Your SlideShare is downloading. ×
  • Like
A Case of Refeinstein's Syndrome
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×

Now you can save presentations on your phone or tablet

Available for both IPhone and Android

Text the download link to your phone

Standard text messaging rates apply
Published

 

Published in Health & Medicine
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads

Views

Total Views
1,233
On SlideShare
0
From Embeds
0
Number of Embeds
1

Actions

Shares
Downloads
36
Comments
0
Likes
0

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. PROF.DR.G.SUNDARAMURTHY’S UNIT BHARGAVI.K.
  • 2.
    • 17 yr old female came to the op with chief c/o
    • coarse voice…
    • h/o loss of appetite+
    • h/o lethargy +
  • 3.
    • No h/o fever
    • No h/o recurrent cough with expectoration
    • No h/o post nasal drip
    • No h/o hemoptysis
  • 4.
    • No h/o dysphagia
    • No h/o intolerance to cold
    • No h/o constipation
    • No h/o alopecia
    • No h/o galactorrhoea
  • 5.
    • No h/o hot flushes
    • No h/o palpitations
    • No h/o visual disturbances
  • 6. PAST H/O
      • NO SIGNIFICANT MEDICAL ILLNESSES IN THE PAST OR SURGICAL INTERVENTION IN THE PAST.
      • NOT A K/C/O HYPOTHYROIDISM
      • No h/o psychiatric disorders
      • DEVELOPMENTAL H/O : normal
  • 7.
    • PERSONAL H/O
    • takes mixed diet
    • No h/s/o of eating disorders
    • NO h/s/o substance abuse
    • Not an athlete- subject to strenuous exercise
    • MENSTRUAL H/O
      • NOT ATTAINED MENARCHE.. NOT EVALUATED PRIOR.
  • 8. FAMILY H/O
      • Born of non consanguinous marriage.
      • Parents healthy.
      • 1 sibling –male 21 yrs. Healthy.
  • 9.
    • A CASE OF PRIMARY AMENORRHOEA WITH COARSE VOICE
  • 10. IN THE LINES OF…
    • CONSTITUTIONAL DELAY
    • HYPOTHYROIDISM
    • HYPERPROLACTINEMIA
    • PREMATURE OVARIAN FAILURE
    • DSD
  • 11.
    • Gc fair
    • Afebrile
    • Hydration fair
    • No pallor/icterus/cyanosis/clubbing
    • No significant lymphadenopathy
  • 12.
    • Ht,wt- appropriate for age.
    • Hirsute features+
    • No digital anomalies
    • No ext markers for congenital heart disease.
  • 13.
    • Pulse -88/min
    • BP- 120/70 mm hg
    • CVS
    • s1s2+ no murmurs.
    • RESPIRATORY SYSTEM-
    • nvbs+: no additional sounds.
    • CNS
    • Nfnd .
  • 14.
    • EXMN OF EAR,NOSE , THROAT - normal.
    • EXMN OF ORAL CAVITY -normal.
    • PER ABDOMEN- soft, no organomegaly, no free fluid.
  • 15.
    • BREASTS- TANNER STAGE I
    • PUBIC HAIR- TANNER STAGE III
    • AXILLARY HAIR- SPARSE
  • 16.
    • PER VAGINAL
    • AMBIGUOUS EXTERNAL GENITALIA
    • PENIOSCROTAL HYPOSPADIAS
  • 17.
    • A CASE OF DISORDER OF SEX AND DEVELOPMENT
  • 18. DISORDERS OF SEX AND DEVELOPMENT 46 XX OVOTESTICULAR 46 XY CAH
  • 19.
    • BLOOD SUGAR -88 mgs
    • RFT :urea -18
    • creatinine- 0.8 mgs
    • S.electrolytes:
    • Na-140, K- 4,
    • Cl- 98,HCO3-28mEq/L
  • 20.
    • CBC : TC-6800,DC-P48 L52 E2
          • HB:11.2 GMS, ESR-5/12
          • PLATELETS-1.0
    • URINE ANALYSIS -normal
    • ECG- NSR
    • C-XRAY -normal
  • 21. THYROID FUNCTION TESTS
    • Thyroid function tests
  • 22.
    • LH : 12.85 mIU/ml
    • NORMAL VALUES
    • FOLLICULAR PHASE:1.9 -12.5
    • MIDCYCLE PHASE:8.7-76.3
    • LUTEAL PHASE:0.5-16.9
    • MENOPAUSAL:>50
    • FSH : 7.60 mIU/ml
    • NORMAL VALUES
    • FOLLICULAR PHASE:1.9 -10.2
    • MIDCYCLE PHASE:3.4-33.4
    • LUTEAL PHASE:1.5-9.1
    • MENOPAUSAL:23-116
  • 23.
    • TESTOSTERONE : 3.37 pg/ml.
    • NORMAL VALUES
    • MALE: 8.9-42.5
    • FEMALE:0.2-3.09
    • PROGESTERONE : 0.88 ng/ml.
    • NORMAL VALUES
    FOLLICULAR PHASE:0.11-1.08 LUTEAL PHASE:0.95-5.0
  • 24.
    • Estradiol levels :55 pg/ml.
    • Normal values
    • Follicular phase:30-60 pg/ml
    • Preovulatory phase:110-410
    • Luteal phase:19-160
  • 25.
    • High testosterone
    • High LH
    • High Estradiol
    • Normal FSH
  • 26.
    • ULTRASOUND ABDOMEN AND PELVIS
  • 27.  
  • 28. USG PELVIS
  • 29.
    • BIOPSY OF INGUINAL STRUCTURES
  • 30.
    • CONFIRMED THE PRESENCE OF SEMINIFEROUS TUBULES,LOBULI TESTIS AND RETE TESTIS .
  • 31. COARSE VOICE, PRIMARY AMENNORRHOEA HORMONE PROFILE TESTOSTERONE,LH USG PELVIS ABSENT UTERUS,OVARIES BIOPSY OF INGUINAL STRUCTURES-TESTIS
  • 32.
    • ?
  • 33.
    • KARYOTYPING
  • 34.
    • 46 XY
  • 35. DIAGNOSIS
    • A CASE OF INCOMPLETE ANDROGEN INSENSITIVITY SYNDROME
    • REFEINSTEIN’S SYNDROME
  • 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 
  • 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 
  • 38. ? PARTIAL AIS
    • Penioscrotal hypospadias
    • Ambiguous external genitalia
    • Hypoplastic wolfian duct derivatives
    • Absent mullerian duct derivatives
    • Undescended testicular gonads
    • Presence of pubic n axillary hair- but scanty
    • Increased LH AND TESTOSTERONE, normal FSH.
  • 39. MANAGEMENT
    • PSYCHOLOGICAL COUNSELLING OF THE PATIENT AND PARENTS
    • TO CONTINUE SEX OF REARING AS FEMALE
  • 40.
    • DEPT OF PLASTIC SURGERY, GSH
    • b/l orchidectomy,
    • herniorrhaphy and
    • clitoroplasty.
  • 41.
    • Planned next for vaginal reconstuction
    • Planned breast enhancement- silicone implantation
    • Now placed under estrogen supplements- on follow up .
  • 42. PRIMARY AMENNORRHOEA WITH DELAYED PUBERTY BONE AGE- CONSTITUTIONAL DELAY THYROID PROFILE LH, FSH, PROLACTIN INCREASED LH,FSH NORMAL LH,FSH
  • 43. INCREASED LH,FSH KARYOTYPING 45 X ( turner’s) 46 XX (pure gonadal dysgenesis) 46 XY (swyer’s)
  • 44. NORMAL LH, FSH PROLACTIN HIGH IMAGING MRI ABNORMAL- PITUITARY CAUSES NORMAL MRI EATING DISORDERS STRESS
  • 45. AMENNORHOEA WITH NORMAL PUBERTY ULTRA SONOGRAM UTERUS PRESENT HYPOTHYROIDISM HYPERPROLACTINEMIA FSH LEVELS LOW- MRI HIGH FSH- PREMATURE OVARIAN FAILURE
  • 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
  • 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
  • 48. Ovotesticular disorders of sexual development
    • Appearance of the genitalia varies widely in this condition. While ambiguity is the rule, the tendency is toward masculinization.
    • The most common karyotype is 46,XX, although mosaicism is common
  • 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
  • 50.
    • ANOMALOUS SEXUAL DEVELOPMENT
  • 51.
    • I.DISORDERS OF GONADAL DIFFERENTIATION
    • II.FEMALE PSEUDOHERMAPHRODITISM
    • III.MALE PSEUDOHERMAPHRODITISM
    • IV.UNCLASSIFIED FORMS
  • 52.
    • .TESTICULAR UNRESPONSIVENESS - LEYDIG CELL HYPOPLASIA
    • .INBORN ERRORS OF TESTOSTERONE BIOSYNTHESIS
    • . DEFECTS IN ANDROGEN DEPENDENT TARGET TISSUES
    • DYSGENETIC MALE PSEUDOHERMAPHRODITISM
    • .DEFECTS IN ANTI MULLERIAN HORMONE RESPONSE
    • .MATERNAL INGESTION OF PROGESTAGENS
    • .ENVIRONMENTAL CHEMICALS
  • 53.
    • I.END ORGAN RESISTANCE TO ANDROGENIC HORMONES
    • A. syndrome of complete androgen resistance
    • B. syndrome of incomplete androgen resistance C. androgen resistance in phenotypically normal males
    • II.DEFECTS IN TESTOSTERONE METABOLISM BY PERIPHERAL TISSUES
    • 5 alpha reductase deficiency
  • 54.
        • Grade 1: PAIS
      • Male genitals, infertile
        • Grade 2: PAIS
      • Male genitals but mildly ‘under-masculinized’
        • Grade 3: PAIS
      • Male genitals more severely ‘under-masculinized’
        • Grade 4 : PAIS
      • Ambiguous genitals
        • Grade 5: PAIS
      • Essentially female genitalia, with enlarged clitoris
        • Grade 6: PAIS
      • Female genitalia with pubic/underarm hair
        • Grade 7: CAIS Female genitalia with little to no pubic/underarm hair
    Exists along continuum depending on degree of mutation in AR gene
  • 55. Androgen Receptor Gene
    • AIS results from mutations in the androgen receptor gene, located on the long arm of the X chromosome (Xq11-q12).
    • 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.
    • Mutations include complete or partial gene deletions, point mutations and small insertions or deletions.
  • 56.
    • Mullerian duct inhibitor suppresses the mullerian ducts and prevents the development of internal female sex organs in males
      • Wolffian ducts help develop the rest of the internal male reproductive system and suppress the Mullerian ducts
      • Defective androgen receptors cause the wolffian ducts and genitals to be unable to respond to the androgens testosterone and dihydrotestosterone.
  • 57.
    • -testicular feminization
    • Syndrome of Morris
    • Prevelance about 1 in 44,000-60,000 live male births
  • 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
  • 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:
  • 60.
    • REIFENSTEIN SYNDORME
    • Incidence- 1 in 1, 30,000 LIVE BIRTHS
    • Synonyms:
    • Gilbert-Dreyfus Syndrome
    • Incomplete Testicular Feminization
    • Lubs Syndrome
    • Rosewater Syndrome
    • Type I Familial Incomplete Male Pseudohermaphroditism
  • 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
  • 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:
  • 63.
    • DURING PREGNANCY
      • Chorionic villus sampling, ultrasound and amniocentesis
    • AFTER BIRTH
      • Hormone profile
      • Usg pelvis
      • karyotyping
  • 64. Special dynamic endocrine tests
    • HCG STIMULATION TEST
    • ADMINISTRATION OF STEROIDS – DECREASED RESPONSE IN SEX HORMONE BINDING GLOBULIN
    • EVIDENCE OF ABNORMAL ANDROGEN BINDING IN A GENITAL SKIN FIBROBLAST
  • 65.
      • SURGERIES
        • Orchidectomy or gonadectomy
      • Vaginal lengthening
        • Genital plastic surgery
        • Phalloplasty
        • Vaginoplasty
        • clitoroplasty
  • 66. HORMONE REPLACEMENT THERAPY
    • ESTROGEN
    • Progesterone
    • Route-oral,transdermal or vaginal
    • Prevention of osteoporosis
  • 67.
    • EMOTIONAL AND PSYCHOLOGICAL SUPPORT
    • WHEN AND HOW TO DISCLOSE THE NEWS TO THE PATIENT
    • FAMILY : GUIDANCE IF THEY ARE CARRIERS AND DECISION ON FURTHER CHILD BIRTHS
    • ANDROGEN INSENSITIVITY SUPPORT GROUPS
    PSYCHOLOGICAL ISSUES
  • 68. THANK YOU