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primary hyperparathyroidism ( phpt ) is a disease characterized by elevated or inappropriately normal parathyroid hormone ( pth ) levels due to excessive secretion by one or more parathyroid glands .
the classical form of the disease is characterized by hypercalcemia , kidney stones , and severe bone disease .
the routine measurement of serum calcium as a screening tool has led to a sharp increase in the incidence of a new presentation of the disease , namely , asymptomatic phpt , whose demonstration of bone involvement depends exclusively on the bone densitometry data [ 24 ] .
the association with kidney disease , nephrocalcinosis , and nephrolithiasis is well established in the hptp and has been reported in several studies .
found a prevalence of 7% in 271 individuals with the disorder and 1.6% in 500 healthy patients evaluated by sonography .
the risk of hospitalization due to urolithiasis is increased for patients with hptp even ten years after parathyroidectomy [ 5 , 6 ] .
currently a new phenotype has arisen , in which normocalcemia is observed , despite persistently high levels of pth . in this situation ,
a thorough search for causes of secondary hyperparathyroidism , particularly vitamin d deficiency , is imperative [ 79 ] .
the demonstration of normocalcemic phpt is even more difficult as there are no guidelines for routine pth measurement , as hptp is most frequently identified during the investigation of reduced bone density [ 9 , 10 ] .
  we retrospectively reviewed the medical records of 70 patients with phpt from our institution , who were divided into two groups : 33 patients with normal serum calcium levels and 37 with hypercalcemia  ( serum calcium   10.2  mg / dl ) .
the following clinical data were obtained : gender , age , weight , height , and bmi .
the diagnostic criteria for nphpt were as follows : apart from normal serum calcium and high pth levels , serum 25ohd levels above 30  ng / ml , absence of bisphosphonates , thiazide diuretics , anticonvulsants or lithium use , glomerular filtration rate greater than 60  ml / min , using the formula modification of diet in renal disease  ( mdrd ) , and the absence of other metabolic bone diseases or gastrointestinal diseases associated with malabsorption or liver disease .
all patients had a urinary ca / cr ratio of less than 240  mg / g cr , demonstrating the absence of hypercalciuria .
serum calcium was determined using the johnson and johnson vitros 950 system  ( rochester , ny , usa ) with reference value 8.4 to 10.2  mg / dl , serum 25-hydroxyvitamin d using the diasorin liaison competitive chemiluminescent immunoassay  ( stillwater , mn , usa ) 10% coefficient of variation , with the following reference values : normal : 30 to 60  ng / ml ) , serum pth using the chemiluminescence method , immulite 2000  ( siemens , llanberis , gwynedd , uk ) , with intra- and interassay coefficients of variation of 4.2 to 5.7% and 6.3 to 6.8% , respectively , and serum c - telopeptide when using the electrochemiluminescence assay , elecsys systems , roche diagnostics , mannheim , germany , reference value 50450  pg / ml
. bone mineral density  ( bmd ) and t - score were evaluated at the lumbar spine  ( l1l4 ) , femoral neck , and distal radius  ( lunar corporation madison , wisconsin , usa ) .
the correction of serum calcium levels in relation to albumin was performed using the following formula : corrected calcium = calcium found + ( 4-serum albumin )  0.8 .
patients who had clinical manifestations of nephrolithiasis were evaluated by ultrasound , and the results of the examinations were obtained from the medical records .
  pearson 's chi - square test or fisher 's exact test and the student 's t - test with equal or unequal variances were used for comparisons .
verification of the hypothesis of equal variances was performed using levene 's f test , and the level of significance used in interpreting the statistical test was 5% .
the prevalence of nephrolithiasis in the normocalcemic group was 18.2% and 18.9% in the hypercalcemic group ( p = 0.937 ) .
fifteen percent of normocalcemic patients had a previous history of fractures compared to 10.8% of hypercalcemic patients , although there was no statistically significant difference ( p = 0.726 ) table 2 . in both groups ,
the bone mineral density in the lumbar spine was 0.95  0.24  g / cm ( t score : 1.3 ) , femoral neck 0.76  0.15  g / cm ( t score : 1.75 ) , and distal radius 0.54  0.15  g / cm
ls bmd was normocalcemic 0.95  0.22  g / cm versus hypercalcemic 0.95  0.26  g / cm , p = 0.885 and fn bmd : normocalcemic 0.73  0.15  g / cm versus hypercalcemic 0.79  0.19  g / cm , p = 0.123 .
patients with normocalcemia had bmd values in the distal radius significantly higher than the hypercalcemic patients ( p = 0.046 ) , as shown in table 3 .
in the present study we found a high prevalence of kidney stones in nphpt , suggesting that the normocalcemia condition does not mean that the patient is without clinical manifestations . in relation to a history of fractures , we found a similar occurrence in the two groups with 15.2% in the normocalcemic and 10.8% in the hypercalcemic .
we also observed that the bone mineral density in the distal radius was more preserved in the normocalcemic group than in the hypercalcemic group , although there were no significant differences in the lumbar spine and femoral neck . 

lundgren et al . , in a sample of 109 patients , found that 17 ( 16% ) had normal levels of calcium with elevated pth characterizing nphpt . in our institution ,
marques et al . found a prevalence of nphpt of 8.9% in a population of 156 postmenopausal women with osteoporosis .
these data suggest that it is not a rare condition and therefore needs to be investigated in all patients with reduced bone mineral density .
in contrast , in a population - based survey conducted in sweden , the prevalence of nphpt , in postmenopausal women was 0.6% .
lowe et al . , in a series of 37 normocalcemic patients , found a frequency of nephrolithiasis of 14% , which is comparable with our findings , and a history of fracture of 11% .
marques et al . showed an occurrence of kidney stones of 28.6% in osteoporotic women with nphpt in contrast to 0.7% in noncarriers .
for clinical fractures they found a 21.4% prevalence in nphpt compared with 16.2% in those not affected .
our study showed a preservation of cortical bone in patients with the normocalcemic form of the disease , and this is in agreement with the findings of lowe et al . , who showed a deterioration , particularly in ls bmd .
one study showed that after an oral calcium load , normocalcemic subjects had an inadequate suppression of pth compared with hypercalcemic subjects .
the high frequency of kidney stones and fractures in normocalcemic primary hyperparathyroidism could be explained by the possible lower renal and bone sensitivity to the biological effects of pth , although this hypothesis needs further investigation .
gomes et al . stated that another possibility could be the presence of non-184 pth circulating molecules , such as a 784 pth fragment , blocking the calcemic effect of 184 pth and preventing hypercalcemia .
our data suggests that nphpt may not be an idle condition as it may progress to complication regardless of the development of hypercalcemia .
controversies regarding the suggestion that nphpt should be treated , since the disease can lead to a deterioration in bone mineral density , fractures , and kidney stones .
thus , the routine determination of pth could detect these individuals early on in an attempt to prevent an unfavorable clinical course .
there is no consensus about when to treat patients with hptpn , but if there is progression to clinical complications such as urolithiasis , bone mass loss , or fractures , surgery is indicated .
finally , a new phenotype of nphpt was recently described in a population - based survey mros ( osteoporosis fractures in men ) . using less rigid criteria for the diagnosis of nphpt ( gfr >  40  ml / min and serum 25ohd <  20  mg / ml ) , the authors found a 0.7% prevalence of the disease that was associated with a significantly higher ls bmd in comparison with the elderly men without nphpt .
our findings revealed a high prevalence of urolithiasis in normocalcemic primary hyperparathyroidism , but with preservation of the cortical bone , corroborating the belief that the disease is not an indolent condition and needs to be not only investigated but also treated when complications are diagnosed .
introduction . 
 normocalcemic primary hyperparathyroidism ( nphpt ) is considered a variant of the more frequent form of the disease characterized by normal serum calcium levels with high pth . 
 the higher prevalence of renal stones in patients with hptp and the well established association with bone disorders show the importance of studies on how to manage asymptomatic patients . objective . to compare the clinical and laboratory data between the normocalcemic and mild hypercalcemic forms of phpt 
 . methods . 
 we retrospectively evaluated 70 patients with phpt , 33 normocalcemic and 37 mild hypercalcemic . 
 results . 
 the frequency of nephrolithiasis was 18.2% in normocalcemic patients and 18.9% in the hypercalcemic ones ( p = 0.937 ) . 
 fifteen percent of normocalcemic patients had a previous history of fractures compared to 10.8% of hypercalcemic patients , although there was no statistically significant difference ( p = 0.726 ) . 
 conclusion . 
 our data confirms a high prevalence of urolithiasis in normocalcemic primary hyperparathyroidism , but with the preservation of cortical bone . 
 this finding supports the hypothesis that this disease is not an idle condition and needs treatment .