|Year : 2015 | Volume
| Issue : 1 | Page : 17-20
Baseline characteristics of patients on growth hormone therapy: Experience of two centers from South India
Babulreddy Hanmayyagari1, Mounika Guntaka2, Sunitha Chadalavada3, Voleti Sri Nagesh4, Sudhakar Reddy Pendyala5, Sridevi Patnala6
1 Department of Endocrinology, ESI Hospital, Hyderabad, Andhra Pradesh, India
2 Department of Biochemistry, Prime Hospital, KPHB, Hyderabad, Andhra Pradesh, India
3 Department of Endocrinology, ESI Hospital, Visakhapatnam, Andhra Pradesh, India
4 Department of Endocrinology, Care Hospital, Banjara Hills, Hyderabad, Andhra Pradesh, India
5 Department of Endocrinology, Yashoda Hospital, Hyderabad, Andhra Pradesh, India
6 Department of Endocrinology, Apollo Hospital, Secunderabad, Hyderabad, Andhra Pradesh, India
|Date of Web Publication||16-Mar-2015|
Dr. Babulreddy Hanmayyagari
Flat No - 507, Emerald Block, My Home Jewel, Madinaguda, Hyderabad - 500 049, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Objective: The objective of this study is to determine the age at presentation, etiology and other characteristics of short children who are on growth hormone therapy (GHT) at a tertiary care hospital.
Materials and Methods: This cross-sectional study analyzed 96 children on GHT. All the children were assessed clinically, hormonally, radiologically, and genetic analysis were done wherever needed. GH deficiency (GHD) was diagnosed in the presence of short stature (height standard deviation score <2) and peak GH levels <10 ng/ml. Bone age (BA) was estimated by using Greulich-Pyle Atlas.
Results: Of 96 patients on GHT for short stature, 49 (51%) were male and 47 (49%) were female. Primary GHD (42.7%) was the most common diagnosis, followed by idiopathic short stature (ISS) and the rest were small-for-gestational age, multiple pituitary hormone deficiency, organic pituitary lesions and genetic syndromes. Mean chronological age at presentation was 9.5 ± 2.3 years (median: 10 years, range: 3-16 years), mean height age was 6.4 ± 1.8 years (median: 6.5 years, range: 1-14 years), mean BA was 6.8 ± 2.1 years (median: 7.4 years, range: 1.3-15 years) and mean height at presentation was 110 ± 18.2 cm (median: 120 cm, range: 74-142 cm). Two girls entered puberty during the study period and were managed with simultaneous GH and gonadotropin-releasing hormone analog treatment.
Conclusion: We conclude idiopathic GHD is the most common etiology in our patients on GHT followed by idiopathic short stature (ISS). In order to improve outcomes, short children need to be evaluated at the earliest.
Keywords: Growth hormone deficiency, growth hormone therapy, insulin like growth factor-1 and its binding protein-3, short stature
|How to cite this article:|
Hanmayyagari B, Guntaka M, Chadalavada S, Nagesh VS, Pendyala SR, Patnala S. Baseline characteristics of patients on growth hormone therapy: Experience of two centers from South India. J NTR Univ Health Sci 2015;4:17-20
|How to cite this URL:|
Hanmayyagari B, Guntaka M, Chadalavada S, Nagesh VS, Pendyala SR, Patnala S. Baseline characteristics of patients on growth hormone therapy: Experience of two centers from South India. J NTR Univ Health Sci [serial online] 2015 [cited 2020 Apr 2];4:17-20. Available from: http://www.jdrntruhs.org/text.asp?2015/4/1/17/153305
| Introduction|| |
Indications for growth hormone therapy (GHT) are increasing, as newer indications are being added to the existing pool. When introduced in 1958, GH available in the form of human GH (hGH) extracted from cadaveric pituitaries, was indicated only for children of GH deficiency (GHD) and it was only in 1985, that there was a switch from this hGH to recombinant (rhGH) obtained from DNA-recombinant techniques, after reports of Creutzfeldt-Jakob disease More Details in hGH recipients.  Since then, rhGH been approved not only for GHD, but also for a series of non-GH deficient disorders, such as chronic renal failure, Turner syndrome, small-for-gestational age (SGA), Prader-Willi syndrome More Details, idiopathic short stature (ISS), SHOX gene haploinsufficiency, Noonan syndrome,  and adult GHD. 
Even though, GH is indicated for the various above reasons, there was scarcity of data on this from India. Here, we present the clinical profile of 96 short statured children on recombinant GHT, who were evaluated and diagnosed; and are presently undergoing treatment and follow-up at a tertiary medical care center.
| Subjects and Methods|| |
This cross-sectional observational study carried out in the Department of Endocrinology of ESI Hospital, Sanathnagar, Hyderabad and ESI Hospital Vizag from August 2011 to March 2013. A total of 96 patients treated with recombinant GH were studied.
Growth hormone therapy was given to patients having short stature with GHD or other indications. All patients underwent initial clinical, hematologic, metabolic and endocrine screening along with thyroid function tests. For height measurement, head was positioned in Frankfurt plane, the head projection was placed at the crown of the head and the measurement was recorded to the nearest 0.1 cm. Care was taken to record heights on subsequent visits on the same apparatus and by a single observer. Growth parameters were first plotted and followed on Khadilkar et al. growth charts. 
Growth hormone deficiency was diagnosed by the presence of short stature (height standard deviation score <2) and peak GH levels <10 ng/ml following standard clonidine stimulation test. Insulin like growth factor and its binding protein 3 (IGF-1/IGF-BP3) were also measured to supplement stimulation test. Children born SGA and failing to achieve catch-up growth were investigated to rule out other causes of short stature and subsequently, growth velocity was monitored. ISS was considered in children with short stature, low growth velocity, without any associated medical cause and normal GH response to provocative testing (these children were followed for at least 3-6 months for growth velocity before starting GHT). Those with structural lesions (viz., cranio pharyngioma, Rathkes cleft cyst) were re-evaluated with IGF-1 at 6-12 weeks of the postoperative period before the initiation of GHT. Karyotyping was carried out in those female subjects where the etiology was in doubt, to rule out Turner's syndrome and the help of the Genetics Department was taken wherever necessary. IGF-1 generation test was carried out in patients when baseline GH levels >15 ng/dl to rule out GH insensitivity. ,
| Results|| |
Recombinant GH was used in a subcutaneous dose of 0.2-0.3 mg/kg/week given at bedtime daily for patients with GHD, 0.375 mg/kg/week for patients with other syndromes and chronic kidney disease (CKD) patients and 0.40 mg/kg/week for SGA children. Most of our patients were on regular treatment and received their medicine 90% of time. Subjects with multiple pituitary hormone deficiency (MPHD) were treated with appropriate hormone replacement therapy. The children were followed 3 monthly for height, weight and pubertal status along with monitoring of blood glucose, thyroid status, and bone age (BA) assessment. BA was estimated by using Greulich and Pyle chart. Statistical analysis done with Student's t-test, where all values were expressed as mean ± standard error of the mean, and a value of P ≤ 0.05 was taken as statistically significant.
Profile of the patients
Of 96 patients on GHT for short stature, 49 (51%) were male and 47 (49%) were female. Primary GHD was the most common diagnosis, followed by ISS and the rest were SGA, MPHD, organic pituitary lesions, genetic syndromes (Turner's syndrome, Arskog-Scott syndrome, Silver- Russell syndrome More Details, Noonans, and Cornelia de Lange syndrome) and CKD [Table 1], [Figure 1]. Mean chronological age at presentation was 9.5 ± 2.3 years (median-10 years, range: 3-16 years) the oldest child on GHT, was a 16-year-old Turners syndrome child, and mean height age was 6.4 ± 1.8 year (median: 6.5 years, range: 1-14 years). Mean BA was 6.8 ± 2.1 years (median: 7.4 years, range: 1.3-15 years). Mean age at presentation did not differ significantly (P = 0.17) between male (8.6 ± 3.1 years; median-9.5 years, range: 3.5-13 years) and female (9.4 ± 2.6 years, median-9.8 years, range: 5-16 years). Mean height at presentation was 110 ± 18.2 cm (median-120 cm, range: 74-142 cm), among all patients on GHT. Mean height of patients with syndromes was better (116.0 ± 15.5 cm) than in patients with other etiology (112.8 ± 15 cm), as they had presented at an earlier age. However, the difference between them was not statistically significant (P = 0.41). Mean height at onset did not differ significantly among male (111.7 ± 15.6 cm) and female patients (115.7 ± 16.4 cm) (P = 0.22) [Table 2] and [Table 3].
Two girls entered puberty during the study period. In these children, we have started simultaneous GH and gonadotropin-releasing hormone analogue treatment. Another two patients developed arthralgias during the initial course of treatment, which subsided with reduction in the dose for a short period. Four patients developed hypoythyroidism, among whom two patients had Turners syndrome and one was diagnosed to have panhypopitutarism. One patient developed tonsillomegaly and he subsequently underwent tonsillectomy. None of the study patients in our study developed impaired glucose tolerance, slipped epiphysis, pseudotumor cerebri, scoliosis or pancreatitis.
| Discussion|| |
In this observational study, we have presented data on clinical profile of short statured patients on GHT. We believe that the strength of the study lies in the fact that as ESI patients, these children are getting free GH, which ensured that these patients are on regular treatment. The large number of patients attending our out-patient department, referred from all corners of the state has led to accumulation of this substantial data in a short period of 18 months. Though short stature has been studied extensively worldwide, , similar studies are quite scarce in Indian literature, as evaluation of short stature in a systematic manner and interpretation of data remains problematic.
Short stature may be a disability and can be distressing to the child or adolescent.  Early diagnosis followed by proper treatment is essential to improve outcome. Hence, it is recommended that any child with an abnormally slow growth rate (height velocity), height below 3 rd percentile, or height considerably below the genetic potential and presence of any features suggestive of endocrine disorders deserves further evaluation. Assessment of growth requires reliable growth measurements with the data plotted on suitable growth charts. In this study, the mean age at initiation of GHT was 9 years, which was significantly later when compared with western counterparts, due to nonavailability of specialty care, delay in the diagnosis or late presentation. The classical phenotype described for GHD is less conspicuous in our patients, the reasons for which are not clear.
In our study, the most common indication for GHT was idiopathic GHD (42.7%). In the database of KIGS, 11.66% were GH deficient and among them 75% had idiopathic GHD, whereas, a study from North India reported that 86.5% had isolated GHD (IGHD) and another study from South India reported only 33.3% patients with IGHD among 30 patients.  Mean age at presentation was 9.5 ± 2.3 years in this study, which is about 2.5 years lesser than a multicentric study by Khadilkar et al.,  but is comparable to other Indian studies. ,,, Surprisingly half of our patients were girls which is more than in other Indian studies possibly because of free availability of GHT at ESI. Mean age at presentation was almost similar among patients with idiopathic GHD and patients of other etiology (viz., systemic disease, ISS and genetic syndromes) that is, 10 versus 11 year.
Mean height at presentation in this study was 115.7 ± 17.5 cm, which is higher than in other Indian studies. ,, This indicates that cohorts in the other studies had more marked retardation of growth. This is also evident from BA deficit, which was 3 years in the present study was corresponding to others, , whereas in another study this was only 2 years.  Mean height of patients with systemic diseases was lower than that in other groups, as they presented at an earlier age. Mean height of patients with genetic syndromes are much lesser than the rest of the people.
Hypothyroidism was detected in 20 of our patients during the evaluation of our patients, primary hypothyroidism in 16 and secondary hypothyroidism in four patients (one each from Rathke's cell cyst, craniophryngioma, panhypopitutarism, empty sella). We did GH dynamic studies only after normalization of thyroid levels in this subgroup. Five out of nine Turners syndrome patients were hypothyroid (55.5%). IGHD was diagnosed in a patient of overt hypothyroidism, who in spite of normal thyroid stimulating hormone, continues to have severe short stature over a period of 1 year.
Perhaps this is the largest study of its kind from India and findings of the present study will help clinicians in developing insights into etiological factors and age-sex distribution of Indian children who require GHT.
Our current study has the following limitations:
- We have not done the "insulin tolerance test," which is considered the gold standard to establish GHD, due to lack of facilities and trained persons at our center. However, nevertheless, we have supplemented the standard clonidine stimulation test by measurement of IGF-1 and IGF-BP3.
- We estimated BA with Greulich-Pyle Atlas More Details, because standard RUS score of Tanner Whitehouse two methods was not available at our center. We are presently on the course of a long term follow-up study to accumulate data to present a review article.
- We have not done any molecular genetic study in patients of IGHD.
| Conclusion|| |
We conclude idiopathic IGHD is the most common etiology in our patients on GHT, followed by ISS. In order to improve treatment outcome, short stature needs to be evaluated at an early stage with lower growth compromise, to improve outcomes.
| References|| |
Fradkin JE. Creutzfeldt-Jakob disease in pituitary growth hormone recipients. Endocrinologist 1993;3:108-14.
Richmond E, Rogol AD. Current indications for growth hormone therapy for children and adolescents. Endocr Dev 2010;18:92-108.
Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML, et al
. Evaluation and treatment of adult growth hormone deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2006;91:1621-34.
Khadilkar VV, Khadilkar AV, Cole TJ, Sayyad MG. Crosssectional growth curves for height, weight and body mass index for affluent Indian children, 2007. Indian Pediatr 2009;46:477-89.
Rudman D, Kutner MH, Blackston RD, Cushman RA, Bain RP, Patterson JH. Children with normal-variant short stature: Treatment with human growth hormone for six months. N Engl J Med 1981;305:123-31.
Copeland KC, Underwood LE, Van Wyk JJ. Induction of immunoreactive somatomedin C human serum by growth hormone: Dose-response relationships and effect on chromatographic profiles. J Clin Endocrinol Metab 1980;50:690-7.
Moayeri H, Aghighi Y. A prospective study of etiology of short stature in 426 short children and adolescents. Arch Iran Med 2004;7:23-7.
Colaco P, Desai M. Identification of a child with short stature. Indian Pediatr 1990;27:1159-64.
Frindik JP, Kemp SF, Hunold JJ. Near adult heights after growth hormone treatment in patients with idiopathic short stature or idiopathic growth hormone deficiency. J Pediatr Endocrinol Metab 2003;16 Suppl 3:607-12.
Kannan V, Usharani K. Human growth hormone therapy: Longterm responses in 30 children with growth hormone deficiency. Indian J Pediatr 1991;58 Suppl 1:65-9.
Khadilkar VV, Khadilkar AV, Nandy M, Maskati GB. Multicentric study of efficacy and safety of growth hormone use in growth hormone deficient children in India. Indian J Pediatr 2007;74:51-4.
Bajpai A, Kabra M, Gupta AK, Menon PS. Growth pattern and skeletal maturation following growth hormone therapy in growth hormone deficiency: Factors influencing outcome. Indian Pediatr 2006;43:593-9.
Menon PS, Virmani A, Sethi AK. Biosynthetic growth hormone therapy in children with growth hormone deficiency: Experience at AIIMS, New Delhi. Indian J Pediatr 1991;58 Suppl 1:71-7.
Garg MK, Pakhetra R, Dutta MK, Gundgurthi A. Response to growth hormone therapy in Indian patients. Indian J Pediatr 2010;77:639-42.
[Table 1], [Table 2], [Table 3]