Indian J Pediatr (May 2015) 82(5):397–398 DOI 10.1007/s12098-015-1717-3
EDITORIAL COMMENTARY
Pituitary Size and Response of Growth Hormone Deficient Children to Growth Hormone Therapy P. S. N. Menon
Received: 23 January 2015 / Accepted: 29 January 2015 / Published online: 3 March 2015 # Dr. K C Chaudhuri Foundation 2015
Significant strides have been made on growth hormone (GH) therapy in children and adolescents over the past five decades. The launch of recombinant human GH (rHGH) in 1985 eliminated the risk of Creutzfeldt-Jakob disease with cadaveric GH; ensured an ongoing unlimited supply and also increased the number of children eligible for therapy. The indications for rHGH therapy were expanded to include many chronic nonendocrine diseases associated with significant short stature. Despite mounting evidence of efficacy and safety of GH in various growth disorders, the cost of therapy remains the major constraint in developing countries. GH therapy in children with short stature enables them to reach genetic height potential with appropriate pubertal maturation consistent with genetic and ethnic background and target height. Therapy with GH induces rapid catch up growth during the first two to three years of treatment, increasing height velocity two to four-fold above the pretreatment height velocity during the first year of therapy. In subsequent years, the height velocity declines and follows a normal pattern of growth. Final height improves on average by 8–11 cm compared with untreated children with GH deficiency [1]. The response widely varies among individuals. Over the years the rigorous cut offs used for diagnosis of GH deficiency were amended to include more children in the ambit of GH treatment. The old criteria of peak GH levels >5 ng/ml following two stimulation tests for diagnosis of growth hormone deficiency (GHD) have made way for a single GH stimulation test with peak GH levels of 10 ng/ml [2].
P. S. N. Menon (*) Department of Pediatrics, Jaber Al-Ahmed Armed Forces Hospital, Kuwait City, Kuwait e-mail: [email protected]
Partial GHD (stimulated GH levels in the subnormal range) is now accepted as an indication for GH therapy. Many centers have done away with GH stimulation tests with assays for insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP3); however reliability still remains a major issue [3]. There are very few studies from India on the short and long term effects of rHGH therapy. The age at which the GHD is diagnosed is late, the duration of therapy is short and the number of patients included in the studies is small [4]. Most pediatric endocrinologists in India advise a conservative dose to reduce the cost of therapy. The number of children seeking GH therapy is on the rise but the number of children with GHD receiving GH therapy is too little as government or private financial support is limited. Advances in imaging techniques especially magnetic resonance imaging (MRI) have helped us to understand pituitary morphology in GH deficiency. The tetrad of hypoplastic or absent pituitary, absent pituitary stalk, absent or ectopic posterior pituitary hyperintensity and presence of empty sella are accepted as the hallmarks of non-tumoral forms of GH deficiency [5–7]. The lack of precise definitions for size and volume of pituitary and the length and thickness of its stalk were major roadblocks in older studies. There are very few studies on normative data on pituitary size in children [8]. Structural pituitary abnormalities can be detected in approximately 50–70 % of patients with non-tumoral GHD [9–11]. In general these abnormalities are seen more often in patients with combined forms (90 %) than isolated forms of GH deficiency (20–50 %) [12]. There are a few studies from India and the observations vary. A study from Delhi showed that isolated GH deficiency is not related to transection or compression of the pituitary stalk [13]. Another study from Chandigarh observed that the number of imaging abnormalities was comparable in children with isolated and combined
398
GH deficiency; but those with severe forms of GH deficiency (GH levels
EDITORIAL COMMENTARY
Pituitary Size and Response of Growth Hormone Deficient Children to Growth Hormone Therapy P. S. N. Menon
Received: 23 January 2015 / Accepted: 29 January 2015 / Published online: 3 March 2015 # Dr. K C Chaudhuri Foundation 2015
Significant strides have been made on growth hormone (GH) therapy in children and adolescents over the past five decades. The launch of recombinant human GH (rHGH) in 1985 eliminated the risk of Creutzfeldt-Jakob disease with cadaveric GH; ensured an ongoing unlimited supply and also increased the number of children eligible for therapy. The indications for rHGH therapy were expanded to include many chronic nonendocrine diseases associated with significant short stature. Despite mounting evidence of efficacy and safety of GH in various growth disorders, the cost of therapy remains the major constraint in developing countries. GH therapy in children with short stature enables them to reach genetic height potential with appropriate pubertal maturation consistent with genetic and ethnic background and target height. Therapy with GH induces rapid catch up growth during the first two to three years of treatment, increasing height velocity two to four-fold above the pretreatment height velocity during the first year of therapy. In subsequent years, the height velocity declines and follows a normal pattern of growth. Final height improves on average by 8–11 cm compared with untreated children with GH deficiency [1]. The response widely varies among individuals. Over the years the rigorous cut offs used for diagnosis of GH deficiency were amended to include more children in the ambit of GH treatment. The old criteria of peak GH levels >5 ng/ml following two stimulation tests for diagnosis of growth hormone deficiency (GHD) have made way for a single GH stimulation test with peak GH levels of 10 ng/ml [2].
P. S. N. Menon (*) Department of Pediatrics, Jaber Al-Ahmed Armed Forces Hospital, Kuwait City, Kuwait e-mail: [email protected]
Partial GHD (stimulated GH levels in the subnormal range) is now accepted as an indication for GH therapy. Many centers have done away with GH stimulation tests with assays for insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP3); however reliability still remains a major issue [3]. There are very few studies from India on the short and long term effects of rHGH therapy. The age at which the GHD is diagnosed is late, the duration of therapy is short and the number of patients included in the studies is small [4]. Most pediatric endocrinologists in India advise a conservative dose to reduce the cost of therapy. The number of children seeking GH therapy is on the rise but the number of children with GHD receiving GH therapy is too little as government or private financial support is limited. Advances in imaging techniques especially magnetic resonance imaging (MRI) have helped us to understand pituitary morphology in GH deficiency. The tetrad of hypoplastic or absent pituitary, absent pituitary stalk, absent or ectopic posterior pituitary hyperintensity and presence of empty sella are accepted as the hallmarks of non-tumoral forms of GH deficiency [5–7]. The lack of precise definitions for size and volume of pituitary and the length and thickness of its stalk were major roadblocks in older studies. There are very few studies on normative data on pituitary size in children [8]. Structural pituitary abnormalities can be detected in approximately 50–70 % of patients with non-tumoral GHD [9–11]. In general these abnormalities are seen more often in patients with combined forms (90 %) than isolated forms of GH deficiency (20–50 %) [12]. There are a few studies from India and the observations vary. A study from Delhi showed that isolated GH deficiency is not related to transection or compression of the pituitary stalk [13]. Another study from Chandigarh observed that the number of imaging abnormalities was comparable in children with isolated and combined
398
GH deficiency; but those with severe forms of GH deficiency (GH levels
