Michael B Ranke

Michael B Ranke
University Children´s Hospital - University of Tübingen

Doctor of Medicine

About

699
Publications
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23,314
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Publications

Publications (699)
Article
Full-text available
Context Prediction of adult height (AH) is important in clinical management of short children. The conventional methods of Bayley-Pinneau (BP) or Roche-Wainer-Thissen (RWT) have limitations. Objective To develop a set of algorithms for AH prediction in patients with idiopathic short stature (ISS) which are specific for combinations of predicting v...
Article
Full-text available
The BoneXpert method for automated determination of bone age from hand X-rays was introduced in 2009 and is currently running in over 200 hospitals. The aim of this work is to present version 3 of the method and validate its accuracy and self-validation mechanism that automatically rejects an image if it is at risk of being analysed incorrectly. Th...
Article
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The new WHO reference standard allows for the definition of serum antibodies against various SARS-CoV-2 antigens in terms of binding antibody units (BAU/mL) and thus to compare the results of different ELISA systems. In this study, the concentration of antibodies (ABs) against both the S- and the N-protein of SARS-CoV-2 as well as serum neutralizat...
Article
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The syndrome of impaired GH secretion (GH deficiency) in childhood and adolescence had been identified at the end of the 19 th century. Its non-acquired variant (naGHD) is, at childhood onset, a rare syndrome of multiple etiologies, predominantly characterized by severe and permanent growth failure culminating in short stature. It is still difficul...
Article
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Assessment and management of children with growth failure has improved greatly over recent years. However, there remains a strong potential for further improvements by use of novel digital techniques. A panel of experts discussed developments in digitalization of a number of important tools used by pediatric endocrinologists at the third 360° Europ...
Article
Background/aims: We hypothesized that modelling catch-up growth (CUG) as developed for coeliac disease (CD), might also fit CUG in adequately treated children with juvenile hypothyroidism (JHT) or growth hormone deficiency (GHD). Methods: We used a monomolecular function for all available prepubertal data on height SDS minus target height SDS (a...
Preprint
Background: Patients infected with SARS-CoV-2 exhibit a highly variable clinical course, varying from barely discernible signs of disease, to moderate flu-like symptoms and, occasionally, with life-threatening pneumonia and/or cytokine storm. The relationship between the nasopharyngeal virus load, IgA and IgG antibodies to both the S1-RBD-protein a...
Article
Full-text available
Context Individual patients vary in their response to growth hormone (GH). No large scale genomewide studies have looked for genetic predictors of GH responsiveness. Objective To identify genetic variants associated with GH responsiveness. Design Genomewide association study Setting Cohorts from multiple academic centers and a clinical trial Pa...
Article
Background Severe early-onset obesity (SEOO) in children is a common feature of monogenic obesity. Gene defects of the leptin-melanocortin pathway can be analysed biochemically and genetically. The aim of this study was to search for children with leptin deficiency or biologically inactive leptin in a cohort of children with SEOO and to study assoc...
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The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary...
Article
Background/aims: There is little information how rhGH treatment affects height in NS. This study aims to analyze data from the NS patients assembled in KIGS over 25 years. Patients/methods: Of 613 (389 m/224 f) NS patients documented, 476 (302 m/174 f) were treated for 1 year, 237 (160 m/77 f) of which served to develop a 1st year height velocit...
Article
Background Children with non-acquired (na) growth hormone deficiency (GHD) diagnosed over decades in one center may provide perspective insight. Methods naGHD is divided into idiopathic GHD (IGHD), GHD of known cause (cGHD) and GHD neurosecretory dysfunction (NSD); time periods: <1988 (I); 1988–1997 (II); 1998–2007 (III); 2008–2015 (IV). Descripti...
Article
During the phase of using hGH extracted from pituitaries (pit hGH) - 1958-1985 - fundamental experience related to the diagnosis and treatment was accumulated. However, since recombinant hGH (rhGH) had become available diagnosis and treatment of GHD were conducted world-wide in a more standardized way. Treatment with rhGH was also accompanied by do...
Article
Growth hormone (GH) research and its clinical application for the treatment of growth disorders span more than a century. During the first half of the 20th century, clinical observations and anatomical and biochemical studies formed the basis of the understanding of the structure of GH and its various metabolic effects in animals. The following per...
Article
Silver-Russell syndrome (SRS) is a rare congenital disorder, characterized by a wide spectrum of signs and symptoms, which vary significantly between affected individuals. The understanding of the genetic basis of the phenotype has advanced greatly during the past decades. Together with the typical clinical picture intrauterine growth retardation a...
Article
Background Growth prediction models (GPMs) exist to support clinical management of children treated with growth hormone (GH) for growth hormone deficiency (GHD), Turner syndrome (TS) and for short children born small for gestational age (SGA). Currently, no prediction system has been widely adopted. Content The objective was to develop a stand-alo...
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Conclusions: HbA1c seems to be more reliable than OGTT for diabetes screening in overweight and obese children and adolescents. The optimal HbA1c threshold for identifying patients with diabetes was found to be 42 mmol/mol (6.0%). What is Known: • The prevalence of obesity is increasing and health problems related to type 2 DM can be serious. Howe...
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Context and aims: Functional leptin deficiency is characterized by high levels of circulating immunoreactive leptin (irLep), but a reduced bioactivity of the hormone due to defective receptor binding. As a result of the fact that affected patients can be successfully treated with metreleptin, it was aimed to develop and validate a diagnostic tool...
Article
Background: Information about disease-specific and gender-associated differences over longer time of short children treated with recombinant human growth hormone is missing. Methods: We analyzed data at growth hormone (GH) start in prepubertal children diagnosed with idiopathic GH deficiency (IGHD), congenital GHD, acquired GHD, idiopathic short...
Article
Background: Diabetes and prediabetes are defined based on different methods such as fasting glucose, glucose at 2-hour in oral glucose tolerance test (OGTT), and glycated hemoglobin A1c (HbA1c). These parameters probably describe different deteriorations in glucose metabolism limiting the exchange between each other in definitions of diabetes. Ob...
Article
Reliable laboratory analysis is fundamental to diagnostics, therapy, and follow-up of growth disturbance and secretory dysfunction of growth hormone (GH) and insulin-like growth factor I (IGF-I). Currently available commercial assays have their limitations, as they show large variations in hormone concentrations measured. The recommendations of an...
Article
Background: Children born small for gestational age (SGA) are at risk for the metabolic syndrome (MetS) as adults. We examined whether indicators of MetS could be identified in pre-pubertal children born very preterm. Methods: Parameters associated with MetS were studied in 141 pre-pubertal schoolchildren with either very low birth weight (VLBW)...
Article
The aim of this study was to analyze changes in adipose tissue (AT) distribution, intrahepatic lipids (IHL), and insulin resistance (IR) among a group of obese adolescents undergoing a 7-months low-level lifestyle intervention. Thirty-nine obese Caucasian adolescents (mean age 13.9 years, body mass index standard deviation score (BMI-SDSLMS) 2.14)...
Article
Turner Syndrome (TS) is a rare disorder, characterized by numerous signs and symptoms, which are also highly variable in their expression in individuals. The understanding of the genetic basis of the phenotype has advanced greatly during the past decades. The most consistent features, which negatively affect the quality of life in these individuals...
Article
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The IGF system comprises two IGFs (IGF-1, IGF-2), two IGF-receptors (IGF-R1, IGF-R2), and six IGF binding proteins (IGFBPs) with a high affinity for IGFs. The IGFBPs, of which IGFBP-3 is the most abundant in postnatal blood, link with IGFs and prevent them from being degraded; they also facilitate IGF transport through body compartments. The intera...
Article
Zusammenfassung Eine zuverlässige Laboranalytik bildet einen Grundpfeiler für die Diagnostik, Therapie und Verlaufskontrolle von Wachstumsstörungen und Störungen der Sekretion von Wachstumshormon (GH) und Insulin-Like Growth Factor I (IGF-I). Die gegenwärtig verfügbaren kommerziellen Assays weisen jedoch Defizite auf, die zu großen Unterschieden de...
Article
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Background/aims: In addition to genome-wide association studies (GWAS), height-associated genes may be uncovered by studying individuals with extreme short or tall stature. Methods: Genome-wide analysis for copy number variants (CNVs), using single nucleotide polymorphism (SNP) arrays, was performed in 49 index cases born small for gestational a...
Article
Thyroid disorders are the most frequent disorders of the endocrine system and are, for physicians of any specialisation and for lay people, the most typical examples of endocrine diseases. Goiter, hyperthyroidism and hypothyroidism - particularly in its severest form of cretinism – all have impressive clinical features that have been featured in hi...
Article
In light of the growing number of surviving children born very preterm, there is an increasing focus on their long-term outcomes in terms of growth, metabolic status, and neurocognitive development. Therefore, it is of importance to follow such children from birth onwards with the aim of identifying the causes of atypical development, developing pr...
Article
Background/aims: Growth hormone (GH) treatment is approved for short children born SGA but not for AGA. Our aim was to study the effect of GH in short VLBW SGA and AGA children. Methods: The study group comprised 44 prepubertal short children with a birth weight <1,500 g: 27 AGA (12 females) and 17 SGA (6 females). Mean values at GH start were (...
Article
Objective: While in adults not total body- or visceral fat mass, but liver fat content was found to independently determine insulin resistance, it is unclear whether these relationships are already present in obese adolescents. Methods: Thirty-nine overweight/obese adolescents were matched for sex and BMI with 39 adults. To compare the age- and...
Article
In children presenting with short stature, physicians often limit themselves to descriptive diagnoses such as idiopathic short stature or small for gestational age. Flechtner and colleagues now report a high frequency of bone dysplasias in these children, raising questions about the process of diagnosing short stature.
Article
Objective Growth hormone (GH) increases lean body mass and reduces fat mass. However, the long-term changes in weight status during growth hormone treatment, according to age and weight status at onset of treatment, have not previously been reported in large datasets.Methods Changes in BMI-SDS between starting GH treatment and attaining near adult...
Article
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Background: The insulin-like growth factor (IGF) receptor (IGF1R) is essential for normal development and growth. IGF1R mutations cause IGF-1 resistance resulting in intrauterine and postnatal growth failure. The phenotypic spectrum related to IGF1R mutations remains to be fully understood. Methods: Auxological and endocrinological data of a pat...
Article
Background: Fetal growth failure has been associated with an increased risk of hypertension, cardiovascular disease and diabetes in adulthood. Exploring the mechanisms underlying this association should improve our understanding of these common adult diseases. Patients and methods: We investigated 225 SNPs in 10 genes involved in growth and gluc...
Article
Ullrich-Turner syndrome (UTS) girls often present with short stature in adolescence to the endocrinologist when the efficacy of growth hormone (GH) to improve growth remains unknown and parameters to estimate individual GH responsiveness have yet to be determined. Objective: Retrospective evaluation of adult height (AH) and predicted adult height a...
Article
Determination of bone age is routinely used for following up substitution therapy in congenital adrenal hyperplasia (CAH) but today is a procedure with significant subjectivity. The aim was to test the performance of automatic bone age rating by the BoneXpert software package in all radiographs of children with CAH seen at our clinic from 1975 to 2...
Article
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Objective: The aim of this study was to identify the prevalence of eating disorder symptoms in obese adolescents participating in a lifestyle intervention for weight loss and to investigate possible relationships with weight change, general psychopathology, and health-related quality of life (HRQOL). Method: At the beginning and after completion...
Article
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The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or ch...
Article
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Background Response to growth hormone (GH) therapy may vary between individual patients. Therefore the use of GH in children should be closely monitored to avoid over, under, or ineffective treatment regimens. The treatment response can be evaluated using growth prediction models. In an effort to improve the accuracy of these prediction models, Ran...
Article
Idiopathic short stature (ISS) is defined as shortness in childhood without a specific cause. ISS may be familial or nonfamilial and may be associated with or without delay of pubertal development. Treatment can be considered in an attempt to reduce the psychological burden caused by short stature in childhood and adult life. If counselling alone i...
Article
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Study question: In girls and adolescents with Turner syndrome (TS), is there a correlation between serum AMH levels and karyotype, spontaneous puberty and other biochemical markers of ovarian function, or growth hormone (GH) therapy? Summary answer: Serum anti-Müllerian hormone (AMH) correlates with karyotype, pubertal development, LH, FSH and a...
Article
Treatment with growth hormone (GH) has become standard practice for replacement in GH-deficient children or pharmacotherapy in a variety of disorders with short stature. However, even today, the reported adult heights achieved often remain below the normal range. In addition, the treatment is expensive and may be associated with long-term risks. Th...
Article
Aim: A new method (BX AHP) for adult height prediction (AHP), based on automated bone age (BoneXpert®, here called autBA) assessment, has been developed and validated. The aim of this study was to evaluate the performance of autBA and BX AHP in comparison with manual Greulich-Pyle bone age (manBA) and Bayley-Pinneau AHP (BP AHP) in children with u...
Article
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Objectives: Neuroimaging has become an essential part of the diagnostic process in children with GH deficiency (GHD). The aim of the study was to document the frequency of neuroanatomical abnormalities in a very large cohort of children with GHD and to relate these findings to patient clinical characteristics. Design and methods: Results of magn...
Article
The study aim was to develop and validate models for long-term prediction of growth in prepubertal children with idiopathic growth hormone deficiency (GHD) or Turner syndrome (TS) for optimal, cost-effective growth hormone (GH) therapy. Height was predicted by sequential application of annual prediction algorithms for height velocity in cohorts of...
Article
Full-text available
A number of radiogrammetrical metacarpal indices are in use, some of which have been adapted for children. The purpose of this study was to compare four known indices-bone mineral density (BMD), relative cortical area, Exton-Smith index, bending breaking resistance index-and the more recently defined pediatric bone index (PBI) according to the two...
Article
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Because the criteria for genetic screening of short children are unknown, we performed genetic analysis of 199 short children born small for gestational age (SGA) or with normal birth size (idiopathic short stature, ISS). After selection with a modified scoring system for SHOX and a novel score for IGF1 and IGF1R defects, direct sequencing and mult...
Article
No abstract available.
Article
Aims: We hypothesized that Methods: Prospective longterm outcome follow-up-study of 141 preterm children born 1995–1997 GA P 10/10 (%) 14.3 vs. 18.6; K-ABC IQ mean 94.1 vs. 91.6). Children with height P10: M-ABC TIS >10 (%) 33.3 vs. 14.3. Within the group of children with short stature (<10th percentile) at the age of 8, there were children born SG...
Article
Prediction algorithms suggest factors determining short- and long-term growth response to growth hormone (GH) in Turner's syndrome (TS). A total of 133 patients (group A; 53% with karyotype 45,X) completed 1 year of treatment and 77 patients (group B) reached adult height (AH) after >4 years on GH treatment. The patients were analysed for factors d...
Article
Full-text available
IGFBP3 immunoreactivity may appear elevated in patients with chronic kidney disease (CKD), in part due to accumulation of low molecular fragments. The importance of these IGFBP3 variants for binding and inactivation of IGF1 and their relevance for the impaired growth of uremic children are unclear. Nevertheless, IGFBP3, measured as total (t-)IGFBP3...
Article
To investigate the impact of variants of the FTO gene (rs1421085, rs17817449, rs9939609) in obese children before and after lifestyle intervention. Design: Longitudinal, clinical intervention study with an increase in physical activity, and nutritional recommendations based on the 'Optimized Mixed Diet for German Children and Adolescents' (Research...
Article
The Tanner-Whitehouse (TW) method for bone age determination has been the basis for many population studies and it is used in many clinics. However, TW bone age raters can differ systematically from each other. The aim of the study was to present a new standard version of TW bone age rating implemented by the automated BoneXpert method and calibrat...
Article
Manual bone age (BA) rating in precocious puberty (PP) is associated with considerable rater variability. The aim was to evaluate a new method for automated Greulich and Pyle (GP) BA determination in children with PP. Seven hundred forty-one archived X-rays from 13 boys and 103 girls with PP or early puberty of various etiologies (age range at time...
Article
We review seven methods for adult height prediction (AHP) based on bone age, ranging from the Bayley–Pinneau method, published in 1952, to the BoneXpert method, published in 2009. These models are based on four different methods for bone age assessment including Greulich–Pyle, Tanner–Whitehouse, Fels, and the automated BoneXpert method. The aim of...
Article
We hypothesized that overweight children with growth hormone deficiency (GHD) demonstrate a lower response to growth hormone (GH) as a result of a misclassification since obesity is associated with lower GH peaks in stimulation tests. Anthropometric data, response, and responsiveness to GH in the first year of treatment were compared in 1.712 prepu...
Article
Many children with idiopathic short stature (ISS) remain short as adults. Height can be improved permanently by growth hormone (GH) treatment, as in children with Turner syndrome or born small for gestational age. Although GH treatment for ISS is an approved indication in the United States, there is ongoing controversy in Europe about approving GH...
Article
Zusammenfassung Neugeborene mit einer sehr niedrigen Geburtslänge oder einem sehr niedrigen Geburtsgewicht, die mehr als 2 Standardabweichungen unterhalb des Durchschnitts eines Vergleichskollektivs gleichen Gestationsalters liegen, sind definitionsgemäß „small for gestational age“ (SGA). Die Ursachen für die zu niedrigen Geburtsmaße sind vielfälti...
Article
Growth hormone (GH) is an accepted treatment for short children born small for gestational age (SGA). The aim of this analysis was to compare the growth response to GH in children with low birth weight born SGA or appropriate for gestational age (AGA). This retrospective observational study is from one center. Of all the children with a birth weigh...
Article
Full-text available
This review examines the role of skeletal maturity ('bone age', BA) assessment in clinical practice. BA is mainly used in children with the following conditions: short stature (addressed in part 1 of this review), tall stature, early or late puberty, and congenital adrenal hyperplasia (all addressed in part 2). Various manual and automatic methods...
Article
Full-text available
If height-limiting treatment is being considered for a child with tall stature, skeletal maturity is invaluable in the selection of appropriate patients for treatment, determining appropriate age of treatment commencement, monitoring progress of treatment, and determining the expected treatment effect on adult height. In precocious puberty, bone ma...