In recent years the immunomodulatory actions of vitamin D, a steroid hormone, have been extensively studied. In 2020, due to the COVID-19 pandemic, the question arose as to 25(OH)D status would be ...related to susceptibility to SARS-CoV-2 infection, since several studies pointed out a higher prevalence and severity of the disease in populations with low levels of 25(OH)D. Thus, we investigated the 25(OH)D levels in adults "Detected" positive for SARS CoV-2 by RT-PCR (reverse transcriptase polymerase chain reaction) test, and in negative controls, "not Detected", using the Fleury Group's examination database, in Sao Paulo, Brazil. Of a total of 14.692 people with recent assessments of 25(OH)D and RT-PCR tests for COVID-19, 2.345 were positive and 11.585 were negative for the infection. The groups did not differ in the percentage of men and women, or in the age distribution. There were no differences in the distribution of 25(OH)D between the two groups (p = 0.08); mean 25(OH)D of 28.8 ± 21.4 ng/mL and 29.6 ± 18.1 ng/mL, respectively. In the specific population studied, clinical, environmental, socioeconomic and cultural factors should have greater relevance than 25(OH)D in determining the susceptibility to COVID-19.
Purpose
The aims of this study were to assess the role of an in-house competitive thyroglobulin assay (Tg-c) in the follow-up of metastatic differentiated thyroid carcinoma (DTC) patients who ...presented underestimated Tg measurements by immunometric assays (Tg-IMA) and to compare the results with IMA and LC-MS/MS Tg methods.
Methods
This prospective study included 40 patients. Twenty-one with metastatic disease: 14 had Tg-IMA levels inappropriately low or undetectable (eight patients with positive and six with borderline TgAb) and seven had high Tg-IMA levels. Nineteen had an excellent response to therapy. The competitive assay employs a polyclonal antibody produced in rabbits immunized with human Tg, Tg labeled with biotin, and for the solid phase separation, a monoclonal anti-rabbit IgG antibody adsorbed to microtiter plates.
Results
All 14 patients with structural disease and underestimated levels of Tg-IMA presented detectable Tg-c levels. The median Tg-c level in the group with positive TgAb was 183 µg/L (range: 22–710 µg/L), and 58 µg/L (range 23–148 µg/L) in the borderline TgAb group. The levels of Tg-LC-MS/MS were detectable in some patients (range < 0.5–18 µg/L). All seven patients with high Tg-IMA presented also high levels of Tg-c. Only 2/19 patients with excellent response had Tg-c levels above the functional sensitivity.
Conclusions
The competitive assay was able to detect Tg in all patients, even in the presence of serum TgAb, and may be an option in patients with underestimated Tg-IMA and relevant structural disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introduction
Heterozygotes (HZs) for 21‐hydroxylase deficiency (21OHD) are highly prevalent, ranging from 1:60 to 1:11 for classic and nonclassic (NC) forms, respectively. Detection of HZ and ...asymptomatic NC by CYP21A2 genotyping is valuable for genetic counselling, but costly, complex and narrowly available. Adrenocorticotropic hormone (ACTH)‐stimulated serum 17‐hydroxyprogesterone (17P) and 21‐deoxycortisol (21DF) discriminate 21OHD phenotypes effectively, notably if measured simultaneously by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS).
Objective
This study was performed to reassess former LC‐MS/MS‐defined post‐ACTH 21DF, 17P and cortisol (F) cutoffs in family members at risk for 21OHD.
Design and Patients
Prospective study in which we screened 58 asymptomatic relatives from families with 21OHD patients and compared post‐ACTH steroid phenotypes with subsequent genotypes.
Results
Post‐ACTH 21DF, 17P, F and (21DF + 17P)/F ratio segregate NC, HZ and wild‐type (WT) phenotypes (subsequently genotyped) with some overlap. New receiver operating characteristic curve‐defined cutoffs for post‐ACTH 21DF, 17P and (21DF + 17P)/F ratio are 60 ng/dl, 310 ng/dl and 12 (unitless). Twenty‐six of 33 HZ and all 6 NC (82.1%) had post‐ACTH 21DF > 60 and 17P > 310 ng/dl, whereas 17/19 WT (89.5%) had values below cutoffs. Post‐ACTH 21DF and 17P had a strong positive correlation (r = .9558; p < .001). A (21DF + 17P)/F ratio > 12 correctly identified 36 of 39 HZ plus NC (92.3% sensitivity) with 84.2% specificity (16 of 19 WT). Given the high frequency of 21OHD HZ, the negative prediction of ratio values below 12 excludes heterozygosity in 99.8% and 99.1% for classic and NC mutations, respectively.
Conclusions
Reassessed ACTH‐stimulated 21DF and 17P cutoffs by LC‐MS/MS (60 and 310 ng/dl, respectively) correctly recognised 82.5% HZ plus NC, but combined precursor‐to‐product ratio (21DF + 17P/F) cutoff of 12 was superior, identifying 92.3% HZ plus NC. Since one WT subject is an outlier (potential HZ), these values would be somewhat better reinforcing their utility for screening asymptomatic relatives at risk for 21OHD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Context:
Calcitonin (CT) is a sensitive marker of medullary thyroid carcinoma (MTC) and is used for primary diagnosis and follow-up after thyroidectomy. However, persistently elevated CT is observed ...even after complete surgical removal without evidence of a recurrent or persistent tumor.
Objective:
To investigate the presence of assay interference in the serum CT of MTC patients who are apparently without a structural disease.
Patients and Methods:
We studied three index MTC cases for CT assay interference and 14 patients with metastatic MTC. The CT level was measured using an immunofluorometric assay. Screening for assay interference was performed by determination of CT levels before and after serum treatment with polyethylene glycol. Additionally, samples were analyzed by chromatography on ultra-performance liquid chromatography and protein A-Sepharose.
Results:
Patients with biochemical and structural disease showed CT mean recovery of 84.1% after polyethylene glycol treatment, whereas patients suspected of interference showed recovery from 2–7%. The elution profile on UPLC showed that the immunometric CT from these three patients behaved like a high molecular mass aggregate (>300 kDa). Additionally, when these samples were applied to the protein A-Sepharose, CT immunoreactivity was retained on the column and was only released after lowering the pH.
Conclusions:
For the first time, our results show the presence of a novel pitfall in the CT immunoassay: “macrocalcitonin.” Its etiology, frequency, and meaning remain to be defined, but its recognition is of interest and can help clinicians avoid unnecessary diagnostic investigations and treatment during the follow-up of MTC.
The lack of vitamin D is a major changeable factor involved in the pathophysiology of osteoporosis. Since the major source for this hormone is its cutaneous synthesis via ultraviolet radiation (UVR), ...we studied the serum level of 25-hydroxyvitamin D (25OHD) in 250 free-living elderly people (79.1 years old) from a subtropical region according to the UVR incidence and its correlations with parathormone (PTH) and ionized calcium. UVR and 25OHD differed according to the season of the year (P<0.001), with greater radiation in the summer and less in the winter, whereas the 25OHD peak and nadir occurred in autumn and spring, respectively. The highest 25OHD mean was 67.2 nmol/l, and the lowest was 29.1 nmol/l corresponding, respectively, to the measure of the month subsequent to the one of most and least sunlight incidence. Clustered by season, the correlation between UVR and 25OHD for the following seasons was r=0.98 and between the PTH and 25OHD of corresponding seasons, r=-0.95. Vitamin D deficiency occurred in 15.4% of patients, insufficiency in 41.9% and secondary hyperparathyroidism in 55%. In conclusion, we found a seasonal variation in 25OHD levels that strongly correlated with the PTH levels when separated by the seasons of the year. The 25OHD levels correlated with the UVR of the previous quarter, requiring no less than 30 days for serum changes arising from exposure to or deprivation of UVR to be observed. The prevalence of vitamin D deficiency/insufficiency found was greater than expected, even when compared to countries exposed to less solar irradiation. Thus, measures to encourage greater sun exposure and food enrichment policies should also be considered.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Thyroglobulin (Tg) is the major glycoprotein produced by the thyroid gland, where it serves as a template for thyroid hormone synthesis and as an intraglandular store of iodine. Measurement of Tg ...levels in serum is of great practical importance in the follow-up of differentiated thyroid carcinoma (DTC), a setting in which elevated levels after total thyroidectomy are indicative of residual or recurrent disease. The most recent methods for serum Tg measurement are monoclonal antibody-based and are highly sensitive. However, major challenges remain regarding the interpretation of the results obtained with these immunometric methods, particularly in patients with endogenous antithyroglobulin antibodies or in the presence of heterophile antibodies, which may produce falsely low or high Tg values, respectively. The increased prevalence of antithyroglobulin antibodies in patients with DTC, as compared with the general population, raises the very pertinent possibility that tumor Tg may be more immunogenic. This inference makes sense, as the tumor microenvironment (tumor cells plus normal host cells) is characterized by several changes that could induce posttranslational modification of many proteins, including Tg. Attempts to understand the structure of Tg have been made for several decades, but findings have generally been incomplete due to technical hindrances to analysis of such a large protein (660 kDa). This review article will explore the complex structure of Tg and the potential role of its marked heterogeneity in our understanding of normal thyroid biology and neoplastic processes.
Medullary thyroid carcinoma (MTC), a tumor of the parafollicular C cells of the gland, comprises 3-5% of all malignant thyroid neoplasms. Calcitonin, a polypeptidic hormone secreted by the neoplastic ...cells, is considered a very sensitive and specific MTC tumor marker. Patients with MTC usually present elevated serum calcitonin levels, which correlate with tumor burden and prognosis.
To describe a case of advanced MTC with normal serum calcitonin and review the literature on this subject.
A case study was performed.
There were no interventions.
A case of advanced MTC with normal serum calcitonin was studied.
Serum calcitonin was measured by two distinct assays, a chemiluminescent immunometric and an in-house two-site monoclonal antibody-based immunofluorometric assay. To rule out a "hook effect," or posttranslational modifications of calcitonin molecule, serum dilutions and tumor immunohistochemistry for calcitonin with the same antibodies used for serum calcitonin measurements were performed. Serum calcitonin levels were within the normal range in both assays, whereas the tumor stained strongly positive for calcitonin. These findings suggest that the tumor was able to produce but not to secrete the calcitonin protein. Five other cases of advanced MTC with normal serum calcitonin levels had been previously reported.
We present an unusual case of advanced MTC with normal serum calcitonin levels. Awareness of MTC cases presenting with normal serum calcitonin levels is important in clinical practice and is particularly relevant to centers that use this test for screening.
Consuming a low-iodine diet (LID) is a widely accepted practice before administering radioiodine (131I) to evaluate and to treat thyroid disease. Although this procedure is well established for the ...management of patients with differentiated thyroid cancer, its use in patients with benign disease is unclear. So, we aimed to evaluate the influence of a LID on the outcome in patients with Graves' disease (GD) treated with 131I.
We evaluated 67 patients with GD who were divided into 2 groups: one group (n = 31) consumed a LID for 1-2 weeks, and the second group (n = 36) was instructed to maintain a regular diet (RD).
The LID group experienced a 23% decrease in urinary iodine after 1 week on the diet and a significant 42% decrease after 2 weeks on the diet. The majority (53%) of the patients in the LID group had urinary iodine levels that were consistent with deficient iodine intake. However, there was no difference in the rate of hyperthyroidism's cure between the LID and the RD groups 6 months after 131I therapy. Furthermore, the therapeutic efficacy did not differ in patients with varying degrees of sufficient iodine intake (corresponding urinary iodine levels: < 10 μg/dL is deficient; 10-29.9 μg/dL is sufficient; and > 30 μg/dL is excessive).
In the present study, we demonstrated that although a LID decreased urinary iodine levels, those levels corresponding with sufficient or a mild excess in iodine intake did not compromise the therapeutic efficacy of 131I for the treatment of GD.
Identification of the correct etiology of diabetes brings important implications for clinical management. In this report, we describe a case of a 4-year old asymptomatic girl with diabetes since age ...2, along with several individuals in her family with different etiologies for hyperglycemia identified in youth. Genetic analyses were made by Sanger sequencing, laboratory measurements included HbA1c, lipid profile, fasting C-peptide, pancreatic auto-antibodies (glutamic acid decarboxylase GAD, Islet Antigen 2 IA-2, and anti-insulin). We found a Gly178Ala substitution in exon 5 of GCK gene in three individuals co-segregating with diabetes, and type 1 diabetes was identified in two other individuals based on clinical and laboratory data. One individual with previous gestational diabetes and other with prediabetes were also described. We discuss difficulties in defining etiology of hyperglycemia in youth in clinical practice, especially monogenic forms of diabetes, in spite of the availability of several genetic, laboratory, and clinical tools.
Magnesium is an important electrolyte for very many cell functions and its deficiency may lead to a wide spectrum of diseases. We report a clinical case of hypomagnesemia resulting from the chronic ...use of a proton pump inhibitor (PPI). PPIs are drugs widely used in medical practice, and a growing number of cases of PPIs causing hypomagnesemia have been described. Our aim was to monitor the clinical and electrolyte findings during recovery from hypomagnesemia caused by long-term PPI use.
A 65-year old female who had been using omeprazole for 10 years, presented with arrhythmia and paresthesia of the lower and upper limbs that had been attributed to severe hypomagnesemia, hypocalcemia, and hypoparathyroidism. Her laboratory tests revealed the following results: magnesium 0.6 mg/dL (NR: 1.5 to 2.5 mg/dL), calcium 7.3 mg/dL (NR: 8.5 to 10.2 mg/dL), parathyroid hormone (PTH) 13.3 pg/mL (NR: 15 to 65 pg/mL), and low urinary calcium and magnesium excretion. Her electrocardiogram disclosed typical, prolonged QT interval, ST depression, and U waves. We discuss the differential diagnoses, pathophysiology, and reversibility of symptoms after effective treatment of the hypomagnesemia.
this report emphasizes that even if long-term PPI users appear largely asymptomatic, life-threatening arrhythmias can present very suddenly. Long-term PPI users should be monitored for otherwise unexplained hypomagnesemia, hypocalcemia, functional hypoparathyroidism and associated symptoms.
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