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Endocrine > Male Gonadal Disorders - Exam 4 > Flashcards

Male Gonadal Disorders - Exam 4 Flashcards

1
Q

Hypothalamic-Pituitary-Gonadal (HPG) first becomes active at ______. What hormones are made where? How often is it released?

A

puberty

Hypothalamus secretes GnRH, stimulating the anterior pituitary to release FSH and LH

pulsatile release every 2 hours

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2
Q

____ stimulates the _____cells of the testes to regulate ______ and produce ____. ______ provides a _____ feeback

A

FSH

Sertoli cells

spermatogenesis

inhibin B

inhibin B

negative feedback

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3
Q

____ stimulates ______ synthesis in the _____ cells of the testes. _____ provides a negative feedback and assists ____ in spermatogenesis

A

LH

testosterone

Leydig

testosterone

FSH

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4
Q

____ attaches to the ____ cells via LH receptor which stimulates ?????

A

LH

Leydig

the uptake of cholesterol by the cellular mitochondria and initiates steroidogenesis

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5
Q

What 2 things can testosterone be converted to? Where does the conversion take place?

A

Dihydrotestosterone¹ (DHT) or Estradiol

takes place in the peripheral tissues

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6
Q

testosterone plus _____ (enzyme) = Dihydrotestosterone

testosterone plus _____ (enzyme) = estradiol

A

5alpha- reductase

CYP12 (also called aromatase)

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7
Q

**90% of testosterone is ______. What are some functions of testosterone?

A

excreted

Wolffian duct
bone formation
muscle mass
spermatogenesis
sexual health (libido, erection, orgasm)
mood/behavior (increases aggression, decreases anxiety/depression, provides sense of mental well-being)
improves congnition/memory

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8
Q

**What are some functions of DHT?

A

external genitalia
prostate growth
acne
facial/body hair
scalp hair loss

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9
Q

**What are some functions of estradiol?

A

hypothalamic/pit feedback
bone reabsorption
growth plate closure
gynecomastia
vascular and behavioral effects

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10
Q

95% of circulating testosterone is synthesized in the _____, the remainder is produced by the _____. How much is active?

A

testicles

adrenal gland

only the remaining 2% is in active form

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11
Q

Name the 2 plasma proteins that testosterone is bound to. Which one has a greater affinity?

A

**sex hormone–binding globulin¹ (SHBG) (60%) - has greater affinity

albumin (38%)

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12
Q

____ of testosterone is unbound (physiologically active). Can testosterone unbind easily?

A

2%

albumin bound testosterone can dissociate readily in the capillaries becoming an active hormone

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13
Q

Testosterone is metabolized in the ___and excreted in the ___

A

liver

kidneys

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14
Q

What layer of the adrenal gland makes greater amounts of androgens? What age does it start?

A

zona reticularis

between 6-8 years old

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15
Q

What is sex maturation accelerated by? What is produced? How old?

A

sex maturation is accelerated by the activation of the HPG axis and the production of GnRH, LH, FSH and testosterone

begins around 9

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16
Q

What are the stages of male development called?

A

Tanner Stages 1-5

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17
Q

Prepubertal, no pubic hair. What tanner stage?

A

stage 1

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18
Q

sparse, straight pubic hair along the base of the penis, enlargement of testes and scrotum, scrotal skin reddens and changes in texture. What Tanner stage?

A

stage 2

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19
Q

Hair is darker, coarser and curlier and extends over the mid-pubis. enlargement of the penis and further growth of the testes. What tanner stage?

A

stage 3

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20
Q

Hair is adult-like in appearance but does not extend to thighs. increased size of penis with growth in breadth and development of glans, testes and scrotum larger, scrotal skin darker. What tanner stage?

A

stage 4

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20
Q

hair is adult like in appearance and extends from thigh to thigh, full adult genitalia. What tanner stage?

A

stage 5

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21
Q

How do you measure testicle size? Prepubertal size is ____. Pubertal is ____/ Adult are _____

A

Prader orchidometer - beads labeled by volume

Prepubertal sizes are 1 to 3 mL
Pubertal sizes are 4 to 12 mL
Adult sizes are 12 to 25 mL

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22
Q

If you do NOT have orchidometer, what size do the testicles have to be in order to be considered “entered puberty’?

A

Testicular size >2.5 cm longitudinally generally indicates that the child has entered puberty

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23
Q

What is precocious male puberty defined as? What do you need to document?

A

evidence of puberty in boys before age 9

the patients Tanner stage

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24
Q

What are the 2 types of precocious puberty. Define them

A

Isosexual - premature development of phenotypically appropriate secondary sexual characteristics

Heterosexual - development of secondary sexual characteristics of the opposite sex

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25
Q

What are the 2 subtypes for isosexual precocious puberty

A

gonadotropin-dependent (central precocious puberty [CPP])

gonadotropin-independent - (peripheral precocious puberty)

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26
Q

What is central precocious puberty? Is it gondadotropin independent or dependent?

A

premature activation of the GnRH pulse generator leading to inappropriately elevated gonadotropin (LH/FSH) levels for age

gonadotropin-dependent

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27
Q

What is peripheral precocious puberty? Is it gondadotropin independent or dependent?

A

androgens from the testis or the adrenal glands are increased, with low levels of gonadotropins

gonadotropin-independent

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28
Q

What are the 3 causes of central Isosexual Precocious Male Puberty? Which one is MC?

A
  1. Idiopathic** MC
  2. Hypothalamic hamartoma or other lesions
  3. CNS tumor or inflammatory state
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29
Q

What are 5 causes of peripheral Isosexual Precocious Male Puberty

A
  1. Congenital adrenal hyperplasia
  2. hCG/androgen-secreting tumor
  3. McCune-Albright syndrome
  4. Familial male-limited precocious puberty
  5. Exogenous androgens
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30
Q

If you are concerned about central precocious puberty, what is the first thing you need to exclude? How? What are some historic red flags? PE red flags?

A

CNS lesions

brain MRI with contrast

historical red flags: headaches, new onset seizures, memory or personality changes, loss of balance, visual changes, N/V,

PE red flags: abnormal neurologic exam (weakness, numbness, tingling)

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31
Q

Peripheral precocious puberty is caused by ??? Where are some common locations?

A

hCG activates the LH receptors on the Leydig cells stimulating testosterone production

tumor locations
gonads, brain, liver, retroperitoneum, and anterior mediastinum

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32
Q

What is virilization?

A

the development of male physical characteristics in a female or precociously in a male

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33
Q

What is McCune -Albright syndrome? Is it more common in females or males?

A

Acquired mutation in the Gsα subunit activating adenylyl cyclase resulting in steroidogenesis stimulating testosterone production

MC- females

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34
Q

McCune- Albright syndrome is an acquired mutation in the _____ activating ______ resulting in ????

A

Gsα subunit

adenylyl cyclase

steroidogenesis stimulating testosterone production

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35
Q

What is the triad for McCune-Albright syndrome?

A

bone dysplasia: limping, pain or fracture cafe-au-lait skin pigmentation precocious puberty

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36
Q

McCune Albright Syndrome can also stimulate other endocrine systems, give 3 examples

A

thyrotoxicosis
growth hormone excess (gigantism or acromegaly)
Cushing Disease

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37
Q

Familial male-limited precocious puberty is peripheral or central? What is it caused by?

A

An autosomal dominant disorder caused by activating mutations in the LH receptor, leading to testosterone synthesis

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38
Q

Familial male-limited precocious puberty is an ______ disorder caused by _______. What does it lead to?

A

autosomal dominant disorder

activating mutations in the LH receptor

leading to testosterone synthesis

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39
Q

What is an important hx question to ask a pt for precocious male puberty?

A

When did dad/brothers do through puberty? What age?
Any hx of exogenous sex steroid exposure?

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40
Q

The size of ____ can help differentiate between central and peripheral causes. Why?

A

testicles

if HPG axis has activated (central) the sertoli cells will increase in number leading to a larger testicle

peripheral causes the HPG is not activated and there is excessive testosterone but no FSH, so the Sertoli cells will not be larger and the testicle will remain small

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41
Q

If one testicle is larger than the other, what are you thinking?

A

testicular tumor secreting hCG- peripheral precocious puberty

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42
Q

What is an imaging tool that is used to assess precocious puberty? How do you interpret it?

A

assesses bone age of the LEFT wrist and hand

rapid growth/change indicative of high concentrations of sex steroids due to CPP or peripheral precocity

slow change: benign pubertal variant with low sex steroid concentration

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43
Q

What is step 1 in dx precocious male puberty?

A

serum testosterone will be high (high in both central and peripheral causes)

serum LH and FSH
high in central
low/normal in peripheral

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44
Q

What is step 2 in dx precocious male puberty?

A

figure out if it is central or peripheral

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45
Q

**What do you do if the LH/FSH test are borderline high or on the upper limit of normal?

A

GnRH-analogue stimulation test

give leuprolide which stimulates the anterior pituitary to release LH/FSH

central: LH will rise because the HPG axis is active

peripheral: no rise in LH because the HPG axis is still inactive

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46
Q

**When is leuprolide used?

A

as part of the GnRH-analogue stimulation test to figure out if the cause is central or peripheral.

central: LH will rise
peripheral: no change in LH

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47
Q

What is step 3 in dx precocious male puberty? What tests would you order?

A

look for the peripheral source

Serum hCG ->elevated in hCG tumor

Dehydroepiandrosterone (DHEA) -> elevated in CAH and adrenal tumors

17α-hydroxyprogesterone ->elevated in CAH
normal in other etiologies

Genetic testing if concern for LH/ Gsα subunit mutations
if clinical presentation is consistent with MAS

48
Q

_____ and ____ will be elevated in congenital adrenal hyperplasia

A

17α-hydroxyprogesterone

Dehydroepiandrosterone (DHEA)

49
Q

____ will be elevated in CAH and adrenal tumors of the zona reticularis

A

Dehydroepiandrosterone (DHEA)

50
Q

What is step 4 in dx precocious male puberty?

A

imaging to find the tumor

51
Q

would order ____ is trying to find hCG tumor

would order ___ if trying to find leydig-cell tumor

A

chest/abdomen CT

testicular US

52
Q

What is the management of central PP?

A

tumor: tx underlying cause

idiopathic: long acting GnRH agonists (leuprolide) to shut it off

53
Q

**What is the MOA of leuprolide? What happens in the short term? long term?

A

chronic stimulation of the GnRH receptors in the pituitary leads to desensitization of the receptor and decreased release of LH/FSH

short: increase LH/FSH due to initial stimulation

long: prolonged stimulation reduces LH/FSH to prepubertal levels

54
Q

What are the effects of leuprolide?

A

halts early pubertal development
delays bone maturation, prevent early epiphyseal closure, thus increasing final height

55
Q

Leuprolide comes in what form? How often?

A

injection only: 1 month, 3 month and 6 month formulations

56
Q

What is the management of peripheral PP due to congenital adrenal hyperplasia?

A

suppress androgen production with glucocorticoids

57
Q

What is the management for McCune-Albright syndrome and familial male-limited precocious puberty? What are the drug classes of each

A

spironolactone and anastrozole

androgen receptor antagonist: spironolactone

aromatase inhibitors: anastrozole (Arimidex)

58
Q

What is the MOA of aromatase inhibitors [anastrozole (Arimidex)]?

A

blocks conversion of testosterone to estradio

59
Q

What is the alternative management of McCune-Albright syndrome and familial male-limited precocious puberty? What are you at risk for?

A

Steroid synthesis inhibitor - ketoconazole - requires high dosing leading to a risk of hepatotoxicity

60
Q

What is the goal of therapy for precocious male puberty?

A

halt further sexual development and prevent premature closure of the epiphyseal plates

61
Q

What is delayed puberty defined as ? What are the 2 categories?

A

lack of testicular enlargement by age 14 OR incomplete genital growth within 5 years of initial signs of puberty

Primary and secondary hypogonadism

62
Q

What is primary hypogonadism?

A

hypergonadotropic hypogonadism secondary to primary gonadal failure (15%)

63
Q

What are causes of secondary hypogonadism? Which cause is MC?

A

**constitutional delay of growth and puberty¹ (CDGP) (60%)- MC aka late bloomers

functional hypogonadotropic hypogonadism caused by systemic illness or malnutrition (20%) such as chronic dz, malnutrition, anorexia

hypogonadotropic hypogonadism caused by genetic or acquired defects in the hypothalamic-pituitary region (10%)

64
Q

What is the MC congenital abnormality that causes primary hypogonadism? What is it caused by?

A

Klinefelter syndrome - a genetic condition that results when a male is born with an extra copy of the X chromosome.

This results in damage to the seminiferous tubules and, usually, damage to the Leydig cells as well

65
Q

What are some congenital abnormalities that can lead to delayed male puberty?

A

microphallus - defined as a stretched penile length of less than 2.5 standard deviations (SDs) below the mean for age

cryptorchidism - a condition in which one or both of the testes fail to descend from the abdomen into the scrotum

renal agenesis - a congenital defect of the absence of one or both kidneys

66
Q

What is microphallus defined by?

A

defined as a stretched penile length of less than 2.5 standard deviations (SDs) below the mean for age

67
Q

What can the height/arm span tell you when assesses someone for delayed male puberty? What size in cm is considered prepubertal testicular size?

A

arm span exceeding height by > 5 cm suggesting a delayed epiphyseal closure due to hypogonadism

<2.5 cm longitudinally or 1-3 mL on the prader orchidometer

68
Q

What are the 3 initial tests you want to order for a delayed male puberty pt? What will each show?

A

Xray - left hand and wrist to assess bone age
-bone age will be delayed relative to chronological age

serum testosterone- will be low for age

LH/FSH elevated - primary hypogonadism/gonadal failure
LH/FSH low for age - secondary hypogonadism

69
Q

If bone age is delayed relative to chronological age and growth velocity is normal, what is the most likely cause?

A

constitutional delay of growth and puberty (CDGP) aka late bloomers

70
Q

if a pt presents with delayed male puberty but has a negative family hx, what do you do next?

A

look for other etiologies:

pituitary hormone deficiencies, malnutrition, hyperprolactinemia, chronic diseases, CNS disorders
Imaging (CT/MRI) of suspected tumors

71
Q

How do you manage constitutional delay of growth and puberty?

A

2 options: reassurance with f/u vs. testosterone therapy

consider testosterone if patients self-esteem is affected as a result of stature and/or prepubertal appearance

72
Q

you start a pt on testosterone for secondary hypogonadism, what do you need to monitor?

A

interrupted therapy after 6 months to determine whether endogenous LH and FSH secretion has ensued

73
Q

How long does a pt need to be on testosterone for primary hypogonadism?

A

indefinite therapy

74
Q

adding an ______ to a pt with delayed male puberty may allow attainment of greater final adult height. Why?

A

aromatase inhibitor: anastrozole

blocks conversion of testosterone to estradiol preventing epiphyseal closure

75
Q

Define hypogonadism. What is the key word?

A

a failure of the testes to produce an adequate amount of testosterone

TESTES

76
Q

What is hypergonadotropic? What is the problem? Are testosterone and LH high or low?

A

pathology in the testes themselves

primary: low testosterone with high LH

77
Q

What is hypogonadotropic? Where is the problem? Are testosterone and LH high or low?

A

insufficient hormone secretion from the pituitary/hypothalamus

low testosterone with normal/low LH

78
Q

ambiguous genitalia/male pseudohermaphroditism onset usually begins when?

A

2nd-3rd month of fetal development

79
Q

defects in testicular descent leading to cryptorchidism as well as micropenis usually onset when?

A

3rd trimester of fetal development

80
Q

hypogonadism that onsets after birth and before adulthood, what will it present like?

A

Symptoms of delayed puberty

81
Q

How will hypogonadism present if it starts after puberty?

A

Decreased energy, loss of libido, decreased morning erections¹ within days-wks of onset
Loss of facial/axillary/pubic hair, decrease muscle mass, increased fat mass and loss of bone mineral density occurs after several years of untreated disease
infertility

82
Q

______ is responsible for keeping sperm healthy

A

testosterone

83
Q

What are the goals of hypogonadism?

A

determine if onset was before or after puberty

determine if patient has normal genitalia

determine if hypogonadism is primary or secondary

84
Q

When is the best time to get a serum testosterone level?

A

first thing in the morning between 8-10am, total testosterone

85
Q

What are 4 instances in which testosterone therapy is indicated?

A

lack of puberty onset by age 14

primary testicular failure (hypergonadotropic hypogonadism)

severe hypogonadotropic hypogonadism of any etiology with serum testosterone levels less than 150 ng/mL

age-related hypogonadism

86
Q

_____ a decrease in testosterone production starting between the 4th-6th decades of life and progresses slowly with age. In what 2 instances is the rate of decline more?

A

andropause

greater decline in obese men and those with chronic illness

87
Q

What is the pathophys behind age related hypogonadism?

A

pulsatile GnRH secretion diminishes, pituitary response to GnRH is reduced, and testicular response to LH becomes impaired

aka all the things are decreased

88
Q

LH levels have a gradual rise with aging, ______ is the likely cause of declining androgen levels

A

testis dysfunction

89
Q

When is testosterone therapy indicated in age related hypogonadism? What is the goal of therapy?

A

recommended if at least 3 symptoms of androgen deficiency who have testosterone levels <200 ng/dL and benefits outweigh risk

S/S: erectile dysfunction, poor morning erection, low libido, depression, fatigue, and inability to perform vigorous activity

maintenance of secondary sexual characteristics; increased libido; improved muscle strength, fat-free mass, and bone density

90
Q

What is the normal range of total testosterone? What does it include? What is normal values based on?

A

250 to 1000 ng/dL (adult male)

includes both protein bound and unbound

sex and age

91
Q

When is the best time to draw a total testosterone? What do you do if the test comes back low?

A

Fasting specimen between 8-10 AM preferred

repeat if first assessment is low

92
Q

What does free testosterone assess? When is free testosterone test indicated?

A

Assesses amount of testosterone not bound to albumin or SHBG

indicated if total testosterone is abnormal

93
Q

What should you be thinking if there is NOT a linear correlation between free and total testosterone?

A

if linear correlation is absent consider abnormality in function or level of SHBG

94
Q

_____ is ordered to further evaluate low testosterone. What does a high value indicate? What does a low value indicate?

A

LH/FSH

high: primary hypogonadism

normal/low: secondary hypogonadism

95
Q

______ refers to enlargement of the male breast resulting from excess estrogen action and is usually the result of an increased estrogen/androgen ratio

A

Gynecomastia

96
Q

True gynecomastia is associated with _____ tissue that is ____ cm in diameter and often _____

A

glandular breast

> 4

tender

97
Q

When is normal physiological gynecomastia seen?

A

newborn

during puberty (10-14) due to high estrogen to androgen ratio in early stages of puberty

aging: increase in fat tissue and increased aromatase activity leading to increase estradiol

98
Q

pathologic gynecomastia results from ______. What are some common causes?

A

increased aromatase activity

testicular or hCG tumors : gonads, brain, liver, retroperitoneum, and anterior mediastinum
adrenal tumors
chronic liver disease
malnutrition
hyperthyroidism
familial gynecomastia
drugs: LOTS of drugs can cause it* 20% of cases

99
Q

gynecomastia seen in adolescents will be _____ but usually absent in _____

A

painful/tender

adults: no pain/tenderness

both may also have nipple sensitivity

100
Q

What is the consistency of the breast tissue that is commonly found in gynecomastia? What will fatty tissue feel like?

A

breast tissue will be glandular and tender

fatty tissue is diffuse and nontender

need to preform breast exam seated and supine

101
Q

If gynecomastia is present, what else do you need to check?

A

testicular examination & measurement

note presence of mass and testicular size and secondary sexual characteristics

also need to check abdomin for adrenal mass, hCG secreting mass of the liver, retroperitoneum

102
Q

What is the management for neonatal and pubertal gynecomastia? Androgen deficiency? hCG tumor?

A

reassurance

testosterone therapy

imaging and refer to surgeon

103
Q

If regression of gynecomastia is not observed and it has been less than 12 months, what is the treatment? What about severe symptoms or present for longer than 12 months?

A

selective estrogen receptor modulator (tamoxifen)
aromatase inhibitor [anastrozole (Arimidex)

surgery

104
Q

What schedule drug is testosterone? Does it restore fertility?

A

schedule 3

does NOT restore fertility

105
Q

What are some route of testosterone?

A

injectable
gel/solution
pellets
nasal gel
oral

106
Q

What are the 2 names of the injectable testosterone? How often is it given? What is the drawback to this method?

A

Testosterone enanthate and T. cypionate

q2 weeks

results in peaks and troughs which can affect a pt’s mood, sexual desire and energy level

107
Q

_____ is the extra-long acting injectable testosterone. What is the dosing schedule? Where is it given?

A

Aveed - testosterone undecanoate)

First dose is followed by 2nd dose at 4 wks with all subsequent doses occurring every 10 wks

Requires in office administration followed by 30-minute observation

108
Q

What form of testosterone? Testosterone levels should normalize within a month of therapy and remain steady throughout 24 hours. How long does it take to exert its full effect?

A

Gel (AndroGel, Testim, and Fortesta) and Solution (Axiron)

4-6 hours

109
Q

How often are the testosterone pellets inserted? What is the name?

A

3-6 pellets surgically inserted q 3-6 months into the buttocks, lower abdominal wall, or thigh

Testopel

110
Q

What is the goal of establishing testosterone therapy?

A

restoration of testosterone levels into the mid-normal range

promote the development of and maintain secondary sexual characteristics and normal sexual function

build and sustain normal bone and muscle mass

111
Q

**What is the testosterone required monitoring? injectable? gel? nasal gel/pellets/oral tablets?

A

Monitor testosterone level 3–6 months after initiation of testosterone therapy

injectable: measure midway between injections

gel: assess anytime after pt has been on therapy for a least 1 week

nasal gel/pellets/oral tablets: measure periodically 1 month after initiation

112
Q

What other non-testosterone labs also need to be monitored when a pt is on testosterone therapy?

A

Check hematocrit at baseline, at 3–6 months and then annually. If hematocrit is >54%, stop therapy

dexa scan after 1-2 years of testosterone therapy

40 years of age or older with baseline PSA >0.6 ng/mL, perform digital rectal examination and check PSA level before initiating treatment, at 3–6 months

113
Q

When do you need to refer to urology when monitoring a pt on testosterone?

A

An increase in serum PSA concentration >1.4 ng/mL within any 12-month period of testosterone treatment.

A PSA velocity >0.4 ng/mL per year using PSA level after 6 months of testosterone administration as reference (applicable only if PSA data are available for a period exceeding 2 years).

Detection of a prostatic abnormality on digital rectal examination.

114
Q

What are 2 CI for testosterone therapy?

A

metastatic prostate cancer

breast cancer

115
Q

testosterone therapy suppresses _____ and decreases ______

A

spermatogenesis

testicular size

116
Q

What is the Endocrine Society’s guidelines for testosterone therapy?

A

avoid testosterone replacement in patients with mild vague symptoms and borderline/low testosterone on only one occasion

“trial” therapy should be avoided

testosterone therapy suppresses the pituitary-testicular axis

testosterone therapy suppresses spermatogenesis and decreases testicular size

117
Q
A

Endocrine (14 decks)

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