Male gonadal function and dysfunction (male hypogonadism). Emphasis where made on the causes, types of male hypogonadism, diagnosis and treatment methods.
5. 1. Tubular compartment
Germ cells
Sertoli cell: also known as the nurse or mother cells or
sustentacular cells support spermatogenesis. Their
proliferation is triggered by testosterone and FSH
secretion (has FSH-receptor on its membranes) and also
Inhibited by inhibin.
Sperm cells
Two cellular compartments involved in spermatogenesis
6. 2. Interstitial Compartment
Leydig cells:
Produce testosterone (dihydrotestosterone, DHEA and
androstenedione) by respond to luteinizing hormone (LH) with
steroid production (primarily testosterone).
7. Functions of testosterone
Converted to DHT (more active)in tissues e.g. prostate gland.
Testosterone is also converted to oestradiol in adipose tissue
by aromatase enzyme
Actions
– Male sexual differentiation
– Maintains male secondary sexual characteristics
– Regulation of GnRH secretion
– Spermatogenesis
– Normal male sexual function and behaviour
– Maintenance of bone mineral density
10. ***This will be a hard task for someone with hypogonadism due to fatigue and loss of
strength***
I’VE GOT THE
‘T’ FOLKS
11. Androgen Deficiency Symptoms
Musculoskeletal
– Decreased vigour and physical energy
– Diminished muscle strength
Sexuality
– Decreased interest in sex
– Reduction in frequency of sexual activity
– Poor erectile function/arousal
– Loss of nocturnal erections
– Reduced quality of orgasm
– Reduced volume of ejaculate
12. Mood disorder and cognitive function
– Irritability & lethargy
– Decreased sense of well-being
– Lack of motivation
– Low mental energy
– Difficulty with short-term memory
– Depression
– Low self-esteem
– Insomnia
– Nervousness
Androgen Deficiency Symptoms
14. – Diminished muscle mass
– Loss of body hair
– Abdominal obesity
– Gynecomastia
– Testes frequently normal, occasionally small
Physical Signs
Androgen Deficiency Symptoms
15. History and Physical (Symptoms and Signs)
Exclude reversible illness, drugs,
nutritional deficiency
Do you suspect altered SHBG?
Low T
Morning Total T
Normal T, LH+FSH
Not Hypogonadism
Follow up
Normal T
Repeat T
Check LH+FSH
If altered SHBG,
Use free or bio- T
Semen
analysis
if fertility issue
Keys: ‘T’ means Testosterone
How to investigate for Androgen Deficiencies
16. MALE HYPOGONADISM: Definition
A decrease in either of the two major
functions of the testes:
– sperm production
– testosterone production
17. Types of Male Hypogonadism
Secondary hypogonadism
Primary hypogonadism
18. Confirmed low T (Total < 300 ng/dl)
OR
Free or Bio T < normal (Free T <5 ng/dl)
Low T
Low / normal LH+FSH
Prolactin, iron salts
Other pituitary hormones
Low T
High LH+FSH
Karyotype
Klinefelter Syndrome
Other Testicular Insult
Secondary Hypogonadism
Primary Hypogonadism
MRI in certain cases
20. Kallman’s syndrome
Failure of GnRH secretion and neuronal development
Associated with anosmia (smelling disorder) and hyposmia (75%)
1 in 10,000
Male : female ratio 4:1
Diagnosis
– Low/undetectable testosterone, LH and FSH
– Other pituitary functions are normal
– Normal hypothalamus/pituitary on MRI, but absence of olfactory
bulb
Treatment
– Exogenous testosterone replacement
– Gonadotrophins if fertility required
21. Acquired or genetic (rare cases of GnRH receptor gene
mutation)
In acquired cases men may
– have gone through normal puberty
– Present with low libido, erectile dysfunction or
infertility
– Acquired cases may go into remission after
testosterone or gonadotropin therapy.
22. Miscellaneous causes of secondary
hypogonadism
Stress
Systemic illness
Structural
– Any pituitary tumour esp. prolactinomas
– Associated with other hormonal deficiencies
Drugs
– Anabolic steroids
– Cocaine and opiates
– Any drugs causing hyperprolactinaemia
Hemochromatosis
Endocrine – Cushing's, prolactinoma
Prader-Willi syndrome – 15q mutation – obesity and mental
retardation
Laurence-Monn-Biedl syndrome – obesity and mental retardation.
24. Opiates and hypogonadism
Long-acting opioid analgesics suppress the hypothalamic-pituitary
gonadal axis in men and produce symptomatic androgen deficiency
(up to 74%).
Opiates of all kinds cause reduced release of GnRH, LH, testosterone
(free testosterone).
This usual follows a dose dependent exposure and correlates to
reduction in libido and subjective erectile dysfunction.
Also leads to osteoporosis
NB: **I did not find any literature on special treatment or testosterone
replacement in this group. (though I suspect using a opioid antagonist or
stopping use of opiates might work)
25. Klinefelter’s syndrome
First described by Harry Klinefelter 1942
1:500 men affected
Extra X chromosome causes primary hypogonadism with
testosterone deficiency
Clinically
– Reduced testicular volume
– Tall eunachoid stature
– Reduced body hair
– Gynaecomastia
– Intellectual dysfunction in 40%
20 time increased risk of carcinoma of breast
26. Klinefelter’s Syndrome
Most common endocrine cause of Primary
hypogonadism
FSH always
T variably affected (T or normal)
Fertility rare (in mosaics only)
Treatment: T only if needed
– Will not reverse infertility
27. Signs:
Eunuchoidal body habitus
Variable androgenization
Long extremities (LS>US)
Karyotype: XXY
Klinefelter’s Syndrome
28. NB: So the klinefactor is having 47 chromosomes instead of 46
Trisomy
29. Low testosterone
Elevated LH/FSH
Azospermia
Definitive diagnosis is based on
karyotyping
– 47XXY or 46XY/47XXY
(mosaic)
Counselling
– Klinefelter’s Syndrome
Association UK
[http://www.ksa-uk.co.uk]
Androgen replacement
therapy
30. Noonan Syndrome
Autosomal dominant disorder (variable penetrance)
Normal karyotype
Phenotype is like that of Turners syndrome
– Low set ears
– Right sided congenital heart defects (left-sided in Turners)
– Epicanthic folds
– Short stature
– Webbed neck
– Cryptorchism (50% of males)
– Primary hypogonadism
Can affect either sex
31. 1 in 10,000 births
These patients have a translocation of part of the
Y chromosome with the X chromosome
Phenotype is similar to Klinefelter's
May also have short stature and hypospadias
32.
33. A 35 year old man presents with infertility & azoospermia. He was at
puberty at the age of 15, has normal libido and shaves every other day.
He is 72” tall, 180#, with gynecomastia and small testes
Has normal thyroid & phallus
The Testosterone level is low, LH high, FSH high
QUESTION???
Can you guys give me your tentative diagnosis with reasons and
also the best diagnostic test to establish your definitive diagnosis?
o
k
oCase 1
34. A 19 year old boy presents with inability to smell his girl friends perfume &
azoospermia
He is 175cm tall, 53kg weight, with his arm slightly than his height at
177.5cm. He had a normal voice and his pubic hair were adult like in
texture and type.
On endoscopy his olfactory fissures were patent and MRI images shows
that the olfactory bulb is absent.
The Testosterone level is low and other pituitary functions were found to
be normal with MRI.
QUESTION???
Can you guys give me your tentative diagnosis with reasons and
what type of hypogonadism is this disease?
o
k
oCase 2
35. A 54 year old man was asked by his wife of 35years old to go visit a physician
concerning his inability to perform well in bed (low libido and erectile
dysfunction). The man in addition complaint to the clinician about a long
time worsening fatigue.
On physical examination, he is found to be obese with BMI=31.
There is no evidence of gynecomastia
The testicles and prostate are normal
Lab evaluation reveals serum testosterone level of 180ng/dl
(ref. range: 249-836)
QUESTION???
What is your tentative diagnosis and why?
o
k
oCase 3
36.
37. Total vs. Free vs. Bioavailable
Testosterone (male)
60%
38%
2%
Affinity for SHBG
is at least 4X higher
vs. albumin
Greenspan’s Basic &Clinical Endocrinology, 8th edition
38. REFERENCES
Greenspan’s Basic &Clinical Endocrinology, 8th edition
Per Williams Textbook of Endocrinology 11th edition
[http://www.ksa-uk.co.uk]
Wikipedia [www.wikipedia.org]: kallman’s, klinefecter’s,
Nooman’s syndrome, XX males, etc....