Puberty And Adolescence Flashcards
how does McCune Albright syndrome present
2 of 3:
unilateral cafe au lait spots
polyostotic fibrous displasia (deformity and fractures)
autonomous hypersecretion of hormones at a young age (precocious puberty, hyperprolactinaemia, acromegaly, giantism, cushings, hyperthyroid)
what is the pathological basis for McCune-Albright syndrome
a point mutation in the GNAS1 gene which would usually inhibit GTPase activity
this leads to the persistent activation of cAMP- mediated endocrine secretion
which conditions may feature cafe au lait macules
neurofibromatosis 1 and 2 tuberous sclerosis ataxia telangiectasia Fanconi's anaemia MEN 1 McCune Albright syndrome - unilateral, coast of maine
what is the inheritance pattern of congential adrenal hyperplasia
autosomal recessive
what is the most common form of CAH
21 hydroxylase deficiency
this prevents the production of cortisol (and 80% also aldosterone) leading to the increased production of sex hormones (testosterone)
what is the presentation of CAH
virilisation of ext genitals in female infants
enlargement of penis and pgmentation of scrotum in male infants
80% of males are salt losing –> adrenal crisis at 1-3 wks
PRECOCIOUS puberty
how might CAH be detected
increased levels of metabolic precursor 17 alpha hydroxyprogesterone in the blood
in salt losing CAH what biochemical abnormalities might you see
low plasma sodium
high plasma potassium
metabolic acidosis
hypoglycaemia
what are the causes of precocious puberty
CENTRAL idiopathic secondary PERIPHERAL genetic precocious breast development virilisation
list some secondary central causes of precocious puberty
CP/hydrocephalus/encephalitis tumours/masses (CRANIOPHARYNGIOMA, neurofibromatosis [optic nerve glioma] hypothalamic hartoma) trauma chronic inflammatory conditions radiotherapy sexual abuse adoption
list 2 genetic peripheral causes of precocious puberty
McCune-Albright syndrome
Testotoxicosis
list some conditions with precocious breast development in peripheral causes of precocious puberty
premature thelarche
thelarche variant (with increased height velocity +/- cyclical vaginal bleeding)
hypothyroidism (increased TRH)
ovarian cyst
list three virilising peripheral causes of precocious puberty
adrenarche
CAH
Cushing’s
adrenal tumours
what is thelarche
isolated breast development
no other symptoms of sexual precocity
happens in infants and preschool children
what is the management of premature thelarche
usually resolves, just needs follow up
what might investigations of premature thelarche show
normal bone age
pre-pubertal pelvic USS
oestradiol undetectable in standard assays
LHRH test pronounced FSH response, low LH
what is adrenarche
adrenal puberty: acne BO pubic and axillary hair normal genitalia
what might be shown on investigation for adrenarche
bone age may be advance by 1 yr (esp if overweight)
17OHP normal
testosterone/oestrodiol normal
DHEAS and androstenedione raised
what is the management of adrenarche
explanation and reassurance
association with later PCOS - advise to avoid weight gain
who is more likely to go through exaggerated adrenarche
girls
Mediterranean/indian/african ethnicity
what are the signs of central precocious puberty
onset < 8 years old CONSONANT progressive breast development growth spurt pubic and axillary hair, BO, acne mood swings can lead to menarche untreated
what would you see on investigation of central precocious puberty
detectable oestriol, LH, FSH Response to LHRH (LH dominant) bone age >2 yr advanced pelvic USS- enlarged ovaries, follicles, endometrial stripe normal MRI of pituitary
what are the difference between central and peripheral causes of precocious puberty
CENTRAL: is gonadotrophin dependant and consonant
LHRH >5 LH>FSH
PERIPHERAL
gonadotrophin independant
non-consonant
LHRH < 5 FSH>LH
how is central precocious puberty managed
GnRH analogue to inhibit LH/FSH secretion which stops at the age of 11-12
what is testotoxicosis
symmetrical enlargement of the testes
autosomal dominant
due to LH receptor activating mutations
what might investigations of peripheral precocious puberty show
detectable oestradiol LH and FSH undetectable LHRH testing shows no response bone age advance by >2 years pelvic USS may show increased size of ovaries and uterus, follicles and endometrial stripe
what is the definition of delayed puberty
complete absence of physical signs of puberty by:
13 in females
14 in males
more common in boys
what are the main causes of delayed puberty
central failure (hypogonadotrophic hypogonadism)
primary gonadal failure (hypergonadotrophic hypogonadism)
hyperprolactinaemia
PCOS
Chronic illness (coeliac, IBD, cyanotic heart disease)
what is the most common cause of delayed puberty
constitutional delay
often familial
child is short during childhood and has long legs compared to back
list some causes of central failure in delayed puberty
constitutional delay
structural abnormalities of hte brain (tumours CRANIOPHARYNGIOMA, infiltration, infections)
Kallman’s syndrome (isolated LH and FSH deficiency)
Low BMI/eating disorders/excessive exercise
single gene defects
Prada Willi
Panhypopituitarism
list some single gene defects which lead to hypogondaotrophic hypogonadism
DAX-1
LHR
FSHR
leptin and leptin R
list some of the causes of primary gonadal failure
Klinefelters XXX females XO Turner's Gonadal dysgensis Testicular/ovarian failure Androgen insensitivity syndrome single gene defects enzyme defects chemotherapy pelvic irradiation bilateral cryptorchism (uncorrected before 8yrs)
list some enzyme defects which might lead to hypergonadotrophic hypogonadism
17 alpha hydroxylase
5 alpha reductase
17 ketosteroid reductase
what is kallmann’s syndrome
isolated gonadotrophin releasing hormone deficiency most commonly due to mutations in the KAL1 gene
affects in 10000 male births
what is associated with Kallmann’s syndrome
anosmia (KAL1 also codes for ansomin)
occasionally cleft palate
renal agenesis
cerebral abnormalities (colour blindness)
what is androgen insensitivity syndrome
pts are phenotypically female but genotypically male with male gonadal sex, resulting from insensitivity of tissues to androgens
what is the inheritance pattern of AIS
X-linked recessive
only 2/3 of AIS is inherited
what is puberty
physiological sequence of events characterised by:
- development of 2ndry characteristics
- acceleration of somatic growth
- advancement of bone maturation
- behavioural and psychological changes
what is adolescence
transition from childhood dependance to adult autonomy
how is the onset of puberty triggered
in the hypothalamus
begins producing larger quantities of GnRH in a pulsatile manner
this switches on the production and pulsatile release of LH and then FSH (GONADARCHE)
what is normal adrenarche
activation of the adrenal glands (6-8yrs)
can precede puberty by 1 year
not under the influence of LH/FSH
what is require for GH production and also has a permissive action on the tissues for GH
thyroid hormone
at what age is peak height velocity reached
12 yrs in girls (B2-3)
14 yrs in boys (TV 12-15mls)
what is non-consonance
pathological sequence of development not under the guidance of the HPG axis
often presents with virilisation from the adrenal glands
what are the physical signs of Turner’s
facial:
- micrognathia (small chin)
- epicanthic folds
- low set ears
- fish-like mouth
- hypertelorism
- ptosis
- strabismus
neck
- short webbed neck
- redundant skin folds at back of neck
- low hairline
chest:
shield like chest with widely space nipples
upperlimb:
- short fourth metacarpal/metatarsal
- hyperplastic nails
- lymphoedema
- increased carrying angle of elbow
what are the physical signs of Klinefeltes’s
soft finely wrinkled hairless facial skin gyaecomastia reduced pubic hair small testes tall
what are the physical signs of Prader Willi disease
constant hunger - weight gain short stature hypotonia learning difficulties behavioural problems
