19. Endocrine aspects of male hypogonadism Flashcards
Testosterone
Steroid hormones
Secreted both in men and women – Testes, Ovary and Adrenal
Normal young men produce about 7 mg each day, of which less than 5% is derived from adrenal secretions
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)
Testosterone: testes
The testes contain two anatomical units:
Seminiferous tubules in which inhibin B and anti-Müllerian hormone are synthesized by Sertoli cells and sperm are produced.
An interstitium containing Leydig cells that produce androgens and peritubular myoid cells.
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 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 α-dihydrotestosterone before it binds to the androgen receptor
Alternatively, testosterone can be aromatized to estrogens, which exert effects that are independent of, opposite to, or synergistic to those of androgen
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
Brief description of male hypogonadism
Decrease in one or both of the two major functions of the testes: sperm production or testosterone production.
Disease of the testes (primary hypogonadism) or disease of the hypothalamus or pituitary (secondary hypogonadism)
Primary hypogonadism: Testosterone below normal and the serum LHand/orFSH are above normal.
Secondary hypogonadism: Testosterone below normal and the serum LHand/orFSH are normal or low.
Causes of hypogonadism
Primary: Klinefelter syndrome Cryptorchidism Infection-mump Radiation Trauma Torsion Idiopathic
Secondary: Congenital GnRH deficiency Hyperprolactinemia GnRH analog Androgen Opioids Illness Anorexia nervosa Pituitary disorder
Clinical features of hypogonadism
First trimester – female genitalia to ambiguous genitalia to partial virilization
Third trimester – micropenis
Prepubertal – failure to undergo or complete puberty
Adults
Adolescents and young adults who have not yet completed puberty appear younger than their chronologic age.
They may also present with small genitalia, difficulty gaining muscle mass in spite of vigorous exercise, lack of a beard, and failure of the voice to deepen
Adult: Decreased libido and depressed mood. Decreased muscle mass and hair. Gynecomastia and infertility.
Symptoms/signs of hypogonadism
Incomplete sexual development, eunuchoidism
Decreased Sexual desire & activity
Decreased Spontaneous erections
Breast discomfort, gynecomastia
Decreased Body hair (axillary & pubic), shaving
Very small or shrinking testes (esp < 5 ml)
Inability to father children, low/zero sperm counts
Decreased Height, low-trauma fracture, low BMD
Decreased Muscle bulk & strength
Hot flushes, sweats
Less specific symptoms/signs of hypogonadism
Decreased energy, motivation, initiative, aggressiveness, self-confidence
Feeling sad or blue, depressed mood, dysthymia
Poor concentration and memory
Sleep disturbance, increased sleepiness
Mild anemia
Normochromic, normocytic, in the female range
Increased body fat, BMI
Diminished 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 in hypogonadism
Puberty and sexual development Past/present major illnesses Past/present nutritional deficiency All prescription & nonprescription drugs Relationship problems Sexual problems Major life events Related family history Recent changes in body (breasts) Testicle problems
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 testosteron
Free or bioavailable
Do not screen during acute or subacute illness
Illness, malnutrition, and certain medications may temporarily lower testosterone
