Case presentation
Short stature and pubertal delay
General Data
S.C.B Caucasian male
14. 3 years old
Adress: Brasov County Patient was referred by local endocrinologist for
investigation of short stature. First admission in Endocrinology Clinic Tg.Mure on March 2010. Chief complain:
Easy fatigue
Medical History
Born by spontaneous delivery at 38 weeks of gestation
Breech position ! Weight =2750 g (1050th percentile) Length = 47 cm (50th percentile).
Second child of a family with 4 healthy children
non-consanguineous parents father was 27 years old/mother was 26 years old at delivery. No puberty delay in parents!
No signs of hypoglycemia or respiratory distress during the
neonatal period
His psychomotor development was normal
Medical History
Language development was retarded Mild intellectual disability with learning disability
He is in the 6Th class
His father height = 164 cm His mother height = 145 cm,
His target height was 161.0 cm (- 1.95 SD ).
Target height in cm for a boy = [(mother's height in cm + 13) + father's height in cm)]/2
Physical examination
Appearance:
Short
Immature-appearing, Developmentally delayed male patient.
H= 125 cm (-4.86 SD),
W= 24.5 kg (-4.95 SD),
BMI =15.7 kg/m2 (-2.08 SD)
Physical examination
Sitting height = 61 cm
US:LS ratio =0.95
Growth velocity
Physical examination
Skin & Mucosa:
pale, dry
Adipose tissue:
normal represented
Musculoskeletal system:
normal aspect, muscle weekness
Cardiovascular apparatus:
BP: 80/50 mmHg,
Normal sinus rhythm 60 b/min Holosystolic murmurs grade 3/VI
Physical examination
Genitourinary:
small, but normally formed phallus;
unilateral right cryptorchidism, but normal scrotum.
Nervous system:
Mild mental retardation, Behavior problems
Endocrine Examination
Pituitary tumor syndrome:
Absent headache or visual distubances
No polyuria, polydipsia Short stature
Thyroid gland:
small size normal consistency
Adrenal glands:
muscle weakness, pale, dry skin
Endocrine Examination
Gonads: Puberty Tanner I prepubertal Left testicular volume 3 ml Unilateral right cryptorchidism PH I, G I
Diagnosis
Short stature and pubertal delay
Short stature ESPE Clasification
Primary Growth Failure
Clinically defined syndrome SGA with failure of catch-up growth Skeletal dysplasia
Secundary growth failure
Malnutrition Disorders of organ system GH deficiency Primary IGF-1 deficiency and resitance Other endocrine disorder Metabolic disorder Psychosocial Iatrogenic
Idiopathic short stature
Familial Nonfamilial
Wit JM, Ranke MB, Kelnar CJH, Hormone Research, 68: 1-120, 2007
Laboratory routine analyses
VSH 16mm/h G 95mg/dl Uree 44.5 mg/dl Mg 2.11 mg/dl GGT 13U/l Amilaze 29U/l Leu 4340/6360/mm3 Col 167 mg/dl Creatinin 0.53 mg/dl P 4.23 mg/dl Bil T 0.56 mg/dl LDL-Chol 89mg/dl Urine sample negative; sediment with1-2 leucocytes, seldom bacteria Hgb 10.4/9.74g/dl HDL-C 71.5 mg/dl Na 140mmol/l Fe 12.7mol/l Bil D 0.19 mg/dl HTC 31.8/31.1% TG 30 mg/dl K 4.1mmol/l GOT 28U/l FA 222U/l TCT 346000/mm3 Ac. Uric 2 mg/dl Ca 9.26/10.37 mg/dl GPT 11U/l LDH 254U/l
Normochrome normocytic anemia - mild form
Bone age
11.04 Years (TW 20) The Tanner Whitehouse
system: TW20
a score is assigned to 20 of the
epiphyses in the hand and wrist having compared them with the standards in the Atlas. the scores are summed and compared with standard tables.
Bone age alternative methods
The Greulich and Pyle method:
the radiograph of the whole hand and
wrist is compared with images in the Atlas
Hormonal Assesment
FT4 TSH PRL FSH LH Cortisol 8 A.M. Cortisol after Synachten 0.33 2.507 31.47 0.8 0.18 1.669 4.659 VN 0.82-1.63ng/dl VN - 0,38-4.31UI/ml VN 3.6-16.3ng/ml VN 1.6-8UI/ml VN 0.5-4 UI/ml VN 6.4-21g/dl
Combined Pituitary Hormone Deficiency: Secondary hypothyroidism Pubertal delay possible central hypogonadism Adrenal insufficiency - possible central Hyperprolactinemia
Endocrine tests
Not done
ACTH
Peak of LH and FSH in response to GnRH IGF -1, GH ?
First
substitution for hypothyroidism!!! Rp/ Prednison 5mg/day
Priming ?
adrenal
failure
and
L-Thyroxine 50 mcg/day normal FT4
Children with age greater than 10y who are not yet in puberty may not show an optimal growth hormone response to provocation tests unless the patient is primed with testosterone or estrogen No consensus on priming
Endocrine tests
Clonidine test and IGF 1 determination
IGF 1 GH basal GH peak after Clonidine <25 0.17 0.11 VN 220-972ng/ml VN < 20 ng/ml
Insulin tolerance test with GH and cortisol
determination was impossible on practical grounds
May be dangeours because of concomitent adrenal
insufficiency !!
Imaging findings
Sella turcica X-Ray (March 2010): Normal size and form
MRI scan of his brain and pituitary anterior pituitary hypoplasia ectopic posterior pituitary. absent pituitary stalk normal midline structures
Other examination
Abdominal ultrasound normal
Cardiologic evaluation innocent systolic
murumur
Ophtalomological evaluation normal
Final diagnosis
Combined Pituitary Hormone Deficiency.
GH, TSH, ACTH Deficiency. Pubertal delay .Hypogonadotropic Hypogonadism ?
Hyperprolactinemia
Anterior pituitary hypoplasia
Ectopic posterior pituitary Unilateral cryptorchidism
Normochrome normocytic anemia
Mild mental retardation
Differential diagnosis:
Craniopharyngioma
Primary malignant tumors (germinal tumors)
Rathke cleft cyst Trauma Langerhans cell histiocytosis
Specific gene mutation:
Prop 1, Pit 1, Hesx1, Sox3 ??
Treatment
L -Thyroxine 50 microg/day
Prednison 5 mg/day
Treatment for cryptorchidism
hCG - administration of 1500 - 2500 units twice
weekly for four weeks - not available at that moment
Side effects of administration of hCG
enlargement of the penis, growth of pubic hair, increased testicular size, aggressive behavior during administration.
Orchidopexy not performed
Treatment
Somatropinum (rhGH),
s.c.- 0.025-0.035 mg/kg/day
0.6 mg/day Possible side effects glucose intolerance or diabetes mellitus, slipped capital femoral epiphysis, local reactions, benign intracranial hypertension, hypothyroidism
Evolution
6 month later Poor compliance
Treatment only with rGH !
H= 129 cm (- 4.74 SD)
No further pubertal
development
