Citations

Abstract Context: Most thyroglobulin (Tg) assays have a sensitivity of 0.5–1 ng/ml. A minority of patients with undetectable T4-suppressed Tg levels have a recombinant human TSH (rhTSH)-stimulated Tg above 2 ng/ml and identifiable residual disease. Objective: The objective was to determine whether a Tg assay with improved sensitivity could eliminate the need for rhTSH stimulation when baseline Tg is below 0.1 ng/ml. Design: A retrospective study of two academic endocrine practices was conducted. Population: A total of 194 patients undergoing rhTSH stimulation participated in the study. Results: Of the 80 patients with Tg below 0.1 ng/ml, two (2.5%) had rhTSH-stimulated Tg above 2 ng/ml. One other patient with stimulation to 0.3 ng/ml and negative 123I scan had an ultrasound-detected malignant lymph node resected. None had 131I/123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. If T4-suppressed Tg was 0.1–0.5 or 0.6–2.0 ng/ml, rhTSH Tg was above 2 ng/ml in 24.2 and 82.4%, respectively. Conclusions: Patients with differentiated thyroid carcinoma and a T4-suppressed serum Tg below 0.1 ng/ml rarely have a rhTSH-stimulated Tg above 2 ng/ml, and none of these patients had 131I or 123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. We recommend monitoring such patients with a T4-suppressed Tg level and periodic neck ultrasonography. An increase in T4-suppressed serum Tg to a detectable level or the appearance of abnormal lymph nodes by physical or ultrasound exam should prompt further investigation.

Abstract Context: We have recently introduced liquid chromatography-tandem mass spectrometry (LC-MS/MS) for 25-hydroxyvitamin D2 (25OHD2) and 25OHD3 testing. During subsequent clinical use, we identified significantly elevated results in some infants. We hypothesized this might represent assay interference caused by C-3 epimers of 25OHD2 or 25OHD3. Objective: Our aims were to 1) determine the prevalence of C-3 epimers of 25OHD2 or 25OHD3 in human serum, and 2) identify the patient populations that might be affected. Study Design: We modified our LC-MS/MS method to allow detection of C-3 epimers. We retested specimens from four patient groups with the new method and an extracted RIA: 1) children less than 1 yr old, 2) children 1–18 yr old, 3) adults aged 20–87 yr with liver disease, and 4) adults aged 19–91 yr without liver disease. Results: In 172 children from group 1 with detectable 25OHD2 or 25OHD3, we identified C-3 epimers in 39 (22.7%). The epimers contributed 8.7–61.1% of the total 25-OHD. There was an inverse relationship between patient age and epimer percentage (r = 0.48; P < 0.002). The RIA gave accurate 25-OHD results that correlated with the modified LC-MS/MS method. No C-3 epimers were detected in any of the other groups. Conclusions: Significant concentrations of C-3 epimers of 25OHD2 or 25OHD3 are commonly found in infants. This can lead to overestimation of 25-OHD levels. Measurements in children less than 1 yr should therefore be performed with an assay that allows accurate detection of 25-OHD in the presence of its C-3 epimers.

Cardiovascular complications are the leading cause of morbidity and mortality in autosomal dominant polycystic kidney disease. Pkd2 + /− vascular smooth muscle cells (VSMCs) have an abnormal phenotype and defective intracellular Ca 2+ ([Ca 2+ ] i ) regulation. We examined cAMP content in vascular smooth muscles from Pkd2 + /− mice because cAMP is elevated in cystic renal epithelial cells. We found cAMP concentration was significantly increased in Pkd2 + /− vessels compared with wild-type vessels. Furthermore, reducing the wild-type VSMC [Ca 2+ ] i by Verapamil or BAPTA-AM significantly increased cellular cAMP concentration (mainly by phosphodiesterase [PDE] inhibition), the rate of VSMC proliferation (determined by direct cell counting, 3 H-incorporation, FACS analysis of cells entering S phase, and quantitative Western PCNA and ERK1/2 analyses), and the rate of apoptosis (by Hoechst staining, FACS analysis of the Annexin-V positive cells, and quantitative Western Bax, cytochrome c , and activated caspase 9 and 3 analyses). The low [Ca 2+ ] i induced VSMC proliferation was independent of cAMP/B-Raf signaling, while that of apoptosis was promoted by cAMP. In summary, Pkd2 + /− VSMCs have elevated cAMP levels. This elevation can also be induced by reducing [Ca 2+ ] i in wild-type VSMCs. The [Ca 2+ ] i reduction and cAMP accumulation can cause an increase in both cellular proliferation and apoptosis, resembling Pkd mutant phenotype.