Endocrine manifestations in adults with 22q11.2 deletion syndrome: a retrospective single-center cohort study.

INTRODUCTION AND OBJECTIVE: Patients with the 22q11.2 deletion syndrome (22q11DS) frequently display cardiological and psychiatric diseases, but are also at increased risk for endocrine manifestations. The aim of this study was to evaluate the screening, prevalence, and management of hypoparathyroidism and thyroid disease in patients with 22q11DS, to evaluate the metabolic profile, and to compare these results with current literature and guidelines. DESIGN: We performed a retrospective study of patients with genetically confirmed 22q11DS, followed at the center for human genetics of the University Hospitals Leuven, resulting in a cohort of 75 patients. Medical history, medication, and laboratory results concerning hypoparathyroidism, thyroid dysfunction, and the metabolic profile were collected. RESULTS: Of the total cohort, 26 patients (35%) had at least one hypocalcaemic episode. During hypocalcaemia, parathyroid hormone (PTH) was measured in only 12 patients with 11 having normal or low PTH, confirming a diagnosis of hypoparathyroidism. Recurrent episodes of hypocalcaemia occurred in seventeen patients (23%). Adherence to the guidelines was low, with 13% of patients having a yearly serum calcium evaluation, 12% receiving daily calcium supplements, and 20% receiving non-active vitamin D. Hypothyroidism was present in 31 patients (44%) and hyperthyroidism in 6 patients (8%). Information on body mass index (BMI) was available in 52 patients (69%), of which 38% were obese (BMI ≥ 30 kg/m2). CONCLUSION: Hypoparathyroidism, hypothyroidism, and obesity are common endocrine manifestations in patients with 22q11DS but are probably underdiagnosed and undertreated, indicating the need for multidisciplinary follow-up including an endocrinologist.

Endocrine disorders in patients with Fabry disease: insights from a reference centre prospective study.

CONTEXT: Fabry Disease (FD) is a rare X-linked storage disease characterised by a-galactosidase A deficiency and diffuse organ accumulation of glycosphingolipids. Enzyme replacement and chaperone therapies are only partially effective. It remains unclear if FD-related endocrine disorders contribute to the observed morbidity. OBJECTIVE: To investigate the function of the endocrine system in patients with FD. DESIGN: We conducted an observational prospective study from 2017 to 2020. SETTING AND PATIENTS: We included 77 patients with genetically confirmed FD (27 men, 20/27 Classic, 7/26 Late Onset phenotype, 50 women, 41/50 and 9/50 respectively), who are systematically followed by our reference centre. RESULTS: 36/77 (46.8%) patients had VitD deficiency (25(0H)VitD <20 µg/L) despite the fact that 19/36 (52.8%) were substituted with cholecalciferol. Only 21/77 (27.3%) patients had normal VitD levels without VitD substitution. 11/77 (14.3%) had significant hypophosphatemia (p < 0.80 mmol/L). Three new cases (3.9%) of subclinical, two (2.6%) of overt and six (7.8%) of known hypothyroidism were identified. Of note, men had significantly higher renin levels than women [61.4 (26.1-219.6) vs.25.4 (10.9-48.0) mU/L, p = 0.003]. There were no major abnormalities in adrenal, growth and sex-hormone axes. Patients of Classic phenotype had significantly higher High-Density Lipoprotein Cholesterol (HDL-C) levels (p = 0.002) and in men those levels were positively correlated with globotriaosylsphingosin (Lyso-Gb3) values. 10/77 (13%) of the patients were underweight. CONCLUSIONS: VitD supplementation should be considered for all patients with FD. Thyroid screening should be routinely performed. Malnutrition should be prevented or treated, particularly in Classic phenotype patients. Overall, our data suggest that FD specialists should actively seek and diagnose endocrine disorders in their patients.

Hypothalamic Inflammation as a Potential Pathophysiologic Basis for the Heterogeneity of Clinical, Hormonal, and Metabolic Presentation in PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. It is a heterogeneous condition characterized by reproductive, endocrine, metabolic, and psychiatric abnormalities. More than one pathogenic mechanism is involved in its development. On the other hand, the hypothalamus plays a crucial role in many important functions of the body, including weight balance, food intake, and reproduction. A high-fat diet with a large amount of long-chain saturated fatty acids can induce inflammation in the hypothalamus. Hypothalamic neurons can sense extracellular glucose concentrations and participate, with a feedback mechanism, in the regulation of whole-body glucose homeostasis. When consumed nutrients are rich in fat and sugar, and these regulatory mechanisms can trigger inflammatory pathways resulting in hypothalamic inflammation. The latter has been correlated with metabolic diseases, obesity, and depression. In this review, we explore whether the pattern and the expansion of hypothalamic inflammation, as a result of a high-fat and -sugar diet, may contribute to the heterogeneity of the clinical, hormonal, and metabolic presentation in PCOS via pathophysiologic mechanisms affecting specific areas of the hypothalamus. These mechanisms could be potential targets for the development of effective therapies for the treatment of PCOS.

Selenium in Endocrinology-Selenoprotein-Related Diseases, Population Studies, and Epidemiological Evidence.

Selenium (Se), apart from iodine, iron, and calcium, is one of the nutrient-derived key elements strongly affecting the endocrine system. However, no specific hormonal "feedback" regulation for Se status has yet been identified, in contrast to the fine-tuned hormone network regulating Ca2+ and phosphate balance or hepcidin-related iron status. Since its discovery as an essential trace element, the effects of Se excess or deficiency on the endocrine system or components of the hypothalamic-pituitary-periphery feedback circuits, the thyroid hormone axis, glucoregulatory and adrenal hormones, male and female gonads, the musculoskeletal apparatus, and skin have been identified. Analysis of the Se status in the blood or via validated biomarkers such as the hepatically derived selenoprotein P provides valuable diagnostic insight and a rational basis for decision making on required therapeutic or preventive supplementation of risk groups or patients. Endocrine-related epidemiological and interventional evidence linking Se status to beneficial or potentially adverse actions of selected selenoproteins mediating most of the (patho-) physiological effects are discussed in this mini-review. Autoimmune thyroid disease, diabetes and obesity, male fertility, as well as osteoporosis are examples for which observational or interventional studies have indicated Se effects. The currently prevailing concept relating Se and selenoproteins to "oxidative stress," reactive oxygen species, radical hypotheses, and related strategies of pharmacological approaches based on various selenium compounds will not be the focus. The crucial biological function of several selenoproteins in cellular redox-regulation and specific enzyme reactions in endocrine pathways will be addressed and put in clinical perspective.

Vitamin D effects and endocrine diseases.

A lack of vitamin D has been linked to autoimmune diseases including type 1 diabetes, autoimmune thyroiditis and to obesity. The prevalence of vitamin D deficiency is higher in diabetic or obese children and patients with thyroiditis compared to healthy controls. Moreover, low vitamin D values seem to be associated with major complications and poor glycemic control, in particular in obese children. Supplementation with vitamin D, which has immune-regulatory properties, may support our therapies and improve the outcomes in different diseases. Although some studies suggest a possible role of vitamin D in the etiology of autoimmune diseases and obesity, data on supplementation benefits are inconclusive and further studies are needed. In this paper, we focus on the current evidence regarding vitamin D function in endocrine diseases and possible benefits of its supplementation in pediatric age.

Maternal metabolic syndrome and selenium: Endocrine energy balance during early programming.

BACKGROUND: Maternal metabolic syndrome during gestation and lactation leads to several Se-status-related metabolic changes in offspring. MS leads to hepatomegaly, liver oxidation, resistance to insulin challenges and selenoptroteins expression upregulation, producing an energy imbalance in hepatocytes. As Se is necessary for correct heart function, Se deposits are depleted and selenoproteins expression downregulated in heart; this depletion being related to cardiovascular damage. Recently, selenoproteins have been directly implicated in the central endocrine regulation of appetite and energy homeostasis. METHODS: To obtain information about how Se is involved in regulating endocrine peripheral energy balance during MS process, two experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65% and Se: 0.1 ppm). At the end of lactation (21d old), the pups' appetite profile, tissular Se deposits and peptides from gastrointestinal tract (including pancreas), leptin, skeletal growth markers and cytokines in serum were measured. RESULTS: MS-exposed pups present changes in Se homeostasis, appetite profile and endocrine energy balance signals related to impaired insulin secretion and high leptin serum values. This profoundly affects the pups' growth profile since muscle and bones are in catabolic process and brown adipose tissue (BAT) mass decreases. CONCLUSION: These results indicate that the pups are suffering a process similar to diabetes type 1 which appeared when dams received low Se dietary supply and they point to Se as an important marker and key treatment for these disorders during gestation and lactation that affect future adult health.

Immunotherapy in oncology: a new challenge for radiologists. / Inmunoterapia en oncología: un nuevo desafío radiológico.

OBJECTIVE: In patients with oncologic disease, immunotherapy has become established as an alternative or complementary therapy to traditional treatment options (surgery, radiotherapy, and chemotherapy). Currently available immunotherapy modes can be divided into two types: passive and active. The active type strengthens the immune system's response to tumor cells by activating both humoral immunity and cell-mediated immunity, using the adaptive response. This article aims to analyze the radiologic patterns of the response to immunotherapy through immune-response-related criteria and to describe the main adverse effects associated with this treatment approach. CONCLUSION: Imaging tests play a fundamental role in the follow-up of oncologic patients and in the assessment of their response to treatment. Immunotherapy represents a challenge for radiologists both in the evaluation of the response to immunotherapy and in the detection of the adverse effects associated with this treatment approach.

Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors.

PURPOSE: There are sparse data defining the dose response of radiation therapy (RT) to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. We examined the correlation between RT dose to these structures and development of endocrine dysfunction in this population. MATERIALS AND METHODS: Dosimetric and clinical data were collected from children and young adults (< 26 years of age) with brain tumors treated with proton RT on three prospective studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone, adrenocorticotropic hormone, and gonadotropins were determined clinically and serologically. Incidence of deficiency was estimated using the Kaplan-Meier method. Multivariate models were constructed accounting for radiation dose and age. RESULTS: Of 222 patients in the study, 189 were evaluable by actuarial analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with 31 patients (14%) excluded from actuarial analysis for having baseline hormone deficiency and two patients (0.9%) because of lack of follow-up. One hundred thirty patients (68.8%) with medulloblastoma were treated with craniospinal irradiation (CSI) and boost; most of the remaining patients (n = 56) received involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency, growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency. CONCLUSION: Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors.

Final adult height and endocrine complications in young adults with ß-thalassemia major (TM) who received oral iron chelation (OIC) in comparison with those who did not use OIC.

BACKGROUND: Relatively little is known about endocrine function, bone mineral health, and growth during oral iron chelation therapy in ß-thalassemia major patients (TM) on treatment with deferasirox. AIMS OF THE STUDY: To study the frequency of endocrine complications, IGF-1 levels and final adult standing height (FA-Ht) in patients with BTM in two groups of adult patients. PATIENTS AND METHODS: The first group (Group A; 15 patients, 6 females and 9 males) received oral iron chelation therapy (OIC) with deferasirox for 6 years before puberty; the second group (Group B;40 patients) attained the FA-Ht before the use of OIC (iron chelation therapy with deferoxamine (DFO) given subcutaneously, since the age of 2 years). In both groups liver iron concentration was measured using FerriScan ® R2-MRI method. Furthermore, the FA-Ht, bode mass index (BMI), and insulin growth factor-1 (IGF-1) in a selected group of adult patients [9 with normal growth hormone (GH) secretion (GHN) and 8 with GH deficiency (GHD; peak GH response to provocative test  with clonidine: < 7 ng/ml), who were on iron chelation therapy with DFO given subcutaneously that was changed to oral deferasirox during the last 5-6 years. These 15 patients were not treated with rhGH. RESULTS: Adults with BTM who received OIC for 6 years or more before attaining their FA-Ht, had lower liver iron concentration (LIC) assessed by FerriScan® R2-MRI, fasting glucose level (FBG) and liver enzymes (ALT and AST), and a better FA-Ht expressed in standard deviation score (FA-Ht-SDS), and higher IGF-1 SDS versus those who did not receive OIC before attaining FA-Ht. The prevalence of endocrinopathies, including hypothyroidism and hypogonadism were significantly lower in Group A versus Group B.  Comparison between the group with normal GHN and those with GHD showed that the FA-Ht-SDS of those with GHD (159.1± 6.42 cm). Ht-SDS = -2.5 ± 0.9) was significantly decreased compared to the group with NGH (Ht = 163.5 ± 5.2 cm, Ht-SDS = -1.74 ± 0.83).  The IGF-1-SDS did not differ between the two groups. Neither ferritin level nor IGF-1 concentrations were correlated with the Ht-SDS. The final FA-Ht-SDS correlated significantly with the peak GH secretion (r = 0.788, p = 0.0008). The FA-Ht-SDS were positively related to their mid-parental height (r=0.58, P <0.01). CONCLUSIONS: The use of OIC years before the end of puberty was associated with a significantly lower prevalence of endocrinopathies, improvement of LIC and FA-Ht. The final adult height of patients with BTM and GHD was significantly shorter compared to their pears with NGH. rhGH therapy can be recommended for the treatment of thalassemic children and adolescents with GHD in addition to proper blood transfusion and intensive chelation to improve their final height.

Iron Chelation Therapy as a Modality of Management.

Introduction of MRI techniques for identifying and monitoring tissue iron overload and the current understanding of iron homeostasis in transfusion-dependent (TDT) and non-transfusion-dependent thalassemia have allowed for a more robust administration of iron chelation therapies. The development of safe and efficient oral iron chelators and the insights gained from large-scale prospective studies using these agents have improved iron overload management. A significant reduction in iron toxicity-induced morbidity and mortality and improvements in quality of life were observed in TDT. The appropriate management of tissue-specific iron loading in TDT has been portrayed using evidence-based data obtained from investigational studies.

Endocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody.

The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin. As endocrinopathies were prevalent in the majority of paediatric-onset AQP4-Ab NMOSD, endocrine surveillance and in particular early aggressive weight management is required for patients with AQP4-Ab NMOSD.

Rehabilitation Interventions to modify endocrine-metabolic disease risk in Individuals with chronic Spinal cord injury living in the Community (RIISC): A systematic review and scoping perspective.

CONTEXT: Endocrine-metabolic disease (EMD) risk following spinal cord injury (SCI) is associated with significant multi-morbidity (i.e. fracture, diabetes, heart disease), mortality, and economic burden. It is unclear to what extent rehabilitation interventions can modify EMD risk and improve health status in community-dwelling adults with chronic SCI. OBJECTIVES: To characterize rehabilitation interventions and summarize evidence on their efficacy/effectiveness to modify precursors to EMD risk in community-dwelling adults with chronic SCI. METHODS: Systematic searches of MEDLINE PubMed, EMBASE Ovid, CINAHL, CDSR, and PsychInfo were completed. All randomized, quasi-experimental, and prospective controlled trials comparing rehabilitation/therapeutic interventions with control/placebo interventions in adults with chronic SCI were eligible. Two authors independently selected studies and abstracted data. Mean differences of change from baseline were reported for EMD risk outcomes. The GRADE approach was used to rate the quality of evidence. RESULTS: Of 489 articles identified, 16 articles (11 studies; n=396) were eligible for inclusion. No studies assessed the effects of rehabilitation interventions on incident fragility fractures, heart disease, and/or diabetes. Individual studies reported that exercise and/or nutrition interventions could improve anthropometric indices, body composition/adiposity, and biomarkers. However, there were also reports of non-statistically significant between-group differences. CONCLUSIONS: There was very low-quality evidence that rehabilitation interventions can improve precursors to EMD risk in community-dwelling adults with chronic SCI. The small number of studies, imprecise estimates, and inconsistency across studies limited our ability to make conclusions. A high-quality longitudinal intervention trial is needed to inform community-based rehabilitation strategies for EMD risk after chronic SCI.

Evaluation of endocrine and metabolic dysfunctions after hematopoietic stem cell transplantation in children: a study from Turkey.

BACKGROUND: Endocrine organs are highly susceptible to effects of high-dose chemotherapy. The objective of the study was to evaluate endocrine and metabolic complications after hematopoietic stem cell transplantation (HSCT) in children. METHODS: The patients who underwent HSCT in our center from April 2010 to October 2014 with at least 1 year follow-up were analyzed retrospectively. RESULTS: One-hundred children (M/F:59/41; mean age 8.9±4.8 years, mean follow-up time 3.4±1.2 years) were included in the study. Female hypogonadism was the most common endocrine dysfunction (35.7%), followed by growth impairment (29.4%), malnutrition (27.4%), dyslipidemia (26%), low bone mineral density (BMD) (25%), hypothyroidism (13%) and insulin resistance (12%). Patients who underwent HSCT >10 years of age were significantly at risk for hypogonadism, metabolic syndrome, growth impairment and malnutrition (p<0.05). CONCLUSIONS: Endocrine or metabolic dysfunctions are more prevalent in children who are older than 10 years of age at HSCT. Children who underwent HSCT should be followed-up by a multidisciplinary team during puberty and adolescence.

Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Childhood leukaemia survivors' experiences of long-term follow-ups in an endocrine clinic - A focus-group study.

The survival rate after childhood cancer has improved markedly and today more than 80% of patients will survive. Many childhood cancer survivors suffer from late complications due to radiotherapy and chemotherapy. Survivors of Acute Lymphoblastic Leukaemia (ALL), treated with cranial radiotherapy, are at a particularly high risk of having endocrine complications. PURPOSE: To illuminate childhood ALL survivors' experiences of a long-term follow-up in an endocrine clinic. METHOD: Data collection carried out using semi-structured focus-group interviews. Fifteen ALL survivors were included in the study, divided into 4 groups. Data was analysed with conventional qualitative content analysis. RESULTS: The survivors' experiences were captured in the theme: "The need for understanding and support in order to manage daily life". An understanding of their situation, as well as support for managing daily life was fundamental. Lack of understanding and support from the community was connected with a fear for the future. The follow-up at the endocrine clinic was shown to be crucial for increasing the survivors' understanding of late complications. The past feeling of being out of control was replaced with an increased self-confidence. CONCLUSION: Many leukaemia survivors experienced their daily lives as a struggle and as a complicated issue to cope with. The theme "understanding and support to manage daily life" mirrors how the survivors are in need of knowledge and support in order to handle and understand their complex situation after surviving leukaemia. Offering understanding and support with a holistic approach, may be a way in which to strengthen the survivors' health.

Endocrinopathies in adolescents with thalassaemia major receiving oral iron chelation therapy.

BACKGROUND: Endocrinopathies are common in patients with thalassaemia major (TM) despite parenteral iron chelation therapy with deferoxamine. There are only a few studies on the efficacy of oral deferiprone in preventing endocrine dysfunction. AIM: To determine the growth and endocrine complications in children with TM receiving oral iron chelation with deferiprone. METHODS: All adolescents with TM receiving regular blood transfusion and deferiprone were evaluated prospectively for growth and pubertal status over a 1-year period. Tests for endocrine function included oral glucose tolerance test, calcium, phosphate, alkaline phosphatase, parathyroid hormone and thyroid profile and, in those with delayed/arrested puberty, sex steroids and gonadotropins. Clonidine-stimulated growth hormone (GH) was measured in patients with height ≤-3 SD. RESULTS: 89 patients [51 males, 38 females, mean (SD) age 13·6 (2·5) years] were evaluated. Mean (SD) pre-transfusion haemoglobin was 9·2 (1·1) g/dl and the mean (SD) age of starting deferiprone was 5·1 (2·4) years. Mean (SD) ferritin was 9159 (3312) pmol/L (normal <2247). 49 (55%) subjects were of short stature and 25 (27%) had a height Z-score ≤ -3. GH testing was performed in 19 patients, of whom 17 had peak GH values <10 µg/L. Delayed puberty and/or hypogonadism was present in 54·1% patients at or beyond the age of normal puberty. Impaired glucose tolerance/diabetes mellitus, hypoparathyroidism and primary hypothyroidism (subclinical) were present in 13·0%, 10·1% and 8·9%, respectively. Overall, 44 (49·4%) adolescents had at least one endocrinopathy. CONCLUSION: Adolescents with TM on oral iron chelation therapy with deferiprone experienced a high prevalence of growth faltering and endocrinopathies which was comparable to that previously reported with deferoxamine. A combination of deferoxamine and deferiprone may be necessary to prevent growth and endocrine problems.

Asymptomatic Interhypothalamic Adhesions in Children.

With the use of high-resolution MR imaging techniques, we have increasingly observed anomalies of the hypothalamus characterized by a band of tissue spanning the third ventricle between the hypothalami, often without associated clinical sequelae. Historically, hypothalamic anomalies are highly associated with symptoms referable to a hypothalamic hamartoma, midline congenital disorder, hypothalamic-pituitary dysfunction, or seizures, with very few asymptomatic patients reported. The interhypothalamic tissue described in our cohort was observed incidentally through the routine acquisition of high-resolution T1WI. No referable symptoms were identified in most of the study group. In the appropriate patient population in which associated symptoms are absent, the described hypothalamic anomalies may be incidental and should not be misdiagnosed as hypothalamic hamartomas.

Effect of cancer treatment on hypothalamic-pituitary function.

The past 30 years have seen a great improvement in survival of children and young adults treated for cancer. Cancer treatment can put patients at risk of health problems that can develop many years later, most commonly affecting the endocrine system. Patients treated with cranial radiotherapy often develop dysfunction of the hypothalamic-pituitary axis. A characteristic pattern of hormone deficiencies develops over several years. Growth hormone is disrupted most often, followed by gonadal, adrenal, and thyroid hormones, leading to abnormal growth and puberty in children, and affecting general wellbeing and fertility in adults. The severity and rate of development of hypopituitarism is determined by the dose of radiotherapy delivered to the hypothalamic-pituitary axis. Individual growth hormone deficiencies can develop after a dose as low as 10 Gy, whereas multiple hormone deficiencies are common after 60 Gy. New techniques in radiotherapy aim to reduce the effect on the hypothalamic-pituitary axis by minimising the dose received. Patients taking cytotoxic drugs do not often develop overt hypopituitarism, although the effect of radiotherapy might be enhanced. The exception is adrenal insufficiency caused by glucocorticosteroids which, although transient, can be life-threatening. New biological drugs to treat cancer can cause autoimmune hypophysitis and hypopituitarism; therefore, oncologists and endocrinologists should be vigilant and work together to optimise patient outcomes.