Precious puberty, Primary amenorrhea Flashcards
What is precious puberty?
Pubertal development <8yrs
What is the most common cause of precious puberty? How common in girls/boys?
Idiopathic
74% girls
40% boys
What are the 2 main catergories of precious puberty?
GnRH-dependant (early activation of HPO axis)
GnRH-independant
List some causes of GnRH dependant?
Idiopathic
CNS abnormalitites (7% girls, 25% boys)
- Space occupying lesion
- Infection
- Head injury
- Tuberous sclerosis, neurofibromatosis
- Late/incomplete CAH
Typically experience a growth spurt
List causes of GnRH-independent of precious puberty
1) Topical/systemic androgens/oestrogens
2) Tumous - ovarian/adrenal
3) Severe hypothyroidism
4) McCune-Albright syndrome
5) CAH
What % of female precious puberty is caused my McCune Albright Syndrome
5%
Describe McCune-Albright Syndrome
Genetic condition, hight GTPase activity
- Bone fibrous dysplasia → ‘ground-glass’ cortex, risk fractures, osteomalacia
- Hyperfunctioning endroniopathy, not from pituitary hormones
- Hyperthyroid, cushings
- Precious puberty
High oestrogen/testosterone, low FSH/LH - Cafe-au-lait spots
What questions in the Hx should be asked for precious puberty?
Cerebral problems - trauma, encephalitis
Symptoms suggestive of space occupying lesion - headache, seizures, visual symptoms
Onset and progression - abrupt + rapid progression suggests oestrogen secreting tumour
Symptoms suggestive of abdominal mass - pain, urinary / bowel disturbance
Symptoms of hypothyroidism
Growth spurt - may help distinguish between precocious puberty and premature telerache
Iso-sexual or heterosexual
Drug history - oestrogens / androgens
Family history - precocious puberty, inherited syndromes such as CAH / neurofibromatosis
Social history - psycho-social problems
What features should be looked for examination for precious puberty?
Height & weight
Neurological examination including optic discs
Skin- caf- au lait spots / neurofibromas
Signs of virilisation - deepening of voice, hirsutism, increased muscle mass
Stage breast and hair development
Abdominal examination - mass
Examine external genitalia for evidence of oestrogenisation / virilisation
Vaginal examination not valuable
What investigations should be ordered for Ix precious puberty?
XRAY L hand/wrist - bone age ?greater than chronological age
Serum LH,FSH, DHEA-S, Oestradiol, TSH
- Random LH level in puberty range → advance PP
GnRH stimulation test
Pelvis USS
MRI head
If evidence of hyperandrogenaemia, what tests should be ordered?
Testosterone
17-OH-poregesterone
DHEA
+/- ACTH stimulation test
?Mild form CAH
What the treatment aims when managing precious puberty?
1) Dx + Tx life threatening conditions - tumour/intra-cranial
2) Arrest maturation until normal age of puberty
3) Diminish secondary sexual charaterisitics
4) Maximise eventual height
5) Avoid emotional problems/provide contraception
What is the mainstay for Tx for previous puberty?
GnRH analogues - usually depot (not effective for non GnRH causes, CAH/McCune Albright
What is the definition of primary amenorrhoea
No pubertal growth spurt/secondary sexual characteristic by age 14
or
No menstruation by age 16
How many stages to the tanner scale?
5 stages
Breast development and pubic hair
What is the most common cause of primary amenorrhoea?
Constitutional delay
Diagnosis of exclusion
Describe LH/FSH pre-puberty?
Low circulating levels
FSH>LH
Explained start of puberty
Increased production of GnRH from hypothalamus in pulsatile fashion.
Occurs between ages 10-14 girls and 12-16 in boys.
Causes episodic pulses of LH especially at night.
As puberty advances both FSH and LH during the day, becoming more fequent.
Leads to increased gonadal steroid synthesis
LH>FSH
What effect does FSH and LH have on the oocyte?
LH stimulates theca cells to produces androstenedione
FSH stimulates granulose cell to convert androstenedione into oestrogen and progesterone
Normal menstruation is dependant on what 5 things?
- Normal karyotype/gene - development internal/external genitalia
- Normal CNS hypothalamic response & production of GnRH
- Normal pituitary response to GnRH & production of gonadotropins
- Anotmically & biochemical normal ovaries (and adrenals), with normal response to gonadotropins
- Presence of normal uterus, vagina and end-organ response to ovarian and adrenal steroids
An example of abnormal karyotype is Turners syndrome. What is the karyotype?
45X
What genetics abnormlaties can cause Turners
- non disjunctions during meiosis, most often in sperm, 45 X
- Mosaics 45X or 46XX
- Structural abnormality of X chromosome, Xp deletion
Symptoms depend on how much of X chromosome is missing
How common is turner syndrome?
1 in 2000-3000 births
Explain turners syndrome
- Streak gonads, absent secondary sexual characteristics
- Short stature,
- Webbed neck (cystic hygroma), wide carrying angle
- Lymphoedema
- High LS/FSH - Hypergonadotrophic, hypogonadism
- Cardiovascular: Coarctation of aorta, bicuspid aortic valve
- Horseshoe kidneys
- T2DM, Hypothyroidism
What happens is turners syndrome occurs due to mosaics 45X/46XX
Mosaics 45X or 46XX → Fewer anatomical, 20% sufficient oestrogen to menstruate
Can also occur due to Xp deletions
Treatment turners
Growth hormone in childhood
Sex hormone replacement in adolescent
Names causes of hypothalamic hypogonadism in females
Genetic:
Kallmans syndrome
Idiopathic secondary hypogonaism
Acquired
Hypperprolactinaemia
Pituitary dysfunction (tumour, surgery, trauma, infection)
Eating disorder (Malnutrition)
Excessive exercise
Drugs
Obesity
Chronic conditions
Describe Kallmans syndrome
Maldevelopment of neurones in arcuate nucleus from the hypothalamus, derived from the olfactory bulb
Low GnRH, Low LH/FSH, low sex hormones
Normal level other pituitary hormones
Lack primary & secondary sexual characteristics, infertility
Where is prolactin excreted from?
Anterior pituitary gland - lactotroph cells
Effect of prolactin on GnRH?
Inhibits GnRH, high prolactin = Hypogonadotrophic Hypogonadism
What hormone inhibits the release of prolactin?
Stimulates release?
Dopamine inhibits
Thyrotopin releasing hormone
Causes of high prolactin?
Physiological (pregnancy)
Pituitary adenoma (lactotroph cells)
Hypothyroidism (high TRH)
Medications (Dopamine antagonist, oestrogens)
Damage to hypothalamic pituitary stalk - trauma, nearby tumour, surgery
Symptoms of high prolactin in women
Galactorhoea
Amennhoroea
Headache, impaired vision
Men → Gynaecomastia/erectile dysfunction
Ix high prolactin
Pregnancy test
MRI head
Treatment prolactinoma
Domapine agonist - cabergoline, bromocriptine
List some gonadal/adrenal causes of primary amenorrhoea
- Late onset congenital adrenal hyperplasia
- Gonadal agenesis/dysgenesis - 46XX or 46XY with failure of development
- Galactosaemia
- Premature ovarian failure - idiopathic, chemotherapy/radiotherapy as child
Why does congenital adrenal hyperplasia occur?
Overgrowth of adrenal glands due to lack of steroid producing enzyme
What is the most common enzyme deficient in CAH?
21 hydroxylase definicency - decrease in aldosterone/cortisol, high 17a hydroxyprogesteone, progesterone, higher production of androgens
→ Low aldosterone - Salt wasting, Low K, high Na
→ Low cortisol - hypoglycaemia
→ High androgen - Masculisation of female genitals, early secondary sexual characterise
Second most common enzyme deficiency in CAH?
11B hydroxylase definicency
Similar to 21 hydroxylase but also have hypertension due to high 11 deoxycoriticosterone (acts like a weaker aldoestetone)
The 3rd most common deficiency in CAH 17a-hydroxylase deficincy, how does it present?
Low cortisol and testosterone → poorly developed genitals
High aldosterone precursors → High Na, Low K, HTN
Draw table for 21, 11b and 17a hydrolase deficiency and differences in androgen, aldosterone and cortisol
List causes of abnormal end organs response
Mullerian aplasia - Mayer-Rokitanksky-Kuster-Hause syndrome
Androgen insensitivity syndrome
5 alpha reductase deficiency
Vaginal atresia
What is the 1st and 2nd most common cause of primary ammenorhoea in adolescents?
1 Turner
2 MRKH syndrome
What would find on clinical examination of a person with Mayer–Rokitansky–Kuster–Hauser syndrome?
Normal growth
Normal age app secondary sexual characteristics
Normal external genitalia
Patulous urethra
Vaginal vault short or absent, maybe vaginal dimple
Uterus not palpated
What would be seen on USS for a person with Mayer–Rokitansky–Kuster–Hauser syndrome?
Absence of uterus and fallopian tunes
Normal ovaries
May have urinary tract abnormality
What would be seen hormone profile for a person with Mayer–Rokitansky–Kuster–Hauser syndrome?
Normal
What would be found on examination of a person with androgen insensitivity syndrome?
Present after puberty
Normal breast development
Absent/scanty pubic/axillary hair, short blind-ending vagina, absent uterus/cervix
Karotype of person with androgen insensitivity syndrome?
XY genotype (male), produce androgens but insensitivity to the hormone
Can be complete, partial or mild
What would be found on USS for patient with androgen insensitivity syndrome?
Testes within abdomen/inguinal canal - cryptorchdism
What would be found on hormone profile for androgen insensitivity syndrome?
Testosterone - male range (excess testosterone covered into oestrogen)
Oestrogen between male and female range
LH levels raised
FSH in normal male range
Effect of cryptorchdism, how should this be managed?
High risk of testicular cancer
Gonadectomy after puberty + oestrogen replacement therapy
What is the effect of 5 alpha reductase deficiency?
How is it inherited?
5alpha reductase converts testosterone to the more potent or dihydrotestosterone
Autosomal recessive
How does 5 alpha reductase deficiency present?
Poor masculinisation of external genitalia in male foetus
Uterus, tubes, vagina are absent as production of mullein hormone inhibitory factor is normal
Development of wollfian ducts
Virilisation occurs at puberty due to increase of testicular testosterone
How does vaginal atresia present?
Cyclical abdominal pain with retrograde menstruation and development of endometriosis
Traverse vaginal septum
Absent vagina and non functions uterus (can also have abnormal renal)
What questions should be asked in Hx for primary amenorrhoea?
- Age
- Development of secondary sexual characteristics / hirsutism + virilisation
- Cyclical abdominal pain
- Exercise / eating disorder
- Sense of smell
- Visual symptoms / headache suggestive of pituitary tumour
- Family history of delayed puberty / hirsutism + virilisation
- History of chemotherapy / radiotherapy
What examinations should be performed for primary ammenorhoea?
- Weight and height for age
- Stage of breast / pubic + axillary hair development
- Features of Turners syndrome
- External genitalia - haematocolpos + exclude the presence of testes within the inguinal canal / labia.
- no indication for pelvic examination in women who are not sexually active. Determine presence of ovaries / uterus / vagina using trans-abdominal ultrasound scan*
What Ix for primary ammorhoea?
Pelvic USS - ?uterus
Next steps depend of prescence/absence of uteru
