Puberty & Disorders

Question 1

Puberty is transition from non-reproductive to reproductive state - mature gametes. Secondary characteristics develop (primary are present at birth).

What are the main changes in males (apart from obv)

Answer 1

Vas deferens lumen increases
Androgens enlarge larynx. Adams apple, voice deepens
PHV = 10.3 cm/year reached at 14 years
Testosterone from Leydig cells stimulates meiosis & spermatogenesis in Sertoli cells- boys fertile at the beginning of puberty

Question 2

Puberty is transition from non-reproductive to reproductive state - mature gametes. Secondary characteristics develop (primary are present at birth).

What are the main changes in females? (apart from obv)

Answer 2

Thelarche (breast budding)– first outward sign of estrogen activity represents reawakening of HPG axis.
Myometrium responds to estrogen.
Height= (PHV) around 9 cm/year, reached at 12 years.
Increase in ovarian size and follicular growth

Question 3

What are the two endocrine events of puberty?
What do LH and FSH stimulate?

Answer 3

Adrenarche occurs first: adrenal gland cells mature + release androgens. This leads to pubarche (pubic + axillary hair)

After adrenarche is gonadarche= activation of the HPG axis–> FSH & LH synthesis + secretion, which activate gonad function

LH stimulates gonadal steroid synthesis and secondary sex characteristics, whereas FSH stimulates spermatogenesis and testes growth (m), and folliculogenesis w steroid synthesis (f)

Question 4

Describe adrenarche in more detail.
what is remodelled, what is start of Adrenarche marked by + how this changes with age, possible causes?

Answer 4

Adrenarche: adrenal gland remodelling changes adrenal secretion from the zona reticularis. The zona reticularis isn’t apparent in neonates- only develops in adrenarche.

Start of adrenarche is marked by the secretion of DHEA & DHEAS- responsible for pubarche.
Increasing gradually from ~age 10, peaking in mid 20s, then they decline throughout life. Other adrenal steroids are not affected.

Possible causes: unknown trigger, leptin or insulin or normal adrenal gland remodelling.

Question 5

Describe DHEAS transport and conversion, leading to pubarche
What is pubarche associated with?
when is pubarche considered precocious in girls vs boys?

Answer 5

DHEAS enters the circulation and is transported to target tissues where it can be converted to testosterone or DHT.

Responsible for axillary & pubic hair (pubarche). Pubarche is associated w: acne, increased sebum, infection, abnormal keratinization

Considered precocious before 8 yrs (girls) or 9 yrs (boys).

Question 6

Pubarche has an effect on PSUs. What are these and what are the different types?

Answer 6

PSUs= pilosebaceous unit. 2 types:
Sebaceous PSUs: small hair w big sebaceous gland at the bottom. Respond to androgens and increase sebum, which can block pores–> acne

Vellus PSUs: have small sebaceous glands, upon androgen exposure can differentiate into:
- Terminal : coarse facial hair
- Apocrine : axilliary/pubic hair, also have scent glands\ give off odour

Question 7

when does HPG first get activated + how long are GNRH hormones restrained for?
How is GnRH released and how do we measure its release?

Answer 7

HPGA 1st activated at 16 weeks. Pulsatile GnRH secretion continues in foetus until 1-2 yrs postnatally.
GnRH neurones ‘restrained’ during postnatal period and reactivated at gonadarche.

GnRH is released in a pulsatile manner
Hard to measure GnRH bc only small amounts of it in circulation
Also, produced by hypothalamus into portal circulation–> too invasive to measure directly. So, instead we measure LH

Question 8

How does the release of GnRH vary throughout life?

Answer 8

Pre-puberty: overall low GnRH secretion. No diurnal variations

Early/mid puberty: higher GnRH levels. secretion at night. Levels drop in day

Mid/late puberty: high GnRH secretion throughout day. Secretion still higher at night, though less diurnal variation

Adult: GnRH secretion decrease. Pulses mainly in day, not night

Question 9

What are the epiphyses?
What else happens in puberty that is related to the bones?
when does puberty growth spurt occur in girls vs boys?

Answer 9

The epiphyses are the rounded ends of long bones that are initially separate to the shaft
Initially low oestrogen when HPGA reawakens promotes linear bone growth at the start of puberty–> rapid growth spurt.
As oestrogen rises, the epiphysis fuses to the diaphysis (shaft) and growth can no longer occur

Growth spurt=an interaction between GH and oestrogen (in m&f)
Occurs ~2 yrs earlier in girls as oestrogen spikes 2yrs earlier–> earlier epiphyseal closure

Question 10

What stimulates the onset of puberty? Describe the three different theories.

Answer 10

Body fat: puberty is occurring earlier as nutrition has improved. Anorexia or malnutrition delays puberty
Theory that 17-18% body fat initiates puberty and 22% to maintain menstrual cycle – possible link with Leptin levels.

Inherent (genetic): maturation needs 1000-3000 GnRH synthesising neurones, and sufficient Kisspeptin neurones.

Kisspeptin: newest theory- mutations in Kisspeptin activate or inactivate puberty initiation

Question 11

What is consonance? Explain the variation in puberty between boys and girls

Answer 11

Question 12

How do doctors communicate with each other regarding puberty?
Also what are the psychological changes in puberty?

Answer 12

Because there is such variation, doctors communicate about pts using Tanner stages instead of age (see below)

Psychological changes: Increasing need for independence
Increasing sexual awareness/interest
Development of sexual personality

Question 13

Central precocious puberty
What is maintained?, causes
Give an example of a specific cause and the investigations and treatment for it

Answer 13

Central precocious puberty, gonadotrophin-dependent:
Consonance is maintained, but, puberty occurs much earlier

Causes: excess GnRH secretion OR Excess Gonadotrophin secretion. These can be caused by tumours by both hypothalamus and pituitary

FOR EXAMPLE: Hypothalamic hamartoma: found in 1/3 of pts, seen on MRI. Treated w injection leuprodex 3.75 mg (GnRH agonist) single dose i/m once in 28 days, w follow‑up on secondary sexual characteristics

Question 14

What is the treatment for central precocious puberty?

Answer 14

• GnRH analogues can be administered constantly to suppress the HPG axis, suppressing puberty until the age of 11 or 12
• Surgery, radiotherapy and chemotherapy are options if a pituitary tumour is at fault

Question 15

Peripheral precocious (pseudo) puberty? What are the 4 causes of it

T C S M

Answer 15

Loss of consonance. Causes:

Testotoxicosis: activating LHr mutation causes early androgen production by Leydig/Theca. No rise in FSH–>FSHr on Sertoli cells not activated, so no spermato/folliculogenesis

CAH: excess androgen production in the zona reticularis, causing precocious puberty w/o elevated gonadotrophins

A sex steroid secreting tumour or exogenous steroids

McCune-Albright: constitutive AC activation–> hyperactivity of gonadotrophin signalling pathways. Also causes Café-au-lait skin

Question 16

A 6-year-old boy was referred for an evaluation of precocious puberty. The patient had been in good health until one year prior to his referral when he began to show unusual acne on his forehead. The boy had been noted to have rapid body growth, presence of pubic hair, and an enlarging penis three months before being brought to clinic.

His radiological bone age was 12 years, testosterone level at 5.33 ng/ml, which had increased to 8.36 ng/ml three months after the initial visit. The LH was less than 0.100 mIU/ml, FSH was 0.179 mIU/ml. Testicular ultrasonography revealed a hypervascular heterogenous echogenic mass, size about 2.3 x 1.0 cm in the left testis.

What is the diagnosis?

Answer 16

Functioning Leydig cell adenoma

When removing and sequencing the tumour, there was a mutation at the LHr gene, keeping it in the on position
This explains the excess testosterone production by Leydig cells without getting the signal

Question 17

what is Pubertal delay?

Answer 17

Absence of secondary sexual maturation by 14years in boys; 13years in girls OR absence of menarche by 18years

Question 18

What are 3 causes of pubertal delay?

Answer 18

Constitutional delay: common cause of growth + puberty delay. Seen more in boys, often hereditary, involves many genes.
Here puberty starts later, but goes at normal pace once it starts. Secondary to chronic illness eg. diabetes, CF

Hypogonadotrophic hypogonadism (low LH+ FSH)

Hypergonadotrophic hypogonadism (high LH + FSH, but low levels of sex steroids):

Question 19

What are the 3 different causes of hypogonadotrophic hypogonadism
what about the 3 causes of hypergonadotrophic hypogonadism?

Answer 19

Hypogonadotrophic hypogonadism (low LH+ FSH). Causes:
Kallman’s syndrome: mutation of X-linked KAL gene impairs GnRH neurone migration
Hypopituitarism & impaired gonadotrophin structure
High doses / long-term opioid or gcc use

Hypergonadotrophic (high LH + FSH, but low levels of sex steroids). Causes
Gonadal dysgenesis decreases sex steroids–> little neg feedback–> excessive LH+FSH secretion
Gonadal dysgenesis w a normal karyotype (eg secondary to mumps infection)
Congenital causes like Klinefelter’s (47XXY) & Turner’s (45XO)