Male Aspects of Hypogandism Flashcards
1
Q
How is Testosterone present in males?
- where is it secreted?
A
- it is secreted in both men and women
- Testes, Ovary, Adrenal
- normal young men produce ~7mg daily
- < 5% is from adrenal secretions
- largely bound to plasma protein in the blound
- 2% is present as a free hormone
- >50% is bound to albumin
- 44% is bound to Sex Hormone-Binding Globulin (SHBG)
- 2% is present as a free hormone
2
Q
What is SHBG and how does it present to men vs women?
- controls
A
- Sex hormone-binding globulin is the binding protein which testosterone binds to
- it’s conc. in men is 1/3 - 1/2 less than what is present in women
- prepubertal boys and hypogonadal men have higher SHBG levels than other males
- SHBG conc. is increased by estrogen administration and hyperthyroidism
- SHBG conc. is decreased by androgen administration and hypothyroidism
- the conc. of SHBG I normal does not affect the bioavailability of testosterone as the hypothalamic-pituitary system adjusts the synthesis of testosterone to ensure a steady-state availability of the hormone
3
Q
Describe the anatomy of the Testes
A
- Seminiferous tubules composed of
- Sertoli cells
- produce inhibin B and anti-Müllerian hormone
- germ cells
- sperm is produced here
- Sertoli cells
- Interstitium containing
- Leydig cells
- these produce testosterone and other androgens
- peritubular myoid cells
- Leydig cells
4
Q
What is the synthesis pathway for androgens?
A
5
Q
Explain the physiology of the hypothalamic-pituitary-testicular axis
A
- there are pulsatile releases of Gonad-Releasing Hormone (GnRH) from the hypothalamus
- acts on gonadotroph cells in the anterior pituitary gland
- causes release of LH and FSH
- these work on Leydig cells and Sertoli cells respectively
- Leydig cells are stimulated to produce testosterone
- this acts as an inhibitor of GnRH release from the hypothalamus
- Sertoli cells produce Inhibin B
- which act on gonadotroph cells in the pituitary to inhibit the release of Gonads
- FSH is also involved in spermatogenesis
6
Q
Explain the mechanism of Action of Testosterone
A
- testosterone penetrates the target cells whose growth and function it stimulates and effects the cells DNA synthesis
- 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
7
Q
What is the effect of Testosterone in the body?
A
- 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
8
Q
What are the effects of low testosterone?
A
- Depressed
- Constant fatigue
- increased risk of AZD
- Increased Fat tissue
- Increased Risk of ED & Low libido
- Increases risk of osteoporosis
9
Q
What is Male Hypogonadism?
- primary vs secondary
A
- When there is a decrease in one or both of sperm production or testosterone production in the testes
- this can be due to a disease of the tests (primary) or the hypothalamus or pituitary (secondary)
- Primary hypogonadism: Testosterone below normal and the s_erum LH and/or FSH are above normal._
- Secondary hypogonadism: Testosterone below normal and the serum LH and/or FSH are normal or low.
10
Q
What are the causes of primary hypogonadism?
A
- Klinefelter syndrome
- most common cause, due to an extra X chromosome in men
- Cryptorchidism
- unilateral or bilateral undescended testes - in the abdominal cavity or inguinal canal by age of 1
- Infection (mumps orchitis)
- Radiation
- Trauma
- Torsion
- Idiopathic
11
Q
What are causes of secondary hypogonadism?
A
- Congenital GnRH deficiency
- may be associated with Kallmann’s Syndrome
- Hyperprolactinemia
- GnRH analogue
- Androgen
- Opioids
- Illness
- Anorexia nervosa
- Pituitary disorder
12
Q
What are clinical features of male hypogonadism?
A
- First trimester – female genitalia to ambiguous genitalia to partial virilization
- Third trimester – micropenis
- Prepubertal – failure to undergo or complete puberty
- may appear younger than their chronological age
- small genitalia, difficulty gaining muscle mass, lack of a beard, failure of the voice to deepen
- As Adults
- decreased libido and depressed mood
- decreased muscle mass and hair
- gynecomastia and infertility
13
Q
What are symptoms/ signs of hypogonadism?
A
- Incomplete sexual development, eunuchoidism
- decreased Sexual desire & activity
- decreased Spontaneous erections
- Breast discomfort, gynecomastia
- decreased Body hair (axillary & pubic), decreased 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
14
Q
What are less specific symptoms/ signs of hypogonadism?
A
- decreased energy, motivation, initiative, aggressiveness, self-confidence
- Feeling sad or blue, depressed mood, dysthymia
- Poor concentration and memory
- Sleep disturbance, increased sleepiness
- Mild anaemia
- Normochromic, normocytic, in the female range
- Increased body fat, BMI
- Diminished physical or work performance
15
Q
Give conditions with high prevalence of hypogonadism where a screen is suggested
A
- Sellar mass, radiation to sella, other sellar disease
- On meds that affect T production or metabolism
- Glucocorticoids, ketoconazole, opioids
- HIV-associated weight loss
- ESRD (end-stage renal disease) and maintenance hemodialysis
- Moderate to severe COPD
- Osteoporosis or low trauma fracture (esp if young)
- Type 2 diabetes mellitus
- Infertility
16
Q
What would be relevant in a medical history if hypogonadism is suspected?
A
- 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
17
Q
What should be assessed in an examination for suspected hypogondaism?
A
- 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
18
Q
What investigations should be done for hypogonadism?
A
- Serum testosterone
- LH/FSH
- SHBG
- LFT
- Semen analysis
- Karoyotyping
- Pituitary function testing
- MRI
- DEXA scan
19
Q
What are the guidelines for screening and the screening tests?
A
- 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
20
Q
What is the pathway for a hypogonadism screen?
A
21
Q
What is Sex Hormone Binding Globulin what effects it’s circulation?
A
- SHBG is the binding protein that 97% of testosterone binds to
What lowers SHBG
- Moderate obesity
- Nephrotic syndrome
- Hypothyroidism
- Use of
- Glucocorticoids
- Progestins
- Androgenic steroids
- acute illness and malnutrition
What raises SHBG
- Aging
- Hepatic cirrhosis
- Hyperthyroidism
- Anticonvulsants
- Estrogens
- HIV infection
22
Q
What is the pathway after confirmed low or free testosterone?
A
23
Q
What is the treatment for low Testosterone?
A
- Testosterone as
- Gel
- Injection
- BUccal/ Patch/ Pellet
24
Q
What are contraindications to Testosterone Therapy?
A
- Breast or prostate cancer
- Lump/hardness on prostate exam by DRE
- PSA >3 ng/ml that has not been evaluated for prostate cancer
- Severe untreated BPH (AUA/IPSS >19)
- Erythrocytosis (hematocrit >50%)
- Hyperviscosity
- Untreated obstructive sleep apnea
- Severe heart failure (class III or IV)
25
Q
What is Gynecomastia?
- presentation
- prevelance
A
- 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 0.5 cm in diameter (usually underlying the nipple)
- Imbalance between androgen and estrogen
- 60% of boys during puberty - transient
- 30-70% in adult men
26
Q
What are the causes of Gynecomastia
A
- Persistent pubertal gynecomastia
- Drugs
- spironolactone, cimetidine, ketoconazole, recombinant human growth hormone, estrogens, hCG, GnRH agonists, antiandrogens
- Idiopathic
- Cirrhosis or malnutrition
- Hypogonadism
- Testicular tumour
- Hyperthyroidism
- Chronic renal insufficiency –Leydig cell dysfunction
27
Q
What evaluatory questions should be considered when presented with potential gynecomastia?
A
- Is the breast enlargement of recent onset or associated with pain or tenderness?
- Is the breast enlargement due to increased glandular tissue or is it only adipose tissue (pseudogynecomastia)?
- Are there findings suggestive of breast cancer?
- Is there evidence of a testicular tumor, which might lead to gynecomastia by producing estrogen or stimulating its production?
- Can a cause for the breast enlargement be identified?
- Is the patient troubled by the breast enlargement?
28
Q
What are key things when taking a history for presenting Gynecomastia?
A
- Duration
- Breast pain/tenderness
- Systemic disease
- Weight gain or loss
- Use of medication/recreational drugs
- Exposure to chemicals
- Fertility
- Sexual function
- Family history
29
Q
What examinations need to be done with presenting gynecomastia?
A
- Virilisation
- Testicular size
- Penis
- Sign of CLD or CRF
- Thyroid
- Breast
30
Q
What investigations should be carried out if Gynecomastia is considered?
A
- Testosterone
- LH/FSH
- Prolactin
- LFT/U&Es
- B-hCG
- TFT
- Estrogen
- U/S-Mamogram
31
Q
What is the treatment for Gynecomastia?
A
- Conservative- Reassurance
- Treatment of cause
- Tamoxifen
- Surgery
