Endocrine aspects of male hypogonadism Flashcards
Testosterone
Steroid hormone
Normal young men produce about 7mg each day
In blood is largely bound to plasma protein, with only about 2% present as free hormone
Anatomical units of testes
Seminiferous tubules in which inhibin 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
Testosterone: the hypothalamic pituitary testicular 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 involved in spermatogenesis and inhibin B secretion
Testosterone: mechanism of action
Penetrates the target cells whose growth and function it stimulates
Androgen target cells convert testosterone to 5 alpha-dihydrotestosterone before it binds to the androgen receptor
Alternatively, testosterone can be aromatized to oestrogens
Testosterone action
Regulation of gonadotropin 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
Male hypogonadism
Decrease in one or both of the two major functions of the testes: sperm production or testosterone production
Primary hypogonadism
Disease of the testes
Testosterone below normal and the serum LH and/ or FSH are above normal
Secondary hypogonadism
Disease of the hypothalamus or pituitary
Testosterone below normal and the serum LH and/ or FSH are normal or low
Causes of primary hypogonadism
Klinefelter Syndrome
Cryptorchidism
Infection- mump
Radiation
Trauma
Torsion
Idiopathic
Causes of secondary hypogonadism
Congenital GnRH deficiency
Hyperprolactinaemia
GnRH analog
Androgen
Opioids
Illness
Anorexia nervosa
Pituitary disorder
Clinical features of hypogonadism
First trimester- female genitalia to ambiguous genitalia to partial virilisation
Third trimester- micropenis
Prepubertal- failure to undergo or complete puberty
Adults
Symptoms/ signs of hypogonadism
Incomplete sexual development, eunuchoidism
Decreased sexual desire and activity
Decreased spontaneous erections
Breast discomfort, gynaecomastia
Decreased body hair (axillary and pubic)
Very small or shrinking testes
Decreased height, low trauma fracture, low BMD
Decreased muscle bulk and strength
Hot flushes, sweats
Less specific signs/ symptoms
Decreased energy motivation, initiative, aggressiveness, self confidence
Feeling sad or blue, depressed mood, dysthymia
Poor concentration and memory
Sleep disturbance, increased sleepiness
Mild anaemia
Increased body fat, BMI
Diminished physical or work performance
Conditions with a high prevalence of hypogonadism
Sellar mass, radiation to sella, other sella disease
On meds that affect T production or metabolism
HIV associated weight loss
ESRD and maintenance haemodialysis
Moderate to severe COPD
Osteoporosis or low trauma fracture
Type 2 diabetes mellitus
Infertility
Examination
Amount of body hair
Breast exam for enlargement/ tenderness
Size and consistency of testicles
Size of the penis
Signs of severe and prolonged hypogonadism
Arm span
Investigations
Serum testosterone
LH/FSH
SHBG
LFT
Semen analysis
Karoyotyping
Pituitary function testing
MRI
DEXA scan
Guidelines on screening
Initial screen= morning total testosterone
Confirmation= repeat morning total testosterone
Do not screen during acute or subacute illness
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
Testosterone
- gel
- injection
- buccal/ patch/ pellet
Monitoring
Testosterone
PSA
FBC
DRE
DEXA
Contraindications to testosterone therapy
Breast or prostate cancer
Lump/ hardness on prostate exam by DRE
PSA>3ng/ml that has not been evaluated for prostate cancer
Severe untreated BPH
Erythrocytosis
Hyperviscosity
Untreated obstructive sleep apnoea
Severe heart failure
Gynaecomastia
A benign proliferation of the glandular tissue of the male breast
May be unilateral or bilateral
Diagnosed on exam as a palpable mass of tissue at least 0.5cm in diameter
Imbalance between androgen and oestrogen
Causes of gynaecomastia
Persistent pubertal gynaecomastia
Drugs
Idiopathic
Cirrhosis or malnutrition
Hypogonadism
Testicular tumour
Hyperthyroidism
Chronic renal insufficiency
