Calcium-regulated parathyroid hormone secretion in adynamic renal osteodystrophy

Kidney International, Vol. 48 (1995), pp. 838—843

Calcium-regulated parathyroid hormone secretion in adynamic renal osteodystrophy CHERYL P. SANCHEZ, WILLIAM G. GOODMAN, JORGE A. RAMIREZ, BARBARA GALES, THoMAs R. BELIN, GINO V. SEGRE, and ISIDRO B. SALUSKY Departments of Pediatrics, Radiology, Medicine and Biomathematics, UCLA School of Medicine, Los Angeles, California; and the Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

intense calcitriol therapy, the ingestion of large amounts of

Calcium-regulated parathyroid hormone secretion in adynamic renal osteodystrophy. Hypercalcemia and low serum parathyroid hormone

calcium orally, high dialysate calcium levels and treatment with peritoneal dialysis [3, 4, 10, 11], each of which can lower parathyroid hormone (PTH) secretion. Although the regulation of PTH secretion has been extensively evaluated in patients with secondary hyperparathyroidism [12— 15], little is known about parathyroid gland function in patients with adynamic renal osteodystrophy. Felsenfeld et al reported that both the set point and the slope of the sigmoidal calcium-PTH curve were lower in adult hemodialysis patients with the adynamic lesion than in those with osteitis fibrosa [161. These findings were based, however, on studies done during hemodialysis procedures

(PTH) levels are features of the adynamic lesion (AD) of renal osteodystrophy, but there is little information about parathyroid gland function in this disorder. Therefore, the four parameter model was used to evaluate calcium-regulated PTH release in patients with either adynamic bone or secondary hyperparathyroidism (OF) as documented by bone biopsy and in normal volunteers (NL). Patients had undergone CCPD for 20 4.2 months, and all received calcium carbonate as the sole phosphate-binding agent. During two hours infusions of sodium citrate, the rate of decline in serum ionized calcium levels did not differ among groups; serum PTH levels rose from 136 38 to 342 140 pg/mI in AD and from 691 99 to 869 121 pg/mi in OF. Maximum PTH levels were 322 42% of baseline values in AD but only 146 9.7% of baseline in OF (P < 0.001), and the increase above baseline levels in AD did not differ from that in NL (300 25%, NS). During calcium infusions, serum PTH Jevels fell from 164 75 to 39 11 pg/mI in AD and from 622 76 to 171 29 pg/mi

when rapid changes in plasma pH, glucose, phosphorus and magnesium levels can influence parathyroid gland funcion [17— 221. Moreover, analysis of the data were not completed using the four parameter model originally developed by Delean et al [23] and applied by Brown [241. The current study was undertaken, therefore, to characterize

in OF; minimum serum PTH levels, expressed as a percentage of pre-infusion values, were 25 2% in AD and 26 5% in OF (NS). The slope of the sigmoidal calcium-PTH curve was less in AD than in OF (54 27 versus 127 149 pg/ml/mmol, P < 0.05), suggesting a decrease in sensitivity of the parathyroids to changes in ionized calcium; however, set point values were 1.20 0.01, 1.22 0.01 and 1.21 0.01 mmollliter in AD, OF and NL, respectively. The results indicate that abnormalities in

the pattern of PTH release using the four parameter model in patients with bone biopsy-proven adynamic lesions of renal Os-

the set point for calcium-regulated PTH release do not account for marked differences in serum PTH levels in patients with low-turnover and high-turnover skeletal lesions of renal osteodystrophy.

teodystrophy. The results were then compared with data obtained in patients with osteitis fibrosa and in normal volunteers.

Secondary hyperparathyroidism due to parathyroid gland hyperplasia often leads to the development of osteitis fibrosa cystica

Dynamic tests of parathyroid hormone secretion were done in 30 patients who had been treated with continuous cycling peritoneal dialysis (CCPD) for 20.0 4.2 months. The mean age of the patients was 14.9 0.5 years; 17 were girls and 13 were boys. All

Methods

in patients with chronic renal failure [1, 21. More recently, however, adynamic lesions of bone without aluminum toxicity

patients had undergone iliac crest bone biopsy after double

have been reported in a substantial proportion of adults and

tetracycline labeling, and the skeletal lesions of renal osteodystrophy were classified using criteria previously reported by our laboratory [1]; 22 patients had osteitis fibrosa and 8 patients had adynamic lesions of bone. All patients used calcium carbonate as minimally elevated serum parathyroid hormone (PTH) levels [3—91, features that may reflect a state of relative hypoparathy- the primary phosphate binding agent. For patients with osteitis fibrosa, all had been treated with daily roidism in subjects with advanced renal failure. Factors implicated doses of oral calcitriol. The duration of vitamin D therapy in this in the pathogenesis of adynamic renal osteodystrophy include group of patients averaged 14 3 months, and the dose ranged from 0.25 to 0.75 j.tg/day; oral calcitriol was discontinued, howchildren undergoing regular dialysis [3—7]. Adynamic renal osteodystrophy is characterized by frequent episodes of hypercalcemia, by reduced rates of bone formation and by either normal or

ever, four weeks prior to study. Of the eight patients with Received for publication February 1, 1995 and in revised form April 17, 1995 Accepted for publication April 17, 1995

adynamic skeletal lesions, three were diagnosed on bone biopsies obtained four weeks after stopping daily oral calcitriol therapy. The remaining five patients developed adynamic bone after 12

© 1995 by the International Society of Nephrology

months of intermittent calcitriol therapy; the average dose of 838

839

Sanchez et al: Parathyroid gland function and adynamic bone

calcitriol in this subgroup was 1.3

0.3 g thrice weekly. Dynamic assessments of parathyroid gland function were done 48 hours after the previous dose of calcitriol in those undergoing intermittent calcitriol therapy. Study subjects were admitted to the Clinical Research Center

(CRC) at UCLA for all dynamic tests of parathyroid gland function [12]. After serum samples for basal serum PTH and calcitriol levels were collected, two-hour infusions of sodium citrate or calcium gluconate were done on consecutive days as previously described [12]. No peritoneal dialysis exchanges were done during any of the infusions. Serum ionized calcium levels were lowered on the first day of

study during infusions of sodium citrate, and ionized calcium levels were increased on the second day of study during infusions

of calcium gluconate [12]. Blood samples for measurements of serum ionized calcium and intact parathyroid hormone levels were obtained 30, 15, and 0 minutes before each infusion and every ten minutes thereafter. Serum ionized calcium levels were monitored after completing each infusion until values returned to

Table 1. Biochemical determinations and selected bone parameters in patients with adynamic lesions or secondary hyperparathyroidism Adynamic lesion

(N=8) Total calcium mg/dl Ionized calcium mmol/liter Phosphorus mg/di Alkaline phosphatase lU/liter Intact PTH pg/mI Calcitriol pg/mi Aluminum uglliter Eroded bone perimeter° % Bone formation rateb im2/mm2/day

9.4 1.23

5.3 101 136

0.4 0.02 0.3

20' 39C

24 7

84

2.7 19

0.4' 14°

Secondary hyperparathyroidism

(N=22) 8.8

1.21

6.0

0.3 0.01 0.3

309 44 691 99

12 3 11

1

9.8 0.7 1130

114

Values are means SEM. a

Normal range 0.5—4.3% b Normal range 97—613 jrm2/mm2/d

P < 0.01 compared to those with secondary hyperparathyroidism

baseline levels. Serum samples for ionized calcium determinations were drawn anaerobically, and measurements were done using a

Results Serum biochemical parameters calcium-specific electrode (Radiometer ICA-Il, Copenhagen, The serum levels of total and ionized calcium, phosphorus and Denmark). Although the reported values for serum ionized calcium are adjusted to pH 7.4, all patients had serum pH levels calcitriol did not differ in patients with adynamic lesions and those that fell within the normal range at the time of study. Serum pH with osteitis fibrosa (Table 1). In contrast, serum alkaline phosvalues also did not change substantially from pre-infusion levels phatase and PTH levels were higher in those with osteitis fibrosa during infusions of either sodium citrate or calcium gluconate. (P < 0.01). The values for eroded bone perimeter and the rate of Blood samples for PTH determinations were separated by cen- bone formation in each group are consistent with results previtrifugation, immediately snap-frozen on solid CO2 and stored at ously reported in patients with either adynamic renal osteodystrophy or secondary hyperparathyroidism (Table 1). —70°C until assay [12].

The results of dynamic tests of parathyroid gland function obtained in 20 healthy volunteers using the same study protocol are included for reference; the mean age of the eleven female and nine male volunteer subjects was 21 2 years [12]. All studies were approved by the UCLA Human Subject Protection Committee, and informed consent was obtained from all patients and all parents.

Changes in serum ionized calcium and PTH during sodium citrate infrsions Serum ionized calcium levels fell progressively during infusions

of sodium citrate in both groups of patients (Fig. 1). Values decreased from 1.23 0.02 mmol/liter to 0.98 0.03 mmol/liter in those with adynamic lesions and from 1.21 0.01 mmol/liter to 1.03 0.01 mmol/liter in patients with osteitis fibrosa. Neither the

rate of change in serum ionized calcium nor the total decrease from baseline values differed between groups. The mean decreTotal serum calcium, phosphorus and alkaline phosphatase ment in serum ionized calcium was 0,25 0.06 mmol/liter in levels were done using methods previously described [1, 12]. Biochemical determinations

Calcitriol levels in serum were determined by radioreceptor assay

[25] and intact [1—84] PTH levels were measured using an immunoradiometric assay [26].

patients with adynamic lesions and 0.18 0.03 mmol/liter in those with osteitis fibrosa (NS). Serum PTH levels increased as serum ionized calcium levels fell

during infusions of sodium citrate (Fig. 1). On average, serum PTH levels were highest at 20 minutes in patients with osteitis Statistical analysis fibrosa, and values declined modestly thereafter. In contrast, All values are expressed as the mean standard error. Baseline maximum serum PTH levels were achieved at 60 minutes in serum ionized calcium levels represent the average of three patients with adynamic renal osteodystrophy, and values did not determinations obtained before the start of each infusion. Com- decrease during the remainder of the infusion period (Fig. 1). parisons between groups were done using analysis of variance with Overall, serum PTH levels rose from 136 38 pg/mI to 342 140 contrasts and either paired or unpaired t-tests with appropriate pg/ml in patients with adynamic renal osteodystrophy and from correction for multiple comparisons. The sigmoidal curve which 691 99 pg/mi to 869 121 pg/mi in those with osteitis fibrosa. shows the relationship between serum ionized calcium and PTH When expressed as a percentage of pre-infusion values, the levels was evaluated using the four parameter model developed by magnitude of the increase in serum PTH during sodium citrate Rodbard and Hutt as described by Brown [241. Accordingly, the infusions was greater in patients with adynamic renal osteodysset point is defined as the level of serum ionized calcium at which trophy than in those with osteitis fibrosa, 322 42% versus 146 the serum PTH level is halfway between the maximum value 10%, P < 0.01, whereas values did not differ between patients with obtained during hypocalcemia and the minimum value achieved the adynamic lesion and normal volunteers, 322 42% versus 300 25%, NS (Fig. 2). during hypercalcemia.

840

Sanchez et a!: Parathyroid gland function and adynamic bone

A

A

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*

1.60

1.25

o 1.20

1.50

1.15

1.40

1.10 1.05

o

E 1.00 0.95 Cl) 0.90

*

1.30

1.20

C/) 1.10

0 10 20 30 40 506070 80 90 100110120

0 10 20 30 40 50 60 70 80 90 100 110 120 Time, minutes

Time, minutes B

B

1400 1200

I-

1000 800 600 400 200

*

*****

**

TTT

0 0

10 20 30 40 50 60 70 80 90 100 110 120 Time, minutes

Fig. 1. Serum ionized calcium (A) and PTH levels (B) during two-hour

infusions of sodium cifrate in patients with secondaty hyperparathyroidism (•) or adynamic lesions of bone (E.). Values are means SEM. Reference values for normal subjects (NL) are depicted by the dashed line. Asterisks denote differences between patients with adynamic lesions and those with secondaiy hyperparathyroidism; *p < QØ1, **p < 0.05.

500

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400 300

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700 600 500

**

** **

400

300

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a 200

****

100

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0 10 20 30 40 50 60 70 80 90 100 110 120 Time, minutes

Fig. 3. Serum ionized calcium (A) and PTH levels (B) during two-hour

infusions of calcium gluconate in patients with secondaty hyperparathyroid-

SEM. ism (S) or adynamic lesions of bone (LI). Values are means Reference values for normal subjects (NL) are depicted by the dashed

line. Asterisks denote differences between patients with adynamic lesions and those with secondary hyperparathyroidism; *P < 0.05. **p < 0.01.

increase in serum ionized calcium was somewhat greater in patients with adynamic renal osteodystrophy, 0.30 0.07 mmol/ liter, than in those with osteitis fibrosa, 0.21 0.03 mmol/liter,

NS, and values did not differ from those observed in normal

200 0o

0

*

100

0

•

0 10 20 30 40 50 60 70 80 90 100 110 120 Time, minutes

Fig. 2. Serum PTH levels, expressed as a percentage of pre-infusion values, during two-hour sodium citrate infusions in patients with secondary hyperparathyroidism (•) or adynamic lesions of bone (LI). Values are means sEM; the error bars for subjects with secondary hyperparathyroidism are smaller than the symbols. Values for normal subjects (NL) are depicted by

volunteers, 0.31 0.02 mmol/liter, NS (Fig. 3) [12]. Despite identical rates of calcium administration in each group, serum ionized calcium levels were substantially higher at all sampling intervals beyond 60 minutes in patients with adynamic lesions (Fig. 3). Moreover, the rate of increase in serum ionized calcium during the final hour of calcium infusions was greater in subjects with adynamic renal osteodystrophy, 0.04 0.01 mmol/liter, than in those with osteitis fibrosa, 0.02 0.01 mmol/liter, P < 0.05 (Fig. 3).

Serum PTH levels decreased in each study group during

the dashed line. Asterisks denote differences between patients with infusions of calcium gluconate (Fig. 3). Values fell from 164 75 adynamic lesions and those with secondary hyperparathyroidism; *p < pg/mI to 39 Ii pg/mI in patients with adynamic lesions and from < 0.001. 0.05, 622 76 pg/ml to 171 29 pg/mI in those with osteitis fibrosa.

Changes in serum ionized calcium and PTH during calcium gluconate infusions Serum ionized calcium levels increased progressively in each group during infusions of calcium gluconate (Fig. 3); values rose from 1.24 0.02 mmol/liter to 1.54 0.02 mmol/liter in patients with adynamic lesions and from 1.20 0.01 mmol/liter to 1.41 0.02 mmol/liter in those with osteitis fibrosa. Although baseline

ionized calcium levels did not differ among groups, the overall

Serum PTH levels declined to 25 2.0% and 26 5.0% of baseline levels in patients with adynamic lesions and osteitis fibrosa, respectively (Fig. 4). Minimum serum PTH levels, expressed as a percentage of pre-infusion values, were achieved at the end of the 120-minute calcium infusions in both groups, and the percentage change from pre-infusion values at each 10-minute sampling interval did not differ in patients with adynamic renal osteodystrophy and those with osteitis fibrosa. Construction of the sigmoidal curve depicting the relationship between serum ionized calcium and PTH levels demonstrated no

Sanchez et al: Parathyroid gland function and adynamic bone 125

-

841

j1500

100

11:

.c 75 0 50

25 0 0

0 10 20 30 40 50 60 70 80 90 100 110 120 Time, minutes

Fig. 4. Serum PTH levels, expressed as a percentage of pre-infusion values,

during two-hour calcium gluconate infusions in patients with seconda,y hypeiparathyroidism (•) or adynamic lesions of bone (Li). Values are means SEM. Reference values for normal subjects (NL) are depicted by the dashed line.

0.90

1.00 1.10 1.20 1.30 1.40 Serum ionized calcium, mmol/Iiter

1.50

Fig. 6. The relationship between the serum levels of ionized calcium and PTH in patients with secondaiy hyperparathyroidism (•) or adynamic lesions

SEM. Values for normal subjects (NL) are (Li). Values are means depicted by the dashed line. In contrast to Figure 5, the results are as presented as the mean concentration of PTH in serum rather than as a percentage of the maximum value achieved during hypocalcemia.

100

iI- 75

and with results presented by Messa et al in patients with moderate renal failure [27]. Overall, the data suggest that set

.E

point abnormalities do not account for the wide variation in serum PTH levels in patients with different types of renal osteodystrophy, including those with the adynamic lesion. Despite similar values for set point, the shape of the sigmoidal curve which depicts the relationship between the serum levels of

E 50 i5E5

25 0 1.00

1.10

1.20

1.30

1.40

Serum ionized calcium, mmol/Iiter

ionized calcium and PTH differed substantially in patients with adynamic renal osteodystrophy. The slope of the mid portion of the sigmoidal curve corresponding to serum ionized calcium levels

at or near the set point was less in patients with the adynamic lesion than in those with osteitis fibrosa. Thus, although serum PTH levels changed appropriately with increases or decreases in Reference values for normal subjects (NL) are depicted by the dashed the serum level of ionized calcium within the normal physiologic line. The slope of the curve for patients with the adynamic lesion is less than that for patients with secondaiy hyperparathyroidism or normal range in patients with the adynamic lesion, the magnitude of change in PTH per unit change in serum ionized calcium was less subjects, *p < 0.05. than in patients with overt secondary hyperparathyroidism or in normal human volunteers. The attenuated PTH secretory redifferences between groups in estimates of the set point; values sponse in patients with adynamic renal osteodystrophy suggests

Fig. 5. The sigmoidal curve depicting the relationship between the serum levels of ionized calcium and PTH in patients with secondaiy hypeiparathyroidism (•) or adynamic lesions of bone (Li). Values are means SEM.

were 1.20 0.01 mmol/liter in patients with adynamic lesions and 1.22 0.01 mmollliter in those with osteitis fibrosa, NS (Fig. 5).

In contrast, the slope of the sigmoidal curve at the set point was less in patients with adynamic lesion, 54 9.6 pg/mi mmol, than in those with osteitis fibrosa, 127 31 pg/mi mmol (P < 0.05). When expressed as a percentage of the maximum serum PTH level observed during sodium citrate-induced hypocalcemia, the lowest serum PTH values achieved during calcium gluconate infusions reached 11% in those with adynamic renal osteodystrophy and 18% in patients with osteitis fibrosa (NS). Discussion

The results of the current study indicate that the set point for calcium-regulated PTH release in patients with adynamic renal osteodystrophy does not differ from that of patients with overt secondary hyperparathyroidism. Despite marked differences in basal serum PTH levels, estimates of the set point in neither group varied substantially from values obtained in normal adult volunteers [12]. The absence of set point differences for patients with overt secondary hyperparathyroidism compared to normal subjects is consistent with data previously reported from our institution by Ramirez et al [12] in patients undergoing regular dialysis

that the parathyroid glands are less sensitive to variations in serum ionized calcium in this disorder.

Few studies have evaluated parathyroid gland function in patients with adynamic renal osteodystrophy, and none has compared the results of dynamic tests of parathyroid gland function in such patients with data obtained in normal humans. Felsenfeld et al reported that both the slope and the set point of the sigmoidal calcium-PTH curve were lower in patients with adynamic lesions than in those with osteitis fibrosa regardless of whether there was concurrent evidence of bone aluminum accumulation [161. Unfortunately, these studies employed rapid increases or decreases in serum calcium during hemodialysis to elicit changes in PTH

release, and the methods employed for data analysis did not conform to those required by the four parameter model 1241. In particular, the definition of set point differed substantially from that utilized by Brown [241. It is likely that methodologic considerations largely account for differences between the current results and those reported previously [16]. This distinction is important, however, because the physiologic relevance of terms such as the set point depends upon the consistent application of the four parameter model for in vivo dynamic tests of parathyroid gland function, since the method was

842

Sanchez et al: Parathyroid gland function and adynamic bone

originally developed for studies of PTH secretion by parathyroid cells in vitro [24]. In this regard, several groups of investigators using variations of the technique described by Brown and colleagues have suggested that calcitriol therapy modifies the set point for calcium-regulated PTH release in patients with secondary hyperparathyroidism [13, 14, 28, 29], but subsequent in vivo studies using the four parameter model have failed to confirm these findings [30].

final 60 minutes in patients with adynamic renal osteodystrophy than in those with osteitis fibrosa, and the rate of increase during two-hour infusions was similar to that observed in normal subjects. It is likely that differences in the rates of bone formation and skeletal turnover account for these results. Using calcium kinetic studies, Kurz et a! reported that the uptake of calcium into bone was lower in patients with adynamic renal osteodystrophy than in those with secondary hyperparathyroidism [9]. In subjects with normal or reduced rates of bone formation, the capacity of the skeleton to incorporate additional calcium and to blunt the rise in

and by the same amount in each study group, but the rate of rise in serum PTH was considerably less in patients with the adynamic

in the absence of renal function. It is likely, therefore, that the loss

values did not differ from normal in patients with adynamic renal osteodystrophy, and values at the end of two-hour citrate infusions were substantially greater than in patients with secondary hyperparathyroidism. Such findings indicate that the secretory reserve of the parathyroids is preserved in patients with adynamic renal osteodystrophy despite relatively low basal serum levels of PTH. Indeed, the ability to raise serum PTH levels above baseline

Despite relatively low basal values, a further decline in serum PTH levels was seen in patients with adynamic renal osteodystrophy during infusions of calcium gluconate. Indeed, the percentage decrease from baseline levels did not differ from that observed in patients with secondary hyperparathyroidism. Minimum serum PTH values in each group were greater, however, than in normal

values during sustained reductions in serum ionized calcium

calcium levels and/or intense calcitriol therapy may contribute to the relatively low serum PTH levels characteristic of adynamic

The mechanism which accounts for the blunted secretory response of the parathyroids in patients with adynamic renal osteodystrophy remains uncertain. During infusions of sodium serum ionized calcium following an exogenous calcium load is less citrate, serum ionized calcium levels decreased at the same rate than in subjects with high rates of skeletal remodeling, particularly of skeletal buffering capacity for calcium contributes to the lesion. In contrast, the percentage increase from pre-infusion development of hypercalcemia in patients with adynamic lesion.

exceeds that of patients with secondary hyperparathyroidism [31].

volunteers. Although persistent calcium loading, high serum

Similar gradual yet sustained increases in serum PTH levels during infusions of sodium citrate were also noted in a recent report from our group in pediatric patients with established secondary hyperparathyroidism after four months of treatment with large intermittent doses of calcitriol [30]. Whether this pattern of increase in serum PTH levels during citrate-induced hypocalcemia reflects the release of newly synthesized hormone during sustained hypocalcemia or a rise in the proportion of parathyroid cells actively secreting PTH is not known. Sun et al

renal osteodystrophy, the ability of the parathyroid glands to appropriately diminish PTH release in response to increasing

have suggested that the fraction of parathyroid cells that actively secrete PTH in vitro increases as the medium calcium concentration is reduced [31], and changes in the proportion of cells that release peptide hormones have been documented in other endocrine tissues such as the pituitary gland [32]. A gradual recruit-

normal subjects or patients with osteitis fibrosa. This finding suggests that the parathyroid glands are less sensitive to acute

hypocalcemia in patients with the adynamic lesion. It is noteworthy that the serum levels of PTH did not decrease

approaches values seen in normal subjects. Without evidence that calcium-regulated PTH release is abnormal in patients with either adynamic renal osteodystrophy or secondary hyperparathyroidism, the results suggest that differences in the functional size of parathyroid glands rather than abnormalities in the regulation of

serum ionized calcium levels is retained. In summary, the set point for calcium-regulated PTH release

does not differ from normal in patients with adynamic renal osteodystrophy. Despite low basal values, serum PTH levels change appropriately with variations in serum ionized calcium. The slope of the sigmoidal curve depicting the relationship between serum ionized calcium and PTH levels is less than that of

changes in serum ionized calcium in patients with the adynamic

lesion. In contrast, the secretory reserve of the parathyroids

during sustained hypocalcemia is preserved. Therefore, the perment of quiescent parathyroid cells to active secretion could, centage rise in serum PTH is greater in patients with adynamic therefore, account for the progressive rise in serum PTH during renal osteodystrophy than in those with osteitis fibrosa, and it

toward the end of sodium citrate infusions in patients with adynamic renal osteodystrophy. In contrast, peak values were achieved after only 20 minutes in patients with secondary hyper-

parathyroidism, and serum PTH levels declined thereafter. A PTH release by calcium account for the marked differences in decrease in serum PTH levels after an initial early peak are serum PTH levels in patients with low-turnover and high-turnover commonly seen during sustained periods of hypocalcemia both in patients with overt secondary hyperparathyroidism and in normal

skeletal lesions of renal osteodystrophy.

Acknowledgments depletion of intracellular stores of hormone [33]. The absence of This study was supported in part by USPHS grants DK-35423 and a late decline in serum PTH levels during sodium citrate infusions RR-00865, and by funds from the Casey Lee Ball Foundation.

subjects, and this pattern of PTH release may represent the in patients with the adynamic lesion of renal osteodystrophy

Reprint requests to Isidro B. Salusky, M.D., UCLA Medical Center, underscores the adequacy of the parathyroid secretory reserve in Division of Pediatric Nephrology, A2—383 MDCC, 10833 Le Conte Ave., Los this disorder. Angeles, California 90095-1 752, USA. Hypercalcemia often develops in patients with adynamic skeletal lesions, and serum calcium levels are generally higher in this References

subgroup of patients than in those with other lesions of renal osteodystrophy [3, 4, 11]. During calcium gluconate infusions, serum ionized calcium levels increased more rapidly during the

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