Search for other papers by David S McLaren in
Google Scholar
PubMed
Search for other papers by Aarani Devi in
Google Scholar
PubMed
Search for other papers by Nikolaos Kyriakakis in
Google Scholar
PubMed
Search for other papers by Michelle Kwok-Williams in
Google Scholar
PubMed
Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK
Search for other papers by Robert D Murray in
Google Scholar
PubMed
Multimodality cancer therapy has led to remarkable improvements in survival of childhood and young adult cancer, with survival rates exceeding 85%. Such remission rates come with their own adverse sequelea or ‘late effects’. Although the cause of these late effects is multi-factorial, radiation-related adverse effects are one of the most prevalent. Hypopituitarism is a recognised complication of irradiation of brain tumours distant to the hypothalamo-pituitary (HP) axis when the axis is included within the exposed field. Much of the data concerning the development of hypopituitarism, however, relate to early forms of photon-based radiotherapy. In this narrative review, we discuss advances in individual radiotherapy techniques currently used in treating brain tumours and their theoretical benefits based primarily on dosimetric studies. Increasingly precise radiation techniques, including advances in the delivery of photons (i.e. intensity-modulated radiotherapy) and proton beam therapy, are now available options. The premise behind these newer techniques is to reduce the dose and volume of normal tissue irradiated whilst maintaining an effective radiation dose to target tissue. When treating brain tumours distant to the HP axis the expectation, based upon dosimetric studies, is that newer forms of radiotherapy will less frequently involve the HP axis in the exposed field, and where incorporated within the field it will be exposed to a lower radiotherapy dosage. Intuitively the dosimetric studies should translate into significant reductions in the prevalence of HP dysfunction. These data are promising; however, to date there are minimal robust clinical data to determine if the theoretical benefits of these newer techniques on HP dysfunction is to be realised.
Amsterdam Public Health, Quality of Care, Amsterdam, The Netherlands
Search for other papers by Chiara Jongerius in
Google Scholar
PubMed
Amsterdam Public Health, Quality of Care, Amsterdam, The Netherlands
Search for other papers by Marij A Hillen in
Google Scholar
PubMed
Amsterdam Public Health, Quality of Care, Amsterdam, The Netherlands
Search for other papers by Ellen M A Smets in
Google Scholar
PubMed
Search for other papers by Mathijs J Mol in
Google Scholar
PubMed
Search for other papers by Eefje S Kooij in
Google Scholar
PubMed
Search for other papers by Maria A de Nood in
Google Scholar
PubMed
Search for other papers by Edwin S Dalmaijer in
Google Scholar
PubMed
Search for other papers by Eric Fliers in
Google Scholar
PubMed
Search for other papers by Johannes A Romijn in
Google Scholar
PubMed
Department of Rare Disorders and Disabilities, Oslo University Hospital, NevSom, Oslo, Norway
University of Oslo, Norwegian Centre for Mental Disorders Research (NORMENT) and KG Jebsen Centre for Neurodevelopmental Disorders, Oslo, Norway
Search for other papers by Daniel S Quintana in
Google Scholar
PubMed
The patient–physician relationship is a critical determinant of patient health outcomes. Verbal and non-verbal communication, such as eye gaze, are vital aspects of this bond. Neurobiological studies indicate that oxytocin may serve as a link between increased eye gaze and social bonding. Therefore, oxytocin signaling could serve as a key factor influencing eye gaze as well as the patient–physician relationship. We aimed to test the effects of oxytocin on gaze to the eyes of the physician and the patient–physician relationship by conducting a randomized placebo-controlled crossover trial in healthy volunteers with intranasally administered oxytocin (with a previously effective single dose of 24 IU, EudraCT number 2018-004081-34). The eye gaze of 68 male volunteers was studied using eye tracking during a simulated video call consultation with a physician, who provided information about vaccination against the human papillomavirus. Relationship outcomes, including trust, satisfaction, and perceived physician communication style, were measured using questionnaires and corrected for possible confounds (social anxiety and attachment orientation). Additional secondary outcome measures for the effect of oxytocin were recall of information and pupil diameter and exploratory outcomes included mood and anxiety measures. Oxytocin did not affect the eye-tracking parameters of volunteers’ gaze toward the eyes of the physician. Moreover, oxytocin did not affect the parameters of bonding between volunteers and the physician nor other secondary and exploratory outcomes in this setting. Bayesian hypothesis testing provided evidence for the absence of effects. These results contradict the notion that oxytocin affects eye gaze patterns or bonding.
Search for other papers by Dan Liang in
Google Scholar
PubMed
Search for other papers by Han Chen in
Google Scholar
PubMed
Search for other papers by Li-Yong Zhong in
Google Scholar
PubMed
Purpose
Intracranial germ cell tumors frequently arise from the midline of the brain, occasionally presenting as bifocal diseases. The predominant lesion might affect clinical characteristics and neuroendocrine outcomes.
Method
A retrospective cohort study involving 38 patients with intracranial bifocal germ cell tumors was performed.
Result
Twenty-one patients were assigned to the sellar-predominant group, while the other 17 patients were assigned to the non-sellar-predominant group. Differences in gender ratio, age, manifestation, the incidence of metastasis, the incidence of elevated tumor markers, human chorionic gonadotropin levels in serum and in cerebrospinal fluid, diagnostic method, and tumor type were not significant between the sellar-predominant group and the non-sellar-predominant group. Before treatment, the sellar-predominant group had a higher incidence of adenohypophysis hormone deficiencies and central diabetes insipidus than those of the non-sellar-predominant group, without significant differences. After multidisciplinary therapy, the sellar-predominant group also had a higher incidence of adenohypophysis hormone deficiencies and central diabetes insipidus than those of the non-sellar-predominant group. The differences in the hypothalamic–pituitary–adrenal (HPA) axis impairment (P = 0.008), hypothalamic–pituitary–thyroid (HPT) axis impairment (P = 0.048), and hypothalamic–pituitary–gonad (HPG) axis impairment (P = 0.029) were significant between sellar-predominant group and non-sellar-predominant group, while the others were not. At median 6 (3, 43) months of follow-up visit, sellar-predominant group had a higher incidence of adenohypophysis hormone deficiencies than those of non-sellar-predominant group. The differences in the HPA impairment (P = 0.002), HPT impairment (P = 0.024), and HPG impairment (P < 0.000) were significant, while the others were not. Further comparison of the neuroendocrine function between different subtypes of sellar-predominant patients indicated that the differences in adenohypophysis hormone deficiencies and central diabetes insipidus were not significant between the two subtype groups.
Conclusion
Bifocal patients with different predominant lesions present similar manifestations and neuroendocrine disorders before treatment. Non-sellar-predominant patients would have better neuroendocrine outcomes after tumor treatment. The distinction of the predominant lesion in patients with bifocal intracranial germ cell tumor plays a valuable role in predicting neuroendocrine outcomes, as well as in optimizing long-term neuroendocrine management during survival time.
Search for other papers by Kevin C J Yuen in
Google Scholar
PubMed
Search for other papers by Gudmundur Johannsson in
Google Scholar
PubMed
Search for other papers by Ken K Y Ho in
Google Scholar
PubMed
Search for other papers by Bradley S Miller in
Google Scholar
PubMed
Search for other papers by Ignacio Bergada in
Google Scholar
PubMed
Search for other papers by Alan D Rogol in
Google Scholar
PubMed
Growth hormone deficiency (GHD) is a clinical syndrome that can manifest either as isolated or associated with additional pituitary hormone deficiencies. Although diminished height velocity and short stature are useful and important clinical markers to consider testing for GHD in children, the signs and symptoms of GHD are not always so apparent in adults. Quality of life and metabolic health are often impacted in patients with GHD; thus, making an accurate diagnosis is important so that appropriate growth hormone (GH) replacement therapy can be offered to these patients. Screening and testing for GHD require sound clinical judgment that follows after obtaining a complete medical history of patients with a hypothalamic–pituitary disorder and a thorough physical examination with specific features for each period of life, while targeted biochemical testing and imaging are required to confirm the diagnosis. Random measurements of serum GH levels are not recommended to screen for GHD (except in neonates) as endogenous GH secretion is episodic and pulsatile throughout the lifespan. One or more GH stimulation tests may be required, but existing methods of testing might be inaccurate, difficult to perform, and can be imprecise. Furthermore, there are multiple caveats when interpreting test results including individual patient factors, differences in peak GH cut-offs (by age and test), testing time points, and heterogeneity of GH and insulin-like growth factor 1 assays. In this article, we provide a global overview of the accuracy and cut-offs for diagnosis of GHD in children and adults and discuss the caveats in conducting and interpreting these tests.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jesper Krogh in
Google Scholar
PubMed
Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Search for other papers by Peter Plomgaard in
Google Scholar
PubMed
Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Search for other papers by Ruth Frikke-Schmidt in
Google Scholar
PubMed
Search for other papers by Sten Velschow in
Google Scholar
PubMed
Department of Pediatrics, Copenhagen University Hospital - Herlev & Gentofte, Copenhagen, Denmark
Search for other papers by Jesper Johannesen in
Google Scholar
PubMed
Search for other papers by Linda Maria Hilsted in
Google Scholar
PubMed
Search for other papers by Malene Schrøder in
Google Scholar
PubMed
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Ulla Feldt-Rasmussen in
Google Scholar
PubMed
Repeated blood sampling is required in certain clinical and research settings, which is currently performed by drawing blood from venous catheters requiring manual handling of each sample at the time of collection. A novel body-worn device for repeated serial samples, Fluispotter®, with automated extraction, collection, and storage of up to 20 venous dried blood spot samples over the course of 20 h may overcome problems with current methods for serial sampling. The purpose of this study was to assess the performance and safety of Fluispotter for the first time in healthy subjects. Fluispotter consists of a cartridge with tubing, a reservoir for flushing solution, pumps and filterpaper, and a multi-lumen catheter placed in the brachial vein. We recruited healthy subjects for testing in an in-hospital setting. Fluispotter was attached by an anesthesiologist to 22 healthy subjects of which 9/22 (40.9%) participants had all 20 samples taken, which was lower than the goal of complete sampling in 80% of the subjects (P = 0.02). The main reason for sample failure was clogging of blood flow which was observed in 11/22 (50%) of the participants. No serious adverse events occurred, and the participants rated the pain from the insertion and the removal of catheter as very low. A cortisol profile showed nadir values at midnight and highest values at 05:00 h. Although full sampling was not successful in all participants, the Fluispotter technology proved safe and highly acceptable to the participants producing the expected cortisol profile without the requirement of staff during sample collection.
Search for other papers by Ja Hye Kim in
Google Scholar
PubMed
Search for other papers by Yunha Choi in
Google Scholar
PubMed
Search for other papers by Soojin Hwang in
Google Scholar
PubMed
Search for other papers by Ji-Hee Yoon in
Google Scholar
PubMed
Search for other papers by Jieun Lee in
Google Scholar
PubMed
Search for other papers by Min Jae Kang in
Google Scholar
PubMed
Search for other papers by Gu-Hwan Kim in
Google Scholar
PubMed
Search for other papers by Han-Wook Yoo in
Google Scholar
PubMed
Search for other papers by Jin-Ho Choi in
Google Scholar
PubMed
Objective
This study was performed to investigate the molecular characteristics and frequency of copy number variations (CNVs) of ANOS1 in patients with Kallmann syndrome (KS) or normosmic isolated hypogonadotropic hypogonadism (nIHH) using multiplex ligation-dependent probe amplification (MLPA) analysis and sequencing.
Methods
Among 45 patients from 43 independent families, Sanger sequencing, next-generation sequencing (NGS), or microarray was performed in 24 patients from 23 families, and MLPA was performed in 19 patients who did not show rare sequence variants (n = 18) or ANOS1 amplification by PCR (n = 1).
Results
Seven patients (four patients with KS, one patient with nIHH, one prepubertal boy with anosmia, and one newborn patient) from six families (6/43, 14%) harbored molecular defects in ANOS1 including a nonsense mutation (c.1140G>A (p.W380*)), a frameshift mutation (c.1260del (p.Q421Kfs*61)), a splice site mutation (c.1449+1G>A), an exon 7 deletion, a complete deletion, and 7.9 Mb-sized inversion encompassing ANOS1. The complete deletion of ANOS1 was identified in a neonate with a micropenis and cryptorchidism. Unilateral renal agenesis was found in three patients, whereas only one patient displayed both synkinesia and sensorineural hearing loss. There was no reversal of hypogonadotropic hypogonadism in any patient during 9.1 ± 2.9 years of treatment with testosterone enanthate.
Conclusions
Molecular defects in the ANOS1 gene could be identified in 14% of probands including various types of CNVs (3/43, 7.0%). Comprehensive analysis using sequencing and analysis for CNVs is required to detect molecular defects in ANOS1.
Search for other papers by Brijesh Krishnappa in
Google Scholar
PubMed
Search for other papers by Ravikumar Shah in
Google Scholar
PubMed
Search for other papers by Saba Samad Memon in
Google Scholar
PubMed
Search for other papers by Chakra Diwaker in
Google Scholar
PubMed
Search for other papers by Anurag R Lila in
Google Scholar
PubMed
Search for other papers by Virendra A Patil in
Google Scholar
PubMed
Search for other papers by Nalini S Shah in
Google Scholar
PubMed
Search for other papers by Tushar R Bandgar in
Google Scholar
PubMed
Objectives
High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.
Design
We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (<6.5 vs 6.5–12 vs >12 weeks) of glucocorticoid treatment according to disease severity.
Results
A total of 153 PAH patients from 83 publications were included. The median age at presentation was 41 (32.5–48) years with a female preponderance (70.3%). Visual field recovery was significantly better with i.v. (91.7%) as compared to oral (54.5%) route and high dose (100%) and very high dose (90.9%) as compared to medium dose (20%) of glucocorticoids. Corticotroph axis recovery was greater in i.v. (54.8% vs 28.1% oral, P = 0.033) route and increasing glucocorticoid dose group (0% vs 38.1% vs 57.1%), attaining statistical significance (P = 0.012) with very high-dose. A longer duration of treatment (>6.5 weeks) was associated with better corticotroph and thyrotroph recovery. The need for rescue therapy was lower with i.v. route (38% vs 17.5%, P = 0.012) and with increasing glucocorticoid doses (53.3% vs 34.3% vs 17.3%, P = 0.016). In severe disease, visual field and corticotroph axis recovery were significantly higher with i.v. route and very high-dose steroids. The adverse effects of glucocorticoids were independent of dose and duration of treatment.
Conclusions
Very high-dose glucocorticoids by i.v. route and cumulative longer duration (>6.5 weeks) lead to better outcomes and could be considered as first-line treatment of severe PAH cases.
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Mette Marie Baunsgaard in
Google Scholar
PubMed
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Anne Sophie Lind Helligsoe in
Google Scholar
PubMed
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Louise Tram Henriksen in
Google Scholar
PubMed
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Torben Stamm Mikkelsen in
Google Scholar
PubMed
Search for other papers by Michael Callesen in
Google Scholar
PubMed
Search for other papers by Britta Weber in
Google Scholar
PubMed
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Henrik Hasle in
Google Scholar
PubMed
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Niels Birkebæk in
Google Scholar
PubMed
Objective
Growth hormone deficiency (GHD) is the most common endocrine late effect in irradiated survivors of childhood brain tumors. This study aimed to determine the prevalence of GHD in adults treated with proton or photon irradiation for a brain tumor in childhood and to detect undiagnosed GHD.
Design
This study is a cross-sectional study.
Methods
We investigated GHD in 5-year survivors from two health regions in Denmark treated for childhood brain tumors with cranial or craniospinal irradiation in the period 1997–2015. Medical charts were reviewed for endocrinological and other health data. Survivors without a growth hormone (GH) test at final height were invited to a GH stimulation test.
Results
Totally 41 (22 females) survivors with a median age of 21.7 years (range: 15.1–33.8 years) at follow-up and 14.8 years (range: 5.1–23.4 years) since diagnosis were included; 11 were treated with proton and 30 with photon irradiation; 18 of 21 survivors were previously found to have GHD; 16 of 20 survivors with no GH test at final height were tested, 8 (50 %) had GHD. In total, 26 of 41 patients (63%) had GHD. Insulin-like growth factor-1 (IGF-1) is associated poorly with the insulin tolerance test (ITT).
Conclusion
This study identified a high prevalence of undiagnosed GHD in survivors with no GH test at final height. The results stress the importance of screening for GHD at final height in survivors of childhood brain tumors with prior exposure to cranial irradiation, irrespective of radiation modality and IGF-1.
Significance statement
This cross-sectional study reports a prevalence of 63% of GHD in irradiated childhood brain tumor survivors. Furthermore, the study identified a considerable number of long-term survivors without a GH test at final height, of whom, 50% subsequently were shown to have undiagnosed GHD. Additionally, this study confirmed that a normal serum IGF-1 measurement cannot exclude the diagnosis of GHD in irradiated survivors. This illustrates the need for improvements in the diagnostic approach to GHD after reaching final height in childhood brain tumor survivors at risk of GHD. In summary, our study stresses the need for GHD testing in all adult survivors treated with cranial irradiation for a brain tumor in childhood irrespective of radiation modality.
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
Search for other papers by Savi R Shishkov in
Google Scholar
PubMed
Università “Federico II” di Napoli, Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Naples, Italy
Search for other papers by Luigi Tuccillo in
Google Scholar
PubMed
Search for other papers by Violeta M Iotova in
Google Scholar
PubMed
Search for other papers by Rosario Pivonello in
Google Scholar
PubMed
Search for other papers by Iris CM Pelsma in
Google Scholar
PubMed
Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology & Metabolism, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
Search for other papers by Alberto M Pereira in
Google Scholar
PubMed
Adult Chair of MTG Pituitary of Endo-ERN
Search for other papers by Nienke R Biermasz in
Google Scholar
PubMed
Search for other papers by the Endo-ERN Reference Centers of the Main Thematic Group: Hypothalamic and Pituitary Conditions, Endo-ERN Pituitary Transition of Care Study Group in
Google Scholar
PubMed
Rare endocrine conditions present specific diagnostic and management challenges for healthcare providers, one of which is the understudied transition of care. Despite the need for guidance regarding transition, consensus on structured and protocolled approaches is lacking. Therefore, we aimed to map the current clinical practice and identify unmet needs regarding transition of care for patients with pituitary disease in the reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN). A survey-based, cross-sectional study using the EU Survey tool was performed and completed by 46 physicians (n) from 30 RCs (N). Transition is a common practice among RCs (n = 44/46), usually accomplished by a multidisciplinary team meeting (N = 20/30). Criteria for start and end of transition were defined in half of the RCs, with 16.7% of centers providing dissimilar answers. Transition readiness was assessed by >75% of the RCs, mostly by unvalidated means (e.g. subjective opinions, informal consultations). Pituitary-specific transition assessment tool was applied in one RC only. Transition protocols were present in only 9% of RCs, while in many RCs, transition decisions were taken in combined adult-pediatric meetings or based on clinicians’ personal judgment. A minority of physicians evaluated the effectiveness of transition-related interventions (n = 11/46) or medical outcomes (n = 8/46). Patient-reported outcome measures were infrequently used (n = 4/46). Identified unmet needs included the development of guidelines (n = 5/46) and EU-wide approach (n = 2/46). This study exemplifies the unmet needs for a structural definition of the transition period and transition management for patients with rare hypothalamic and pituitary conditions from healthcare providers’ perspective.
Princess Máxima Center for Pediatric Oncology, AB Utrecht, The Netherlands
Search for other papers by Ichelle Maa van Roessel in
Google Scholar
PubMed
Princess Máxima Center for Pediatric Oncology, AB Utrecht, The Netherlands
Search for other papers by Boudewijn Bakker in
Google Scholar
PubMed
Princess Máxima Center for Pediatric Oncology, AB Utrecht, The Netherlands
Search for other papers by Hanneke M van Santen in
Google Scholar
PubMed
Search for other papers by Wassim Chemaitilly in
Google Scholar
PubMed
Childhood cancer survivors are at risk for developing endocrine disorders, including deficits in growth hormone, thyroid hormone and sex hormones. The influence these hormones have on cell growth and metabolism has raised concerns regarding the safety of their use as treatments in survivors of childhood cancer and brain tumors. This article offers a summary of current knowledge, controversies and areas for future research pertaining to this area.
