Delayed and precocious puberty Flashcards
What in particular should be done when assessing the karyotype in Turner’s?
Examination of at least 20 cells
Because of the likelihood of Mosaicism
How should pubertal induction be done in delayed puberty due to hypergonadotrophic hypogonadism?
Always commence oestrogen alone for induction of puberty - timing/duration depends on age
If identified in childhood:
- start age 10 year
- Low dose 6.25mcg transdermal oestradiol patches
- Initially at night time
- Dose increased at 6 monthly intervals
- Progesterone introduced after 2-3 years
If identified in adolescence (most cases):
- Start low dose transdermal estradiol 12.5 mcg
- Commence progesterone after 6-12 months, or if breakthrough bleeding starts
- Progesterone usually given as medoxyprogesterone or micronised progesterone for 14 days in luteal phase
- Can be transitioned to COCP for long term MHT treatment until age of menopause
What is the definition of delayed pubertal development in girls?
Absence of secondary sexual characteristics by age 13
(or 14 in boys)
What is the definition and presentation of precocious puberty?
Onset of pubertal development before the age of 8 (girls) or 9 (boys)
Presentation:
Girls - breast buds and pubic hair growth <8yo OR menarche <9yo
Boys - testicular volume >4ml and pubic hair growth <9yo
What is the classic triad of findings in McCune Albright syndrome?
Skin: Cafe au lait skin lesions
Bone: Fibrous dysplasia of bones. Normal bone tissue replaced by fibrous tissue- results in weakening, lytic lesions. Fractures and skeletal abnormalities etc.
Endocrine: Gonadotrophin-independent precocious puberty (often around age 5) due to oestrogen released from ovary in high amounts. Can also have hyperthyroidism, cushing’s, acromegaly, hyperprolactinemia
What proportion of precocious puberty is caused by central causes vs peripheral causes
Central = 80% Peripheral = 20%
What are central / gonadotrophin dependent causes of precocious puberty?
- Majority idiopathic 75%
- Intracranial causes
- Brain tumours (either direct or indirect effect on GnRH)
- Congenital CNS malformations (arachnoid cysts, myelomeningocele, hydrocephalus)
- CNS injury (trauma / infection / bleed / post irradiation)
- Paraneoplastic syndromes
- germ cell tumours secreting HCG (gonads, liver, brain, mediastinum)
- hepatoblastoma
- germ cell tumours secreting HCG (gonads, liver, brain, mediastinum)
What are peripheral / gonadotrophin independent causes of precocious puberty?
Any cause of elevated oestrogen or androgens from a peripheral source - The HPG axis is not activated
- Benign follicular ovarian cysts are commonest cause.
- Hormone-producing ovarian tumours (granulosa cell tumours, sertoli-leydig cell tumours)
- McCune Albright Syndrome: mutation of the GNAS1 gene. Classic triad is follicular ovarian cysts and precocious puberty, cafe au lait spots, fibrous dysplasia of bones.
- Exogenous administration of oestrogen
- Adrenal causes:
- CAH is commonest cause of androgen excess in boys and girls.
- Adrenal tumours (DHEAS +++)
- Severe longstanding hypothyroidism
Additional causes in boys:
Testosterone secreting tumours of the testis
Paraneoplastic germ cell tumours secreing HCG - stimulate LH receptors on testes.
What investigations are useful in precocious puberty?
Investigation should be undertaken by a paediatric endocrinologist - not usually gynaecologist.
From O&G Magazine (2017) and TOG 2012:
- A careful history and examination are essential
- A growth assessment should include height, height velocity, weight and body proportions - plotted on age specific growth charts
Bloods:
- Serum LH and FSH levels (baseline)
- GnRH (LHRH) stimulation test (LH and FSH) (performed as a day case, with a stimulated LH >5IU/L being considered abnormal (sensitivity >98%, specificity 100%)).
- Estradiol/testosterone levels
- Adrenal steroids, e.g. 17 OH progesterone, DHEAS and androstenedione (raised in CAH and adrenal tumours)
- Adrenocorticotrophic hormone stimulation test (to identify steroid synthesis defects, e.g. CAH)
- Free thyroxine and TSH
- Serum prolactin levels (may be raised in chronic hypothyroidism, McCune–Albright syndrome or prolactinomas or point towards pituitary stalk compression)
- Urinary steroid profile (to identify and quantify excess adrenal androgens)
Imaging
- Left wrist X-ray for bone age
- Pelvic ultrasound (size, shape of uterus, endometrial thickness and ovarian morphology)
- Cranial magnetic resonance imaging/computed tomography (CT) for central causes
- CT adrenals (adrenal masses) if adrenal causes
- Skeletal survey/bone scan (McCune–Albright syndrome)
What is the treatment of precocious puberty?
Ususally under care of paediatric endocrinologist
Main aim is to slow growth trajectory and bone age
Not all children need treatment i.e. if close to normal age of puberty and no underlying pathology identified, adult height may be unaffected
Central / gonadotrophin-dependent cause:
- GnRH analogues (leupoprelin or goserelin) to supress GnRH secretion from hypothalamus and thus reduce FSH/LH release
- 3-6 monthly height and tanner stage assessment
- Annual bone age X-ray assessment
- Treatment withdrawn at age 10-11 to allow normal puberty to progress at the correct time
Peripheral Gondaotrophin-independent cause:
Treat underlying cause (i.e. surgical excision of ovarian tumours/cysts)
McCune Albright - Vitamin D, bisphosphonates, some evidence for estrogen supression with aromatase inhibitors (letrozole) and SERM (tamoxifen) - but safety concerns
What is the prevalence of Turner Syndrome
1:2500 female live births
What are antenatal USS features of Turner Syndrome
Increased nuchal thickness/translucency
Cystic hygroma
Cardiac anomalies - bicuspid aortic valve, coarctation of the aorta
Renal anomalies - horseshoe kidney, pelvic kidney
Non-immune fetal hydrops
Fetal growth restriction
Short limbs
How does Turner Syndrome present
Heterogenous due to possible mosaicism 45XO/45XX - usually milder phenotype than pure 45XO
Classic triad:
- infertility (95%)
- Delayed puberty or primary amennorrhea (Premature ovarian failure +/- streak gonads)
- Short stature
Other features:
Facial features: sloping eyes, high palate, low set ears, strabismus
Broad/’shield’ chest with Widely spaced nipples
Short and webbed neck
Short 4th metacarpal
Lymphoedema
Cardiac anomaly: coarctation of the aorta, bicuspid aortic valve
Renal anomaly: horseshoe kidney, pelvic kidney
Endocrine: hypothyroidism, insulin resistance
What is the management of Turner Syndrome?
Genetic councelling
Psychosocial support
Administration of growth hormone to improve adult height
Induction of puberty
Lifelong MHT with oestrogen and progesterone
IVF with donor egg when fertility required
In cases with Y chromosome mosaicism and gonadal dysgenesis, the streak ovaries thould be removed due to increased risk of gonadoblastoma and malignant change
Management of associated endocrine abnormalities (hypothyroidism, insulin resistance)
Management of cardiac or renal abnormalities (bicuspid aortic value, coarctation of aorta, horseshoe kidney etc)
What are the genetics of Kallman’s syndrome?
Most cases are sporadic, without prior family history.
X-linked disorder owing to a mutation to the KAL-1 gene.
Can also be inhertied in austosomal dominant and autosomal recessive by a variety of other mutations.
