Male Abnormal Puberty - Marifke Flashcards Preview

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Flashcards in Male Abnormal Puberty - Marifke Deck (27):
1

Define premature male puberty

Onset of pubertal development at an age earlier than expected based upon established normal standards

In the US, this is generally considered <9 years old

2

Give the Tanner Stage of each of the following:

  • Enlargement of the scrotum and testes with reddening and textural changes of the scrotal skin
  • Prepubertal
  • Increased size of penis with further growth of the testes
  • Adult genitalia
  • Increased size of the penis with growth in breadth and development of the glans, testes, and scrotum. The scrotum skin darkens.

  • Stage 2
  • Stage 1
  • Stage 3
  • Stage 5
  • Stage 4

3

By approximately what age (on average) should boys reach Tanner Stage 5?

~15

4

What is GDPP?

Is this more common in boys or girls?

Early maturation of the hypothalamic-pituitary-gonadal axis, resulting in premature puberty

Most idiopathic cases are in girls (80% of cases are idiopathic)

5

Give some causes of GDPP

Idiopathic

Hamartoma (benign, most frequent CNS tumor in very young children)

Other CNS tumors: astrocytoma, ependymoma, pinealoma, optic and hypothalamic glioma

CNS irritation or lesions: hydrocephalus, cysts, trauma, inflammatory disease, congenital midline defects

Genetics: Kisspeptin 1 gene and KISS-1R (gain on function mutations); MKRN3 (loss of function)

Primary hypothyroidism

6

Give (7) broad underlying causes of GIPP

  • Leydig cell tumors
  • HcG-decreting germ cell tumors
  • Familial male limited premature puberty
  • Adrenal pathologies
  • Exogenous estrogen
  • Pituitary gonadotropin secreting tumors
  • McCune Albright syndrome

7

Describe the Isosexual form of GIPP

Leydig cell tumors or 

8

What is the classic triad of McCune Albright syndrome?

  • Peripheral premature puberty
  • Care au lait skin pigmentation
  • Fibrous dysplasia of bone

9

What enzymatic defects of adrenal steroid biosythesis might lead to GIPP?

  • 11-beta hydroxylase deficiency
  • 3-beta hydroxysteroid dehydrogenase type II deficiency
  • Hexose 6 phosphate dehydrogenase deficiency
  • PAPSS2 deficiency

10

What is incomplete premature puberty?

Premature puberty due to increased adrenal androgen production with isolated male hormone mediated sexual characteristics

Can manifest as premature andrenarche or premature thelarche (breast development)

11

Describe premature adrenarche and premature thelarche in terms of:

  • Gonadotropin levels
  • LH response after GnRH stimulation
  • Sex steroid hormone levels
  • Clinical features
  • Additional evaluation required

Premature adrenarche

  • Prepubertal LH levels
  • No LH response to GnRH stimulation
  • elevated DHEAS (Tanner 2, >50ug/dL), 17-OHP and testoerone normal, early pubertal response to ACTH
  • No other signs of pubertal development; normal growth rate. Onset after 6 years of age. Associated frequenyly with brain injury, obesity, SGA (smalle for gestational age)
  • Monitor for possible early signs of full puberty

Premature thelarche

  • Prepubertal LG levels
  • No LH response, normal FSH response
  • Pre-pubertal sex steroid levels
  • No other signs of pubertal development; growth rate normal
  • Monitor for possible early progression to full puberty

12

Describe the evaluation of GDPP in terms of:

  • Gonadotropin levels
  • LH response to GnRH stimulation
  • Sex steroid hormone levels
  • Clinical features
  • Additional evaluation required

  • Pubertal levels with prominent LH pulses during sleep (LH>0.6IU/L)
  • Pubertal response: LH >7IU/L
  • Pubertal values of estradiol (>9ph/mL), testosterone (20-1200 ng/dL) and DHEAS
  • Early pubertal development, but with normal progression timing and sequence. Includes enlargement of the testes or ovaries/uterus. Bone age is greater than chronological age
  • Evaluate with contrast MRI to rule out CNS abnormality, measure hCG in boys to rule out hCG-secreting tumor, examine skin and do skeletal survey to rule out McCun-Albright syndrome

13

The giant table on slide 21 crits you for 42 nature damage and knocks you prone. Despite this, you can name the one unifying diagnostic feature of all 9 listed etiologies of GIPP. What is it?

Absent LH response to GnRH stimulation test

14

In the setting of GIPP (premature puberty unresponsive to GnRH test), you observe elevated hCG and a mediastinal mass. What disease are you immediately suspicious of and what test(s) should you order next?

Klinefelter syndrome

Order karyotype and testicular ultrasound

15

Broadly, what is the treatment approach to GDPP?

Direct therapy for the underlying pathology (if identifiable). This may inlcude surgery (except for benign hypothalamic hamartoma -> does not require surgery)

GnRH agonist

16

What is the primary goal of treatment for any premature puberty disorder?

Achieve normal adult height

17

What is an example of a drug used as a GnRH agonist?

How is it given?

How long should therapy last?

When does puberty 're-appear' following termination of treatment?

Leuprolide - initially stimulates, then causes complete (reversible) suppression of pituitary gonadotropins

Given once monthly by IM injection ('depot') 0.3mg/kg (or start 11.25mg and titrate upwards)

Continue until about 12 years of age (variable depending on bone age, height, and 'social desire to join peers in puberty')

Normal puberty returns ~17 months after cessation of therapy

18

Broadly, what is the treatment strategy for GIPP?

Give some examples

Address the underlying cause

Congenital adrenal hyperplasia: glucocorticoid therapy

McCune-Albright: anti-androgens with aromatase inhibitor

Familial Male Limited Premature Puberty: spironolactone, an anti-androgen, and testolactone (aromatase inhibitor)

Secondary GDPP (consequence of GIPP treatment): GnRH agonist therapy

 

19

What is the treatment approach for Incomplete premature puberty?

No therapy required. Follow closely.

20

Name (4) GnRH agonists

Histreline acetate

Leuprolide

Goserelin

Triptorelin

21

Define delayed male puberty

Absence or incomplete development of secondary sexual characteristics based on an age where 95% of peers have initiated sexual maturation (>14 years of age in USA)

22

Broadly, what is the treatment approach to any etiology of delayed male puberty

Address underlying cause (if possible)

Watchful waiting

Androgen therapy

23

What is the most common etiology of delayed male puberty?

Name three others

Constitutional delay (53%)

Functional hypogonadotropic hypogonadism (19%) -> illness or stress-driven

Hypogonadotropic hypogonadism (12%)

Hypergonadotropic hypogonadism (13%)

24

Describe the major features of Klinefelter's Syndrome

  • Long bone abnormalities of leg (independent of testosterone deficiency)
  • Psychosocial abnormality involving social interactions (poor insight/judgement)
  • Impairment of higher-level linguistic competence (vocabulary and language intact)
  • Attention deficit and impulsiveness
  • Increased risk of certain diseases, including
    • Pulmonary diseases (bronchitis, bronchiectasis, emphysema)
    • Cancer (germ cell, breast, NHL)
    • Varicose veins
    • SLE
    • Diabetes mellitus

25

What is observed with primary hypogonadism? What disease should be considered in the differential?

What is observed with secondary hypogonasism?

  • Primary: low testosterone and/or sperm with high LH and FSH
    • consider karyotyping for Klinefelter's Syndrome
  • Secondary: low testosterone and/or sperm with low or inappropriately normal LH and FSH
    • Requires pituitary workup

26

Name some causes of primary male hypogonadism

Name some causes of secondary male hypogonadism

Primary

  • Congenital defects
  • Genetic defects (e.g. Klinefelter's)
  • Bilateral orchitis due to mumps
  • Bilateral testicular torsion or varicocele
  • Irradiation
  • Cytotoxic drugs

Secondary

  • Pituitary disorders (tumors, panhypopituitarism)
  • Hypothalamic disorders (Kallman's syndrome)

27

Describe the clinical workup for evaluation of hypogonadism

  • H&P shows symptoms and signs of hypogonadism
  • Measure morning total T (7am-9am, fasting)
    • If normal, follow-up later
    • If low, exclude reversible illness, drugs, nutritional deficiency
  • If first test was low and confounding factors ruled out, measure T, LH, and FSH (also SFA if fertility issue; free T if altered SHBG suspected)
    • if normal, follow-up later
    • If confirmed low T, determine primary or secondary from LH and FSH
  • If Low T, high FSH + LH: primary
    • Karyotype for Klinefelter's
  • If low T, low or normal LH + FSH
    • Evaluate prolactin, iron, other pituitary hormones
    • MRI pituitary (if indicated by hormone studies)

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