The document describes two patients, an 8-year-old boy and an 11-year-old girl, who have been exhibiting stunted growth for several years. Their physical examinations and lab results indicate proportionate short stature and delayed puberty. Based on their high growth hormone levels but low IGF-1 levels, the doctor suspects they may have growth hormone insensitivity syndrome. This would require further molecular genetic testing to confirm. The document discusses the typical features and management of growth hormone insensitivity syndrome if that is found to be the diagnosis.

1. Dr. Satyajit Mallick
MD student(Final Part)
Endocrinology and Metabolism
BSMMU

2. Particulars of the patients
X Y
Age 8 yrs 11 yrs
sex male female
Date of birth 27,Nov, 2007 17,Dec.2004
Studying in class 2 Nursery

3. Chief complaints
 Stunted growth for 5 years in case of the boy and 8
years in case of the girl
 Delayed appearance of secondary sexual characters in
both

4. H/O present illness
 According to the statement of the patient’s parent ,the
girl ,(Y )was apparently alright till 3 years of age with
normal developmental milestone, failed to develop
properly thereafter. Her height is almost constant for
last 8 years as compared with her peers.
 They noticed their son also facing the same problem
since he was of 2 years.

5. Their secondary sexual characteristics are also
underdeveloped like pubic and axillary hairs, voice
change, muscle mass and genital growth .
No change of clothing and shoe size for last 8 years
in case of the girl(Y) and for last 5 years in case of the
boy(X)
.

6.  Their eating habit is normal. No abnormality
regarding bowel and bladder habit
 Their mental growth seem normal now. She is
currently studying well in class 2 with good academic
performance and her brother just started school in
Nursery who is also doing well

7.  There is no h/o of convulsion, meningitis, head
injury, cranial irradiation.
 There is no history of blood transfusion,
palpitation, breathlessness, long standing
diarrhoea , feeding problem or any systemic
disease.

8. Birth History…
 On query their intrauterine periods were uneventful,
mother was relatively healthy during and after
pregnancy.
 They both were delivered following full term vaginal
delivery at home and was uneventful. Birth weight was
approximately 3kg without any documentation.
 They both were well breastfed and weaned at normal
time. They have been well fed since childhood and no
signs of malnutrition or malabsorption was seen.

9. H/o past illness. . .
There is no history of Br. asthma, PTB, congenital
heart disease, malabsorption ,DM or other
chronic illness since childhood.
No psychosocial deprivation or similar problems among
parents.

10.  Family history:
 Father and mother alive, in good health
• H/O consanguinous marriage
• Their elder brother who is 19 years old, has
average height and body build.
• Their elder sister died at the age of 19 months
from acute watery diarrhoea
• H/O short stature in their paternal side
of one sister and one brother , who died at 4
years and 2 years of age respectively

11. H/O of immunization
 Immunized according to EPI schedule

12. General examination
 Appearance: short with
dysmorphic face
 Body built: below average
 Nutrition: below average
 Anaemia:absent
 Jaundice: absent
 Cyanosis: absent
 Clubbing: absent
 Edema: absent
 Dehydration: absent
 Thyroid gland: normal
 Lymph nodes: not palpable
 JVP: not raised
 Vital signs
Pulse: 80 b/min (boy) and
76b/min(girl)
Resp. rate: 16 breaths/min(b0y)
and 20/min(girl)
Temperature: normal

13.  Frontal bossing
 Shallow orbit
 Saddle nose
 Dental caries (in case of
b0y)
 Poor deveopment of
facial bones

14. Other systemic examinations
Revealed no other abnormalities

18. Physical examination
Anthropoemetry boy girl
Height 78 cm 85 cm
Wt 7.5 kg 9 kg
BMI 12.1 kg/m2 12.45 kg/m2
Arm span 76 cm 84 cm
Upper segment 42 cm 44cm
Lower segment 36 cm 42 cm
US:LS 1.16 1.02
Growth percentile Ht – below 5th
Wt-below 5th
Ht-below 5th
Wt-below 5th

19. Plotted Graph of stature-for-age and weight-for-age percentile

20. Contd…
 Tanner’s staging:
boy girl
Testicular volume-nil Breast bud-B 0
Stretched penile
length-2 cm
Pubic hair-Absent,P0
Pubic hair- absent, P0

21. Height of parents: father- 160cm,
mother- 155.5cm
 Mid parental height: ( 160+155.5+13)/2 =162.75cm

22. Provisional diagnosis
 Proportionate short stature with delayed puberty due
to..
 1.Panhypopituitarism
 2.Isolated growth hormone deficiency

23. Investigations:

24. boy girl Reference value
TSH 2.37 μIU/ml 2.28 μIU/ml 0.4-4.1 μIU/ml
T4 8.75 μg/dl 11.89μg/dl 4.5-12.0 μg/dl
Cortisol (morning
sample)
21.0 μg/dl 26.1μg/dl 3.7-19.4
μg/dl
Cortisol (Evening
sample)
8.30 μg/dl 7.70 μg/dl 2.9-17.3 μg/dl
Human growth
hormone
(hGH)
20.57 ng/ml 31.89 ng/ml Male:7-17yrs
0.3-14.90 ng/ml
Female:
7-17yrs
0.6-23.80 ng/ml

25. Bone age of the boy (3-4 yrs)

26. Bone age of the girl (6-7 years)

27. girl’s skull x-ray

28. Boy’s skull xray

29.  So, are we dealing with
Growth Hormone insensitivity/resistance syndrome ?

30.  PROBLEM LIST:
 Raised Growth hormone level
 Investigations to confirm the diagnosis..Growth
hormone insensitivity/resistance syndrome
 Management plan

31.  Molecular genetic investigations have shown that this
disorder is mainly associated with mutations in the gene
for the GH receptor. These can result in defective
hormone binding to the ectodomain or reduced
efficiency of dimerization of the receptor after hormone
occupancy. There are exceptionally low levels of
growth factor (IGF-1) and its principal carrier
protein, insulin-like growth factor binding protein 3.

32.  The principal feature of Laron syndrome is abnormally
short stature (dwarfism).
 Physical symptoms include: prominent forehead,
depressed nasal bridge, underdevelopment of
mandible, truncal obesity,[8] and micropenis in males.
In spite of very low levels of serum IGF-1, the breasts of
females reach normal size, and may be large in relation
to body size.[9] It has been suggested that
hyperprolactinemia may contribute to this.[10] Seizures
are frequently seen secondary to hypoglycemia. Some
genetic variations decrease intellectual capacity.[11]

33.  Administration of GH has no effect on IGF-1
production, therefore treatment is mainly by
biosynthetic IGF-1. IGF-1 must be taken before puberty
to be effective
 IPLEX (Mecasermin rinfabate) is composed of
recombinant human IGF-1 (rhIGF-1) and its binding
protein IGFBP-3. It was approved by the U.S. Food and
Drug Administration (FDA) in 2005 for treatment of
primary IGF-1 deficiency or GH gene deletion.[15][16]
Side effects from IPLEX are hypoglycemia.

34. Acknowledgements
 Professor Md. Farid Uddin
Founder Chairman, Dept. of Endocrinology
BSMMU
 Professor M. A. Hasanat
Chairman, Dept. of Endocrinology
BSMMU
• All the Faculty members,seniors and my colleagues

35. THANK YOU