A Case of Refeinstein's Syndrome

1,727 views

Published on

Published in: Health & Medicine
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,727
On SlideShare
0
From Embeds
0
Number of Embeds
82
Actions
Shares
0
Downloads
52
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide

A Case of Refeinstein's Syndrome

  1. 1. PROF.DR.G.SUNDARAMURTHY’S UNIT BHARGAVI.K.
  2. 2. <ul><li>17 yr old female came to the op with chief c/o </li></ul><ul><li>coarse voice… </li></ul><ul><li>h/o loss of appetite+ </li></ul><ul><li>h/o lethargy + </li></ul>
  3. 3. <ul><li>No h/o fever </li></ul><ul><li>No h/o recurrent cough with expectoration </li></ul><ul><li>No h/o post nasal drip </li></ul><ul><li>No h/o hemoptysis </li></ul>
  4. 4. <ul><li>No h/o dysphagia </li></ul><ul><li>No h/o intolerance to cold </li></ul><ul><li>No h/o constipation </li></ul><ul><li>No h/o alopecia </li></ul><ul><li>No h/o galactorrhoea </li></ul>
  5. 5. <ul><li>No h/o hot flushes </li></ul><ul><li>No h/o palpitations </li></ul><ul><li>No h/o visual disturbances </li></ul>
  6. 6. PAST H/O <ul><ul><li>NO SIGNIFICANT MEDICAL ILLNESSES IN THE PAST OR SURGICAL INTERVENTION IN THE PAST. </li></ul></ul><ul><ul><li>NOT A K/C/O HYPOTHYROIDISM </li></ul></ul><ul><ul><li>No h/o psychiatric disorders </li></ul></ul><ul><ul><li>DEVELOPMENTAL H/O : normal </li></ul></ul>
  7. 7. <ul><li>PERSONAL H/O </li></ul><ul><li>takes mixed diet </li></ul><ul><li>No h/s/o of eating disorders </li></ul><ul><li>NO h/s/o substance abuse </li></ul><ul><li>Not an athlete- subject to strenuous exercise </li></ul><ul><li>MENSTRUAL H/O </li></ul><ul><ul><li>NOT ATTAINED MENARCHE.. NOT EVALUATED PRIOR. </li></ul></ul>
  8. 8. FAMILY H/O <ul><ul><li>Born of non consanguinous marriage. </li></ul></ul><ul><ul><li>Parents healthy. </li></ul></ul><ul><ul><li>1 sibling –male 21 yrs. Healthy. </li></ul></ul>
  9. 9. <ul><li>A CASE OF PRIMARY AMENORRHOEA WITH COARSE VOICE </li></ul>
  10. 10. IN THE LINES OF… <ul><li>CONSTITUTIONAL DELAY </li></ul><ul><li>HYPOTHYROIDISM </li></ul><ul><li>HYPERPROLACTINEMIA </li></ul><ul><li>PREMATURE OVARIAN FAILURE </li></ul><ul><li>DSD </li></ul>
  11. 11. <ul><li>Gc fair </li></ul><ul><li>Afebrile </li></ul><ul><li>Hydration fair </li></ul><ul><li>No pallor/icterus/cyanosis/clubbing </li></ul><ul><li>No significant lymphadenopathy </li></ul>
  12. 12. <ul><li>Ht,wt- appropriate for age. </li></ul><ul><li>Hirsute features+ </li></ul><ul><li>No digital anomalies </li></ul><ul><li>No ext markers for congenital heart disease. </li></ul>
  13. 13. <ul><li>Pulse -88/min </li></ul><ul><li>BP- 120/70 mm hg </li></ul><ul><li>CVS </li></ul><ul><li>s1s2+ no murmurs. </li></ul><ul><li>RESPIRATORY SYSTEM- </li></ul><ul><li> nvbs+: no additional sounds. </li></ul><ul><li>CNS </li></ul><ul><li>Nfnd . </li></ul>
  14. 14. <ul><li>EXMN OF EAR,NOSE , THROAT - normal. </li></ul><ul><li>EXMN OF ORAL CAVITY -normal. </li></ul><ul><li>PER ABDOMEN- soft, no organomegaly, no free fluid. </li></ul>
  15. 15. <ul><li>BREASTS- TANNER STAGE I </li></ul><ul><li>PUBIC HAIR- TANNER STAGE III </li></ul><ul><li>AXILLARY HAIR- SPARSE </li></ul>
  16. 16. <ul><li>PER VAGINAL </li></ul><ul><li>AMBIGUOUS EXTERNAL GENITALIA </li></ul><ul><li>PENIOSCROTAL HYPOSPADIAS </li></ul>
  17. 17. <ul><li>A CASE OF DISORDER OF SEX AND DEVELOPMENT </li></ul>
  18. 18. DISORDERS OF SEX AND DEVELOPMENT 46 XX OVOTESTICULAR 46 XY CAH
  19. 19. <ul><li>BLOOD SUGAR -88 mgs </li></ul><ul><li>RFT :urea -18 </li></ul><ul><li> creatinine- 0.8 mgs </li></ul><ul><li>S.electrolytes: </li></ul><ul><li>Na-140, K- 4, </li></ul><ul><li>Cl- 98,HCO3-28mEq/L </li></ul>
  20. 20. <ul><li>CBC : TC-6800,DC-P48 L52 E2 </li></ul><ul><ul><ul><ul><li> HB:11.2 GMS, ESR-5/12 </li></ul></ul></ul></ul><ul><ul><ul><ul><li> PLATELETS-1.0 </li></ul></ul></ul></ul><ul><li>URINE ANALYSIS -normal </li></ul><ul><li>ECG- NSR </li></ul><ul><li>C-XRAY -normal </li></ul>
  21. 21. THYROID FUNCTION TESTS <ul><li>Thyroid function tests </li></ul>
  22. 22. <ul><li>LH : 12.85 mIU/ml </li></ul><ul><li>NORMAL VALUES </li></ul><ul><li>FOLLICULAR PHASE:1.9 -12.5 </li></ul><ul><li>MIDCYCLE PHASE:8.7-76.3 </li></ul><ul><li>LUTEAL PHASE:0.5-16.9 </li></ul><ul><li>MENOPAUSAL:>50 </li></ul><ul><li>FSH : 7.60 mIU/ml </li></ul><ul><li>NORMAL VALUES </li></ul><ul><li>FOLLICULAR PHASE:1.9 -10.2 </li></ul><ul><li>MIDCYCLE PHASE:3.4-33.4 </li></ul><ul><li>LUTEAL PHASE:1.5-9.1 </li></ul><ul><li>MENOPAUSAL:23-116 </li></ul>
  23. 23. <ul><li>TESTOSTERONE : 3.37 pg/ml. </li></ul><ul><li>NORMAL VALUES </li></ul><ul><li>MALE: 8.9-42.5 </li></ul><ul><li>FEMALE:0.2-3.09 </li></ul><ul><li>PROGESTERONE : 0.88 ng/ml. </li></ul><ul><li>NORMAL VALUES </li></ul>FOLLICULAR PHASE:0.11-1.08 LUTEAL PHASE:0.95-5.0
  24. 24. <ul><li>Estradiol levels :55 pg/ml. </li></ul><ul><li>Normal values </li></ul><ul><li>Follicular phase:30-60 pg/ml </li></ul><ul><li>Preovulatory phase:110-410 </li></ul><ul><li>Luteal phase:19-160 </li></ul>
  25. 25. <ul><li>High testosterone </li></ul><ul><li>High LH </li></ul><ul><li>High Estradiol </li></ul><ul><li>Normal FSH </li></ul>
  26. 26. <ul><li>ULTRASOUND ABDOMEN AND PELVIS </li></ul>
  27. 28. USG PELVIS
  28. 29. <ul><li>BIOPSY OF INGUINAL STRUCTURES </li></ul>
  29. 30. <ul><li>CONFIRMED THE PRESENCE OF SEMINIFEROUS TUBULES,LOBULI TESTIS AND RETE TESTIS . </li></ul>
  30. 31. COARSE VOICE, PRIMARY AMENNORRHOEA HORMONE PROFILE TESTOSTERONE,LH USG PELVIS ABSENT UTERUS,OVARIES BIOPSY OF INGUINAL STRUCTURES-TESTIS
  31. 32. <ul><li>? </li></ul>
  32. 33. <ul><li>KARYOTYPING </li></ul>
  33. 34. <ul><li>46 XY </li></ul>
  34. 35. DIAGNOSIS <ul><li>A CASE OF INCOMPLETE ANDROGEN INSENSITIVITY SYNDROME </li></ul><ul><li>REFEINSTEIN’S SYNDROME </li></ul>
  35. 36. PARTIAL AIS COMPLETE AIS Broad spectrum from absent or male Absent Wolfian duct Absent Absent Müllerian duct derivatives  Broad spectrum from female with mild clitoromegaly to male with micropenis and/or hypospadias Female External genitalia  X-linked recessive X-linked recessive Inheritance 
  36. 37. Mutations in AR gene Mutations or deletions in androgen receptor gene Molecular defect  High or normal serum LH and T levels, normal or slightly elevated FSH levels High or normal serum LH and T levels, normal or slightly elevated FSH levels Hormonal diagnosis  Gynecomastia Gynecomastia Puberty  Ectopic, inguinal or intraabdominal, Inguinal or intraabdominal, Testes 
  37. 38. ? PARTIAL AIS <ul><li>Penioscrotal hypospadias </li></ul><ul><li>Ambiguous external genitalia </li></ul><ul><li>Hypoplastic wolfian duct derivatives </li></ul><ul><li>Absent mullerian duct derivatives </li></ul><ul><li>Undescended testicular gonads </li></ul><ul><li>Presence of pubic n axillary hair- but scanty </li></ul><ul><li>Increased LH AND TESTOSTERONE, normal FSH. </li></ul>
  38. 39. MANAGEMENT <ul><li>PSYCHOLOGICAL COUNSELLING OF THE PATIENT AND PARENTS </li></ul><ul><li>TO CONTINUE SEX OF REARING AS FEMALE </li></ul>
  39. 40. <ul><li>DEPT OF PLASTIC SURGERY, GSH </li></ul><ul><li>b/l orchidectomy, </li></ul><ul><li>herniorrhaphy and </li></ul><ul><li>clitoroplasty. </li></ul>
  40. 41. <ul><li>Planned next for vaginal reconstuction </li></ul><ul><li>Planned breast enhancement- silicone implantation </li></ul><ul><li>Now placed under estrogen supplements- on follow up . </li></ul>
  41. 42. PRIMARY AMENNORRHOEA WITH DELAYED PUBERTY BONE AGE- CONSTITUTIONAL DELAY THYROID PROFILE LH, FSH, PROLACTIN INCREASED LH,FSH NORMAL LH,FSH
  42. 43. INCREASED LH,FSH KARYOTYPING 45 X ( turner’s) 46 XX (pure gonadal dysgenesis) 46 XY (swyer’s)
  43. 44. NORMAL LH, FSH PROLACTIN HIGH IMAGING MRI ABNORMAL- PITUITARY CAUSES NORMAL MRI EATING DISORDERS STRESS
  44. 45. AMENNORHOEA WITH NORMAL PUBERTY ULTRA SONOGRAM UTERUS PRESENT HYPOTHYROIDISM HYPERPROLACTINEMIA FSH LEVELS LOW- MRI HIGH FSH- PREMATURE OVARIAN FAILURE
  45. 46. GENITAL TRACT ABNORMALITIES ULTRA SONOGRA m ABSENT UTERUS FORESHORTENED VAGINA KARYOTYP e 46 XX MULLERIAN AGENESIS- ROKITANSKY 46 XY TESTOSTERONE HIGH LOW ANDROGEN INSENSITIVITY OR 5 A RED DEFICIENCY TESTICULAR REGRESSION
  46. 47. CAH 21 OH DEFICIENCY MASCULINISATION SALT WASTING INCREASED 17 OH P 11 OH DEFICIENCY INCREASED DOC SALT RETENTION HYPERTENSION 3 B HSD DEFICIENCY LESS VIRILIZ, SALT LOSING ^DHEA ONLY FORM CAUSING AMB. GENIT IN MALES
  47. 48. Ovotesticular disorders of sexual development <ul><li>Appearance of the genitalia varies widely in this condition. While ambiguity is the rule, the tendency is toward masculinization. </li></ul><ul><li>The most common karyotype is 46,XX, although mosaicism is common </li></ul>
  48. 49. 46 XY DSD ISOLATED DEFICIENCY OF MIS PHENOTYPIC MALE WITH AN INGUINAL HERNIA ON ONE SIDE AND AN IMPALPABLE CONTRALATERAL GONAD DEFICIENT TESTOSTERONE BIOSYNTHESIS ENZYME DEFECTS OR LEYDIG CELL DEFECTS 5 ALPHA REDUCTASE DEFICIENCY EXTREME VIRILISATION AT PUBERTY HIGH T/DHT RATIO PARTIAL GONADAL DYSGENESIS 46 XY OR MOSAICISM ONE GONAD IS DYSGENETIC PURE GONADAL DYSGENESIS B/L STREAK GONADS AIS
  49. 50. <ul><li>ANOMALOUS SEXUAL DEVELOPMENT </li></ul>
  50. 51. <ul><li>I.DISORDERS OF GONADAL DIFFERENTIATION </li></ul><ul><li>II.FEMALE PSEUDOHERMAPHRODITISM </li></ul><ul><li>III.MALE PSEUDOHERMAPHRODITISM </li></ul><ul><li>IV.UNCLASSIFIED FORMS </li></ul>
  51. 52. <ul><li>.TESTICULAR UNRESPONSIVENESS - LEYDIG CELL HYPOPLASIA </li></ul><ul><li>.INBORN ERRORS OF TESTOSTERONE BIOSYNTHESIS </li></ul><ul><li>. DEFECTS IN ANDROGEN DEPENDENT TARGET TISSUES </li></ul><ul><li>DYSGENETIC MALE PSEUDOHERMAPHRODITISM </li></ul><ul><li>.DEFECTS IN ANTI MULLERIAN HORMONE RESPONSE </li></ul><ul><li>.MATERNAL INGESTION OF PROGESTAGENS </li></ul><ul><li>.ENVIRONMENTAL CHEMICALS </li></ul>
  52. 53. <ul><li>I.END ORGAN RESISTANCE TO ANDROGENIC HORMONES </li></ul><ul><li>A. syndrome of complete androgen resistance </li></ul><ul><li>B. syndrome of incomplete androgen resistance C. androgen resistance in phenotypically normal males </li></ul><ul><li>II.DEFECTS IN TESTOSTERONE METABOLISM BY PERIPHERAL TISSUES </li></ul><ul><li>5 alpha reductase deficiency </li></ul>
  53. 54. <ul><ul><ul><li>Grade 1: PAIS </li></ul></ul></ul><ul><ul><li>Male genitals, infertile </li></ul></ul><ul><ul><ul><li>Grade 2: PAIS </li></ul></ul></ul><ul><ul><li>Male genitals but mildly ‘under-masculinized’ </li></ul></ul><ul><ul><ul><li>Grade 3: PAIS </li></ul></ul></ul><ul><ul><li>Male genitals more severely ‘under-masculinized’ </li></ul></ul><ul><ul><ul><li>Grade 4 : PAIS </li></ul></ul></ul><ul><ul><li>Ambiguous genitals </li></ul></ul><ul><ul><ul><li>Grade 5: PAIS </li></ul></ul></ul><ul><ul><li>Essentially female genitalia, with enlarged clitoris </li></ul></ul><ul><ul><ul><li>Grade 6: PAIS </li></ul></ul></ul><ul><ul><li>Female genitalia with pubic/underarm hair </li></ul></ul><ul><ul><ul><li>Grade 7: CAIS Female genitalia with little to no pubic/underarm hair </li></ul></ul></ul>Exists along continuum depending on degree of mutation in AR gene
  54. 55. Androgen Receptor Gene <ul><li>AIS results from mutations in the androgen receptor gene, located on the long arm of the X chromosome (Xq11-q12). </li></ul><ul><li>The AR gene provides instructions to make the protein called androgen receptor, which allows cells to respond to androgens, such as testosterone, and directs male sexual development. </li></ul><ul><li>Mutations include complete or partial gene deletions, point mutations and small insertions or deletions. </li></ul>
  55. 56. <ul><li>Mullerian duct inhibitor suppresses the mullerian ducts and prevents the development of internal female sex organs in males </li></ul><ul><ul><li>Wolffian ducts help develop the rest of the internal male reproductive system and suppress the Mullerian ducts </li></ul></ul><ul><ul><li>Defective androgen receptors cause the wolffian ducts and genitals to be unable to respond to the androgens testosterone and dihydrotestosterone. </li></ul></ul>
  56. 57. <ul><li>-testicular feminization </li></ul><ul><li>Syndrome of Morris </li></ul><ul><li>Prevelance about 1 in 44,000-60,000 live male births </li></ul>
  57. 58. TESTIS GONADS ABSENT OR VESTIGIAL MULLERIAN DUCT DERIVATIVES: USUALLY ABSENT WOLFIAN DUCT DERIVATIVES : FEMALE WITH BLIND VAGINALPOUCH GENITALIA X-LINKED RECESSIVE,MUTATIONS IN AR GENE INHERITANCE 46 XY KARYOTYPE
  58. 59. INCREASED PLASMA LH AND TESTOSTERONE CONCENTRATION,INCREASED ESTRADIOL, FSH LEVELS OFTEN NORMAL RESISTANCE TO ANDROGENIC N METABOLIC EFFECTS OF TESTOSTERONE HORMONE AND METABOLIC PROFILE: GENETIC HETEROGENEITY: RECEPTOR NEGATIVE, UNSTABLE OR RECEPTOR POSITIVE FORM ANDROGEN RECEPTOR STUDIES ABSENT PUBIC AND AXILLARY HAIR,BREAST DEVELOPMENT AND FEMALE HABITUS AT PUBERTY, PRIMARY AMENNORHOEA”HAIRLESS WOMEN” HABITUS:
  59. 60. <ul><li>REIFENSTEIN SYNDORME </li></ul><ul><li>Incidence- 1 in 1, 30,000 LIVE BIRTHS </li></ul><ul><li>Synonyms: </li></ul><ul><li>Gilbert-Dreyfus Syndrome </li></ul><ul><li>Incomplete Testicular Feminization </li></ul><ul><li>Lubs Syndrome </li></ul><ul><li>Rosewater Syndrome </li></ul><ul><li>Type I Familial Incomplete Male Pseudohermaphroditism </li></ul>
  60. 61. TESTIS- USUALLY UNDESCENDED GONADS ABSENT MULLERIAN DUCT DERIVATIVES: RUDIMENTARY-HYPOPLASTIC-NORMAL WOLFIAN DUCT DERIVATIVES : AMBIGUOUS WITH BLIND VAGINAL POUCH-PERINEOSCROTAL OR PENILE HYPOSPADIAS, ASMALL VAGINAL POUCH, A HOODED PHALLUS, UNFUSED PREPUTIAL FOLDS, BIFID SCROTUM, OCCASIONALLY GONADS. GENITALIA X-LINKED RECESSIVE,MUTATIONS IN AR GENE INHERITANCE 46 XY KARYOTYPE
  61. 62. genetic heterogeneity, partial deficiency of normal receptor, mutations lead to qualitatively abnormal receptor. ANDROGEN RECEPTOR STUDIES increased plasma lh n testosterone, increased estradiol, fsh levels normal or slightly increased Partial resistance to androgenic and metabolic effects of testosterone HORMONE AND METABOLIC PROFILE: decreased to normal axillary and pubic hair, beard growth and body hair, gynaecomastia HABITUS:
  62. 63. <ul><li>DURING PREGNANCY </li></ul><ul><ul><li>Chorionic villus sampling, ultrasound and amniocentesis </li></ul></ul><ul><li>AFTER BIRTH </li></ul><ul><ul><li>Hormone profile </li></ul></ul><ul><ul><li>Usg pelvis </li></ul></ul><ul><ul><li>karyotyping </li></ul></ul>
  63. 64. Special dynamic endocrine tests <ul><li>HCG STIMULATION TEST </li></ul><ul><li>ADMINISTRATION OF STEROIDS – DECREASED RESPONSE IN SEX HORMONE BINDING GLOBULIN </li></ul><ul><li>EVIDENCE OF ABNORMAL ANDROGEN BINDING IN A GENITAL SKIN FIBROBLAST </li></ul>
  64. 65. <ul><ul><li>SURGERIES </li></ul></ul><ul><ul><ul><li>Orchidectomy or gonadectomy </li></ul></ul></ul><ul><ul><li>Vaginal lengthening </li></ul></ul><ul><ul><ul><li>Genital plastic surgery </li></ul></ul></ul><ul><ul><ul><li>Phalloplasty </li></ul></ul></ul><ul><ul><ul><li>Vaginoplasty </li></ul></ul></ul><ul><ul><ul><li>clitoroplasty </li></ul></ul></ul>
  65. 66. HORMONE REPLACEMENT THERAPY <ul><li>ESTROGEN </li></ul><ul><li>Progesterone </li></ul><ul><li>Route-oral,transdermal or vaginal </li></ul><ul><li>Prevention of osteoporosis </li></ul>
  66. 67. <ul><li>EMOTIONAL AND PSYCHOLOGICAL SUPPORT </li></ul><ul><li>WHEN AND HOW TO DISCLOSE THE NEWS TO THE PATIENT </li></ul><ul><li>FAMILY : GUIDANCE IF THEY ARE CARRIERS AND DECISION ON FURTHER CHILD BIRTHS </li></ul><ul><li>ANDROGEN INSENSITIVITY SUPPORT GROUPS </li></ul>PSYCHOLOGICAL ISSUES
  67. 68. THANK YOU

×