Serum HMGB1 levels are independently associated with glucose clamp-derived measures of insulin resistance in women with PCOS.

PURPOSE: PCOS is associated with low grade inflammation which could play a role in insulin resistance and ovarian dysfunction. Preliminary findings suggested that serum levels of HMGB1, a cytokine involved in inflammation, might be altered in women with PCOS. Primary aim of this study was to assess whether HMGB1 serum concentrations are associated with PCOS and with the state of insulin resistance of these women. METHODS: Sixty women with PCOS, selected to have a similar proportion of subjects with altered or normal insulin sensitivity, and 29 healthy controls were studied. Serum HMGB1 levels were compared in subgroups of PCOS women and controls. In PCOS women, insulin sensitivity was assessed by the glucose clamp technique and HMGB1 was measured at baseline and after acute hyperinsulinemia. RESULTS: HMGB1 levels were similar in women with PCOS and controls and no elements used for diagnosing PCOS were associated with serum HMGB1. However, HMGB1 concentrations were higher in insulin-resistant vs insulin-sensitive PCOS women (p = 0.017), and inversely associated with insulin-induced total and non-oxidative glucose metabolism. In both subgroups of PCOS women, serum HMBG1 levels significantly increased after acute hyperinsulinemia. CONCLUSIONS: These data suggest that HMGB1 levels are not associated with PCOS per se, but with insulin resistance. Further research should establish the underlying nature of this relationship, and whether this protein might play a role in the metabolic complications of PCOS.

Cancer Decedents' Hospital End-of-Life Care Documentation: A Retrospective Review of Patient Records.

Objective: International standards of end-of-life care (EOLC) intend to guide the delivery of safe and high-quality EOLC. Adequately documented care is conducive to higher quality of care, but the extent to which EOLC standards are documented in hospital medical records is unknown. Assessing which EOLC standards are documented in patients' medical records can help identify areas that are performed well and areas where improvements are needed. This study assessed cancer decedents' EOLC documentation in hospital settings. Methods: Medical records of 240 cancer decedents were retrospectively evaluated. Data were collected across six Australian hospitals between 1/01/2019 and 31/12/2019. EOLC documentation related to Advance Care Planning (ACP), resuscitation planning, care of the dying person, and grief and bereavement care was reviewed. Chi-square tests assessed associations between EOLC documentation and patient characteristics, and hospital settings (specialist palliative care unit, sub-acute/rehabilitation care settings, acute care wards, and intensive care units). Results: Decedents' mean age was 75.3 years (SD 11.8), 52.0% (n = 125) were female, and 73.7% lived with other adults or carers. All patients (n = 240; 100%) had documentation for resuscitation planning, 97.6% (n = 235) for Care for the Dying Person, 40.0% for grief and bereavement care (n = 96), and 30.4% (n = 73) for ACP. Patients living with other adults or carers were less likely to have a documented ACP than those living alone or with dependents (OR 0.48; 95% CI 0.26-0.89). EOLC documentation was significantly greater in specialist palliative care settings than that in other hospital settings (P < .001). Conclusion: The process of dying is well documented among inpatients diagnosed with cancer. ACP and grief and bereavement support are not documented enough. Organizational endorsement of a clear practice framework and increased training could improve documentation of these aspects of EOLC.

Role of Wnt-signaling inhibitors DKK-1 and sclerostin in bone fragility associated with Turner syndrome.

PURPOSE: Girls affected with Turner syndrome (TS) present with low bone mineral density (BMD) and osteopenia/osteoporosis. Thus, they have an increased risk to develop fractures compared to normal population. The aim of this study was to deepen the pathophysiology of skeletal fragility in TS subjects by evaluating the serum levels of Dickkopf-1 (DKK-1) and sclerostin, main regulators of bone mass, as well as the percentage of circulating osteoblast precursors (OCPs). METHODS: Thirty-four TS girls and 24 controls were recruited. All subjects underwent anthropometric measures (height, weight, body mass index-BMI). A peripheral venous blood sample was collected to determine serum levels of active intact parathyroid hormone (PTH), 25-OH vitamin D, calcium, phosphorus, bone alkaline phosphatase (bALP), osteocalcin, sclerostin, DKK-1, RANKL and OPG. OCPs were detected by flow cytometry. In TS subjects bone mineralization was measured at lumbar spine by dual energy X-ray absorptiometry (DXA). RESULTS: bALP, 25-OH Vitamin D, and osteocalcin levels were significant lower in TS subjects than in the controls. Statistically significant higher levels of sclerostin, DKK-1 and RANKL were measured in patients compared with the controls. The percentage of OCPs did not show significant differences between patients and controls. Sclerostin and DKK-1 levels were related with anthropometric parameters, bone metabolism markers, HRT, rhGH therapy, RANKL and lumbar BMAD-Z-score. CONCLUSION: TS patients showed higher levels of sclerostin and DKK-1 than controls which can be related to HRT, and to reduced bone formation markers as well as the increased bone resorption activity.

Service use by older very frequent emergency department users: A retrospective cohort study.

BACKGROUND: Frequent Emergency Department (ED) attendance is a common occurrence, across all patient age groups. Older frequent users of ED are an at-risk group who often have complex, chronic health needs with many requiring out-of-hospital services to support their care. The aim of this study is to identify the characteristics, outcomes and health service use of older, very frequent emergency department (ED) users. METHODS: A retrospective cohort study, at three Australian EDs, comparing first and last ED attendances, by older people (≥65 years) with frequent ED use (≥8 attendances/year). RESULTS: There were 1387 ED attendances in 12 months by 115 patients (median=11). The median age-adjusted Charlson comorbidity score increased between attendances (5 vs 6, p<0.001). From first to last visit, hospital stays exceeding 7 days increased (12% vs 20%, p=0.013), while both ED re-attendances within 28 days (58% vs 20%, p≤0.001) and hospital readmissions within 30 days (39% vs 23%, p=0.016) decreased. In-patient mortality was 11% (n=10/88). There was no change in out-of-hospital services in place at both ED attendances (55% vs 61%, p=0.185). CONCLUSIONS: Out-of-hospital service use did not change despite frequent ED attendance. Older very frequent ED users had increasing co-morbidities over time and often required hospital admission.

Magnetization at the interface of Cr2O3 and paramagnets with large stoner susceptibility.

From the Cr 2p3/2 x-ray magnetic circular dichroism signal, there is clear evidence of interface polarization with overlayers of both Pd and Pt on chromia (Cr2O3). The residual boundary polarization of chomia is stronger for a Pt overlayer than in the case of a Pd overlayer. The reduction of chromia boundary magnetization with a paramagnetic metal overlayer, compared to the free surface, is interpreted as a response to the induced spin polarization in Pt and Pd. Magnetization induced in a Pt overlayer, via proximity to the chromia boundary magnetization, is evident in the polar magneto-optical Kerr measurements. These results are essential to explainations why Pt and Pd are excellent spacer layers for voltage controlled exchange bias, in the [Pd/Co] n /Pd/Cr2O3 and [Pt/Co] n /Pt/Cr2O3 perpendicular magneto-electric exchange bias systems. The findings pave the way to realize ultra-fast reversal of induced magnetization in a free moment paramagnetic layer, with possible application in voltage-controlled magnetic random access memory.

The oldest case yet reported of osteoarthritis in a dog: an archaeological and radiological evaluation.

A century ago the remains of a dog skeleton were found in an archaeological double human burial, near Bonn-Oberkassel (Germany). Recent re-examination of the dog remains revealed that they were about 14,500 years old. Based on the growth plates, the animal was considered to be approximately 7·5 months old at the time of death. Based on the minimal humeral diameter, it was calculated that it was approximately 0·47 m tall at the shoulder and weighed approximately 15·7 kg. The right proximal ulna of this skeleton showed osteoarthritis, manifested by an osteophyte of 5×3×1·5 mm3 at its cranial edge, with no identified primary developmental causes for osteoarthritis. Osteochondritis dissecans, joint incongruity and trauma are possible aetiologies. The left ulna did not reveal any abnormalities.

Associations between two single nucleotide polymorphisms of the adiponectin gene, its circulating concentrations and cardiometabolic risk factors in prepubertal children with and without abdominal obesity.

BACKGROUND: The adiponectin gene has been identified as a susceptibility locus for metabolic syndrome, diabetes and cardiovascular disease. AIM: To examine the influence of two single nucleotide polymorphisms (SNPs) of this gene (+276G>T and +45T>G) on circulating adiponectin concentrations, and to evaluate their relationship with adiposity and cardiometabolic risk factors in prepubertal children with and without abdominal obesity. MATERIAL AND METHODS: 168 children (78M, 6-10 yr) were examined, divided into three groups based on waist circumference (WC). Auxological and biochemical parameters were measured by standard procedures. Adiponectin SNPs were genotyped using TaqMan allelic discrimination assays. RESULTS: Adiponectin concentration correlated inversely with measures of adiposity (rBMIz-score=-0.211, pBMIz-score=0.007; rwc=-0.210, pwc=0.008; rwc/height=-0.215, pwc/height=0.006), and was significantly influenced by blood glucose, insulin and systolic blood pressure (SBP). The +276T-allele carriers had higher SBP and diastolic BP compared to GG-homozygotes (p<0.05), and expressed higher obesity-related measures and lower adiponectin concentrations. As to the +45T>G SNP, the GGsubject had higher total cholesterol and LDL-C concentrations compared to the T-allele carriers (p<0.05), showing worse obesity measures, higher triglyceride, glucose and insulin and lower serum adiponectin values. CONCLUSION: Genetic variants of the adiponectin gene had an impact on adiposity, adiponectin concentrations and some cardiometabolic variables among prepubertal children.

Interactions among pro-inflammatory cytokines, IGF system and thyroid function in pre-pubertal obese subjects.

Obesity is a state of chronic inflammation. Data on IGF system are often discrepant, and their relationships with mediators of inflammation are unknown. Furthermore, changes in thyroid function have been reported. We aimed at investigating the changes in these systems, and verify any relationships among cytokines, IGF system, thyroid function and insulin-insensitivity. Fifty obese pre-pubertal children, and 55 normal-weight subjects comparable for age and sex were enrolled. Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, IL-6 and TNF-alpha were assayed. In obese children insulin, TSH and FT4 were measured also, and the HOMA-IR index was calculated. Increased IGF-II, IL-6 and TNF-alpha, and decreased IGFBP-1 and IGFBP-2 concentrations were found in obese compared to normal-weight children. The IGF-I/IGFBP-3 molar ratio was also reduced in the obese subjects. In the obese children with high HOMA-IR index, IGFBP-1 and -2 serum concentrations were significantly decreased compared with those with normal insulin sensitivity, and in the obese subjects with increased TSH, IGFBP-2 concentrations were lower, and IGFBP-3 levels were higher compared to their counterparts with normal TSH levels. Among the significant correlations, BMISDS was correlated with IGF-II, and TSH. IGF-II concentrations showed a positive relationship with IL-6. TSH was correlated with IGFBP-2 also. The data showed interactions among IL-6, IGF system, insulin sensitivity, and thyroid function with changes being related to the degree of obesity. Chronic inflammation in obese children was confirmed. Some of the changes in the IGF system could be a consequence of insulin resistance and could account also for later complications in obese subjects.

Association of placental insulin, total and activated insulin receptor contents, cortisol and IL-6 concentrations with human birth weight and length: pilot study.

We followed-up, from pregnancy to birth, a group of newborns both IUGR and AGA and we aimed at establishing placental biochemical determinants of birth weight and length. Insulin, total and activated insulin receptor contents (IR), cortisol and IL-6 placental concentrations were assayed in 23 IUGR and 37 AGA subjects at birth, and a multiple regression model was designed and applied to assess the significant biochemical determinants of birth size. IL-6 and activated insulin receptor content were significantly increased in IUGR, whereas insulin, total insulin receptor content, and cortisol placental concentrations were similar in IUGR and AGA. Placental cortisol concentration was found to be significantly and negatively related with both birth length (0.778, P<0.001) and weight (0.508, P<0.008). A negative effect of IL-6 placental concentration was found on birth length (P<0.002). For the first time we provide evidence of a negative association of placental cortisol and IL-6 concentrations on birth size.

Placental cortisol and cord serum IGFBP-2 concentrations are important determinants of postnatal weight gain.

There is a need to identify simple biochemical markers at birth that may predict subjects at risk of growth failure and metabolic complications in later life. Limited research to date has been performed on relationships of specific biochemical determinants at birth with postnatal weight gain and growth. We proposed to establish whether placental cortisol and IL-6 concentrations and cord serum IGF-II and IGFBP-2 concentrations influenced postnatal growth. We followed up from pregnancy 23 IUGR and 37 AGA subjects, and determined placental cortisol and IL-6 concentrations, and cord serum IGF-II, and IGFBP-2 concentrations at birth. We obtained height and weight measurements at 3, 6, 12, 24 months and 5 years of age in 20 IUGR and 15 AGA subjects of comparable gestational age. A multiple linear regression model was designed to establish the effect of the placental and cord serum peptides on postnatal linear growth and weight gain. All IUGR subjects had catch-up growth before 2 years of age. Placental cortisol concentration correlated positively with weight gain during the first 5 years of postnatal growth (P<0.05). Subjects with the highest placental cortisol concentrations were those who showed a greater increase in weight. Cord serum IGFBP-2 concentrations correlated positively with weight gain throughout the 5 year observation period (P:0.003). The subjects with the highest concentrations showed a greater weight gain. Placental cortisol and cord serum IGFBP-2 concentrations were related to postnatal weight gain, suggesting that the fetal environment has long-term effects on growth.

Insulin production and resistance in cystic fibrosis: effect of age, disease activity, and genotype.

AIM: To assess the major determinants of glucose tolerance between age, genotype, and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF-related diabetes (CFRD). SUBJECTS AND METHODS: One hundred and nineteen patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. Homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose/insulin ratio (FGIR) were calculated as indices of IR and insulinogenic index as a marker of pancreatic ß-cell function. All patients underwent an oral glucose tolerance test, and 57 underwent an IVGTT for the calculation of first-phase (FPIR) and acute insulin responses (AIR). RESULTS: The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMAIR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses, glucose tolerance was related to the agegroup, and to the HOMA-IR and insulinogenic indexes. CONCLUSIONS: IGT and CFRD were related mainly to genotype, although, as expected, the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, ß-cell function, and reduced insulin sensitivity to the onset of CFRD; however, further studies are warranted to better elucidate this aspect.

A systems biology approach: new insights into fetal growth restriction using Bayesian Networks.

IL-6, IGF-II and IGFBP-2 concentrations in placental lysates were previously shown to be associated with foetal growth. This study aimed to apply a Bayesian Network (BN) model in order to investigate complex dependencies among biochemical and clinical factors and fetal growth outcome. Twenty-one Intra-Uterine Growth Restricted (IUGR) and 25 Appropriate for Gestational Age (AGA) pregnancies were followed throughout pregnancy. Information was collected on maternal and gestational age, neonatal gender, previous gynaecological history. Total protein content, IGF-II, IGFBP-1, IGFBP-2, IL-6, and TNF-alpha concentrations in placental lysates were measured, and IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6 relative gene expression in placenta assessed. A BN and a hybrid forecasting system were implemented: BN revealed a key role of maternal age and TNF-alpha on IUGR and confirmed a close relationship among IGF-II, IL-6 and foetal growth. A relationship between duration of gestation, appropriateness for gestational age, and placental IL-6 concentration was also confirmed. Compared with other techniques, BN showed a better accuracy. Findings confirmed a major role of maternal age in addition to IGF-II, IL-6 and TNF-alpha in IUGR. A direct role of IGFBP-2 was not shown. BN confirmed to be useful in understanding the system's biology and graphically representing variable relationships and hierarchy, particularly where, as in IUGR, many interactions among predictors exist.

Impairment of insulin receptor signal transduction in placentas of intra-uterine growth-restricted newborns and its relationship with fetal growth.

OBJECTIVE: Intra-uterine growth restriction (IUGR) is related to a higher incidence of type 2 diabetes mellitus. We previously reported reduced adiponectin and increased interleukin 6 (IL6) concentrations in IUGR placentas, which are features of insulin resistance. We aimed to investigate placental insulin receptor (IR) function and activation in human placenta and subsequently the relationships of insulin signalling peptides with placental protein content in IL6, insulin, resistin and adiponectin, and with parameters of fetal growth. DESIGN AND METHODS: Whole villous tissue was collected from 18 IUGR and 24 appropriate for gestational age (AGA) placentas of comparable gestational age. Insulin signalling peptides, suppressors of cytokine signalling-2 (SOCS2), insulin, adiponectin, resistin, and IL6 concentrations were determined by using western immunoblotting or specific research kits. RESULTS: The amount of total IR was similar in both groups but activated IR significantly higher in IUGR. Total IR substrate-1 (IRS1) was increased in IUGR, whereas total IRS2 and activated IRS1 were similar. AKT content was reduced and activated AKT was undetectable in IUGR placentas. c-Jun N-terminal kinase content was reduced in IUGR. Total and activated ERK1/2 was similar in IUGR and AGA groups, and total SOCS2 was increased in IUGR. IL6 lysate concentrations correlated with AKT content and activated IR. Correlations were found also with adiponectin and resistin. SOCS2 correlated negatively with all growth parameters at birth. CONCLUSIONS: IR was more activated in placentas of IUGR compared with AGA; however, signal transduction downstream of the receptor was impaired. The increase in activated IR could be in favour of a compensatory mechanism to increase insulin sensitivity. Close relationships of insulin action in placenta with fetal growth were shown.

The Pathfinder image-guided surgical robot.

This paper first describes the workflow of the Pathfinder image-guided surgical robot that has been designed to replace the stereotactic frame in neurosurgery, and then details the calibration stages employed in order to achieve submillimetre positioning accuracy of a tool tip. The process uses non-linear parameter identification techniques in conjunction with some procedures for camera calibration, which exploit the fact that the camera is mounted to a calibrated robot arm that executes precise motions.

Initial experience in 115 patients with the retrievable Cook Celect vena cava filter.

The aim of this study was to evaluate our experience with the retrievable Cook Celect inferior vena cava (IVC) filter (William Cook, Europe) with regard to insertion, efficiency, ease of retrieval, and any associated complications. A retrospective review was performed of 115 patients (41 female, 74 male, mean age 47.97 years) who underwent Cook Celect IVC filter insertion between December 2005 and October 2007. Filter insertion was successful in all patients. Of the 115 filters inserted, 57 have been successfully retrieved (49.6%) to date. The successful retrieval rate from attempted retrieval was 93.4%. The mean dwell time of successfully retrieved filters was 114.9 days (range 14-267 days). Failed retrievals were due to a thrombosed vena cava (n = 1) and endothelialisation of the filter (n = 3). In the failed retrieval group the mean implantation time was 142 days (range 78-211 days). While this is the first retrospective clinical study on the Cook Celect filter, results to date are promising. We demonstrated an efficacious filter with a high successful retrieval rate of 93.4% and a low complication rate. The filter was assessed with extended dwell times (range 14-267 days). Failed retrieval secondary to hook endothelialisation continues to be an issue with this filter. We recognize that a limitation of our study was the lack of systematic follow-up for clinically silent complications. Further studies to evaluate longer term outcomes and effectiveness of this filter are warranted.

Radiation exposure and the justification of computed tomography scanning in an Australian hospital emergency department.

In an emergency department (ED), computed tomography (CT) is particularly beneficial in the investigation of high-speed trauma patients. With the advent of multidetector CT (MDCT) scanners, it is becoming faster and easier to conduct scans. In recent years, this has become evident with an increasing number of CT requests. Patients who have multiple CT scans during their hospital stay can receive radiation doses that have an increased theoretical risk of induction of cancer. It is essential that the clinical justification for each CT scan be considered on an individual basis and that due consideration is given to the radiation risk and possible diagnostic benefit. The current lack of a central State or Commonwealth data repository for medical images is a contributing factor to excessive radiation dosage to the population. The principles of justification and radiation risks are discussed in this study.

Guidelines for the management of hospital-acquired pneumonia in the UK: report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy.

These evidence-based guidelines have been produced after a systematic literature review of a range of issues involving prevention, diagnosis and treatment of hospital-acquired pneumonia (HAP). Prevention is structured into sections addressing general issues, equipment, patient procedures and the environment, whereas in treatment, the structure addresses the use of antimicrobials in prevention and treatment, adjunctive therapies and the application of clinical protocols. The sections dealing with diagnosis are presented against the clinical, radiological and microbiological diagnosis of HAP. Recommendations are also made upon the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy in HAP/ventilator-associated pneumonia.

Credentialing for radiology.

Patients expect to receive safe, predictable and high-quality care delivered by competent professionals. Thus, it has become important to provide specific training in existing and new modalities and prove on-going clinical expertise. Hospital credentialing is the process by which the competence of a doctor is determined by the hospital management. In Australia, radiologists participate in a mandatory program of continuing professional development and are also required to maintain a logbook of procedures. The Conjoint Committee for the Recognition of Training in Peripheral Endovascular Therapy has been established to advise the respective subspecialty groups on the requirements for accreditation. This article examines some of the issues the committee has considered in preparing the criteria to assist institutions for the purposes of credentialing and gives an Australian perspective on future trends.

Interleukin-6 and insulin-like growth factor system relationships and differences in the human placenta and fetus from the 35th week of gestation.

The integrity of the insulin-like growth factor (IGF) system is essential for normal fetal growth. Cytokine and IGF-IGFBP relationships have been shown in specific tissues, but it is unknown whether these occur in the placenta. We aimed to assess possible differences in the IGF system depending on gestational age (GA) from week 35 to 40, and to study relationships of IL-6 with components of the IGF system in the placenta and newborn infant. We followed 32 normal births and collected whole villous tissue and cord serum. Total RNA was extracted from the placenta samples, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins were assayed in placenta lysates and cord serum using specific commercial kits. Two groups of subjects (Group 1, 35-37 weeks GA, N=12 and Group 2, 38-40 weeks GA, N=20) were studied. In placenta, IGF-I mRNA was more abundant than IGF-II mRNA at all times and together with IGFBP-1mRNA were less expressed at term. IGFBP-2 and IL-6 mRNAs were higher after week 37 GA. IL-6 and IGFBP-2 gene expression were closely related. The corresponding proteins showed similar differences to the genes but IGF-I was undetectable in the lysates, whereas IGF-II was abundant. IGFBP-2 concentrations were very high and greater than those of IGFBP-1. In the newborn, no difference was seen in any cord serum protein after week 35 GA. IGFBP-1 was negatively correlated with parameters of neonatal size. In conclusion, this study reports new insights into IL-6, IGF-IGFBP relationships within the human placenta and shows the importance of comparing subjects with the same GA.

Assessment of serum IGF-I concentrations in the diagnosis of isolated childhood-onset GH deficiency: a proposal of the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP/ISPED).

The diagnosis of GH deficiency (GHD) is based on the measurement of peak GH responses to pharmacological stimuli. Pharmacological stimuli, however, lack precision, accuracy, are not reproducible, are invasive, non-physiological and some may even be hazardous. Furthermore, different GH commercial assays used to measure GH in serum yield results that may differ considerably. In contrast to GH, IGF-I can be measured on a single, randomly-obtained blood sample. A review of the available data indicates that IGF-I measurement in the diagnosis of childhood-onset isolated GHD has a specificity of up to 100%, with a sensitivity ranging from about 70 to 90%. We suggest an algorithm in which circulating levels of IGF-I together with the evaluation of auxological data, such as growth rate and growth, may be used to assess the likelihood of GHD in pre-pubertal children.