DISORDERS OF PUBERTY

•	Normal puberty.
•	Tanner staging system.
•	Delayed puberty.
•	Precocious puberty.
•	Normal variants of development.

Normal puberty

1.	It is the period during which:

a.	Sexual maturation is completed.

b.	Resulting in capacity to reproduce.

2.	Hypothalamic-Pituitary-Gonadal Axis:

a.	Puberty requires the maturity of the hypothalamic-pituitary axis, the mechanism of which is unknown. 

b.	GnRH released from the hypothalamus stimulates the release of FSH and LH from the anterior pituitary.

c.	LH acts on Leydig cells of the testes to synthesize and release testosterone and on the corpus luteum in the ovaries together with FSH to produce estradiol.

d.	Testosterone and estradiol are the sex hormones responsible for the changes occurring during puberty.

3.	Changes during puberty:

a.	Growth spurt.

b.	Maturation of primary sexual characteristics: gonads and genitals.

c.	Appearance of secondary sexual characteristics: sexual hair, breast development, voice change:

i.	pubarche: pubic hair development.

ii.	thelarche: breast development.

d.	Menarche: onset of menstruation.

e.	Spermarche.

4.	Normal female development

a.	Onset: 8 – 13 years.

b.	Duration: 3.5 years (2 – 6 years).

c.	First sign: breast development, then pubic hair development.

5.	Normal male development

a.	Onset: 9 – 13.5 years.

b.	First sign: enlargement of testes and scrotum, with development of reddening and thickening of the scrotal skin followed by pubarche and growth of the penis.

c.	Increased testicular size to > 4mls.

Tanner staging system

Stage	Breast	Pubic hair	Genital in boys	
1	Preadolescent	Preadolescent	Preadolescent	
2	Breast bud	Long, fair straight hair, sparse along labia or base of penis.	Enlargement of scrotum, with reddening and thickening of scrotal skin.	
3	Breast & areolae enlarged & elevated but no separation of contours.	Darker, coarser, curlier, sparse.	Enlargement of penis, further growth of scrotum.	
4	Areola & papilla form a mound above the contour of the breast.	Adult type hair, small area covered than in adult.	Further growth of penis & scrotum, darker scrotal skin.	
5	Mature	Adult, spread to medial surface of thighs.	Adult.	

Delay puberty

1.	Definition:

a.	Lack of development by 13 years in girls and 15 years in boys.

b.	Poor progress or arrest after puberty has begun.

c.	> 5 years elapsed between onset and menarche, or completion of male genital development.

d.	Delay in puberty occurs in any condition where the bone age is delayed; bone age correlates with developmental and pubertal stage, and puberty normally occurs when the bone age is pubertal, irrespective of the chronological age.

2.	Causes of delayed puberty

a.	Hypogonadotropin:

i.	constitutional delay: usually familial, associated with poor growth and a delayed bone age.

ii.	chronic illness: poor nutrition, e.g. cystic fibrosis, juvenile arthritis.

iii.	endocrine causes: hypopituitarism, isolated gonadotrophin deficiency, Kallmann’s syndrome, hypothyroidism, hyperprolactinaemia.

b.	Hypergonadotropin:

i.	gonadal dysgenesis: Turner, Klinefelter, Noonan.

ii.	gonadal damage: vascular damage, irradiation, infection, torsion or autoimmune disease.

3.	Clinical examination:

a.	Accurate staging of puberty.

b.	Assessment of growth parameters.

c.	Evaluation for evidence of chronic disease.

d.	Syndromal or endocrine features.

4.	Investigations:

a.	Baseline FSH, LH, testosterone, estradiol.

b.	GnRH stimulation test:

i.	low LH/FSH rise means prepubertal.

ii.	elevated LH/FSH implies primary gonadal failure.

c.	Thyroid function tests.

d.	Karyotype for Turner, Klinefelter.

e.	FBC and film: chronic anaemias.

f.	U&E: renal failure.

g.	X-ray of left wrist and hand for bone age:

i.	bone age < chronological age: constitutional delayed puberty.

ii.	bone age = or > chronological age: primary gonadal failure due to syndromal, endocrine or iatrogenic causes.

5.	Delayed puberty in girls

a.	More likely to be pathological.

b.	Lack onset by 13 years, no menses by 16 years.

c.	Therapy:

i.	start at 12 – 14 years old.

ii.	estrogen 6 – 12 months.

iii.	add progesterone later to induce regular withdrawal bleeding.

6.	Delayed puberty in boys

a.	Usually constitutional delay.

b.	History of short stature / constitutional growth delay.

c.	Therapy:

i.	constitutional delay: short course of androgens for 3 – 6 months to induce entry into puberty.

ii.	true gonadotropin deficiency or gonadal failure: oral androgen for 3 – 6 months, later convert to i/m depot testosterone esters 3 – 4 weekly.

Precocious puberty

1.	Definition

a.	Onset < 8 in girls and < 9 in boys.

b.	True / central precocious puberty: occurs when hypothalamic control mechanism for puberty is prematurely turned on, leading to early gonadal maturation.

c.	Pseudoprecocious / incomplete / peripheral puberty: not due to premature activation of the hypothalamic control system.

d.	True precocious puberty is far commoner in girls than in boys.

e.	In girls, it is usually idiopathic, whereas in boys the diagnosis is more often a central nervous system disorder, e.g. intracranial tumor or malformation.

f.	Problems:

i.	final height is short.

ii.	disruptive behavior, male aggression.

iii.	emotionally labile.

iv.	inappropriate attraction to opposite sex.

v.	menstruation.

2.	Causes

a.	True precocious puberty:

i.	idiopathic (90% of girls).

ii.	CNS insults: trauma, meningitis, tumor.

iii.	late treatment of CAH.

b.	Pseudoprecocious puberty:

i.	gonadal tumors.

ii.	adrenal tumors.

iii.	HCG secreting tumors.

iv.	CAH in males.

v.	McCune – Albright syndrome.

3.	McCune – Albright syndrome

a.	Triad of:

i.	precocious puberty.

ii.	polyostotic fibrous dysplasia.

iii.	Cafe-au-lait spots.

b.	Autonomous hyperfunction of multiple endocrine glands.

c.	Occurs predominantly in girls.

d.	Clinical features:

i.	hyperthyroidism.

ii.	Cushing’s syndrome.

iii.	growth hormone excess.

iv.	hyperprolactinaemia.

v.	phosphaturia causing rickets.

vi.	repeated fractures and bony deformities.

vii.	cranial nerve compression.

4.	Clinical examination:

a.	Accurate staging of puberty.

b.	Assessment of growth parameters.

c.	Evaluation of central nervous system, adrenal glands and gonads.

5.	Investigations:

a.	Baseline LH, FSH, testosterone, estradiol: differentiate true and peripheral causes.

b.	GnRH stimulation test: inject IV GnRH, rise in LH and FSH 30 minutes later implies true central puberty.

c.	DHEAS: high in adrenal tumors.

d.	hCG: can be produced by various tumors.

e.	Thyroid function tests.

f.	X-ray of left wrist and hand for bone age: 

i.	normal bone age: premature adrenarche, thelarche, or ingestion of exogenous sex steroids.

ii.	accelerated bone age: central precocity.

g.	Skeletal survey: suspected McCune – Albright syndrome.

h.	US of pelvis, testes, adrenal glands.

I.	Brain CT or MRI for various intracranial pathologies. 

6.	Management

a.	GnRH analogue given monthly i/m depot for central precocious puberty.

b.	Continuous non-pulsatile GnRH induces state of secondary hypogonadism.

c.	Stop progression of puberty and reclaim compromised growth potential.

d.	Alternatives:

i.	cyproterone acetate and medroxyprogesterone.

ii.	inhibitors of sex hormone production.

iii.	spironolactone with testolactone.

7.	Contrasexual precocious puberty

a.	Feminization in boys:

i.	gynaecomastia: idiopathic, pubertal, obesity, Klinefelter.

ii.	estrogen secreting hormones: hepatic, testicular, adrenal.

iii.	exogenous: drugs.

b.	Virilization in girls:

i.	congenital adrenal hyperplasia (CAH).

ii.	virilizing tumors.

iii.	polycystic ovarian syndrome.

iv.	idiopathic hirsutism.

Normal variants of development

1.	Premature thelarche in girls

a.	Isolated premature breast development.

b.	Occurs during two age periods.

c.	First two years of life.

d.	Persists or increase from birth and regresses before 24 months.

e.	Due to higher ovarian hormones or extra-responsive breast tissues.

f.	Second period after 6 years; may regress.

2.	Premature pubarche in girls and boys

a.	Early development of sexual hair without other sexual characteristic development.

b.	Result of premature adrenarche.

c.	Early increase in adrenal androgen production.

d.	Occurs during 6 – 8 years.

e.	Girls are more affected than boys.

f.	Higher DHEA.

g.	Exclude late-onset CAH.

3.	Premature menarche

a.	Uncommon.

b.	Must exclude pathological causes first – PV bleeding is pathological till proven otherwise.

c.	May be transient elevation of estradiol due to benign ovarian cyst.

d.	Benign and self-limiting.

4.	Pubertal gynaecomastia

a.	Common in boys during puberty.

b.	Onset: 10 – 12 years of age.

c.	Peak occurrence: 13 – 14 years.

d.	Last 18 – 24 months.

e.	Complete involution by 16 – 17 years.

f.	Due to imbalance between estrogen and androgen action.