Background Graves' disease (GD) is an autoimmune thyroid disease (AITD) with a peak incidence between 30 and 50 years of age. Although children and adolescents may also develop the disease, the genetic background of paediatric‐onset GD (POGD) remains largely unknown. Here, we looked for similarities and differences in the genetic risk factors for POGD and adult‐onset GD (AOGD) as well as for variants associated with age of GD onset. Materials and methods A total of 1267 GD patients and 1054 healthy controls were included in the study. Allele frequencies of 40 established and suggested GD/AITD genetic risk variants (39 SNPs and HLA‐DRB1*03) were compared between POGD (N = 179), AOGD (N = 1088) and healthy controls. Subsequently, multiple linear regression was used to explore the relationship between age of GD onset and genotype for each locus. Results We identified six POGD risk loci, all of them were also strongly associated with AOGD. Although for some of the analysed variants, including HCP5 (rs3094228), PRICKLE1 (rs4768412) and SCGB3A2 (rs1368408), allele frequencies differed nominally between POGD and AOGD patients, these differences were not significant after applying multiple testing correction (Pcor = 0.05/40 = 1.25 × 10−3). Regression analysis showed that patients with higher number of HCP5 risk alleles tend to have a significantly earlier onset of GD (P = 6.9 × 10−5). Conclusions The results of our study revealed that POGD and AOGD share multiple common genetic risk variants. Moreover, we demonstrated for the first time that HCP5 polymorphism is associated with an earlier age of GD onset in a dose‐dependent manner.
context. Some adrenal tumors, such as pheochromocytoma, can be life-threatening. Therefore it is crucial to distinguish them from other lesions, especially prior to surgery. Chromogranin A (CgA) seems to potentially be a good marker for tumors of chromaffin origin.objective. To assess the differentiating value of CgA in the diagnostic work-up of pheochromocytoma.design. Retrospective study of operated patients with adrenal incidentaloma with lesions > 10 Hounsfield's units (HU) on CT.subjects and methods. Thirty patients (11 males, 19 females; aged 61.5±21 years) were enrolled in the study. Patients using medications interfering with the assessment of CgA and metanephrines were excluded. Two groups were formed: those with pheochromocytoma (Ph, n=16) and those with non-pheochromocytoma (N-Ph, n=14) lesions. Data included radiological features of masses, serum CgA and 24-hour urine metanephrines (24 -HUM) concentrations.results. No difference in 24-HUM level nor tumor size or density was found between groups Ph and N-Ph. Median serum CgA concentration was higher in Ph group compared to the ) ng/mL, respectively (P=0.04). In Ph group, the size of the lesion correlated negatively with density (r= -0.53, P=0.042). No significant correlation in CgA, 24-HUM, density or size of the lesion was found. Performed curve receiver operating characteristic (ROC) showed AUC=0.7232 for CgA. Taking into account CgA serum value of ≤ 50 ng/mL (sensitivity: 93.75%, specificity: 50.00%, P=0.012), we proposed an algorithm for management of lesions > 10 HU on CT.conclusion. CgA level ≤ 50 ng/mL might be useful in initial screening evidence for the exclusion of pheochromocytoma. It is crucial to eliminate factors interfering with the measurements.
Background. carcinoid syndrome (cs) is a rare syndrome, most commonly associated with neuroendocrine neoplasms (nens) of the small intestine. carcinoid syndrome consists of diarrhea, vomiting, abdominal pain, cutaneous flushing, teleangiectasias, bronchoconstriction and increased perspiration. diagnosis of carcinoid syndrome remains a challenge and it is often delayed. Objectives. the aim of this study was to characterize patients with cs and define the most sensitive, primary diagnostic tools for cs. Material and methods. 26 consecutive patients admitted to the department because of carcinoid-like symptoms. diagnosis of cs was based on clinical findings and laboratory data (levels of 5-hydroxyindoloacetic acid). diagnosis of nen was based on laboratory findings, imaging studies (us, ct, gallium-68-dota tate Pet-ct) and histopathological analysis. cs due to nen was diagnosed in 16 subjects (nen-cs). Results. the most common symptoms in non-nen were increased perspiration, flushes and diarrhea. cga was elevated (40%; n = 4) in this group. However, elevated levels of 5-Hiaa and liver lesions were not presented. in the nen-cs symptoms were reported more often: flush (93.7%; n = 15), diarrhea (87.5%; n = 14), abdominal pain and teleangiectasis (81.2%; n = 13). elevated cga and 5-Hiaa were noted in 87.5% (n = 14) and 81.2% (n = 13) respectively. us and ct revealed liver metastases in all patients. the mean duration of symptoms before diagnosis was 28.6 months. Conclusions. the combination of several symptoms of carcinoid syndrome and liver lesion in easily available abdominal imaging (us and/or ct) should prompt physicians to quick referral to centres specialized in the diagnosis and treatment of nen. Key words: carcinoid syndrome, chromogranin a, 5-Hiaa.Wstęp. zespół rakowiaka (carcinoid syndrome -cs) występuje najczęściej w przebiegu nowotworów neuroendokrynnych (neuroendocrine neoplasms -nen) przewodu pokarmowego z ogniskiem pierwotnym w jelicie cienkim. do głównych objawów należą luźne wypróżnienia, nudności, bóle brzucha, zaczerwienienia twarzy, teleangiektazje, skurcz oskrzeli i wzmożona potliwość. rozpoznanie zespołu rakowiaka jest najczęściej opóźnione. Cel pracy. charakterystyka pacjentów z zespołem rakowiaka i ustalenie podstawowego narzędzia diagnostycznego. Materiał i metody. do badania włączono 26 pacjentów przyjętych do kliniki z powodu objawów zespołu rakowiaka. diagnostyka cs obejmowała ocenę kliniczną oraz badania dodatkowe (stężenie kwasu 5-hydroksyindolooctowego). diagnostyka nowotworu neuroendokrynnego obejmowała badania laboratoryjne oraz obrazowe (usg, tk, 68ga-dota tate Pet/ct) oraz badanie histopatologiczne. cs w przebiegu nen został stwierdzony u 16 pacjentów (nen-cs). Wyniki. najczęściej zgłaszanymi objawami w grupie badanych non-nen były: wzmożona potliwość, zaczerwienienia twarzy oraz biegunki. stężenie cga było podwyższone (40%; n = 4) w tej grupie. nie stwierdzono podwyższenia stężenia kwasu 5-hydroksyindolooctowego i zmian ogniskowych w wątrobie. w grupie nen-cs najczęściej zgłaszane ob...
A 40-year-old man with a history of chest pain, nausea, and palpitation was admitted to hospital due to hypercalcaemia and renal function exacerbation. On admission the patient's condition revealed signs of dehydration and tachycardia. Moreover, the patient complained of painful ribs. Laboratory tests revealed a high calcium level of 3.69 mmol/L, normal parathormone (PTH) -18.4 pg/mL, and vitamin D deficiency -22.14 ng/mL (Tab. 1). Serum phosphate, magnesium, potassium, and sodium were within the normal range, and there were no acid-base-balance disturbances. Abdominal ultrasound offered no important findings. However, low-dose whole-body computed tomography scanning displayed an advanced diffused osteolysis in numerous bones ( Fig. 1). Additionally, some rib fractures were present. Consecutively, further biochemical analyses found mild normocytic anaemia, an elevated erythrocyte sedimentation rate of 94 mm and lactate dehydrogenase of 325 U/L, monoclonal gammopathy features in protein electrophoresis, and a k/l serum ratio equal to 1696.1.The above led to a suspicion of non-PTH-mediated hypercalcaemia (NPTH-H) in the course of multiple myeloma (MM). Treatment then included intravenous fluids, forced diuresis, and calcitonin and zoledronic acid administered following an improvement of renal function (a glomerular filtration rate of 49 mL/min/1.73 m 2 ). Unexpectedly, a severe (0.2 mmol/L) hypophosphataemia with hypophosphaturia (< 0.1 mmol/L) occurred four days later. Tubular reabsorption of phosphate (TRP) was within the normal range -0.895 (0.85-0.95), while the tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) decreased significantly to 0.19 mmol/L (1.0-1.35). On the other hand, prior to bisphosphate administration, these parameters were consecutively 0.52 and 0.43 mmol/L, with phosphate concentration 0.82 mmol/L and its excretion in urine at 5.4 mmol/L, together with features of mild acute kidney injury (Tab. 1). The PTH level increased slightly.Despite the patient's relatively stable state, insufficient oral supplementation of phosphate and severity of observed hypophosphataemia accounted for resorting to the application of intravenous phosphate infusion, which was continued for four days. Concomitant treatment i.a. involved alphacalcidol and cholecalciferol.To confirm neoplastic disease, bone marrow biopsy was performed, revealing a level of infiltration of pathological plasma cells equal to 42.7%. DiscussionMultiple myeloma is a neoplastic disease characterised by lytic lesions of bones [1]. The diagnosis is rare in adults under 40 years old (approximately 2%), with average age at diagnosis being 70 years. MM-related hypercalcaemia is caused by osteoclast activation involving a receptor activator of the NF-kB (RANK) system, as accompanied by hydrogen and cytokine release -mainly of interleukin-6, sclerostin, and the glycoprotein Dickkopf-1 (DKK-1) [2]. Zoledronate therefore serves as a standard treatment because it binds to hydroxyapatite complexes at metabolically active
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