Bariatric surgery is established as a highly effective treatment for obesity and related metabolic complications. Although once seen as a last resort for patients with obesity, given the data demonstrating the profound weight loss, improvement in comorbidity and safety, perceptions have since shifted. There is evidence from 12 RCTs demonstrating its safety and efficacy in terms of weight loss which is sustained in the long term with a resultant improvement in co-morbidity. Clinicians are increasingly recognising the importance of timely intervention to maximise the effects of bariatric surgery, particularly in light of the low likelihood of being able to adequately manage patients with medication or lifestyle interventions alone. The inclusion of bariatric surgery in the standard treatment algorithm has been a step forward in the approach to treating patients with obesity. What remains challenging for clinicians is knowing which procedure is most beneficial to patients. There is no level one data demonstrating the superiority of one procedure over another. Head to head RCTs are ongoing which may shed light on this question; however, it is likely that there is no single procedure that will be demonstrated to be the gold standard. Herein we review the most commonly performed procedures along with the evidence available to support their effects with regards to weight loss and metabolic changes along with their limitations and recognised risks. The aim is to provide a general framework to allow clinicians to take advantage of the variety of operative approaches to tailor their treatment strategy to the individual patient.
Alexis Sudlow, Carel W le Roux, and Dimitri J Pournaras
Mardia López-Alarcón, Jessie N Zurita-Cruz, Alonso Torres-Rodríguez, Karla Bedia-Mejía, Manuel Pérez-Güemez, Leonel Jaramillo-Villanueva, Mario E Rendón-Macías, Jose R Fernández, and Patricia Martínez-Maroñas
Childhood obesity is associated with stress. However, most treatment strategies include only dietary and physical activity approaches. Mindfulness may assist in weight reduction, but its effectiveness is unclear. We assessed the effect of mindfulness on stress, appetite regulators, and weight of children with obesity and anxiety. A clinical study was conducted in a pediatric hospital. Eligible children were 10–14 years old, BMI ≥95th percentile, Spence anxiety score ≥55, and who were not taking any medication or supplementation. Participants were assigned to receive an 8-week conventional nutritional intervention (CNI) or an 8-week mindfulness-based intervention plus CNI (MND-CNI). Anthropometry, body composition, leptin, insulin, ghrelin, cortisol, and Spence scores were measured at baseline and at the end of the intervention. Anthropometry was analyzed again 8 weeks after concluding interventions. Log-transformed and delta values were calculated for analysis. Thirty-three MND-CNI and 12 CNI children finished interventions; 17 MND-CNI children accomplished 16 weeks. At the end of the intervention, significant reductions in anxiety score (−6.21 ± 1.10), BMI (−0.45 ± 1.2 kg/m2), body fat (−1.28 ± 0.25%), ghrelin (−0.71 ± 0.37 pg/mL), and serum cortisol (−1.42 ± 0.94 µg/dL) were observed in MND-CNI children. Changes in anxiety score, ghrelin, and cortisol were different between groups (P < 0.05). Children who completed 16 weeks decreased BMI after intervention (−0.944 ± 0.20 kg/m2, P < 0.001) and remained lower 8 weeks later (−0.706 ± 0.19 kg/m2, P = 0.001). We concluded that mindfulness is a promising tool as an adjunctive therapy for childhood obesity. However, our findings need confirmation in a larger sample population.
Kunal Thakkar, Swati Ramteke-Jadhav, Rajeev Kasaliwal, Saba Samad Memon, Virendra Patil, Puja Thadani, Nilesh Lomte, Shilpa Sankhe, Atul Goel, Sridhar Epari, Naina Goel, Anurag Lila, Nalini S Shah, and Tushar Bandgar
Most common incidentally detected sellar-suprasellar region (SSR) masses are pituitary adenomas, followed by craniopharyngioma, rathke’s cleft cyst, hypophysitis, and meningioma. Besides these, certain unusual SSR lesions can sometimes present as diagnostic challenges, where diagnosis is often made post-operatively on histopathology, the pre-operative suspicion of which might have influenced the management strategies. Series describing such masses are few.
To present clinical, biochemical, and radiological characteristics and management outcomes of rare SSR lesions other than pituitary adenomas, craniopharyngioma, rathke’s cleft cyst, hypophysitis, and meningioma.
Design, setting, patients
Retrospective case record analysis of patients with uncommon SSR masses (from January 2006 to December 2016).
Our series consisted of ten patients, five with neoplastic and five with non-neoplastic lesions. Neoplastic masses included granular cell tumor (n = 2), astrocytoma (n = 1), malignant peripheral nerve sheath tumor (MPNST, n = 1), and metastasis from occult papillary carcinoma of thyroid (n = 1), while non-neoplastic masses were aspergillus abscess (n = 1), sterile abscess (n = 1), and tubercular abscess (n = 1), aneurysm of left internal carotid artery (n = 1), and ruptured dermoid cyst (n = 1). All patients (except one) presented with headache and/or visual disturbance. Only one patient had acromegaly while most others had hypopituitarism. We describe detailed MRI characteristics of each of the lesion. Seven patients underwent trans-sphenoidal surgery. Post-operatively, five patients had permanent diabetes insipidus, while two patients died in early post-operative period.
Our series expand the differential diagnostic considerations of SSR lesions. Most of the rare SSR masses present with symptoms of mass effects and hypopituitarism. Except for some non-neoplastic lesions like sellar abscesses, aneurysms, and dermoid cysts which can have some specific imaging characteristics that can provide clue to pre-operative diagnosis, most of the other neoplastic masses have overlapping radiological features, and pre-operative suspicion remains difficult.
Katherine U Gaynor, Irina V Grigorieva, Samantha M Mirczuk, Sian E Piret, Kreepa G Kooblall, Mark Stevenson, Karine Rizzoti, Michael R Bowl, M Andrew Nesbit, Paul T Christie, William D Fraser, Tertius Hough, Michael P Whyte, Robin Lovell-Badge, and Rajesh V Thakker
Hypoparathyroidism is genetically heterogeneous and characterized by low plasma calcium and parathyroid hormone (PTH) concentrations. X-linked hypoparathyroidism (XLHPT) in two American families is associated with interstitial deletion-insertions involving deletions of chromosome Xq27.1 downstream of SOX3 and insertions of predominantly non-coding DNA from chromosome 2p25.3. These could result in loss, gain, or movement of regulatory elements, which include ultraconserved element uc482, which could alter SOX3 expression. To investigate this, we analysed SOX3 expression in EBV-transformed lymphoblastoid cells from three affected males, three unaffected males, and four carrier females from one XLHPT family. SOX3 expression was similar in all individuals, indicating that the spatiotemporal effect of the interstitial deletion-insertion on SOX3 expression postulated to occur in developing parathyroids did not manifest in lymphoblastoids. Expression of SNTG2, which is duplicated and inserted into the X chromosome, and ATP11C, which is moved telomerically, were also similarly expressed in all individuals. Investigation of male hemizygous (Sox3 −/Y and uc482 −/Y) and female heterozygous (Sox3 +/ − and uc482 +/ −) knockout mice, together with wild-type littermates (male Sox3 +/Y and uc482 +/Y, and female Sox3 +/+ and uc482 +/+), revealed Sox3 −/Y, Sox3 +/ −, uc482 −/Y, and uc482 +/ − mice to have normal plasma biochemistry, compared to their respective wild-type littermates. When challenged with a low calcium diet, all mice had hypocalcaemia, and elevated plasma PTH concentrations and alkaline phosphatase activities, and Sox3 −/Y, Sox3 +/ −, uc482 −/Y, and uc482 +/ − mice had similar plasma biochemistry, compared to wild-type littermates. Thus, these results indicate that absence of Sox3 or uc482 does not cause hypoparathyroidism and that XLHPT likely reflects a more complex mechanism.
Carla Scaroni, Nora M Albiger, Serena Palmieri, Davide Iacuaniello, Chiara Graziadio, Luca Damiani, Marialuisa Zilio, Antonio Stigliano, Annamaria Colao, Rosario Pivonello, and the Altogether to Beat Cushing’s Syndrome (ABC) study group
The distinction between pseudo-Cushing’s states (PCS) and Cushing’s syndrome (CS) poses a significant clinical challenge even for expert endocrinologists. A patient’s clinical history can sometimes help to distinguish between them (as in the case of alcoholic individuals), but the overlap in clinical and laboratory findings makes it difficult to arrive at a definitive diagnosis. We aim to describe the most common situations that can give rise to a condition resembling overt endogenous hypercortisolism and try to answer questions that physicians often face in clinical practice. It is important to know the relative prevalence of these different situations, bearing in mind that most of the conditions generating PCS are relatively common (such as metabolic syndrome and polycystic ovary syndrome), while CS is rare in the general population. Physicians should consider CS in the presence of additional features. Appropriate treatment of underlying conditions is essential as it can reverse the hormonal abnormalities associated with PCS. Close surveillance and a thorough assessment of a patient’s hormone status will ultimately orient the diagnosis and treatment options over time.
D A Dart, K Ashelford, and W G Jiang
Advanced prostate cancer is often treated with AR antagonists which target the androgen receptor (AR) on which the growth of the tumour depends. Prostate cancer often develops AR-antagonist resistance via a plethora of mechanisms, many of which are as yet unknown, but it is thought that AR upregulation or AR ligand-binding site mutations, may be responsible. Here we describe the production of cell lines based on LNCaP and VCaP, with acquired resistance to the clinically relevant AR antagonists, bicalutamide and enzalutamide. In these resistant cells, we observed, via RNA-seq, that new variants in the 3′UTR of the AR mRNA were detectable and that the levels were increased both with AR-antagonist treatment and with hormonal starvation. Around 20% of AR transcripts showed a 3 kb deletion within the 6.7 kb 3′UTR sequence. Actinomycin D and luciferase fusion studies indicated that this shorter mRNA variant was inherently more stable in anti-androgen-resistant cell lines. Of additional interest was that the AR UTR variant could be detected in the sera of prostate cancer patients in a cohort of serum samples collected from patients of Gleason grades 6–10, with an increasing level correlated to increasing grade. We hypothesise that the shorter AR UTR variant is a survival adaptation to low hormone levels and/or AR-antagonist treatment in these cells, where a more stable mRNA may allow higher levels of AR expression under these conditions.
Ling Zhou, Zhexin Ni, Wen Cheng, Jin Yu, Shuai Sun, Dongxia Zhai, Chaoqin Yu, and Zailong Cai
Polycystic ovary syndrome (PCOS) is a chronic endocrine and metabolic disease. Gut microbiota is closely related to many chronic diseases. In this study, we conducted a cross-sectional study and recruited 30 obese (OG) and 30 non-obese (NG) women with PCOS, 30 healthy women (NC) and 11 healthy but obese women (OC) as controls to investigate the characteristic gut microbiota and its metabolic functions in obese and non-obese patients with PCOS. The blood and non-menstrual faecal samples of all the participants were collected and analysed. As a result, the Hirsutism score, LH/FSH and serum T level in NG and OG both increased significantly compared with their controls (P < 0.05). High-throughput 16S rRNA gene sequencing revealed that the abundance and diversity of the gut microbiota changed in patients with PCOS. The linear discriminant analysis (LDA) indicated that Lactococcus was the characteristic gut microbiota in NG, while Coprococcus_2 in OG. Correlation heatmap analysis revealed that the sex hormones and insulin levels in human serum were closely related to the changes in the gut microbiota of NG and OG. Functional prediction analysis demonstrated that the citrate cycle pathway enriched both in NG and OG, and other 12 gut bacterial metabolic pathways enriched in NG. This study highlighted significant differences in the gut microbiota and predictive functions of obese and non-obese women with PCOS, thereby providing insights into the role and function of the gut microbiota that may contribute to the occurrence and development of PCOS in obese and non-obese women.
Bettina Winzeler, Michelle Steinmetz, Julie Refardt, Nicole Cesana-Nigro, Milica Popovic, Wiebke Fenske, and Mirjam Christ-Crain
The syndrome of inappropriate antidiuresis (SIAD) is a common condition in hospitalized patients. It is crucial to establish the cause of SIAD, especially in order to exclude underlying malignancy. As malignant SIAD may be due to a paraneoplastic synthesis of arginine vasopressin, we hypothesized that its stable surrogate marker copeptin can be used as a diagnostic tool to differentiate between malignant and non-malignant SIAD.
Prospective observational study. We analyzed data from 146 SIAD patients of two different cohorts from Switzerland and Germany. Patients were included while presenting at the emergency department and underwent a standardized diagnostic assessment including the measurement of copeptin levels.
Thirty-nine patients (median age: 63 years, 51% female) were diagnosed with cancer-related SIAD and 107 (median age: 73 years, 68% female) with non-malignant SIAD. Serum sodium levels were higher in cancer-related versus non-malignant SIAD: median (IQR) 124 mmol/l (120; 127) versus 120 mmol/l (117; 123) (P<0.001). Median (IQR) copeptin levels of patients with cancer-related SIAD were 11.1 pmol/l (5.2; 37.1) and 10.5 pmol/l (5.2; 25.2) with non-malignant SIAD (P = 0.38). Among different cancer entities, patients suffering from small-cell lung cancer showed the highest copeptin values, but overall no significant difference in copeptin levels between cancer types was observed (P = 0.46).
Copeptin levels are similar in cancer-related and non-malignant SIAD. Therefore, Copeptin does not seem to be suitable as a marker of malignant disease in SIAD.
L E Zijlstra, D M van Velzen, S Simsek, S P Mooijaart, M van Buren, D J Stott, I Ford, J W Jukema, and S Trompet
Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes.
In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45–4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45–60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke.
Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24–1.07) comparing subclinical hyperthyroidism and 0.90 (0.58–1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism).
In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.