Endocrine Sequelae Research Articles

Growth hormone deficiency and other endocrinopathies after childhood brain tumors: results from a close follow-up in a cohort of 242 patients.

Brain tumors are the most common solid tumor in children. The prevalence of survivors from these cancers has been increasing, presenting endocrine sequelae in more than 40% of the cases. Our aim was to characterize the endocrinopathies diagnosed in this population, exploring the outcomes of growth hormone treatment. We have performed a retrospective analysis of the survivors that were followed-up through a close protocol at our endocrine late-effects clinic. 242 survivors, followed during 6.4 (0-23.4) years, were considered. The median age at tumor diagnosis was 6.7 (0-18) years and pilocytic astrocytoma was the most frequent neoplasm (33.5%). The prevalence of endocrinopathies was of 71.5%, with growth hormone deficiency being the most frequent (52.9%). An indirect correlation between the age at the beginning of somatropin and growth velocity in the first year of treatment was observed. Those treated with craniospinal radiotherapy presented a smaller final upper/lower segments ratio comparing with those that only received cranial radiotherapy. However, their final height was not compromised when compared to their family height target. We found pubertal delay in 12%; accelerated/precocious puberty in 13.2%; central and primary hypogonadism in 21.9% and 3.3%, respectively; primary and central hypothyroidism in 23.6% and 14.5%, respectively; thyroid nodules in 7.4%; ACTH deficiency in 10.3% and diabetes insipidus in 12%. This study reveals a higher prevalence of endocrinopathies in brain tumors survivors and explores the influence of craniospinal irradiation in the adult body proportions. It reinforces the importance of routine follow-up among survivors.

Temporal trends in craniopharyngioma management and long-term endocrine outcomes: A multicentre cross-sectional study.

The optimal management of craniopharyngiomas remains controversial. To examine temporal trends in the management of craniopharyngioma with a focus on endocrine outcomes. This was a cross-sectional, multicentre study. Patients treated between 1951 and 2015 were identified and divided into four quartiles. Demographics, presentation, treatment and outcomes were collected. In total, 142 patients with childhood-onset craniopharyngioma (48/142; 34%) and adult-onset disease (94/142; 66%) were included. The median follow-up was 15years (IQR 5-23years). Across quartiles, there was a significant trend towards using transsphenoidal surgery (P<.0001). The overall use of radiotherapy was not different among the four quartiles (P=.33). At the latest clinical review, the incidence of GH, ACTH, gonadotrophin deficiencies and anterior panhypopituitarism fell significantly across the duration of the study. Anterior panhypopituitarism was not affected by treatment modality (surgery vs surgery and radiotherapy) (P=.23). There was no difference in the incidence of high BMI (≥25kg/m2 ) among the four quartiles (P=.14). BMI was higher in patients who treated with surgery and radiotherapy than those treated with surgery only (P=.006). Tumour regrowth occurred in 51 patients (51/142; 36%) with no difference in regrowth among quartiles over the time course of the study (P=.15). We demonstrate a significant reduction in panhypopituitarism in craniopharyngioma patients over time, most likely because of a trend towards more transsphenoidal surgery. However, long-term endocrine sequelae remain common and lifelong follow-up is required.

Proton Radiotherapy to Preserve Fertility and Endocrine Function: A Translational Investigation

Photon radiation therapy (x-ray radiation therapy [XRT] and gamma-ray radiation therapy [GRT]) of tumors close to ovaries causes reproductive and endocrine sequelae due to ovarian primordial follicle depletion. Given its finite range, proton radiation therapy (PRT) can preserve ovarian function when ovaries are positioned distal to the spread-out Bragg peak (SOBP) in tumors of the abdominopelvic region. This study compared anti-Müllerian hormone (AMH) levels (a biomarker of ovarian function) and primordial follicle survival after invivo mouse pelvic GRT versus PRT. One hundred twenty-four female prepubertal mice received sham, GRT, or PRT with ovaries positioned at various depth with respect to the proton SOBP, with single doses of 1.8 or 0.2 Gy. AMH was measured at baseline, 1, 3, and 8 weeks after treatment, and the total number of surviving primordial follicles was counted. Multivariable linear mixed-effects modeling was used to assess the relationship between radiation therapy modality and dose on AMH and primordial follicle survival. For ovaries beyond the SOBP, ovarian function (P = .5) and ovarian primordial follicle (OPF; P = 1.0) were spared relative to sham controls. For ovaries in the SOBP plateau, ovarian function and primordial follicle reserve 8 weeks after treatment were reduced for all groups: 1.8 Gy GRT (βAMH = -4.9 ng/mL; βOPF = -728.2/animal), 1.8 Gy (relative biological effectiveness [RBE] = 1.1) PRT (βAMH = -5.1 ng/mL; βOPF = -728.2/animal), 0.2 Gy GRT (βAMH = -2.5 ng/mL; βOPF = -595.1/animal), and 0.2 Gy (RBE = 1.1) PRT (βAMH = -3.0 ng/mL; βOPF = -555.4/animal) relative to sham controls (all differences P < .001). This study uses an animal model to demonstrate the safety of proton therapy in sparing fertility. Ovaries positioned beyond the SOBP during PRT maintain ovarian reserve, suggesting that a proton beam has no energy and exit dose beyond SOBP. This study proposes that proton therapy is much safer than photon radiation therapy to protect ovarian follicles with the same dose, and it supports further testing of proton therapy for abdominopelvic tumors in young women.

SAT-054 Gigantism and Hypothalamic Obesity: Rare Endocrine Manifestations of Neurofibromatosis Type 1

Background: Neurofibromatosis type 1 (NF-1) is a heritable, autosomal dominant, multisystem disorder caused by mutations or deletions in NF1, with approximately 30-50% of cases arising from de novo mutations. In the pediatric population, growth hormone deficiency is among one of the most commonly described endocrine sequelae, although aberrations of pubertal development are also commonly seen. Clinical Case: A 3-year-old female, who was clinically diagnosed with NF-1 at the age of 4 months based on the presence of multiple café-au-lait macules, underwent screening MRI, which noted a left optic glioma and a hypothalamic mass favored to represent a hypothalamic glioma. Review of her growth chart showed a height much greater than the 99th percentile, with an increase in height velocity beginning 1 year prior. Weight was also noted to be much greater than the 99th percentile, with an increase in weight gain coinciding with the timing of alterations in linear growth. Mid-parental height is at the 95th percentile, and the patient’s height had tracked between the 86th and the 99th percentiles until age 2 years. Weight had tracked between the 68th and the 95th percentiles during that period. Initial laboratory evaluation showed an IGF-1 of 644 ng/mL (26-164 ng/mL). Gonadotropins were prepubertal; prolactin and thyroid studies were normal. ACTH stimulation demonstrated a rise in serum cortisol from 6.8 mcg/dL to 30.2 mcg/dL at 60 minutes. Growth hormone failed to suppress following an oral glucose load with a baseline GH of 4.4 ng/mL and values of 3.7, 6.5, 6.8, and 9.0 ng/mL at time +30, +60, +90, and +120 minutes respectively. Leuprolide stimulation did not show significant rises in gonadotropins. Bone age was advanced by more than 1 year. The patient was started on subcutaneous octreotide with a decrease in IGF-1 to 258 ng/mL after 1 month of therapy. On treatment, linear growth velocity slowed with no interval height gain over the initial 1-month period; however, the patient’s weight continued to increase with a gain of 1.8 kg. Parents additionally reported hyperphagia, which prompted concern for hypothalamic obesity in the setting of her known hypothalamic mass. Thyroid function remained normal on somatostatin therapy. To date, there has been no concern for diabetes insipidus. Conclusion: Growth hormone excess may rarely complicate a diagnosis of NF-1 in the setting of intracranial gliomas. Increased height velocity and/or tall stature for family should raise clinical suspicion and prompt evaluation. Hyperphagia and significant increases in weight in the setting of hypothalamic gliomas in patients with NF-1 should raise suspicion for hypothalamic obesity and prompt lifestyle modifications to curb ongoing weight gain.

MON-098 Risk of Long-Term Endocrine Sequelae in Survivors of Progressing Childhood Optic Pathway Glioma Treated by Upfront Chemotherapy: Preliminary Analyses of 102 Subjects from the French Multicentric BB-SFOP Registry

For the brain tumor committee of SFCE (Societe ´ Française des Cancers de l’Enfant). Objective: Therapeutic approach favors chemotherapy as the first-line-treatment in progressing OPG. There are few data on long term endocrine outcomes of aggressive OPG treated by upfront chemotherapy. Our main objective was to describe the long-term endocrine sequelae in these patients and to identify potential early predictors of the endocrine involvement. Subjects and methods: Children diagnosed with OPG at an age younger than 16 years from the French multicentric BBSFOP registry were included. They were treated with upfront chemotherapy according to the BB-SFOP protocol in France between June 1990 and December 2004, and subsequent treatment (second-line chemotherapy, surgery, radiotherapy) was used depending on tumor progression. They underwent a late evaluation with clinical and biological assessment between January 2011 and March 2016. Results: One hundred and two patients were included in our study. The mean age at tumor diagnosis was 3.3±0.3 years. The mean time of follow-up was 13.9±3.7 years. A history of precocious puberty was present in 36% of the subjects. At least one endocrine deficiency was present in 93% of the subjects (GHD 74%, TSH deficiency 57%, ACTH deficiency 36%, hypogonadotropism 33%, gonadic deficiency 30%, diabetes insipidus 15%; inappropriate AVP secretion 7%). 37% of males and 39% of females were overweight or obese. Mean adult height, reached in 51 subjects, was -1.2±1.3 SDS in males, and -0.7±1.4 SDS in females. Chemotherapy only was protective from pituitary deficiencies (odds ratio 0.19 to 0.37, P < 0.05). NF1 was protective from TSH and ACTH deficiencies (odds ratio 0.25 to 0.35, P < 0.05). Tumor volume on diagnostic MRI was not predictive of pituitary deficiencies. Gonadic deficiency was significantly more frequent in males than females (46,5% vs 12.2%, P < 0.05), and associated with chemotherapy only (OR 3.2, P < 0.05) and NF1 (OR 4.8, P < 0.05). Overweight/Obesity was associated with ACTH deficiency (OR 5, P < 0.05).Conclusion: Obesity and late endocrine dysfunction were frequent in subjects treated by upfront chemotherapy for aggressive OPG during childhood. However, chemotherapy only, when possible, was protective from pituitary involvement.

Are hypothalamic- pituitary (HP) axis deficiencies after whole brain radiotherapy (WBRT) of relevance for adult cancer patients? \u2013 a systematic review of the literature

BackgroundCranial radiotherapy (cRT) can induce hormonal deficiencies as a consequence of significant doses to the hypothalamic-pituitary (HP) axis. In contrast to profound endocrinological follow-up data from survivors of childhood cancer treated with cRT, little knowledge exists for adult cancer patients.MethodsA systematic search of the literature was conducted using the PubMed database and the Cochrane library offering the basis for our debate of the relevance of HP axis impairment after cRT in adult cancer patients. Against the background of potential relevance for patients receiving whole brain radiotherapy (WBRT), a particular focus was set on the temporal onset of hypopituitarism and the radiation dose to the HP axis.ResultsTwenty-eight original papers with a total of 1728 patients met the inclusion criteria. Radiation doses to the HP area ranged from 4 to 97 Gray (Gy). Hypopituitarism incidences ranged from 20 to 93% for adult patients with nasopharyngeal cancer or non-pituitary brain tumors. No study focused particularly on hypopituitarism after WBRT. The onset of hypopituitarism occurred as early as within the first year following cRT (range: 3 months to 25.6 years). However, since most studies started follow-up evaluation only several years after cRT, early onset of hypopituitarism might have gone unnoticed.ConclusionHypopituitarism occurs frequently after cRT in adult cancer patients. Despite the general conception that it develops only after several years, onset of endocrine sequelae can occur within the first year after cRT without a clear threshold. This finding is worth debating particularly in respect of treatment options for patients with brain metastases and favorable survival prognoses.

Is Chemotherapy Implicated in the Development of Hypopituitarism in Childhood Cancer Survivors?

Endocrine sequelae are a frequent result of therapy aimed at inducing remission in childhood cancer survivors. Hypopituitarism is the consequence of insults directed at the hypothalamo-pituitary axis, in particular surgery and radiotherapy. The question of whether chemotherapy, in the absence of concomitant radiotherapy, can induce hypopituitarism in susceptible individuals has been raised by a number of studies over the last 30 years. Where described the pituitary hormone deficit in question is almost exclusively growth hormone. Studies have been of variable quality, with endocrine testing that fails to hold up to scrutiny. There is thus no robust data to support this hypothesis, in particular no single agent or class of chemotherapeutic agent has been implicated, and the mechanism of action remains elusive.

Co-Occurrence of Multiple Endocrine Abnormalities Induced by the DIHS/DRESS.

Background Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse reaction caused by specific drugs. However, little information is available about sequelae following DIHS/DRESS resolution from an endocrinologist's perspective. This study aimed to investigate the endocrine sequelae following DIHS/DRESS, from clinical feature to etiology. Methods We retrospectively analyzed the patients diagnosed with DIHS/DRESS in Peking Union Medical College Hospital (PUMCH) during the period of 1 January 2012 to 31 December 2017, and those who developed endocrine disorders after DIHS/DRESS were further examined. We also reviewed the literature, from 1 January 2000 to 31 December 2017, on involvement of endocrine glands in DIHS/DRESS patients. Results Three patients developed both autoimmune thyroid disease (AITD) and type 1 diabetes (T1DM)/fulminant type 1 diabetes (FT1DM) of the 45 patients. Seven cases involving more than two endocrine glands were reported in the literature. Our results indicated that DIHS/DRESS is a potential etiological factor of autoimmune polyendocrine syndrome (APS), especially APS III. Conclusions Patients require careful long-term follow-up after DIHS/DRESS. Involvement of endocrine glands, especially FT1DM, should always be monitored in patients with a history of DIHS/DRESS. This study indicated that DIHS/DRESS could lead to APS, especially APS III, providing novel insights into the etiological factors of APS.

Long-Term Endocrine and Metabolic Consequences of Cancer Treatment: A Systematic Review.

The number of patients surviving ≥5 years after initial cancer diagnosis has significantly increased during the last decades due to considerable improvements in the treatment of many cancer entities. A negative consequence of this is that the emergence of long-term sequelae and endocrine disorders account for a high proportion of these. These late effects can occur decades after cancer treatment and affect up to 50% of childhood cancer survivors. Multiple predisposing factors for endocrine late effects have been identified, including radiation, sex, and age at the time of diagnosis. A systematic literature search has been conducted using the PubMed database to offer a detailed overview of the spectrum of late endocrine disorders following oncological treatment. Most data are based on late effects of treatment in former childhood cancer patients for whom specific guidelines and recommendations already exist, whereas current knowledge concerning late effects in adult-onset cancer survivors is much less clear. Endocrine sequelae of cancer therapy include functional alterations in hypothalamic-pituitary, thyroid, parathyroid, adrenal, and gonadal regulation as well as bone and metabolic complications. Surgery, radiotherapy, chemotherapy, and immunotherapy all contribute to these sequelae. Following irradiation, endocrine organs such as the thyroid are also at risk for subsequent malignancies. Although diagnosis and management of functional and neoplastic long-term consequences of cancer therapy are comparable to other causes of endocrine disorders, cancer survivors need individually structured follow-up care in specialized surveillance centers to improve care for this rapidly growing group of patients.

MECHANISMS OF ENDOCRINOLOGY: Endocrinology of opioids

The use of opioids has grown substantially over the past two decades reaching the dimensions of a global epidemic. These drugs have effects on multiple levels of the endocrine system through mechanisms which are still not fully elucidated, and awareness of their endocrine sequelae is vital for all specialists prescribing or managing patients on them. Hypogonadism is the most well-recognised consequence of opioid use (prevalence 21–86%) which, however, may remain undiagnosed with potential adverse outcomes for the patients. Although less frequent, cortisol deficiency can also be found. Furthermore, there is a negative impact on bone health (with reduced bone mineral density and increased fracture risk) and occasionally hyperprolactinaemia, whereas the clinical significance of alterations in other hormones remains to be clarified. Discontinuation or reduction of the opioid and, in cases of chronic pain, consideration of alternative therapies for pain relief are potential management options. Hormonal replacement, especially when the above measures are not practically feasible, needs to be considered. Further studies are needed to clearly establish the prevalence of hormonal abnormalities with various regimes, doses and routes of opioids and to address reliably the long-term benefits and risks of hormonal treatment in patients on opioids. Until evidence-based, safe and cost-effective clinical guidelines become available, periodical assessment of the gonadal and adrenal function (particularly when relevant clinical manifestations are present) and evaluation of the bone health status are advised.

Tuberculosis of the central nervous system in children.

Central nervous system tuberculosis (CNS TB) in children is still a socioeconomic problem in developing countries. It has varied manifestations, symptoms are nonspecific, diagnosis can be challenging, and treatment may be difficult. It is often missed or overlooked. Among the various pathological entities, tuberculous meningitis is the most common and devastating manifestation. The resultant vasculitis, infarction, and hydrocephalus can be life-threatening. It can have grave cognitive, intellectual, and endocrine sequelae if not treated in time resulting in handicap, especially in resource constraint countries. Early diagnosis and treatment of tuberculous meningitis is the single most important factor determining outcome. Tuberculous hydrocephalus needs to be recognized early, and cerebrospinal fluid diversion procedure needs to be performed in adequate time to prevent morbidity or mortality in some cases. Tuberculous pachymeningitis and arachnoiditis are rare in children. Tuberculous abscess can mimic pyogenic abscess and requires high index of suspicion. Calvarial tuberculosis is seen in children and responds well to antituberculous chemotherapy. Drug-resistant tuberculosis is a formidable problem, and alternate chemotherapy should be promptly instituted. The pathogenesis, clinical features, diagnosis, and management of central nervous system tuberculosis in children are summarized. Heightened clinical suspicion, early diagnosis, appropriate antituberculous treatment, and surgery in relevant situation are essential for a gratifying outcome and preventing complications.

Adrenal crisis in a 14-year-old boy 12 years after hematopoietic stem cell transplantation.

SummaryWe report on a boy of Albanian descent with the history of juvenile myelomonocytic leukemia (JMML). JMML was diagnosed at the age of 17 months and treated by hematopoietic stem cell transplantation (HSCT). At the age of 14.3 years, about 12 years after HSCT, he was hospitalized with an adrenal crisis. Hormone findings were consistent with primary adrenal insufficiency. Autoimmune adrenalitis was confirmed by positive autoantibodies against 21-hydroxylase and adrenal tissue. Since autoimmune Hashimoto thyroiditis was already known from the age of 9 years, we assume that both diseases are part of the spectrum of autoimmune polyglandular syndrome (APS) type 2. APS type 2 is a rare endocrine disease characterized by Addison’s disease along with autoimmune thyroid disease and/or type 1 diabetes.Learning points:Endocrine sequelae after hematopoietic stem cell transplantation (HSCT) are common and can develop over a long period.Primary adrenal insufficiency after HSCT is absolutely rare.The combination of adrenal autoimmune disease and Hashimoto thyroiditis is consistent with autoimmune polyglandular syndrome type 2.

Long-term endocrine sequelae of patients with beta-thalassemia following bone marrow transplantation in childhood/adolescence

Long-term endocrine sequelae of patients with beta-thalassemia following bone marrow transplantation in childhood/adolescence

Endocrine sequelae of immune checkpoint inhibitors.

Cancer immunotherapy has introduced a novel class of drugs known as immune checkpoint inhibitors (ICIs). They enhance antitumour immunity by blocking negative regulators (checkpoints) of T cell function that exist on both immune and tumour cells. ICIs targeting CTLA-4 and PD-1/PDL-1 have dramatically changed the outcome of patients with several advanced-stage malignancies but they may lead to a variety of inflammatory toxicities and autoimmune consequences. The main endocrine immune-related adverse events (IRAEs) include hypophysitis, primary thyroid dysfunction, adrenalitis and type 1 diabetes mellitus. In general, the management of endocrine IRAEs requires assessment of their severity, in moderate or severe cases interruption of the checkpoint inhibitor and use of corticosteroid or alternative immunosuppression and appropriate hormone replacement or treatment when necessary.

Endocrine sequelae in childhood cancer survivors

Thanks to the advances in cancer treatment, the five-year survival rate after childhood cancer has increased up to 80%. Therefore 1/500 young adults will be a survivor. Endocrine sequelae are most common, affecting 40–60% of survivors. The most frequent sequelae include growth failure and gonadal and thyroid diseases. Sequelae occur more frequently in survivors from central nervous system tumors, leukemia, and lymphoma. Their development will depend on the type of cancer, its location, age at diagnosis, and treatment administered. Treatments associated to more endocrine sequels are cranial radiotherapy and hematopoietic cell transplantation. Because of the high prevalence of endocrine sequelae, international guidelines recommend endocrinologists to prospectively evaluate the survivors. As some of these endocrine changes will not develop until adult life, transition programs should be implemented, and active investigation should be made to decrease the endocrine consequences of cancer treatment.

Secuelas endocrinológicas en supervivientes de cáncer infantil

Thanks to the advances in cancer treatment, the five-year survival rate after childhood cancer has increased up to 80%. Therefore 1/500 young adults will be a survivor. Endocrine sequelae are most common, affecting 40-60% of survivors. The most frequent sequelae include growth failure and gonadal and thyroid diseases. Sequelae occur more frequently in survivors from central nervous system tumors, leukemia, and lymphoma. Their development will depend on the type of cancer, its location, age at diagnosis, and treatment administered. Treatments associated to more endocrine sequels are cranial radiotherapy and hematopoietic cell transplantation. Because of the high prevalence of endocrine sequelae, international guidelines recommend endocrinologists to prospectively evaluate the survivors. As some of these endocrine changes will not develop until adult life, transition programs should be implemented, and active investigation should be made to decrease the endocrine consequences of cancer treatment.

Long-term follow-up of endocrine function among young children with newly diagnosed malignant central nervous system tumors treated with irradiation-avoiding regimens.

The adverse effects of irradiation on endocrine function among patients with pediatric brain tumor are well documented. Intensive induction chemotherapy followed by marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) without central nervous system (CNS) irradiation has demonstrated efficacy in a proportion of very young children with some malignant CNS tumors. This study assessed the long-term endocrine function of young children following chemotherapy-only treatment regimens. A retrospective chart review was performed on 99 patients under 6 years of age with malignant brain tumors newly diagnosed between May 1991 and October 2010 treated with irradiation-avoiding strategies. Thirty patients survived post-AuHCR without cranial irradiation for a mean of 8.1 years (range 3.0-22.25 years). The patient cohort included 18 males and 12 females (mean age at AuHCR of 2.5 years, range 0.8-5.1 years). All 30 surviving patients had documented normal age-related thyroid function, insulin-like growth factor binding protein 3 (IGF-BP3), prolactin, testosterone, and estradiol levels. Insulin-like growth factor 1 age-related levels were abnormal in one child with normal height. Ninety-seven percent of patients had normal cortisol levels, while follicle-stimulating hormone and LH levels among females were normal in 83% and 92%, respectively, and in 100% of males. Growth charts demonstrated age-associated growth within 2 standard deviations of the mean in 67% of patients. Of 10 patients (33%) with short stature, 6 had proportional diminutions in both height and weight. These findings demonstrate that the use of relatively brief, intensive chemotherapy regimens including marrow-ablative chemotherapy with AuHCR results in fewer endocrine sequelae than treatment schemes utilizing CNS irradiation.

Does Stereotactic Radiosurgery Positively Impact the Local Control of Atypical Teratoid Rhabdoid Tumors?

Atypical teratoid rhabdoid tumors (ATRTs) are rare and aggressive tumors, usually affecting patients younger than 3 years of age, that are characterized by a poor prognosis. Nowadays multimodal management, including surgery, chemotherapy and radiation therapy (RT), is advocated depending on the patients' age and tumor stage, even if no consensus exists regarding the best treatment modality. Local RT seems to be the most effective treatment in prolonging progression-free and overall survival rates, although RT might not be used on younger children because of the risk of neurocognitive and endocrine sequelae. Stereotactic radiosurgery (SRS) is a valuable alternative therapeutic option to conventional RT because of the more conformal dose delivery. The aim of this study was to review the available literature on SRS in the management of ATRT. The authors carried out a systematic review of PubMed, Web of Science, and Google Scholar for clinical reports dealing with SRS for the management of ATRT. Nine studies describing 12 patients treated with SRS for ATRT were included in the analysis. Patient's clinical features, radiosurgical treatment characteristics, and follow-up data of the pertinent literature were reviewed critically. SRS represents a feasible and effective therapeutic option in the management of ATRT. Local control has been reported in 66.7% of cases; however, 33.3% of patients experienced poor survival because of craniospinal tumor dissemination. SRS should be considered in the multimodal treatment of ATRT, and future studies should focus on a better definition of the role played by SRS in their management.

MANAGEMENT OF ENDOCRINE DISEASE: Neuroendocrine surveillance and management of neurosurgical patients.

Advances in the management of traumatic brain injury, subarachnoid haemorrhage and intracranial tumours have led to improved survival rates and an increased focus on quality of life of survivors. Endocrine sequelae of the acute brain insult and subsequent neurosurgery, peri-operative fluid administration and/or cranial irradiation are now well described. Unrecognised acute hypopituitarism, particularly ACTH/cortisol deficiency and diabetes insipidus, can be life threatening. Although hypopituitarism may be transient, up to 30% of survivors of TBI have chronic hypopituitarism, which can diminish quality of life and hamper rehabilitation. Patients who survive SAH may also develop hypopituitarism, though it is less common than after TBI. The growth hormone axis is most frequently affected. There is also accumulating evidence that survivors of intracranial malignancy, who have required cranial irradiation, may develop hypopituitarism. The time course of the development of hormone deficits is varied, and predictors of pituitary dysfunction are unreliable. Furthermore, diagnosis of GH and ACTH deficiency require dynamic testing that can be resource intensive. Thus the surveillance and management of neuroendocrine dysfunction in neurosurgical patients poses significant logistic challenges to endocrine services. However, diagnosis and management of pituitary dysfunction can be rewarding. Appropriate hormone replacement can improve quality of life, prevent complications such as muscle atrophy, infection and osteoporosis and improve engagement with physiotherapy and rehabilitation.

A Benchmark for Preservation of Normal Pituitary Function After Endoscopic Transsphenoidal Surgery for Pituitary Macroadenomas

We report a contemporary consecutive series of 80 patients operated on for benign pituitary macroadenomas, followed endocrinologically for at least 3months postoperatively. These patients were systematically evaluated preoperatively by high-resolution magnetic resonance imaging designed to detect the position of normal gland relative to the lesion. The rate of preservation of normal pituitary was critically analyzed using this strategy combined with endoscopic transsphenoidal resection. This is a retrospective review of 46 women and 34 men with mean postoperative follow-up of 14 months (range, 3-30 months). The lesions encountered consisted of 80 pituitary macroadenomas (55 nonfunctioning, 18 acromegaly, 5 prolactinoma, 1 Cushing, one thyroid-stimulating hormone). Pituitary endocrine status was determined preoperatively and at most recent follow-up, and categorized as normal or impaired, based on laboratory studies showing new hormone deficiency or the need for pituitary hormone replacement therapy. Fifty-three patients (66.3%) had normal endocrine function preoperatively; 3 (5.7%) had loss of function postoperatively (1 transient). Twenty-seven patients (33.8%) had impaired function preoperatively; postoperatively 20 (74.1%) were unchanged, and 5 (18.5%) were worse; 2(7.4%) recovered lost pituitary function. Of 80 patients undergoing resection, 5 (6.3%) had worsened pituitary function postoperatively. Patients with recurrent lesions (n= 5, 6.3%) and those presenting with pituitary tumor apoplexy (n= 5, 6.3%) were more likely to become further impaired. Other endocrine sequelae included 2 patients with permanent postoperative diabetes insipidus and 3 with transient symptomatic syndrome of inappropriate secretion of antidiuretic hormone. The preservation and restoration of hormonal function are essential to assessing the outcome of surgery and to the patient's quality of life. Careful analysis of the anatomy of the pituitary lesions and their effect on the anatomy and physiology of the pituitary gland are crucial to success and allow modern technological advances to provide fewer complications of therapy and improved outcomes for our patients. The benchmarks provided in this article are a stimulus for even better results in the future as we take advantage of technical and conceptual advances and the benefits of multidisciplinary collaboration.