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