Growth disorder: Precocious Puberty Flashcards
Define precocious puberty.
- *Females:** Development of 1 pubertal changes <8 years or menarche <10 years.
- *Males:** Development of 1 pubertal changes <9 years.
It also results in accelerated skeletal development with an impaired final height.
What are the two forms of precocious puberty?
- Gonadotrophin-dependent (also central) (GDPP; due to premature activation of the hypothalamopituitary-gonadal axis)
- Gonadotrophin-independent (also peripheral) (GIPP; due to autonomous secretion of sex steroids)
What is the pathophysiology of GDPP?
The hypothalamo-pituitary-gonadal axis is prematurely activated.
The pattern of endocrine change is the same as in normal puberty (i.e., pubertal development is consonant).
What is the pathophysiology of GIPP?
The secretion of sex steroids is autonomous and independent of the central hypothalamic GnRH pulse.
There is loss of normal feedback regulation and sex steroid concentrations are typically elevated with low levels of gonadotrophins.
Pubertal development does not follow the pattern of normal puberty (i.e., it is disconsonant).
Prolonged sex steroid exposure in GIPP has a direct maturational effect on the hypothalamus and can accelerate the onset of centrally mediated puberty, leading to GDPP.
Explain the aetiology/risk factors for GDPP.
Idiopathic: Most common cause in females (90%) but rare in males (less than 10%).
Brain neoplasms such as optic nerve gliomas (e.g., in association with neurofibromatosis), craniopharyngiomas, or hamartomas. Hamartomas of the tuber cinereum are congenital tumours composed of a heterotopic mass including GnRH neurosecretory neurones, frequently associated with GDPP, and often occurring before 3 years of age, particularly in males. Other tumours include astrocytomas, ependymomas, pineal tumours.
Cranial radiotherapy.
Neurodisability conditions such as hydrocephalus, cerebral palsy, post-infection such as meningitis or encephalitis.
Post-traumatic head injury.
Gain-of-function mutations in GPR54, a G protein-coupled receptor that is a ligand for kisspeptin, can cause GDPP. The interaction between GPR54 and kisspeptin is necessary for GnRH function.
Midline forebrain abnormalities such as holoprosencephaly or septo-optic dysplasia.
Association with child adoption and sexual abuse.
Explain the aetiology/risk factors for GIPP.
Ovarian causes: Follicular cysts of the ovary, granulosa cell tumours, Leydig’s cell tumours, and gonadoblastoma.
Testicular causes: Leydig’s cell tumours and a defect of luteinising hormone (LH) receptor function (testotoxicosis or familial GIPP). The latter is caused by an activating mutation in the LH receptor gene.
Adrenal causes: 21-hydroxylase congenital adrenal hyperplasia (CAH) in males results in GIPP. CAH in females presents with signs of virilisation (e.g., pubic and axillary hair and clitoromegaly) but no breast development. Other adrenal causes include Cushing’s syndrome and an adrenal virilising tumour.
McCune-Albright syndrome (MAS): A sporadic condition caused by a somatic activating missense mutation in the gene encoding the alpha-subunit of the G-protein that stimulates cyclic AMP production. It results in the classic triad of GIPP, café au lait spots, and fibrous dysplasias of the bone. Precocious puberty due to MAS is much more common in girls than in boys. Autonomous hyperfunctioning most commonly involves the ovary, but other endocrine involvement includes the thyroid (thyrotoxicosis), adrenals (Cushing’s syndrome), pituitary (gigantism/acromegaly or hyperprolactinaemia), and parathyroid glands (hyperparathyroidism).
Exposure to exogenous hormones such as the contraceptive pill or testosterone gels may be responsible for early pubertal development in some patients.
Summarise the epidemiology of precocious puberty.
1:5000 children; GDPP 10x more common in F (possibly due HPG-axis requiring less GnRH for activation). Black girls enter menarche usually half a year earlier than white girls (12.2 yrs vs. 12.9 yrs). Age of menarche has gone down over the last century but not over last 40 years. Since the rate of obesity has increased, that also has been associated with an earlier age of menarche. Family history plays a role.
What are the male genital stages in Tanner’s stages of puberty?
- Preadolescent
- Lengthening of penis
- Increased length and circumference
- Glans penis, scrotal darkening
- Adult genitalia
What are the pubic hair changes in Tanner stages of puberty?
- Preadolescent, no sexual hair
- Long downy hair along labia/base of penis
- Dark, coarser, curlier hair
- Filling out towards adult distribution
- Adult in quantity and type, medial thigh spread
What are the female breast changes in Tanner stages of puberty?
- Prepubertal
- Breast bud
- Juvenile smooth contour
- Areola/nipple project above breast
- Same shape nipple and breast
What are the signs and symptoms of precocious puberty?
General: Early development of stages of puberty (Tanner stages; see Delayed puberty). Must perform full cranial and peripheral nerve examination to identify intracranial pathology.
Specific: Signs specific to individual syndromes, e.g. hyperpigmented lesions in McCune–Albright syndrome.
What are appropriate investigations for precocious puberty?
Bloods: LH/FSH/testosterone/oestrogen/LHRH levels.
Radiology:
- CT/MRI brain if neurological cause suspected
- USS of the uterus and ovaries or testes
- Wrist X-ray: for assessment of bone age
What is the management for precocious puberty?
Referral to specialist paediatric endocrinologist.
What are possible complications associated with precocious puberty?
Early bone maturation and reduced eventual adult height. May be associated with psychological problems. May indicate the presence of an intracranial/gonadaltumour or other serious problem.
What is the prognosis of precocious puberty?
Depends on underlying pathology.
