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Gigantism is abnormally large growth due to an excess of growth hormone during childhood, before the bone growth plates have closed. Causes The most common cause of too much growth hormone release is a noncancerous (benign) tumor of the pituitary gland.
Growth hormone deficiency - wikipedia, the free encyclopedia, Growth hormone deficiency (ghd) is a medical condition, caused by problems arising in the pituitary gland, in which the body does not produce enough growth hormone (gh).. Growth hormone treatment - wikipedia, the free encyclopedia, Medical uses hgh deficiency in children. Growth hormone deficiency diagnosis - endocrineweb, Growth hormone deficiency diagnosis exams and tests to diagnose growth hormone deficiency.
The growth hormone test measures the amount of growth hormone in the blood. How the Test is Performed Blood is typically drawn from a vein, usually from the inside of the elbow or the back of the hand. Our New BMJ website does not support IE6 please upgrade your browser to the latest version or use alternative browsers suggested below. Objective: To evaluate the efficacy of recombinant growth hormone for increasing adult height in children treated for idiopathic isolated growth hormone deficiency. Participants: All 2852 French children diagnosed as having isolated idiopathic growth hormone deficiency whose treatment started between 1987 and 1992 and ended before 1996.
Conclusion: The effect of growth hormone is unclear in many patients treated for so called idiopathic isolated growth hormone deficiency. The effect on adult height is unclear because of a lack of controlled trials and analysis, and that subgroups, rather than entire populations, are analysed.
Growth hormone has been used for four decades, initially as an extract and now in recombinant form, but we still know little about its long term effects on adult height.1 No long term controlled trial has been performed, and evaluation of the effect of growth hormone is based on comparisons with historical controls or on changes in height. Most published studies have reported the short term (1 to 2 years) effects of growth hormone.
From 1973 to 1997, every prescription of growth hormone in France had to be approved by a central agency (Association France-Hypophyse). In 1997, we presented data for height for 1700 patients, 55% of whom had received growth hormone of human origin.12 We then collected data on adult height of patients treated solely with recombinant growth hormone for idiopathic isolated growth hormone deficiency.
Our present study included all French children who were diagnosed with isolated idiopathic growth hormone deficiency whose treatments began between 1 July 1987 and 31 December 1992 and who had attained adult height by September 1999 (fig 1). We identified patients as having growth hormone deficiency according to the criteria used at the time, which included data on height, two growth hormone stimulation tests, or assessment of spontaneous growth hormone secretion.12 Growth hormone assays were performed by the centres where children were receiving treatment.
At baseline and follow up visits (every three to six months), paediatric endocrinologists recorded the height, weight, age, bone age,16 and pubertal stage of the patients, 17 18 together with the dose of growth hormone they were taking, the frequency of injections, and any associated treatments.
Fig 2 Changes in height in standard deviation (SD) score in patients treated with growth hormone, relative to beginning of treatment (top) and in absolute values.
We prospectively collected follow up data in 1998-9 from doctors or from patients who provided “self reported” values for height and weight. We calculated standard deviation (SD) scores of height and weight for age, sex, or gestational age, and target height.12 Age at onset of puberty was expressed in standard deviations.
Table 1 Baseline characteristics and details of growth hormone therapy for the children in the study. We classified patients according to whether treatment was completed (1524, 53.4%) or stopped early (table 2). The continued increase in height after early termination of growth hormone treatment indicated that changes in height standard deviation scores were not necessarily directly due to growth hormone.
In a separate analysis (1048 prepubertal patients for whom the onset of puberty could be recorded), age at onset of puberty was positively associated with outcome and accounted for 5% of outcome variance.
Fig 3 Changes in height in prepubertal patients treated with growth hormone (top) and proportion of patients who reached pubertal Tanner stage 217–18 (bottom). We found that children treated for idiopathic growth hormone deficiency had a mean adult height 8-10 cm below that of the general population and did not reach their target height.


Studies generally assess change in height and assume that all improvement results directly from treatment. We should also consider methodological aspects, such as whether the diagnosis of growth hormone deficiency was valid in our study population. Finally, we selected a subgroup of the patients treated for growth hormone deficiency; patients with non-idiopathic growth hormone deficiency or abnormalities on pituitary magnetic resonance imaging were excluded, and patients with early onset growth hormone deficiency were excluded by the design of the study focusing on adult height. Our patients data are similar to patients in other studies in terms of age and height standard deviation scores at the start of treatment (tables 5 and 6).
Overall, the onset of puberty was delayed considerably in our patients, as in the Pharmacia International Growth Database,31 and variables linked to pubertal delay positively were associated with adult height. Long term treatment with growth hormone has no clearcut benefit in a large proportion of patients treated for so called idiopathic isolated growth hormone deficiency.
Long term controlled trials to evaluate the effects of growth hormone treatment in patients who do not have growth hormone deficiency are needed, given the number of children treated worldwide. We thank Vean Eng Ly, Sabine Ximenes, and Dr Elisabeth Kind for their invaluable contributions. Funding The study was supported by a grant from Programme Hospitalier de Recherche Clinique AOM96016. Most of the patients have pubertal delay and a spontaneous growth potential, which must be taken into account when measuring the effect and cost effectiveness of treatments. The Association France Hypophyse decided annually whether the treatment should be continued. 5 20 We grouped the potential predictors into those accounting for regression towards the mean, those describing genetic growth potential, those describing the child at baseline, and those describing growth hormone and associated treatments (see table 3). Growth is a multifactorial process and baseline differences between patients who completed treatment and those that did not may hinder comparison.
The proportion of patients entering puberty was higher for completers than for non-completers at an equivalent time point (fig 3). Children who stopped treatment early continued to grow and reached similar adult heights to patients who completed treatment.
This strongly suggests that many had constitutional delay in growth and puberty, which should not be confused with growth hormone deficiency.
Most of the patients actually have pubertal delay and a potential for spontaneous catch up, which must be taken into account when measuring the effect and cost effectiveness of growth hormone treatments. We should try to identify predictive markers for short stature in adults and focus intervention on patients at higher risk.
Drs Noel Cabet, Valerie Porra, Stephane Chen, and Francine Mallet also participated in data collection. The health care provider wraps an elastic band around the upper arm to apply pressure to the area and make the vein swell with blood. Next, the health care provider gently inserts a needle into the vein.
Growth hormone deficiency should be clearly distinguished from pubertal delay, and criteria should restrict the definition to patients with severely and permanently altered growth hormone secretion as our results support the use of growth hormone in such patients. The issue of diagnostic criteria for growth hormone deficiency has been widely considered,7–11 but profiles of patients treated around the world do not always fit the strict definitions, with little change in profile over time. We tested variables in each group as predictors of outcome after adjusting for variables identified at previous stages. Therefore, we constructed a multivariate model of factors explaining adult height (table 3).
Pubertal delay accounted for a large proportion of the catch-up growth observed, and children with severe growth hormone deficiency had better outcomes than children with borderline diagnoses.
Instead, we studied all children who started treatment; in this population, growth continued in children who stopped treatment before the end of growth.


Such selection may focus on patients who responded well to treatment, providing an overoptimistic view of the results (fig 2). The diagnosis of idiopathic isolated growth hormone deficiency should be restricted to a small minority of patients with severely and permanently altered growth hormone secretion: our results support the use of growth hormone in such patients.
We also thank all the physicians involved in the follow up of patients and in the review process at Association France-Hypophyse. The most effective medications are somatostatin analogs (such as octreotide or long-acting lanreotide), which reduce growth hormone release. Dopamine agonists (bromocriptine mesylate, cabergoline) have also been used to reduce growth hormone release, but these are generally less effective.
Normal results in retests of growth hormone secretion were the reason for non-completion in 14%.
In the final model (table 4), target height and birth weight and regression towards the mean accounted for 33% of outcome variance. Multivariate analysis showed that patients who did not complete the treatment did better, and that length of treatment was positively associated with outcome. Growth velocity is an important diagnostic criterion26–28 but was only slightly reduced in our patients compared with normative values for age and sex. The following clinicians were involved in the follow up of a large number of children in the study: Jacques Battin, Pascale Berlier, Michel Bost, Jean-Jacques Bouquier, Raja Brauner, Jacques Bringer, Jean-Pierre Charvet, Pierre Chatelain, Michel Colle, Paul Czernichow, Michel David, Francois Despert, Pierre-Andre Doyard, Herve Dubourg, Robert Dumas, Blandine Esteva, Christine Fedou, Anne Fjellestad-Paulsen, Patrick Garandeau, Philippe Garnier, Christine Gendrel, Francois Girard, Micheline Gourmelen, Muriel Houang, Roger Jean, Monique Jesuran, Jean-Claude Job, Jean-Georges Juif, Yves Lebouc, Marcel Lecornu, Bruno Leheup, Anne Lienhardt, Jean-Marie Limal, Eric Mallet, Georges Malpuech, Roger Mariani, Catherine Naud-Saudreau, Isabelle Oliver, Andre Orsetti, Christian Pauwels, Marc Petrus, Catherine Pienkowski, Theresa Pierret, Michel Pierson, Graziella Pinto, Olivier Puel, Raphael Rappaport, Marie-Charles Raux-Demay, Denis Reiss, Pierre Rochiccioli, Bernard Sablayrolles, Charles Saab, Gilbert Simonin, Sylvie Soskin, Charles Sultan, Jean-Edmond Toublanc, and Jacques Weill. Pegvisomant, a medication that blocks the effect of growth hormone, may be used. Radiation therapy has also been used to bring growth hormone levels to normal. The main outcome response—the difference between adult and baseline heights (standard deviation scores)—was approximately normally distributed. Variables determined at baseline that predicted a good outcome were age, bone age delay, and prepubertal status.
Patients who completed the treatment generally had more severe growth hormone deficiency and increased in height with longer treatments. However, these patients are typical of patients treated worldwide for growth hormone deficiency. Our study design also enabled us to take into account the potential for spontaneous catch up of patients treated. However, it can take 5 - 10 years for the full effects to be seen and almost always leads to low levels of other pituitary hormones. Radiation has also been linked to learning disabilities, obesity, and emotional changes in children. Once the blood has been collected, the needle is removed, and the puncture site is covered to stop any bleeding. In infants or young children, a sharp tool called a lancet may be used to puncture the skin and make it bleed.
Most of the variation in height gain was explained by regression towards the mean, patients' characteristics, and delay in starting puberty.
Two potential predictors (initial dose of growth hormone and maximum stimulated peak level of growth hormone) were log transformed to yield normally distributed variables. Thus, older patients presenting no signs of puberty and with marked bone age delay had better outcomes. All data were obtained from routine examination in daily practice and various growth hormone tests and assays were used, therefore their reliability may be questioned.
The blood collects into a small glass tube called a pipette, or onto a slide or test strip.
As all models were adjusted for baseline height, they describe adult height gain — that is, the difference between adult and baseline height expressed in standard deviations — and adult height itself (in standard deviations).5 We used the SAS statistical package for analysis. Whether or not treatment was completed, and length of treatment were independent predictors.



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