Growth Hormone Disorders Research Articles

Probiotic Bacillus amyloliquefaciens C-1 Improves Growth Performance, Stimulates GH/IGF-1, and Regulates the Gut Microbiota of Growth-Retarded Beef Calves.

Growth retardation of calves is defined as a symptom of impaired growth and development, probably due to growth hormone disorder as well as natural and environmental factors in livestock. The growth-promoting effects of probiotics were determined in 50 growth-retarded growth calves. They were supplied with Bacillus amyloliquefaciens C-1 (Ba, 4 × 1010CFU/d, n = 16), B. subtilis (Bs, 4 × 1010CFU/d, n = 18), and negative control (NC, n = 16) for 30 days. Pre- and post-intervention, the growth performance (weight gain rate, feed intake and feed conversion rate) was analyzed, the serum GH, IGH-1 and immunoglobulin levels were assayed, and the fecal microbiota was detected. Calves in Ba and Bs groups demonstrated increased body weight gain, feed intake and GH/IGF-1 levels, as well as a more efficient feed conversion rate, compared with NC group (P < 0.05). Additionally, the abundances of bacteria contributing to the production of energy and SCFAs (short chain fatty acids), including Proteobacteria, Rhodospirillaceae, Campylobacterales, and Butyricimonas were increased compared with NC group (P < 0.05, FDR < 0.1); and the suspected pathogens, which included Anaeroplasma and Acholeplasma were decreased (P < 0.05, FDR < 0.1) in both the Bs and Ba groups. Akkermansia, which is involved in the intestinal mucosal immune response, was increased in Bs group after intervention (P < 0.05, FDR < 0.1), but exhibited no obvious difference in Ba group. The increased bacterial genera in Ba group were Sphaerochaeta and Treponema (P < 0.05, FDR < 0.1). These results indicate that the probiotics B. amyloliquefaciens and B. subtilis exhibited similar therapeutic potential in terms of growth performance by regulating hormones, and improving the intestinal and rumen development in growth-retarded animals.

Classification of Patients With GH Disorders May Vary According to the IGF-I Assay.

Insulinlike growth factor I (IGF-I) measurement is essential for the diagnosis and management of growth hormone (GH) disorders. However, patient classification may vary substantially according to the assay technique. We compared individual patient data and classifications obtained with six different IGF-I assay kits in a group of patients with various GH disorders. In this cross-sectional study, we measured IGF-I with six immunoassays in 102 patients with active or treated acromegaly or GH deficiency. IGF-I normative data previously established for the same six assay kits were used to classify the patients (high, low, or normal IGF-I levels), using both raw data and standard deviation scores (SDSs). Pairwise concordance between assays was assessed with Bland-Altman plots and with the percentage of observed agreement and the weighted κ coefficient for categorized IGF-I SDS. We observed marked variability both across each individual's IGF-I raw data and across IGF-I SDS values obtained with each of the six immunoassays. Pairwise concordance between assay values, as assessed with the weighted κ coefficient, ranged from 0.50 (moderate) to 0.81 (excellent). Even when using normative data obtained in the same large population of healthy subjects and when using calculated IGF-I SDSs, agreement among IGF-I assay methods is only moderate to good. Differences in assay performance must be taken into account when evaluating and monitoring patients with GH disorders. This argues for the use of the same IGF-I assay for a given patient throughout follow-up.

Quantitative and Selective Analysis of Feline Growth Related Proteins Using Parallel Reaction Monitoring High Resolution Mass Spectrometry.

Today immunoassays are widely used in veterinary medicine, but lack of species specific assays often necessitates the use of assays developed for human applications. Mass spectrometry (MS) is an attractive alternative due to high specificity and versatility, allowing for species-independent analysis. Targeted MS-based quantification methods are valuable complements to large scale shotgun analysis. A method referred to as parallel reaction monitoring (PRM), implemented on Orbitrap MS, has lately been presented as an excellent alternative to more traditional selected reaction monitoring/multiple reaction monitoring (SRM/MRM) methods. The insulin-like growth factor (IGF)-system is not well described in the cat but there are indications of important differences between cats and humans. In feline medicine IGF–I is mainly analyzed for diagnosis of growth hormone disorders but also for research, while the other proteins in the IGF-system are not routinely analyzed within clinical practice. Here, a PRM method for quantification of IGF–I, IGF–II, IGF binding protein (BP) –3 and IGFBP–5 in feline serum is presented. Selective quantification was supported by the use of a newly launched internal standard named QPrEST™. Homology searches demonstrated the possibility to use this standard of human origin for quantification of the targeted feline proteins. Excellent quantitative sensitivity at the attomol/μL (pM) level and selectivity were obtained. As the presented approach is very generic we show that high resolution mass spectrometry in combination with PRM and QPrEST™ internal standards is a versatile tool for protein quantitation across multispecies.

The kidneys play a central role in the clearance of rhGH in rats

The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rhGH in non-anesthetized rats, anesthetized rats and in nephrectomized anesthetized rats. Clearance in non-anesthetized rats was 290ml/h/kg. This was reduced to 185ml/h/kg by anesthesia and further reduced to 18ml/h/kg by nephrectomy. As nephrectomy was able to reduce clearance with 90%, we conclude that renal clearance plays a pivotal role in the elimination of rhGH in rats.

Insulin-like growth factor I in cats: validation of an enzyme-linked immunosorbent assay and determination of biologic variation.

Insulin-like growth factor I (IGF-I) measurements are used in veterinary medicine for diagnosing growth hormone disorders. IGF-I assays are subject to interference by IGF-binding proteins (IGFBP) which may not be efficiently removed by standard extraction methods. Adding excess IGF-II during analysis may improve accuracy. The purpose of the study was to validate a commercial human IGF-I ELISA which uses excess IGF-II for feline samples and to evaluate biologic variation. Precision was determined by calculating the coefficient of variation (CV). Accuracy was determined by recovery after removal of IGFBP, addition of IGF-I, and linear dilution after the addition of IGFBP. Biologic variation was determined by repeated sampling in 7 cats. There was interference by IGFBP in the high measuring range, resulting in falsely low IGF-I concentrations. This was overcome by the addition of high concentrations of IGF-II. Untreated serum had a measured/expected ratio of 98-115% compared to serum where IGFBP had been removed. Recovery after the addition of IGF-I was 83-112%. Inter- and intra-assay CVs ranged from 2.4% to 5.0% which is within the minimum acceptance criteria based on biologic variation. The reference interval of IGF-I was wide (90-1207 ng/mL) and there was a significant association between body weight and ln IGF-I (P < .000001). This human ELISA is suitable for feline samples, but interfering IGFBP can cause falsely low concentrations. It is recommended to dilute samples such that IGF-I is < 28 ng/mL on the standard curve to grant for sufficient IGF-II for binding of interferent IGFBP.

Contextualized analysis of a needs assessment using the Theoretical Domains Framework: a case example in endocrinology.

BackgroundThe Theoretical Domains Framework (TDF) is a set of 14 domains of behavior change that provide a framework for the critical issues and factors influencing optimal knowledge translation. Considering that a previous study has identified optimal knowledge translation techniques for each TDF domain, it was hypothesized that the TDF could be used to contextualize and interpret findings from a behavioral and educational needs assessment. To illustrate this hypothesis, findings and recommendations drawn from a 2012 national behavioral and educational needs assessment conducted with healthcare providers who treat and manage Growth and Growth Hormone Disorders, will be discussed using the TDF.MethodsThis needs assessment utilized a mixed-methods research approach that included a combination of: [a] data sources (Endocrinologists (n:120), Pediatric Endocrinologists (n:53), Pediatricians (n:52)), [b] data collection methods (focus groups, interviews, online survey), [c] analysis methodologies (qualitative - analyzed through thematic analysis, quantitative - analyzed using frequencies, cross-tabulations, and gap analysis). Triangulation was used to generate trustworthy findings on the clinical practice gaps of endocrinologists, pediatric endocrinologists, and general pediatricians in their provision of care to adult patients with adult growth hormone deficiency or acromegaly, or children/teenagers with pediatric growth disorders. The identified gaps were then broken into key underlying determinants, categorized according to the TDF domains, and linked to optimal behavioral change techniques.ResultsThe needs assessment identified 13 gaps, each with one or more underlying determinant(s). Overall, these determinants were mapped to 9 of the 14 TDF domains. The Beliefs about Consequences domain was identified as a contributing determinant to 7 of the 13 challenges. Five of the gaps could be related to the Skills domain, while three were linked to the Knowledge domain.ConclusionsThe TDF categorization of the needs assessment findings allowed recommendation of appropriate behavior change techniques for each underlying determinant, and facilitated communication and understanding of the identified issues to a broader audience. This approach provides a means for health education researchers to categorize gaps and challenges identified through educational needs assessments, and facilitates the application of these findings by educators and knowledge translators, by linking the gaps to recommended behavioral change techniques.

Parallel Workflow for High-Throughput (&gt;1,000 Samples/Day) Quantitative Analysis of Human Insulin-Like Growth Factor 1 Using Mass Spectrometric Immunoassay

Insulin-like growth factor 1 (IGF1) is an important biomarker for the management of growth hormone disorders. Recently there has been rising interest in deploying mass spectrometric (MS) methods of detection for measuring IGF1. However, widespread clinical adoption of any MS-based IGF1 assay will require increased throughput and speed to justify the costs of analyses, and robust industrial platforms that are reproducible across laboratories. Presented here is an MS-based quantitative IGF1 assay with performance rating of >1,000 samples/day, and a capability of quantifying IGF1 point mutations and posttranslational modifications. The throughput of the IGF1 mass spectrometric immunoassay (MSIA) benefited from a simplified sample preparation step, IGF1 immunocapture in a tip format, and high-throughput MALDI-TOF MS analysis. The Limit of Detection and Limit of Quantification of the resulting assay were 1.5 μg/L and 5 μg/L, respectively, with intra- and inter-assay precision CVs of less than 10%, and good linearity and recovery characteristics. The IGF1 MSIA was benchmarked against commercially available IGF1 ELISA via Bland-Altman method comparison test, resulting in a slight positive bias of 16%. The IGF1 MSIA was employed in an optimized parallel workflow utilizing two pipetting robots and MALDI-TOF-MS instruments synced into one-hour phases of sample preparation, extraction and MSIA pipette tip elution, MS data collection, and data processing. Using this workflow, high-throughput IGF1 quantification of 1,054 human samples was achieved in approximately 9 hours. This rate of assaying is a significant improvement over existing MS-based IGF1 assays, and is on par with that of the enzyme-based immunoassays. Furthermore, a mutation was detected in ∼1% of the samples (SNP: rs17884626, creating an A→T substitution at position 67 of the IGF1), demonstrating the capability of IGF1 MSIA to detect point mutations and posttranslational modifications.

Product wastage from modern human growth hormone administration devices: a laboratory and computer simulation analysis

BackgroundTreatment of growth hormone disorders typically involves daily injections of human growth hormone (GH) over many years, incurring substantial costs. We assessed the extent of undesired GH loss due to leakage in the course of pen preparation prior to injection, and differences between the prescribed dose, based on patient weight, and the actual delivered dose based on pen dosing increments in five GH administration devices.MethodsNorditropin® prefilled FlexPro®, NordiFlex®, NordiLet®, and durable NordiPen®/SimpleXx® 5 mg pens (Novo Nordisk A/S, Bagsværd, Denmark) and durable Omnitrope® Pen-5 devices (Sandoz, Holzkirchen, Germany) were tested (n = 40 for each device type). Product wastage was measured in accordance with validated protocols in an ISO (International Organization for Standardization) 11608-1 and Good Manufacturing Practice compliant laboratory. The average mass of wasted GH from each device type was measured in simulations of dripping with the needle attached prior to injection and while setting a dose. Statistical significance (P < 0.05) was confirmed by Student’s t-test, and a model was constructed to estimate mean annual GH wastage per patient in cohorts of pediatric patients with GH disorders.ResultsMean GH mass wasted with the needle on prior to injection was 0.0 μg with Norditropin pens, relative to 98 μg with Omnitrope Pen-5. During dose dialing, 0.0–2.3 μg of GH was lost with Norditropin pens versus 0.8 μg with Omnitrope Pen-5. All Norditropin and Omnitrope device comparisons were statistically significant. Modeling GH wastage in a US cohort showed 5.5 mg of annual GH wastage per patient with FlexPro versus 43.6 mg with Omnitrope, corresponding to 7–8 additional pens per patient annually.ConclusionOverall, Norditropin pens resulted in significantly less wastage than the Omnitrope Pen-5. The study suggests that GH devices of the same nominal volume exhibit differences that may affect the frequency of GH prescription refills required to remain adherent to therapy.

Hormonal Causes of Male Sexual Dysfunctions and Their Management (Hyperprolactinemia, Thyroid Disorders, GH Disorders, and DHEA)

Besides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD). To review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD. A systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence-Based Medicine-Levels of Evidence (March 2009) was applied when possible. The most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed. Only severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL-induced suppression on gonadotropin secretion. The latter is PRL-level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin-like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function. While the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in regulating male sexual functioning.

OR07-2 Simultaneous stimulation of human 20 kDa growth hormone and 22 kDa growth hormone secretion by ghrelin

The World Anti Doping Agency has banned the use of recombinant human growth hormone (rhGH). Regardless, rogue athletes may use rhGH in pursuit of improved performance. Current immunoassaybased detection of illicit use of rhGH is complicated by the short half-life of injected rhGH, by the chemical identity of rhGH and a native growth hormone (GH), and by the physiologically high peaks of GH that occur with the pulsatile secretion of GH by a normal pituitary. We hypothesized that injection of rhGH changes the expression patterns of GHmessenger RNA (mRNA) in circulating white blood cells and of microRNA (miRNA) in plasma. Objective: To measure circulating GH mRNA and miRNAs in humans. Methods: We used reverse-transcription quantitative polymerase chain reaction (RT-qPCR) with nested primers to detect and quantify GHmRNA.We usedmiRNAmicroarrays to identify rhGH-dependent miRNA expression and then measured the concentrations of selected miRNAs by RT-qPCR. Following Institutional Review Board approval, we obtained whole-blood or plasma, from 9 healthy volunteers and from 36 patient volunteers. All patients had known or suspected disorders of growth hormone production including panhypopituitarism treated with physiologic doses of rhGH (0.2 to 0.8mg/day) and acromegaly. Results: GH mRNA was quantified in blood from all healthy volunteers and patients with disorders of GH at concentrations ranging from 36 to 4815 copies/100 mL blood. The intra-individual GH mRNA concentration varied less than 3-fold in 17 samples collected over the period of one year in a healthy, athletic volunteer; however, variability increased markedly in the group with pituitary disorders. Initially, 9 specimens from: 3 patients receiving therapeutic growth hormone replacement, 4 patients with acromegaly, and 2 normal controls, were subject to plasma-derived miRNA microarrays. Of 1105 miRNA’s measured in each microarray, 3 were present in plasma of all rhGH replacement users and undetectable in all patients with acromegaly and normal controls. Conclusions: The narrow intra-individual range of its concentration suggests that GH mRNA in blood is not present as a result of pulsatile secretion and thus is worthy of study as a marker of doping with supraphysiologic amounts of rhGH. Further investigation of miRNA in plasma should be performed on samples obtained before and after administration of supraphysiologic amounts of rhGH to confirm the preliminary results in patients receiving therapeutic replacement doses of rhGH.

OR07-1 Circulating RNAs as markers of growth hormone doping

The World Anti Doping Agency has banned the use of recombinant human growth hormone (rhGH). Regardless, rogue athletes may use rhGH in pursuit of improved performance. Current immunoassaybased detection of illicit use of rhGH is complicated by the short half-life of injected rhGH, by the chemical identity of rhGH and a native growth hormone (GH), and by the physiologically high peaks of GH that occur with the pulsatile secretion of GH by a normal pituitary. We hypothesized that injection of rhGH changes the expression patterns of GHmessenger RNA (mRNA) in circulating white blood cells and of microRNA (miRNA) in plasma. Objective: To measure circulating GH mRNA and miRNAs in humans. Methods: We used reverse-transcription quantitative polymerase chain reaction (RT-qPCR) with nested primers to detect and quantify GHmRNA.We usedmiRNAmicroarrays to identify rhGH-dependent miRNA expression and then measured the concentrations of selected miRNAs by RT-qPCR. Following Institutional Review Board approval, we obtained whole-blood or plasma, from 9 healthy volunteers and from 36 patient volunteers. All patients had known or suspected disorders of growth hormone production including panhypopituitarism treated with physiologic doses of rhGH (0.2 to 0.8mg/day) and acromegaly. Results: GH mRNA was quantified in blood from all healthy volunteers and patients with disorders of GH at concentrations ranging from 36 to 4815 copies/100 mL blood. The intra-individual GH mRNA concentration varied less than 3-fold in 17 samples collected over the period of one year in a healthy, athletic volunteer; however, variability increased markedly in the group with pituitary disorders. Initially, 9 specimens from: 3 patients receiving therapeutic growth hormone replacement, 4 patients with acromegaly, and 2 normal controls, were subject to plasma-derived miRNA microarrays. Of 1105 miRNA’s measured in each microarray, 3 were present in plasma of all rhGH replacement users and undetectable in all patients with acromegaly and normal controls. Conclusions: The narrow intra-individual range of its concentration suggests that GH mRNA in blood is not present as a result of pulsatile secretion and thus is worthy of study as a marker of doping with supraphysiologic amounts of rhGH. Further investigation of miRNA in plasma should be performed on samples obtained before and after administration of supraphysiologic amounts of rhGH to confirm the preliminary results in patients receiving therapeutic replacement doses of rhGH.

Administration Burden Associated With Recombinant Human Growth Hormone Treatment: Perspectives of Patients and Caregivers

Patients treated with recombinant human growth hormone (rhGH) for growth hormone disorders follow a challenging treatment schedule. This study assessed patient and caregiver experiences with rhGH therapy treatment regimens. Patients 13 years or older with growth hormone deficiency and caregivers completed Web-based surveys. A total of 61 patients and 239 caregivers participated. Storage of rhGH was considered burdensome by more than a third. More than 51% considered storage "somewhat more" to "much more of a burden" relative to the burden while not traveling. "Away from home or traveling" was the most frequently endorsed reason for missing a dose. rhGH treatment while traveling is challenging because of rhGH storage burden.

Oral manifestations in growth hormone disorders

Growth hormone is of vital importance for normal growth and development. Individuals with growth hormone deficiency develop pituitary dwarfism with disproportionate delayed growth of skull and facial skeleton giving them a small facial appearance for their age. Both hyper and hypopituitarism have a marked effect on development of oro-facial structures including eruption and shedding patterns of teeth, thus giving an opportunity to treating dental professionals to first see the signs and symptoms of these growth disorders and correctly diagnose the serious underlying disease.

Retracted: A Possible Case of Hypopituitarism in Neolithic China

ABSTRACTA human skeleton with a possible case of hypopituitarism is reported. The individual (burial M53) is from the site of Guanjia, a Neolithic settlement in northern China, dated to the Late Yangshao period (6000–5500 bp). On the basis of the fully erupted third permanent molars and moderate occlusal dental wear resulting in substantial exposure of dentine, the initially estimated age‐at‐death was placed between 26 and 33 years. However, dimensions of the postcranial skeleton fall significantly below and outside the range from contemporaneous adult populations, and along with delayed epiphyseal fusion present throughout the skeleton, the postcranial age is concordant to that of an 11‐ to 13‐year‐old child. Most long bone epiphyses display incomplete fusion or are entirely unfused, but a lack of microporosity in the metaphyseal areas near growth plates indicates a cessation of longitudinal bone growth. Because no signs of porotic hyperostosis,cribra orbitalia, periosteal lesions or linear enamel hypoplasia are observed, the restricted growth of this individual is likely caused by a growth hormone disorder and is unrelated to nutritional deficiencies or systemic infection. Copyright © 2011 John Wiley &amp; Sons, Ltd.

Yetişkin Sağlıklı Bir Türk Toplum Örnekleminde İnsülin-Benzeri Büyüme Faktörü-I ve IGF-Bağlayıcı Protein-3 Seviyeleri

Amaç: İnsülin benzeri büyüme faktörü-I (IGF-I) ve IGF-bağlayıcı protein-3 (IGFBP 3) seviyeleri büyüme hormonu (GH) ilişkili hastalıkların tanısında önemli belirteçlerdir. Normal IGF-I ve IGFBP- 3 seviyeleri farklı etnik gruplar arasında değişkenlik göstermektedir ve farklı populasyonlara göre belirlenenen referanslar bazı tanı, tedavi ve izlemde bazen yanlış yönlenmeye neden olabilmektedir. Biz bu amaçla sağlıklı yetişkin Türk toplum örnekleminde IGF-I ve IGFBP-3 düzeylerini inceledik. Gereç ve Yöntemler: Sekiz yüz otuz üç olgu (512 kadın, 321 erkek) çalışmaya alındı. Serum IGF-I ve IGFBP-3 seviyeleri tüm olgularda bir immünoradyometrik tetkikle ölçüldü. Çalışma populasyonu yaş grupları (18-20, 21-23, 24-25, 26-30, 31-40, 41-50, >50 yaş) ve cinsiyet gruplarına (<30 yaş populasyon kadın ve erkekler olarak ayrılırken >30 yaş grubunda birlikte) ayrıldı ve sonuçlar üretici firmanın referans bir toplumu temsil eden referans değerleri ile karşılaştırıldı. Bulgular: Serum IGF-I değerleri ≤30 yaştaki bütün kadın yaş gruplarında referans seviyelerinden istatistiksel olarak anlamlı düzeyde daha yüksekti (p< 0.05). Erkeklerde sadece 26-30 yaş arası grupta IGF-I seviyeleri istatistiksel olarak anlamlı düzeyde daha yüksekti (p< 0.05). Otuz yaş üstündeki cinsiyet yönünden birlikte ele alınan gruplarda IGF-I seviyeleri referans seviyelerinden istatistiksel olarak daha yüksekti (p< 0.05). Serum IGFBP-3 seviyeleri 24-25 yaş arası grupta her iki cinsiyette, 18-20 yaş arası grupta ise erkeklerde referans değerlerinden daha düşüktü (p< 0.05). Serum IGFBP-3 seviyeleri 26-30 yaş arası grupta erkeklerde ve >30 yaş üstünde cinsiyet yönünden birleşik gruplarda istatistiksel açıdan anlamlı derecede daha yüksekti (p< 0.05). Sonuç: Çalışma populasyonumuzdaki serum IGF-I konsantrasyonları ticari kitin referans değerlerinden genelde daha yüksekti. GH'la ilişkili bozukluklarla ilgilenen merkezlerin tanı ve izlemde olası hatalardan kaçınabilmek amacıyla kendi populasyonlarının normal IGF-I ve IGFBP-3 değerlerini belirlemeleri yararlı olabilecektir.

Endocrine Hypertension: Diagnosis and Management of a Complex Clinical Entity

Hypertension is a major contributor to vascular morbidity and mortality. Endocrine hypertension (EH) refers to secondary hypertension caused by specific endocrine abnormalities. The significance of EH is that the identification of the underlying disorder and its management may lead to partial or complete normalization of blood pressure. When EH is suspected thorough investigation with biochemical and imaging testing are necessary to establish or exclude mineralocorticoid, catecholamine, glucocorticoid, thyroid, parathyroid or growth hormone disorders as well as rare hereditary syndromes. In addition, it is important to differentiate benign from malignant tumors. The present review provides an update on the pathophysiology and clinical presentation of EH. We also discuss the diagnostic work-ups and therapeutic strategies.

Foreword

We gratefully acknowledge the work of the Guest Editors Beverly MK Biller, Hugo Fideleff, Vera Popovic and Felipe Casanueva on the EJE special issue 15 years of KIMS® and 5 years of ACROSTUDY™ Their contribution to the management of adult patients with growth hormone disorders. This acknowledgement was omitted by mistake from EJE 161 (Suppl 1) S1–S2.

Sheehan's syndrome and its impact on bone mineral density

Introduction. Although there have been few studies investigating osteoporosis in isolated hormone deficiencies or other causes of hypopituitarism, the relationship between Sheehan's syndrome (SS) and osteoporosis has not been investigated. In the present study, we aimed to evaluate bone mineral density (BMD) in patients with SS in comparison with healthy women.Methods. Sixty-one patients with SS and 62 matched healthy controls were included. Biochemical, hormonal assessments and BMD evaluations were carried out in patients and controls, and a subgroup analysis according to menopausal status was done (premenopausal < 50 years; postmenopausal > 50 years).Results. The mean levels of serum anterior pituitary hormones were significantly lower in pre- and postmenopausal patients with SS compared with respective control groups (p < 0.0001). For both pre- and postmenopausal subjects, compared with respective controls, serum calcium and ALP levels, femur-T score, femur-Z score, spine (L1–L5)-T score, spine (L1–L5)-Z score and BMD values were lower, and phosphorus and parathyroid hormone (PTH) levels were higher in patients with SS.Conclusions. Patients with SS had low BMD. The possible mechanism responsible for osteoporosis may be hypogonadism, growth hormone deficiency and disorders of parathyroid hormone and calcium metabolism. But the contribution of each anterior pituitary hormone deficiency on bone loss should be clarified in further prospective studies.

Phenotypic aspects of growth hormone- and IGF-I-resistant syndromes.

Major advances in the diagnosis and characterisation of growth hormone (GH) and IGF-I resistant disorders have occurred during the past 15 years. With these advances has come the realisation that there is broad phenotypic variation within these diagnostic categories. We discuss the current status of endocrine and molecular evaluation, focussing on the phenotypic characteristics of genetic defects in the GH-IGF-I axis.

Standardization of the IMMULITE systems growth hormone assay with the recombinant IS 98/574

The diagnosis of disorders of growth hormone (GH) secretion is based on the measurement of GH before and after dynamic stimulation or suppression tests. Over the years, specific cut-off values have been proposed without taking account of the considerable variation in results obtained using different methods for analysing GH. Recent publications have recommended the standardization of GH assays using IS 98/574, which is calibrated in mass and units (U). The IMMULITE range of GH assays have been recalibrated using this standard. We analysed 745 samples using the current and the restandardized GH assay kits. This series of samples contained 90 stimulation tests and seven suppression tests. The data comparing the current and restandardized assays show a similar relationship for both basal and stimulated GH values for all IMMULITE platforms. There is a negative bias by the restandardized assay above approximately 20 microg/L. A conversion can be derived from this study which would mean that patient GH results expressed in milliunits per litre of IMMULITE in-house derived standard will be approximately three-fold of that expressed in micrograms per litre of IS 98/574. Use of IS 98/574 offers standardized reporting in microgram per litre IS 98/574. This will permit compliance with the consensus recommendations and the development of a firm evidence base for defining decision-making GH values.