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Evidence on vitamin D and parathyroid hormone (PTH) status in patients with early kidney impairment is limited. We aimed to determine the associations among kidney function, vitamin D, and PTH status in community-dwelling elderly patients with mild-to-moderate kidney impairment. Community-dwelling elderly patients were enrolled in this Institutional Review Board approved cross-sectional study. The eligibility criteria were as follows: age > 60 years, no recent hospitalization within the past 12 months, no conditions that affect vitamin D status including vitamin D supplementation, and eGFR > 30 mL/min/1.73 m2. Serum 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) levels were assessed. A total of 226 patients were enrolled. Data were expressed as mean ± SD. The mean serum 25(OH)D was 26.61 ± 10.44 ng/mL and the mean serum PTH was 50.67 ± 22.67 pg/mL. The prevalence of vitamin D deficiency [25(OH)D 65 pg/mL] were 25.3% and 18.1%, respectively. Patients with eGFR 30−

Background Thyroid gland size is a required parameter for radioactive iodine (RAI) dose calculation for radioactive iodine therapy (RAIT) of Graves’ disease. Comparing between ultrasonography and palpation, previous studies showed that the former provided more accurate thyroid sizes. However, there have been no studies comparing success of RAIT when either of these two methods is used to determine thyroid gland size. The aim of this study is to evaluate the outcome of RAIT using thyroid gland size measured by ultrasonography compared with palpation for RAI dose calculation. Methods We prospectively enrolled Graves’ disease patients who presented for the first RAIT. Thyroid gland sizes of all participants were determined by both ultrasonography and palpation on the day of RAIT. Participants were then randomized into ultrasound (US) or palpation groups for which RAI dose administered was calculated using the thyroid size obtained by the method assigned to their groups. Primary outcome was success of RAIT at 6 months, defined by the ability to discontinue antithyroid drugs (ATDs). Secondary outcomes were factors associated with success of RAIT. Results One hundred patients completed the study, 52% were in the US group and 42% were in the palpation group. Success rate of RAIT at six months was higher in the palpation group (58.3% vs 38.5%, p = 0.047). Among patients who had successful RAIT, the palpation group had a higher rate of hypothyroidism than did US group (78.6% vs 60%) as well as higher RAI dose (9.5 ± 3.6 millicuries in palpation group vs 7.1 ± 4.8 millicuries in US group, p = 0.005). There were no factors associated with favorable outcome, including sex; age; weight; type or dose of previous ATDs; duration of disease; baseline thyroid function tests; baseline anti-TSH receptor antibody levels and urine iodine. There was a poor correlation between thyroid sizes, obtained by ultrasonography and palpation (correlation coefficient = 0.578). The least discrepancy in size was observed when thyroid glands were between 40 and 60 grams (g). The highest difference was seen in patients with thyroid sizes Conclusion Success of RAIT was higher in palpation group than in US group. Overestimation of thyroid gland size accounted for the higher RAI dose and success of palpation group at the expense of more hypothyroidism. Low constant value per gram of thyroid tissue in the calculation formula might underlie the overall low success rate. Palpation tended to incorrectly estimate the size when thyroid gland is either small (=60 g). Therefore, adequate constant value in the calculation formula and obtaining thyroid gland size by ultrasonography prior to RAIT in patients with extreme thyroid sizes may be beneficial. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Background High-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D. Materials and methods T2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of β-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks. Results Mean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA1c from baseline in the LS and HS groups was -0.1% and +0.1% (p=0.03) at 6 weeks, and -0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks. Conclusion Switching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA1c (0.1%) without causing cognitive decline.

Nuntakorn Thongtang, Jirasak Piyapromdee, Natthakan Tangkittikasem, Kittichai Samaithongcharoen, Nithiwat Srikanchanawat, Sutin Sriussadaporn Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Nuntakorn ThongtangDivision of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok 10700, ThailandTel +66 2-419-7799Fax +66 2-419-7792Email nuntakorn@hotmail.comIntroduction: Statin intensification is required in patients who have high-risk for cardiovascular events. However, it is unclear if this is needed in whom plasma LDL-C target was achieved with low-dose statin for primary prevention. We investigated the efficacy and safety of switching from low-dose statin to high-intensity statin among type 2 diabetes (T2D) who had achieved plasma LDL-C < 100 mg/dl with low-dose statin treatment.Methods: T2D patients with no atherosclerotic cardiovascular disease who had plasma LDL-C level < 100 mg/dl while taking simvastatin ≤ 20 mg/day were randomized to continue using the same dosage of simvastatin (low-dose statin group; LS) for 12 weeks, or to switch to atorvastatin 40 mg/day for 6 weeks, and then, if tolerated, to atorvastatin 80 mg/day for 6 weeks (high-intensity statin group; HS). Biochemical test and adverse events were evaluated at baseline, 6 weeks, and 12 weeks.Results: One hundred and fifty patients (76 LS, 74 HS, mean age 58.9± 8.9 years, 72% female) were included. The mean baseline plasma LDL-C level on statin was slightly higher in the HS group (71.9± 13.6 vs. 68.1± 14.2 mg/dl, p=0.09). The HS group had a significantly lower plasma LDL-C level at both 6 and 12 weeks (both p< 0.001). Plasma LDL-C < 40 mg/dl was found more frequently in the HS group (23.0% vs. 3.9%, p< 0.001). Discontinuation of statin due to adverse effects was more frequent in the HS group (5.4% vs. 1.3%, p=0.38 for atorvastatin 40 mg/day, 12.2% vs. 1.3%, p=0.03 for atorvastatin 80 mg/day). No serious adverse events were observed in either group.Conclusion: Switching from low-dose statins to high-intensity statins resulted in a significant reduction in plasma LDL-C levels, and was fairly well tolerated during a 12-week study period.Keywords: efficacy, safety, high-intensity statin, primary prevention, Thai patients, type 2 diabetes

Background. The long-term continuation of the low-dose antithyroid drug (ATD) beyond the standard duration of ATD therapy of 12–18 months to prevent recurrent hyperthyroidism (RH) is recommended with low quality of evidence. Objectives. To examine whether long-term continuation of low-dose ATD beyond the recommended duration of treatment would provide a benefit in the prevention of RH in patients with Graves’ hyperthyroidism (GH) who achieved euthyroid status with a standard course of ATD therapy. Methods. A 36-month prospective randomized controlled study was conducted in 184 patients who had first diagnosed GH and were treated with a standard regimen of ATD therapy using methimazole (MMI) until achieving euthyroidism that was stably maintained for at least 6 months with a low-dose of (2.5–5 mg/day) MMI. All patients had neither a history of adverse effects from MMI, recurrent GH, severe and active ophthalmopathy nor conditions known to affect thyroid function before randomization. The patients were randomized into 2 groups: one group (92 cases) was assigned to discontinue (DISCONT-MMI) and the other (92 cases) was assigned to continue low-dose MMI (CONT-MMI) that was taken at the time of enrollment. The patients in both groups were followed up at 3, 6, 12, 18, 24, 30, and 36 months. The rate of RH was compared between both groups, and the adverse effects and risk factors of RH were also studied. Results. At the end of the 36-month study, 83 cases in CONT-MMI and 90 cases in DISCONT-MMI were eligible for analysis. The cumulative rates of RH in CONT-MMI were significantly lower than those in DISCONT-MMI at every follow-up time point (1.2% vs. 11.2%, 6.8% vs. 18.4%, 11.0% vs. 27.2%, 11.0% vs. 35.0%, and 11.0% vs. 41.2% at 6, 12, 18, 24, and 36 months, respectively; p < 0.01 ). Cox proportional hazard multivariate analysis showed that there were 2 factors independently associated with the risk of RH, including continuation of low-dose MMI therapy, which decreased the risk of RH by 3.8 times (HR = 0.26, p = 0.007 , 95% CI = 0.10–0.70) and age onset of hyperthyroidism before 40 years, which increased the risk of RH by 2.9 times (HR = 2.9, p = 0.015 , 95% CI = 1.23–6.88). Neither minor nor major adverse effects of low-dose MMI therapy were observed during the study period. Conclusions. In Graves’ hyperthyroid patients with no or nonsevere ophthalmopathy who have completed a standard course of methimazole therapy without an adverse effect and have achieved an euthyroid status that is stably maintained with low-dose methimazole, a long-term continuation of the low-dose methimazole of 2.5–5 mg daily is effective and safe in the prevention of recurrent hyperthyroidism or maintenance of euthyroid status as long as the low-dose methimazole is continued. (TCTR20170705002).

Background. Little is known about the association among skin color, sunlight exposure. and vitamin D status in Southeast Asian population. Objective. To investigate the association between skin color measured by von Luschan chromatic scale (VLCS) and vitamin D status in Thai medical ambulatory patients. Methods. Medical ambulatory patients were enrolled. The eligibility criteria were as follows: aged >18 years, stable medical conditions, and no conditions directly affecting vitamin D status. Serum 25-hydroxyvitamin D [25(OH)D] levels were assessed. Skin color at the outer forearm was assessed using VLCS which grades skin color from the lightest score of 1 to the darkest score of 36. Patients were systematically interviewed to estimate daily sunlight exposure time. Results. A total of 334 patients were enrolled. Data were expressed as mean ± SD. The mean serum 25(OH)D was 25.21 ± 10.06 ng/mL. There were 17 (5.1%), 217 (65.0%), and 100 (29.9%) patients who had light brown (VLCS score 18–20), medium brown (VLCS score 21–24), and dark brown (VLCS score 25–27) skin colors, respectively. The mean serum 25(OH)D level was higher in patients with dark brown skin than in patients with medium brown and light brown skin (28.31 ± 10.34 vs. 24.28 ± 9.57 and 19.43 ± 9.92 ng/mL, respectively, both p < 0.05 ). Multivariate analysis showed that darker skin color and increased sunlight exposure time were independently associated with decreased odds of vitamin D deficiency (dark brown vs. light brown: odds ratio, 0.263, 95% CI: 0.081–0.851, p = 0.026 ; medium brown vs. light brown: odds ratio, 0.369, 95% CI: 0.987–1.003, p = 0.067 ; sunlight exposure time odds ratio per 1 minute/day increase 0.955, 95% CI: 0.991–1.000, p = 0.037 ), after adjusting for possible confounders. Conclusions. We found that darker skin color at sunlight exposure area and increased sunlight exposure time were independently associated with decreased odds of vitamin D deficiency in Thai medical ambulatory patients.

Background High-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D. Materials and Methods T2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of β-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks. Results Mean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA1c from baseline in the LS and HS groups was −0.1% and +0.1% (p=0.03) at 6 weeks, and −0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks. Conclusion Switching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA1c (0.1%) without causing cognitive decline.

C-peptide suppression test (CPS) was shown to diagnose the cause of hyperinsulinemic hypoglycemia, i.e. insulinoma, as effectively as supervised 72-hour fast test with less time consuming and cost. In the conventional CPS, regular insulin (RI) is used to induce hypoglycemia that subsequently suppresses endogenous insulin secretion. As RI is measurable in plasma insulin (PI) assay, plasma C-peptide (PCP) but not PI response is therefore used for assessment of endogenous insulin secretion in CPS using RI. As rapid acting insulin analogs (RA) are not measurable in a selected PI assay, both PCP and PI levels can be used to assess endogenous insulin secretion if an RA is used instead of RI in CPS. There is no study on PI and PCP responses to RA in insulinoma. This study aimed to examine efficacy of modified CPS, so-called insulin and C-peptide suppression test (ICPS) by using an RA (insulin aspart) in the diagnosis of insulinoma. Ten patients, 7 with histopathological proven insulinoma (IN) and 3 with non-insulinoma (non-IN), underwent ICPS. Blood samples were collected for measurement of plasma glucose (PG), PCP, and PI using a Roche Cobas 8000 module e602 which does not measure insulin aspart at before and every 10-20 minutes during intravenous infusion of insulin aspart at the rate of 0.05-0.075 unit/kg/hr. The test was terminated if the patients had a PG level of

Background Vitamin D has been reported to be associated with many allergic diseases. There are a limited number of the studies of vitamin D supplementation in patients with chronic spontaneous urticaria (CSU). This study aims to study the relationship between vitamin D and CSU in terms of serum vitamin D levels, and the outcomes of vitamin D supplementation. Methods A literature search of electronic databases for all relevant articles published between 1966 and 2018 was performed. The systematic literature review was done following Preferred Reporting Items for Systematic Reviews and Meta-analysis recommendations. Results Seventeen eligible studies were included. Fourteen (1321 CSU cases and 6100 controls) were concerned with serum vitamin D levels in CSU patients. Twelve studies showed statistically significant lower serum vitamin D levels in CSU patients than the controls. Vitamin D deficiency was reported more commonly for CSU patients (34.3–89.7%) than controls (0.0–68.9%) in 6 studies. Seven studies concerned with vitamin D supplementation in CSU patients showed disease improvement after high-dosages of vitamin D supplementation. Conclusion CSU patients had significantly lower serum vitamin D levels than the controls in most studies. However, the results did not prove causation, and the mechanisms were not clearly explained. Despite the scarcity of available studies, this systematic review showed that a high dosage of vitamin D supplementation for 4–12 weeks might help to decrease the disease activity in some CSU patients. Well-designed randomized placebo-controlled studies are needed to determine the cut-off levels of vitamin D for supplementation and treatment outcomes.

BackgroundPituitary metastasis is a rare condition with a poor prognosis. Very few patients with pituitary metastasis are symptomatic. It is often associated with presence of co-existing metastases to other organs. Isolated pituitary metastasis as the first presentation of primary malignancy is uncommon.Case presentationA 72-year-old woman presented with a 2-month history of polyuria, increasing thirst and unexplained weight loss. Esophagogastroduodenoscopy (EGD) was scheduled as part of the investigation. She was keptnilper osfor 10 h prior to EGD, after which she developed alteration of consciousness. Further investigation revealed hypernatremia with sodium level of 161 mmol/L and low urine osmolality of 62 mOsm/kg. Her urine output was 300 mL per hour. Diabetes insipidus (DI) was diagnosed based on evidence of polyuria, hypernatremia, and low urine osmolality. Her urine output decreased and urine osmolality increased to 570 mOsm/kg in response to subcutaneous desmopressin acetate, confirming central DI. Pituitary magnetic resonance imaging showed a heterogeneous gadolinium enhancing lesion at the sellar and suprasellar regions, measuring 2.4 × 2.6 × 3.9 cm compressing both the hypothalamus bilaterally and the inferior aspect of optic chiasm as well as displacing the residual pituitary gland anteriorly. The posterior pituitary bright spot was absent. These MRI findings suggested pituitary macroadenoma. There were also multiple small gadolinium-enhancing lesions up to 0.7 cm in size with adjacent vasogenic brain edema at the subcortical and subpial regions of the left frontal and parietal areas, raising the concern of brain metastases. Pituitary hormonal evaluation was consistent with panhypopituitarism. Histopathological and immunohistochemical studies of the pituitary tissue revealed an adenocarcinoma, originating from the lung. Computed tomography of the chest and abdomen was subsequently performed, showing a 2.2-cm soft tissue mass at the proximal part of right bronchus. There was no evidence of distant metastases elsewhere. The final diagnosis was adenocarcinoma of the lung with pituitary metastasis manifesting as panhypopituitarism and central DI. Palliative care along with hormonal replacement therapy was offered to the patient. She died 4 months after diagnosis.ConclusionDiagnosis of pituitary metastasis is challenging, especially in patients with previously undiagnosed primary cancer. It should be considered in the elderly patients presenting with new-onset central DI with or without anterior pituitary dysfunction.

Several studies have shown high prevalence of low serum 25-hydroxyvitamin D (25OHD) level in severe chronic kidney disease (CKD). However, studies on vitamin D status in patients with mild to moderate kidney impairment such as stages 1 to 3b CKD are limited. This cross-sectional study aimed to examine vitamin D status in doing-well ambulatory patients with stable medical conditions who had mild to moderate kidney impairment defined by estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73m2. All patients had no conditions known to affect vitamin D status including vitamin D supplementation and were assessed for renal function, 25OHD, and parathyroid hormone (PTH) levels. Data are expressed as mean ± SD (range) or % as appropriate. There were 333 patients with a mean age of 64.5 ± 10.3 years old (26 - 88), 67.9% were elderly (aged >60), and 63.7% were female. The patients’ major underlying diseases included type 2 diabetes mellitus (71.5%), hypertension (69.1%), dyslipidemia (82.8%), and coronary artery disease (6.9%). Mean serum 25OHD was 25.1 ± 10.1 ng/mL (3.0 - 70.0). 42.1%, 29.7% and 2.7 % of the patients had 25OHD of 20 - 60), the prevalence of 25OHD of 20

Tada Kunavisarut, Sutin Sriussadaporn, Raweewan LertwattanarakDivision of Endocrinology and Metabolism, Siriraj Hospital, Mahidol University, Bangkok, ThailandBackground: The aim of this study was to investigate beta-cell function and examine whether sulfonylureas (SUs) are still useful in patients with type 2 diabetes (T2DM) who failed to maintain optimal glycemic control with a combination of maximum dosages of metformin and SU.Method: T2DM who had HbA1c >8% during treatment with a combination of maximum dosages of metformin and SU were studied. After enrollment, the patients were assigned to continue maximum dosages of SU and metformin for 2 weeks and then underwent the first oral glucose tolerance test (OGTT), the Max-SU OGTT. After the Max-SU OGTT, SUs were discontinued for 4 weeks and the second OGTT, the Discont-SU OGTT, was performed. After the Discont-SU OGTT, the same SU was restarted at 25% of the maximum dosage (25%Max-SU). After taking 25%Max-SU for 4 weeks, the third OGTT, the 25%Max-SU OGTT, was performed. Metformin at the same dosage was continued throughout the study. Normal OGTT (NGT) subjects, matched for age and body mass index (BMI), were also studied.Results: There were 25 T2DM and 28 NGT subjects. There was no difference in age and BMI between the two groups. The beta-cell function during Max-SU was 0.1, which was higher than 0.06 during Discont-SU (p

Statin intensity classification according to American College of Cardiology/American Heart Association (ACC/AHA) 2013 guideline. (PPTX 63Â kb)

Dietary phosphorus restriction up-regulates intestinal vitamin D receptor (VDR), but the tissue specificity of the up-regulation and the mechanism of receptor accumulation remain unknown. Therefore, the effects of low phosphorus diet (LPD) on VDR content in intestine, kidney, and splenic monocytes/macrophages were examined. Male Sprague-Dawley rats weighing 50-100 g were fed a normal diet (NPD; 0.6% Ca, 0.65% P) as controls followed by an LPD (0.6% Ca, 0.1% P) for 1-10 days (D1-D10). LPD rapidly decreased serum P levels by D1 from 11.11 +/- 0.19 mg/dl (mean +/- SE) to 4.98 +/- 0.37 mg/dl (n = 9). LPD increased total serum Ca from 10.54 +/- 0.09 mg/dl to 11.63 +/- 0.15, 12.17 +/- 0.15, and 12.39 +/- 0.18 mg/dl by D1, D2, and D3, respectively, and then remained stable. Serum 1,25-(OH)2D3 rapidly increased from 123 +/- 5.4 pg/ml to 304 +/- 35 pg/ml by D1, reached a plateau through D5, and then gradually increased to 464.9 +/- 27.7 pg/ml by D10. Intestinal VDR quantitated by ligand binding assay increased 3.5-fold from 169.6 +/- 13.7 fmol/mg of cytosol protein in rats fed NPD (n = 12) to a peak of 588.3 +/- 141.88 fmol/mg of protein by D3 (n = 6; p < 0.001) and then decreased to a plateau level of 2.5-fold greater than NPD (p < 0.05) during D5 to D10. In contrast, LPD did not up-regulate kidney or splenic monocyte/macrophage VDR. Northern blot analysis showed that intestinal VDR mRNA increased 2-fold by D2 (n = 3) of LPD and then gradually decreased to control levels after D5. In contrast, kidney VDR mRNA levels did not change during the first 5 days of P restriction and then subsequently decreased to 50% of NPD controls. The results of these studies indicate that VDR up-regulation during dietary phosphorus restriction is tissue-specific and that the mechanism of the up-regulation is time-dependent. Acutely (D1-D5), phosphorus restriction up-regulates intestinal VDR through increased VDR gene expression, whereas chronic (D5-D10) phosphorus restriction appears to alter VDR metabolism through nongenomic mechanisms that are consistent with prolongation of the half-life of the receptor. The nature of the tissue-specific regulation of VDR during phosphorus restriction remains to be determined.

Objective Six known genes responsible for maturity-onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early-onset type 2 diabetes. Patients and methods Fifty-one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha, GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non-diabetic controls, were classified as potentially pathogenic mutations. Results We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the studied probands. Conclusions Mutations of the six known MODY genes may not be a major cause of MODY and early-onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early-onset type 2 diabetes.

We measured the cell-mediated immune response to GAD and bovine beta-casein in 38 type 1 and 37 type 2 diabetic patients who visited diabetic clinics or who were hospitalized in Bangkok, Thailand, and in 43 normal controls, by using a lymphoproliferation assay. Positive results against GAD were found in 29/38 (76.3%) type 1, 6/37 (16.2%) type 2 diabetic patients and 1/43 (2.3%) normal controls. Positive results against bovine beta-casein were found in 18/38 (47.4%), 5/37 (13.5%) and 1/43 (2.3%) of these subjects, respectively. The frequencies of the positive results and the magnitude of the responses to both antigens in type 1 diabetic patients were significantly higher than those in the other two groups (P0.001). In addition, the prevalence of a positive lymphoproliferative response to these antigens in type 1 diabetic patients was higher than that of anti-GAD antibody positivity in the same group of subjects (26.3%). Thus, the prevalence of positive lymphoproliferative response to GAD in type 1 diabetic patients studied was higher than the prevalence of other autoimmune markers previously reported in type 1 diabetic patients in Thailand.

OBJECTIVE: Hyperthyroidism in pregnancy occurs with a prevalence of 0.05--0.2% and has been shown to affect neonatal outcomes. Fetal weight increases markedly during the third trimester of pregnancy. This retrospective study was performed to examine the effect of maternal hyperthyroidism during late pregnancy on neonatal birth weight (NBW). DESIGN: Medical and obstetric records of 293 pregnant women with present and past history of hyperthyroidism were retrospectively reviewed. PATIENTS: There were 188 records of 181 patients with adequate data for inclusion in the analysis. The patients were divided into two groups according to the maternal thyroid function during the third trimester of pregnancy: hyperthyroidism (HT; 35 cases) and euthyroidism (ET; 153 cases). MEASUREMENTS: Maternal thyroid function tests were periodically evaluated before and during the third trimester of pregnancy. Neonatal thyroid function tests and birth weight of the newborn infants were also assessed. RESULTS: There was no significant difference of maternal age between HT and ET groups mean +/- SD (27.6 +/- 5.5 vs. 29.2 +/- 5.4 years). The NBW of the HT group was not significantly different from that of the ET group (2880 +/- 590 vs. 3019 +/- 426 g). However, the prevalence of infants with low birth weight (LBW) defined as NBW of lower than 2500 g in HT group was 22.9% which was significantly higher than the 9.8% in the ET group (P = 0.039, OR = 2.7, 95%CI = 1.1--7.1) and 9.7% of infants born to healthy mothers at Siriraj Hospital (control group) between 1991 and 1995 (P = 0.01, OR = 2.7, 95%CI = 1.3--6.1). The 90% CI for the true difference between the prevalence of LBW infants born to ET and HT mothers was 0.7--25.4. There was no significant difference in the prevalence of LBW infants in ET and control groups. Multiple logistic regression analyses showed that maternal hyperthyroidism during the third trimester of pregnancy was an independent factor associated with increased prevalence of LBW infants (P = 0.037, OR = 4.1, 95%CI = 1.1--15.0). CONCLUSIONS: Maternal hyperthyroidism during the third trimester of pregnancy independently increases the risk of low birth weight by 4.1-fold. Appropriate management of hyperthyroidism throughout pregnancy is essential in the prevention of this undesirable neonatal outcome.

OBJECTIVE Previous studies of the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a favourable result with methimazole (MMI). However, the efficacy of a single daily dose of propylthiouracil (PTU) was inconsistent. The present prospective randomized study was conducted to compare the efficacy of a single daily dose of MMI and PTU in the induction of euthyroidism in patients with Graves' disease. SUBJECTS Seventy-one patients with newly diagnosed Graves' disease were studied. METHODS AND MEASUREMENTS Patients were randomized to two groups to receive once daily dose of either 15 mg MMI or 150 mg PTU for 12 weeks. The therapeutic efficacy was determined biochemically by serum total T3, total T4 and TSH levels at baseline and at 4, 8 and 12 weeks during the study period. RESULTS There was no significant difference in baseline characteristics. Serum total T3 levels of the MMI group were significantly lower than those of the PTU group after four weeks of the treatment (3.54 +/- 0.72 vs. 5.49 +/- 2.74 nmol/l, P < 0.05) through the end of the study (2.22 +/- 1.42 vs. 4.30 +/- 1.78 nmol/l, P < 0.05). The changes in serum total T4 levels occurred in the same direction as serum total T3 levels but a significant difference was observed only after eight weeks of the treatment (MMI vs. PTU; 101.67 +/- 54.05 vs. 176.32 +/- 66.92 nmol/l, P < 0.05). At the end of the study, more patients in the MMI group had both serum total T3 and T4 levels less than the upper limit of the normal range compared to the PTU group (77.1% vs. 19.4%). Hypothyroidism was observed in 31.4% of the patients in the MMI group but not in the PTU group. CONCLUSIONS During 12-weeks' treatment of Graves' hyperthyroidism, a single daily dose of 15 mg of MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg of PTU. Once daily regimen of MMI not only decreased serum T3 and T4 levels more rapidly but also induced euthyroidism four times more effectively than did the once daily regimen of PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of hyperthyroidism.

Achieving fasting plasma glucose (FPG) target may not reflect hemoglobin A1c (HbA1c) target achievement.Illustrate the blood glucose patterns contributing to HbA1c7% in patients whose FPG was130 mg/dl and correlation between HbA1c and plasma glucose at various times. The contribution of caloric intake, carbohydrate consumption and glycemic index of food to plasma glucose were determined.Patients with type 2 diabetes, attended out-patient clinics at Siriraj Hospital, who had FPG of130 mg/dl but HbA1c level of7% were invited to participate in this 4-week study. They were treated with single or combined oral hypoglycemic agents except for alpha glucosidase inhibitors and glinide. Each patient performed self monitoring of capillary plasma glucose (CPG) before and 2 hours after each meal and before retiring to bed on the most convenient day in the first and fourth weeks and monitored two CPG before breakfast and before dinner weekly. Daily food intake was recorded in the logbooks.The observed patterns of CPG in 60 cases were postprandial hyperglycemia with FPG of130 mg/dl in 21.7%, a high pre-meal and post-meal CPG with FPG of130 mg/dl in 36.7% and elevated all fasting, pre-meal and post-meal CPG in 41.7% of the patients. The correlation coefficients between HbA1c at the end of the present study and CPG were 0.345, 0.40 and 0.337 at pre-breakfast, pre-lunch and pre-dinner, respectively (p = 0.01). The correlation coefficients between HbA1c and 2 hours CPG post-lunch, post-dinner and bed time were 0.402, 0.412 and 0.472, respectively (p = 0.01). The correlation between CPG and caloric intake, carbohydrate consumption or glycemic index of food were not observed.Elevated blood glucose at all times was the commonest finding in type 2 diabetic patients whose FPG130 mg/ dl but HbA1c level7%. A sole measurement of FPG should not be used to assure optimal glycemic control. Significant correlations between HbA1c and pre- or post- meal CPG indicated that frequent monitoring of pre- and post- meal could be used in assessing overall glycemic control.

To compare the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in patients with hyperthyroidism.One hundred fifty patients with proven hyperthyroidism were randomly allocated into the high (74 patients) and low (76 patients) dose regimen of I-131 treatment. Four patients of the high dose group and one patient of the low dose group were excluded because of lost follow-up. A gland-specific dosage was calculated on the estimated weight of thyroid gland and 24-hour I-131 uptake. The high and low I-131 dose regimens were 150 microCi/gm and 100 microCi/gm, respectively. The first mean radioiodine activity administered to the high and low dose group was 10.2 and 8 mCi, respectively. Repeated treatment was given to 25 patients of the high dose group and 40 patients of the low dose group. Clinical outcome and calculated costs for outpatient attendances, and laboratory tests together with initial and subsequent treatments were evaluated for one year after I-131 treatment. Elimination of hyperthyroidism that resulted in either euthyroidism or hypothyroidism was classified as therapeutic success. The cost effectiveness was also compared.At 6 months after treatment, 45 (64.3%) patients receiving high dose and 59 (78.7%) patients receiving low dose were hyperthyroidism. Clinical outcome at one year showed persistence of hyperthyroidism in 21 (30%) patients of the high dose regimen and 36 (48%) patients of the low dose regimen. At one year post treatment, it was demonstrated that the high dose regimen could eliminate hyperthyroidism in a significantly shorter time than the low dose regimen, i.e., 259.6 days and 305.5 days, respectively, p = 0.008). For the persistent hyperthyroid patients, the average total cost of treatment in the low dose group was significantly higher than that of the high dose group, i.e., 13,422.78 baht and 10,942.79 baht, respectively; p = 0.050).A high dose regimen of radioactive iodine treatment is more effective than the low dose regimen. The successful outcome of a high dose regimen occurred significantly earlier than that of the low dose regimen. For the persistent hyperthyroid patients, the average total cost in the low dose group was significantly higher than that of the high dose group.

Antibodies specific to human insulin, in sera of Thai diabetic patients and normal healthy individuals, were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit, displacement ELISA and radioimmunoassay (RIA). Among 36 insulin-treated patients, the antibodies were detected in 22, 23 and 20 individuals, by RIA, commercial ELISA kit and displacement ELISA, respectively. Among those who had never previously received insulin therapy, RIA showed positive results in 5/11 patients with insulin-dependent diabetes mellitus (IDDM) and 1/2 patients with fibrocalculous pancreatic diabetes (FCPD); but were negative in all 26 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 30 normal healthy individuals. The commercial ELISA kit could detect such insulin autoantibodies (IAA) in 4/11 IDDM, 3/26 NIDDM, 2/2 FCPD patients and 4/30 normal controls; while the displacement ELISA showed positive IAA detection in 5/11 IDDM, 2/26 NIDDM, 2/2 FCPD and 2/30 normal controls. By using RIA as the 'gold standard', the commercial ELISA kit had 92.86% sensitivity, 87.01% specificity, 88.57% accuracy, 72.22% positive predictive value and 97.10% negative predictive value; while these indices for the displacement ELISA were 85.71%, 90.01%, 89.52%, 77.42% and 94.59%, respectively.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength.To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength.In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated.Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p0.01) and QCT (5.7%, p0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p0.0001), total hip (10.8%, p0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p0.0001).Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.

The objectives of this study were to examine the effects of hyperthyroidism on glucose tolerance, insulin secretion, and insulin sensitivity.Thirty-eight patients with hyperthyroidism and twenty-six healthy volunteers with matching age and body mass index were included. Patients with conditions known to affect glucose metabolism were excluded. An oral glucose tolerance test was performed after the diagnosis of hyperthyroidism and again when they achieved euthyroid state. Areas under the glucose and insulin curves were used to assess plasma glucose and insulin responses, respectively. Beta-cell function was determined by the corrected insulin response (CIR) and homostatic model assessment model 2 (HOMA2-%B). Peripheral insulin sensitivity was determined by the insulin activity (IA) and HOMA2-%S.The prevalence of glucose intolerance in hyperthyroid state was 39.4% [impaired glucose tolerance (IGT) 31.5% and diabetes mellitus (DM) 7.9%]. This was significantly higher than that of 30.7% [IGT 19.2% and DM 11.5%] in healthy volunteers (p0.05). Glucose intolerance was associated with higher systolic blood pressure, higher mean arterial pressure, lower CIR, and higher T4 levels but not with the levels of T3. IA and HOMA2-%S significantly improved when achieving a euthyroid state despite the increase in body mass index.In conclusion, glucose intolerance is common in hyperthyroidism. Both impaired insulin secretion and decreased peripheral insulin sensitivity are the factors contributing to the development of abnormal glucose tolerance in the hyperthyroid state.

Examine the clinical and biochemical features including serum intact PTH (iPTH) and plasma PTH-related peptide (PTHrP) levels in patients with malignancy-associated hypercalcemia (MAHC).Forty-eight patients with histopathological or cytological proven malignancies and MAHC who were admitted to Siriraj Hospital were studied.The malignancies that caused MAHC were squamous cell carcinoma (45.8%), non-squamous cell solid tumors (31.3 %), and hematological malignancies (22.9%). Most patients (93.8%) had advanced stage malignancies. Corrected serum total calcium (cTCa) levels were 10.8-19.1 mg/dL (13.6 +/- 2.4) and severe hypercalcemia was observed in 17 cases (40.5%). Serum iPTH levels were 0.95-17.1 pg/mL (3.9 +/- 3.6). Most patients had suppressed serum iPTH levels of10 pg/mL. Plasma PTHrP levels were 0.2-44.0 pmol/L (3.8 +/- 6.8). There were 27 cases (56.3%) that had humoral hypercalcemia of malignancy (HHM) with plasma PTHrP levels of1.5 pmol/L, and 22 cases had squamous cell carcinoma. There was no difference in serum cTCa, phosphorus, alkaline phosphatase, and iPTH levels between patients with HHM and non-HHM. In 48 MAHC patients, serum cTCa correlated to plasma PTHrP (r = 0.35, p = 0.029) and to serum iPTH (r = 0.49, p = 0.003). In 25 patients with HHM, a stronger correlation between serum cTCa and serum iPTH (r = 0.55, p = 0.005) but not between serum cTCa and plasma PTHrP levels (r = 0.41, p = 0.05) was observed. Stepwise multiple regression analyses showed that serum iPTH but not plasma PTHrP levels independently correlated to serum cTCa levels (r = 0.39, p = 0.04).The clinical manifestations of MAHC observed in the present study were similar to those previously reported. Serum calcium correlated to serum iPTH more strongly than to plasma PTHrP levels. The low but detectable serum iPTH level might play a role in the development of severe MAHC particularly in HHM.

Weerachai Srivanichakorn,1 Apiradee Sriwijitkamol,2 Aroon Kongchoo,2 Sutin Sriussadaporn,2 Nattachet Plengvidhya,2 Raweewan Lertwattanarak,2 Sathit Vannasaeng,2 Nuntakorn Thongtang2 1Division of Ambulatory Medicine, 2Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand Background: The benefit of sulfonylureas (SUs) to patients with type 2 diabetes mellitus receiving long-term insulin treatment is unclear. This study evaluated glycemic control and beta-cell function after SU withdrawal in these patients. Methods: In this 8-week randomized controlled study, patients with type 2 diabetes who had been treated with insulin for at least 3 years plus moderate to high doses of SUs were randomly assigned to withdrawal (n=16) or continuation (n=16) of SUs. Clinical characteristics, glycemic control, hypoglycemic events, and insulin secretion, including homeostasis model assessment of beta-cell function (HOMA-B) score, C-peptide concentration, and Matsuda index, were evaluated at baseline and after 2 and 8 weeks. Results: Thirty patients (16 in the SU withdrawal group and 14 in the SU continuation group) completed the study. Median duration of diabetes was 17 (range 5–40) years. Baseline clinical characteristics, glycemic control, and HOMA-B were similar in the two groups, but the mean fasting C-peptide concentration was higher in the SU withdrawal group. After 8 weeks, the SU withdrawal group showed a significant increase in mean glycosylated hemoglobin levels from 7.8%±0.5% (62±5 mmol/mol) to 8.6%±1.2% (71±13 mmol/mol; P=0.002), whereas the SU continuation group showed a slight but not significant increase from 7.7%±0.5% (61±5 mmol/mol) to 7.9%±1.2% (63±13 mmol/mol; P=0.37). Insulin secretion, as measured by C-peptide and HOMA-B, decreased by 18% and 36%, respectively, in the SU withdrawal group. Hypoglycemic events were significantly more frequent in the SU continuation group whereas body weight did not change significantly in either group. Conclusion: Withdrawal of SU from patients with type 2 diabetes receiving long-term combination treatment with SU and insulin resulted in deterioration of glycemic control and insulin secretion. Keywords: insulin, sulfonylurea withdrawal, type 2 diabetes, long-term combination

The objective of this study was to investigate the postprandial response of leptin, an appetite-regulating hormone, to different macronutrient mixtures in Thai meals. A within-subject repeat measurement was performed. Two groups of healthy Thais (10 men and 10 women in each group) received a single meal of equal calories composed either a high carbohydrate, low fat, low protein diet (HC-LFLP, carbohydrate:fat:protein = 70%:15%:15%) or a low carbohydrate, high fat, high protein diet (LC-HFHP, carbohydrate:fat:protein = 20%:50%:30%). Fasting and 30-minute interval postprandial blood levels of leptin, insulin and glucose were measured for a 2-hour period. In comparison to the LC-HFHP meal, the HC-LFLP meal produced a greater increase in glucose and insulin levels, but halted leptin from decreasing. Postprandial leptin levels were suppressed by a LC-HFHP meal but not by a HC-LFLP meal. The reduced leptin in conjunction with lower glucose and insulin levels may encourage overeating in habitual LC-HFHP diet consumers.

Fibrocalculous pancreatopathy is a form of diabetes, associated with tropical chronic calcific pancreatitis, in which islet beta-cell loss and pancreatic stone formation are found. It is likely to be a multifactorial disease with both genetic and environmental components. Regenerating (reg) gene encodes protein that has been involved in pancreatic lithogenesis and the regeneration of islet cells and therefore the abnormality of reg genes could be associated with fibrocalculous pancreatopathy. In this study, regla and reg1beta mRNAs were isolated from peripheral blood lymphocytes obtained from 16 patients with fibrocalculous pancreatopathy, 42 patients with type 1 diabetes, 37 patients with type 2 diabetes, and 22 normal controls. mRNAs were amplified by reverse-transcription polymerase chain reaction (RT-PCR) and analysed by a single strand conformation polymorphism (SSCP) technique. The reg1alpha and reg1beta mRNAs were isolated, indicating the ectopic expression of these genes in peripheral blood lymphocytes; however, variation among mobility patterns was not observed in the SSCP analysis of the RT-PCR products. The results indicated that there was no abnormality of the regla and reg1beta mRNAs obtained from the study groups.

In order to investigate whether there would be any association between abnormalities of either reg1 alpha or reg1 beta gene and diabetes mellitus in man, these two genes were analyzed in 42 patients with type 1 diabetes mellitus, 12 with fibrocalculous pancreatopathy, 37 with type 2 diabetes mellitus, and 22 normal controls, by PCR-SSCP analysis and nucleotide sequencing technique. Polymorphism in the reg1 alpha gene resulted in three mobility patterns in the PCR-SSCP analysis, due to nucleotide constituents at position -10 before exon 1 being either C/C, T/C or T/T. These three mobility patterns were observed in every group of subjects. The analysis of reg1 beta gene showed nucleotide substitutions in exon 4 in one patient, exon 5 in another patient with type 1 diabetes, and in exon 4 and intron 5 in one patient with fibrocalculous pancreatopathy. The nucleotide substitutions in exon 4 in the patient with type 1 diabetes and that with fibrocalculous pancreatopathy occurred at codons 103 and 84 while that in exon 5 in the patient with type 1 diabetes occurred at codon 141, changing the codons from CAT to CAC, GTG to GCG, and ACT to AAT and resulting in H103H silent, V84A and T141N missense mutations, respectively. In conclusion, using PCR-SSCP and nucleotide sequence analyses, we did not find any association between abnormalities of either reg1 alpha or reg1 beta gene with any type of diabetes studied.

To determine whether a fasting plasma glucose (FPG) cutpoint of 7.0 mmol/l can be appropriately used for detection of diabetes mellitus (DM) in the Thai population, different FPG cutpoints were evaluated for their efficacy in the diagnosis of DM. A plasma glucose level ofor = 11.1 mmol/l at 2 h after a 75-g oral glucose tolerance test (OGTT) was used as the gold standard criterion for diagnosis of DM. OGTT was performed in 496 subjects who were at risk of developing diabetes. They were 120 males and 376 females, 14-76 years old (mean +/- S.D. = 45.0 +/- 12.2 years). Plasma glucose level was determined in NaF preserved plasma using the glucose oxidase method. Diagnosis of DM was made in 22.8% of cases by the gold standard criterion as compared to 4.2% by using FPG values ofor = 7.8 mmol/l. The sensitivity of the FPG cutpoint of 7.8 mmol/l was 18.6%. Diagnosis of DM using FPGor = 7.0 mmol/l improved the sensitivity to 33.6% with a positive predictive value of 100% and highest Youden's index of 0.836. The receiver operating characteristic curve of FPG revealed the best cutpoint to lie between 5.6-6.0 mmol/l. A FPG cutpoint of6.0 mmol/l over-estimated the prevalence of diabetes. DM and impaired glucose tolerance were noted in 65.6 and 29.5% of the subjects who had FPG values between 6.0 and 6.9 mmol/l, respectively. We conclude that FPG cutpoint of 7.0 mmol/l is applicable to a high risk Thai population for detection of DM. OGTT is recommended for definitive determination of glucose tolerance status in those individuals with FPG values between 6.0 and 6.9 mmol/l.

Dietary P restriction increases renal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] biosynthesis through stimulation of proximal tubule 25-hydroxyvitamin D3-1 alpha-hydroxylase (1-OHase). Because insulin-like growth factor I (IGF-I) is required for 1-OHase stimulation by low-P diet (LPD) and because 1-OHase stimulation by low-Ca diet and parathyroid hormone is lost with aging, studies were undertaken to determine whether 1-OHase activity during LPD is impaired with age and whether IGF-1 can increase 1-OHase activity in adult rats. Five days of LPD increased in vitro 1-OHase activity in young (97.3 +/- 13.5 vs. 49.7 +/- 6.8 pg.mg protein-1.5 min-1, P < 0.005) but not adult (42.3 +/- 5.37 vs. 41.2 +/- 8.9) rats. In LPD-fed adult rats, recombinant human IGF-I (rhIGF-I, 1.4 mg.kg body wt-1.day-1) for 72 h increased 1-OHase (65.2 +/- 5.88 vs. 95.1 +/- 7.26 pg.mg protein-1.5 min-1, P < 0.005). The results show that the rise in 1-OHase activity during LPD is lost in adult rats and that rhIGF-I can overcome the inhibition and stimulate renal 1-OHase activity to levels observed in young animals. The studies indicate that the age-related loss of 1-OHase activity is reversible.

Studies of the relationship between PTH structure and function in the activation of protein kinases have revealed that different regions within the biologically active PTH-(1-34) peptide are responsible for different functions. The first two N-terminal amino acids are required for plasma membrane adenylyl cyclase stimulation, and the C-terminal region 29-32 is necessary for the translocating activity of protein kinase C. In the present study, we explored the structure-function relationship of human (h) PTH in the regulation of the vitamin D receptor (VDR) in osteoblast-like cells (ROS 17/2.8). VDR-rich cytosol extract was prepared after the confluent cells were incubated with different hPTH fragments for 16 h. hPTH-(1-34) at concentrations of 10(-9)-10(-7) M caused a dose-dependent decrease in VDR content from a control level of 70.2 +/- 2.2 fmol/mg protein to 62.1 +/- 3.3 (-16%) at 10(-9) M, 52.3 +/- 5.3 (-25.5%; P0.02) at 10(-8) M, and 45.5 +/- 3.5 fmol/mg protein (-35.3%; P = 0.001) at 10(-7) M (n = 6). hPTH-(1-31) also decreased VDR content from 65.5 +/- 3.6 to 55.2 +/- 7.9 (-19.5%) at 10(-9) M, 44.3 +/- 5.8 (-32.4%; P0.05) at 10(-8) M, and 40.6 +/- 3.2 fmol/mg protein (-38.9%; P0.05) at 10(-7) M (n = 6). Incubation of ROS 17/2.8 cells with 0.5 nM 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] led to up-regulation of VDR content by 340-370% of the control value. hPTH-(1-34) decreased the VDR up-regulatory effect of 1,25-(OH)2D3 from 340% to 230% of the control value at 10(-8) M (P0.0001) and 170% of the control value (P0.0001) at 10(-7) M, respectively (n = 6). hPTH-(1-31) also decreased the receptor up-regulatory effect of 1,25-(OH)2D3 from 370% to 286% (P0.02) at 10(-8) M and 220% (P0.002) at 10(-7) M, respectively (n = 6). hPTH-(3-34) and -(13-34) at concentrations of 10(-9)-10(-7) M did not decrease VDR content in either the absence or presence of 1,25-(OH)2D3. Quantitation of VDR messenger RNA by reverse transcription-polymerase chain reaction showed that PTH-(1-34) and -(1-31) at 10(-7) M, but not PTH-(3-34) and -(13-34), inhibited ROS 17/2.8 cell VDR gene expression in both the absence and presence of 1,25-(OH)2D3.(ABSTRACT TRUNCATED AT 400 WORDS)