L22: Puberty And Sex Development Flashcards
What is the definition of puberty
The physiological, morphological, behavioural changes as the gonads switch from the infertile to adult forms
When does growth at puberty occur
Adolescent growth spurt
What is a adolescent growth spurt
Rapid increase in individuals height and weight as a consequence of gonadal sex steroids
What are the 3 phases of adolescent growth spurt
1) Time of minimum growth velocity
2) peak height velocity
3) time of decreasing growth velocity (epiphyseal fusion)
When does the time of minimum growth velocity occur
Just before puberty starts
What occurs during peak height velocity
Maximum height velocity is reached
What occurs in time of decreasing velocity
Growth rate decreases until the epiphyseal fusion of long bones occur
What is the average height gain during puberty in boys
28cm
What is the average height gain in females
25cm
Which sex has growth occuring before
Female
What are the secondary sexual characteristics of girls
Breast development
Pubic hair and axillary hair
What is breast development controlled by
Ovarian oestrogens
What is the pubic hair and axillary hair controlled by
Ovarian and adrenal androgens
What are the secondary sexual characteristics that occurs in males during puberty
Development of penis, scrotum
Pubic hair
Enlargement of larynx (deepening voice)
Increase in body muscle mass
Which hormones controls the secondary sexual characteristics in males
Androgens such as testosterone and DHEA
How do we rate the development of secondary sexual characteristics as clinicians
Tanner stage
How many stages does the tanner stage involve
5 stages
With the tanner stage what do we asses in males
Pubic hair
Growth of penis
In girls using the tanner stage what do we assess
Pubic hair
Breast development
What is the timing of puberty stages in girls like
1) pubic hair and breast development occur first
2) this is accompanied by onset of growth spurt
3) after the peak of height velocity periods occur
What is the timing of puberty in males
1) pubic hair and increase in testicular volume of 4cm occurs
2) this results in penile growth
3) peak height then occurs later on
In boys what indicates that puberty has started
Testicular volume of 4cm at average age of 10-14 years
In girls what indicates that puberty has started
Breast development tanner stage of 2 at average age of 9.2-13.2 years
What are the factors that are needed for puberty to occur
Sex chromosomes
Functioning HPG axis
Responsiveness of tissue to hormones
What are the physical changes controlled by
Gonadal sex steroids
Which gonadal sex steroid control the physical changes in females
Oestrogen
Which gonadal sex steroid control the physical changes in males
Testosterone
What hormones are the gonadal sex steroids regulated by
LH/FSH from the anterior pituitary gland
What is the LH/FSH secretion regulated by
GNRH Pulsatile secretion from the hypothalamus
During puberty what does LH levels show
Circadian rhythms
What is the circadian rhythm of LH like in puberty
Early- mid puberty: low spikes and less frequent LH
Mid-late puberty: high spike and more frequent LH
What is the definition of precocious puberty
Onset of secondary sexual characteristics before 8 years in female and 9 years in males or menarche before 9 years in females
What is the definition of delayed puberty
Absence of secondary sexual characteristics by 13 years in females and 14 years in males
If there is delayed puberty in males and females what are they at risk of
Osteoporosis due to decrease bone mass
Which ethnic group can present with precocious puberty
African-Caribbean
What are the 2 ways in which precocious puberty can present
Concordant
Discordant
What does concordant mean
Puberty follow the normal sequence of events in order
What does discordant mean
Sequence of events is random e.g pubic hair but small testis
What is the likely cause of concordant precocious puberty
Central gonadotropin activation
What is the likely cause of discordant precocious puberty
Peripheral sec hormone production
In central precocious puberty what happen
1) early activation of GNRH in the hypothalamus
2) LH/FSH release is stimulated
3) this leads to gonadal sex hormone production
What happens in peripheral precocious puberty
1) GNRH secretion is silent
2) there are no LH/FSH release
3) there is however an increase in gonadal sex steroids due to a problem at the gonads, adrenal glands or a secreting tumour
What is adrenarche
The onset of adrenal androgen production not in the gonads that reflects maturation of the zona reticularis in the adrenal glands
Describe the process that occurs during adrenal gland maturation
1) foetal zone of adrenal gland produces many adrenal androgen precursors
2) the zona glomerulusa and zona fasciculata form- no androgen forms
3) in mid late childhood zona reticularis forms so adrenal androgen is produced
4) the zona reticularis completely forms in the early adolescence which results in increase of androgen i.e DHEA
What are the clinical features of Adenarche
Growth acceleration
Pubic hair/ axillary growth
Mild acne
Body odour
The the process of adenarche independent to central puberty regulation
Yes but adenarche occurs within the onset of central puberty
What so premature adenarche
The onsent of androgen secretion from adrenal glands before 8 years in females and 9 years in males
If someone presents with adrenarche what do we need to exclude
Precocious puberty
Enzyme defects
Virilizing tumours that secrete androgen
What is the diagnostic test to differentiate between central and peripheral precocious puberty
GNRH (LHRH) stimulation test test
How does a GNRH test work
1) you inject 100mcg GNRH analogue
2) measure LH/FSH at 30 and 60 mins
If the patient has a central precocious puberty what would the results be after a GNRH test
1) an increase in LH and FSH
2) higher LH than FSH
If a patient has peripheral precocious puberty what would be the results after a GNRH Test
LH and FSH will remain flat
What are the causes of central precocious puberty
- idiopathic precocious puberty
- CNS tumours
- CNS disorders
- psychosocial
- secondary central precocious puberty i.e CAH
What are the causes of peripheral precocious puberty
- increased androgen secretion i.e CAH due to 21 hydroxylase deficiency
- gonadotropin secreting tumours
- ovarian cyst
- Oestrogen secreting neoplasm
- hypothyroidism
What are the consequences of precocious puberty
- psychological symptoms: adolescent behaviour, altered self image
- growth: growth will finish early so you will have a short stature
- metabolic: glucose intolerance, diabetes, cardiovascular complications
What is the treatment of central precocious puberty
Long acting GNRH analogues
How does long acting GNRH analogues work
Down regulate GNRH receptors so GNRH cannot cause the release of LH/FSH
What is the definition of delayed puberty
Absence of secondary sexual characteristic by 13 years in girls and 14 years in boys or first period after 15 years in girls
What are the 2 types of gonadal failure
Primary gonadal failure
Secondary gonadal failure
What is the primary gonadal failure due to
Problem at gonads
What is secondary gonadal failure due to
Problem at higher centres
What happens to the LH/FSH levels in primary gonadal failure
Increase as they try to stimulate the gonads and do not have a negative feedback
In secondary gonadal failure what are the levels of LH/FSH like
Low due to a problem at the higher centres
What are the levels of gonadoropins like in primary gonadal failure
Hypergonadotrophic i.e LH/FSH
Hypogonadism i.e sex steroids
What are the level of gonadotropin in secondary gonadal failure like
Hypogonadroptrophins i.e LH and FSH
Hypogonadism i.e sex steroids
In central hypogonadism i.e secondary gonadal failure what can the HPG axis be
Intact
Impaired
If there is intact HPG axis in secondary gonadal failure what do we need to check for
other chronic diseases such as hypothyroidism that is affecting the HPG axis to become activated
What do we need to look for if there is an impaired HPG axis in secondary gonadal failure
- Tumours in the hypothalamus that have destroyed gonadotrophs
- Trauma to the head
- Congenital anomalies
What are the primary gonadal failure causes in males
- Bilateral testicular damage: cyptochidism, torsion, haemochromatosis
- syndromes associated with cryptochidism
What are the primary gonadal failure causes in females
Disorders of sex development
Toxic damage
What are the primary gonadal failure causes in both sexes
Turners syndrome
Klinefelters syndrome
Chemotherapy
What is the first line investigation of gonadal failure
Full blood count
Karyotype for turners or klinefelters
Basal LH, FSHm oestradiol, testosterone
Bone age
If the test results show high LH, FSH and low oestradiol and testosterone what type of gonadal failure does this indicate
Primary gonadal failure
What is the second line investigation for gonadal failure
GNRH test
HCG stimulation test- males
Pelvis USS- females
Ovarian antibodies
What is the treatment for delayed puberty in males
Replace testosterone
What is the treatment for delayed puberty in female
Replaces oestrogen
When we treat delayed puberty with testosterone/ oestrogen what do we need to do to the levels
Titrate it very slowly to mimic the natural puberty development
What is the definition of ambiguous genitalia
Appearance of external genitalia that is ambiguous when sex assignment is not possible at birth
What are the 3 ways to define sex development
Chromosomal sex
Gonadal sex
Phenotype sex
What is sex determination by
Chromosomal sex to gonadal sex
What is sex differentiation by
Gonadal sex to phenotype sex
Which gene on the Y chromosome determine male sex development into the testicles
SRY gene
What cells are in the testes
Leydig cells
Sertoli cells
What hormone does the Sertoli cells produce during embryological development
Anti mullerian hormone (AMH)
What does AMH cause
Regression of mullerian/female structures
What hormone does the leydig cells produce
Testosterone s
What structure in the embryo does testosterone lead to
Wolffian structures
In Sertoli cells what is testosterone converted to
DHEA
Which enzyme converts the testosterone to DHEA
5 alpha reductase enzyme
What structures from the Müllerian duct is formed
Ovary
Fallopian tubes
Uterus
Proximal 1/3rd of vagina
What structure does the wolffian duct form in males
Testicles
Epididymis
Vas deferens
Seminal vesicle
What are the important external genitalia in the embyro
Genital tubercle
Genital swelling
Urethral folks and grove
In females what does the genital tubercle give rise to
Clitoris
In males what does the genital tubercle give rise to
Glans of penis
In females what does the urethral fold give rise to
Labia minora
In males what does the urethral folds give rise to
Corpus spngiosum
Which hormone influences the development of the EXTERNAL genitalia
Dihydrotestosterone produced by the testicles
What are the 3 main subgroups of disorders of sex development
1) chromosomal DSD
2) DSD 46 XY
4) DSD 46 XX
What does chromosomal DSD involve
Turners syndrome
Klinefelters syndrome
What does DSD XY involve
Disorders of testicular development
Disorders of synthesis of androgen
What does DSD 46 XY involve
Disorders of ovarian development
Excess production of androgens
Explain what occurs in 5 alpha reductase deficiency
1) testesterone is bound to SHBG and becomes free and enters the cell
2) testosterone is converted to DHT by 5 alpha reductase
3) DHT binds to androgen receptors
4) androgen receptors travel to the nucleus and activate specific response elements in the genome to activate protein expression and process
5) in 5 alpha reductase deficiency these processes cannot take place for external genitalia development
What is androgen insensitivity syndrome
When there is a defect in the Andorgen receptor (AR) so DHT cannot bind or travel to the nucleus to activate genes
