Abnormal Puberty

Question 1

Puberty: awakening of the HPG (Hypothalamic, pituitary, gonadal axis)

Answer 1

Childhood- HPG axis is easily suppressed by any negative feedback of sex steroids

Puberty- GnRH pulsatility and the pituitary’s responsiveness to GnRH increase, LH peaks nocturnally, in early puberty (coinciding with greater nocturnal GnRH pulsility), Clinically a detectability lutenizing hormone (LH), is the 1st biochemical marker of HPG pubertal activation

Question 2

Pubertal timing rules of thumb

Answer 2

Females: Precocious Puberty <8 yo, Normal 8-13, delayed >13 yo

Males: precocious<9 yo, Normal 9-14 yo, Delayed >14yo

The rule of 2s
Female- Thlarche (breast) at 10 yo+- 2 yrs, Thelarrche occurs 2 yrs before menarche, menarche at 12 yo+- 2 yrs

Pubarche (Pubic hair growth), usually coincides within a year or two of the start of puberty (breast or testicular deveopment)

Question 3

Abnormal Puberty

Answer 3

Factors to consider
Timing- precocious or delayed
Cause- adrenal versus gonadal activity, gonadotropin dependent or independent (note- adrenals not driven by gonadotropins)
Pathologic or Variant of normals

Question 4

Types of precocious puberty

Answer 4

1. Gonadotropin dependent (GDPP) precocious puberty, detectable luteinizing hormone (LH)- indicates pubertal pituitary activity, Central precocious puberty GnRH/LHFSH driven
2. Gonadotropin Independent (GIPP) precocious puberty, Undetectable LH, also peripheral precocious puberty Not GnTH, LH or FSH driven
3. Incomplete precocious puberty Slow or non progressive development, isolated premature thelarche or isolated premature adrenerche

Question 5

Benign Premature Adrenarche

Answer 5

Exam: Pubic hair, acne, axillary hair, and/or body odor (ADRENAL INVOLVEMNET)
No pubertal growth acceleration, No clitoral/phallic testicular enlargement

Not HPG/ACTH driven due to development and activation of reticularis (17 20 lyase)

Studies- Normal 8AM 17 hydroxy progesterone (rules out CAH, from 21 hydroxylase deficiency)
DHEA- S (adrenarche versus adrenal tumor)
Bone age normal- 2 yr acceleration

Question 6

Gonadotropin dependent precocious puberty

Answer 6

Detectable LH indicates hypothalamic pituitary activation is driving puberty

Females- 95% of cases idiopathic- no evidence of CNS or other identifiable lesions

Males- >90% cases have pathologic CNS lesions, CNS tumors, congenital CNS anatomic abnormalities, CNS injury or diseases like neurofibromatosis type 1

Question 7

Treatment of Gonadotropin Dependent precocious puberty (GDPP)

Answer 7

long acting GnRH analogs block the binding of endogenous GnRH pulses at the pituitary

Pulses of GnRH are required for normal LH and FSH production and secretion

Drugs- Leuprolide depot (every 3 months or Histrelin implant (2yrs)

Elevated LH drawn after GnRH analog suggests GDPP

Question 8

Gonadotropin independent precocious puberty (GIPP)

Answer 8

GIPP= sex steroid production is independent of pituitary gonadotropin activity

Undetectable basal LH and lack of significant rise in LH following GnRH analog stimulation

Progressive pubertal development and growth acceleration

Differential includes non classical (late onset) congenital adrenal Hyperplasia, Gonadal/adrenal tumors, hepatic Germ cell tumors, McCune Albright syndrome, Testoxicosis

Question 9

Delayed Puberty

Answer 9

Late Bloomer , Constitutional delay of growth and puberty

Hypogonadotropic hypogonadism- Secondary or tertiary hypogonadism, inappropriately low LH and FSH, Congenital- pituitary /hypothalamus abnormalities, acquired CNS Tumors, CNS surgery, CNS irradiation etc

Functional Hypogonadotrphic hypogonadism: Chronic disease/malnutriotion (anorexia, cystic fibrosis, heart disease)

Hypergonadotrophic hypogonadism: primary hypogonadism, Elevated LH and FSH but lack of appropriate gonadal response, anorchia, AI gonadal failure, turner or klinefelter syndromes, chemotherapy, radiation

Question 10

Constitutional delay of growth and puberty CDGP aka late bloomer

Answer 10

variant of normal, non pathologic, often a family history of a similar late bloomer pattern, expect delay of adrenarche, gonadarche, and bone age, normal prepubertal growth but peers undergoing pubertal growth acceleration–> decreased height percentile, given a delayed bone age, the expected adult height is consistent with did parental height range

Question 11

treatment of delayed puberty

Answer 11

Constitutional delay of growth and puberty testosterone (males) or estradiol in females to accelerate growth /dev if signicant delay and psychological

Hypogonadotrophic hypogonadism- if functional- treat pathalogy (weight gain in anorexia, celiac diet)

T or E for irreversible damage to CNS with progesterone in females

Hypergonadotrophic hypogonadism ( gonadal insufficiency/failure) T or E