L19 - Endocrine aspects of male hypogonadism Flashcards
Testosterone
Steroid hormones
Secreted both in men and women - testes, ovary and adrenal
Normal young men produce about 7mg each day, of which less than 5% is derived from adrenal secretions
How does testosterone travel in the blood?
Testosterone in blood is largely bound to plasma protein, with only about 2% present as free hormone
- about half (>50%) is bound to albumin
- 44% is bound to sex hormone-binding globulin (SHBG)
2 anatomical units of the testes
Seminiferous tubules in which inhibit B and anti-Mullerian hormone are synthesised by Sertoli cells and sperm are produced
An interstitium containing Leydig cells that produce androgens and peritubular myoid cells
Synthesis of androgens
Cholesterol is converted into pregnenolone using LH
Pregnenolone is converted into progesterone and DHEA
Both of these are converted into testosterone
Testosterone is broken down into DHT via 5A reductase and estradiol by aromatase from FSH
Testosterone: The HPA axis
Pulsatile secretion of GnRH
Secretion of LH and FSH
LH and FSH are composed of two glycoprotein chains
LH is involved in release of testosterone
FSH is involved in spermatogenesis and Inhibin B secretion
Testosterone: mechanism of action
Like other steroid hormones, testosterone penetrates the target cells whose growth and function it stimulates
Androgen target cells generally convert testosterone to 5 a-dihydrotestosterone before it binds to the androgen receptor
Alternatively, testosterone can be aromatised to oestrogens, which exert effects that are independent of, opposite to, or synergistic to this of androgen
Testosterone action
Regulation of gonadotrophin secretion by the hypothalamic pituitary system
Initiation and maintenance of spermatogenesis
Formation of the male phenotype during embryogenesis
Promotion of sexual maturation at puberty and its maintenance thereafter
Increase in lean body mass and decrease in fat mass
Hypogonadism: decrease in 2 major functions of the testes
1) Sperm production
2) Testosterone production
Definition of primary hypogonadism
Disease of the testes
Testosterone below normal and the serum LH/FSH are above normal
Definition of secondary hypogonadism
Disease of the hypothalamus or pituitary
Testosterone below normal and the serum LH/FSH are normal or low
Primary causes of hypogonadism
Klinefelter syndrome
Cryptorchidism
Infection-mump
Radiation
Trauma
Torsion
Idiopathic
Secondary causes of hypogonadism
Congenital GnRH deficiency
Hyperprolactinaemia
GnRH analog
Androgen
Opioids
Illness
Anorexia nervosa
Pituitary disorder
Clinical features of hypogonadism
First trimester - female genitalia to ambiguous genitallia to partial virilization
Third trimester - micropenis
Prepubertal - failure to undergo or complete puberty
Adults
Symptoms/signs of hypogonadism
- Incomplete sexual development, eunuchoidism
- Decreased sexual desire & activity
- Decreased spontaneous erections
- Breast discomfort, gynaecomastia
- Decreased body hair (axillary and pubic)
- Very small or shrinking testes (esp<5ml)
- Inability to father children, low/zero sperm count
- Decrease in height, low-trauma fracture, low BMD
- Decrease in muscle bulk and strength
- Hot flushes, sweats
Less specific symptoms/signs of hypogonadism
Decreased energy, motivation, initiative, aggressiveness, self-confidence
- Feeling sad, depressed mood, dysthymia
- Poor concentration and memory
- Sleep disturbance, increased sleepiness
- Mild anaemia - normochromic, normocytic, in the female range
- Increased body fat, BMI
- Decreased physical or work performance
Conditions with a High Prevalence of hypogonadism (Screening Suggested)
-Sellar mass, radiation to sella, other sellar disease
-On meds that affect T production or metabolism
=>Glucocorticoids, ketoconazole, opioids
-HIV-associated weight loss
-ESRD and maintenance hemodialysis
-Moderate to severe COPD
-Osteoporosis or low trauma fracture (esp if young)
-Type 2 diabetes mellitus
-Infertility
Relevant Medical History
- Puberty and sexual development
- Past/present major illnesses
- Past/present nutritional deficiency
- All prescription and non-prescription drugs
- Relationship problems
- Sexual problems
- Major life events
- Related family history
- Recent changes in body (breasts)
- Testicle problems
Look out for recreational drug use, eating disorders and excessive exercise
Examination of hypogonadism
-Amount of body hair
-Breast exam for enlargement/tenderness
-Size and consistency of testicles
-Size of the penis
-Signs of severe & prolonged hypogonadism
=>loss of body hair
=>reduced muscle bulk and strength
=>osteoporosis
=>smaller testicles
-Arm span
Investigations for hypogonadism
Serum testosterone LH/FSH SHBG LFT Semen analysis Karoyotyping Pituitary function testing MRI DEXA scan
Guidelines on screening for hypogonadism
Initial screen = morning total testosterone
- levels are highest in the morning
- normal testosterone is generally age dependent
Confirmation = repeat morning total testosterone
-free or bioavailable
Do not screen during acute or subacute illness
-illness, malnutrition, and certain medications may temporarily lower testosterone
What lowers SHBG?
-Moderate obesity
-Nephrotic syndrome
-Hypothyroidism
-Use of
=>glucocorticoids
=>progestins
=>androgenic steroids
What raises SHBG?
- Ageing
- Hepatic cirrhosis
- Hyperthyroidism
- Anticonvulsants
- Oestrogens
- HIV infection
Treatment for hypogonadism
Testosterone
- gel
- injection
- buccal/patch/pellet
Monitoring of hypogonadism
Testosterone
PSA
FBC
DRE
DEXA
