The Manchester Triage System in a Pediatric Emergency Department of an Austrian University Hospital: A Retrospective Analysis of Urgency Levels.

OBJECTIVES: The Manchester Triage System (MTS) has entered widespread international use in emergency departments (EDs). This retrospective study analyzes urgency of patient visits (PV) at the ED of the Clinic for Pediatrics at the Medical University of Innsbruck. METHODS: We collected demographic and outcome information, including PV urgency levels (UL) according to the MTS, for 3 years (2015-2018), separating PV during regular office hours (ROH; 8:00 am to 5:00 pm) from PV during afternoon and night hours (5:00 pm to 8:00 am), and PV on weekdays from PV on weekends and bank holidays (WE). RESULTS: A total of 56,088 PV were registered with a UL. Most (68.4%) PV were classified as nonurgent. During ROH, more PV per hour (PV/h) were recorded than during afternoon and night hours (3.0 PV/h vs 1.6 PV/h), with a higher proportion of less urgent cases during ROH. On WE, the amount of PV/h was higher than on weekdays (3.6 PV/h vs 2.8 PV/h), with a higher proportion of nonurgent cases (74.6% vs 68.6%). Likelihoods of inpatient admission and hospital stay lengths increased in step with UL. CONCLUSIONS: The MTS proved useful for delineating UL distributions. The MTS analyses may be of value in managing EDs. Prompted by the results of our study, a general practice pediatric care unit was established to support the ED during WE.

Gene expression signatures predict response to therapy with growth hormone.

Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.

Comprehensive genotyping and clinical characterisation reveal 27 novel NKX2-1 mutations and expand the phenotypic spectrum.

BACKGROUND: NKX2-1 encodes a transcription factor with large impact on the development of brain, lung and thyroid. Germline mutations of NKX2-1 can lead to dysfunction and malformations of these organs. Starting from the largest coherent collection of patients with a suspected phenotype to date, we systematically evaluated frequency, quality and spectrum of phenotypic consequences of NKX2-1 mutations. METHODS: After identifying mutations by Sanger sequencing and array CGH, we comprehensively reanalysed the phenotype of affected patients and their relatives. We employed electrophoretic mobility shift assay (EMSA) to detect alterations of NKX2-1 DNA binding. Gene expression was monitored by means of in situ hybridisation and compared with the expression level of MBIP, a candidate gene presumably involved in the disorders and closely located in close genomic proximity to NKX2-1. RESULTS: Within 101 index patients, we detected 17 point mutations and 10 deletions. Neurological symptoms were the most consistent finding (100%), followed by lung affection (78%) and thyroidal dysfunction (75%). Novel symptoms associated with NKX2-1 mutations comprise abnormal height, bouts of fever and cardiac septum defects. In contrast to previous reports, our data suggest that missense mutations in the homeodomain of NKX2-1 not necessarily modify its DNA binding capacity and that this specific type of mutations may be associated with mild pulmonary phenotypes such as asthma. Two deletions did not include NKX2-1, but MBIP, whose expression spatially and temporarily coincides with NKX2-1 in early murine development. CONCLUSIONS: The high incidence of NKX2-1 mutations strongly recommends the routine screen for mutations in patients with corresponding symptoms. However, this analysis should not be confined to the exonic sequence alone, but should take advantage of affordable NGS technology to expand the target to adjacent regulatory sequences and the NKX2-1 interactome in order to maximise the yield of this diagnostic effort.

Weight and body mass index (BMI): current data for Austrian boys and girls aged 4 to under 19 years.

BACKGROUND: BMI reference charts are widely used to diagnose overweight, obesity and underweight in children and adolescents. AIM: To provide up-to-date national reference values for Austria. METHODS: A cross-sectional sample of over 14 500 children and adolescents (4-19 years) stratified by provinces according to age- and sex-specific population proportions was drawn via schooling institutions (kindergartens, schools and vocational colleges). The generalized additive models for location, scale and shape were used for a flexible estimation of percentile curves. RESULTS: Austrian boys and girls have higher average weight compared with previous prevalence data. BMI centiles matching BMI values at age 18 years, which are used for defining thinness, overweight and obesity in adults, were calculated. In Austria, using reference values as thresholds, ∼18% of boys and 12% of girls are overweight (with thresholds passing through BMI 25.00-29.99 kg/m(2) in adults) and 5% of boys and 3% of girls are obese (with thresholds passing through BMI ≥30.00 kg/m(2) in adults). CONCLUSION: Overweight and obesity are common in Austria and their prevalence is increasing (using the same IOTF reference for international comparison). Up-to-date national BMI reference values are provided to classify children and adolescents according to the proposed overweight and obesity thresholds.

Undescended testis: A roundtable discussion based on clinical scenarios - Part 1.

Undescended testis (UDT, cryptorchidism) is the most common congenital anomaly of the genital tract. Despite its high incidence, the management of UDT varies between specialties (urology, pediatric surgery, pediatric urology, pediatric endocrinology). Therefore, as the European Association of Urology - Young Academic Urologists Pediatric Urology Working Group, we requested experts around the world to express their own personal approaches against various case scenarios of UDT in order to explore their individual reasoning. We intended to broaden the perspectives of our colleagues who deal with the treatment of this frequent genital malformation.

Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto's thyroiditis.

BACKGROUND: Alterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, partly associated with latent Cytomegalovirus (CMV) infection. The present study was aimed to investigate proportions of lymphocytes, their relation to CMV-seropositivity and the replicative history of CD45RA + expressing T cells in Hashimoto's thyroiditis (HT, n = 18) and healthy controls (HC, n = 70). METHODS: Proportions of peripheral T cells were investigated by flow cytometry. The replicative history was assessed by T cell receptor excision circles (TRECs) and relative telomere length (RTL). Expression of CD62L was analyzed by immunohistochemistry in thyroid sections. The role of CMV was assessed by serology, ELISPOT assay and in situ hybridization. RESULTS: Our results demonstrated a significant increase of CD28-negative T cells, associated with CMV-seropositivity in HT patients. HT showed abundant CD45RO + T cells with peripheral loss of CD62L-expressing CD8 + CD45RA + T cells, the latter mainly depending on disease duration. CD62L was expressed in thyroid lymphocyte infiltrations. The diagnosis of HT and within the HT group CMV-seropositivity were the main determinants for the loss of CD28 expression. RTL was not different between HC and HT. HT showed significantly lower TRECs in CD4 + CD45RA + T cells compared to HC. CONCLUSIONS: Patients with HT display a peripheral T cell phenotype reminiscent of findings in elderly persons or other autoimmune disorders. Whether these mechanisms are primary or secondary to the immunological alterations of autoimmune conditions should be investigated in longitudinal studies which may open research on new therapeutic regimes for treatment of HT and associated autoimmune diseases.

Austrian height and body proportion references for children aged 4 to under 19 years.

BACKGROUND: Previous studies have demonstrated differences between national and the WHO reference curves in children older than 5 years. Moreover, reference curves for body proportions (sitting height, subischial leg length and their ratio) based on state-of-the-art statistics are not available. AIM: To develop reference curves for height and body proportions for use in Austria and compare the curves with WHO reference curves. To estimate and statistically investigate extreme percentiles. SUBJECTS AND METHODS: A sample of ∼14 500 children between 4-19 years of age was drawn via schooling institutions, stratified by provinces according to age- and sex-specific population proportions. GAMLSS models were used for a flexible estimation of percentile curves. RESULTS AND CONCLUSIONS: After the age of 5 years national reference curves are more suitable than the WHO reference curves for clinical use in Austria. These height curves are very similar to the German reference curves published recently. Therefore, these reference curves for criteria of body proportions are recommended for use in other populations. Further validation studies are needed to establish whether the recently recommended -2.5 and -3.0 SD for height are a sensitive and specific cut-off in the diagnostic work-up for children with a suspected growth disorder using this new Austrian height chart.

Higher Prevalence of Adverse Childhood Experiences in Transgender Than in Cisgender Individuals: Results from a Single-Center Observational Study.

Adverse childhood experiences (ACE) have been shown to have a tremendous negative impact on health outcomes later in life. This study presents data on the prevalence of ACEs, psychological distress, and trauma-related symptoms in transgender and gender-diverse (TGD) people compared to cisgender people. TGD adults (n = 35) and a matched sample of nonpsychiatric hospital patients (n = 35) were surveyed between September 2018 and March 2019. Participants completed the Maltreatment and Abuse Chronology of Exposure Scale to assess ACEs, as well as the Brief Symptom Inventory and the Essener Trauma Inventory to assess psychological distress and trauma-related symptoms. TGD patients reported a higher number of ACEs than cisgender patients (0.7 vs. 2.4; p < 0.001; d = 0.94). A total of 28.6% of TGD vs. 5.7% cisgender patients reported four or more ACEs (p < 0.001). The most common forms of ACEs were parental abuse (54.3%) and peer abuse (54.3%). No significantly increased prevalence of sexual abuse was found (p > 0.05). TGD patients also reported a higher prevalence of depression (48.4% vs. 5.7%, p < 0.001), posttraumatic stress disorder symptoms (59.4% vs. 13.8%, p < 0.001), and anxiety (58.1% vs. 28.6%, p = 0.016). Health care providers should be aware of and assess ACEs, especially in vulnerable groups such as TGD people, and create a safe place through open-minded, affirming care.

Pituitary Stalk Interruption Syndrome - Clinical Presentation and Management of a Potentially Life-threatening Disease in Newborns.

Pituitary stalk interruption syndrome (PSIS) is a rare congenital disease resulting in hypopituitarism of variable degree. Serious courses, due to severe combined pituitary insufficiency, are even rarer and associated with a very early manifestation immediately after birth. First clinical signs are elusive and lead to delayed diagnosis and treatment, often resulting in life-threatening complications. Objective of the current report is to point out early leading symptoms and key issues of neonatal manifested PSIS to increase the awareness, improve the clinical management and thereby enable an early diagnosis and treatment to prevent further complications. This report presents and compares the clinical course and management of two male newborns with manifested PSIS. Early leading symptoms were the same in both patients, including recurrent hypoglycaemia, hyponatraemia, jaundice, cholestasis, sucking weakness and genital abnormalities. Patient 1 developed an infection-induced adrenal crisis, persistent substitution-dependent thrombocytopenia and convulsions due to severe hypoglycaemia in delayed PSIS diagnosis. In patient 2, due to recognised above-mentioned symptoms, endocrine testing and a subsequent cerebral magnetic resonance imaging were performed early and he was diagnosed and treated before major complications occurred. Genetic testing was performed in both patients. GLI2 gene mutation (NM_005270.5:c.2537del; p.(Pro846Argfs*66)) heterozygous was detected in patient 1. No mutation was found in patient 2. Conclusively, the early diagnosis of neonatal PSIS is indispensable in the treatment and prevention of the possible severe clinical manifestation of this orphan disease. Therefore, increased awareness for early leading symptoms and proper clinical management are crucial.

[Emergency card, emergency medication, and information leaflet for the prevention and treatment of adrenal crisis (Addison crisis): an Austrian consensus document]. / Notfallausweis, Notfallmedikation und Informationsmaterial zur Prävention und Therapie der Nebennierenkrise (Addison-Krise): Ein österreichisches Konsensusdokument.

A central goal of the adrenal insufficiency management is the prevention of acute adrenal insufficiency (also known as adrenal crisis or Addison crisis). This consensus document was generated in order to achieve better implementation and harmonization of measures for the prevention and treatment of acute adrenal insufficiency in Austria. The following measures are generally recommended for all patients with adrenal insufficiency and are outlined in this manuscript: (1) Provision of a "steroid emergency card" and possibly also a medical alert bracelet or necklace (or similar identification). (2) Provision of a hydrocortisone injection kit (or alternative glucocorticoid preparations) for emergency use plus sufficient oral glucocorticoid doses for stress situations/illness. (3) Education of patients and relatives on glucocorticoid stress dosing and "sick day rules" as well as on self-injection of hydrocortisone. (4) Provision of a treatment guideline (information leaflet) for the prevention and therapy of the adrenal crisis, which should also be shown to healthcare staff if necessary. (5) Provision of an emergency phone number (contact details) of the responsible endocrine specialist team or other trained staff. (6) Reinforcement of patient education on a regular basis (preferably yearly). This consensus document also includes recommendations for glucocorticoid dosing in the perioperative setting as well as in various other stress situations.

Hydrocortisone dosing in children with classic congenital adrenal hyperplasia: results of the German/Austrian registry.

OBJECTIVE: Treatment of classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH but recommendations regarding dosage/administration are inconsistent. The aim of this study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicenter CAH registry. DESIGN: The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included. METHODS: A custom-made electronic health record software is used at the participating centers. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4. RESULTS: We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean (lower-upper quartiles) daily HC dose (mg/m² body surface area) was 19.4 (18.9-19.8) for patients <3 months (n = 329), 15.0 (14.6-15.3) for age ≥3-12 months (n = 463), 14.0 (13.7-14.3) for age 1-5.9 years (n = 745), 14.2 (14.0-14.5) for age 6 years to puberty entry (n = 669), and 14.9 (14.6-15.2) during puberty to 18 years (n = 801). Fludrocortisone was administered in 74.1% of patients with a median daily dosage of 88.8 µg. CONCLUSION: Our analyses showed that still a high proportion of children are treated with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily practice.

Guideline Adherence and Registry Recruitment of Congenital Primary Hypothyroidism: Data from the German Registry for Congenital Hypothyroidism (HypoDok).

Neonatal screening for congenital primary hypothyroidism (CH) is mandatory in Germany but medical care thereafter remains inconsistent. Therefore, the registry HypoDok of the German Society of Pediatric Endocrinology and Diabetology (DGKED) was analyzed to evaluate the implementation of evidence-based guidelines and to assess the number of included patients. Inclusion criteria were (i) date of birth between 10/2001 and 05/2020 and (ii) increased thyroid-stimulating hormone (TSH) at screening and/or confirmation. The cohort was divided into before (A) and after (B) guideline publication in 02/2011, to assess the guideline's influence on medical care. A total of 659 patients were analyzed as group A (n = 327) and group B (n = 332) representing 17.5% and 10.3% of CH patients identified in the German and Austrian neonatal screening program during the respective time period. Treatment start and thyroxine doses were similar in both groups and consistent with recommendations. Regular follow-ups were documented. In the first three years of life, less than half of the patients underwent audiometry; developmental assessment was performed in 49.3% (A) and 24.8% (B) (p < 0.01). Documentation of CH patient care by pediatric endocrinologists seemed to be established, however, it reflected only a minority of the affected patients. Therefore, comprehensive documentation as an important instrument of quality assurance and evidence-based medicine should be legally enforced and officially funded in order to record, comprehend, and optimize care and outcome in patients with rare diseases such as CH.

D-glyceric aciduria is caused by genetic deficiency of D-glycerate kinase (GLYCTK).

D-glyceric aciduria is a rare inborn error of serine and fructose metabolism that was first described in 1974. Most affected individuals have presented with neurological symptoms. The molecular basis of D-glyceric aciduria is largely unknown; possible causes that have been discussed are deficiencies of D-glycerate dehydrogenase, triokinase, and D-glycerate kinase. In 1989, van Schaftingen has reported decreased D-glycerate kinase activity in the liver of a single patient with D-glyceric aciduria. However, this analysis has not been performed in other affected individuals, and the underlying defect has remained unknown on the gene level until now. We report three patients with deficiency of D-glycerate kinase. They are of Serbian, Mexican, and Turkish origin and include the patient initially reported in 1974. All had homozygous mutations in exon 5 of the GLYCTK gene encoding D-glycerate kinase: c.1448delT (p.Phe483SerfsX2), c.1478T>G (p.Phe493Cys), or c.1558delC (p.Leu520CysfsX108). Transient overexpression of the variant GLYCTK genes in HEK293 cells clearly showed loss of enzyme activity and immunoreactivity when compared to the reference enzyme. Our work has revealed mutations in the GLYCTK gene as the cause of D-glycerate kinase deficiency and D-glyceric aciduria and provides a noninvasive approach for further diagnostic workup and research.

Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study.

BACKGROUND: Age- and sex-specific reference intervals are an important prerequisite for interpreting thyroid hormone measurements in children. However, only few studies have reported age- and sex-specific pediatric reference values for TSHbasal (TSH), free T3 (fT3), and free T4 (fT4) so far. Reference intervals are known to be method- and population-dependent. The aim of our study was to establish reference intervals for serum TSH, fT3, and fT4 from birth to 18 years and to assess sex differences. METHODS: 2,194 thyroid hormone tests obtained from a hospital-based pediatric population were included into our retrospective analysis. Individuals with diagnoses or medications likely to affect thyroid function were primarily excluded, as well as the diagnostic groups, if different from the purely healthy subgroup (n = 414). Age groups were ranging from 1 day to 1 month, 1 - 12 months, and 1 - 5, 6 - 10, 11 - 14, and 15 - 18 years, respectively. Levels of fT3, fT4 and TSH were measured on Advia(R) Centaur automated immunoassay system. RESULTS: The final sample size for reference data creation was 1,209 for TSH, 1,395 for fT3, and 1,229 for fT4. Median and 2.5/10/25/75/90/97.5 percentiles were calculated for each age group. Males had greater mean fT3 concentrations than females (p < 0.001). No sex-differences were found for TSH and fT4 between age-matched serum samples. Median concentrations of fT3, fT4 and TSH were greatest during the first month of life, followed by a continuous decline with age. CONCLUSION: Our results corroborate those of previous studies showing that thyroid hormone levels change markedly during childhood, and that adult reference intervals are not universally applicable to children. Moreover, differences of our reference intervals compared to previous studies were observed, likely caused by different antibody characteristics of various analytical methods, different populations or undefined geographic covariates, e.g. iodine and selenium status.

The role of selenium, vitamin C, and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma.

BACKGROUND: Thyroid physiology is closely related to oxidative changes. The aim of this controlled study was to evaluate the levels of nutritional anti-oxidants such as vitamin C, zinc (Zn) and selenium (Se), and to investigate any association of them with parameters of thyroid function and pathology including benign and malignant thyroid diseases. METHODS: This controlled evaluation of Se included a total of 1401 subjects (1186 adults and 215 children) distributed as follows: control group (n = 687), benign thyroid disease (85 children and 465 adults); malignant thyroid disease (2 children and 79 adults). Clinical evaluation of patients with benign thyroid disease included sonography, scintigraphy, as well as the determination of fT3, fT4, TSH, thyroid antibodies levels, Se, Zn, and vitamin C. Besides the routine oncological parameters (TG, TSH, fT4, ultrasound) Se was also determined in the cases of malignant disease. The local control groups for the evaluation of Se levels were taken from a general practice (WOMED) as well as from healthy active athletes. Blood samples were collected between 8:00 and 10:30 a.m. All patients lived in Innsbruck. Statistical analysis was done using SPSS 14.0. The Ho stated that there should be no differences in the levels of antioxidants between controls and thyroid disease patients. RESULTS: Among the thyroid disease patients neither vitamin C, nor Zn nor Se correlated with any of the following parameters: age, sex, BMI, body weight, thyroid scintigraphy, ultrasound pattern, thyroid function, or thyroid antibodies. The proportion of patients with benign thyroid diseases having analyte concentrations below external reference cut off levels were 8.7% of cases for vitamin C; 7.8% for Zn, and 20.3% for Se. Low Se levels in the control group were found in 12%. Se levels were significantly decreased in cases of sub-acute and silent thyroiditis (66.4 +/- 23.1 microg/l and 59.3 +/- 20.1 microg/l, respectively) as well as in follicular and papillary thyroid carcinoma. The mean Se level in the control group was 90.5 +/- 20.8 microg/l. CONCLUSION: The H0 can be accepted for vitamin C and zinc levels whereas it has to be rejected for Se. Patients with benign or malignant thyroid diseases can present low Se levels as compared to controls. Low levels of vitamin C were found in all subgroups of patients.

Refining clinical phenotypes in septo-optic dysplasia based on MRI findings.

Septo-optic dysplasia (SOD) is a heterogeneous brain midline anomaly associated with ophthalmological, endocrinological, and/or neurodevelopmental symptoms. The clinical phenotype correlates with abnormal brain magnetic resonance imaging (MRI) findings. However, variations of the septum pellucidum (SP) appearance and their clinical impact have not been studied in depth. Sixty-eight patients with optic nerve hypoplasia (ONH) were investigated for the presence of associated SP anomalies and correlations between clinical findings and their MRI abnormalities established. Thirty patients had either complete (n = 22) or partial (n = 8) absence of the SP. Pituitary hormone deficiencies were present in 64% or 25% of the cases, respectively. Neurological symptoms did not occur in patients with SP remnants or unilateral ONH. Hippocampus abnormalities (43%) that have not been described before in SOD and falx abnormalities (17%) correlated significantly with neurological symptoms and developmental delay (p < 0.05 and p < 0.01, respectively). Maternal age at birth was low (21.2 years) and drug abuse during pregnancy was reported in 27% of the patients. Twelve patients with pituitary anomaly and ONH but normal SP showed similar clinical and MRI features, and were classified as SOD-like. The remaining 26 patients were not assigned to SOD. We conclude that unilateral ONH and SP remnants are associated with a milder SOD phenotype. Hippocampus abnormalities and falx abnormalities seem to constitute important features of severe clinical disease, irrespective of SP appearance. Our anamnestic data support the hypothesis of vascular disruption during embryogenesis.

Sequential measurements of IGF-I serum concentrations in adolescents with Laron syndrome treated with recombinant human IGF-I (rhIGF-I).

Background Recombinant human insulin-like growth factor 1 (rhIGF-I) has been approved as an orphan drug for the treatment of growth failure in children and adolescents with severe primary IGF-I deficiency (SPIGFD) with little pharmacokinetic data available. Therefore, sequential measurements of serum IGF-I, glucose, potassium, insulin and cortisol were performed in patients treated with rhIGF-I to evaluate their significance in safety and efficacy. Methods Repetitive blood samples were taken after meals before and 30, 60, 120, 180 and 360 min after rhIGF-I injections in two male patients with Laron syndrome at times of dose adjustments. Results Maximal IGF-I concentrations were observed 2 h after injections (495 ng/mL) and concentrations were still higher 6 h after injections than at baseline (303 ng/mL vs. 137 ng/mL). Thirteen percent of all and 33% of maximum IGF-I concentrations were greater than +2 standard deviation score (SDS) calculated for bone age (BA) (IGF-I SDS BA) rather than chronological age (CA) as BA was significantly delayed to CA by 3.2 years (p=0.0007). Height velocities correlated with individual maximum IGF-I SDS BA (ρ=0.735; p<0.0001). Serum insulin, cortisol and glucose did not correlate with IGF-I concentrations, but serum potassium showed a negative correlation (ρ=-0.364; p<0.0001) with IGF-I concentrations. Conclusions Sequential measurements of serum IGF-I, glucose and potassium in patients with Laron syndrome may aid in optimizing and individualizing rhIGF-I treatment. IGF-I concentrations should be referenced according to BA which better reflects the biological age. The inverse correlation of IGF-I and serum potassium concentrations after injections of rhIGF-I has not been reported before and warrants further consideration.