Puberty Flashcards
Normal puberty order
Growth acceleration (not maximal) -> Thelarche -> Adrenarche/Pubarche -> Peak height velocity -> Menarche
Etiology of thelarche
initial activity of HPO axis -> estrogen
Etiology of adrenarche/pubarche
Adrenal hormones -> hair growth
Zona reticularis: High P450c17, Low 3BHSD
How long between adrenarche and pubarche
2-3 years
How long between peak height velocity and menarche
6 months
What mediates peak height velocity?
GH -> IGF-1 -> IGFBP-1/3
First hormonal change in puberty
Nighttime LH pulses
- One year before breast buds form, nocturnal LH pulses change
- LH levels exceed those of FSH
- LH amplitude increases x10, FSH amplitude increases x 2 -> decrease in the FSH/LH ratio
- LH amplitude then rises to 20-40x greater than pre-pubertal levels
- LH bioactivity increases through glycosylation
First sign of male puberty
Testicular enlargement
Important neuropeptides/proteins/metabolic factors responsible for rise in GnRH with puberty
Stimulatory: NPY (controversial), Glutamate, Kisspeptin, Tachykinins (Neurokinin B, TACR3/TAC3), Leptin, Insulin,
Inhibitory: GABA, MKRN3, Ghrelin
Premature puberty definition
Signs of secondary sexual development occurring before the age of eight years in girls and the age of nine years in boys are considered premature and warrant careful evaluation
How to differentiate between central and peripheral premature puberty
GnRH Stim test
• High LH after stim -> gonadotropin dependent (central)
• Low/normal LH after stim -> gonadotropin independent (peripheral)
Central (gonadotropin-dependent) premature puberty etiologies
90% idiopathic
CNS lesions
Previous excess sex steroid exposure
Pituitary gonadotropin-secreting tumors
Secondary component of McCune-Albright syndrome
Poorly controlled CAH
Central premature puberty treatment
GnRH agonist
Central premature puberty genetics
- Gain-of-function mutations in kisspeptin 1 gene (KISS1) and its receptor (KISS1R)
- Loss-of-function mutation in MKRN3 (imprinted gene in Prader-Willi critical region)
- Loss-of-function mutation in DLK1 (delta-like 1 homolog)
CNS lesions leading to central premature puberty
Hamartomas, CNS tumors, CNS radiation
Peripheral (gonadotropin-independent) premature puberty etiologies in females (2)
Ovarian cysts – most common Ovarian tumors (Granulosa cell \> Sertoli/Leydig, pure Leydig, gonadoblastoma)
Peripheral (gonadotropin-independent) premature puberty etiologies in males (3)
Leydig cell tumors
HCG-secreting germ cell tumors
Activating mutation in LH receptor
Inheritance and pathophysiology of activating LH receptor mutation causing peripheral premature puberty
Autosomal dominant; premature Leydig cell maturation and testosterone secretion
Presentation of activating LH receptor mutation causing peripheral premature puberty in boys
Precocious puberty with normal spermatogenesis but arrested
Presentation of activating LH receptor mutation causing peripheral premature puberty in girls
Girls are not affected clinically, because (similar to hCG-secreting germ tumors) activation of both the LH and FSH receptors is required for estrogen biosynthesis