious puberty
(central, gonadotropin-dependent)
• Bone age is accelerated
• FSH and LH elevation after LH-RH is diagnostic
test
• (LH/FSH > 2)
• LH  LH/FSH ratio < 1  Prepubertal
•  LH  LH/FSH ratio > 1  Pubertal
• MRI of CNS is necessary to exclude the neoplasia
Treatment of true precocious puberty
• Purpose of treatment
– To prevent psychosocial distress
– To improve final height outcome because growth will stop at
that age, resulting in short stature.
• Treat the underlying cause
• GnRH analogue
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Lupron depot ped, leuprolide acetate
Desensitizes the pituitary
Blocks LH and FSH secretion
Prevents continued sexual development for the duration of
the treatment
• Growth may almost stop while on therapy
• ± addition of growth hormone remains controversy
Precocious pseudopuberty in girls
(gonadotropin-independent)
• McCune - Albright syndrome
• Ovarian cysts
– Isolated follicular cysts with E2 production. Selflimiting with spontaneous regression
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Ovarian tumors
Acceleration of bone age
FSH and LH are low after LH-RH stimulation
Estrogens are elevated
Precocious pseudopuberty in boys
(gonadotropin-independent)
• Congenital adrenal hyperplasia (CAH)
– Undiagnosed or inadequately treated simple virilising form of CAH
caused by 21-hydoxylase deficiency.
– Neonatal screening.
• Testotoxicosis
– Activating mutation of LH receptor. AD inheredited.
• Tumors
– Gonadal (testosterone-secreting Leydig cell tumor)
– Adrenal (adenoma, carcinoma)
• Exogenous androgens (anabolic steroids – iatrogene, doping)
– McCune Albright Syndrome
• Acceleration of bone age
• FSH and LH are low after LH-RH stimulation
• Testicular or adrenal steroids are elevated
Precoccious puberty-treatment
• Gonadotropin-dependent PP
• Idiopathic
– GnRH (LH-RH) analog to block LH-RH receptor of
pituitary gland
• Organic – tumor or cysts
– Surgery
• Gonadotropin independent (pseudopuberty)
– Treat underline cause
– Testicular, ovarian or adrenal tumors –surgery
– CAH – substitution of corticosteroids
Delayed puberty
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Delayed puberty - definition
• Initial physical changes of puberty are not
present
• by age 13 years in girls
– (or primary amenorhoe at 15.5-16y)
• by age 14 years in boys
Types of delayed puberty
• Gonadotropin dependent
– Hypogonadotropic hypogonadism
– Low LH/FSH
– Central, chronic disease
• Gonadotropin independent
– Hypergonadotropic hypogonadism
– High LH/FSH
– Peripheral cause (gonads)
GnRH or gonadotropin dependent
• Idiopathic
• sporadic or familial (associated with
constitutional growth delay)
• Chronic diseases with bone age delay and growth
retardation due to different pathophysical
mechanismes (malnutrition, anemia, acidosis,
hypoxia,...anorexia nervosa, cystic fibrosis,
chronic renal insuficiency,..)
• Psychosocial deprivation
GnRH or gonadotropin dependent
• Hypogonadotropic hypogonadism
• Gonadotropin deficiency
– LH only (fertile eunuch syndrome)
– FSH and LH
– Congenital (genetic, syndromes) - Kallman syndrome –mutation
of KAL gene, mutation of DAX1 gene, Prader-Willi syndrome ,...
– Acquired - cranial irradiation, hemosiderosis, granulomtous
disease
• Associated with others pituitary hormones deficiencies
– Congenital – empty sella syndrome, genetic-transcription factors,
disruption of pituitary stalk (breech delivery),...
– Acquired – tumors, inflamation, irradiation, trauma....
Kallman Syndrome
• A syndrome of isolated gonadotropin
deficiency
• 1/10,000 males, 1/50,000 females
• KAL-1 gene
• Present with ANOSMIA or HYPOSMIA
• Can also be associated with harelip, cleft
palate, and congenital deafness
Syndromes Associated with Pubertal Delay
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Prader-Willi syndrome
Laurence Moon syndrome
Septo-optic dysplasia
Bardet-Biedl syndrome
Gonadotropin independent
(hypergonadotrophic)
Boys
• Congenital
– Anorchia
– Chromosomal abnormalities (Klinefelter syndrome,
Noonan syndrome…)
• Disorders in androgen synthesis or action
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Acquired
Autoimunne inflamation (APS)
Radio or chemotherapy
Traumatic
Surgery
Klinefelter’s Syndrome
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45 XXY most common (2/3)
Tall in childhood, with euchanoid body habitus
More female type fat distribution
puberty is delayed
Small testicles & gynecomastia
90-100% are infertile
Klinefelter's syndrome
(Williams Textbook of Endocrinology, 10th ed, 2003)
Previous photos
• A 19-year-old phenotypic male with chromatin-positive
seminiferous tubule dysgenesis (Klinefelter's syndrome).
• The karyotype was 47,XXY, gonadotropin levels were
elevated, and testosterone levels were low normal.
• Note normal virilization with long legs and gynecomastia (B,
C). The testes were small and firm and measured 1.8 × 0.9
cm.
• Testicular biopsy revealed a severe degree of hyalinization of
the seminiferous tubules and clumping of Leydig cells.
• D, A 48-year-old male with 47,XXY Klinefelter's syndrome with
severe leg varicosities.
Gonadotropin independent
(hypergonadotrophic hypogonadism)
Girls
• Congenital
– Billateral ovarian torsion
– Chromosomal abnormalities (Turner syndrome, pure
gonadal dysgenesis, Noonan syndrome…)
• Acquired
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Autoimunne inflamation (APS)
Radio or chemotherapy
Traumatic
Surgery
Turner syndrome
• Karyotype 45,X (60%), (45,X/46,XX, structural
abnormalities of X chromosome)
• Incidence 1/2000
• Short stature (final height 142-147 cm)
• web neck
• Gonadal dysgenesis - streak gonad
• Autoimmune: Hashimoto’s thyroditis, Addison’s
• Mild insulin resistance
• Essential hypertension
• hearing loss /No mental defect
• Impairment of cognitive function: mathematical
ability↓
• Visual–motor coordination, spatial-temporal
processing↓
• Y chromosome predisposed to gonadoblastoma
H. Turner, 1938
Investigation of Delayed Puberty
• Investigations depend on clinical presentation, but may
include
– Bone age
– Hormone levels (IGF-1, FSH, LH, estradiol, testosterone,
DHEAS, prolactin, TSH)
– Karyotype
– Hormone stimulation tests
• GnRH stimulation test
• GH stimulation test
– Imaging
• MRI brain if gonadotropins low & no obvious cause of
hypogonadotropic hypogonadism
• US or MRI pelvis
Treatment of delayed Puberty
• Treat underline cause
• Time of therapy initiation may vary and
individualized
• Testosterone supplementation
• Estrogen for girls