Puberty

Question 1

Define the tanner stages (breast)

Answer 1

1. Pre-pubertal. Elevation of papilla only
2. Breast bud stage. Elevation of breast and papilla as small mound, enlargement of areola.
3. Further enlargement of breast and areola
4. Projection of areola and pilla to form a secondary mound above the level of the breast.
5. Mature stage. Projection of papilla only

Question 2

Define the tanner stages (pubic hair)

Answer 2

1. Pre-pubertal. No pubic hair
2. Sparse growth of long, slightly pigmented downy hair, straight or only slightly curled, along labia/base of penis
3. Hair is darker, coarser and curlier, spreads over the superior junction of labia majora
4. Adult type hair, but area covered is smaller than most adults (no spread to medial thighs)
5. Adult hair quality and quantity, spread is to the medial surface of the thighs

Question 3

What is the average age of menarche

Answer 3

12.9 years (Caucasian girls) and 12.3 years (African American girls)

Question 4

_____ is the most important factor in stimulating maturation of chondrocytes and osteoblasts, ultimately leading to epiphysial fusion

Answer 4

Estrogen

Question 5

In males, LH stimulates the ____ to produce ____ and FSH stimulates the _____ to produce _____

Answer 5

• LH –> Leydig cells –> testosterone
• FSH –> Sertoli cells –> inhibin

Question 6

In females, LH stimulates the ____ to produce ____ and FSH stimulates the _____ to produce _____

Answer 6

• LH –> theca cells –> androgens (minor role until menarche)
• FSH –> granulosa cells –> estrogen and follicles –> inhibin

Question 7

How long does the mini-puberty of infancy last? Why does it happen?

Answer 7

• Lasts a few months up to 2 years.
• Happens due to decreased circulating estrogen/testosterone causing reduction of negative inhibition of gonadotropinc

Question 8

What lab values define central precocious puberty?

Answer 8

• Basal LH over 0.3 U/L
• Peak LH over 5.5 after Lupron

Question 9

Increasing the frequency of GnRH pulses _____ the LH:FSH ratio

Answer 9

Increases

Question 10

Define delayed puberty

Answer 10

Girl >13 years or boy >14 years without signs of pubertal development

Question 11

List a differential diagnosis for delayed puberty

Answer 11

• Constitutional delay of growth and puberty
• Hypogonadotropic hypogonadism
  
  • CNS disorders (tumors, infection, trauma, irradiation)
  • Isolated hypo hypo (Kallman)
  • Multiple pituitary hormone deficiencies
  • Chronic disease
  • Weight loss/anorexia nervosa
  • Increased physical activity (female athletes)
  • Hypothyroidimsm
  • Prader Willi, Bardet Biefl
• Hypergonadotropic hypogonadism
  
  • Males: Klinefelter, cryptorchidism, vanishing testes
  • Females: Turner
  • Primary gonadal failure (chemotherapy, radiation, surgery)
  • XX and XY gonadal dysgenesis

Question 12

List 3 tumors that cause delayed puberty

Answer 12

• Craniopharyngioma (remember: calcifications!)
• Germinoma
• Glioma
• Astrocytoma
• Hyperprolactinemia/Prolactinoma

Question 13

What genes are affected in Kallman syndrome?

Answer 13

• X-linked Kallman syndrome: KAL1
• Kallman syndrome 2: FGFR1
• Kallman syndrome 3: PROKR2, PROK2

Question 14

List 5 genes that can cause hypogonadotropic hypogonadism

Answer 14

• Kallman (KAL1, FGFR1, PROKR2)
• SF1
• HESX1
• LHX3
• PROP1

Question 15

List 5 clinical features of Klinefelters

Answer 15

1. Decreased upper to lower segment ratio
2. Small, firm testes
3. Increased incidence of developmental delay/personality disorders
4. Delayed/variable puberty development
5. Gynecomastia
6. Tall stature

Question 16

List 10 clinical features of Turner syndrome

Answer 16

• Short stature
• Delayed puberty/amenorrhea
• Streak gonads
• Structural anomalies of the kidney
• Vascular anomalies of the left heart (coarctation, bicuspid aortic valve)
• Hypertension
• Micrognathia, fish mouth (downturned corners of mouth)
• Ptosis
• Low-set or deformed ears
• Frequent otitis media, hearing loss
• Broad shield-like chest, widely spaced nipples
• Hypoplastic areolae
• Short neck with low posterior hairline, webbing of neck
• Short fourth metacarpals
• Cubitus valgus
• Extensive nevi
• Hypoplastic nails
• Normal IQ but difficulty with math/geometry
• Increased incidence of autoimmune hypothyroidism

Question 17

List a differential diagnosis for precocious puberty

Answer 17

• CENTRAL
  
  • Idiopathic CPP
  • CNS tumor or hamartoma
• PERIPHERAL
  
  • Males: HCG secreting tumor, Leydig cell tumor, familial gonadotropin-independent secual precocity with premature Leydig and germ cell maturation
  • Females: Granulosa cell tumor, follicular cyst

Question 18

Which gonads are more resistant to chemotherapy, ovaries or testes?

Answer 18

Ovaries

Question 19

List 7 clinical features of Noonan syndrome

Hint: “Pseudo-Turner”

Answer 19

• Webbed neck
• Ptosis
• Short stature
• Cubitus valgus
• Lymphedema
• Triangular facies
• Pectus excavatum
• Right heart disease
• Developmental delay
• Cryptorchidism

Question 20

Define precocious puberty

Answer 20

• Secondary sexual characteristic before
  
  • Age 9 in boys
  • Age 8 in girl (controversial, age 7-8 in Caucasians and 6-7 in African American girls MAY be normal but should prompt referral and investigation)

Question 21

List a differential diagnosis for precocious puberty

Answer 21

• CENTRAL
  
  • Constitutional
  • Idiopathic
  • CNS disorders (tumor, infection, trauma, radiation, following androgen exposure)
• PERIPHERAL
  
  • Males: LH/FSH-secreting tumors, excessive androgen production, testicular or adrenal tumors, virilizing CAH, premature Leydig and germinal cell maturation
  • Females: ovarian cysts, estrogen-secreting neoplasm, severe hypothyroidism
  • Males and females: McCune albright syndrome, exogenous androgens/estrogens

Question 22

List 3 chromosomal syndrome associated with precocious puberty

Answer 22

• Williams-Beuren
• Russell-Silver
• Temple
• Prader Willi
• Rett

Question 23

How do hypothalamic hamartomas cause precocious puberty?

Answer 23

• Secrete GnRH OR
• Secrete TGF-alpha which stimulates GnRH secretion

Question 24

List 3 tumors that secrete gonadotropins and stimulat precocious puberty in males

Answer 24

• Hepatoma/hepatoblastoma
• Teratoma/choriocarcinoma of mediastinum, gonas, retroperitoneum, pineal gland
• CNS germinoma

Question 25

What is Van Wyk-Grumback syndrome?

Answer 25

Hypothyroidism causing precocious puberty and galactorrhea

Question 26

List 5 manifestations of McCune Albright syndrome

Answer 26

* Cafe at lait macules * Precocious puberty * Polyostotic fibrous dysplasia, hearing loss * Hyperthyroidism * Cushings, adrenal nodules * Acromegaly * Hyperprolactinemia * Hyperparathyroidism * Hyperphosphatemic hyperphosphaturia rickets * Ovarian cysts