Late recurrence of a single gland primary hyperparathyroidism-Atypical parathyroid adenoma or misdiagnosed parathyroid carcinoma.

Key Clinical Message: This case report aims to raise awareness of differential diagnoses of hypercalcemia and primary hyperparathyroidism, including parathyroid carcinoma and atypical adenoma, and to highlight the diagnostic challenges. Abstract: Parathyroid carcinoma is a rare and often fatal cause of primary hyperparathyroidism and hypercalcemia. To date, there is still no clear-cut diagnostic pathway for parathyroid carcinoma established, which results in major diagnostic ambiguity and complexity. Clinical differentiation between benign parathyroid adenoma and carcinoma is challenging and ultimately the diagnosis remains histopathological. We present a case of a 58-year-old female patient with parathyroid tumor recurrence after parathyroidectomy because of primary hyperparathyroidism. The first tumor was histologically classified as an atypical parathyroid adenoma by a specialized endocrine pathologist. Eleven years after the primary tumor resection a new tumor recurred. Retrospectively, after the tumor recurrence, the primary diagnosis of the atypical adenoma was questioned, and the tumor was temporarily classified to rather be a parathyroid carcinoma. This case aims to raise awareness for the diagnostic challenge of parathyroid carcinomas as a rare cause of primary hyperparathyroidism and therewith to improve treatment and prognosis.

Candesartan-Induced Enteropathy That Mimics Celiac Disease in a 90-Year-Old Patient.

Sprue-like enteropathy (SLE) is a clinical syndrome similar to celiac disease and has been associated with the use of various angiotensin receptor blockers (ARBs), a class of medications frequently used in the management of hypertension. Currently, there has only been one documented case report which has observed this occurrence with the use of the ARB candesartan. A 90-year-old female patient presented with chronic diarrhea and weight loss of unclear etiology. Diagnostic esophagogastroduodenoscopy and ileocolonoscopy were macroscopically unremarkable, but histological samples revealed complete villous atrophy, chronic mucosal inflammation, and intraepithelial T-lymphocytic infiltration. However, serological studies could not confirm celiac disease as a cause for the patient's symptoms of malabsorption. After exclusion of other intestinal inflammation etiologies with noted ongoing candesartan use, the diagnosis of SLE was made, and candesartan therapy was discontinued. Additionally, we decided to initiate a lactose-free diet. Clinical remission was achieved without any recurrences. Candesartan is a commonly prescribed therapeutic agent in the treatment of hypertension. Our case underlines the importance of considering it as a potential cause for unexplained symptoms of malabsorption.

Immune-mediated Gastritis in a Patient with metastatic Lung Cancer due to Therapy with the immune Checkpoint Inhibitor Pembrolizumab - Differences and Similarities in Comparison to "endogenous" autoimmune Type A Gastritis and a review of literature.

Immune checkpoint inhibitors are increasingly used in advanced malignant diseases and are well-known for their good results. With the blockade of immune checkpoints, the probability of immune-related adverse events is also increased.We present a 54-year-old female patient with advanced NSCLC. She was treated with pembrolizumab and developed a stable disease under therapy. After six cycles, she presented with massive epigastric pain to our emergency department. Gastroscopy showed severe erosive-fibrinous pangastritis without the involvement of the esophagus, duodenum, or other immune-related adverse effects. Histology showed the complete destruction of the gastric mucosa. We concluded an immune-mediated gastritis by pembrolizumab, after the exclusion of other differential diagnoses.Despite treatment with prednisolone and marked improvement of her symptoms, the mucosa was never fully reconstituted into a healthy mucosa.Furthermore, we collected published reports of similar cases and conducted a comparison with features of a typical, endogenous type A gastritis to highlight similarities and differences.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) after SARS-CoV-2 vaccination: Two cases from Germany with unusual presentation.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare clinical condition that has emerged during the mass immunization against SARS-CoV-2. Reports indicate that VITT may also be induced by other vaccines, such as the human papillomavirus vaccine, or occur independently of vaccination. Its recognition requires a high index of suspicion, especially in patients presenting with thrombocytopenia and thrombosis several days after vaccination with an adenoviral vector-based vaccine against SARS-CoV-2. Bleeding manifestations do not exclude VITT, as initially assumed. It is of great importance to perform the appropriate diagnostic tests early in the course of the disease, as false-negative results may occur and many aspects of VITT are not fully understood. These two cases from Germany demonstrate unusual presentations of VITT.

Primary hypothyroidism resolves after switching from L-thyroxine solid tablets to liquid oral substitution. A rare case without evidence of an underlying gastrointestinal malabsorption syndrome.

A case of refractory primary hypothyroidism is presented. Despite laboratory-guided hormonal substitution, the patient remained hypothyroid. Multiple diagnostic tests ruled out all known causes of levothyroxine malabsorption. Interestingly, clinical and laboratory responding was promptly achieved, after switching the application format from solid tablets to liquid formula.

Hepatic Encephalopathy Is Not Always due to Liver Cirrhosis.

Hepatic encephalopathy (HE) is a frequent and debilitating complication of liver disease and is oftentimes associated with hyperammonaemia. However, hyperammonaemia may occur in underlying conditions other than acute or chronic liver failure and clinical awareness is needed in order to be recognized and treated properly. A 24-year-old woman presented herself to our emergency department with acute confusion and altered mental state due to severe hyperammonaemia. The patient was diagnosed in the age of 14 with ornithine transcarbamylase (OTC) deficiency and was incompliant regarding her diet and suggested medication to treat this disorder. She was treated with sodium benzoate 250 mg/kg i.v., sodium phenylbutyrate/sodium phenylacetate 250 mg/kg i.v., L-arginine 250 mg/kg i.v., and received continuous hemofiltration. Under simultaneous medical treatment and haemodialysis, ammonia levels dropped to normal within 24 h and symptomatic encephalopathy ceased completely. OTC deficiency is rare in adults, and the majority of patients are diagnosed in childhood. It can lead to death if not diagnosed and treated properly. Our case underlines the importance of considering causes of HE other than liver cirrhosis.

Surgical treatment of metastatic VIPoma: a case report.

VIPoma, a neuroendocrine tumour mostly occurring in the human pancreas and producing high levels of vasoactive intestinal peptide, is a rare disease that presents with a wide spectrum of symptoms, including intense diarrhoea, hypokalaemia, and cardiac complications, with life-threatening consequences. In most cases, metastatic lesions are present at VIPoma diagnosis. Treatment options include symptomatic therapy, chemotherapy, radiation and surgery. Due to its low incidence, there are no evidence-based therapy recommendations to date. Here, we present a case of a 39-year-old woman with severe symptoms due to VIPoma of the pancreas with diffuse hepatic metastasis, who underwent simultaneous resection of the primary tumour, extensive liver resection and radiofrequency ablation. The patient was released in good health and was recurrence-free during 12 months surveillance. According to the existing literature and our own experience, surgical procedures appear to be the most promising therapy option for cases with diffuse hepatic metastasis, offering patients relief from their symptoms and (chemo)therapy-free time.

The diagnostic challenge of abdominal tuberculosis in nonendemic countries: A case series from a tertiary hospital in Germany.

Abdominal tuberculosis is a rare clinical condition in nonendemic countries and should be included as differential diagnosis by unspecific abdominal complaints, especially in patients with immigration background from high-prevalence regions.

Successful Treatment of an Immune-Mediated Colitis Induced by Checkpoint Inhibitor Therapy in a Patient with Advanced Melanoma.

Immune checkpoint inhibitors (ICIs) have been used as immunotherapeutic agents in several malignancies because of their ability to modify the T cell-mediated response against tumor cells. Dual checkpoint inhibition improves remission rates in patients with metastatic melanoma compared to monotherapy. However, a higher incidence of toxicity, including immune-related colitis, has been reported before. A 54-year-old female was diagnosed with malignant melanoma on her left upper arm. Because of progressive metastatic disease, a rescue therapy with nivolumab (Opdivo®) 1 mg/kg and ipilimumab (Yervoy®) 3 mg/kg was initiated and a clinical and radiological remission was achieved. Two weeks after completing the third cycle of the ICI therapy, the patient presented with persistent hemorrhagic diarrhea, nausea and abdominal pain. A diagnostic colonoscopy revealed multiple ulcerative lesions and hemorrhagic colitis of the sigmoid and rectum. Due to the ongoing treatment with nivolumab and ipilimumab, the diagnosis of a checkpoint inhibitor-induced colitis was made and immunosuppression with local and systemic steroids, such as mesalazine was initiated. In order to achieve a long-lasting steroids reduction, we decided to start with infliximab (Remicade® 5 mg/kg body weight i.v. every 2 weeks). Clinical remission was achieved and prednisolone could be subsequently discontinued. Infliximab, in combination with mesalazine, could successfully induce a long-lasting remission without steroids. The treatment of ICI-induced colitis did not lead to a reoccurrence of malignant melanoma after 2 years of follow-up.

Autoimmune hypophysitis secondary to therapy with immune checkpoint inhibitors: Four cases describing the clinical heterogeneity of central endocrine dysfunction.

INTRODUCTION: Immune checkpoint inhibitors are becoming increasingly important in oncology. Immune-related adverse events, including autoimmune hypophysitis, have been reported before. CASE REPORT: We present a case series of three males and one female, suffering from either malignant melanoma or renal cell carcinoma, who developed hypophysitis under Nivolumab and/or Ipilimumab. A wide range of clinical manifestations from asymptomatic hypophysitis, headache, general weakness, loss of appetite, visual field impairment, and confusion to acute life-threatening Addison crisis was observed.Management and outcome: All patients received corticosteroids. Immune checkpoint inhibitors were discontinued in three cases until resolution of symptoms. DISCUSSION: The objective of our report is to raise the awareness of physicians, regarding this rare clinical entity, which may become life-threatening, if not promptly recognized and properly treated.

[Off-label use of Budesonide suspensions to treat a patient with lymphocytic esophagitis]. / Off-label Anwendung einer budesonidhaltigen Suspension für die Behandlung einer lymphozytären Ösophagitis.

BACKGROUND: Lymphocytic esophagitis (LyE) is a rare chronic inflammatory disease of the esophagus, which shares clinical characteristics with the eosinophilic esophagitis. The most important part of its treatment is proton pump inhibitors (PPIs). Referring to locally acting steroids, evidence-based treatment strategies are missing. CASE REPORT: A 62-year-old patient presented for evaluation of his chronic dysphagia with previously diagnosed multiple oesophageal stenoses. Endoscopy revealed diffusely distributed esophageal rings and furrows and the diagnosis of LyE was established after immunohistochemical analysis of multiple mucosal biopsies. We initiated therapy with budesonide in the form of capsules (Entocort 3 × 3 mg Hartkapseln® once daily). During the course of the treatment, we initiated the off-label use of suspensions (Budenobronch® 0.5 mg twice daily) routinely used in the treatment of patients with asthma or COPD to increase the patient΄s acceptance of this therapy which was diminished because of his dysphagia. Under this therapy, clinical and later histological remission was achieved. CONCLUSION: Our case report is meant to describe an empirical therapeutic concept, which led to clinical and histological remission of chronic LyE.

Haemorrhagic small bowel melanoma metastasis: a clinical rarity.

We report on a clinical case with haemorrhagic small bowel metastases in a malignant melanoma patient with anaemia, diagnosed using small bowel video capsule endoscopy (VCE). A 67-year-old male patient with a previous diagnosis of malignant melanoma presented with anaemia and vertigo on admission. The standard diagnostic protocol for gastrointestinal (GI) bleeding investigation including a gastroscopy, colonoscopy and small bowel capsule endoscopy, as well as abdominal sonography and a restaging protocol including chest-abdomen-pelvis CT (CAP-CT), echocardiography and ECG was applied. Gastroscopy and colonoscopy were not conclusive in determining the bleeding source. VCE provided evidence for numerous haemorrhagic small bowel metastases. The CAP-CT was unremarkable for small bowel findings. Due to a diffuse metastatic disease diagnosed in heart, brain, liver, spleen and bone metastasis, the patient was treated in a conservative/palliative manner. VCE can provide precious information about GI bleeding of unknown origin when classical diagnostic methods are non-conclusive.

[Off-label use of Budesonide suspensions to treat a patient with lymphocytic esophagitis]. / Off-label Anwendung einer Budesonidhaltigen Suspension für die Behandlung einer lymphozytären Ösophagitis.

Background Lymphocytic esophagitis (LyE) is a rare chronic inflammatory disease of the esophagus, which shares clinical characteristics with the eosinophilic esophagitis. The most important part of its treatment is proton pump inhibitors (PPIs). Referring to locally acting steroids, evidence-based treatment strategies are missing. Case Report A 62-year-old patient presented for evaluation of his chronic dysphagia with previously diagnosed multiple oesophageal stenoses. Endoscopy revealed diffusely distributed esophageal rings and furrows and the diagnosis of LyE was established after immunohistochemical analysis of multiple mucosal biopsies. We initiated therapy with budesonide in the form of capsules (Entocort 3 × 3 mg Hartkapseln® once daily). During the course of the treatment, we initiated the off-label use of suspensions (Budenobronch® 0.5 mg twice daily) routinely used in the treatment of patients with asthma or COPD to increase the patient΄s acceptance of this therapy which was diminished because of his dysphagia. Under this therapy, clinical and later histological remission was achieved. Conclusion Our case report is meant to describe an empirical therapeutic concept, which led to clinical and histological remission of chronic LyE.

Pulmonary Embolism in Pneumonia: Still a Diagnostic Challenge? Results of a Case-Control Study in 100 Patients.

This study evaluated the diagnostic value of D-dimer, CRP, and leucocytes count to detect an underlying pulmonary embolism (PE) in patients with pneumonia. A predictive model of an underlying PE, based on laboratory markers and clinical symptoms, was our ultimate objective. Overall 100 patients underwent a computed tomography angiography (CTA) of the lung: 54 with coexistence of PE and pneumonia (cases) and 46 with pneumonia without PE (controls). Cases and controls were matched 1 : 1. Symptoms and paraclinical findings were registered on admission. Receiver operating characteristic (ROC) curves, search for an optimal threshold, and conditional logistic regression analysis were conducted. D-dimer has a moderate ability to detect PE in pneumonia. Sensitivity of D-dimer was estimated at 97.78% and specificity at 11.11%. No optimal cut-point has acceptable diagnostic ability. After excluding patients with sepsis, sensitivity was reduced to 96.97%, whereas specificity increased to 16.13%. Consolidation in chest X-ray and positive D-dimer predict better an underlying PE as D-dimer itself. Thus, discriminatory power of the prediction model (AUC of 0.740) is not much greater than D-dimer (AUC of 0.703). No threshold that could increase the diagnostic value of D-dimer or a prediction model which is significantly better than D-dimer itself was identified.

CMV Colitis in Immunocompetent Patients: 2 Cases of a Diagnostic Challenge.

CMV infections are generally thought to be opportunistic by immunosuppression. Many literature cases though indicate that CMV infections can be also observed in immunocompetent patients. We present an unusual case of an extensive concentric benign stenosis due to CMV colitis and a case of coexistence with Crohn's Disease, both observed in nonimmunosuppressed individuals. The right diagnosis was set after implementation of multiple unsuccessful treatment strategies. Our purpose is therefore to familiarize clinicians involved with the diagnosis and treatment of gastroenterological diseases with this entity.

[Autoimmune hepatitis and membranous glomerulonephritis under immune therapy in chronic hepatitis C]. / Autoimmunhepatitis und membranöse Glomerulonephritis unter Immuntherapie einer chronischen Hepatitis C.

A 63-year-old patient is evaluated for an unclear weight loss with general malaise and fatigue for several months. Serological examination reveales the first diagnosis of a hepatitis-C-virus-genotype-1b-infection with an initial viral load of 980 000 IU / ml. The duration of the infection is suggested to be more than 6 months. Because of the initially elevated anti-nuclear-antibodies (ANA) the diagnosis of an autoimmune hepatitis needs to be excluded. All other liver related autoantibodies and the immunoglobulins (Ig) IgG, IgA and IgM are normal. A liver biopsy is conducted. After a short test with non-pegylated interferon (IFN) liver enzymes remain stable and treatment with pegylated IFN-alfa-2a and ribavirin (RBV) is initiated. The patient is a "rapid viral responder" and his viral load is found under the detection limit within 4 weeks under therapy. On the 16th week, liver enzymes increase rapidly. ANA's and IgG-immunoglobulins are positive. A second lever biopsy does not confirm the diagnosis of autoimmune hepatitis and the treatment is continued under careful observation of all relevant liver parameters. 21 weeks after the initiation of the treatment, massive peripheral edema, hypoproteinemia and proteinuria are observed. The renal biopsy reveales membranous glomerulonephritis. Because of the preserved renal function, no acute immunosuppression is initiated and the treatment gets completed after overall 24 weeks. Liver and renal parameters return quickly back to normal after treatment discharge. This is the first report of a combined autoimmune reaction with development of autoimmune hepatitis and glomerulonephritis under INF and RBV antiviral therapy for a chronic hepatitis-C-infection. The occurrence of autoimmune manifestations should especially be considered in genetically susceptible individuals or those with positive autoimmunity markers. The initiation of INF for the treatment of chronic hepatitis-C-infection has to be critically evaluated since nowadays alternative, INF-free therapeutic regimens are available.

Treatment with daily consensus interferon (CIFN) plus ribavirin in non-responder patients with chronic hepatitis C: a randomized open-label pilot study.

BACKGROUND/AIMS: Therapeutic options for hepatitis C non-responder patients are limited. METHODS: We initiated an open-label pilot study to investigate the efficacy of CIFN plus ribavirin on viral kinetics, sustained virological response (SVR), and histological response in hepatitis C non-responder patients. Seventy-seven patients were enrolled to receive CIFN given daily in combination with 1000/1200 mg ribavirin. An 8-week induction-dosing regimen of 18 microg CIFN, followed by 9 microg for 40 weeks was compared to 9 microg CIFN for 48 weeks. 90% of patients were infected with HCV-genotype 1. RESULTS: Overall, 82% of the patients demonstrated an early virological response, 65% had an end-of-treatment response, and the SVR was 30%. Interferon/ribavirin non-responders demonstrated a SVR of 22%. Induction-dosing resulted in a greater first-phase HCV-RNA decay that, however, did not translate to better SVRs, presumably due to more dose modifications. High ALT, younger age, and second-phase viral kinetics were associated with SVR. Only sustained responders and relapse patients showed an improved liver histology. CONCLUSIONS: Daily dosing of CIFN plus ribavirin may be a promising concept for selected non-responder patients before considering therapies which are anti-viral but not curative. However, motivation and compliance are requisites and a CIFN induction is not required.

Genetic classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination.

Thyroid carcinoma is a common endocrine cancer with a favorable prognosis if subjected to timely treatment. However, the clinical identification of follicular thyroid carcinoma (FTC) among patients with benign thyroid nodules is still a challenge. Preoperative fine needle aspiration-based cytology cannot always differentiate follicular carcinomas from benign follicular neoplasias. Because current methods fail to improve preoperative diagnosis of thyroid nodules, new molecular-based diagnoses should be explored. We conducted a microarray-based study to reveal the genetic profiles unique to FTC and follicular adenomas (FAs), to identify the most parsimonious number of genes that could accurately differentiate between benign and malignant follicular thyroid neoplasia. We confirmed our data by quantitative RT-PCR and immunohistochemistry in two independent validation sets with a total of 114 samples. We were able to identify three genes, cyclin D2 (CCND2), protein convertase 2 (PCSK2), and prostate differentiation factor (PLAB), that allow the accurate molecular classification of FTC and FA. Two independent validation sets revealed that the combination of these three genes could differentiate FTC from FA with a sensitivity of 100%, specificity of 94.7%, and accuracy of 96.7%. In addition, our model allowed the identification of follicular variants of papillary thyroid carcinoma with an accuracy of 85.7%. Three-gene profiling of thyroid nodules can accurately predict the diagnosis of FTC and FA with high sensitivity and specificity, thus identifying promising targets for further investigation to ultimately improve preoperative diagnosis.