INTRODUCTION:

There are many intrinsic and extrinsic factors affect the dynamics of the growth process which can define the body height and growth spurt. Regulation of growth process affected by various endocrine systems and their secretions like pituitary-growth hormone and thyroid hormones. (1)

Short stature (SS) considers when person height is ≤ 22 (standard deviation) (SD) beneath the average for the age and sex. Causes of short stature can be classified to endocrine causes that include growth hormone deficiency, hypothyroidism and non- endocrine causes include familial, chronic disease, "constitutional delay of growth and puberty"(CDGP) (2) in which there are unnoted variations within the (pituitary-gonad) besides the (growth hormone-IGF-1 axis) which results in postponed in maturity of skeletal and (puberty spurt.(3)

Child’s genetics are responsible for final adult height. Child with familial short stature access within the height extent of the "parents" (4).

Growth hormone deficiency (GHD) diagnosis is depends on auxology, skeletal age, "biochemical analyses" like (growth hormone) stimulation tests and (insulin-like growth factor 1 (IGF-1)) and (magnetic resonance imaging (MRI) (5)

The aim of our study is to detect (causes of short stature) in children and teenagers and to estimate the clonidine effectiveness on "growth hormone" level.

METHODS:

The study was carried out in Al- Btool Teaching Obstetric Hospital in Diayla province at the period from March to September 2016. The study population consisted of 50 patients all of which were clinically short stature persons and they had given approval for evaluating their GH secretion. All patients assessed to a routine assessment that included medical history and physical examination. Height of each patient was recorded on standard growth charts.

The initial GH screening was carried out by testing basal GH level, and its level after subjecting the patients to clonidine stimulation at a dose of (0.15 mg/m2). Samples of blood were drawn at zero time, half an hour, one hour, one hour and half and two hours.

All blood samples were collected in disposable sterilized syringes then serum separated in disposable, plain tubes and stored at –20C° until analyzed for GH. Serum GH analyzed by using ELISA technique (Abcam, UK). The lower limitation of GH measurement was 0.5ng/ml. A (peak GH level of 7 ng/ml) or more was regarded a sufficient (secretory response of GH (6) Below this cut-off, individuals are regarded as GH deficient within the fitting clinical context. (7) SPSS version (19) were used to enter and analyze data.

RESULTS:

Fifty patients with short stature) were included in the study with age ranging from (1 to 18 years). The main (cause of short stature in our study group was GHD seen in 44 (88%) of patients.

In this study [4 out of 50 patients (8%)] were hypothyroidism. Renal disease was found in 1 patient (2%). Idiopathic short stature was seen in 1 case (2%) which represented in table (1).

Table (1): Causes of short stature among study groups

Detected Disease	No.	%	Statistics
GHD	44	88	p-value= 0.000 (HS)
Hypothyroidism	4	8
Renal disease	1	2
Idiopathic cause	1	2
Total	50	100

HS= highly significant

The results of present study showed that all patients had height lower than normal (SD ˃ 2 below the mean) when compared with height at normal growth chart (Table 2).

Table (2): Height of patients (Mean ±SD) among different age groups

Age/ year	No.	%	Height/cm	Statistic
Age/ year	No.	%	M±SD	Statistic
1 - 5	15	30	81.20±3.120	P-value= 0.000 (HS)
6 - 10	18	36	98.28±4.434
11 - 15	13	26	132.77±2.651
15-18	4	8	124.25±10.299
Total	50	100	104.20±3.569

Table 3 show hormonal analysis of GH after and before clonidine stimulation that represent changes in the level of GH among different age groups that showed significant differences in GH level after stimulation.

Table (3) Level of growth hormone before and after stimulation among different age groups

Age/ year	GH level before stimulation	GH level after stimulation
Age/ year	Mean ±SD	Mean ±SD
1 - 5	2.280±1.2835	12.873±23.6706
6 - 10	2.544±1.4143	5.872±9.6938
11 - 15	2.446±2.8710	6.662±9.0773
15-18	2.050±.6758	3.500±1.1518
Statistic	p-value= 0.250 (NS)	p-value= 0.038 (S)

DISCUSSION:

The Prevalence of short stature and its outcomes in children are well studied in Westward countries (8,9). Certain study in Jordan clarified prevalence of SS was 4.9 % (10)

It has been shown that (SS) is associated with cardiovascular disorders (11). In addition, short stature in females was shown to inversely affect the survival and health of her offspring (12).

In present study it was obvious that growth hormone deficiency (GHD) was a major cause of "short stature " in 44 out of 50 patients (88%) followed by hypothyroidism (8%) (Table 1). That is in agreement with the results of study in Pakistan (13) where cleared that 69% cases of "short stature" were GHD. While other researchers like Rabbani et al (14), Awan et al (15) reported deficiency of growth hormone as cause of "short stature" in 10.7%, 13.9% in children and adolescents respectively.

In our study most of patients (36%) were between (6-10) years of age which show in table (2) (P-value=0.000), Fahim et al reported that (72.6%) of patients presented to them nearly within same age group. While Indian study reported the mean age of GHD patients range from 8.6 to 14 years old (16), which is mostly because late recognition of growth failure by their parents.

Administration of clonidine orally was clarified to stimulate secretion of GH in normal individuals (17) and was after that assayed as a test for GHD (18). The results of this study demonstrated that growth hormone level had increment after clonidin intake with significant differences among different age groups (table 3, P=0.038). That result defined responsiveness of growth hormone to clonidine and its useful drug in GHD diagnosis in short stature children.

CONCLUSION:

(Growth hormone deficiency) was a main cause of "short stature". Clonidine was effective therapy in stimulation and support the level of growth hormone.

REFERENCES:

1. Hogler W and Shaw N. Childhood Growth Hormone Deficiency, Bone Density, Structures and Fractures: Scrutinizing the Evidence. Clin. Endocrinol. 2010; 72, 281-289

2. Lam WF, Hau WL and Lam TS. Evaluation of referrals for genetic investigation of short stature in Hong Kong. Chinese Med J. 2002, 115(4):607–611.

3. Soliman AT and Sanctis VD. An approach to constitutional delay of growth and puberty. Indian J Endocrinol Metabol. 2012, 16(5): 698–705.

4. Ranke MB, Grauer ML, Kistner K, Blum WF and Wollmann HA. Spontaneous adult height in idiopathic short stature. Hormone Res. 1995, 44(4):152–157.

5. Alatzoglou KS, Webb EA, Le Tissier P, and Dattani M T. Isolated growth hormone deficiency (GHD) in childhood and adolescence: recent advances,”Endocr. Rev., 2014, 35 (3), 376–432.

6. The Health Services Human Growth Hormone Committee. Comparison of intravenous insulin and oral clonidine tolerance tests for growth hormone secretion. Arch Dis Child. 1981, 56: 852-854.

7. Hoffman DJ. Growth retardation and metabolic programming: implications and consequences for adult health and disease risk. J Pediatr (Rio J). 2014, 90(4): 325-8.

8. Moayeri H and Aghighi Y. A prospective study of etiology of short stature in 426 short children and adolescents. Age 2004, 14 (1.7):13–3.

9. Colaco P and Desai M. Identification of a child with short stature. Indian Paediatr 1990, 27(11):1159–64.

10. Ayman A. Zayed Abdallah M, Beano Faris I. Haddadin. Prevalence of short stature, underweight, overweight, and obesity among school children in Jordan. BMC Public Health BMC series 2016;(16):1040.

11. Schroeder DG, Martorell R and Flores R. Infant and child growth and fatness and fat distribution in Guatemalan adults. Am J Epidemiol. 1999;149(2):177–85.

12. Dewey KG and Begum K. Long-term consequences of stunting in early life. Matern Child Nutr. 2011;7 Suppl 3:5–18.

13. Jawa A, Riaz SH, Assir MZK, Afreen B, Riaz A and Akram J. Causes of short stature in Pakistani children found at an Endocrine Center. Pak J Med Sci. 2016;32(6):1321-1325.

14. Waqar Rabbani M, Imran Khan W, Bilal Afzal A and Rabbani W. Causes of short stature identified in children presenting at a tertiary care hospital in Multan Pakistan. Pak J Med Sci 2013;29(1):53–7.

15. Awan TM, Sattar A and Khattak EG. Frequency of growth hormone deficiency in short statured children. J Coll Physicians Surg Pak 2005;15(5):295–8.

16. Mathew J, Ekaterina K, Kanakatte M, Prasanna K, and Harshal C. Challenges in the Diagnosis and Management of Growth Hormone Deficiency in India. International J. Endocrin. 2016; 1-11.

17. Gil-Ad I, Topper E, Laron Z. Oral clonidine as a GH stimulation test. Lancet 1979; 2, 278-280.

18. Menon P.S.N, Gupta P and Karmarkar MG .High and low dose clonidine tests for the diagnosis of growth hormone deficiency ; Indian Pediat. (31) February 1994;145-151.

Received on 15.12.2018 Modified on 22.01.2019

Research J. Pharm. and Tech. 2019; 12(5):2356-2358.

DOI: 10.5958/0974-360X.2019.00394.9