| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
Departments of Medicine, Pediatrics, and Biomathematics (W.G.G., T.R.B., A.J.V.H., I.B.S.), University of California at Los Angeles School of Medicine, Los Angeles, California 90095; Division of Endocrinology, Department of Internal Medicine (J.D.V.), University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; and Endocrine Unit (H.J.), Massachusetts General Hospital, Boston, Massachusetts 02114
Address all correspondence and requests for reprints to: William G. Goodman, Division of Nephrology, 7–155 Factor Building, University of California at Los Angeles Medical Center, 10833 Le Conte Avenue, Los Angeles, California 90095 E-mail: wgoodman{at}ucla.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Several groups of investigators have used in vivo dynamic tests of parathyroid gland function to reconstruct the inverse sigmoidal curve that depicts the relationship between blood ionized calcium and serum PTH levels and to measure the set point for calcium-regulated PTH release in patients with 2°HPT because of chronic renal failure (10, 12, 13, 14). Early reports suggested that the set point was increased in this disorder (12, 14, 15, 16), but recent evidence indicates that set point values do not differ from normal in subjects with uncomplicated uremic 2°HPT (13, 17). Technical and methodological considerations partly account for the disparity among experimental results, and fundamental differences in the modeling of PTH secretion in vivo may also contribute (9, 18). As such, alternative methods for assessing calcium-sensing by the parathyroid glands in vivo are of considerable interest.
In addition to in vivo studies based on analyses of the sigmoidal relationship between blood ionized calcium and serum PTH levels, iv calcium infusions have been used to study calcium-sensing by the parathyroids in several clinical disorders including 1°HPT and FBHH (2). This approach has provided insight into the separate roles of parathyroid gland enlargement and set point disturbances as modifiers of PTH secretion. Because parathyroid gland hyperplasia and alterations in the set point for calcium-regulated PTH release can each affect PTH secretion in chronic renal failure, the current study was undertaken to characterize the response to calcium infusions in patients with either moderate or advanced 2°HPT. Results were compared with data obtained in subjects with normal renal and parathyroid gland function and in patients with 1°HPT.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
All patients receiving regular dialysis were clinically stable; in the 31 subjects categorized as 2°HPT, an iliac crest bone biopsy after double tetracycline labeling was obtained to document the histologic subtype of renal bone disease. The skeletal lesions of renal osteodystrophy were classified by histomorphometric criteria reported elsewhere (19). Twenty-nine patients had overt osteitis fibrosa, whereas two had mild lesions of 2°HPT. None of the patients had bone aluminum deposition as judged by histochemical staining methods, and none were taking aluminum-containing medications.
Bone biopsy was done at the time of parathyroidectomy in six of eight Pre-PTX patients. In each case, there was evidence of extensive marrow fibrosis and marked increases in eroded bone perimeter and osteoclast number, findings that confirmed the presence of severe 2°HPT. None had evidence of bone aluminum deposition as judged by histochemical staining methods.
Patients with end-stage renal disease were managed by continuous cycling peritoneal dialysis using a dialysate calcium concentration of 1.75 mmol/L or by thrice weekly hemodialysis using a dialysate calcium of 1.25 mmol/L. The mean age of patients with 2°HPT was 15.6 ± 4.9 yr, range 9–38 yr, and the duration of dialysis before study was 26 ± 31 months. There were 18 female and 13 male subjects. All patients had previously been treated with daily oral doses of calcitriol, but vitamin D therapy was withdrawn at least 4 weeks before study.
The mean age of Pre-PTX patients was 32 ± 14 yr; five subjects were female and three were male. The duration of dialysis before evaluation was 5.5 ± 2.5 yr. All Pre-PTX patients had received calcitriol in the past, but none were given active vitamin D sterols during the 4 weeks immediately before study. The ages of patients with 1°HPT were 16, 64, and 82 yr, respectively; all three were women.
The average age of volunteer subjects was 21 ± 2 yr; 11 were women and 9 were men. None of the subjects with NL had a history of chronic illness or metabolic bone disease (13). All studies were approved by the UCLA Human Subjects Protection Committee, and written informed consent was obtained from all patients and volunteers.
Subjects were evaluated during 2-day admissions to the General Clinical Research Center at UCLA as previously described (13, 17). On the first day of study, 2-h iv infusions of sodium citrate were done to gradually lower blood ionized calcium concentrations to a level at least 0.2 mmol/L below preinfusion values; the dose of sodium citrate ranged from 28–118 mg/kg per h (13, 20). Blood samples for measurements of ionized calcium and PTH were obtained 30, 15, and 0 min before and every 10 min during sodium citrate infusions.
The following day, 2-h iv infusions of 10% calcium gluconate were done to gradually raise blood ionized calcium concentrations to a level at least 0.2 mmol/L above preinfusion values. The dose of calcium gluconate ranged from 2–8 mg/kg per h (13). Blood samples for measurements of ionized calcium and PTH were obtained as described previously for infusions of sodium citrate. The average of measurements obtained 30, 15, and 0 min before starting each infusion was used to determine basal values for blood ionized calcium and serum PTH for each day of study (13, 17).
Blood ionized calcium levels were monitored during calcium infusions using a calcium-specific electrode (Radiometer ICA-II, Copenhagen, Denmark); blood samples were collected anaerobically, and measurements were obtained immediately thereafter. Serum samples for PTH determinations were separated by centrifugation immediately after collection, snap frozen on solid CO2, and stored at -70 C until assay (13, 17). Ionized calcium levels were monitored after stopping calcium infusions until values returned to baseline levels. None of the patients underwent dialysis during either infusion.
Biochemical determinations
Determinations of total calcium, phosphorus, alkaline phosphatase, calcitriol, and PTH levels in serum were done using methods described elsewhere (13, 19). Serum PTH levels were measured using an immunoradiometric assay for the intact (1–84) hormone (21), and serum calcitriol levels were determined by radioreceptor assay (22).
Statistical analysis
All data are expressed as the mean ± 1 SD. Comparisons among groups were done using ANOVA with contrasts (23). Baseline blood ionized calcium and serum PTH values for each study subject represent the average of three separate determinations obtained before the start of iv infusions. Results obtained during infusions of calcium gluconate and sodium citrate were evaluated by ANOVA for repeated measures and by paired t tests with appropriate correction for multiple comparisons among groups (23).
The sigmoidal curve that describes the relationship between blood ionized calcium and serum PTH levels was determined for each study subject using the combined results obtained during sodium citrate and calcium gluconate infusions as described in detail elsewhere (7, 13). According to the four parameter model, the set point for calcium-regulated PTH release represents the ionized calcium concentration at which serum PTH levels are midway between the maximum value achieved during hypocalcemia and the minimum value attained during hypercalcemia (7, 13). A complete assessment of the sigmoidal curve in 26 patients from the current study has been reported elsewhere (17).
Results obtained during calcium gluconate infusions were separately analyzed to assess the inhibitory effect of increasing blood ionized calcium concentrations on PTH release. To improve the linear fit of the data, serum PTH levels, expressed as the natural logarithm (ln) of percent preinfusion values, were plotted against the corresponding blood ionized calcium concentration at each 10-min interval as previously described (2). Linear regression analysis was done using the method of least squares (23), and slope and y-intercept values were compared using the t statistic (23). A monoexponential curve fitting algorithm of the form y = A e-kt + B was also used to examine the curvilinear relationship between blood ionized calcium and serum PTH levels during iv calcium infusions; these results are presented as mean values with 95% confidence intervals (24).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
), and values exceeded
200 pg/mL in all patients; thus, 29 of 31 patients had bone biopsy
evidence of osteitis fibrosa, whereas 2 had mild lesions of 2°HPT. As
expected, serum PTH levels in Pre-PTX patients were greater than in
subjects with 2°HPT (Table 1). Although values were considerably
lower than in either group of subjects with uremic 2°HPT, serum PTH
levels in all three patients with 1°HPT exceeded the upper
limit of normal (Table 1).
|
). Blood ionized calcium levels were markedly
elevated, however, in patients with 1°HPT, and values exceeded those
in Pre-PTX patients (Table 1). Neither age nor gender distribution
differed among groups (Table 1).
As reported previously in a smaller number of patients (13), set point
estimates obtained using the four parameter model did not differ
between subjects with 2°HPT and those with NL (Table 1), but there
were marked differences in the response to calcium infusions between
groups. When expressed as a percentage of preinfusion levels to account
for differences in baseline values, serum PTH levels declined more
slowly during 2-h calcium infusions in patients with 2°HPT, and
values at each 10-min sampling interval remained substantially higher
than in normal volunteers (Fig. 1). Both
the rate of increase, 0.105 ± 0.039 vs. 0.154 ±
0.045 mmol/L per h, and the total increase in blood ionized calcium,
0.23 ± 0.07 vs. 0.30 ± 0.09 mmol/L, were less,
however, in patients with 2°HPT than in subjects with normal renal
and parathyroid gland function, P < 0.05 for each.
|
Although neither the rate of change in blood ionized calcium nor the
total increase in ionized calcium differed between patients with
2°HPT and subjects with NL (Fig. 2),
serum PTH levels fell to 24.7 ± 11.2% of preinfusion values in
patients with 2°HPT and to 12.0 ± 3.5% of preinfusion values
in those with normal renal and parathyroid gland function,
P < 0.005 (Fig. 3). The
lowest serum PTH levels achieved during calcium infusions occurred
after 90–100 min in patients with 2°HPT, whereas nadir PTH levels
were seen after only 50–60 min in subjects with NL (Fig. 3).
|
|
). The lowest serum PTH level achieved during calcium
infusions was 44.1 ± 8.2% of preinfusion values in Pre-PTX
patients; this result exceeded that observed both in normal volunteers,
P < 0.001, and in those with 2°HPT,
P < 0.001. Similarly, serum PTH levels declined to
only 50.0 ± 29.6% of preinfusion values during calcium infusions
in patients with 1°HPT; nadir PTH levels were higher than those of
normal subjects or patients with 2°HPT, P < 0.001
for each, but nadir PTH levels did not differ between 1°HPT and
Pre-PTX [not significant (NS)].
The relationship between the total increase in blood ionized calcium
during 2-h calcium infusions and serum PTH levels at the end of
infusions also differed from normal in each group of patients with
hyperparathyroidism (Fig. 4). When
compared with normal subjects who demonstrated equivalent increases in
blood ionized calcium, serum PTH levels at the end of 2-h calcium
infusions were substantially higher in patients with 2°HPT (Fig. 4).
Smaller reductions in serum PTH levels from preinfusion values were
observed both in Pre-PTX patients and in those with 1°HPT (Fig. 4)
despite equivalent increases in blood ionized calcium; the results did
not differ, however, between Pre-PTX and 1°HPT (Fig. 4).
|
and 6). The slope of this regression
reflects the extent to which serum PTH levels decrease as ionized
calcium concentrations rise, and values differ according to the size of
parathyroid adenomas in patients with 1°HPT (2). Because the largest
fractional reductions in serum PTH occurred during the first 30–60 min
of calcium infusions in each group, and because the rates of increase
in blood ionized calcium did not differ during this interval, separate
slope determinations were obtained not only for the full 120 min of
study but also for both the initial 30 min and the first 60 min of
calcium infusion in each subject.
|
|
and 3). A better linear fit
of the log transformed PTH data was obtained when results for the
initial 30 min and for the first 60 min of calcium gluconate infusions
were examined separately (Figs. 5 and 6). For each interval, slope
values were lower in patients with 2°HPT than in subjects with NL
(Figs. 5 and 6). Even greater reductions in slope were seen in Pre-PTX
patients, and slope values in this group were less than in patients
with 2°HPT, P < 0.05. Slope estimates did not differ
in Pre-PTX and 1°HPT, but the relationship between serum PTH levels
and blood ionized calcium concentration was displaced to the right in
both groups (Figs. 5 and 6).
A monoexponential curve fitting algorithm was also used to examine the
full 120-min PTH suppression curve in NL, 2°HPT, and Pre-PTX (Table 2). The amplitude of suppression
during calcium infusions was less in 2°HPT than in NL, whereas the
half-time of suppression was greater in 2°HPT than in NL (Table 2).
Basal serum PTH values, or the lowest serum PTH levels achieved toward
the end of 2-h calcium infusions, were also greater in 2°HPT than in
NL. The amplitude of suppression was further reduced in Pre-PTX
patients, whereas both the half-time of suppression and basal PTH
values were substantially greater in Pre-PTX patients than in 2°HPT
(Table 2).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Alterations of the regulation of PTH secretion by calcium have been documented by several techniques in 1°HPT and FBHH, but the role of a calcium-sensing defect in 2°HPT because of chronic renal failure remains controversial (1, 2, 5, 9, 10, 11, 18, 25). In FBHH, an inactivating mutation of one allele of the gene encoding the calcium-sensing receptor modifies the normal relationship between blood ionized calcium and serum PTH levels; thus, higher than normal calcium concentrations are required to fully suppress PTH release from the parathyroid glands, and persistent hypercalcemia develops (4). A set point abnormality is the term most often used to describe this disturbance, reflecting the physiological regulation of PTH secretion around a calcium level that is higher than that of subjects with normal parathyroid gland function (1, 2, 18).
Set point disturbances have also been documented using both in vitro and in vivo methods in 1°HPT (5, 6, 7, 25). In addition to a set point abnormality, however, differences in parathyroid gland size can separately affect PTH secretion in patients with 1°HPT; thus, calcium infusions fail to lower PTH levels normally, whereas equivalent increases in blood ionized calcium fully suppress PTH release in patients with FBHH and in normal subjects (2). The results of the current investigation confirm the attenuated response to calcium infusions in subjects with 1°HPT, providing further support for the view that parathyroid gland enlargement independently modifies the inhibitory effect of calcium on PTH release by the parathyroid glands even in subjects with a set point abnormality.
Since parathyroid gland hyperplasia is an integral feature of 2°HPT because of chronic renal failure, parathyroid gland enlargement almost certainly contributes to excess PTH secretion in this disorder (26, 27). Several groups of investigators have used in vivo dynamic tests of parathyroid gland function to study the regulation of PTH secretion by calcium in 2°HPT, but a number of methodological considerations limit the interpretation of these results (9, 10, 12, 13, 14, 18). The influence of variations in parathyroid gland size on estimates of the set point in vivo cannot be adequately controlled, and reliable noninvasive measures of parathyroid gland size are not yet available (9, 18); this may partially explain why alterations in the set point have not been a consistent finding using in vivo dynamic tests of PTH secretion in patients with renal 2°HPT (10, 12, 13, 14, 28). Alternative methods for evaluating the regulation of PTH release by calcium in patients with chronic renal failure are, therefore, of considerable interest.
In the current investigation, estimates of the set point for calcium-regulated PTH release were obtained using the four parameter model of Brown et al. in patients with uncomplicated 2°HPT, in subjects with treatment-refractory 2°HPT who were about to undergo parathyroidectomy, in patients with 1°HPT, and in subjects with normal renal and parathyroid gland function. As reported previously in a smaller number of patients (13), neither basal blood ionized calcium levels nor estimates of the set point differed from normal in 2°HPT, but the inhibitory effect of calcium on PTH release was markedly attenuated when the response to iv calcium infusions was separately examined. The rate of decline in serum PTH levels from preinfusion values was reduced, and the lowest serum PTH level achieved during calcium infusions was substantially greater in 2°HPT than in normal volunteers. Changes similar to these were reported by Indridason and co-workers (29) when high dialysate calcium concentrations were used to raise blood ionized calcium levels during hemodialysis procedures in patients with 2°HPT. Further reductions in the inhibitory effect of calcium on PTH secretion were seen in Pre-PTX patients, whereas the response to calcium infusions did not differ between Pre-PTX patients and those with 1°HPT. Set point estimates and basal blood ionized calcium levels were modestly elevated in Pre-PTX patients, but values were considerably higher in those with 1°HPT.
The higher set point values determined in vivo in the current study in Pre-PTX and in 1°HPT are in agreement with the early in vitro findings of Brown et. al. using dispersed parathyroid cells obtained from glands harvested at surgery from patients with either primary or 2°HPT; thus, in vitro measurements of the set point for calcium-regulated PTH release exceeded those determined in normal parathyroid cells in both clinical disorders (5, 30, 31). The results of these in vitro studies and findings reported subsequently by others using dispersed parathyroid cell preparations (32, 33, 34) serve as the basis for the contention that the set point for calcium-regulated PTH release is abnormal in 2°HPT because of chronic renal failure. Previous investigations have not, however, assessed patients with less advanced 2°HPT and compared the results with data obtained concurrently in normal volunteers, subjects with advanced 2°HPT, and those with 1°HPT as reported herein. Such studies have not been possible using in vitro techniques because parathyroid tissue is not readily available from patients with mild or moderate uremic 2°HPT who do not require surgical treatment. Similarly, although Kifor et al. (35) demonstrated reductions in parathyroid cell calcium receptor expression both in 1°HPT and in advanced 2°HPT, the level of calcium receptor expression in less severe 2°HPT remains unknown.
To further characterize calcium-sensing by the parathyroid glands in vivo, serum PTH levels, expressed as the natural logarithm (ln) of percent preinfusion values, were plotted against the corresponding blood ionized calcium concentration at each 10-min interval during calcium gluconate infusions. The slope of this relationship, which reflects the decline in PTH per unit increase in ionized calcium, was less in patients with 2°HPT than in subjects with normal renal and parathyroid gland function. Similar decreases in slope were reported by Khosla et al. (2) in 1°HPT in which a reduction in the inhibitory effect of calcium on PTH release corresponded to the weight of parathyroid tissue removed surgically; thus, patients with large parathyroid adenomas had less negative slope values, whereas those with small parathyroid tumors had more negative slope values that did not differ from those determined in normal subjects.
The reduction in the slope of the relationship between log transformed serum PTH values and blood ionized calcium levels reported previously in 1°HPT was confirmed in the current study. When compared with subjects with normal renal and parathyroid gland function, slope values were also less both in subjects with 2°HPT and in Pre-PTX patients; the extent of the change in slope was greater, however, in Pre-PTX than in 2°HPT, whereas there were no differences in slope values between Pre-PTX and 1°HPT. Overall, the current results strongly suggest that functional parathyroid gland enlargement accounts for the blunted inhibitory effect of calcium on PTH release not only in 1°HPT but also in both moderate and advanced 2°HPT.
As reported previously, the slope of the regression between blood ionized calcium and serum PTH levels does not differ from normal in patients with FBHH (2), a finding that stands in marked contrast to the results of the current investigation in subjects with 2°HPT, in Pre-PTX patients, and in those with 1°HPT (2). As such, the molecular defect that accounts for an increase in the set point for calcium-regulated PTH release in FBHH is insufficient to fully explain the suboptimal inhibitory effect of calcium on PTH release in either primary or 2°HPT as assessed by the slope of the PTH suppression curve during iv calcium infusions; this change more likely reflects the increase in parathyroid gland mass in both disorders.
Neither alterations in the degradation of PTH nor the detection of carboxy-terminal fragments of PTH by the immunoradiometric assay for intact 1–84 PTH are likely to account for differences among groups in the slope of decline in serum PTH levels during calcium infusions (36, 37). Carboxy-terminal PTH fragments are rapidly cleared from the circulation in subjects with normal renal function (38), and serum creatinine values were normal in all patients with 1°HPT in the current study. Variations in the serum half-life of PTH during calcium infusions also cannot account for differences in the rate of decline in serum PTH values between subjects with 2°HPT and Pre-PTX patients, because both groups of subjects had end-stage renal disease with minimal or no residual renal function. In addition, variations in PTH half-life would not influence the steady state level of PTH achieved at maximum suppression during calcium infusions, which differed substantially among groups.
In the current study, basal serum ionized calcium levels did not
differ from normal in patients with 2°HPT, but values were moderately
elevated in Pre-PTX patients and even more markedly increased in those
with 1°HPT. Because high basal ionized calcium levels are an integral
feature of both 1°HPT and FBHH (2), the absence of this change in
2°HPT argues against an alteration in the set point for
calcium-regulated PTH release in this disorder. In contrast, the higher
blood ionized calcium levels and the rightward displacement of the
relationship between log PTH values and blood ionized calcium in
Pre-PTX patients suggest that a set point disturbance that is less
pronounced than that found in 1°HPT is present in subjects with more
advanced 2°HPT (see Figs. 5 and 6).
Although serum PTH values generally reflect the degree of parathyroid gland hyperplasia in patients with 2°HPT, basal serum PTH levels did not correlate with the overall percentage reduction in serum PTH during 2-h calcium infusions, r = -0.19, NS, or with the slope of the linearized ionized calcium-PTH curve, r = -0.02, NS, either in patients with 2°HPT or in Pre-PTX patients. Such findings differ from those reported previously in 1°HPT (2), and they suggest that the inhibitory effect of calcium on PTH release, although subnormal, does not vary according to the biochemical severity of disease in those with 2°HPT. The lower slope values in Pre-PTX patients are consistent, however, with the more extensive parathyroid gland enlargement that characterizes individuals who require parathyroidectomy to control progressive 2°HPT because of end-stage renal disease.
In summary, the inhibitory effect of calcium on PTH release is diminished in 2°HPT because of chronic renal failure, but the magnitude of the defect does not differ with the biochemical severity of the disorder. More striking reductions in the inhibitory effect of calcium on PTH release are evident in advanced 2°HPT, and the extent of this change is similar to that seen in 1°HPT. Parathyroid gland enlargement rather set point disturbances account for the blunted inhibitory effect of calcium on PTH release both in 1°HPT and 2°HPT, but evidence of a calcium-sensing defect is confined to those with either advanced 2°HPT or 1°HPT. Abnormalities in calcium-sensing by the parathyroids are a late rather than an early consequence of parathyroid gland hyperplasia in patients with end-stage renal disease.
|
Footnotes |
|---|
Received February 10, 1998.
Revised March 31, 1998.
Accepted April 7, 1998.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  J. D. Veldhuis, D. M. Keenan, and S. M. Pincus Motivations and Methods for Analyzing Pulsatile Hormone Secretion Endocr. Rev., December 1, 2008; 29(7): 823 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. M. de Francisco, M. Izquierdo, J. Cunningham, C. Pinera, R. Palomar, G. F. Fresnedo, J. A. Amado, M. G. Unzueta, and M. Arias Calcium-mediated parathyroid hormone release changes in patients treated with the calcimimetic agent cinacalcet Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2895 - 2901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Felsenfeld, M. Rodriguez, and E. Aguilera-Tejero Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1283 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rodriguez, E. Nemeth, and D. Martin The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism Am J Physiol Renal Physiol, February 1, 2005; 288(2): F253 - F264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Bas, E Aguilera-Tejero, A Bas, J C Estepa, I Lopez, J A Madueno, and M Rodriguez The influence of the progression of secondary hyperparathyroidism on the set point of the parathyroid hormone-calcium curve J. Endocrinol., January 1, 2005; 184(1): 241 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Chen and W. G. Goodman Role of the calcium-sensing receptor in parathyroid gland physiology Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1005 - F1011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. H. Jorna, T. J. M. Tobe, R. M. Huisman, P. E. de Jong, J. T. M. Plukker, and C. A. Stegeman Early identification of risk factors for refractory secondary hyperparathyroidism in patients with long-term renal replacement therapy Nephrol. Dial. Transplant., May 1, 2004; 19(5): 1168 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. G. Goodman Medical management of secondary hyperparathyroidism in chronic renal failure Nephrol. Dial. Transplant., March 1, 2003; 18(90003): iii2 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Raposo, L. G. Sobrinho, and H. G. Ferreira A Minimal Mathematical Model of Calcium Homeostasis J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4330 - 4340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Petrasek, R. Samtaney, and D. S. Cohen Glandular regulation of interstitial diffusion: a model and simulation of a novel physiological mechanism Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E195 - E206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Imanishi, H. Tahara, N. Palanisamy, S. Spitalny, I. B. Salusky, W. Goodman, M. L. Brandi, T. B. Drueke, E. Sarfati, P. Urena, et al. Clonal Chromosomal Defects in the Molecular Pathogenesis of Refractory Hyperparathyroidism of Uremia J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1490 - 1498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Olaizola, J. Zingraff, C. Heuguerot, L. Fajardo, A. Leger, J. Lopez, G. Acuna, A. Petraglia, A. Alvarez, H. Caorsi, et al. [99mTc]-Sestamibi parathyroid scintigraphy in chronic haemodialysis patients: static and dynamic explorations Nephrol. Dial. Transplant., August 1, 2000; 15(8): 1201 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Brown, T. T. Brierley, N. Palanisamy, I. B. Salusky, W. Goodman, M. L. Brandi, T. B. Drüeke, E. Sarfati, P. Ureña, R. S. K. Chaganti, et al. Vitamin D Receptor as a Candidate Tumor-Suppressor Gene in Severe Hyperparathyroidism of Uremia J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 868 - 872. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||
) and in 31 patients with 2°HPT (•). Rate
of rise in blood ionized calcium was less, however, in those with
2°HPT. Values are means ± 1 SD.
), and three patients with
1°HPT (
). Values are means ± 1 SD. A subset of
subjects from 2°HPT and from NL were selected to provide comparisons
among groups in whom rates of change in blood ionized calcium did not
differ during calcium gluconate infusions.
