Implications of deferred diagnosis of paediatric intracranial germ cell tumours.

AIMS: This study analysed the clinical features of a cohort of children with intracranial germ cell tumours (IC-GCTs). We retrospectively reviewed timelag between symptoms onset, clinic-radiological findings, diagnosis and outcomes. METHODS: Symptoms at diagnosis were divided into four groups: (1) raised intracranial pressure (RICP); (2) visual impairment; (3) endocrinopathies; (4) other. Total diagnostic interval (TDI), defined as the interval between symptom onset (including retrospective recall of symptoms) and definitive diagnosis of IC-GCT, was calculated and compared to survival rates. RESULTS: Our cohort included 55 children with median follow-up of 78.9 months (0.5-249.9). The majority (63.6%) had germinomas and 10.9% were metastatic at diagnosis. IC-GCTs were suprasellar (41.8%), pineal (36.4%), bifocal (12.7%) or in atypical sites (9.1%). The most common presenting symptoms were related to RICP (43.6%); however, by the time of tumour diagnosis, 50.9% of patients had developed endocrine dysfunctions. All pineal GCTs manifested with RICP or visual impairment. All suprasellar GCTs presented with endocrinopathies. TDI ranged between 0.25 and 58.5 months (median 4 months). Pineal GCTs had the shortest TDI (median TDI 1 month versus 24 months in suprasellar GCTs, p < .001). TDI > 6 months was observed in 47.3% of patients and was significantly associated with endocrine presenting symptoms. No statistically significant difference was found in progression-free survival and overall survival between patients with TDI > 6 months and with TDI ≤ 6 months. CONCLUSION: Approximately half of the IC-GCT patients in this cohort had TDI > 6 months. These presented mostly with endocrine deficits. TDI > 6 months was not associated with increased relapse or mortality rates.

A mutation in the thyroid hormone receptor alpha gene.

Thyroid hormones exert their effects through alpha (TRα1) and beta (TRß1 and TRß2) receptors. Here we describe a child with classic features of hypothyroidism (growth retardation, developmental retardation, skeletal dysplasia, and severe constipation) but only borderline-abnormal thyroid hormone levels. Using whole-exome sequencing, we identified a de novo heterozygous nonsense mutation in a gene encoding thyroid hormone receptor alpha (THRA) and generating a mutant protein that inhibits wild-type receptor action in a dominant negative manner. Our observations are consistent with defective human TRα-mediated thyroid hormone resistance and substantiate the concept of hormone action through distinct receptor subtypes in different target tissues.

Arginine Vasopressin Deficiency in Children with Craniopharyngioma and Cerebral Germ Cell Tumour: Two Sides of the Same Coin. Clinical and Radiological features.

INTRODUCTION: Paediatric brain tumours in the sellar-suprasellar region (SSR) are often associated with arginine vasopressin peptide deficiency (AVPD), either at diagnosis caused by the tumour itself or during follow-up as consequence of treatments. The purpose of this research is to retrospectively describe the neuroradiological characteristics and the timing of AVPD development in a cohort of paediatric patients with craniopharyngioma (CP) or germ cell tumours (GCT). METHODS: We evaluated brain MRI at tumour diagnosis and at the onset of AVPD, as well as recorded clinical, endocrinological and histopathological data, treatments, and outcome. RESULTS: Seventy-two patients with AVPD were included: 46 CP (M: F=25:21) and 26 GCT (M: F=18:8). CPs were suprasellar (63%), sellar (4%) or both (33%). GCTs were suprasellar (65%), pineal (24%) or bifocal (11%). No statistically significant differences were noted in tumour size between CP and GCT. Posterior pituitary bright spot absence was reported at diagnosis or at follow-up (as surgery consequence) in all patients with AVPD, indicating that the absence of hyperintensity is a cardinal feature of AVPD. When measurable, pituitary stalk was thickened in most GCT patients (61.5%). At AVPD diagnosis in GCT, the mean age was 11.9 years; 18 (69%) patients had AVPD at the time of tumour diagnosis, 5 (19.3%) before the diagnosis with a latency of 24.4 months (range 4-48), and 3 (11.5%) during follow-up (mean 24 months, range 4-60) due to tumour recurrence. GCT patients presented with severe endocrinological manifestations (18/26), headache and vomiting (10/26), visual impairment (5/26) and behavioural changes with fatigue (1/26). In CP, the mean age at AVPD diagnosis was 10.3 years; 7 (15.2%) patients had AVPD at time of tumour diagnosis, 37 (80.5%) developed it shortly after neurosurgery and 2 patients (4.3%) after 2 and 4 months from surgery, respectively. Clinically, headache and visual abnormalities were the most frequent clinical symptoms at diagnosis of CP (39/46, 84.8%), with hydrocephalus (16/46, 35%) and displacement of optic chiasm (29/46, 63%) at the initial MRI. While the vast majority of CP patients (93%) received only surgery, all GCT patients received radiation therapy in addition to or instead of surgery. CONCLUSION: An early differential diagnosis in children with AVPD and brain tumours is supported by a good understanding of the clinical features and imaging findings. Expert follow-up is necessary.

Treatment of high risk Sertoli-Leydig cell tumors of the ovary using a gonadotropin releasing hormone (GnRH) analog.

Sertoli-Leydig cell tumors are rare ovarian neoplasms. We report two unusual cases with bilateral SLCTs suggesting evidence of genetic predisposition and at high risk of recurrence. To reduce this risk, we exploited the use of GnRH analog to lower gondadotropin and potentially directly inhibit the tumors through expressed GnRH receptors. We used it as maintenance antitumor therapy for 2 years after completion of chemotherapy, to cover the period of risk for recurrence. Both patients remain in complete remission at >2 years after completing leuprorelin therapy. Of note, both patients carry DICER1 mutations, frequently found in pleuropulmonary blastoma syndrome.

Novel therapeutic approaches for pediatric diencephalic tumors: improving functional outcomes.

Pediatric diencephalic tumors represent a histopathologically and molecularly diverse group of neoplasms arising in the central part of the brain and involving eloquent structures, including the hypothalamic-pituitary axis (HPA), optic pathway, thalamus, and pineal gland. Presenting symptoms can include significant neurological, endocrine, or visual manifestations which may be exacerbated by injudicious intervention. Upfront multidisciplinary assessment and coordinated management is crucial from the outset to ensure best short- and long-term functional outcomes. In this review we discuss the clinical and pathological features of the neoplastic entities arising in this location, and their management. We emphasize a clear move towards 'function preserving' diagnostic and therapeutic approaches with novel toxicity-sparing strategies, including targeted therapies.

National UK guidelines for the management of paediatric craniopharyngioma.

Although rare, craniopharyngiomas constitute up to 80% of tumours in the hypothalamic-pituitary region in childhood. Despite being benign, the close proximity of these tumours to the visual pathways, hypothalamus, and pituitary gland means that both treatment of the tumour and the tumour itself can cause pronounced long-term neuroendocrine morbidity against a background of high overall survival. To date, the optimal management strategy for these tumours remains undefined, with practice varying between centres. In light of these discrepancies, as part of a national endeavour to create evidence-based and consensus-based guidance for the management of rare paediatric endocrine tumours in the UK, we aimed to develop guidelines, which are presented in this Review. These guidelines were developed under the auspices of the UK Children's Cancer and Leukaemia Group and the British Society for Paediatric Endocrinology and Diabetes, with the oversight and endorsement of the Royal College of Paediatrics and Child Health using Appraisal of Guidelines for Research & Evaluation II methodology to standardise care for children and young people with craniopharyngiomas.

Organ-specific management and supportive care in chronic graft-versus-host disease.

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology and the British Society for Bone Marrow Transplantation has reviewed the available literature and made recommendations for the supportive care and management of organ-specific complications of chronic graft-versus-host disease (cGvHD). This guideline includes recommendations for the specific therapy of skin, oral, liver, gut, lung, ocular and genital manifestations of cGvHD and for the supportive care of these patients, including vaccinations and prophylaxis against infection. The goal of treatment should be effective control of GvHD while minimizing the risk of toxicity and relapse.

A case of stage IV neuroblastoma in a child with congenital adrenal hyperplasia (CAH): a case report and review of literature.

Neuroblastoma in a known case of congenital adrenal hyperplasia has rarely been reported. The management of such a patient in the background of hormonal imbalance can be very challenging. In this report, we share our experience in managing such a child and discuss the clinical dilemma.

Initiating growth hormone therapy for children and adolescents.

It is common for children and adolescents on growth hormone (GH) treatment to miss one or more injections per week, thereby compromising their linear growth outcome. Among factors likely to affect treatment concordance are patient education and support in the selection of the most appropriate GH injection device. The authors discovered inconsistencies in the process of starting patients on GH therapy throughout the UK, and found that there were no clinical recommendations to support health professionals starting patients on treatment. This article describes the issues involved and the development of practical recommendations for use when starting paediatric patients on long-term GH therapy.

Case report: Fluctuating tumor markers in a boy with gonadotropin-releasing hormone-independent precocious puberty induced by a pineal germ cell tumor.

GnRH-independent precocious puberty (GIPP) can be the presenting clinical picture experienced by patients with secreting germ cell tumor (GCT). Indeed, as luteinizing hormone (LH) and human chorionic gonadotropin (hCG) share identical α-subunits and similar ß-subunits, an increased secretion of ß-hCG may result in a precocious activation of Leydig cells. Though the co-occurrence of raised ß-hCG levels and signs of precocious virilization usually prompts a complete oncological work-up, the diagnostic and therapeutic management of GCT-induced GIPP may be challenging. We report the case of a 6.2 year-old boy presenting with clinical and biochemical findings consistent with GIPP (discrepancy between overt virilization and pre-pubertal testicular volume, suppressed gonadotropins and remarkably raised testosterone). Brain imaging detected a bilobed cyst of the pineal gland, while serum and cerebrospinal baseline assessment initially ruled out raised alpha-fetoprotein or ß-hCG levels. Nevertheless, a strict biochemical follow-up highlighted a fluctuant trend of tumor markers, with a more aggressive behavior and recurrent erections occurring as a result of unpredictable phases of raised testosterone and serum/cerebrospinal ß-hCG, followed by sudden spontaneous decrease. Accordingly, a secreting pineal GCT was suspected. Given the fluctuating trend of tumor markers, surgery was initially kept on hold and a combined treatment with bicalutamide (androgen receptor blocker) and anastrozole (aromatase inhibitor) was undertaken in order to prevent the patient from experiencing further virilization and excessive bone age maturation. Subsequently, a progression in the size of the pineal tumor prompted surgical resection and a diagnosis of secreting GCT was histologically confirmed. Accordingly, the patient was started on adjuvant chemo- and radiotherapy. Antineoplastic treatment was followed by persistent and remarkable decrease of tumor markers and by a complete pubertal arrest. We reported the challenging diagnosis of a secreting pineal GCT in a patient with GIPP and a fluctuating trend of tumor markers, testosterone levels and associated clinical signs, hence prompting the indication for a systematic assessment and a strict monitoring whenever a patient with GnRH-independent precocious puberty shows clinical or radiological markers potentially consistent with a GCT.

Sex steroid priming in short stature children unresponsive to GH stimulation tests: Why, who, when and how.

Despite decades of experience, the diagnosis of growth hormone deficiency (GHD) remains challenging, especially in peripubertal children. Failure to respond to GH stimulation tests (GHSTs) is needed to confirm GHD, but long-standing controversies regarding the number of tests needed and the interpretation of GH peaks are still a matter of debate worldwide. Diagnostic workup is even more problematic in short children with slow growth and delayed sexual development: they often exhibit low GH peaks under GHST, which often normalize as puberty progresses. Consequently, this transient suboptimal response to GHST may result in GH overtreatment, carrying both health and economic concerns. Considering the complex and bound link between GH axis and sex steroids, the use of sex steroid priming prior to GHST might be helpful in peripubertal setting. However, its use is still controversial. There is no consensus regarding patient selection, timing, dose, and preparation of sex steroids. In this review, we aim to overview the use of sex steroid priming in clinical practice, highlighting the need to develop appropriate guidelines in order to overcome diagnostic pitfalls in peripubertal age.

Endocrine manifestations of paediatric intracranial germ cell tumours: from diagnosis to long-term follow-up.

PURPOSE: We examined endocrine manifestations in a cohort of paediatric patients with IC-GCTs at diagnosis and during follow-up, integrating clinical, radiological, histopathological and laboratory data. METHODS: Diabetes insipidus (DI), growth hormone deficiency (GHD), hypothyroidism, adrenal insufficiency, precocious puberty (PP)/hypogonadism were diagnosed clinically and biochemically. The prevalence of endocrine manifestations was compared to survival rates. RESULTS: Our population included 55 children (37 males, 18 females) diagnosed with IC-GCT with a median follow-up of 78.9 months from diagnosis (range 0.5-249.9). At tumour diagnosis, 50.9% patients displayed endocrinopathies: among them, 85.7% were affected by DI, 57.1% central adrenal insufficiency, 50% central hypothyroidism, 28.5% GHD, 10.7% hypogonadotrophic hypogonadism, 10.7% PP. These patients presented predominantly with suprasellar germinoma. If not diagnosed previously, endocrine disorders arose 15.15 months (1.3-404.2) after end of treatment (EOT) in 16.4% patients. At least one endocrinopathy was identified in 67.3% of subjects at last follow-up visit, especially GHD and adrenal insufficiency. DI, hypothyroidism, and adrenal insufficiency occurred earlier than other abnormalities and frequently preceded tumour diagnosis. Subjects with and without endocrine manifestations who survived beyond 12 months after EOT did not show significant difference in overall survival and progression-free survival (p = 0.28 and p = 0.88, respectively). CONCLUSION: Endocrinopathies were common presenting symptoms in our population. If present at diagnosis, they often persisted hence after. The spectrum of endocrinopathies expanded during follow-up up to 33.7 years after EOT. Although they did not seem to affect survival rate in our cohort, close lifelong surveillance is mandatory to provide the best care for these patients.

EANO, SNO and Euracan consensus review on the current management and future development of intracranial germ cell tumors in adolescents and young adults.

The incidence of intracranial germ cell tumors (iGCT) is much lower in European and North American (E&NA) than in Asian population. However, E&NA cooperative groups have simultaneously developed with success treatment strategies with specific attention paid to long-term sequelae. Neurological sequelae may be reduced by establishing a diagnosis with an endoscopic biopsy and/or cerebrospinal fluid (CSF) and/or serum analysis, deferring the need to perform a radical surgery. Depending on markers and/or histological characteristics, patients are treated as either germinoma or non-germinomatous germ cell tumors (NGGCT). Metastatic disease is defined by a positive CSF cytology and/or distant drops in craniospinal MRI. The combination of surgery and/or chemotherapy and radiation therapy is tailored according to grouping and staging. With more than 90% 5-year event-free survival (EFS), localized germinomas can be managed without aggressive surgery, and benefit from chemotherapy followed by whole ventricular irradiation with local boost. Bifocal germinomas are treated as non-metastatic entities. Metastatic germinomas may be cured with craniospinal irradiation. With a 5-year EFS over 70%, NGGCT benefit from chemotherapy followed by delayed surgery in case of residual disease, and some form of radiotherapy. Future strategies will aim at decreasing long-term side effects while preserving high cure rates.

Peer Review of Paediatric Endocrine Services in the UK: A Template for Quality and Service Improvement.

BACKGROUND: Independent peer review of healthcare services can complement existing internal-, institutional-, and national-level regulatory mechanisms aimed at improving quality of healthcare. However, this has not been reported for paediatric endocrinology services in the UK. We aimed to test feasibility and acceptability through a first cycle of a national peer review of paediatric endocrine services. METHODS: Tertiary centres in paediatric endocrinology across the UK were assessed against 54 quality standards, developed by the British Society for Paediatric Endocrinology and Diabetes (BSPED) in five domains of healthcare by a team comprising paediatric endocrinologists and specialist nurses. The evaluation was supported by a self-assessment. A post-peer-review questionnaire was used as feedback. RESULTS: All 22 centres in the UK underwent independent peer review between 2011 and 2017. Each served a median population of 2.6 million (range 1-8 million) and offered 1,872 (range 779-6,738) outpatient consultations annually. A total of 43 (range 30-49) standards were met in combined evaluation of all centres. Variance of adherence for essential standards ranged from 52 to 97% at individual centres with 90% adherence demonstrated by 32% of centres. Post-review feedback showed 20/22 (95%) validating the utility of the peer review. CONCLUSIONS: The BSPED peer review of all UK centres providing paediatric endocrine services is shown to be feasible and provides a quality benchmark for replication by national services.

Response to GH Treatment After Radiation Therapy Depends on Location of Irradiation.

OBJECTIVES: Cancer survivors with GH deficiency (GHD) receive GH therapy (GHT) after 1+ year observation to ensure stable tumor status/resolution. HYPOTHESIS: Radiation therapy (RT) to brain, spine, or extremities alters growth response to GHT. AIM: Identify differences in growth response to GHT according to type/location of RT. METHODS: The Pfizer International Growth Database was searched for cancer survivors on GHT for ≥5 years. Patient data, grouped by tumor type, were analyzed for therapy (surgery, chemotherapy, RT of the focal central nervous system, cranial, craniospinal, or total body irradiation [TBI] as part of bone marrow transplantation), sex, peak stimulated GH, age at GHT start, and duration from RT to GHT start. Kruskal-Wallis test and quantile regression modeling were performed. RESULTS: Of 1149 GHD survivors on GHT for ≥5 years (male 733; median age 8.4 years; GH peak 2.8 ng/mL), 431 had craniopharyngioma (251, cranial RT), 224 medulloblastoma (craniospinal RT), 134 leukemia (72 TBI), and 360 other tumors. Median age differed by tumor group (P < 0.001). Five-year delta height SD score (SDS) (5-year ∆HtSDS; median [10th-90th percentile]) was greatest for craniopharyngioma, 1.6 (0.3-3.0); for medulloblastoma, 5-year ∆HtSDS 0.9 (0.0-1.9); for leukemia 5-year ∆HtSDS, after TBI (0.3, 0-0.7) versus without RT (0.5, 0-0.9), direct comparison P < 0.001. Adverse events included 40 treatment-related, but none unexpected. CONCLUSIONS: TBI for leukemia had significant impact on growth response to GHT. Medulloblastoma survivors had intermediate GHT response, whereas craniopharyngioma cranial RT did not alter GHT response. Both craniospinal and epiphyseal irradiation negatively affect growth response to GH therapy compared with only cranial RT or no RT.

The Predictive Value of Insulin-Like Growth Factor 1 in Irradiation-Dependent Growth Hormone Deficiency in Childhood Cancer Survivors.

BACKGROUND: The literature contains conflicting reports on the value of low insulin-like growth factor 1 (IGF-1) levels in predicting radiation-induced growth hormone (GH) deficiency (GHD) in childhood cancer survivors (CCS). These reports often involve small samples of patients who have received irradiation or mixed cohorts including non-irradiated subjects. OBJECTIVE: We undertook an analysis of the predictive value of low IGF-1 in CCS at risk for GHD after cranial radiotherapy involving the hypothalamic-pituitary (HP) area in a large single-centre cohort. METHODS: We performed a retrospective analysis on 158 CCS diagnosed with GHD between January 1, 2003 and October 31, 2017 and identified 117 patients who received radiation for tumours not direct ly involving the HP area. RESULTS: In this cohort, IGF-1 levels <-2 standard deviation scores (SDS) had a sensitivity of 31.9% for GHD; however, they were statistically more frequent (p = 0.0023) and had a higher sensitivity (45.6%) among patients with severe GHD. At final height reassessment, IGF-1 <-2 SDS had a sensitivity of 35.0% for GHD, but a positive predictive value of 100%. Finally, pretreatment IGF-1 values showed no correlation with the number of impaired pituitary hormonal axes in patients with multiple pituitary deficiencies. CONCLUSIONS: IGF-1 levels <-2 SDS showed a low sensitivity at predicting radiation-induced GHD both in childhood and in adulthood, but a high positive predictive value for GH status at final height reassessment.

Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function.

CONTEXT: Steroidogenic factor 1 (SF1/AdBP4/FTZF1, NR5A1) is a nuclear receptor transcription factor that plays a key role in regulating adrenal and gonadal development, steroidogenesis, and reproduction. Targeted deletion of Nr5a1 (Sf1) in the mouse results in adrenal and gonadal agenesis, XY sex-reversal, and persistent Müllerian structures in males. Consistent with the murine phenotype, human mutations in SF1 were described initially in two 46,XY individuals with female external genitalia, Müllerian structures (uterus), and primary adrenal failure. OBJECTIVE: Given recent case reports of haploinsufficiency of SF1 affecting testicular function in humans, we aimed to identify SF1 mutations in a cohort of individuals with a phenotypic spectrum of 46,XY gonadal dysgenesis/impaired androgenization (now termed 46,XY disorders of sex development) with normal adrenal function. METHODS AND PATIENTS: The study included mutational analysis of NR5A1 in 30 individuals with 46,XY disorders of sex development, followed by functional studies of SF1 activity. RESULTS: Heterozygous missense mutations in NR5A1 were found in four individuals (four of 30, 13%) with this phenotype. These mutations (V15M, M78I, G91S, L437Q) were shown to impair transcriptional activation through abnormal DNA binding (V15M, M78I, G91S), altered subnuclear localization (V15M, M78I), or disruption of the putative ligand-binding pocket (L437Q). Two mutations appeared to be de novo or germline changes. The other two mutations appeared to be inherited in a sex-limited dominant manner because the mother is heterozygous for the change. CONCLUSIONS: These studies demonstrate that SF1 mutations are more frequent than previously suspected causes of impaired fetal and postnatal testicular function in 46,XY individuals.

Endocrine Long-Term Follow-Up of Children with Neurofibromatosis Type 1 and Optic Pathway Glioma
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BACKGROUND/AIMS: Children with optic pathway glioma (OPG) face sequelae related to tumour location and treatment modalities. We aimed to assess the prevalence of hypothalamic-pituitary dysfunctions in children with neurofibromatosis type 1 (NF1) and OPG who did not receive radiotherapy or surgical resection. The causative role of tumour location on endocrinopathy development is investigated. METHODS: A retrospective follow-up study of 40 children with NF1 and OPG evaluated between August 1996 and May 2015 was undertaken. Patients who underwent radiotherapy or surgical resection were excluded and 36 patients were studied. Tumour location was classified according to the Dodge criteria: stage I, optic nerve alone; stage II, optic chiasm with or without optic nerve involvement; and stage III, involvement of the hypothalamus or other adjacent structures. RESULTS: Endocrinopathies were diagnosed in 20/36 (55.6%) children during a mean follow-up of 9.1 (0.2-13.6) years: 0/4 OPGs were Dodge stage I, 12/21 (57.1%) stage II, and 8/11 (72.7%) stage III. The first endocrinopathy was found at a mean age of 7.4 (5.0-13.2) years, 2.4 (0-6.7) years after tumour diagnosis. We found growth hormone deficiency (GHD; 36.1%), central precocious puberty (33.3%), obesity with insulin resistance/impaired glucose tolerance (11.1%), early puberty (5.5%), GH excess (5.5%), ACTH deficiency (5.5%), hypogonadotropic hypogonadism (2.7%), and thyrotropin deficiency (2.7%). GHD was transient in all of those who were retested. CONCLUSION: This population is at high risk of endocrinopathies due to tumour location. Lifelong endocrine follow-up is recommended.
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The pre-operative endocrine assessment of craniopharyngiomas.

Pre-operative endocrinopathies are common in patients presenting with craniopharyngiomas. Clinical features may not be obvious and careful pre-operative endocrine assessment is essential. Failure to recognise and address pre-operative diabetes insipidus and secondary hypoadrenalism is potentially fatal. We review the available published data on pre-operative endocrine dysfunction and suggest an approach to assessment and management before surgery.

Diabetes insipidus in craniopharyngioma: postoperative management of water and electrolyte disorders.

Pre-operative central diabetes insipidus has been reported in 8-35% of patients affected with craniopharyngioma, and in 70-90% after surgery. The management of postoperative polyuria and polydipsia can be challenging and fluid balance needs to be closely monitored. The classical triphasic pattern of endogenous vasopressin secretion--an initial phase of symptomatic diabetes insipidus occurring 24 hours after surgery; a second phase of inappropriate vasopressin secretion potentially causing hyponatraemia; and a third phase with a return to diabetes insipidus occurring up to 2 weeks later--is often complicated by cerebral salt wasting and thirst disorders. Inadequate adrenal replacement therapy and anticonvulsant agent treatment may increase the risk of life-threatening hyponatraemia in the course of desmopressin (DDAVP) treatment. Appropriate management, in order to avoid life-threatening or disabling electrolyte disturbances, requires a good grasp of the relevant pathophysiology. We review here the pathophysiology and management of the multiple fluid disorders encountered following surgery for craniopharyngiomas.