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Flashcards in Male Reproductive Disorders Deck (25):
1

What is the basic physiology of the Hypothalamic-Pituitary-Testicular axis and how does this affect hypogonadism?

The reproductive axis is comprised of a series of interconnecting feedback loops between the hypothalamus (GnRH), the anterior pituitary (FSH, LH) and the testes. Hypogonadism can result from a defect at any level of the HPG axis.

2

What sorts of disorders may result in hypogonadism?

Disorders may be mechanical:
congenital absence of the testes
damage to the testes

Hormonal defect:
GnRH
LH and/or FSH
Testosterone production.

The defect can be congenital or acquired.

3

What are the two classes of hypogonadism?

Hypogonadotropic
Hypergonadotropic

4

What are the lab values and clinical signs of hypogonadotropic hypogonadism?

low LH and FSH and low testosterone, and impotence

5

What is the cause of congenital hypogonadotropic hypogonadism?

Congenital -- This defect is termed GnRH deficiency (or Kallman's syndrome when associated with anosmia,(loss of smell) or normosmic hypogonadotropiv hypogonadism ).
Due to a failure of migration of GnRH neurons to migrate to the hypothalamus. GnRH neurons are born in the olfactory placode in the nose. In utero, the neurons migrate with the olfactory neurons across the cribiform plate into the forebrain, to the hypothalamus. The signals for neuronal migration and gene expression are under intensive investigation. These patients have an “intact hardware, but the software program is missing”.

6

What are the common pathways for acquired hypogonadotropic hypogonadism?

a. Acquired defects are the most common cause of low Testosterone: observed after severe illness, surgery, or stress, or with obstructive sleep apnea, narcotics or repeated glucocorticoid injections.
b. A deficiency in LH and FSH can be seen with an INFILTRATIVE DISEASE (eg. hemochromatosis) that block production and or release of the pituitary gonadotropins. In hemachromatosis, iron deposition is selectively in gonadotropes. Patients also have liver disease, diabetes, and congestive heart failure.
c. In addition, some PITUITARY TUMORS make hormones that block the GnRH-induced LH and FSH signal such as prolactin, growth hormone, and ACTH. Prolactinomas are the most common pituitary tumor.

7

What additional hormone level should be examined in patients with hypogonadotropic hypogonadism and low LH, FSH, and testosterone levels?

prolactin levels

8

What are the lab values and clinical signs of hypergonadotropic hypogonadism?

High FSH &/or LH, and impotence

9

What are some causes of congenital hypergonadotropic hypogonadism?

congenital anorchia and vanishing testes syndrome
Klinefelter's syndrome
mutations in the androgen receptor

10

What occurs in congenital hypergonadotropic hypogonadism caused by congenital anorchia and vanishing testes syndrome

An insult to the fetus (before 10-12 weeks of gestation) interrupts testicular development. The GnRH-induced gonadotropin signal is high in an attempt to stimulate the failing gonad.
HIGH LH and FSH levels and LOW testosterone levels.

11

How does Klinefelter's syndrome result in hypergonadotropic hypogonadism?

A genetic defect of XXY is associated with a failing testes, with no spermatogenic elements, no Sertoli cells, but intact Leydig cells.
Small testes and delayed or incomplete puberty, gynecomastia, eunuchoid body habitus and infertility.
Often elevated FSH levels (due to lack of inhibin B), normal LH and low normal testosterone.
With time there is progressive tubular fibrosis and destruction of the Leydig cells; testosterone levels drop and LH levels rise. Risk for these men include increase in breast cancer (they need mammograms) and need for androgen replacement. Fertility is not possible.

12

What can happen if an XY person has a defect in the androgen receptor?

If mild they present with hypospadias, or ambiguous genitalia

If complete they present as females with inguinal gonads and a blind vaginal pouch and the disorder is called testicular feminization.

The estrogenization is excellent and the patients with complete defects are raised successfully as women after gonadectomy and estrogen replacement.

13

What do labs look like for someone with an androgen receptor mutation?

HIGH LH, FSH, Testosterone and Estradiol, but no clinical effects of the androgen because of the steroid receptor mutation.

14

What can cause acquired hypergonadotropic hypogonadism

mechanical and cytotoxic trauma to the testes such as torsion, mumps orchitis, alcohol, chemotherapy or radiation, infiltrative diseases, diabetes

15

What do lab values show in acquired hypergonadotropic hypogonadism

Early rise in FSH,(due to loss of inhibin) followed later by increase in LH and decline in testosterone. These patients eventually require androgen replacement.

16

Glycoprotein tumor of the pituitary

Uncommon cause of hypergonadotropic hypogonadism

Tumor of the pituitary that overproduces inactive pituitary gonadotropins (α, LHβ, and/or FSHβ).

Headache, blurred vision, elevated α subunit level as a tumor marker or elevated prolactin level due to stalk compression.

High FSH or LH levels and low testosterone levels, the latter occurring because the FSH or LH are abnormal and inactive, and the tumor mass compresses the normal pituitary, inhibiting the normal LH and FSH production.

Unfortunately, there is no lab test to accurately predict who has a tumor. You must just think of the disease and if things don't fit, obtain a MRI. Surgery is the treatment of choice.

17

Treatments for Male Hypogonadism

Androgen Replacement- for all if fertility is not an issue

Gonadotropin Therapy- for men with pituitary or hypothalamic defects

Pulsatile GnRH therapy- for men with hypothalamic defects

18

Risks of androgen replacement therapy

Polycythemia
Benign prostatic hypertrophy
Elevation of LDL cholesterol

19

GONADOTROPIN THERAPY

Initially hCG to provide an LH like signal to the testis. If no FSH is being produced by the pituitary, additional therapy with human menopausal gonadotropin is necessary

20

Which drugs can cause gynecomastia?

antiandrogens: spironolactone, flutamide

psychoactive drugs: phenothiazines, antidepressants

abuse: alcohol, heroin, marijuana

21

Endocrine causes of gynecomastia

1. primary hypogonadism due to leydig cell damage (klinefelters, testicular trauma, chemotherapy)

2. hyperprolactinemia

3. hyperthyroidism

4. androgen receptor mutations (testicular feminization)

22

Tumors that can cause gynecomastia

Germ cell tumors (make choronic gonadotropin (hCG) that stimulates estrogens and androgens)

Leydig cell tumors (make estrogens +/- testosterone)

feminizing adrenal tumors (make estrogens)

23

Causes of erectile dysfunction

Vascular: predicted by hypertension, high cholesterol

Neurogenic: diabetes, spinal cord injury, toxins (alcohol, lead)

Hormonal

Psychogenic: performance anxiety

Iatrogenic: antiandrogens, psychotropic medications, narcotics, marijuana, cocaine

24

Treatment of erectile dysfunction

Psychotherapy: no randomized studies

Change meds, stop alcohol, improve systemic diseases

Drug therapy: type 5 phosphodiesterase inhibitors (sildenafil, vardenafil, tadenafil)

Penile injections: prostaglandin E

Vacuum pump devices

25

What are the two most common causes of acquired hypogonadotropic hypogonadism?

Narcotics
Exogenous supplements