Delay in Diagnosis of Autoimmune Polyendocrine Syndrome Type 2 as a Consequence of Misinterpretation of Gastrointestinal Symptoms.

Background: Type 2 autoimmune polyendocrine syndrome (APS-2) is characterized by the presence of at least two of three endocrinopathies: Addison's disease, autoimmune thyroiditis, and diabetes type 1. The prevalence of APS-2 is estimated to be 1 : 1000 to 1 : 20.000 in the general population. Diagnosis of APS-2 often is delayed due to its rarity and wide spectrum of clinical symptoms. Case Presentation. A 27-year-old presented with a 6-month history of abdominal pain, vomiting, diarrhea, weakness, fatigue, and 15 kg of weight loss. The patient was diagnosed with Crohn's disease in a local hospital and referred to our institution because of treatment failure. Colonoscopy performed in this hospital identified irregular mucosal erosions in terminal ileum, and the microscopy of biopsy specimens demonstrated nonspecific inflammation. On physical examination, the patient appeared cachectic. Blood pressure was 90/60 mmHg. Laboratory results were significant for severe hyponatremia and mild hyperkalemia. Morning cortisol was low, and adrenocorticotropic hormone (ACTH) concentration was high. An ACTH stimulation test did not present any increase in serum cortisol, which confirmed primary adrenal insufficiency. Antithyroid peroxidase antibody (anti-TPO) as well as both anti-21-hydroxylase antibodies and antiglutamic acid decarboxylase antibodies (GAD65) were positive. So, the diagnosis of APS-2 was made, and the replacement doses of hydrocortisone and fludrocortisone has brought a rapid improvement in all clinical symptoms; colonoscopy showed normal. Conclusion: The case presented herein highlights rapidly progressive nature of untreated APS-2 and that the diagnosis of APS-2 may be challenging.

Hepatic complications of peptide receptor radionuclide therapy with Lutetium-177 and Yttrium-90 in patients with neuroendocrine neoplasm.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors originating from neuroendocrine cells spread throughout the body, forming the so-called diffuse endocrine system. The gold standard in treating unresectable or disseminated, progressive, and well-differentiated NENs is therapy with radiolabeled somatostatin analogs (peptide receptor radionuclide therapy - PRRT). PRRT is a method based on peptides combined with beta-emitting radionuclides. The study aimed to assess the early and long-term liver complications after administration of Lutetium-177 or Lutetium-177 combined with Yttrium-90. We enrolled 27 patients treated with [177Lu]Lu-DOTATATE with an activity of 7.4 GBq (200 mCi) and 9 patients received the tandem treatment [90Y]Y-DOTATATE + [177Lu]Lu-DOTATATE with an activity of 3.7 GBq (50 mCi + 50 mCi). In the assessment of early as well as long-term complications, no significant effect of the applied treatment on the parameters of liver injury was found. Regarding liver function PRRT was a safe treatment for patients with highly or moderately differentiated, unresectable, or diffuse NENs.

A rare combination of tumor-induced osteomalacia caused by sinonasal glomangiopericytoma and coexisting parathyroid adenoma: case report and literature review.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare, acquired disease of renal phosphate wasting and disturbed vitamin D homeostasis as a result of the action of a phosphaturic protein - FGF-23, produced by a neoplasm. Although the clinical and biochemical profile of the syndrome is characteristic, it remains underreported and unrecognized by clinicians. Hyperparathyroidism is rarely associated with oncogenic osteomalacia, but it should be considered because of potentially life-threatening hypophosphatemia caused by both conditions. CASE PRESENTATION: We report a case of a 42-year-old woman admitted to the Department of Otolaryngology of the Military Institute of Medicine in Warsaw for the endoscopic resection of hormonally active glomangiopericytoma extending into the anterior skull base. She presented with a 5-year history of musculoskeletal pain and progressive weakness of the extremities which finally led her to become bedridden. After the excision of the tumor her symptoms and laboratory results gradually improved except increasing PTH serum levels. Further examination revealed a parathyroid proliferative tumor, which was surgically removed. The patient walked without aids at follow-up 16 months after the surgery. CONCLUSIONS: This case is unusual because of tumor-induced osteomalacia and parathyroid adenoma occurring concomitantly. Further investigations of FGF-23 and PTH interplay should be conducted to elucidate the pathogenesis of hyperparathyroidism and tumorigenesis in some cases of TIO. By presenting this case, we wanted to remind clinicians of a rare and misdiagnosed paraneoplastic syndrome and highlight the importance of monitoring PTH concentrations during the follow-up of patients with TIO.

Diabetic kidney disease: Are the reported associations with single-nucleotide polymorphisms disease-specific?

BACKGROUND: The genetic backgrounds of diabetic kidney disease (DKD) and end-stage kidney disease (ESKD) have not been fully elucidated. AIM: To examine the individual and cumulative effects of single-nucleotide polymorphisms (SNPs) previously associated with DKD on the risk for ESKD of diabetic etiology and to determine if any associations observed were specific for DKD. METHODS: Fourteen SNPs were genotyped in hemodialyzed 136 patients with diabetic ESKD (DKD group) and 121 patients with non-diabetic ESKD (NDKD group). Patients were also re-classified on the basis of the primary cause of chronic kidney disease (CKD). The distribution of alleles was compared between diabetic and non-diabetic groups as well as between different sub-phenotypes. The weighted multilocus genetic risk score (GRS) was calculated to estimate the cumulative risk conferred by all SNPs. The GRS distribution was then compared between the DKD and NDKD groups as well as in the groups according to the primary cause of CKD. RESULTS: One SNP (rs841853; SLC2A1) showed a nominal association with DKD (P = 0.048; P > 0.05 after Bonferroni correction). The GRS was higher in the DKD group (0.615 ± 0.260) than in the NDKD group (0.590 ± 0.253), but the difference was not significant (P = 0.46). The analysis of associations between GRS and individual factors did not show any significant correlation. However, the GRS was significantly higher in patients with glomerular disease than in those with tubulointerstitial disease (P = 0.014) and in those with a combined group (tubulointerstitial, vascular, and cystic and congenital disease) (P = 0.018). CONCLUSION: Our results suggest that selected SNPs that were previously associated with DKD may not be specific for DKD and may confer risk for CKD of different etiology, particularly those affecting renal glomeruli.

Evaluation of the usefulness of positron emission tomography with [18F]fluorodeoxylglucose performed to detect non-radioiodine avid recurrence and/or metastasis of differentiated thyroid cancer - a preliminary study.

BACKGROUND: About 30% of patients with disseminated differentiated thyroid cancer (DTC) may experience a loss of iodine uptake. It is associated with higher aggressiveness of the tumour and a reduced 10-year survival rate. The diagnosis of non-radioiodine avid DTC metastases remains a diagnostic challenge. A helpful technique for this diagnosis is positron emission tomography with 2-[¹8F]fluoro-2-deoxy-D-glucose (PET/CT with [¹8F]FDG). On the other hand, there are still discussions about the clinical value of using exogenous thyroid-stimulating hormone (TSH) stimulation before PET/CT with [¹8F]FDG. The aim of the study was the assessment of the usefulness of PET/CT with [¹8F]FDG under TSH suppression and stimulation of TSH performed in the detection of non-radioiodine avid DTC metastases, as well as determination of the thyroglobulin concentration under suppression and stimulation of TSH, which influences the result of PET/CT with [¹8F]FDG in patients with non-radioiodine avid DTC. MATERIAL AND METHODS: Retrospective analysis of 37 PET/CT with [¹8F]FDG performed in patients with DTC diagnosed and treated at the Department of Endocrinology and Isotope Therapy of the Military Institute of Medicine from January 2018 to July 2020. Of these, PET/CT with [¹8F]FDG under exogenous rhTSH stimulation was performed in 22 patients and PET/CT with [¹8F]FDG under TSH suppression in 15 was performed. In all analyzed patients, the result of diagnostic whole-body scintigraphy (WBS) using 80 MBq ¹³¹I under rhTSH stimulation was negative, and the concentration of thyroglobulin after stimulation (sTg) was greater than 1.0 ng/mL. RESULTS: In the group of patients examined under TSH suppression, non-radioiodine avid in PET/CT with [¹8F]FDG were found in 6 out of 15 patients (40%) and in the group of patients examined under rhTSH stimulation in 10 out of 22 patients (45%). The differences between the groups were not statistically significant. The analysis of the receiver operating characteristic (ROC) curves allowed to determine the cut-off point for the positive result of PET/CT performed under TSH suppression with sTg concentration of 11.03 ng/mL. In the group of studies performed under rhTSH stimulation, the cut-off point for sTg was 6.3 ng/mL. There was no statistically significant difference between the baseline thyroglobulin (natTg) and sTg levels and the positive PET/CT result. The administration of rhTSH before the PET/CT examination also had no statistically significant effect on the maximum standard uptake value (SUVmax) of the dominant lesion identified in the PET/CT. CONCLUSIONS: 1) PET/CT with [¹8F]FDG is a useful tool for detection of non-radioiodine avid recurrence and/or metastases of DTC. 2) The concentration of natTg and sTg is highly correlated with a positive result of PET/CT with [¹8F]FDG. 3) The concentration of natTg is comparable with sTg in predicting a positive result of PET/CT with [¹8F]FDG. 4) The cut-off point for a positive result of PET/CT for natTg was 1.36 ng/mL and for sTg was 7.05 ng/mL.

Peritoneal dialysis in an adult patient with tetralogy of Fallot diagnosed with incomplete Alagille syndrome.

BACKGROUND: Alagille syndrome is an autosomal dominant disorder usually caused by pathogenic variants of the JAG1 gene. In the past, cholestasis was a condition sine qua non for diagnosis of the syndrome. However, recent advancements in genetic testing have revealed that clinical presentations vary from lack of symptoms, to multiorgan involvement. Tetralogy of Fallot, the most frequent complex congenital heart defect in Alagille Syndrome, very rarely leads to renal failure requiring dialysis - there are only single reports of such cases in the literature, with none of them in Alagille Syndrome. CASE PRESENTATION: A 41-year-old woman suffering from cyanosis, dyspnea and plethora was admitted to the hospital. The patient suffered from chronic kidney disease and tetralogy of Fallot and had been treated palliatively with Blalock-Taussig shunts in the past; at admission, only minimal flow through the left shunt was preserved. These symptoms, together with impaired mental status and dysmorphic facial features, led to extensive clinical and genetic testing including whole exome sequencing. A previously unknown missense variant c.587G > A within the JAG1 gene was identified. As there were no signs of cholestasis, and subclinical liver involvement was only suggested by elevated alkaline phosphatase levels, the patient was diagnosed with incomplete Alagille Syndrome. End-stage renal disease required introduction of renal replacement therapy. Continuous ambulatory peritoneal dialysis was chosen and the patient's quality of life significantly increased. However, after refusal of further treatment, the patient died at the age of 45. CONCLUSIONS: Tetralogy of Fallot should always urge clinicians to evaluate for Alagille Syndrome and offer patients early nephrological care. Although tetralogy of Fallot rarely leads to end-stage renal disease requiring dialysis, if treated palliatively and combined with renal dysplasia (typical of Alagille Syndrome), it can result in severe renal failure as in the presented case. There is no standard treatment for such cases, but based on our experience, peritoneal dialysis is worth consideration. Finally, clinical criteria for the diagnosis of Alagille Syndrome require revision. Previously, diagnosis was based on cholestasis - however, cardiovascular anomalies are found to be more prevalent. Furthermore, the criteria do not include renal impairment, which is also common.

What do we know about pulmonary blastoma?: review of literature and clinical case report.

Pulmonary blastoma (PB) is a rare form of lung tumour and is accountable for 0.25-0.5% of primary pulmonary malignancies. Initially pulmonary blastoma was divided into three subtypes: biphasic pulmonary blastoma (BPB) consisting of an epithelial and mesenchymal component, well differentiated fetal adenocarcinoma (WDFA) built of well differentiated epithelium and a mesenchymal component and malignant pleuropulmonary blastoma (PPB). Prognosis in this type of cancer is really poor. We present a current review of literature and a clinical case report. Treatment of PB is very difficult. Data and recommendations about the treatment of pulmonary blastoma are still available therefore we should use only observations and clinical case reports.

First year survival of patients on maintenance dialysis treatment in Poland.

Retrospective analysis of demographic and clinical data of all patients starting dialysis over two years in our Department (n = 105) has been conducted. Factors such as type of dialysis treatment, reason of end-stage renal disease, Body Mass Index (BMI), laboratory tests results, number and cause of death during first year of dialysis were taken under consideration. Five patients have been excluded from the analysis of mortality (four received renal transplantation, one changed dialysis center). Twenty tree deaths have been noted during first year of dialysis treatment. Nine of them occurred during the first three months of therapy. The leading cause of death was cardio-vascular events (n = 14, 60.9%), the second was malignancy (8, 34,8%), one patient died due to catheter associated infection. Malignancy as a cause of end-stage renal disease, lack of outpatient nephrology care, acute mode of beginning renal replacement therapy and lack of erythropoiesis stimulating agents therapy were associated with higher risk of all-cause mortality during first year of dialysis. Being under the outpatient nephrology care, etiology of ESRD other than malignancy and erythropoiesis stimulating agents therapy were independently associated with better survival during this period of time. Other independent variables did not reach statistical significance. To conclude, in order to improve one year survival of dialysis patients, outpatient nephrology care with adequate amount of visits and associated dialysis therapy should be employed.

[Use of rituximab in the induction of remission of severe, resistant and recurrent form of polyangiitis associated with c-ANCA antibodies - case report]. / Zastosowanie rituksimabu w indukcji remisji ciEZkiej, opornej na leczenie postaci zapalenia naczyN z obecnoSciA przeciwciaL c-ANCA - opis przypadku.

Indications for rituximab (RTX) have recently widened. We present a case of 25-years old patient with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis of high disease activity. The patient in severe condition, massive changes of nasal sinuses, with destruction of the orbit bones, with inflammatory infiltrations of the optical nerves and end stage renal disease was admitted to Nephrology Clinic to begin renal replacement therapy (RRT). Chest HRCT reveled changes of "frosted glass", enlarged mediastinal lymphatic nodes and fluid in pleural cavities. C-ANCA antibodies was 23 IU/ml (norm: <2IU/ml). Due to the lack of therapeutic possibilities (exceeded cumulative dose of cyclophosfamide, recurrence of the disease during treatment with mycophenolate mofetil) rituximab was introduced. After proving high expression of CD 20 antigen on the surface of B lymphocytes, two doses of rituximab were administrated (1,0g every two weeks). 8 weeks after the second dose remission of lungs disorders was observed, c- ANCA level decreased to 3,7IU/ml and the granulomatous mass around the optical nerve was stable. 12 months later another supporting dose of rituximab was administrated. Now, 18 months after relapse of the disease patient is in good condition waiting for kidney transplantation. Rituximab is save, well tolerated and effective. Particularly high efficiency of RTX have been observed against lung disorders. No significant remission of granuloma infiltration in the orbits has been noted. Better evaluation of efficiency and safety of rituximab needs further evaluation.

Determining the enzymatic activities of iodothyronine 5'-deiodinases in renal medulla and cortex.

INTRODUCTION: Thyroid hormone disorders in patients with chronic kidney disease (CKD) are a result of impaired conversion of T4 to T3. The importance of kidneys in thyroid hormones conversion is not fully understood. The activities of different types of iodothyronine deiodinases in the kidney structures have not been determined yet. The aim of this study was to determine the activity of deiodinase type 1 (D1) and type 2 (D2) in renal cortex and medulla in renal cancer patients. MATERIAL AND METHODS: Samples of renal cortex and medulla (ten patients) or renal cortex alone (13 patients) were taken from kidneys resected because of malignant cancer, from a site opposite to the cancer. Resections were performed in the 23 patients (seven female and 16 male) who were 52-82 years old. The material was stored at -72 oC. RESULTS: Activity of D1 in renal cortex was 3.785 ± 2.041 fmol 125I/mg protein/minute and activity of D2 was 0.236 ± 0.125 fmol 125I/mg protein/minute. There was a strong positive correlation between D1 and D2 activities in renal cortex (r = 0.890, p 〈 0.001). Activity of D1 in renal medulla was 2.157 ± 2.176 fmol 125I/mg protein/minute, and activity of D2 was 0.168 ± 0.095 fmol 125I/mg protein/minute. A positive correlation between D1 and D2 in renal medulla (r = 0.661, p = 0.038) was observed as well. Activities of D1 in cortex and medulla were strongly and positively associated (r = 0.794, p = 0.006), whereas there was no correlation between the activities of D2 in cortex and medulla (r = 0.224, p = 0.553). CONCLUSIONS: Results presented in this study suggest that both cortical and medullary D1 and D2 may be involved in thyroid hormone metabolism. This finding could be of clinical relevance in patients with impaired renal function.