Urinary excretion of thyroid hormone in CKD patients: a proof-of-concept of nephrogenic hypothyroidism.

PURPOSE: Patients with chronic kidney disease (CKD) complicated by hypothyroidism exhibit a higher prevalence of urine protein than that in the general population. This study was aimed at investigating thyroid hormones and thyroid hormone-binding proteins excreted in urine to elucidate the urine protein-associated underlying mechanisms of hypothyroidism. METHODS: Between November 2016 and August 2018, thyroid function (serum free T3 [sFT3], free T4 [sFT4], and thyroid-stimulating hormone [sTSH]), kidney function (estimated glomerular filtration rate [eGFR]), thyroid antibodies and albumin (Alb) were evaluated in 99 Japanese CKD patients with proteinuria at our outpatient clinic. A urine examination was also performed to assess the following parameters: total T3, total T4, TSH, Alb, preAlb, thyroid-binding globulin, and protein. RESULTS: The median patient age at study recruitment was 60 years; 50 patients (50.5%) were male. The median eGFR and Alb level were 20.3 ml/min/1.73 m2 and 3.8 g/dL, respectively. 21 patients (21.2%) were diagnosed with nephrotic syndrome (NS). The median sFT3, sFT4, and sTSH levels were within normal limits. Approximately 70% of the patients had thyroid dysfunction and 51.5% had overt or subclinical hypothyroidism without predominantly antibody positive. Regarding NS and non-NS patients, age and Alb were significantly different between these groups, while sex and eGFR were not significant, but the urinary T4 and TSH levels were higher in the NS group; thus, more severe hypothyroid. CONCLUSION: We found a significant association between hypothyroidism and NS regardless of sex and antibodies. Urinary loss of thyroid hormones must be a factor influencing hypothyroidism independent of autoimmunity.

Fibroblast growth factor 23-Klotho and mineral metabolism in the first year after pediatric kidney transplantation: A single-center prospective study.

BACKGROUND: The role of fibroblast growth factor 23 (FGF23) levels in mineral metabolism before and after kidney transplantation in pediatric patients is poorly understood. METHODS: We prospectively evaluated 24 patients under 18 years of age (4.5 [3.3-9.8] years) who underwent living kidney transplantation between July 2016 and March 2018, and measured intact FGF23 and serum αKlotho levels, and other parameters of mineral metabolism before and after transplantation (Day 7, 1 and 4 months, and 1 year). Relationships between parameters were examined by linear analysis. RESULTS: FGF23 level was 440.8 [63.4-5916.3] pg/ml pre-transplant and decreased significantly to 37.1 [16.0-71.5] pg/ml at Day 7 post-transplant (-91.6%, p < .001). Thereafter, it remained at normal levels until 1 year. αKlotho level was 785 [568-1292] pg/ml pre-transplant and remained low at Day 7 and 1 month post-transplant, with an increasing trend at 4 months. Post-transplant phosphorus levels were significantly decreased compared with pre-transplant, with a lowest level of 1.7 [1.3-2.9] mg/dl, -5.7 [-6.8, -3.8] SD at Day 4, followed by gradual recovery. Phosphorus levels and the ratio of tubular maximum phosphate reabsorption were significantly and negatively associated with pre-transplant FGF23 until 4 months of post-transplant. Pre-transplant αKlotho was negatively associated with pre-transplant FGF23 but not FGF23 or other parameters after transplantation. CONCLUSION: FGF23 in pediatric kidney transplant patients decreased rapidly after transplantation and associated with post-transplant hypophosphatemia and increased phosphorus excretion. Post-transplant αKlotho was low early post-transplant but tended to increase subsequently. Post-transplant αKlotho was unaffected by pre-transplant FGF23 or other factors, suggesting pre-transplant chronic kidney disease status has no effect.

Prevalence of hypothyroidism in Japanese chronic kidney disease patients.

Background: Major symptoms of progressive chronic kidney disease (CKD) are similar to those of hypothyroidism. Hidden symptoms of hypothyroidism underlying CKD are often observed in clinical practice. This study aimed to ascertain the frequency of hypothyroidism complicated by CKD, and to analyze factors impacting thyroid function.Methods: During the period from April 2012 through October 2016, 510 CKD patients at our outpatient clinic were measured thyroid and kidney function for diagnosing hypothyroidism (overt hypothyroidism, OH; subclinical hypothyroidism, SH; non-thyroidal illness, NTI) and evaluating the stage of CKD. All patients were over 15 years of age.Results: There were significant differences in age, estimated glomerular filtration rate (eGFR), urinary protein (UP), and serum albumin (Alb) among patients with OH, SH, and NTI compared to the normal group in univariate and multivariate analyses. UP showed the highest odds ratio of OH, SH, and NTI but no differences were recognized in gender in each group. Frequency distribution showed that the prevalence of thyroid dysfunction was greater among more severe stage of CKD with higher amount of UP. OH and SH did not show high positive ratio of anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb). NTI and normal subjects showed higher positive ratio as 50.0% and 42.9% of TgAb and TPOAb than OH and SH.Conclusions: Hypothyroidism complicated by CKD exhibited a high prevalence. Age, eGFR, UP, and serum Alb were related to the prevalence of hypothyroidism, whereas gender was not and this was contradicted to the prevalence of hypothyroidism in general population. The prevalence of OH and SH was higher among patients with higher stage of CKD with increased UP. Hypothyroidism complicated by CKD may involve different onset mechanisms unrelated to antithyroid antibodies (ATAb). In CKD patients, assessments of OH and SH, as well as NTI, are needed for proper diagnosis.

Changes in the fluid volume balance between intra- and extracellular water in a sample of Japanese adults aged 15-88 yr old: a cross-sectional study.

The fluid volume balance between intracellular water (ICW) and extracellular water (ECW) gradually changes with age and various medical conditions. Comprehension of these physiological changes would aid in clinical decision-making related to body fluid assessments. A total of 1,992 individuals (753 men and 1,239 women) aged ≥15 yr included in this study had their body composition measurements performed at training gyms in 2014. We developed a regression formula to assess the association of age with the ratio of ECW to ICW in these subjects. The mean ages of male and female subjects were 51.2 ± 15.2 and 57.4 ± 15.2 yr, and their mean body mass indexes were 23.4 ± 3.3 and 21.1 ± 2.8 kg/m2, respectively. The total fluid volumes of male and female subjects were 39.6 ± 4.9 and 27.7 ± 3.0 liters, whereas the percent body fat mass per kilogram of body weight were 19 and 26%, respectively. The ECW-to-ICW ratio increased with age because of the steeper decrease in the ICW content than in the ECW content, especially after the age of 70 yr. The regression formulas used for calculating the age-adjusted ECW/ICW ratio were as follows: 0.5857 + 7.4334 × 10-6 × (age)2 in men and 0.6062 + 5.5775 × 10-6 × (age)2 in women. In conclusion, the fluid imbalance between ICW and ECW contents is driven by decreased cell volume associated with aging and muscle attenuation. Therefore, our proposed formula may serve as a useful assessment tool for the calculation of body fluid composition.

Placement of self-expandable metallic stents for tracheal stenosis secondary to thyroid cancer.

The indications and suitable approaches for treating upper airway obstruction secondary to thyroid cancer are controversial. Patients with thyroid cancer generally have a good prognosis, but airway stenosis and vocal cord paralysis are not uncommon. Subglottic airway stenting may be challenging, due to stent migration, granulation tissue formation and supraglottic stenosis. In this study, we evaluated the application of covered self-expandable metallic stents to relieve upper airway obstruction. This was a retrospective study of 5 patients with airway stenosis due to thyroid cancer treated in 2009 and 2010. Immediate airway enlargement was achieved in 3 patients with stenosis at the middle mediastinum. Gradual enlargement over 2 months was observed in the remaining 2 patients with stenosis at the cervical level. The performance status was improved in all 5 patients, including a case with anaplastic carcinoma. The follow-up averaged 13 months (range, 8-27 months). Granulation tissue developed at both ends of the stent in 3 patients, sputum was retained in 2 cases and bacterial colonization was detected in all 5 cases. No stent migration was reported. Additional tracheostomy was required in 2 patients, due to proximal tumor growth or progressive bilateral vocal cord paralysis after 10 and 6 months, respectively. In conclusion, stenting for central airway stenosis secondary to thyroid cancer may be beneficial, even in patients with anaplastic carcinoma. Long-term regular bronchoscopic follow-up is required to monitor complications, as patients with thyroid cancer are at high risk of granulation tissue formation, sputum retention and bacterial colonization.

Video-assisted thoracoscopic surgery for ectopic middle mediastinal thymoma in a patient with myasthenia gravis.

We present a rare case of middle mediastinal thymoma with myasthenia gravis. A 51-year-old man presented with right ptosis and muscle weakness, and received a diagnosis of generalized myasthenia gravis. Computed tomography of the chest showed a 20-mm nodule in the middle mediastinum, suggesting a possible ectopic thymoma. He underwent video-assisted thoracoscopic extended thymectomy and resection of the tumor. Histologic examination revealed an ectopic thymoma and ectopic thymic tissue around the tumor. One year after the operation, his condition remains well controlled solely with tacrolimus. Careful preoperative radiologic examination concerning possible ectopic thymoma outside the dissection area of the extended thymectomy is recommended.

Ciliated muconodular papillary tumor of the lung: a newly defined low-grade malignant tumor with CT findings reminiscent of adenocarcinoma.

A ciliated muconodular papillary tumor has been reported to be a peripheral low-grade malignant tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation. Although ciliated muconodular papillary tumors have not yet been classified according to the World Health Organization classification, they can pose diagnostic and therapeutic problems. Here we report a resected case of ciliated muconodular papillary tumor with computed tomography findings reminiscent of adenocarcinoma, showing a small irregular nodule adjacent to the intersegment pulmonary vein. There was no uptake of F-18 fluorodeoxyglucose positron emission tomography. The patient underwent surgical resection, and a lobectomy was performed because intraoperative needle biopsy suggested neoplastic proliferation. No EGFR mutations were detected. No recurrence was noted during 24-month follow-up after lobectomy.

The relation of initial methimazole dose to the incidence of methimazole-induced agranulocytosis in patients with Graves' disease.

The relation between the incidence of methimazole (methylmercaptoimidazole; MMI)-induced agranulocytosis and initial MMI dose was evaluated in a group of 514 patients with Graves' disease who were treated between 1995 and 2005. One hundred and forty-six (28.40%) patients had received an initial dose of 30 mg MMI and 277 (53.89%) patients had been treated with 15 mg MMI. Nine patients (1.75%) developed agranulocytosis due to MMI treatment. Six (4.11%) of 146 patients who received an initial dose of 30 mg MMI, two (4.54%) of 44 patients given an initial dose of 20 mg MMI, and one (0.36%) of 277 patients given an initial dose of 15 mg MMI developed agranulocytosis. There was a statistically significant difference in agranulocytosis incidence between patients receiving an initial dose of 30 mg MMI and those who received an initial dose of 15 mg. Although 8 (4.10%) of 195 patients in the high-dose group (20 mg or higher) developed agranulocytosis, only 1 (0.31%) of 319 patients in the low-dose group (15 mg or lower) did. In conclusion, the incidence of agranulocytosis with low-dose MMI therapy was ten times lower than that of the high-dose regimen.