Gonadal function/disorders Flashcards
(31 cards)
Most adrenal biosynthetic defects result in
• Virilized female
●Normally virilized male
●Deficiencies:
●Mineralocorticoid
●Glucocorticoid
●21-OHase deficiency
●11-OHase deficiency
How does CYP deficiency manifest in a female
Deficiency of CYP 17
●17α- hydroxylase and 17-20 lyase deficiency
●Rare cause
●Diagnosed due to delayed pubertal development
Female: 46xx:
●Hypertensive
●+/- Hypokalemia
●Primary amenorrhea
●Absent secondary sex characteristics
How does CYP 17 manifest in a male
Complete male pseudohermaphroditism
●Female external genitalia
●Blind-ended vagina
●No mullerian structures
●Testes intra-abdominal
●Leydig cell hyperplasia
●Hypertensive
●+/- Hypokalemia
•Cortisol sufficient
●Tolerates general anesthesia and surgery
Treatment
●Steroids to suppress excess ACTH
●Gonadal steroid replacement
What is β-Hydroxysteroid Dehydrogenase deficiency
β-Hydroxysteroid Dehydrogenase
●Presents early infancy
●Adrenal insufficiency
●Females can be virilized due to DHEA
●Males:
●Normal genital development
●Hypospadias
●Pseudohermaphroditism
Females:
●Can present in puberty with:
●Hyperandrogenemia
●Hirsuitism
●Oligomenorrhea
●Treatment
●Cortisol replacement
What is Steroidogenic Acute Regulatory Protein (StAR) deficiency
StAR Deficiency
●Transports cholesterol to inner mitochondrial membrane
●Rarest form of CAH
●Autosomal recessive
●All adrenal steroids are deficient
●Presents with adrenal insufficiency
●Typically fatal in infancy
Males:
●Female external genitalia
What are the sexes as determined by chromosome (males, females, klinefelter and turner’s syndromes)
●Normal male: 46 XY karyotype
●Normal female: 46 XX karyotype
●Klinefelter’s syndrome: 47 XXY,
48 XXXY, 46 XX/XY mosaic ♂
●Turner’s syndrome: 45 XO, ♀
●The sex chromosomes determine whether the primitive gonads become testes or ovaries
What are some causes of male and female gonadal disorders
Secondary:
●Genetic (abnormalities of hypothalamus or pituitary)
●Kallmann’s: GnRH def
●GnRH receptor mutations
●Isolated LH or FSH deficiency
●Mutations that lead to absence of some pituitary hormones
Secondary & Tumorous
●Pituitary tumours,PrL
●Various brain tumours: craniopharyngioma, astrocytoma
●Head trauma
Mention some facts about Klinefelter’s syndrome
Klinefelter’s syndrome (47 XXY)
● XY gonadal dysgenesis
●LH & FSH receptor mutations
●Testicular infections e.g. mumps
●Chemotherapy and irradiation of gonads
Mention some facts about Turner’s syndrome
Turner’s syndrome (45, XO)
●XX gonadal dysgenesis
●LH & FSH receptor mutations
●Autoimmune ovary resistance
●Chemotherapy and irradiation of gonads
What are some other causes of male and female gonadal disorders
Chemical or cellular defects in androgen synthesis
●Others : Testicular feminization syndrome which may be due to inactive androgen receptor activities
●Primary ovarian failure (POF)
●Polycystic ovarian syndrome
Miscellaneous
●Amenorrhoea
●Oligomenorrhoea
●Hirsutism ; increase in body hair with male pattern distribution (may be genetic and benign)
●Virilism: Testosterone , clitoromegaly, breast atrophy, deep male voice
●Others: Cushing’s syndrome, Acromegaly
What is subfertility
Defined as the failure of a couple to conceive after one year of unprotected intercourse.
●The cause could be either male or female or both
●A full clinical history on the couple e.g. previous pregnancies, use of contraceptives, serious illness, chemotherapy, STDs etc. is required
●♂: Initial semen analysis should be performed i.e. vol., sperm morphology, count, motility etc.
●♀: Needs physical examination by an O&G specialist
●Thorough lab. Investigations in each partner
What does male fertility depend on
Depends on production of adequate numbers of healthy spermatozoa and their subsequent delivery to the upper female tract
●Hindered by hypospadias and impotence
What are some causes of female infertility
Ovulatory failure:
Total, & infrequent ovulation
(Orderly FSH stimulation followed by a midcycle LH surge maturation + ovulation of selected Graafian follicle)
●Hyperprolactinaemia inhibits ovulation (normal in pregnancy and lactation)
Failure of ovaries to respond normally to gonadotrophins e.g. in the polycystic ovary (Stein-Leventhal) syndrome (PCOS)
●Oestrogen effects on endometrium and cervical mucus affect fertility
●Tubal blockage: Salpingitis, PID & pelvic peritonitis can damage ciliated epithelium
●Hypothyroidism (a possibility in obese infertile women)
●Diabetes (badly controlled)
●Uterine fibromyomata:
large ones that distort the uterine cavity or block the interstitial parts of the tubes may cause infertility
Endometriosis:
Seen in women who either have never been pregnant or not been pregnant for some years
●Endometriosis causes peritubular adhesions and is associated with dyspareunia leading to infrequent sexual intercourse
●Fixed retroverted uterus (unlikely cause unless associated with salpingitis and endometriosis)
What are some history required in the investigation of the infertile couple
♀: Menstrual Hx
●Previous gynaecological Hx
●Hx of pelvic infection
●General state of health and nutrition
●♂: Hx of sexual function, erection and ejaculation
●Hx of orchitis and venereal disease
●Frequency of intercours
What are laboratory investigations of subfertility in the male
No endocrine investigation should be done in eugonadal male with normal sperm analysis
●In hypogonadal male, testosterone and gonadotrophins should be investigated
●FSH, LH will be elevated but Testosterone will be decreased in Primary testicular failure
●In hypothalamic –pituitary diseases, there would be low testosterone with low or normal gonadotrophins
Explain seminal fluid analysis
●This should normally be the first step in investigation because it is pointless investigating the female if no sperm are present
●Investigation of the female involves a lot of tests, therefore it is better to start with the few tests in the male After 3 days’ abstinence, a specimen of semen is collected in a sterile plastic container after ? masturbation or coitus using sterile sheath (containing no spermicide) and examined within a few hours.
●The figures given are average and considerable variation occurs from individual to individual
●The figures given reflect the man’s state of health 70 days previously, when the spermatozoa were formed
(we would need to confirm this information)
●For a correct evaluation of male fertility, two or three consecutive specimens of semen may need to be examined especially when the first analysis shows any abnormality
●Azoospermia is the term used when there are no spermatozoa in the semen
●Oligospermia is the term applied when there are less than 10 million spermatozoa per millilitre
●Once the seminal fluid analysis has been carried out and found to be normal, the next steps are tests for ovulation and tubal patency
What are some laboratory investigations of subfertility in the female
NB. Investigation will depend on which phase of the menstrual cycle the woman is in viz; Ovulatory, follicular, luteal etc.
●LH, FSH, E2, Testo, Prolactin, Pg (profiles will depend on the disorder or cause of subfertility)
●In (primary ovarian failure) POF- there is elevated LH, FSH but low E2
How is ovulation tested for
Oral temperature is taken every morning on waking and is recorded on a special temperature chart
●A rise in the basal body temperature of about 0.5ºC in the last 14 days of the cycle indicates that ovulation has taken place
●Examination of the cervical mucus in the mid-cycle will reveal characteristic changes if ovulation has occurred
• Ovulatory mucus is clear and copious, and can be drawn out into a fine thread ‘spinnbarkheit’. On drying it crystallizes out into a fine fern-like pattern
●A sample of blood is taken one week before a period is expected i.e. day 21 of a 28 day cycle. A progesterone level of more than10 ng/ml in this confirms that ovulation has taken place
• Histological examination of premenstrual endometrial biopsy shows secretory changes in the glands after ovulation
●This investigation is commonly combined with laparoscopic examination of the fallopian tubes
What are some tests for tubal patency
Laparoscopic method (invasive)
●Premenstrual laparoscopic examination of the tubes combined with injection of a dilute solution of methylene blue through a tightly fitting cannula placed in the cervical cannal is used to investigate tubal patency
●The uterus distends with the dye and if the tubes are patent, they fill with dye which finally spills from the distal ends
●In distal block there is no spill
●In medial block no dye enters the tubes
●Patients are warned not to get pregnant in the cycle in which such an investigation is carried out
• Hysterosalpingography
What is hysterosalpingography
Injection of a radio-opaque aqueous iodine solution through the cervix under radiographic control remains a most useful investigation for tubal patency
●This test should be performed during the first 10 days of the cycle after menstrual bleeding has ceased but before ovulation has occurred
●An X-ray image intensifier and a television screen are employed
●This test determines the exact site of any tubal blockage
●It also outlines the uterine shape to show any congenital abnormality or any distortion by fibromyomata
●Free spill of the dye, loculation around the distal end or frank occlusion of the tube often with club-shaped ending may be observed
●Minor peritubal adhesions may escape detection by hysterosalpingography
What is a cervical compatibility test
●Cervical ovulatory mucus: copious, clear and shows spinnbarkheit
●After establishment of the corpus luteum and rise in blood progestrone it becomes scanty, viscid and cellular as it was in the early part of the cycle
●Sperm penetration of cervical mucus occurs more readily at the time of ovulation but can be hindered by sperm antibodies
What is a post-coital test
This test is carried out at the time of ovulation ( day 14 of a 28-day cycle)
●6-12 h after intercourse, the cervix is exposed with a bivalve speculum and a sample of cervical mucus is withdrawn with a wire loop or pipette and placed on a warm slide and covered with a coverslip
●The number of progressively motile sperm in a number of high power fields is examined Normally a large number of active sperm will be seen
●When the test is negative it should be repeated in two further cycles at the time of ovulation as determined by the rise in basal body temperature
If all three tests are negative, a sample of the partner’s semen is obtained and a drop of it is placed alongside a drop of the woman’s ovulatory cervical mucus (Kurzrok-Miller test)
What is the mucus invasion test
●If all three tests are negative, a sample of the partner’s semen is obtained and a drop of it is placed alongside a drop of the woman’s ovulatory cervical mucus (Kurzrok-Miller test)
●Invasion of the mucus by sperm is observed over the next 15 minutes
●Normal spermatozoa will immediately start to penetrate normal cervical mucus and will continue to be active in it
●A negative post-coital and mucus invasion test may be due to poor quality cervical mucus indicating a relative deficiency of oestrogen
●Presence of sperm auto-antibodies (♂) in seminal plasma causes clumping of sperm before ejaculation
●Sperm antibodies (♀) in cervical mucus cause agglutination and immobilization of the invading sperm.
●The serum of both partners should then be examined for sperm agglutinating and immobilizing antibodies
What are some pathological causes of amenorrhea
Uterine lesions
•Ovarian lesions
•Pituitary disorders
•Disorders of other endocrine glands
•Psychiatric illness and emotional stress
•Severe general illness
•Drugs causing amenorrhoea
•Surgical operations or radiotherapy
