Cause Of Short Stature Research Articles

SAT-LB17 Triplication of SHOX Downstream Region in Mild Short Stature

Deletions of the downstream flanking regions of the SHOX gene that contain conserved non-coding cis-regulatory DNA elements are a known cause of Leri-Weill dyschondrosteosis or idiopathic short stature (ISS). Functional and comparative genomic studies have demonstrated the existence of four CNE enhancers downstream of SHOX which have transcriptional activity, and a fifth has recently been suggested at approximately X:970,000. Duplications of these downstream regions have also been described in patients with ISS, although with a variable phenotype. We present a family with ISS and the first ever reported SHOX downstream triplication. The index case was a 12-year-old Caucasian female of unrelated parents, born with normal weight and length, and normal hearing/vision and development. At the age of 12, her height was -1.87 SD (-1.35 SD adjusted for parental height). Her growth chart showed a height on the 90th centile at birth, slowly crossing centiles for the first 5 years to the 2nd centile, which she then followed. She had normal proportions and head circumference, and no dysmorphic features apart from inverted nipples. Baseline investigations for short stature were normal, including IGF1, karyotype and celiac screen. Bone age was 1.5 year delayed. Family history: arthritis in the father, early menopause in the mother. Analysis of SHOX and its flanking regions was carried out using Multiplex Ligation-dependent Probe Amplification (MLPA) and direct sequencing of all coding exons. MLPA analysis showed a SHOX downstream triplication with a minimum size of 66kb (X:963670-1029779) and a maximum size of 428kb (X:899389-1327688). The size of the duplication was further defined using array comparative genome hybridization (ACGH) analysis which showed the minimum size to be ~325kb (X:907457-1232802). This triplication includes the proposed regulatory element at ~ X:970,000. The triplication was subsequently shown to be present in the proband’s mother and brother who also have mild ISS. Further analysis of these and other family members is ongoing. The triplication is of a single-sized fragment, and the fragment size is identical to one that has been seen in duplicated form in several other patients, increasing the likelihood that the triplicated fragments are in tandem. The precise mechanism of the pathogenic effect of the triplication is unknown, but it likely exerts a negative effect on SHOXtranscription, reducing its expression and ultimately resulting in SHOX haploinsufficiency. In conclusion, we describe a family with mild ISS and a downstream triplication of the proposed X:970,000 SHOX downstream regulatory element. This provides further evidence for this previously proposed regulatory element downstream of SHOX and adds additional proof that increased dosage of this regulatory element region is a cause of short stature.

Etiological Study of Short Stature among Children Attending Outpatient Department of Pediatrics in a Tertiary Care Medical College Hospital

Background: Short stature is a term applied to a child whose height is two standard deviations or more below the mean height for children of that gender and chronologic age.Familial short stature and Constitutional Growth delay are considered as normal variants, the pathological short stature includes a wide variety of underlying disorders.Chronic systemic disorders, malnutrition, chromosomal or endocrinal disorders lead to a proportionate short stature.While most of the disproportionate short stature are secondary to skeletal dysplasias or resistant rickets.Etiological evaluation plays an important role in identification of physiological as well as pathological causes of short stature.Subjects and Methods:All children of age between 2 and 18 years with height below 2 standard deviation of mean for age and gender were included in the study. Result:A total of 100 children were studied who fulfilled the criteria of short stature, out of which 61 children were male and 39 were female children.Present study showed that females had more pathological variants (72%) than males (46%) whereas males had more physiological variants (54%) than females (28%) with P-value: 0.011Hypothyroidism was more common in females than males with 28% and 8% respectively. Genetic syndrome was more common in females than males with 10% and 3% respectively. Conclusion:Etiological evaluation is of pivotal role in identification of physiological as well as pathological causes of short stature and also helps in modifying the course of stature by means of early intervention.

Prevalence of Celiac Disease in Idiopathic Short Stature Children Presenting in OPD of Children Hospital, Faisalabad

Objective: To determine the prevalence of celiac disease in short statured children. Study Design: Cross Sectional Study. Settings: OPD of Children Hospital, Faisalabad Pakistan. Duration: Six months from March 10, 2016 to August 9, 2016. Methodology: A total of 300 children with 174 female, 126 males were studied, who came in OPD in Children Hospital Faisalabad for the evaluation of their short stature, excluding familial short stature and other causes of short stature (endocrinal, renal & other chronic illnesses). IgA, TTG & IgG antibodies were evaluated. These antibodies were measured by ELISA method and patients whose TTG antibodies were 10 times greater than normal were spared form duodenal biopsy, however patients having antibodies less than 10 times but greater than normal or having equivocal results were under gone for intestinal biopsy for confirmation of celiac disease. Results: We detected out of 300 patients 88 patients were having TTG titer > 10% of the normal value. 29 patients were having increase titer but less than 10 time of the normal value and 7 patients were found to have equivocal results. So, 36 patients were sent for biopsy out of them 32 were found positive for celiac disease. Hence, we detected 40% (n=120) children were having celiac disease. All 78 females, 42 males having celiac disease were at 2SD except 4 patients who were at 3SD. Conclusion: We conclude that prevalence of celiac disease is high in patients with idiopathic short stature and it is important to investigate all children with ISS for celiac disease by measuring TTG antibodies.

Evaluation of Turner Syndrome Knowledge among Physicians and Parents

Objective:Turner syndrome (TS) is one of the most common chromosomal abnormalities and an important cause of short stature and infertility due to ovarian failure in females. The aim was to evaluate the knowledge of TS among physicians and parents of children with TS and to enhance awareness about this subject.Methods:One hundred and forty physicians were included in the study. The study population comprised 37 pediatricians (26.4%), 15 gynecologists (10.7%), 88 family physicians (62.9%) and 30 parents who had daughters with a diagnosis of TS. Two separate questionnaires were administered to evaluate TS knowledge of physicians and parents.Results:According to the self-reports of physicians, 49% had insufficient knowledge of TS, while 15.7% indicated that they had no knowledge of TS. The mean percentage of correct answers was 50.71±16.17% for all physicians. When the entire group of physicians was considered, 67.1% of them did not know the approximate incidence of TS, while 14.3% of them incorrectly indicated that TS was a condition that was seen in boys. The mean percentage of correct answers among parents was 68±15%, and there was no difference between the mothers’ and fathers’ correct answer rates (p=0.063). The majority of parents was not aware of TS-associated diseases and increased malignancy risk in TS.Conclusion:Physician knowledge of TS was poor and that there is a need for continued education about TS at the medical faculty and post-graduate levels.

Etiology of short stature in children attending pediatric endocrinology clinic of a tertiary care hospital in Bangladesh

Background: Short stature is a common problem to practicing pediatricians. It results from various etiologies, which are categorized as normal variants and pathological causes. Normal variant short stature consists of Familial Short Stature (FSS) and Constitutional Growth Delay (CGD), while pathological causes are subdivided into endocrine diseases, clinically defined syndromes, chronic diseases, metabolic diseases and others. There are not so much data available in Bangladesh in this respect. So, present study was conducted to know the common causes of short stature.Methods: This cross-sectional study was done in pediatric endocrinology clinic of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2017 to August 2018. One hundred children with short stature meeting inclusion criteria were recruited after taking an informed consent. The detailed history, physical examination including anthropometric measurements and relevant investigations were done. Data were recorded on a predesigned questionnaire for final analysis.Results: The common causes of short stature identified were familial short stature (FSS) 51% cases, Constitutional Growth Delay (CGD) 14% cases and hypothyroidism 12% cases. Other less common causes of short stature were Growth Hormone Deficiency (GHD) 8% cases, malnutrition 6% cases and genetic syndrome 5% cases.Conclusions: FSS and CGD were the leading cause of short stature in children. Endocrinological causes were the most common cause of short stature after normal variant while nonendocrine causes were the least.

A rare cause of short stature: Kenny-Caffey syndrome type 2 – a case report and literature review

A rare cause of short stature: Kenny-Caffey syndrome type 2 – a case report and literature review

Comparative analysis of the practices of diagnostics and treatment of short stature, established in the outpatient clinics of general practitioners from Pleven and Varna

Introduction: Normal growth of the child is an index of good health, but it is a limited in time process, and for this reason, timely diagnosis and start of treatment of children with short stature (SS) are crucial for achieving adequate adult height and good quality of life. Aim: The aim of the present interview is to study the knowledge of general practitioners (GPs) about growth disorders and to increase the informational level in the process of creating national referral criteria and algorithms for the management of children with SS. Materials and Methods: GPs from Pleven and Varna (n=40, mean age 54.5 ± 8.85 yrs, work experience 25.9 ± 8.8 yrs, working in urban settings – 75%, children in their practices 0-18 - 23 079) have completed a questionnaire with 20 questions. All interviewed GPs defined SS as a problem for children. Almost all of them (80%) indicated use of standards for growth evaluation. They claimed that they provided screening for early detection of SS and they knew where to send a child with growth deviation. The main cause of SS, according to GPs, is genetic predisposition (35%), and that both - GPs and parents, are active in diagnosis of SS (82.5%). However, GPs shared that they were faced with some difficulties in the diagnosis of SS because of the “unclear” path of the patient after directing him to a specialist and that was the reason some of the children with SS to remain undiagnosed. Conclusion: SS is a problem that GPs are conscious of, but there is a strong need of measurements for building the “route” of the patient with SS, starting from the first step – the general practitioner.

Achieving Optimal Short- and Long-term Responses to Paediatric Growth Hormone Therapy

It is over sixty years since the first administration of human growth hormone (GH) to children with GH deficiency, and over thirty years since recombinant human GH has been available for treatment of GH deficiency and a wider range of non-GH deficiency disorders. From a diagnostic perspective, genetic analysis, using single gene or Sanger sequencing and more recently next generation or whole exome sequencing, has brought advances in the diagnosis of specific causes of short stature, which has enabled therapy to be targeted more accurately. Genetic discoveries have ranged from defects of pituitary development and GH action to abnormalities in intracellular mechanisms, paracrine regulation and cartilage matrix formation. The strategy of GH therapy using standard doses has evolved to individualised GH dosing, depending on diagnosis and predictors of growth response. Evidence of efficacy of GH in GH deficiency, Turner syndrome and short children born small for gestational age is reviewed. The importance of critical assessment of growth response is discussed, together with the recognition and management of a poor or unsatisfactory growth response and the organisational issues related to prevention, detection and intervention regarding suboptimal adherence to GH therapy.

Hormone treatment for short statured children? For a critical approach to sociocultural norms about short stature

Children's growth and height are thoroughly and regularly scrutinized by paediatricians and parents alike. A general consensus in treating short statured children with growth hormone (GH) exists when short stature is one of the symptoms of their pathological condition (e.g. Turner syndrome, small for gestational age, chronic renal insufficiency and Prader-Willi syndrome). Idiopathic short stature is instead a controversial diagnostic because it is based on the exclusion of any known medical causes of short stature. By proposing a critical reading of sociocultural norms about short stature, this article suggests that it is important to give a voice to concerned children and that the ethical debate about GH treatment should investigate the best ways in which children can take part in the decision-making process.

PENYAKIT KRONIS SISTEM PERNAFASAN ANAK DENGAN STUNTING

Penyakit kronik pada anak akhir-akhir ini menjadi perhatian dan merupakan isu global. Salah satu penyakit kronik pada anak adalah gangguan sistem pernafasan. Penyakit kronik merupakan salah satu penyebab perawakan pendek atau yang disebut dengan stunting. Anak yang memiliki perawakan pendek apabila tinggi badan berada di bawah – 2 Standar Deviasi (SD) atau di bawah persentil kurva pertumbuhan sesuai usia dan jenis kelamin. Tujuan penelitian ini adalah mendeskripsikan anak dengan stunting dan menganalisis hubungan penyakit saluran pernafasan dengan stunting pada anak, metode penelitian ini menggunakan desain kuantitatif dengan pendekatan korelatif analitik, jumlah populasi 198 teknik pengambilan data total sampling di 22 Posyandu Kelurahan Sidanegara Cilacap. Hasil penelitian menunjukkan sebagian besar berjenis kelamin laki-laki (50,5%), usia balita (mean= 32 bulan, SD= 12,), Berat Badan (mean= 10,7 Kg, SD= 2,1), Tinggi Badan (mean= 81,7 cm, SD= 10,97). Stunting pendek (80,3%) dan sangat pendek (19,7%). Anak dengan Pneumonia (0,5%) dan Batuk Bukan Pneumonia (95,5%). Hasil uji analisis korelasi didapatkan data tidak ada hubungan yang bermakna antara jenis kelamin (pv= 0,914; α= 0,05), usia (pv= 0,599; α= 0,05) dan penyakit kronis sistem pernafasan dengan anak stunting (pv= 0,620; α= 0,05).

Genetics of Growth Disorders-Which Patients Require Genetic Testing?

The second 360° European Meeting on Growth Hormone Disorders, held in Barcelona, Spain, in June 2017, included a session entitled Pragmatism vs. Curiosity in Genetic Diagnosis of Growth Disorders, which examined current concepts of genetics and growth in the clinical setting, in terms of both growth failure and overgrowth. For patients with short stature, multiple genes have been identified that result in GH deficiency, which may be isolated or associated with additional pituitary hormone deficiencies, or in growth hormone resistance, primary insulin-like growth factor (IGF) acid-labile subunit deficiency, IGF-I deficiency, IGF-II deficiency, IGF-I resistance, and primary PAPP-A2 deficiency. While genetic causes of short stature were previously thought to primarily be associated with the GH–IGF-I axis, it is now established that multiple genetic anomalies not associated with the GH–IGF-I axis can result in short stature. A number of genetic anomalies have also been shown to be associated with overgrowth, some of which involve the GH–IGF-I axis. In patients with overgrowth in combination with an intellectual disability, two predominant gene families, the epigenetic regulator genes, and PI3K/AKT pathway genes, have now been identified. Specific processes should be followed for decisions on which patients require genetic testing and which genes should be examined for anomalies. The decision to carry out genetic testing should be directed by the clinical process, not merely for research purposes. The intention of genetic testing should be to direct the clinical options for management of the growth disorder.

Growth Assessment and Vitamin D Level in Egyptian Juvenile Idiopathic Arthritis Patients

Background Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in childhood and is frequently associated with growth retardation. Vitamin D is critical to bone mineral metabolism and to the growth and development of the skeleton. We aimed to evaluate growth pattern and Vitamin D level in patients with JIA and its different subtypes. Materials and Methods 80 JIA patients and 80 healthy controls were included. For all patients and controls we assessed body weight, standing height, body mass index (BMI), Serum 25(OH) D3. Thyroid function tests were assessed to exclude patients with hypothyroidism or autoimmune thyroiditis, liver and renal function tests, calcium, phosphorus, alkaline phosphatase, fasting blood sugar were done to evaluate other causes of short stature. Results JIA patients' mean height, weight, and BMI were significantly lower compared to controls (135.4±22.1 vs. 145.7±21.8, p=0.042 for height), (34.6±13.6 vs. 39.8±11.4, p=0.039 for weight) and (18.52±3.96 vs. 21.73±5.43, p= 0.041 for BMI). Mean serum 25(OH) D3 level was significantly lower in JIA patients than controls (15.69±6.6 ng/ml vs. 31.62±4.9 ng/ml, p<0.0001), patients with systemic onset and seropositive polyarthritis (RF positive) have the lowest 25(OH) D3 level compared with other JIA subtypes. There was significant negative correlation between steroid dose, duration and JIA patients' height (r= -0.456, p=0.017 and r=-0.776, p=0.001 respectively). Serum 25 (OH) D3 level was significantly correlated with patients' height and BMI (r=0.33, p=0.029 and r=0.32, p=0.043). Conclusion The nutritional status of JIA patients is multi-factorial. Onset subtype and low level of vitamin D were found to have an effect on growth parameters as height and body mass index in patients with juvenile idiopathic arthritis.

Characteristics and etiologies of short stature in children: Experience of an endocrine clinic in a Tunisian tertiary care hospital.

BackgroundShort stature is a common reason for referral to pediatric endocrinology clinics. It may be a manifestation of a pathological condition requiring early treatment. The aim of this study was to describe the characteristics and etiologies of short stature among children referred to the pediatric endocrinology clinic of the main pediatric tertiary care center in Tunisia.MethodsRetrospective and descriptive study in the endocrinology unit of children referred for short stature between January 2012 and December 2016. Data on the patients' medical history, physical findings, laboratory tests, bone age and chromosomal analysis were collected.Results470 children (266 males and 204 females) were referred during that period. 214 (45.5%) had normal height, and 80.8% of them were referred by general practitioners. The other 256 children (54.5%) had a confirmed short stature (mean age :7.2 years, mean height: -2.77 SDS). Endocrinological causes were the most common(43% GHD, 4% hypothyroidism) followed by intrauterine growth retardation IUGR (24%), genetic syndromes (8.4%), chronic pediatric diseases (7.8%), skeletal dysplasia (6.2%), normal variant of short stature (5%), and psychosocial deprivation (1.2%). Among non-endocrine causes, Turner syndrome was the most common genetic syndrome (4.4%), achondroplasia the main skeletal dysplasia (4%) and celiac disease the main chronic disease (3.4%).ConclusionsST is largely overestimated in our country. Therefore, it is important to insist on adequate measurement and analysis of growth parameters to avoid unnecessary investigations. GHD and IUGR were the most common causes. Celiac disease, though frequent in Tunisia, is not a common cause of short stature.

Evaluation of SHOX defects in the era of next-generation sequencing.

Short stature homeobox (SHOX) haploinsufficiency is a frequent cause of short stature. Despite advances in sequencing technologies, the identification of SHOX mutations continues to be performed using standard methods, including multiplex ligation-dependent probe amplification (MLPA) followed by Sanger sequencing. We designed a targeted panel of genes associated with growth impairment, including SHOX genomic and enhancer regions, to improve the resolution of next-generation sequencing for SHOX analysis. We used two software packages, CONTRA and Nexus Copy Number, in addition to visual analysis to investigate the presence of copy number variants (CNVs). We evaluated 15 patients with previously known SHOX defects, including point mutations, deletions and a duplication, and 77 patients with idiopathic short stature (ISS). The panel was able to confirm all known defects in the validation analysis. During the prospective evaluation, we identified two new partial SHOX deletions (one detected only by visual analysis), including an intragenic deletion not detected by MLPA. Additionally, we were able to determine the breakpoints in four cases. Our results show that the designed panel can be used for the molecular investigation of patients with ISS, and it may even detect CNVs in SHOX and its enhancers, which may be present in a significant fraction of patients.

Estimation of Serum Zinc Levels in Children with Short Stature

Background: Factors affecting malnutrition in toddlers include genetics, hormones, gender, infectious diseases, and chronic diseases. Nutritional factors that cause stunting include low intake of energy, protein, and micronutrients such as iron, vitamin A, and zinc. Objective: the aim of this study was to estimate the relation between serum zinc levels and short stature among children. Patients and methods: our study included 50 children with short stature (Group I), and 30 children with normal stature as a control group (Group II). Any children with possible genetic, endocrinological cause of short stature, severe nutritional insufficiency, age beyond the 2-10 years range or having any chronic illness or infections were excluded from the study. Results: we found non-significant relations between serum zinc and demographic characteristics among group I cases. Also, we found non-significant relations between serum zinc and anthropometric measures (weight, BMI and head circumference) among group I cases. On the other hand, we found a positive and significant relation between serum zinc level and both of height and height percentile. Also, pallor was associated with significantly lower levels of serum zinc. We found non-significant relations between serum zinc and laboratory investigations among group I cases. The only exception was the moderate positive highly significant correlation between HB and serum zinc level. Conclusion: our study concluded that lower serum zinc level is associated with short stature among preschool children, and is also associated with more anemia, and lower WBCs count.

Estimation of Serum Zinc Levels in Children with Short Stature

Background: Factors affecting malnutrition in toddlers include genetics, hormones, gender, infectious diseases, and chronic diseases. Nutritional factors that cause stunting include low intake of energy, protein, and micronutrients such as iron, vitamin A, and zinc. Objective: the aim of this study was to estimate the relation between serum zinc levels and short stature among children. Patients and methods: our study included 50 children with short stature (Group I), and 30 children with normal stature as a control group (Group II). Any children with possible genetic, endocrinological cause of short stature, severe nutritional insufficiency, age beyond the 2-10 years range or having any chronic illness or infections were excluded from the study. Results: we found non-significant relations between serum zinc and demographic characteristics among group I cases. Also, we found non-significant relations between serum zinc and anthropometric measures (weight, BMI and head circumference) among group I cases. On the other hand, we found a positive and significant relation between serum zinc level and both of height and height percentile. Also, pallor was associated with significantly lower levels of serum zinc. We found non-significant relations between serum zinc and laboratory investigations among group I cases. The only exception was the moderate positive highly significant correlation between HB and serum zinc level. Conclusion: our study concluded that lower serum zinc level is associated with short stature among preschool children, and is also associated with more anemia, and lower WBCs count.

A review of growth hormone deficiency

Abstract Growth hormone deficiency (GHD) is a rare but important cause of short stature in children. It is treatable. However, diagnosis is challenging and often requires referral to a specialist paediatric endocrinologist to facilitate testing and the interpretation of results. Careful history and examination with meticulous auxology data are critical components of the initial evaluation in clinic. Thereafter, further investigations are required to exclude other causes of short stature, and to establish the diagnosis. It is a highly variable condition and to an extent the clinical features depend upon the severity of GHD itself. GH stimulation tests may be indicated in the short child who is growing slowly and who has low growth factor concentrations. There is, however, no consensus with respect to a diagnostic gold standard test for GHD, and this is usually based upon a combination of clinical, biochemical, and neuroradiological data, although molecular diagnosis may aid in years to come. This short article gives an overview of the importance of GHD and offers advice on how to take a history, conduct and examination and begin investigation for a child with suspected GHD. It discusses the known benefits and potential risks of treatment and offers practical advice for the generalist.

Growth hormone peak modifies the effect of BMI on increased systolic blood pressure in children with short stature

Blood pressure (BP), especially systolic BP (SBP), is higher in adult growth hormone deficiency (AGHD) patients than in normal controls. Additionally, obesity is a known risk factor for hypertension, and growth hormone deficiency (GHD) is an important cause of short stature. For children with GHD, attention has been directed solely towards height. Few studies have assessed its potential impact on BP. Here, we investigated the effect of body mass index standard deviation score (BMISDS) on BP in children with short stature. This study included 736 children with short stature divided into two groups based on peak growth hormone (GH) level in GH provocation tests [severe GHD (SGHD) group = 212 children; non-SGHD group = 524 children]. We found that SBP was significantly higher in the SGHD group than in the non-SGHD group (p = 0.045). Additionally, there was a significant positive association between BMISDS and SBP in the SGHD group (β = 3.12, 95% CI: 1.40–4.84, p < 0.001), but no association between these variables was observed in the non-SGHD group. Thus, SGHD patients had a higher SBP than non-SGHD patients. BMISDS is a significant factor for higher SBP in SGHD patients but not in non-SGHD patients.

The Miller-McKusick-Malvaux syndrome: a rare cause of short stature

The Miller-McKusick-Malvaux syndrome: a rare cause of short stature

The Relevance of Insulin-like Growth Factor-1 Concentration as a Screening Test for Diagnosis of Growth Hormone Deficiency

Objective: Growth hormone deficiency (GHD) is one of the most important endocrine and treatable causes of short stature. Insulin-like growth factor 1 (IGF-1) concentration is not recommended to establish the diagnosis of GHD. The aim of our study was to analyze the relevance of IGF-1 concentration as a screening test for the diagnosis of GHD. Materials and Methods: We retrospectively studied patients who were evaluated for short stature at the Endocrinology Department of King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia from January 2015 to December 2018. For IGF-1, laboratory reference ranges were based on age and sex. For all eligible patients, IGF-1 concentration was determined and an ITT was performed. Patients with a peak GH of ≤ 5.0 ng/ml were considered to be GHD and patients with a peak GH of ≥ 5.1 ng/ml were considered non-GHD (nGHD). Results: We retrospectively included 47 patients for analysis. Mean age was 14.7 ± 1.7 years. There were 38 males (80.9%) and 9 females (19.1%) and mean IGF-1 concentration was 146.4 ± 69.4 ng/dl. Results from the ITT indicated that 27 (57.4%) had GHD. Age was not significantly different between GHD and non-GHD (14.7 ± 1.8 vs. 14.8 ± 1.6 years, P = 0.9). There were non-significantly more males than females in GHD patients (59% vs. 50%, P = 0.7). Mean IGF-1 concentration was not significantly different (146.9 ± 70.4 ng/dl vs. 145.7 ± 69.8 ng/dl, P = 0.9). IGF-1 concentration below the reference ranges for age and gender was non-significantly higher in patients with GHD compared to non-GHD (53.8% vs. 46.2%, P = 0.8). The mean peak for GH concentration was significantly lower in patients with GHD (2.2 ± 1.3 ng/ml vs. 9.9 ± 5.6 ng/ml, P &lt; 0.0001). Peak GH concentration was not significantly correlated with IGF-1 concentration (r = 0.213, P = 0.2). We plotted a ROC curve of IGF-1 concentration according to the diagnosis of GHD as established using ITT. The AUC was 49%. An IGF-1 threshold of 154 ng/dl was selected to emphasize sensitivity rather than specificity. With a threshold of 154 ng/dl, sensitivity was 52% (95% confidence interval (95% CI); 32%, 71%), specificity was 40% (95% CI; 19%, 64%) and the negative predictive value for the diagnosis of GHD was 38% (95% CI; 24%, 54%). With a threshold of 105 ng/dl, the sensitivity was 41% and the specificity was 70%. A threshold of 74 ng/dl, gave a positive predictive value of 60% but a negative predictive value of 43%. 7 of the patients with IGF-1 concentration above the threshold of 154 ng/dl (N = 20) were normal and 13 had GH deficiency. These 13 GHD patients had IGF-1 concentration that differs significantly from those of their GH-sufficient counterparts (105 ± 35 vs. 222 ± 49 ng/dl, P &lt; 0.0001). If IGF-1 was used as a screening test (with a concentration threshold of 154 ng/dl) and ITT as a confirmatory test, 20 (43%) out of 47 ITT would not have been performed, leading to the misdiagnosis of 13 GH-deficient adults. Thus, in our study population, such a procedure would misdiagnose 13 out of 27 GHD patients (48%) and yield a sensitivity of 52%. Conclusion: Many reports have already reported that IGF-1 concentration is lower in patients with GHD than in the general population, our study demonstrated the poor negative predictive value of IGF-1 concentration for the diagnosis of GHD, making it the need of the use of the “gold standard” method ITT. This observation remains to be validated by population-based studies.