False positive Herpes Simplex IgM serology in COVID-19 patients correlates with SARS-CoV-2 IgM/IgG seropositivity.

Differentiating COVID-19 from other causes of viral pneumonia, like herpes simplex (HSV), can be complicated by shared clinical and laboratory features. Viral pneumonia is mostly diagnosed based on molecular or serological techniques. Serological immunoassay interferences, often attributed to concurrent appearance of heterologous (viral) immunoglobulins, is well-known, but has not been studied in COVID-19 patients. Following false positive HSV immunoglobulin M (IgM) results in our index patient, 25 other COVID-19 patients were tested for HSV-1/2 IgM with the chemiluminescent Liaison assay and Euroimmun enzyme-linked immunosorbent assay. Forty-five percent of COVID-19 patients tested positive for HSV IgM with Liaison. No HSV indices were positive with Euroimmun enzyme-linked immunosorbent assay, suggesting immunoassay interference. Significant correlation between HSV IgM and SARS-CoV-2 IgM/IgG positivity was found. Adding 0.5% polyvinylpyrrolidone, inhibiting non-specific solid-phase adsorption, abolished interference in 22% of false positive cases, suggesting interference caused by solid-phase reactive IgM. Hence, serologic immunoassay results should be interpreted with caution in COVID-19 patients.

Corticotroph pituitary carcinoma with skeletal metastases masquerading as ectopic ACTH syndrome: a long and winding road to diagnosis.

Summary: Pituitary carcinoma is a rare type of malignancy and only accounts for 0.1-0.2% of all pituitary tumours. Most pituitary carcinomas are hormonally active and they are mostly represented by corticotroph and lactotroph carcinomas. Corticotroph carcinoma can present as symptomatic Cushing's disease or can evolve from silent corticotroph adenoma which is not associated with clinical or biochemical evidence of hypercortisolism. We hereby present a case of a bone-metastasized corticotroph pituitary carcinoma masquerading as an ectopic adrenocorticotropic hormone (ACTH) syndrome in a patient with a history of a non-functioning pituitary macro-adenoma. Our patient underwent two transsphenoidal resections of the primary pituitary tumour followed by external beam radiation therapy. Under hydrocortisone substitution therapy she developed ACTH-dependent hypercortisolism without arguments for recurrence on pituitary MRI and without central-to-peripheral ACTH-gradient on inferior petrosal sinus sampling, both suggesting ectopic production. Ultimately, she was diagnosed with an ACTH-secreting vertebral metastasis originating from the primary pituitary tumour. This case report demonstrates the complex pathophysiology of pituitary carcinoma and the long diagnostic work-up. Certain features in pituitary adenoma should raise the suspicion of malignancy. Learning points: The diagnosis of pituitary carcinoma can only be made based on documented metastasis, therefore, due to the often long latency period between the detection of the primary tumour and the occurrence of metastasis, the diagnostic work-up most often spans over multiple years. Pituitary carcinoma including corticotroph carcinoma is very rare in contrast to pituitary adenoma and only accounts for 0.1-0.2% of all pituitary tumours. Histopathology in pituitary adenoma should certainly accomplish the following goals: accurate tumour subtyping and assessment of tumoural proliferative potential. Repeated recurrence of pituitary adenoma after surgical resection, a discrepancy between biochemical and radiological findings, resistance to medical and radiation therapy, and silent tumours becoming functional are all hallmarks of pituitary carcinoma. Silent corticotroph adenomas are non-functioning pituitary adenomas that arise from T-PIT lineage adenohypophyseal cells and that can express adrenocorticotropic hormone on immunohistochemistry, but are not associated with biochemical or clinical evidence of hypercortisolism. Silent corticotroph adenomas exhibit a more aggressive clinical behaviour than other non-functioning adenomas. Treatment options for corticotroph carcinoma include primary tumour resection, radiation therapy, medical therapy, and chemotherapy. Sometimes bilateral adrenalectomy is necessary to achieve sufficient control of the cortisol excess.

Non-Alcoholic Steatohepatitis Decreases Microsomal Liver Function in the Absence of Fibrosis.

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising across the globe, with the presence of steatohepatitis leading to a more aggressive clinical course. Currently, the diagnosis of non-alcoholic steatohepatitis (NASH) is based on histology, though with the high prevalence of NAFLD, a non-invasive method is needed. The 13C-aminopyrine breath test (ABT) evaluates the microsomal liver function and could be a potential candidate. We aimed to evaluate a potential change in liver function in NASH patients and to evaluate the diagnostic power of ABT to detect NASH. We performed a retrospective analysis on patients suspected of NAFLD who underwent a liver biopsy and ABT. 440 patients were included. ABT did not decrease in patients with isolated liver steatosis but decreased significantly in the presence of NASH without fibrosis and decreased even further with the presence of significant fibrosis. The predictive power of ABT as a single test for NASH was low but improved in combination with ALT and ultrasonographic steatosis. We conclude that microsomal liver function of patients with NASH is significantly decreased, even in the absence of fibrosis. The ABT is thus a valuable tool in assessing the presence of NASH; and could be used as a supplementary diagnostic tool in clinical practice.

The relation between mortality, intramuscular adipose tissue and sarcopenia in hospitalized geriatric patients.

INTRODUCTION: One of the biggest healthcare challenges that arises with increasing age expectations is sarcopenia. However, as a multi-dimensional construct with both neurological and musculoskeletal factors involved, the exact contribution of these different components of sarcopenia to mortality outcomes is not clear. Therefore, in mortality assessment, it is advisable to use subitems of sarcopenia such as the intramuscular adipose tissue (IMAT), instead of using sarcopenia as a construct itself. IMAT is negatively correlated with strength and performance, and positively correlated with mortality, both all-cause and cardiovascular. In this study, IMAT and its relation to long-term mortality, muscle strength and function is studied. MATERIALS AND METHODS: Patients admitted to the University Geriatrics Department during 6 months were screened for muscle mass, strength and function through computed tomography (upper leg), Jamar dynamometer and short physical performance battery, respectively. After 4 years, health status (mortality) was obtained by telephone. RESULTS: Three hundred and two patients were included (69.6% female). Mean IMAT was 29.3 ± 12.3%. There was a positive correlation between IMAT and mortality in the male 70-79-year-old age group (n = 20), but not in the whole cohort. IMAT was negatively correlated with muscle strength and function. CONCLUSION: IMAT is negatively correlated with muscle strength and muscle function. IMAT is correlated with mortality in a specific subgroup of this cohort. This data adds to the discussion of the value of IMAT in the construct of sarcopenia. More studies need to be done regarding the evolution of IMAT in function of time and functional decline.