Ten years follow up of first degree relatives of type 1 diabetes patients: presence of autoimmune biomarkers and the progression to diabetes in a retrospective cohort

ABSTRACT Objective: The aim of the study was to assess the autoimmunity in first degrees relatives (FDR) of patients with type 1 diabetes (T1DM) and the progression to T1DM after 10 years of follow up in the Brazilian population. Subjects and methods: Non-diabetic FDR of T1DM patients were interviewed and blood was drawn for autoantibodies measurement (GADA, IA-2A, IAA, ZnT8A). Serum samples were analyzed by standard radioligand binding assays performed at the Federal University of Rio de Janeiro (GADA, IAA and IA2A), and at the Skäne University Hospital, Sweden (ZnT8A). The FDR were interviewed by phone after 10 years to determine if they had developed T1DM. Descriptive statistical analysis was performed and results were described as means and standard deviation (SD). Results: 81 individuals were analyzed. Thirteen subjects had positive autoantibodies associated with T1DM.10 were positive for 1 autoantibody and 3 subjects were positive for multiple autoantibodies (1 of them showed positivity for 2 autoantibodies - GADA, ZnT8A - and the other two were positive for 3 autoantibodies - GADA, IA2A, ZnT8A). The 3 subjects with multiple positive autoantibodies developed T1DM within 10 years. Conclusions: In Brazilian FDR of T1DM patients, the positivity for multiple autoantibodies indicate a greater chance of progression to T1DM, similar to observed in Caucasians. ZnT8A was helpful in the risk assessment for T1DM development.

Ten years follow up of first degree relatives of type 1 diabetes patients: presence of autoimmune biomarkers and the progression to diabetes in a retrospective cohort.

OBJECTIVE: The aim of the study was to assess the autoimmunity in first degrees relatives (FDR) of patients with type 1 diabetes (T1DM) and the progression to T1DM after 10 years of follow up in the Brazilian population. METHODS: Non-diabetic FDR of T1DM patients were interviewed and blood was drawn for autoantibodies measurement (GADA, IA-2A, IAA, ZnT8A). Serum samples were analyzed by standard radioligand binding assays performed at the Federal University of Rio de Janeiro (GADA, IAA and IA2A), and at the Skäne University Hospital, Sweden (ZnT8A). The FDR were interviewed by phone after 10 years to determine if they had developed T1DM. Descriptive statistical analysis was performed and results were described as means and standard deviation (SD). RESULTS: 81 individuals were analyzed. Thirteen subjects had positive autoantibodies associated with T1DM.10 were positive for 1 autoantibody and 3 subjects were positive for multiple autoantibodies (1 of them showed positivity for 2 autoantibodies - GADA, ZnT8A - and the other two were positive for 3 autoantibodies - GADA, IA2A, ZnT8A). The 3 subjects with multiple positive autoantibodies developed T1DM within 10 years. CONCLUSION: In Brazilian FDR of T1DM patients, the positivity for multiple autoantibodies indicate a greater chance of progression to T1DM, similar to observed in Caucasians. ZnT8A was helpful in the risk assessment for T1DM development.

CA19-9 as a Predictor of Worse Clinical Outcome in Medullary Thyroid Carcinoma.

OBJECTIVE: Medullary thyroid carcinoma (MTC) is a rare disease, and its classic tumor marker is calcitonin. However, recently, very aggressive cases have been reported to also secrete carbohydrate antigen 19-9 (CA19-9), and its role as a marker of worse prognosis has been questioned. The aim of this study was to analyze the relationship between CA19-9 serum levels and MTC outcomes. METHODS: We retrospectively reviewed 122 MTC patients followed in a tertiary cancer center from 1985 to 2017. Clinical-pathologic characteristics, therapeutic approaches, and outcomes were recorded and CA19-9 was collected. RESULTS: Of the 122 patients included in the study, 48 had distant metastases, and at the end of follow-up 18.1% had structural persistent disease and 32.7% had progressive disease. CA19-9 was significantly higher in those who had disease progression than in those who had not (21.4 [14.3-110.9] vs. 7.27 [0.6-44.75] U/mL, p = 0.01) and was also higher in patients who died from MTC (18.4 [14.3-110.9] vs. 7.59 [0.6-67.8] U/mL, p < 0.001). Furthermore, using a ROC curve analysis, the cutoff point for CA19-9 in MTC patients was lower than that observed in pancreatic tumors. CONCLUSION: CA19-9 might have a role as a prognostic factor in addition to calcitonin and carcinoembryonic antigen in metastatic MTC.

Somatostatin receptor subtype 1 might be a predictor of better response to therapy in medullary thyroid carcinoma.

PURPOSE: Medullary thyroid carcinoma (MTC) is a malignant neoplasm of parafollicular cells. Because it is a neuroendocrine tumor, it has known somatostatin receptors (SSTRs). The actual frequencies of the SSTR subtypes and their potential influences (by binding with endogenous somatostatin) on MTC cell proliferation have not been fully elucidated to date. The present study evaluated the occurrence of SSTR subtypes 1, 2, 3 and 5 as well as the possible role that each subtype plays in the clinical evolution of patients with MTC. METHODS: This retrospective, longitudinal study analyzed thyroid surgical material from 42 patients with MTC. Immunohistochemical staining was performed with monoclonal antibodies against subtypes 1, 2, 3 and 5 of SSTR. The histological material was classified as negative, focal positive or diffuse positive, in relation to each of the SSTR subtypes. The initial response to treatment, clinical course and patient mortality rate were assessed and related to the presence of SSTR subtypes. RESULTS: The most prevalent SSTR subtype was SSTR 3, which was found in 81% of the patients, when considering any pattern of positivity. However, subtype 2 had the lowest number of positive patients, with 28.6% demonstrating any positive pattern. Subtypes 1 and 5 had an intermediate prevalence of positivity, with subtype 1 present in 45.2% of the patients and subtype 5 positive in 54.8% of the patients, when considering any pattern of positivity. The presence of STR 1, in the form of diffuse positivity, independently predicted a better response to the initial therapy, with a hazard ratio (HR) of 4.80 (p = 0.03). CONCLUSION: This is the first study to show the correlation of the presence of SSTR1, detected by monoclonal immunohistochemical techniques, and better response to initial treatment and possibly better long-term clinical response in patients with MTC. In addition, these patients had low positivity rates for SSTR2, which might explain the low sensitivity of diagnostic and limited therapeutic response to octrotide based radioisotopes.

Is there a role for peptide receptor radionuclide therapy in medullary thyroid cancer?

BACKGROUND: Medullary thyroid cancer (MTC) is a rare but potentially life-threatening disease with limited therapeutic options. As a neuroendocrine tumor, MTC expresses somatostatin receptors, and therefore, somatostatin-labeled radiopharmaceuticals could be used to treat patients with MTC. OBJECTIVE: The aims of this study were to evaluate tumor shrinkage after Lu-DOTATATE treatment, to analyze the impact on quality of life as accessed by the SF-36 questionnaire, and to demonstrate a possible prognostic role for In-DTPA-octreotide uptake in patients with MTC. PATIENTS AND METHODS: Patients with progressive MTC underwent evaluation using In-DTPA-octreotide. Patients who demonstrated In-DTPA-octreotide uptake were treated with 4 cycles of 200 mCi of Lu-DOTATATE and were evaluated using CT scans over 8 to 12 months of treatment. RESULTS: Of the 16 patients initially enrolled, 9 (56.25%) had lesions that were observed in the In-DTPA-octreotide scans and were eligible for therapy with Lu-DOTATATE. Three patients had a partial response, 3 patients were classified as having stable disease and, 1 patient had a progressive disease. All responders indicated improvement in quality of life 6 to 12 months after therapy. CONCLUSIONS: Treatment with Lu-DOTATATE seems to be an alternative therapy for somatostatin receptor-positive tumors, with very mild adverse effects and quality-of-life improvement, at least during a short-term period. Further studies are needed to determine long-term benefits and to identify which patients are more likely to respond to this modality of therapy.