19 year female presented to a tertiary healthcare centre of Bangladesh with short stature & primary amenorrhea.

2. 19 year female with short
stature & amenorrhea
Dr. Prodipta Chowdhury
Phase-B Resident
Dept. Of Endocrinology

3. Particulars of the patient
• Name : Miss. X
• Age : 19 years
• Sex : Female
• Marital status : Unmarried
• Religion : Islam
• Occupation : Student
• Address : Shreepur, Gazipur
• Date of admission : 19th November, 2023
• Date of examination : 09th December, 2023 and onwards

4. Presenting complaints
• Failure to grow since childhood
• No establishment of menstruation

5. Present illness
Growth failure:
• First noticed at school going age
• Progressive
• No history of chronic systemic illness
• No gastrointestinal symptoms & normal appetite
• Average scholastic performance

6. • No H/O headache, visual field defect, head injury, meningitis or
encephalitis
• No H/O cold intolerance, easy fatiguability, constipation or
hypotensive episodes
• No treatment was sought for the same

7. Menstruation:
• Development of secondary sexual characteristics since the age of 11-13 years
• Thelarche> Puberache
• No sign of virilization
• No establishment of menstruation
• Not even any spot
• No H/O cyclical haematuria or abdominal pain

8. On query, No H/O:
• Hernia, palpable swelling in lower abdomen, abdominal lump
• Acne, excessive hair in any part of body
• Pigmented lesion on face, visual or hearing difficulty
• No other medical conditions eg. DM, HTN, TB or chronic illness.

9. Antenatal history (of mother)
• No history of maternal androgen use, herbal intake
• No history of hirsutism, acne, virilization of mother
• No history of GDM, hypertension
• Pregnancy uneventful

10. Natal history
• Delivered by NVD at term without any complication
• No H/O birth trauma, convulsion
• No H/O lymphedema, neck or auricle abnormality at birth
• Born as a female child with normal looking genitalia with normal birth
weight

11. Post natal history
• No H/O hypoglycemia and hypotension after birth, prolonged
neonatal jaundice
• Normal developmental milestones
• Normal IQ
• Reared as a female child
• Preference for female toys & dresses

12. Family history
• 3rd issue of non-consanguineous parents
• Maternal age at the time of conception: 27 years
• History of 01 IUD & 01 neonatal death in previous 02 pregnancy of mother
• Her other 02 sisters are alive, married, enjoying motherhood
• No family H/O primary amenorrhea, hirsutism, salt crisis, precocious
puberty

13. Personal history
• She went to school at 6 years of age
• Now student of HSC 1st year with average scholastics performance
• She has attraction to male sex since the age of puberty
• Non smoker, non alcoholic
• No H/O sexual exposure

14. Socioeconomic history
• Comes from lower-middle class family.
Immunization history
• As per EPI schedule.
• Two doses of covid-19 vaccine
Past history
• No major surgical or blood transfusion history

15. General examination
• Appearance: Normal
• Anemia: (-)
• Jaundice: (-)
• Cyanosis: (-)
• Clubbing: (-)
• Leuconykia: (-)
• Koilonykia: (-)
• Dehydration: (-)
• Pulse- 86 b/min, regular, without
R-R Or R-F delay
• BP- 110/80 mmHg (on both hand)
• Skin: Acanthosis, otherwise
normal
• Oral cavity: High arched palate
• Thyroid gland: Not Enlarged
• Lymph node: Not palpable
• Bony tenderness: (-)
• R/R: 14 breaths/min
• Temperature- 98° F
• Urine for dipstick test: No
proteinuria & glycosuria

16. Feet appearance

17. Neck & Fist appearance

18. Anthropometric
measurement
• Height : 136 cm
• Weight : 46 kg
• BMI : 24.5 kg/m2
• BSA : 1.32 m2
• Waist circumference : 86 cm
• Hip circumference : 88 cm
• Upper segment :70 cm
• Lower segment : 66 cm
• US : LS : 1.06
• Arm span : 140 cm

19. Tanner staging:
• B: 3
• P: 3 (Female pattern pubic hair distribution)
External genitalia:
• Prader staging:
• Two separate opening: Present

20. Systemic examination
Cardiovascular system examination:
• Pulse: 86 b/min, regular, without R-R Or R-F delay
• BP: 110/80 mmHg (on both hand)
• JVP: Not visible
• Apex beat: Left 5th ICS, just medial to midclavicular line
• Thrill: Absent
• Heart sound: S1+S2+0
• Added sound: Absent

21. Neurological system examination:
• Higher psychic function: Normal
• Cranial nerve including vision & hearing: Normal
• Motor system: Normal
• Sensory system: Normal
Per-abdominal examination:
• Inspection: Normal
• Palpation: No palpable swelling
• Percussion: Tympanitic
• Auscultation: Bowel sound: (+ve)

22. Musculoskeletal system examination:
• Arm & Leg: No deformity
• Spine: Normal
• Gait: Normal
Other system examination:
• No abnormality

23. Salient features
Miss X, 19 year old, brought up as female, hailing from Shreepur Gazipur,
admitted with complaints of progressive growth failure since childhood &
non establishment of menstruation. She began to develop secondary sexual
characteristics at the age of 11-13 years (thelarche> puberache) & there was
no sign of virilization. There was no H/O Cyclical haematuria, abdominal
pain, not even any spotting. No history of chronic systemic illness, no
gastrointestinal symptoms with normal appetite.

24. She gave no H/O headache, visual field defect, head injury, meningitis or
encephalitis. No H/O cold intolerance, easy fatiguability, constipation or
hypotensive episodes. On query, no H/O hernia, palpable swelling in lower
abdomen, abdominal lump, acne, excessive hair in any part of body,
pigmented lesion on face, visual or hearing difficulty, no other medical
conditions eg. DM, HTN, TB or chronic illness. Her antenatal, natal, postnatal
history was unremarkable.

25. She was 3rd issue of her non-consanguineous parents, but her mother
has H/O 01 neonatal death, 01 IUD before her birth. Her other 02
sisters are alive, married, enjoying motherhood. There was no family
H/O primary amenorrhea, hirsutism, salt crisis, precocious puberty. She
was brought up as a female child, with normal IQ, had preference for
female toys & dresses, preference to opposite sex since puberty.

26. On examination: normal appeared female, with acanthosis on neck & high
arched palate, Pulse- 86 b/min, regular, without R-R Or R-F delay, BP- 110/80
mmHg (on both hand), short 3rd metatarsal on both feet, height is 136 cm
(<3rd percentile), weight 46 kg (<5th percentile), BMI 24.5 kg/m2, Tanner
staging: B3, P3 (female pattern) with normal external genitalia. Other
systemic examination including CVS, Neurology, Abdomen, MSK system
revealed no abnormality.

27. Further query

28. Provisional diagnosis
• Turners Syndrome

29. Differential diagnosis
• Panhypopituitarism
• Mullerian agenesis
• Noonan’s syndrome
• Pseudopseudohypoparathyroidism

30. Investigations

31. • CBC:
• Urine R/M/E: Normal
Hemoglobin 13.4 g/dl
ESR 43 mm in 1st hour
WBC 11,160/L
Neutrophil 56%
Lymphocyte 35%
Eosinophil 07%
Platelet 3,00,00/L

32. Name of the inv. Result
FBS: 4.5 mmol/L
2h after 75 gm Glucose 4.4 mmol/L
HbA1C 5.7%
SGPT 212 U/L 164U/L
ALP 139 U/L
GGT 75 U/L
S. Bilirubin 0.5 mg/dL
HBsAg Negative
Anti HCV Negative
ANA Negative

33. Name of the inv. Result
S. Creatinine 0.47 mg/dl
S. electrolytes:
Sodium 141 mmol/L
Potassium 4.0 mmol/L
Chloride 106 mmol/L
T-CO2 23.0 mmol/L
Lipid profile:
Total Cholesterol 261 mg/dL
Triglycerides 345 mg/dL
HDL Cholesterol 54 mg/dL
LDL Cholesterol 138 mg/dL

34. Hormone Profile
Name of the inv. Result Ref. Value
FSH 65.4 U/L 87.89 U/L 2.5-10 U/L
Oestrogen 12 pg/mL 0-160 pg/mL
Testosterone 72 ng/dL 63-120 ng/dL
S. Cortisol 712 nmol/L 138-690 nmol/L
DHEA-S 314 ug/dL 51-321 ug/dL
17-OH Progesterone 1.76 ng/mL 0.1-0.8 ng/mL
S. TSH 1.02 uIU/mL 0.35-5.5 uIU/mL
FT4 1.23 ng/dL 0.7-2 ng/dL

35. USG of whole abdomen
• There is a slit like structure (Lenght-27 mm x AP- 5.8 mm) seen in
posterior to the urinary bladder, which may represent rudimentary
uterus.
• Ovaries are small in size. Volume of right ovary is 0.9 CC & volume of
left ovary is 0.7 CC.
• Impression:
1. Fatty change in liver (G-I).
2. Suggestive of rudimentary uterus.
3. Suggestive of bilateral small ovaries.

36. Xray of Hands

37. CXR P/A view:
• Normal study
Echocardiography:
• No RWMA at rest
• Good LV systolic function (EF: 62%)
• Aortic valve: Normal
Endoscopy of upper GIT:
• Normal upper GIT at endoscopy

38. BMD
Site Z score
BMD of Lumbar 1st to 4th vertebrae (AP) -3.3
Right femoral neck -2.1
Left femoral neck -2.3
Interpretation:
Low bone mass in lumbar vertebrae and both the femoral neck

39. Karyotype
Analysis performed by peripheral blood lymphocyte culture
13/10/22 25/10/23
Chromosome No: 45/46
Sex Chromosome: XO/XY
Autosomes: No numerical or structural
abnormality detected.
Karyotype: 45,XO/46,XY
Total No. of Chromosome: 46/45
No. of Autosome: 22 pairs
No. of Sex Chromosome: XY/X
Karyotype: 46, XY/45,X
Note: Mixed gonadal dysgenesis
(MGD)
Comment: 46, XY / 45,X ;
Mosaicism

41. Type & frequency of chromosome abnormalities in
Turner syndrome

42. SRY gene
detection
SRY gene detection:
• The individual was
tested positive for SRY
gene

43. Confirmed Diagnosis
• Mixed gonadal dysgenesis (45,XO/46,XY)
• SRY gene positive
• Fatty liver disease

44. Referral to
Hepatology

45. Ongoing Treatment
• Diet: Normal
• Tab. Calbo-D - 0+1+0
• Tab. Rosutin 10mg - 0+0+1
• Tab. Ursocol 150mg - 1+0+1

46. Further Management
Plan
• MRI of W/A with special
attention to gonadal structure
• Gonadectomy
• F/U by repeat USG
• Start: Tab. Gynova (2mg) - 0+0+1
• Have to repeat SGPT
• Continue: Tab. Ursocol (150mg) -
1+0+1

47. Problem List
• Regarding menstruation & fertility
• Follow-up BMD with oestrogen
• Follow-up of abnormal LFT

48. Discussion
45,X/46,XY Mosaicism: Phenotypic Characteristics, Growth, and
Reproductive Function—A Retrospective Longitudinal Study
Marie Lindhardt Johansen, Casper P. Hagen, Ewa Rajpert-De Meyts, Susanne Kjærgaard, Bodil L. Petersen, Niels
E. Skakkebæk, Katharina M. Main, and Anders Juul
Department of Growth and Reproduction (M.L.J., C.P.H., E.R.-D.M., N.E.S., K.M.M., A.J.), Department of Clinical
Genetics (S.K.), and Department of Pathology (B.L.P.), Rigshospitalet and Copenhagen University, DK-2100
Copenhagen, Denmark

49. • Objective: The objective was to provide longitudinal data of patients
with 45,X/46,XY mosaicism.
• Design: This was a retrospective, longitudinal study conducted from
June 1990 to January 2012.
• Setting: The study took place at a tertiary pediatric and andrological
referral center.
• Patients or Other Participants: Twenty-five patients (18 boys, seven
girls) with 45,X/46,XY mosaicism and its variants were included and
were compared to healthy controls.

50. • The 45,X/46,XY karyotype represents a wide spectrum of phenotypes,
from Turner females to phenotypically normal males with varying
degrees of genital ambiguity.
• Furthermore, 45,X/46,XY patients often present with short stature.

51. • Limited reports exist on the levels of reproductive hormones in these
patients. High gonadotropin levels have, nonetheless, been described
in male and female patients, as well as low levels of testosterone in
male patients, both regardless of genital ambiguity.
• Gonadal function in most 45,X/46,XY males, even those with genital
ambiguity, seems sufficient for spontaneous puberty.

52. • Short stature and 45,X/46,XY mosaicism seem associated, but
patients appear to benefit from GH treatment.
• Histology from two patients with biopsies from early childhood
indicates that CIS originates before puberty.

53. • Intraabdominal streak-like (i.e. flat, scar-like gonads) and dysgenetic
gonads are thought to pose a significant risk of germ cell malignancy and
should be removed.
• The risk of germ cell tumors in individuals with 45,X/46,XY DSD is estimated
to be 15% to 40%.
• Some have advocated for close monitoring, but imaging is not able to
detect early neoplastic changes in abdominal gonads.