12. Once Pregnancy and cryptomenorrhea are excluded: The patient is a bioassay for Endocrine abnormalities Four categories of patients are identified 1. Amenorrhea with absent or poor secondary sex Characters 2. Amenorrhea with normal 2ry sex characters 3. Amenorrhea with signs of androgen excess 4. Amenorrhea with absent uterus and vagina
13. FSH Serum level Low / normal High Hypogonadotropic hypogonadim Gonadal dysgenesis
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15. FSH Low / normal High Hypothalamic-pituitary Failure Ovarian failure If < 25 yrs or primary amenorrhea karyoptype If < 35 yrs R/O autoimmune disease ?? Ovarian biopsy head CT- scan or MRI - Severe hypothalamic dysfunction - Intracranial pathology
16. Amenorrhea Utero-vaginal absence Karyotype 46- XX Mullerian Agenesis (MRKH syndrome) Andogen Insenitivity (TSF syndrome) . Gonadal regressioon . Testocular enzyme defenciecy . Leydig cell agenisis 46- XY Normal breasts & sexual hair Normal breasts & absent sexual hair Absent breasts & sexual hair
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19. Amenorrhea Signs of androgen excess Testosterone, DHEAS, FSH, and LH DHEAS 500-700 mug/dL DHEAS >700 mug/dL TEST. >200 ng/dL Serum 17-OH Progesterone level Late CAH Adrenal hyperfunction U/S ? MRI or CT Ovarian Or adrenal tumor Lower elevations PCOS (High LH / FSH)
47. How would you evaluate this patient? Total testosterone: 134 ng/dL (176-781) Luteinizing hormone (LH): 26.3 mIU/mL (1.3-13.0) What is the initial diagnosis? Primary hypogonadism What is the next step in work up?
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49. Confirmed low testosterone Check LH+FSH (SA if infertility) High gonadotropins – 1 o Low/low nl gonadotropins – 2 o Karyotype Prolactin, other pituitary hormones, iron studies, sella MRI
50. How would you evaluate this patient? Total testosterone: 134 ng/dL (176-781) Luteinizing hormone (LH): 26.3 mIU/mL (1.3-13.0) What is the initial diagnosis? Primary hypogonadism What is the next step in work up? Karyotype: 47 XXY
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52. Gordon DL et al. Arch Intern Med (1972) 130:720 Abnormality Frequency (%) Abnormal testicular histology 100 Decreased testicular length 99 Azoospermia 93 Low testosterone 79 Decreased facial hair 77 Increased gonadotropins 75 Decreased sexual function 68 Gynecomastia 55 Decreased axillary hair 49 Decreased penis length 41
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57. Case 1 Answer: Full physical examination Serum endocrinology: FSH, LH, prolactin, thyroid function pregnancy test Ultrasound scan of the pelvis (uterus and ovaries)
58. Case 1 Results FSH of 2.2 iu/L LH 15.0 iu/L normal prolactin and thyroid function The ultrasound scan demonstrated the presence of polycystic ovaries and an endometrial thickness of 15 mm.
60. Case 1 Endometrial hyperplasia is a risk factor for oligo / amenorrhoeic women with PCOS because of unopposed oestrogen stimulating progressive hyperplasia and potentially malignancy / adenocarcinoma. Regular withdrawal bleeds should be induced either with cyclical progestogens or the COC pill. If fertility is required then ovulation induction should be instituted with clomifene citrate followed by gonadotrophin therapy if this is unsuccessful. If the patient is overweight she should be encouraged to lose weight. Women with polycystic ovary syndrome have insulin resistance and at an increased of cardiovascular disease and type II diabetes.
61. Case 2 An 18 year old woman presents with primary amenorrhoea (she has never had a period). She has developed small breasts and has some pubic hair. She is very overweight with a body mass index of 39 kg/m 2 . What investigations should be performed in order to make the diagnosis?
62. Case 2 Answer: Full physical examination Serum endocrinology: FSH, LH, prolactin, thyroid function ( pregnancy test) Ultrasound scan of the pelvis (uterus and ovaries)
63. Case 2 Results FSH of 0.5 iu/L LH of 0.5 iu/L normal prolactin and thyroid function The ovaries appear small on ultrasound scan, as does the uterus. What is the diagnosis?
64. Case 2 Hypogonadotrophic hypogonadism Usually of hypothalamic origin and may be congenital, such as Kallmann's Syndrome (association with lack of smell) The low gonadotrophin concentrations have failed to stimulate ovarian development and adequate puberty. The small amount of breast development and pubic hair can be explained by oestrogen being produced in the peripheral fat and adrenal androgen secretion. Overall this patient will be oestrogen deficient and bone mineral densitometry should be performed to exclude osteoporosis.
66. Case 2 If the patient wishes to be pregnant, first line treatment would be pulsatile GnRH or gonadotrophin stimulation of the ovaries with a preparation that contains both FSH and LH bio-activity (ie, one of the traditional hMG preparations rather than recombinant FSH). Otherwise HRT should be given.
67. Case 2 Do you need to image the pituitary / hypothalamus?
68. Case 2 Do you need to image the pituitary / hypothalamus? Yes in adults with secondary amenorrhoea and hypog/hypog or hyperPRL, but tumours less common in adolescents if no other symptoms and normal PRL
69. Case 2 The patient was administered HMG at increasing high doses, but failed to produce any demonstrable follicular growth as assessed both by ultrasound scan and persistently low serum oestradiol concentrations. Can you explain?
70. Case 2 This patient appears to have a second pathology and may well have primary ovarian failure combined with hypothalamic hypogonadotrophic hypogonadism, thus explaining the combination of ovarian failure with low gonadotrophin concentrations.
71. Case 3 An 18 year old woman presents with primary amenorrhoea (she has never had a period). She has a normal body mass index and no other obvious problems. What investigations should be performed in order to make the diagnosis?
72. Case 3 Answer: Full physical examination Serum endocrinology: FSH, LH, prolactin, thyroid function (pregnancy test) Ultrasound scan of the pelvis (uterus and ovaries)
73. Case 3 Results FSH of 0.5 iu/L LH of 0.5 iu/L serum prolactin concentration: 5,000 mu/L What is the diagnosis? What further investigations should be done?
74. Case 3 Hyperprolactinaemia A repeat prolactin should be measured. The diagnosis is likely to be that of a macro-adenoma of the pituitary gland and therefore either MRI or CT imaging of pituitary should be performed. What treatment should be provided?
75. Case 3 Dopamine agonists: Bromocriptine or Cabergoline Check visual fields
76. Case 4 An 18 year old woman presents with primary amenorrhoea (she has never had a period). She has a normal body mass index and no other obvious problems. What investigations should be performed in order to make the diagnosis?
77. Case 4 Answer: Full physical examination Serum endocrinology: FSH, LH, prolactin, thyroid function (pregnancy test) Ultrasound scan of the pelvis (uterus and ovaries)
78. Case 4 Results FSH of 40 iu/L LH of 30 iu/L What is the diagnosis? What further investigations should be done?
79. Case 4 Primary ovarian failure / premature ovarian failure What further investigations should be performed?