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Download - لا يوجد عنوان للشريحة

  1. 1. Hormonal assay in clinical gynecology Prof. Aboubakr Elnashar Benha University Hospital, Egypt Email:
  2. 2. 1. Prolactin 2. TSH 3. FSH & LH 4. Estrogen 5. Progesterone 6. 17 OH progestrone 7. Androgens (Total testosterone, DHEAS)
  3. 3. Prolactin
  4. 4. It is secreted by: Mammotropic cells of the anterior pituitary. It is necessary for initiation & maintenance of lactation Reference values: Premenopuasal: <20 ng/ml Postmenopausal: <12 ng/ml
  5. 5. Conditions for detection of PRL Late morning, fasting, After 60 min rest, Not in late follicular phase, 2nd blood sample if the first is raised
  6. 6. Clinical significance: -Hyposecretion: rare. Pituitary necrosis or infarction -Hypersecretion: Idiopathic, Physiologic, pharmacologic, pathologic
  7. 7. Causes of Hyperprolactinaemia Physiologic Pharmacologic Pathologic Pregnancy Metclorpromide Hypothalamic disorders Lactation Methyldopa PRL secreting tumor Excerise Reserpine Hpothyroidism Eating Cimetidine Addsion’s disease Stress Estrogen Chest wall disease Morphine Chronic renal failure Alcholoic cirrhosis
  8. 8. Relation between The level & the cause: > 100 ng/ml: 60% pituitary tumor. > 300 ng/ml: 100% pituitary tumor Modest elevation can be associated with pituitary tumor
  9. 9. Clinical conditions associate with hyperprolactinaemia 1. Galactorrhea. 2. Oligomenorhea 3. Hirsutism 4. Anovulation 5. Corpus luteum deficiency 6. Infertility
  10. 10. Hyperprolactinaemia without galactorrhea : 66% 1. Inadequate detection 2. Hypoestrogenic state. 3. Inadequate estrogenic or progetational priming of the breast 4. High PRL does interact with the breast receptors
  11. 11. Diagnostic evaluation History & Examination: Exclude : Recent pregnancy, breast stimulation Drugs, Breast or chest lesion Prolactin >20 ng/ml <20 ng/ml TSH Normal High (hypothyroidism) MRI or CT ( Normal or hyperplasia, Microadenoma or Macroadenoma)
  12. 12. TSH
  13. 13. It is secreted by the thyrotrophic cells of the anterior pituitary . It stimulates the growth of the thyroid follicular cells & every step in thyroid hormone synthesis
  14. 14. Reference values: Conventional immunoassay: useful in diagnosis of hypothyroidism.can not dd between normal values & subnormal values in hyperthyroidism Sensitive Immunoassay: can dd Subclinical hypothyroidism: Increase TSH & normal free T4
  15. 15. Clinical conditions associated with thyroid dysfunction: 1. Oligomenorhea 2. Amenorrhea 3. Menorrhagia 4. Anovulation. 5. Inadequate corpus luteum. 4. Subfertility
  16. 16. Sensitive TSH High Normal Low Free T4 Normal thyroid Free T4 Low Normal Normal High Hypothyroidism Free T3 Subclinical hypothyroidism Normal High Subclinical hyperthyroidism Hyperthyroidism
  17. 17. FSH &LH
  18. 19. They are secreted by the anterior pituitary. The alpha subunit is identical for all glycoprotein hormones (TSH, HCG, LH & FSH), but the beta subunit differs. The peak of FSH is coincident with the peak of LH, but it is of lesser magnitude & briefer duration. Following the midcycle surge of LH & FSH, there is drop in both.
  19. 20. Normal values: FSH LH Adult 5-10 mIU/ml 5-20 mIU/ml Mid cycle peak 2 times the basal level 3 times the basal level
  20. 21. Clinical uses: FSH LH 1. Hypogonadotrophic < 5 mIU/ml < 5 IU/ml state e.g. prepubertal & pituitary disorders 2. Hypergonadotropic > 40 mIU/ml >40 mIU/ml state e.g.postmenopuse Ovarian failure 3. PCOS normal or decreased high Follicular phase ratio 1 2
  21. 22. 4. Testing for ovarian function: a. Day 3 FSH < 10 IU/L = normal < 15 IU/L : conception rate is twice when FSH 15-25 IU/L > 25 IU/L ( or age >44) is independently associated with near zero chance of pregnancy
  22. 23. b.Clomiphene citrate challenge test (CCCT) CC 100 mg /day from D5-9 Check FSH on D3 & 10 Sum of FSH >26 IU/L = poor responder LH can be used for assessment of ovarian reserve but FSH is better. FSH rises sooner & more dramatically than LH.
  23. 24. 5. Detection of ovulation LH surge: Follicular rupture occurs 36 h after the onset of serum LH surge & 12 H after LH peak. A positive urine result is often found only 12 h after the onset of serum LH. (around the point of LH peak). So ovulation is expected to occur 24 h after the urine LH surge
  24. 25. LH surge in urine: Quick, sensitive, relatively inexpensive, pinpoint the day of ovulation & has reduced the uncertainty in interpretation of progesterone levels by better-identifying the time of peak progestrone secretion at which to obtain serum
  25. 26.   6. Diagnosis of the cause of precocious puberty: (Breast development <8 y or menstruation <9 y.)
  26. 27. X ray of the lower ends of radius & ulna:bone age a. Retarded: hypothyroidism b. Normal: Partial c. Advanced: FSH : <2 IU/ml) ---- pseudo > 2 mIU/ml) ----- true: CT or MRI -------- Normal (idiopathic) Abnormal (CNS lesion)
  27. 28. <ul><li>7. Diagnosis of the cause of amenorrhea </li></ul><ul><li>Primary A.: </li></ul><ul><li>absence of menstruation by the age of 16 yr regardless of SSC or by the age of 14 yr in absence of SSC </li></ul><ul><li>Secondary A.: </li></ul><ul><li>Cessation of menstruation > 6 months </li></ul>
  28. 29. <ul><li>1. Pregnancy test. </li></ul><ul><li>2. TSH &PRL. </li></ul><ul><li>3. Progestin challenge test: ( MPA 5mgX2X5d) </li></ul><ul><li>+ve: Anovulation </li></ul>
  29. 30. <ul><li>-ve: E + P : </li></ul><ul><li>-ve: outflow or uterine failure  HSG, hysteroscopy, IVP & laparoscopy. </li></ul><ul><li>+ve: Ovarian failure or pituitary-hypothalamic dysfunction. </li></ul>
  30. 31. <ul><li>3. FSH: </li></ul><ul><li>high : Ovarian failure. </li></ul><ul><li>If 1ry: Karyotyping. </li></ul><ul><li>If 2ndry: premature menopause </li></ul><ul><li>Low or Normal : CT of Pituitary-hypothalamic region. </li></ul><ul><li>. Abnormal : pituitary disease </li></ul><ul><li>. Normal : hypothalamic dysfunction. </li></ul>
  31. 32. Estrogens
  32. 33. More than 30 estrogens have been identified, but only 3 estrogens are used in clinical practice: estrone (E!), estradiol (E2), estriol (E3). In contrast to E2 which is secreted almost entirely by the ovary, most E1 is derived from peripheral conversion of androstenedione & from E2 metabolism.
  33. 34. E2 is the most abundant E in premenopausal females, while E1 is the E in highest concentration in postmenopausal females. E2 is the most potent E E1, E2 & E3 are bound to SHBG. E2 & not total E is used for clinical purposes.
  34. 35. Normal values of E2 (pg/ml) Follicular phase: 25-27 Midcycle peak: 200-600 Luteal phase: 100-300 Postmenopausal: 5-25
  35. 36. E2 rises during the 2nd half of the follicular phase & reach a peak 24 h before LH surge & 36 h before ovulation. Following LH surge E2 drops to preovulatory levels, but then rises slightly to 100-300 pg/ml during luteal phase
  36. 37. Clinical applications: 1. E increases in E secreting tumors e.g. granulosa theca cell tumors 2. To classify hypogonadism : E is usually interpreted with gonadotropin measurements
  37. 38. 3. Test for ovarian reserve: Low D3 E2 (<75 pg/ml) combined with normal FSH: good ovarian reserve Evaluation of both E2 & FSH is better predictor of ovarian reserve than using either measurement alone.
  38. 39. 4. An indication of down regulation in the long protocol for superovulation in ART. E2: < 50 pg/ml 5. Monitoring Superovulation in ART: The goal is an E2 level of 200 pg/ml per large (>14 mm) follicle The risk of OHSS is significant if E2 is >4000 pg/ml ( Sperof,2002) The number of follicles & the type of patient should be considered.
  39. 40. 6. Monitoring of induction of ovulation with HMG (Sperof,2002). E2 1000-1500 pg/ml is optimal 1500-2000 pg/ml: increase risk of OHSS >2000 pg/ml: high risk of OHSS, consider cycle cancellation
  40. 41. Progesterone
  41. 42. In the serum: 18% is bound to cortisol binding globulin 79% is bound to albumin 3% is free
  42. 43. Normal values (ng/ml): P level is low prior to the mid cycle gonadotrophin surge. Shortly after that, P begin to rise rapidly reaching peak levels during the middle of the luteal phase (8 days after LH peak). Thereafter, a progressive fall occurs with barely detectable P levels reached prior to menses. Follicular phase: <1 Luteal phase: 5-20 Post menopause: <1
  43. 44. Clinical applications 1. Diagnosis of ovulation: in cases of infertility & DUB a midluteal phase serum level of 5 ng/ml 2. Diagnosis of corpus luteal dysfunction : Midluteal phase level of 10 ng/ml. Sum of 3 progesterone levels from D11-4 before menses: 15 ng/ml
  44. 45. Serum 17 OH progesterone
  45. 46. <ul><li>It is an intermediate metabolite in steroidogenesis in the adrenals </li></ul><ul><li>It is used for diagnosis of enzymatic deficiency in the adrenals. </li></ul><ul><li>Increased 17 OH progesterone indicates congenital adrenal hyperplasia </li></ul><ul><li>Clinical application </li></ul><ul><li>Hirsutism </li></ul><ul><li>Ambigous genitalia </li></ul>
  46. 47. <ul><ul><ul><li>17 oh P(ng/dl) morning </li></ul></ul></ul><ul><li>< 200 > 200 </li></ul><ul><li>Rules out adrenal hyperplasia ACTH stimulation test (0.25 </li></ul><ul><li>21-hydroxylase defiency mg ACTH I.V.& 17 oh P at time </li></ul><ul><li>zero & after 1 hour) </li></ul><ul><li>Normal Abnormal </li></ul><ul><li>Rules out adrenal hyperplasia Adrenal hyperplasia </li></ul>
  47. 48. Androgens
  48. 49. <ul><li>Androgen production </li></ul><ul><li>Androstenedione </li></ul><ul><ul><ul><li>Testosterone </li></ul></ul></ul><ul><li>Adrenal DHEA Ovary </li></ul><ul><ul><ul><li>DHEAS </li></ul></ul></ul>50% 50% 50% 25% 25% 90% 10% 100%
  49. 50. Androgen in the blood Male Normal female Hirsute female Free 3% 1% 2% Albumin 19% 19% 19% SHBG 78% 80% 79%
  50. 51. Normal values (ng/dl): Premenopause Postmenopause Testosterone 20-80 15-70 Androstenedione 60-300 30-150
  51. 52. <ul><li>Free testosterone </li></ul><ul><li>Good correlation with total production rate (= secretion rate + peripheral conversion rate) which correlate well with degree of virilization </li></ul><ul><li>Normal level: 1.5-11.4 pg/ml </li></ul><ul><li>Not done routinely in presence of hirsutism </li></ul><ul><li>Free androgen index (FAI)= TX 100 / SHBG if > 4.5 : PCOS </li></ul>
  52. 53. <ul><li>Dehydoepiandrosterone sulphate (DHEAS) </li></ul><ul><li>The principal contribution of 17 ketosteroids (KS) is from DHES. </li></ul><ul><li>It correlates with urinary 17 KS. It is more reliable indicator of adrenal androgen than 24 h 17 KS. </li></ul>
  53. 54. Clinical application In PCOS: DHEAS > 2ug/ml CC + Corticosteroid (ACOG,2002) In hirsutism: DHEAS: >2 ug/ml COCs + Corticosteroids DHEAS: not essential (Sperof,2002)
  54. 55. DHES is not essential (Speroff,2002) 1. If 17 OHP is normal: adrenal enzyme defect can be excluded . 2. Moderate elevations of DHES can be suppressed by suppression of ovulation. 3. DHES > 700 ug/dl is rare & is associated with high levels of testosterone 4. Imaging of the adrenals is more cost-effective than measuring DHES. N.B:Hyperprolactinaemia can cause an increase in DHEAS. Treatment with Bromocriptin will decrease prolactin & DHEAS
  55. 56. <ul><li>Total teststerone </li></ul><ul><li>Clinical application: </li></ul><ul><li>1. Initial laboratory investigation of hirsutism </li></ul><ul><li>Total testosterone: measures the ovarian & adrenal activity. </li></ul>
  56. 57. Testosterone (ng/dl) >200 <200 U/S of the ovary Anovulation ( FG/I. PRL, endom biopsy) Adenxal mass Nothing Laparotomy CT of the adrenala & ovaries Laparotomy
  57. 58. 2. Evaluation of infant with ambiguous genitalia
  58. 59. Karyotype, Androgens, 17OHP XX Y-containing abnormal karyotype Elevated androgens Normal androgen Elevated 17OHP Normal 17OHP CAH Elevated maternal True H.phrodite (21OH androgen Gonadal dysgenesis 11BOH ) Gonadectomy
  59. 60. Karyotype, Androgens, 17 OHP XY Normal androgens Normal androgens signs of adrenal failure Normal 17OHP normal 17 OHP CAH with 3B IAIS, 5  reductase def, true hph, . Dehydogenase mixed gonadal dysgenesis, block in male. abnormal androgen synthesis Gonadectomy
  60. 61. Thank you Prof. Aboubakr Elnashar Benha University Hospital,Egypt Email: