A Case of Refeinstein's Syndrome
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Transcript of A Case of Refeinstein's Syndrome
PROF.DR.G.SUNDARAMURTHY’S UNITBHARGAVI.K.
17 yr old female came to the op with chief c/o
coarse voice…
h/o loss of appetite+
h/o lethargy +
No h/o fever
No h/o recurrent cough with expectoration
No h/o post nasal drip
No h/o hemoptysis
No h/o dysphagia
No h/o intolerance to cold
No h/o constipation
No h/o alopecia
No h/o galactorrhoea
No h/o hot flushes
No h/o palpitations
No h/o visual disturbances
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
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 exerciseMENSTRUAL H/O
NOT ATTAINED MENARCHE.. NOT EVALUATED PRIOR.
FAMILY H/O
Born of non consanguinous marriage.
Parents healthy.
1 sibling –male 21 yrs. Healthy.
A CASE OF PRIMARY AMENORRHOEA
WITH COARSE VOICE
IN THE LINES OF…
CONSTITUTIONAL DELAYHYPOTHYROIDISMHYPERPROLACTINEMIAPREMATURE OVARIAN FAILUREDSD
Gc fairAfebrileHydration fairNo
pallor/icterus/cyanosis/clubbingNo significant lymphadenopathy
Ht,wt- appropriate for age.Hirsute features+No digital anomaliesNo ext markers for congenital
heart disease.
Pulse -88/minBP- 120/70 mm hg CVS
s1s2+ no murmurs.
RESPIRATORY SYSTEM-
nvbs+: no additional sounds.
CNS
Nfnd .
EXMN OF EAR,NOSE , THROAT- normal.
EXMN OF ORAL CAVITY -normal.
PER ABDOMEN- soft, no organomegaly, no free fluid.
BREASTS- TANNER STAGE I
PUBIC HAIR- TANNER STAGE III
AXILLARY HAIR- SPARSE
PER VAGINAL
AMBIGUOUS EXTERNAL GENITALIA
PENIOSCROTAL HYPOSPADIAS
A CASE OF DISORDER OF SEX
AND DEVELOPMENT
DISORDERS OF SEX AND
DEVELOPMENT
46 XX OVOTESTICULAR 46 XY
CAH
BLOOD SUGAR -88 mgs
RFT :urea -18 creatinine- 0.8 mgs
S.electrolytes:Na-140, K- 4,Cl- 98,HCO3-28mEq/L
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
THYROID FUNCTION TESTS
Thyroid function tests
LH : 12.85 mIU/ml
NORMAL VALUES
FOLLICULAR PHASE:1.9 -12.5
MIDCYCLE PHASE:8.7-76.3
LUTEAL PHASE:0.5-16.9MENOPAUSAL:>50
FSH: 7.60 mIU/ml
NORMAL VALUES
FOLLICULAR PHASE:1.9 -10.2
MIDCYCLE PHASE:3.4-33.4
LUTEAL PHASE:1.5-9.1MENOPAUSAL:23-116
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
Estradiol levels :55 pg/ml.
Normal valuesFollicular phase:30-60 pg/mlPreovulatory phase:110-410Luteal phase:19-160
High testosteroneHigh LH
High Estradiol Normal FSH
ULTRASOUND ABDOMEN AND PELVIS
USG PELVIS
BIOPSY OF INGUINAL STRUCTURES
CONFIRMED THE PRESENCE OF SEMINIFEROUS TUBULES,LOBULI TESTIS AND RETE TESTIS.
COARSE VOICE,PRIMARY AMENNORRHOEA
HORMONE PROFILETESTOSTERONE,LH
USG PELVISABSENT UTERUS,OVARIES
BIOPSY OF INGUINAL STRUCTURES-TESTIS
?
KARYOTYPING
46 XY
DIAGNOSIS
A CASE OF INCOMPLETE ANDROGEN INSENSITIVITY
SYNDROME
REFEINSTEIN’S SYNDROME
COMPLETE AIS
PARTIAL AIS
Inheritance X-linked recessive X-linked recessive
External genitalia
Female Broad spectrum from female with mild clitoromegaly to male with micropenis and/or hypospadias
Müllerian duct derivatives
Absent Absent
Wolfian duct Absent Broad spectrum from absent or male
Testes Inguinal or intraabdominal,
Ectopic, inguinal or intraabdominal,
Puberty Gynecomastia Gynecomastia
Hormonal diagnosis
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
Molecular defect
Mutations or deletions in androgen receptor gene
Mutations in AR gene
? PARTIAL AIS
Penioscrotal hypospadiasAmbiguous external genitaliaHypoplastic wolfian duct derivativesAbsent mullerian duct derivativesUndescended testicular gonadsPresence of pubic n axillary hair- but
scanty Increased LH AND TESTOSTERONE,
normal FSH.
MANAGEMENT
PSYCHOLOGICAL COUNSELLING OF THE PATIENT AND PARENTS
TO CONTINUE SEX OF REARING AS FEMALE
DEPT OF PLASTIC SURGERY, GSH
b/l orchidectomy, herniorrhaphy and clitoroplasty.
Planned next for vaginal reconstuction
Planned breast enhancement- silicone implantation
Now placed under estrogen supplements-on follow up .
PRIMARY AMENNORRHOEA WITH DELAYED PUBERTY
BONE AGE- CONSTITUTIONAL DELAY
THYROID PROFILE
LH, FSH, PROLACTIN
INCREASED LH,FSH NORMAL LH,FSH
INCREASED LH,FSH
KARYOTYPING
45 X( turner’s)
46 XX(pure gonadal dysgenesis)
46 XY(swyer’s)
NORMAL LH, FSHPROLACTIN HIGH
IMAGING MRI
ABNORMAL-PITUITARY CAUSES NORMAL MRI
EATING DISORDERS STRESS
AMENNORHOEA WITH
NORMAL PUBERTY
ULTRASONOGRAM
UTERUS PRESENT
HYPOTHYROIDISMHYPERPROLACTINEMIA FSH LEVELS
LOW- MRIHIGH FSH-
PREMATURE OVARIAN FAILURE
GENITAL TRACT
ABNORMALITIES
ULTRA
SONOGRAm
ABSENT UTERUS FORESHORTENED
VAGINA
KARYOTYPe
46 XX
MULLERIAN AGENESIS-ROKITANSKY
46 XY
TESTOSTERONE
HIGH LOW
ANDROGEN INSENSITIVITY OR
5 A RED DEFICIENCY
TESTICULAR REGRESSION
CAH
21 OH DEFICIENCYMASCULINISATION
SALT WASTINGINCREASED 17 OH P
11 OH DEFICIENCYINCREASED DOCSALT RETENTIONHYPERTENSION
3 B HSD DEFICIENCYLESS VIRILIZ, SALT
LOSING^DHEA
ONLY FORM CAUSING AMB.
GENIT IN MALES
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
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
DYSGENESIS46 XY OR
MOSAICISMONE GONAD IS DYSGENETIC
PURE GONADAL
DYSGENESISB/L STREAK
GONADS
AIS
ANOMALOUS SEXUAL
DEVELOPMENT
I.DISORDERS OF GONADAL DIFFERENTIATION
II.FEMALE PSEUDOHERMAPHRODITISM
III.MALE PSEUDOHERMAPHRODITISM
IV.UNCLASSIFIED FORMS
.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
I.END ORGAN RESISTANCE TO ANDROGENIC HORMONES
A. syndrome of complete androgen resistanceB. syndrome of incomplete androgen resistanceC. androgen resistance in phenotypically normal males
II.DEFECTS IN TESTOSTERONE METABOLISM BY PERIPHERAL TISSUES
5 alpha reductase deficiency
o Grade 1: PAISMale genitals, infertile
o Grade 2: PAISMale genitals but mildly ‘under-masculinized’
o Grade 3: PAISMale genitals more severely ‘under-masculinized’
o Grade 4: PAISAmbiguous genitals
o Grade 5: PAISEssentially female genitalia, with enlarged clitoris
o Grade 6: PAISFemale genitalia with pubic/underarm hair
o Grade 7: CAISFemale genitalia with little to no
pubic/underarm hair
Exists along continuum depending on degree of mutation in AR gene
Androgen Receptor GeneAndrogen 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.
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.
-testicular feminizationSyndrome of MorrisPrevelance about 1 in 44,000-60,000
live male births
KARYOTYPE 46 XY
INHERITANCE X-LINKED RECESSIVE,MUTATIONS IN AR GENE
GENITALIA FEMALE WITH BLIND VAGINALPOUCH
WOLFIAN DUCT DERIVATIVES:
USUALLY ABSENT
MULLERIAN DUCT DERIVATIVES:
ABSENT OR VESTIGIAL
GONADS TESTIS
HABITUS: ABSENT PUBIC AND AXILLARY HAIR,BREAST DEVELOPMENT AND FEMALE HABITUS AT PUBERTY, PRIMARY AMENNORHOEA”HAIRLESS WOMEN”
HORMONE AND METABOLIC PROFILE:
INCREASED PLASMA LH AND TESTOSTERONE CONCENTRATION,INCREASED ESTRADIOL, FSH LEVELS OFTEN NORMALRESISTANCE TO ANDROGENIC N METABOLIC EFFECTS OF TESTOSTERONE
ANDROGEN RECEPTOR STUDIES
GENETIC HETEROGENEITY: RECEPTOR NEGATIVE, UNSTABLE OR RECEPTOR POSITIVE FORM
REIFENSTEIN SYNDORME
Incidence- 1 in 1, 30,000 LIVE BIRTHSSynonyms:Gilbert-Dreyfus Syndrome Incomplete Testicular Feminization Lubs Syndrome Rosewater Syndrome Type I Familial Incomplete Male
Pseudohermaphroditism
KARYOTYPE 46 XY
INHERITANCE X-LINKED RECESSIVE,MUTATIONS IN AR GENE
GENITALIA AMBIGUOUS WITH BLIND VAGINAL POUCH-PERINEOSCROTAL OR PENILE HYPOSPADIAS, ASMALL VAGINAL POUCH, A HOODED PHALLUS, UNFUSED PREPUTIAL FOLDS, BIFID SCROTUM, OCCASIONALLY GONADS.
WOLFIAN DUCT DERIVATIVES:
RUDIMENTARY-HYPOPLASTIC-NORMAL
MULLERIAN DUCT DERIVATIVES:
ABSENT
GONADS TESTIS- USUALLY UNDESCENDED
HABITUS: decreased to normal axillary and pubic hair, beard growth and body hair, gynaecomastia
HORMONE AND METABOLIC PROFILE:
increased plasma lh n testosterone, increased estradiol, fsh levels normal or slightly increasedPartial resistance to androgenic and metabolic effects of testosterone
ANDROGEN RECEPTOR STUDIES
genetic heterogeneity, partial deficiency of normal receptor, mutations lead to qualitatively abnormal receptor.
DURING PREGNANCY Chorionic villus
sampling, ultrasound and amniocentesis
AFTER BIRTH
Hormone profile Usg pelvis karyotyping
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
SURGERIES
Orchidectomy or gonadectomy
Vaginal lengthening
Genital plastic surgery
Phalloplasty
Vaginoplasty
clitoroplasty
HORMONE REPLACEMENT THERAPY
ESTROGENProgesterone
Route-oral,transdermal or vaginal
Prevention of osteoporosis
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