C O N S E N S U S REPORT Indian J Pediatr (Suppl) 1991; 58 : S 81-83

Growth Hormone Therapy of Children with Growth Hormone Deficiency in India

P.S.N. Menon and Meena Desai *

Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, and * Division of Pediatric Emtocrinology, Bai Jerbai Wadia Hospital

for Chidren & Institute of Child Health & Research Centre, Pard, Bombay.

The recent symposium on "Growth Hormone (GH) Replacement and Therapy' ' held in Delhi discussed the etiology, diagnosis and therapy of growth hormone deficiency (GHD) and pharmacodynamics of growth hormone. The discussion was initiated by Dr. Meena Desai (Bombay) who outlined the problems and constraints of GH therapy in India. The purpose was to arrive at some consensus on growth hormone therapy if and when it becomes available in India for children with GHD.

In the past limited availability of GH acted as a barrier to optimal therapy. Now we have entered an era of virtually unlimited supply of GH although the cost remains a limiting factor. This has raised m any new issues and controversies about its use and entitlement to therapy. More sophisticated diagnostic methods such as 24 hour GH profile have led to the concept of 'growth hormone insufficiency' as

Reprint requests : Dr. P.S.N. Menon, Division of Pediatric Endocrinology, Department of Pediatrics, All India ]nstRute of Medical Sciences, Ansari Nagar, New DeIhi-II 0 029.

distinct from 'deficiency'. Adoption of accurate auxologic criteria and defining growth hormone responsiveness has become important. Besides GHD, GH therapy is being tried in Turner syndrome, normal but slowly growing short children, dysmorphic syndromes, skeletal dysplasias and chronic renal failure.

Dr. Desai stressed that in India, as in other developing countries the health priorities are very different. Very few receive financial support from the state or funding agencies. GH therapy which is prohibitively expensive is likely to remain unavailable to the most needy. GH therapy is thus rendered nonviable due to the problems of nonavailability, inadequacy of timely supply and the economic problems of the family. It is necessary to evolve a consensus on early diagnosis and optimal therapy of children with GHD. Obviously the questions which would arise are : who should be entitled for GH therapy, the diagnostic modalities and criteria to be u tilised, who should prescribe and dispense GH, study

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of scientific aspects of therapy and government permission for duty free import.

The precise est imates of the prevalence of GHD in India are not known but almost all the delegates agreed that the frequency of GHD is significant amongst children who are brought to the endocrine clinics primarily for short stature. The nonavailability of well established growth standards for Indian children makes it difficult in identifying children with short stature. Dr. Prisca Colaco (Bombay) observed that almost one third of children with stature less than 5th percentile of ICMR standards have an endocrine cause for short stature. There was some disagreement about the use of ICMR charts for evaluation of height, as the data was derived from subjects belonging to lower socio-economic group. Dr. M.B. Ranke (Germany) s t ressed the importance of the correction for prenatal height, need for pretreatment observation of height velocity for six months to one year and correction of nutritional deficiencies and observing its effect on growth. Both Dr. Ranke and Dr. Muinck-Keizer (Holland) were in favour of using internationally accepted growth charts like Tanner's for all populations as these can lead to better universal understanding. A study published here has shown that between 20 to 25 percent of cases referred to endocrine clinics primarily for short stature are likely to have GH related short stature.

tn India two clinical types of GHD are seen : (i) the typical short child with immature facies and generalised adiposity, and (ii) the thin delicate

looking child without much adipose tissue. There appears to be a high frequency of familial forms of GHD. The importance of nutritional factors and its effect on growth were stressed by many but there was a general agreement that one cannot be mistaken with the other. Basal GH levels are usually elevated in children with protein-energy malnutri t ion (PEM). Intervention programmes for supplementation and correction of deficiencies would lead to a spurt in growth in these children in the absence of any other disease.

Dr. R.J. Dash (Chandigarh) spoke on the diagnostic criteria and the availability of facilities to diagnose GHD in India. He suggested that children with a height less than 10th centile of the growth standards, and growth velocity less than 3 cm/year needed screening for GHD and those below 5th centile who continue to grow slowly after appropriate exclusion of other conditions require definitive treatment. He documented no difference in the bone age as estimated by TW-2 method (RUS) among the Indian, British and Australian populations. However he encountered problems in interpreting absolute levels of GH following stimulation tests for diagnosis of GHD. Dr. Ranke suggested that levels of GH above 10 ng/ml exclude a diagnosis of GHD. The screening tests should be cost efficient and hence many felt that sleep and exercise tests still have a place in India. Single tests have a false positive range of 15 percent and hence two tests are needed before specific diagnosis is established. In general there was a consensus that clonidine is a good and reliable test. It was agreed that clinical. auxologic, radiologic and biochemical

MENON AND DESAI : GH ]HERAPYIN GHD S/83

evaluation are needed to arrive at a diagnosis. A minimum of two stimulation tests should be carried out. ['here was some reservation about the use of insulin test because of the tendency for severe hypoglycemia. Current opinion is to discard the concepts of partial and complete GHD using GH levels as cut off.

The practical aspects of GH therapy were outlined by Dr. H.B. Chandalia (Bombay). He briefly explained the modes of therapy with reference to timing, frequency of administration, dose of GH, route of administration and technique of self administration. The general consensus was that a dose of 12 IU/m 2 body surface area/week or 0.5-0.7 IU/kg/week should be given over 6-7 days of a week subcutaneously preferably at night. In the present context of limited availability, the drug should preferably be used in children with GHD only. Self administration should also be encouraged.

Dr. V. Kannan (Madras) briefly outlined the experience of treating children with GHD with pituitary derived GH in the past. Even though response was good, he observed that a significant number of children manifested hypothyroidism later. Pituitary derived GH is now banned but biosynthetic GH is available; however close monitoring is needed to provide optimal growth without side effects.

Dr. K. Kannan (Madurai) discussed about the assessment of GH therapy. The various aspects which need assessment are bioavailability of the hormone, biochemical responses, clinical and auxological responses, re-evaluation, dose review, side effects and allergy to the drug. The best short term indication of response to treatment is height velocity. There should be a minimum increase in growth velocity of 2 cm/yr or more over the initial velocity. There is a need to increase the dose or frequency of administration if the height velocity is not adequate during the first six months of observation. By and large the new biosynthetic GH therapy appears to be free of side effects.

Dr. P.S.N. Menon (New Delhi) briefly outlined the various other indications of GH therapy besides GHD. These include short normal children, constitutional short stature, Turner syndrome, Noonan syndrome, intrauterine growth retard- ation, osteochondropathies, uremia and chronic renal failure and chronic nonendocrine diseases associated with short stature. There is good evidence of a positive effect of GH in neurosecretory dysfunction and adults with GHD. However the general consensus was that at the present time, in view of the cost, our efforts in India should be concentrated on GHD children.