Plasma concentrations of SSRI/SNRI after bariatric surgery and the effects on depressive symptoms.

Background: Depression and treatment with antidepressants SSRI/SNRI are common in people with morbid obesity who are candidates for bariatric surgery. There is few and inconsistent data about the postoperative plasma concentrations of SSRI/SNRI. The aims of our study were to provide comprehensive data about the postoperative bioavailability of SSRI/SNRI, and the clinical effects on depressive symptoms. Methods: Prospective multicenter study including 63 patients with morbid obesity and therapy with fixed doses of SSRI/SNRI: participants filled the Beck Depression Inventory (BDI) questionnaire, and plasma levels of SSRI/SNRI were measured by HPLC, preoperatively (T0), and 4 weeks (T1) and 6 months (T2) postoperatively. Results: The plasma concentrations of SSRI/SNRI dropped significantly in the bariatric surgery group from T0 to T2 by 24.7% (95% confidence interval [CI], -36.8 to -16.6, p = 0.0027): from T0 to T1 by 10.5% (95% 17 CI, -22.7 to -2.3; p = 0.016), and from T1 to T2 by 12.8% (95% CI, -29.3 to 3.5, p = 0.123), respectively.There was no significant change in the BDI score during follow-up (-2.9, 95% CI, -7.4 to 1.0; p = 0.13).The clinical outcome with respect to SSRI/SNRI plasma concentrations, weight change, and change of BDI score were similar in the subgroups undergoing gastric bypass surgery and sleeve gastrectomy, respectively. In the conservative group the plasma concentrations of SSRI/SNRI remained unchanged throughout the 6 months follow-up (-14.7, 95% CI, -32.6 to 1.7; p = 0.076). Conclusion: In patients undergoing bariatric surgery plasma concentrations of SSRI/SNRI decrease significantly by about 25% mainly during the first 4 weeks postoperatively with wide individual variation, but without correlation to the severity of depression or weight loss.

Localization of Brown Tumors With 18 F-Fluorocholine PET/CT Imaging in Severe Primary Hyperparathyroidism.

ABSTRACT: We present the case of a 68-year-old woman with a painful tibial tumor and fatigue. Histology and laboratory studies were consistent with a brown tumor secondary to initially unrecognized, severe primary hyperparathyroidism. 18 F-fluorocholine PET/CT revealed a large hypermetabolic parathyroid mass and multiple bone foci considered as brown tumors. Unilateral neck exploration confirmed a large parathyroid adenoma. Serum calcium and parathyroid hormone levels normalized quickly, and symptoms subsided gradually after parathyroidectomy. Brown tumors are a rare complication of severe hyperparathyroidism. 18 F-fluorocholine PET/CT allows the localization of parathyroid adenomas and brown tumors, and can be used as a single imaging modality.

Canakinumab in patients with COVID-19 and type 2 diabetes - A multicentre, randomised, double-blind, placebo-controlled trial.

Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1ß (IL-1ß) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.

Proneuropeptide Y and neuropeptide Y metabolites in healthy volunteers and patients with a pheochromocytoma or paraganglioma.

Neuropeptide Y (NPY1-36) is a vasoconstrictor peptide co-secreted with catecholamines by sympathetic nerves, the adrenal medulla, and neoplasms such as pheochromocytomas and paragangliomas (PPGLs). It is produced by the intracellular cleavage of proNPY and metabolized into multiple fragments with distinct biological activities. NPY immunoassays for PPGL have a diagnostic sensitivity ranging from 33 to 100%, depending on the antibody used. We have validated a multiplex micro-UHPLC-MS/MS assay for the specific and sensitive quantification of proNPY, NPY1-39, NPY1-37, NPY1-36, NPY2-36, NPY3-36, NPY1-35, NPY3-35, and the C-flanking peptide of NPY (CPON) (collectively termed NPYs), and determined the NPYs reference intervals and concentrations in 32 PPGL patients before, during, and after surgery. Depending on the peptide measured, NPYs were above the upper reference limit (URL) in 20% to 67% of patients, whereas plasma free metanephrine and normetanephrine, the gold standard for PPGL, were above the URL in 40% and 87% of patients, respectively. Age, sex, tachycardia, and tumor localization were not correlated with NPYs. Plasma free metanephrines performed better than NPYs in the detection of PPGL, but NPYs may be a substitute for an early diagnosis of PPGL for patients that suffer from severe kidney impairment or receiving treatments that interfere with catecholamine reuptake.

18F-Fluorocholine-PET combined with contrast-enhanced CT for localizing hyperfunctioning parathyroid glands and optimizing surgical treatment in patients with hyperparathyroidism.

PURPOSE: Hyperparathyroidism (HPT) is a common disorder. A cure can only be achieved by removing all diseased glands. It is critical to localize the hyperfunctioning glands exactly to prevent extensive surgical exploration. The number of false negative/inconclusive results in standard imaging techniques is high. We aimed to evaluate the diagnostic accuracy of 18F-Fluorocholine-PET in combination with contrast-enhanced CT (FCH-PET/CT) and its sensitivity in patients with primary, secondary/tertiary, and familial HPT with negative and/or discordant findings in ultrasound and/or 99mTc-sestamibi scintigraphy/SPECT/CT. METHODS: A total of 96 patients with HPT and negative/equivocal conventional imaging were referred for FCH-PET/CT. In this retrospective, single institution study, 69 patients, who have undergone surgery and histopathologic workup, were analyzed. Of the 69 patients included, 60 patients suffered from primary HPT, four from secondary or tertiary HPT, and five from familial HPT. Sensitivities, positive predictive values, and accuracies were calculated. RESULTS: Sensitivity/positive predictive value (PPV) per lesion was 87.5/98.3% for primary HPT, 75/100% for secondary/tertiary HPT and 25/66.7% for familial HPT. Sensitivity/PPV per patient was 91.5/98.2% for primary HPT, 100/100% for secondary/tertiary HPT and 50/100% for familial HPT. All patients showed normalized serum calcium levels in the postoperative period. The follow-up rate was 97%. Of the patients included in the study, 58 of 60 patients with primary HPT, and four of four patients with secondary/tertiary HPT showed normal calcium and parathyroid hormone (PTH) levels after six months and were cured. Of the patients with familial HPT, four of five patients were cured. CONCLUSION: Diagnostic accuracy of 18F-Fluorocholine-PET/CT for patients with pHPT is excellent. 18F-Fluorocholine-PET/CT is a valuable tool for endocrine surgeons to optimize the surgical treatment of patients with hyperparathyroidism.

Risk of perioperative thyroid storm in hyperthyroid patients: a systematic review.

BACKGROUND: Thyroid storm is a feared complication in patients with hyperthyroidism undergoing surgery. We assessed the risk of thyroid storm for different preoperative treatment options for patients with primary hyperthyroidism undergoing surgery. METHODS: Pubmed, EMBASE, and The Cochrane Library were searched systematically for all studies reporting on adult hyperthyroid patients undergoing elective surgery under general anaesthesia. Selected studies were categorised based on preoperative treatment: no treatment, antithyroid medication (thionamides), iodine, ß-blocking medication, or a combination thereof. Treatment effect, that is restoring euthyroidism, was extracted from the publications if available. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) or the Cochrane Risk of Bias tool for randomised studies. RESULTS: The search yielded 7009 articles, of which 26 studies published between 1975 and 2020 were selected for critical appraisal. All studies had moderate to critical risk of bias, mainly attributable to risk of confounding, classification of intervention status, and definition of the outcome. All studies reported on thyroidectomy patients. We found no randomised studies comparing the risk of thyroid storm between treated and untreated patients. Cases of thyroid storm were reported in all treatment groups with incidences described ranging from 0% to 14%. CONCLUSION: Evidence assessing the risk of perioperative thyroid storm is of insufficient quality. Given the seriousness of this complication and the impossibility of identifying patients at increased risk, preoperative treatment of these patients remains warranted.

Case report of a pancreatic insulinoma misdiagnosed as epilepsy.

A 55-year-old patient had spent 12 years with unexplained seizures, initially diagnosed as epilepsy and then as a psychiatric disorder. When she was admitted with hypoglycaemia, a fasting test was performed showing blood sugar levels as low as 1 mmol/L with symptoms of neuroglycopenia. Insulinoma was suspected and an MRI showed a large tumour in the tail region of the pancreas. A Dodecanetetraacetic acid-Tyr3-octreotate (DOTATATE) positron emission tomography CT indicated no malignancy and showed no signs of metastasis. The patient underwent surgery, leaving her asymptomatic.

Impact of Adrenal Function on Hemostasis/Endothelial Function in Patients Undergoing Surgery.

CONTEXT: Glucocorticoids regulate hemostatic and endothelial function, and they are critical for adaptive functions during surgery. No data regarding the impact of adrenal function on hemostasis and endothelial function in the perioperative setting are available. OBJECTIVE: We assessed the association of adrenal response to adrenocorticotropic hormone (ACTH) and markers of endothelial/hemostatic function in surgical patients. METHODS: This prospective observational study, conducted at a tertiary care hospital, included 60 patients (35 male/25 female) undergoing abdominal surgery. Adrenal function was evaluated by low-dose ACTH stimulation test on the day before, during, and the day after surgery. According to their stimulated cortisol level (cutoff ≥ 500 nmol/L), patients were classified as having normal hypothalamic-pituitary-adrenal (HPA)-axis function (nHPA) or deficient HPA-axis function (dHPA). Parameters of endothelial function (soluble vascular cell adhesion molecule-1, thrombomodulin) and hemostasis (fibrinogen, von Willebrand factor antigen, factor VIII [FVIII]) were measured during surgery. RESULTS: Twenty-one patients had dHPA and 39 had nHPA. Compared with nHPA, patients with dHPA had significantly lower peak cortisol before (median 568 vs 425 nmol/L, P < 0.001) and during (693 vs 544 nmol/L, P < 0.001) surgery and lower postoperative hemoglobin levels (116 g/L vs 105 g/L, P = 0.049). FVIII was significantly reduced in patients with dHPA in uni- and multivariable analyses; other factors displayed no significant differences. Coagulation factors/endothelial markers changed progressively in relation to stimulated cortisol levels and showed a turning point at cortisol levels between 500 and 600 nmol/L. CONCLUSIONS: Patients with dHPA undergoing abdominal surgery demonstrate impaired hemostasis which can translate into excessive blood loss.

[Modern diagnosis and therapy of benign thyroid diseases]. / Moderne Abklärung und Therapie benigner Schilddrüsenerkrankungen.

Modern diagnosis and therapy of benign thyroid diseases Abstract. Benign thyroid diseases continue to be widespread endocrine disorders. Early recognition of their symptoms and exact diagnosis are the prerequisite of targeted therapy and minimal impairment of the patient's well-being. Drug treatment, radioiodine therapy, thermal ablation procedures and surgery have been shown to be successful treatment options. As guidelines for diagnosis and treatment of patients continue to evolve, an interdisciplinary approach ensures optimal diagnosis and management on every step in the care for these patients. We present three clinical scenarios for benign thyroid disease: the symptomatic goitre, the painful thyroid and the thyroid with hyperthyroidism.

Hypomagnesemia-Induced Cerebellar Syndrome-A Distinct Disease Entity? Case Report and Literature Review.

Clinical consequences of hypomagnesemia are manifold and include various neurological syndromes up to life-threatening conditions. Despite its importance, magnesium is generally not routinely determined leading to an under-recognition of hypomagnesemia-related disorders. In the past years, there are growing numbers of reports of hypomagnesemia-induced cerebellar syndromes (HiCS) with corresponding cerebellar edema, which might be a distinct disease entity. To provide further insights into HiCS, we describe a patient with HiCS and performed a literature review on cerebellar syndromes due to severe hypomagnesemia with regard to the clinical, MRI, and laboratory findings. We identified 17 cases, so including our case, 18 cases contribute to this review. Summarized, HiCS seems to be a distinct disease entity because of the remarkable similarities of clinical, MRI, and laboratory features. It should be diagnosed and treated early to avoid recurrent disease courses, residual symptoms, and potentially life-threatening conditions such as seizures. Physicians must be alert to HiCS as magnesium is usually not part of the routine electrolyte panel.

[CME: Pituitary Incidentaloma in Adults: Key Knowledge for the General Practice]. / CME: Zufallsraumforderung in der Hypophyse bei Erwachsenen: das Wichtigste für die Hausarztpraxis.

CME: Pituitary Incidentaloma in Adults: Key Knowledge for the General Practice Abstract. Incidentally detected pituitary masses, so-called pituitary incidentalomas, are increasing in frequency as the frequency of performing imaging increases. Evaluation of the imaging from a trained neuroradiologist as well as additional endocrinological and, if necessary, neuroophtalmological studies are part of the initial assessment that drives the treatment decision: in the case of benign small lesions with unremarkable assessment results, follow-up is indicated, whereas potentially malignant lesions or lesions with endocrinological or neuroophtalmological irregularities are usually treated. In borderline cases, interdisciplinary work is beneficial for the determination of the case-specific treatment procedure.

[Update: new forms of therapy for type-2-diabetes]. / Update: Neue Therapieformen des Diabetes mellitus Typ 2.

Update: new forms of therapy for type-2-diabetes Abstract. In the past few years medical treatment of type-2-diabetes experienced fundamental changes. New medications were approved which have no intrinsic risk of hypoglycemia and exert weight loss. Cardiovascular outcome trials demonstrated positive effects on cardiovascular morbidity and mortality for GLP-1-receptor agonists and SGLT-2-inhibitors, the latter showing also specific nephroprotective effects. The growing bulk of data leads to modified therapy strategies: Persons with established cardiovascular disease or high cardiovascular risk should be treated primary with these medications. This review starts with an overview on newer antidiabetic substances (DPPIV-inhibitors, GLP-1-receptor agonists, SGLT-2-inhibitors). Then practical aspects of treatment regimens according to actual national and international guidelines are discussed.

[CME/Answers: Pituitary Incidentaloma in Adults: Key Knowledge for the General Practice]. / CME/Antworten zu «Zufallsraumforderung in der Hypophyse bei Erwachsenen: das Wichtigste für die Hausarztpraxis¼.

CME/Answers: Pituitary Incidentaloma in Adults: Key Knowledge for the General Practice Abstract. Incidentally detected pituitary masses, so-called pituitary incidentalomas, are increasing in frequency as the frequency of performing imaging increases. Evaluation of the imaging from a trained neuroradiologist as well as additional endocrinological and, if necessary, neuroophtalmological studies are part of the initial assessment that drives the treatment decision: in the case of benign small lesions with unremarkable assessment results, follow-up is indicated, whereas potentially malignant lesions or lesions with endocrinological or neuroophtalmological irregularities are usually treated. In borderline cases, interdisciplinary work is beneficial for the determination of the case-specific treatment procedure.

Compartment syndrome of the leg after thyroid hormone withdrawal; two cases and a systematic review of the literature.

BACKGROUND: Acute compartment syndrome is a rare complication of severe hypothyroidism. If the symptoms are not recognized promptly and treatment initiated immediately, there is a high risk of permanent damage. Only few other cases of compartment syndrome due to hypothyroidism have been published and the exact pathophysiological mechanism remains unknown. CASE PRESENTATIONS: A 59 year old male developed acute compartment syndrome of his right lower leg after thyroid hormone withdrawal prior to radioiodine remnant ablation after total thyroidectomy for follicular thyroid cancer. He underwent emergency fasciotomy of all four compartments of the lower leg. The muscle tissue in the anterior and lateral compartment was necrotic and was therefore excised. The second patient was a 62 year old female with Hashimoto's thyroiditis, who developed acute compartment syndrome of both lower legs after thyroid hormone withdrawal due to non-compliance. Emergency fasciotomy of all four compartments of both legs was performed. The muscle tissue was viable in all compartments. CONCLUSION: Although compartment syndrome due to hypothyroidism is uncommon, it is a complication physicians should be aware of. The majority of reported cases are caused by an acute withdrawal of thyroid hormones and not by undetected hypothyroidism. No previous case of compartment syndrome caused by an iatrogenic hormone withdrawal in preparation for radioactive iodine has been published. However, as shown in this report, it may be beneficial to inform patients of this rare complication prior to hormone withdrawal in preparation for remnant ablation after thyroidectomy.

[CME: Endogenous Hypercortisolism (Endogenous Cushing's Syndrome)]. / CME: Endogener Hyperkortisolismus (endogenes Cushingsyndrom).

CME: Endogenous Hypercortisolism (Endogenous Cushing's Syndrome) Abstract. Endogenous Cushing's syndrome (eCS) represents a rare disease entity. At the beginning symptoms and signs often are non-specific. However, untreated eCS is associated with a substantial morbidity and mortality rate. This article provides an actual overview about the etiology, clinical presentation and diagnosis of eCS with special focus on specific screening tests.

Recurrent Hypoglycemia in a Case of Congenital Analbuminemia.

In congenital analbuminemia (CAA), mutations in the albumin gene result in a severe deficiency or absence of plasma albumin. Only about 90 cases have been reported to date, but the specific features of glucose and lipid metabolism in congenital analbuminemia have only been studied in a rat model of analbuminemia. We report the case of a female patient hospitalized for a streptococcal skin infection who showed recurrent hypoglycemia. A diagnosis of CAA was confirmed by mutation analysis and by the detection of a single base variation in the ALB gene. Hypoglycemia was first documented after a fasting period during acute illness. Recurrent hypoglycemia persisted despite good general condition and normal nutrition during antimicrobial therapy with moxifloxacin. Several contributing factors causing this hypoglycemia can be discussed. Individuals with CAA are prone to adverse drug effects caused by changes in drug-protein binding properties. It is unclear if specific changes of glucose and lipid metabolism in CAA constitute a risk factor for hypoglycemia.

[Unexpected Postoperative Diagnosis of Parathyroid Carcinoma]. / Unerwartete postoperative Diagnose eines Nebenschilddrüsenkarzinoms.

Unexpected Postoperative Diagnosis of Parathyroid Carcinoma Abstract. Parathyroid carcinoma is a rare endocrine malignancy. It typically presents itself with similar clinical features as seen in patients with primary hyperparathyroidism caused by a parathyroid adenoma. Due to overlapping clinical manifestations, imaging findings and pathological characteristics, the differentiation between benign and malignant parathyroid disease poses a diagnostic challenge, especially prior to surgery. We report the case of a 67-year-old male who presented with symptomatic hypercalcemia and primary hyperparathyroidism. During resection of the enlarged parathyroid gland, suspicious macroscopic features were noticed and the histopathology finding confirmed the malignancy. Parathyroid carcinoma is rarely diagnosed preoperatively, which is mainly due to the lack of distinctive symptoms or morphological features suggesting a malignant disease. As parathyroid carcinoma often has a genetic background, knowledge of mutation status and family history is of high relevance. Surgery with complete resection of the parathyroid carcinoma is the mainstay for a successful treatment and a good prognosis.

Identification of a TMEM127 variant in a patient with paraganglioma and acromegaly.

SUMMARY: The coincidence of a pheochromocytoma or paraganglioma and a pituitary adenoma in the same patient is a rare condition. In the last few years SDHx and MAX mutations have been identified and discussed as a potential causal connection in cases of coincidence. We describe a case of a middle-aged female patient which presented with acromegaly, a growth hormone-secreting pituitary adenoma and a symptomatic neck paraganglioma. The patient was cured by surgery from both the pituitary tumour and the paraganglioma and is well after ten years follow-up. Due to the unusual coexistence of two neuroendocrine tumours, further molecular genetic testing was performed which revealed a variant in the TMEM127 gene (c245-10C>G). LEARNING POINTS: Pheochromocytoma/paraganglioma and coexisting functioning pituitary adenoma are a very rare condition. An appropriate treatment of each tumour entity with a multi-disciplinary approach and regular follow-up is needed. The possibility of a hereditary disease should be considered and genetic workup is recommended. Genetic testing should focus primarily on the genes with mutations related to pheochromocytomas and paragangliomas. Next-generation sequencing with multi-gene panel testing is the currently suggested strategy. Genes associated with paragangliomas and pituitary adenomas are SDHA, SDHB, SDHC, SDHD, SDHAF2, MAX and MEN1, while case reports with VHL, RET and NF1 may represent coincidences. Variants of uncertain significance may need ongoing vigilance, in case novel data become available of these variants.