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CPD Endocrine Review: H-P Gonadal axis

Which gland produces Gonadotropin Releasing Hormone (GnRH)?
hypothalamus

GnRH is released in pulses every how many minutes?
90-120

GnRH stimulates the anterior pituitary to produce what?
luteinizing hormone and follicular stimulating hormone
(gonadotropins)

In the male, what cells do FSH and LH act on?
FSH-->sertoli cells-->spermatogenesis, activation of androgen binding protein
LH-->leydig cells-->manufacture of inhibin-->feedback to hypothal to stop GnRH,
activin-->more GnRH and FSH released,
androgen binding protein (ABP),
Mullerian Inhibitory factor (MIF),
convert cholesterol to testosterone

What region of the Y chromosome causes the male to differentiate from the female embryo?
the SRY region
contains testis determining factor (TDF)
no Y, no SRY, no TDF, you get an ovary: female by default
embryo has both potential until about 6 weeks gestation
Wolffian structure = male: epidid, vas d, seminal vesicles, ejac ducts
Mullerian structure = female: uterus, fallop tubes, cervix, proximal 1/3 of vagina

What enzyme converts testosterone to dihydrotestosterone, the most potent form?
5-alpha-reductase

Name a plant that blocks 5-alpha-reductase thus limiting the manufacture of dihydrotestosterone?
saw palmetto

What enzyme in fat converts testosterone to estradiol?
aromatase

What are the characteristic lab findings in primary hypogonadism?
low testosterone and high LH and FSH

Androgen deficiency in the 2nd and 3rd months of gestation results in what?
gender ambiguity and male pseudohermaphroditism

Androgen deficiency in pre-puberty or early puberty results in what?
altered growth: long bones longer than axis
lower body length > trunk length
arm span > height (eunuchoidal proportions)
altered secondary sexual characteristics: small penis, testes, decr rugae in scrotum
sparse pubic, axillary, chest and facial hair
high pitched voice
gynecomastia

In the adult male, primary hypergonadism is characterized by what?
decreased fertility, libido, impotence
fatigue, weakness
aka hypergonadotropic hypogonadism
mbdt orchitis dt mumps, gonorrhea

What is the most common genetic cause of primary hypogonadism?
Klinefelter's syndrome

Which karyotype is most common in Klinefelter's?
xsome 47 XXY
1/1000 males (kinda common!)

What are the general characteristics of a pt with Klinefelter's syndrome?
abnormal Leydig cells: never enough testosterone
eunuchoidal proportions (long legs short trunk)
small fibrotic testes
gynecomastia
infertile
osteopenic

XXY males have a 20-50x more risk of developing what cancer?
breast cancer

What labs are seen if the hypogonadism is secondary, or caused by the anterior pituitary?
low LH, FSH, Test

What are the major causes of pituitary dysfunction?
tumors, infx, infarct, inflam (sarcoid), infilt (hemochroma), trauma

If someone has secondary hypogonadism, what other hormonal imbalances should be investigated?
hypothyroid and/or Cushing's

What is the risk with oral testosterone supplementation?
liver inflammation and cancer

How does obesity cause gynecomastia?
aromatase from fat converts testosterone to estradiol
most common androgen target tissue defect
What are some other side effects of testosterone replacement?
prostatic hypertorphy
acne
fluid retention
increased HGB dt stim of EPO (beware w/ COPD and apnea pts)
emotional lability

What are the risks of taking anabolic steroids?
they're used to increase muscle mass & strength
negative feedback to the pituitary lowers LH and FSH-->testicular atrophy
body builders and other athletes have reported liver dz incl hepatic tumors

Which hormone is lacking in tertiary hypogonadism?
GnRH-->low everything else
aka hypogonadotropic hypogonadism

How do you tell secondary from tertiary hypogonadism?
use GnRH stimulation test to assess pituitary resonse
if you give GnRH and FSH and LH rise, the hypothalamus dysfx (tertiary)
if no response, the ant pit is problem (secondary)

People with tertiary hypogonadism and anosmia may have what syndrome?
Kallman's syndrome
affects midline structures

What happens to a person with a congenital deficiency in 5-alpha-reductase (5-ARD)?
born with ambiguous genitalia, infertility, hypospadias, mild clitoromegaly
can't convert test to di-hydro-test
**elevated ratio of serum T/DHT
testosterone (normal to high) to dihydrotestosterone (low or none)
autosomal recessive
uterus and fallopian tubes are absent because mullerian inhibiting factor was normal
testes and wolffian structures are intact (epidid, vas d, seminal vesicles)
can be mis-dxd as AIS

What is AIS, androgen insensitivity sydrome?
aka testicular feminization syndrome
x-linked recessive
failure of masculinization of external genitalia in chromosomal male

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