A pitfall of bilateral inferior petrosal sinus sampling in cyclic Cushing's syndrome

Background: Clinical care of patients with cyclic Cushing's syndrome (CS) is challenging. Classical pitfalls include incorrect subtyping, unnecessary surgical procedures and delayed definite treatment. Case presentation: A 43-year-old female suffered from a rapidly cycling ectopic CS. She experienced six cycles of severe hypercortisolism within a 2 year period (maximum plasma cortisol 5316 nmol/L, normal range 124.2-662.4 nmol/L; maximum urinary free cortisol 79,469 nmol/24 h, normal range < 414 nmol/24 h) lasting 2-9 weeks. The episodes were associated with pronounced hypokalemia (lowest K+ value recorded 2.4 mmol/l) and progressive signs and symptoms of CS. A bilateral inferior petrosal sinus sampling (BIPSS) performed during a trough phase was false positive for pituitary ACTH overproduction resulting in unnecessary transsphenoidal surgery while a second BIPSS performed during an active phase was indicative for ectopic CS. The 18F-DOPA PET/CT showed a pancreatic lesion, which was subsequently partially removed. Surprisingly, the histopathology was conclusive for ACTH-positive lymph node metastasis located in the retro-duodenal tissue of an occult neuroendocrine tumor WHO grade II. The primary tumor has not been identified so far and, because of the persistent hypercortisolism, the patient underwent bilateral adrenalectomy. Two years later, ACTH levels started to increase progressively. Percutaneous biopsy of a newly identified suspected lesion in the fifth thoracic vertebra revealed a metastasis with positive staining for ACTH, synaptophysin and chromogranin A. Therapy with carboplatin and etoposide was started and, since then, the patient underwent 12 cycles of chemotherapy. Conclusions: We report the challenging case of a rapidly cycling CS secondary to ACTH-secreting neuroendocrine intestinal tumor of unknown primary. We highlight the importance of performing diagnostic tests only during the phases of active cortisol secretion and as soon as first symptoms appear to avoid pitfalls

COVID-19 in persons aged 70+in an early affected German district: Risk factors, mortality and post-COVID care needs-A retrospective observational study of hospitalized and non-hospitalized patients

BackgroundCohorts of hospitalized COVID-19 patients have been studied in several countries since the beginning of the pandemic. So far, there is no complete survey of older patients in a German district that includes both outpatients and inpatients. In this retrospective observational cohort study, we aimed to investigate risk factors, mortality, and functional outcomes of all patients with COVID-19 aged 70 and older living in the district of Tübingen in the southwest of Germany.MethodsWe retrospectively analysed all 256 patients who tested positive for SARS-CoV-2 in one of the earliest affected German districts during the first wave of the disease from February to April 2020. To ensure inclusion of all infected patients, we analysed reported data from the public health department as well as the results of a comprehensive screening intervention in all nursing homes of the district (n = 1169). Furthermore, we examined clinical data of all hospitalized patients with COVID-19 (n = 109).ResultsThe all-cause mortality was 18%. Screening in nursing homes showed a point-prevalence of 4.6%. 39% of residents showed no COVID-specific symptoms according to the official definition at that time. The most important predictors of mortality were the need for inpatient treatment (odds ratio (OR): 3.95 [95%-confidence interval (CI): 2.00-7.86], pConclusionOur findings demonstrate the importance of a differentiated view of risk groups and long-term effects within the older population. These findings should be included in the political and social debate during the ongoing pandemic to evaluate the true effect of COVID-19 on healthcare systems and individual functional status

Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects

CONTEXT: Exercise training improves glycemic control and increases mitochondrial content and respiration capacity in skeletal muscle. Rodent studies suggest that training increases mitochondrial respiration in adipose tissue. OBJECTIVE: To assess the effects of endurance training on respiratory capacities of human skeletal muscle and abdominal subcutaneous adipose tissue and to study the correlation with improvement in insulin sensitivity. DESIGN: Using high-resolution respirometry, we analyzed biopsies from 25 sedentary (VO2 peak 25.1 ± 4.0 VO2 mL/[kg*min]) subjects (16 female, 9 male; 29.8 ± 8.4 years) with obesity (body mass index [BMI] 31.5 ± 4.3 kg/m2), who did not have diabetes. They performed a supervised endurance training over 8 weeks (3 × 1 hour/week at 80% VO2 peak). RESULTS: Based on change in insulin sensitivity after intervention (using the Matsuda insulin sensitivity index [ISIMats]), subjects were grouped in subgroups as responders (&gt;15% increase in ISIMats) and low-responders. The response in ISIMats was correlated to a reduction of subcutaneous and visceral adipose tissue volume. Both groups exhibited similar increases in fitness, respiratory capacity, and abundance of mitochondrial enzymes in skeletal muscle fibers. Respiratory capacities in subcutaneous adipose tissue were not altered by the intervention. Compared with muscle fibers, adipose tissue respiration showed a preference for β-oxidation and complex II substrates. Respiratory capacities were higher in adipose tissue from female participants. CONCLUSION: Our data show that the improvement of peripheral insulin sensitivity after endurance training is not directly related to an increase in mitochondrial respiratory capacities in skeletal muscle and occurs without an increase in the respiratory capacity of subcutaneous adipose tissue