Abnormal Male Puberty Flashcards
1
Q
Definition – onset of pubertal development at an age earlier than expected based upon established normal standards
A
2
Q
Beginning of enlargement of scrotum and testes; change in texture and reddening of scrotal skin
A
Tanner 2
age 11
3
Q
Beginning growth of the penis, mainly in length; further growth of testes and scrotum
A
Tanner 3
age around 13
4
Q
Further growth of penis in lenght and breadth; further darkening of the scrotal skin
A
Tanner 4
late 13
5
Q
Adult sized genitals
A
6
Q
Premature Male Puberty
- In the United States this would generally be considered less than _______
- Level of concern for further evaluation should increase with decreasing age at presentation
- Initial evaluation at a minimum should include a comprehensive history and physical examination
A
9 years of age
7
Q
Premature Male Puberty
•Three questions to ask
A
Is the child to young to have reached the pubertal milestone in
question?
What is causing the early sexual development?
Is therapy indicated and if so which therapy?
8
Q
Premature Male Puberty
•Classifications
A
- Gonadotropin-dependent premature puberty (GDPP)
- Gonadotropin independent premature puberty (GIPP)
- Incomplete premature puberty
9
Q
- Due to early maturation of the hypothalamic pituitary gonadal axis
- More than 80% of cases are idiopathic
- Almost all idiopathic cases are in girls
A
Gonadotropin-dependent premature puberty (GDPP)
10
Q
•GDPP; most cases are idiopathic, if not the causes are CNS lesions and often Hamartomas which are:
A
Benign
• Most frequent CNS tumor in very young children
11
Q
Most frequent CNS tumor in very young children that causes premature male puberty
A
Hamartomas; often benign and in the CNS
12
Q
Random causes of premature male puberty
A
•Other CNS tumors
- Astrocytoma
- Ependymoma
- Pinealoma
- Optic and hypothalamic glioma
**•CNS irradiation **
13
Q
•Other CNS lesions
- Hydrocephalus
- Cysts
- Trauma
- CNS inflammatory disease
• Congenital midline defects
A
Premature male puberty
14
Q
- Genetics causes of premature male puberty
- Gain of function mutations in ______
- Loss of function mutations in ______
A
Kisspeptin 1 gene and KISS-1R
MKRN3
15
Q
•Previous excess steroid exposure
- Primary hypothyroidism
- Regress with thyroxine therapy
A
More fucking causes of preamture male puberty
16
Q
- Due to excess secretion of sex hormones derived either from gonads or adrenal glands, exogenous sources of steroids, or ectopic production of gonadotropin from a germ cell tumor
- May be gender appropriate or inappropriate
A
GIPP: Gonadotropin independent premature puberty
17
Q
GIPP
•Due to excess secretion of sex hormones derived either from
A
gonads or adrenal glands
exogenous sources of steroids
ectopic production of gonadotropin from a germ cell tumor
18
Q
Premature Male Puberty: GIPP: Isosexual
A
- Leydig cell tumors
- Human chorionic gonadotropin (hCG) secreting germ cell tumors
19
Q
•Premature male puberty from GIPP :
Human chorionic gonadotropin (hCG) secreting germ cell tumors often located in:
A
•Gonads, brain, liver, retroperitoneum, posterior mediastinum
20
Q
- Familial male limited premature puberty, rare
- Result of an activating mutation in _________
A
LH receptor gene
21
Q
Premature Male Puberty
•Adrenal pathology, Androgen secreting tumors, Enzymatic defects and adrenal steroid biosynthesis
A
- 11 beta Beta hydroxylase deficiency
- 3 beta hydroxysteroid dehydrogenase type II deficiency
- Hexose 6 phosphate dehydrogenase deficiency
- PAPSS2 deficiency
22
Q
Premature male puberty with adrenal pathology
A
- Estrogen secreting tumors
- Androgen and estrogen secreting tumors
- Androgen secreting tumors
- Enzymatic defects and adrenal steroid biosynthesis
23
Q
- Rare
- Triad of peripheral premature puberty, café au lait skin pigmentation, and fibrous dysplasia of bone
A
•McCune Albright syndrome
24
Q
- Exogenous estrogen
- Pituitary gonadotropin secreting tumors
• Rare
A
Premature Male Puberty
25
Cause of incomplete premature male puberty
Due to increased adrenal androgen production
•Isolated male hormone mediated sexual characteristics (pubic and/or axillary hair, acne, and apocrine odor)
26
Evaluation for premature male puberty
• History and Onset
• Family history – siblings and parents
* Linear growth acceleration
* Symptoms related to etiology: headaches, seizures, abdominal pain
* History of CNS disease or trauma
27
Examination of premature male puberty; what are we looking for?
* Height, weight, height velocity • Fundoscopic
* Visual fields
* Dermatologic
* Tanner staging
* Bone age
28
* Laboratory and Imaging
* Measure basal LH levels, if elevated \_\_\_\_\_\_
* If not clearly elevated stimulate with GnRH agonist (several protocols available)
* Elevated LH and FSH means GDPP
* Lack of significant increase means GIPP
GDPP
29
* Laboratory and Imaging for premature male puberty
* Measure basal LH levels, if elevated GDPP
* If not clearly elevated stimulate with GnRH agonist (several protocols available)
* Elevated LH and FSH means\_\_\_\_\_
* Lack of significant increase means\_\_\_\_\_
GDPP
GIPP
30
Patient has signs of premature male puberty. You measure basal LH levels and they were elevated.
What do you suspect and what do you do next?
GDPP
• Pituitary MRI
* Estradiol, testosterone, TSH, free T4
* GH if prior cranial irradiation
31
You suspect your pt has premature male puberty. You try to measure LH levles but nothing happens so you stimulate GnRH
results still show lack of significant LH rise. What is the dx and what do you do next?
• If GIPP
Testosterone, estradiol, LH, FSH, cortisol (drawn in the evening), and DHEA, DHEAS, 17 hydroxyprogesterone, hCG
If hCG elevated and tumor in mediastinum a karyotype for Klinefelter syndrome recommended for mediastinal germinoma
• Testicular ultrasound
32
Pt has GIPP, If hCG elevated and tumor in mediastinum a karyotype for
Klinefelter syndrome recommended for mediastinal germinoma
33
Treatment for GDPP
Direct therapy toward underlying pathology for identifiable CNS lesions
Exception includes :benign hypothalamic hamartoma
Majority of patients will require t**reatment with GnRH agonist **
34
Direct therapy toward underlying pathology for identifiable CNS lesions
Exception includes benign hypothalamic hamartoma
Majority of patients will require treatment with GnRH agonist
GDPP
35
* Decision to treat in Premature Male Puberty
* Primary goal to :
* Do not treat primarily to address perceived psychosocial consequences
achieve normal adult height
36
important considerations when treating for premature male puberty
* Age
* Younger age
* Rapid progression
* Rate of maturation • Height prediction
* Less than 160 cm
37
GnRH agonist treatment for GDPP
• Initial stimulation of pituitary gonadotropin secretion followed by a complete but \_\_\_\_\_\_\_\_\_
* Treatment continued until it appears that it is safe and appropriate for puberty to proceed
* Leuprolide depot (one month) given intramuscularly once monthly starting dose of 7.5 mg, 11.25 mg, or 15 mg depending on child’s weight (approximately 0.3 mg/kilogram /dose)
reversible suppression
38
GnRH agonist treatment for GDPP
• Initial stimulation of pituitary gonadotropin secretion followed by a complete but reversible suppression
• Treatment continued until it appears that it is safe and appropriate for puberty to proceed
What is it done with?
• Leuprolide depot (one month) given intramuscularly once monthly starting dose of 7.5 mg, 11.25 mg, or 15 mg depending on child’s weight (approximately 0.3 mg/kilogram /dose)
39
Premature male puberty; how is leuprolide less efficient as a treatement
* Alternatively a 3 month preparation of leuprolide depot if desiring less frequent administration
* Somewhat less clinical evidence for efficacy
* Most patients start at 11.25 mg and titrate upwards, however; males with/without hypothalamic hamartoma generally require 30 mg
* Monitor response after 3 months of therapy and adjust upward if pubertal progression is not suppressed
40
Premature Male Puberty:
• Measure\_\_\_\_\_and \_\_\_\_\_\_\_just prior to second or third monthly dose or after a change in dose
* Measure \_\_\_\_\_\_every 6-12 months
* Success can be measured by performing a diagnostic \_\_\_\_\_\_\_
LH and sex steroid levels
bone age
GnRH agonist stimulation test
41
How do we treat congenital adrenal hyperplasia causing premature male puberty
glucocorticoid therapy
42
Boys rarely affected by McCune Albright syndrome but can be treated with \_\_\_\_\_\_\_and\_\_\_\_\_\_\_ similar to that for familial male limited premature puberty
anti-androgens in combination with an aromatase inhibitor
43
Familial male limited premature puberty can be treated with
spironolactone an anti-androgen and testolactone an aromatase inhibitor
44
•\_\_\_\_\_\_\_\_\_ an inhibitor of androgen sythesis is also effective but can cause hepatotoxicity and adrenal insufficiency
Ketoconazole
45
• Secondary GDPP may develop and can be treated with
GnRH agonist therapy
46
• Incomplete premature puberty treatment
• Does not require therapy but should be examined regularly
47
To block GDPP we need to act at the level of the \_\_\_\_\_
At the level of the hypothalamus: prevent LH and FSH release from the pituitiary by blocking GnRH
48
For GIPP we need to act at the level of the \_\_\_\_\_\_
the testicles and block aromatase
49
Absence or incomplete development of secondary sexual characteristics based on an age where 95% of children that sex and culture have initiated sexual maturation (\> 14 years of age in the United States).
Delayed Male Puberty
50
The disease is usually the result of inadequate gonadal (testicular) steroid secretion, most often caused by _______ from the anterior pituitary, due to defective production of GnRH from the hypothalamus.
defective gonadotropin secretion (LH and FSH)
(can be the result of a variety of hypothalamic, pituitary, and gonadal disorders)
51
Delayed male puberty: etiology is often:
* Etiology can typically be identified through a careful history, physical exam, and series of laboratory and imaging
* Treatment involves watchful waiting versus androgen therapy
52
You see delayed puberty in a boy, what is the first test you should order
Get an LH
53
You get an LH on a boy with delayed puberty, if its low what do you do next?
Get detailed family history; may need to look into adrenal insufficiency
54
Delayed puberty in a boy with high LH and FSH, what do we need to do next?
karyotype
55
most common cause of etiology delayed male puberty
constitutional delay
next is functional hypogonatotropic hypogonadism
56
Patient has hypogonadal, has femal habitis, poorly virilized with gynecomastia and eunuchoidism with a small phallus
Klinefelters syndroem
57
* **Long bone abnormality** of leg independent of that related to testosterone deficiency
* Psychosocial abnormality involving social interactions – **poor insight/judgement**
* I**mpairment of higher level linguistic competence**, but sparing of vocabulary and understanding of language
* **Attention deficit** with resultant impulsiveness
Klinefelter’s Syndrome
58
Klinefelters syndrome causes what type of pulmonary diseases and cancers?
**• Pulmonary diseases**
• Bronchitis, bronchiectasis, and emphysema
* **Cancer**
* Germ cell, breast, and non-Hodgkin lymphoma
59
* Varicose veins : Leg ulcers
* Systemic lupus erythematosus
* Diabetes mellitus
Associated with Klinefelters syndrome
60
Male Hypogonadism
• Primary –
low testosterone and/or sperm with high LH and FSH, consider karyotype for Klinefelter’s Syndrome
61
Male Hypogonadism
## Footnote
Secondary causes
low testosterone and/or sperm with low or inappropriately normal LH and FSH, needs pituitary work up
62
Treatment of Male Hypogonadism
* Treat or address underlying cause and associated conditions
* Treatment options numerous based on patient goals and preferences
* Screen for contraindications to therapy and regularly monitor for adverse events
63
Primary Hypogonadism, we see huge increase in what hormones?
LH and FSH get a huge surge that act on the testes
64
Causes of primary male hypogonadism
FSH and LH increase but still low testosterone
causes testicular agenesis, Klinefelters syndrome, 5alpha reductase and untreated cryptorchidism
65
Seconary causes of male hypogonadism: see low testosterone and low or normal LH
often pituitary disorders, tumors, panhypopituitarism, hypothalmic or Kallmans
66
High levels of testosterone lead to increase estradiol causing:
bone formaiton and breast tissue
67
Testosterone leads to elevated DHT levels; what are the effects?
facial and body hair, acne, scalp hair loss, prostate growth
68
Testosterone has what direct effects on the body
muscle mass, skeletal growth, spermatogenesis, sexual function
69
You suspect your pt has hypogonadism, what do you look for?
Get morning total Testosterone
70
Your patient has low testosterone, what do you do next?
exculde reversible illness/drugs/nutitional deficiency
Repeat T levels
LH and FSH levels should be checked
71
Pt has low T, low or normal LH and FSH, what do you do next
(pt suspicious for hypogonadism)
Get prolactin, iron, and check for pituitary hormones
get MRI if indicated
72
Pt has low T, high LH and FSH, what do we suspect?
Primary hypogonadism
Karyotype for klinefileter
