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Mischa de Ridder, Els Nieveen van Dijkum, Anton Engelsman, Ellen Kapiteijn, Heinz-Josef Klümpen, and Coen R N Rasch

Objective

To perform a nationwide population based study in ATC on incidence, treatment and survival.

Design

Retrospective cohort study.

Methods

All patients with primary ATC between 1989 and 2016 were identified in the Netherlands Cancer Registry (NCR). Of all these patients excerpts from the pathology reports from PALGA: Dutch Pathology registry were linked to the data of the NCR. Standardized incidences were calculated, survival was estimated using Kaplan–Meier method and univariable statistically significant factors were included in a multivariable regression model.

Results

In total, 812 patients were included. Mean standardized incidence rates were 0.18/100 000 (range 0.11–0.27/100 000) with a significant trend over the years with an estimated annual percentage change of 1.3% per year (95% CI 0.4–2.1%). Median overall survival was 2.2 months, and estimated 1-year survival was 12%. Patients without distant metastases at diagnosis had an estimated 1-year survival of 21.6%. Prognostic factors for prolonged survival were double or triple therapy, age below 65 years, M0-status and absence of bilateral lymph node metastases.

Conclusions

ATC is rare, but often lethal, form of thyroid cancer, with a median survival of 2 months and 1-year survival of approximately 10%. The incidence is slightly rising in the Netherlands over the past 3 decades. There appears to be a subgroup of patients that survive longer, mainly those with relatively limited disease who underwent double or triple therapy. Further research is needed to define these patients more distinctively.

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Saskia le Cessie, Jelle J Goeman, and Olaf M Dekkers

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Kristen M Beavers, Katelyn A. Greene, and Elaine W. Yu

Despite well recognized improvements in obesity-related comorbidities, increasing evidence implicates bariatric surgery in the onset of adverse skeletal health outcomes. The purpose of this review is to provide a focused update in three critical areas: 1) emergent data on sleeve gastrectomy and bone loss, 2) evidence linking bariatric surgery to incident fracture, and 3) intervention strategies designed to mitigate surgical bone loss. Better understanding of these issues will inform our treatment of skeletal health for patients planning bariatric surgery.

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Rougin Khalil, Leen Antonio, Michaël R Laurent, Karel David, Na Ri Kim, Pieter Evenepoel, Anton Eisenhauer, Alexander Heuser, Etienne Cavalier, Sundeep Khosla, Frank Claessens, Dirk Vanderschueren, and Brigitte Decallonne

Objective

Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover.

Design

Prospective cohort study.

Methods

Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied.

Results

Of 26 screened patients, 17 were included. The median age was 44 (range 20–75) years. The median time interval between baseline and first follow-up was 13 (6–27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4–12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01–0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7–35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered.

Conclusions

In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.

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Lucie Allard, Frédérique Albarel, Jérôme Bertherat, Philippe Jean Caron, Christine Cortet, Carine Courtillot, Brigitte Delemer, Christel Jublanc, Dominique Maiter, Marie Laure Nunes, Gerald Raverot, Julie Sarfati, Sylvie Salenave, Emmanuelle Corruble, Walid Choucha, and Philippe Chanson

Context

In patients treated with antipsychotics, the rare occurrence of a macroprolactinoma represents a therapeutic challenge.

Objective

Our aim was to evaluate the efficacy and psychiatric safety of dopamine agonists (DAs) prescribed for large macroprolactinomas in patients with psychosis treated with antipsychotics.

Design

This was a multicenter (France and Belgium) retrospective study.

Patients

Eighteen patients treated with antipsychotics were included.

Results

Under DA, median PRL levels decreased from 1247 (117–81 132) to 42 (4–573) ng/mL (P = 0.008), from 3850 (449–38 000) to 141 (60–6000) ng/mL (P = 0.037) and from 1664 (94–9400) to 1215 (48–5640) ng/mL (P = 0.56) when given alone (n = 8), before surgery (n = 7), or after surgery (n = 6), respectively. The prolactinoma median largest diameter decreased by 28% (0–57) in patients under DAs alone (P = 0.02) but did not change when given after surgery. Optic chiasm decompression was achieved in 82% of patients. Five patients (28%) were admitted for psychotic relapse while receiving DAs (but three of them had stopped antipsychotic treatment at that time). A more severe underlying psychosis, rather than the DA treatment itself, may explain such psychiatric admissions.

Conclusion

Even if the DA efficacy on PRL levels and tumor volume in patients with macroprolactinoma under antipsychotic drugs is less impressive than that typically observed, it may be considered satisfactory for half of our patients, particularly in cases of optic chiasm compression. Psychotic exacerbation was unusual in these patients, occurring mostly in those with the most severe psychotic forms. DAs may therefore be used as antitumor treatment for macroprolactinoma in patients with visual involvement, severe headaches or invasion into the skull base who receive antipsychotics.

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Ruth T Casey, Gerlof D Valk, Camilla Schalin-Jäntti, Ashley B Grossman, and Rajesh V Thakker

In viral pandemics, most specifically Covid-19, many patients with neuroendocrine neoplasms (NENs), including phaeochromocytomas, paragangliomas and medullary thyroid carcinoma, may develop Covid-19 in a mild or severe form, or be concerned about the influence of viral infection relative to their anti-tumoral therapy. In general, newly presenting patients should be assessed, and patients recently receiving chemotherapy, targeted therapy or radionuclide therapy, or showing tumour growth, should be closely followed. For previously diagnosed patients, who have indolent disease, some delay in routine follow-up or treatment may not be problematic. However, patients developing acute secretory syndromes due to functional neuroendocrine neoplasms (such as of the pancreas, intestine or lung), phaeochromocytomas and paragangliomas, will require prompt treatment. Patients with life-threatening Covid-19-related symptoms should be urgently treated and long-term anti-tumoral treatments may be temporarily delayed. In patients with especially aggressive NENs, a careful judgement should be made regarding the severity of any Covid-19 illness, tumour grade, and the immunosuppressant effects of any planned chemotherapy, immunotherapy (e.g. interferon-alpha), targeted therapy or related treatment. In other cases, especially patients with completely resected NENs, or who are under surveillance for a genetic disorder, a telephone or delayed consultation may be in order, balancing the risk of a delay against that of the possible development of Covid-19.

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Shakila Thangaratinam, Shamil D Cooray, Nithya Sukumar, Mohammed S B Huda, Roland Devlieger, Katrien Benhalima, Fionnuala McAuliffe, Ponnusamy Saravanan, and Helena J Teede

The COVID-19 pandemic has required rapid transformation and adaptation of healthcare services. Women with gestational diabetes mellitus (GDM) are one of the largest high-risk groups accessing antenatal care. In reformulating the care offered to those with GDM, there is a need to balance the sometimes competing requirement of lowering the risk of direct viral transmission against the potential adverse impact of service changes. We suggest pragmatic options for screening of GDM in a pandemic setting based on blood tests, and risk calculators applied to underlying risk factors. Alternative models for antenatal care provision for women with GDM, including targeting high-risk groups, early lifestyle interventions and remote monitoring are provided. Testing options and their timing for postpartum screening in women who had GDM are also considered. Our suggestions are only applicable in a pandemic scenario, and usual guidelines and care pathways should be re-implemented as soon as possible and appropriate.

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Neil J Gittoes, Sherwin Criseno, Natasha M Appelman-Dijkstra, Jens Bollerslev, Ernesto Canalis, Lars Rejnmark, and Zaki Hassan-Smith

Endocrinologists have had to make rapid changes to services so that resources can be focused on the COVID-19 response to help prevent spread of the virus. Herein we provide pragmatic advice on the management of commonly encountered calcium metabolic problems and osteoporosis. Non-urgent elective appointments should be postponed, and remote consultations and digital health solutions promoted. Patients should be empowered to self-manage their conditions safely. Patients, their caregivers and healthcare providers should be directed to assured national or international online resources and specific patient groups. For patients in acute hospital settings, existing emergency guidance on the management of hyper- and hypo-calcaemia should be followed. An approach to osteoporosis management is outlined. IV zoledronic acid infusions can be delayed for 6–9 months during the pandemic. Patients established on denosumab, teriparatide and abaloparatide should continue planned therapy. In the event of supply issues with teriparatide or abaloparatide, pausing this treatment in the short term is likely to be relatively harmless, whereas delaying denosumab may cause an immediate increased risk of fracture. The challenge of this pandemic will act as a catalyst to innovate within our management of metabolic bone and mineral disorders to ensure best use of resources and resilience of healthcare systems in its aftermath.

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Deborah J Wake, Fraser W Gibb, Partha Kar, Brian Kennon, David C Klonoff, Gerry Rayman, Martin K Rutter, Chris Sainsbury, and Robert K Semple

The COVID-19 pandemic is a major international emergency leading to unprecedented medical, economic and societal challenges. Countries around the globe are facing challenges with diabetes care and are similarly adapting care delivery, with local cultural nuances. People with diabetes suffer disproportionately from acute COVID-19 with higher rates of serious complications and death. In-patient services need specialist support to appropriately manage glycaemia in people with known and undiagnosed diabetes presenting with COVID-19. Due to the restrictions imposed by the pandemic, people with diabetes may suffer longer-term harm caused by inadequate clinical support and less frequent monitoring of their condition and diabetes-related complications. Outpatient management need to be reorganised to maintain remote advice and support services, focusing on proactive care for the highest risk, and using telehealth and digital services for consultations, self-management and remote monitoring, where appropriate. Stratification of patients for face-to-face or remote follow-up should be based on a balanced risk assessment. Public health and national organisations have generally responded rapidly with guidance on care management, but the pandemic has created a tension around prioritisation of communicable vs non-communicable disease. Resulting challenges in clinical decision-making are compounded by a reduced clinical workforce. For many years, increasing diabetes mellitus incidence has been mirrored by rising preventable morbidity and mortality due to complications, yet innovation in service delivery has been slow. While the current focus is on limiting the terrible harm caused by the pandemic, it is possible that a positive lasting legacy of COVID-19 might include accelerated innovation in chronic disease management.

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Juho Kärkinen, Päivi J. Miettinen, Taneli Raivio, and Matti Hero

Objective

To describe the etiology of severe short stature in the Helsinki University Hospital district covering a population of 1.2 million that is subject to frequent growth monitoring and screening rules during childhood.

Design

Retrospective cohort study.

Methods

We identified all subjects born 1990 or later with a height SD score ≤-3, after the age of three years, from the Helsinki University Hospital district growth database. 785 subjects (376 females and 409 males) fulfilled our inclusion criteria; we reviewed their medical records, growth data, and report their underlying diagnoses.

Results

A pathological cause for short stature was diagnosed in 76% of the girls and 71% of the boys (P=NS). Syndromes were the most numerous pathological cause (n=160; 20%), followed by organ disorders (n=127; 16%), growth hormone deficiency (GHD, n=94; 12%), SGA without catch-up growth (n=73; 9%), and skeletal dysplasias (n=57; 7%). Idiopathic short stature (ISS) was diagnosed in 210 (27%) subjects. The probability of growth-related pathology, particularly of a syndrome or skeletal dysplasia, increased with the shorter height SD score and the greater deviation from the target height. Sitting height to height SDS was increased in subjects with ISS, GHD, and SGA (all P < 0.01).

Conclusions

Height ≤ -3 SDS after three years of age usually results from a pathological cause and should be thoroughly investigated in specialized health care. The chance of finding a specific etiology increased with the severity of short stature; and the mismatch with target height.