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Biomedical subjects

S T Haden

Publications and source records attributed to S T Haden.

5 recordsLinked to original sources

The effects of age and gender on parathyroid hormone dynamics.

BACKGROUND AND AIMS: Hyperparathyroidism is a risk factor for bone loss. An age-related increase in parathyroid hormone (PTH) level has been demonstrated in several studies. It has been suggested that the type II osteoporotic syndrome, a condition of increased prevalence among elderly women, may be at least partially caused by elevations in intact parathyroid hormone (iPTH) levels. To date, however, the effects of age and gender per se on PTH dynamics in healthy subjects independent of other risk factors such as vitamin D deficiency and/or impaired renal function that can impact on parathyroid function, remain unknown. In this study, we used citrate and calcium (Ca) infusions to characterize the impact of age and gender on PTH dynamics in normal subjects. SUBJECTS AND METHODS: Twelve young women with mean age +/- SD of 26.4 +/- 1.6 years, 12 young men with mean age of 26.6 +/- 1.3 years, 12 older women with mean age of 68.6 +/- 1.3 years and 12 older men with mean age of 67.2 +/- 1.6 years were studied. The sigmoidal curves relating serum iPTH to serum levels of ionized Ca (Cai) were characterized by maximal and minimal iPTH levels, the set-points (levels of Cai causing half-maximal suppression of iPTH), and the slopes of the curves at the set-points. RESULTS: Baseline serum Ca, Cai, 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D [1,25(OH)2D3] levels, as well as the set-points, slopes and minimal values of the sigmoidal curves relating Cai to iPTH, did not differ among the four groups. iPTH levels at baseline were slightly but not significantly higher in the older age groups (P = 0.18). The maximal iPTH level was 25% higher in the older women than in the younger women, although this difference was not significant (P = 0.29). However, the integrated iPTH responses calculated from the areas under the curves (AUC) of iPTH levels vs. time during the calcium and citrate infusions were significantly higher in postmenopausal women than in young women during both infusions and in older men than in young men during the calcium infusion. There was no effect of gender on serum iPTH levels. CONCLUSIONS: In both women and men, ageing per se, independent of changes in vitamin D economy or renal function, is associated with an increase in integrated PTH secretory response to changes in serum calcium. No alterations in the Cai/iPTH set-point were present. The biological relevance of these modest increments in integrated iPTH levels during dynamic testing in older healthy men and women remain uncertain.

Adult

Calcidiol and PTH levels in women attending an osteoporosis program.

We performed a retrospective study of 237 patients attending a specialty osteoporosis practice. Secondary causes for reduced bone mineral density (BMD) were evaluated in 196 postmenopausal women and 41 premenopausal women; mean age was 56 +/- 13.8 years (mean +/- SD). BMD was measured by dual-energy X-ray absorptiometry (DXA) (QDR 1000W/2000 Hologic). Levels of intact parathyroid hormone (iPTH), calcidiol [25(OH)D], thyroid-stimulating hormone, and 24-hour urinary calcium were measured, and serum and urine protein (SPEP and UPEP) electrophoresis were performed. Overall, 16% of our patients had 25(OH)D levels <15 ng/ml, the lowest acceptable vitamin D level without a concomitant rise in iPTH levels. Among the osteoporotic patients (T score <-2.5 SD), 17% had 25(OH)D levels <15 ng/ml and 7% <10 ng/ml. Among the osteopenic patients (-2.5 < T < -1.0 SD), 11% had 25(OH)D levels <15 ng/ml. Seventeen percent of patients with Z score </=-1.0 SD (low range normal value) had 25(OH)D levels <15 ng/ml. Low 25(OH)D levels were inversely related to high iPTH values (r = 0.30, P < 0.0001). Hypercalciuria was present in 15% of our patients, elevations of PTH levels (>65 pg/ml, upper normal limit of assay) were present in 11.5%, and hyperthyroidism in 4%. A 25(OH)D level of <25 ng/ml in women (n = 86) with no known secondary causes of low BMD was associated with an iPTH level above 49 pg/ml. The measurement of 25(OH)D levels is recommended in the evaluation of secondary causes for reduced BMD. Supplementation with vitamin D appears needed to keep 25(OH)D above 25 ng/ml, the level required to prevent increments in iPTH levels.

Absorptiometry, Photon

The effect of lithium on calcium-induced changes in adrenocorticotrophin levels.

The calcium receptor (CaR) plays a central role in calcium (Ca) sensing by the parathyroid gland and other organs, including the brain. Chronic lithium (Li) therapy causes a significant alteration in Ca-sensing by the CaR-expressing parathyroid chief cells through an unknown mechanism, shifting the PTH set-point (the level of Ca that half-maximally suppresses PTH secretion) to the right. Ca is known to stimulate ACTH levels in normal subjects, and baseline ACTH levels are increased in patients with bipolar disorder. Because the stimulation of ACTH secretion by Ca likely involves the CaR, the aim of this study was to investigate the effects of Li on Ca-induced changes in ACTH levels, using Ca and citrate infusions in seven Li-treated patients and seven controls. During the Ca infusion, increments in serum-ionized Ca concentration (Ca(i)) were accompanied by increments in ACTH levels that were significantly greater in the Li-treated group, P = 0.014, by ANOVA. Also, cortisol levels increased significantly in the Li-treated, but not the control group, during the Ca infusion, P < 0.0001. There was a statistically significant shift in the midpoint of the Ca(i)/ACTH curve, to the right, in the Li-treated group, compared with the controls (P = 0.042), that was largely caused by an effect of Li on Ca(i). However, for comparable levels of Ca(i), there were no significant differences in the levels of ACTH between the two groups. Therefore, within the physiological range of Ca, there was no effect of Li on Ca(i)-induced change in ACTH levels.

Adrenocorticotropic Hormone

Subclinical thyrotoxicosis.

Subclinical thyrotoxicosis is defined as low serum thyrotropin (TSH) and normal serum thyroid hormone concentrations. It must be distinguished from nonthyroidal illness and secondary hypothyroidism. The most common causes are excessive thyroid hormone therapy, autonomously functioning thyroid adenoma, multinodular goiter, and Graves' disease, but many patients have no evident thyroid disease. A few patients have minor symptoms and signs of hyperthyroidism. The likelihood of progression to overt thyrotoxicosis is low, and many patients have normal serum TSH concentrations weeks or months later. Treatment should be based on consideration of the cause of the subclinical thyrotoxicosis, and whether the patient has any clinical manifestations of thyroid hormone excess or underlying problems likely to be aggravated by small increases in thyroid secretion.

Humans

Alterations in parathyroid dynamics in lithium-treated subjects.

Chronic lithium (Li) therapy, used extensively in the treatment of bipolar affective disorders, is one of psychiatry's most effective treatments. The data on the effects of Li on baseline PTH and calcium (Ca) levels are conflicting. A clear resetting of the PTH set-point to the right was documented in vitro; however, the effect of Li on the Ca-PTH axis has not been rigorously studied in vivo. In this study, we used a Ca and citrate infusion protocol to fully characterize PTH dynamics in seven female patients, 40 +/- 11 yr old, on chronic Li therapy for 5.23 +/- 4.0 yr, compared with seven controls, 41 +/- 16 yr old (mean +/- SD). Baseline ionized Ca (Cai) and intact PTH levels were 5.2 +/- 0.06 mg/dL and 38.4 +/- 5.7 pg/mL in the Li group and 4.9 +/- 0.06 mg/dL and 21.2 +/- 5.0 pg/mL in the controls, (mean +/- SEM) P = 0.008 and 0.042, respectively. We defined an inverse sigmoidal curve between Cai and the intact biologically active PTH molecule (iPTH) for the two study groups and demonstrated a significant shift in the iPTH set-point to the right in the Li-treated patients, compared with controls. The set-point was 5.08 +/- 0.04 for the former group and 4.88 +/- 0.04 mg/dL for the latter, P = 0.004. Patients on Li had significantly higher Cai levels during citrate and Ca infusions, P = 0.0008 and 0.012, respectively; however, iPTH levels were not significantly different between the two study groups during either infusion. The shift in the iPTH set-point to the right in the Li-treated patients and the similar iPTH levels, despite higher serum Cai levels during both infusions, establish the presence of a clear alteration in PTH dynamics in patients on chronic Li therapy.

Adult