primary hyperparathyroidism ( phpt ) is a disease characterized by hypercalcemia due to autonomous production of parathyroid hormone ( pth ) .
phpt is the third most common endocrine disorder in the west after diabetes mellitus and thyroid disorders .
overall , about 1% of the adults have phpt in the west , and this figure rises to 2% in people older than 55 years . with the advent of multichannel biochemical screening in the 1970s ,
the clinical profiles of phpt remarkably differ with regions of the world . in developing countries , such as india ,
phpt is still uncommonly diagnosed , overtly symptomatic disease with skeletal , muscular , and renal manifestations .
in contrast , phpt has become an asymptomatic disease in the west with classic manifestations seen only in 2% cases nowadays . in this study
, we describe the clinical characteristics , biochemical profile , and outcome of 78 patients with phpt seen over a period of two decades at a single center from the kashmir valley .
all patients who underwent evaluation and surgery for phpt from january 1996 to december 2015 at sher - i - kashmir institute of medical sciences were included in the study .
a total of 78 patients were identified during the two decades , of whom 29 patients were studied retrospectively ( 19962012 ) and remaining 49 patients were studied prospectively ( 20122015 ) .
the diagnosis of phpt was based on the following : ( i ) persistent elevation of serum calcium above the upper limit of normal range ( 10.5 mg / dl ) ; ( ii ) increased intact pth ( ipth ) ; and ( iii ) histological evidence ( after parathyroid surgery ) of parathyroid adenoma or hyperplasia .
evaluation of the patients included the measurement of serum total calcium , inorganic phosphorus , total alkaline phosphatase ( alp ) , ipth , 25-hydroxy vitamin d ( 25-ohd ) , serum albumin , and 24 hour urinary calcium and creatinine .
serum total calcium , inorganic phosphorus , total alp , and serum creatinine were measured by automated techniques .
the normal laboratory range was 8.510.5 mg / dl for total serum calcium , 2.54.5 mg / dl for serum phosphorus , and 30140 iu / l for serum alp .
radiological survey of hands , skull , lumbar spine , pelvis , and any other suspected or known site of fracture was performed .
imaging studies for localization of parathyroid adenoma included ultrasonography ( usg ) neck and technetium-99 m ( tc ) sestamibi scan .
serum ipth was measured by chemiluminescent immunometric assay and serum 25-ohd was measured by radioimmunoassay .
vitamin d deficiency was defined as serum 25-ohd level < 20 ng / ml . in patients
in whom a single parathyroid adenoma was localized on tc sestamibi scan , unilateral neck exploration was performed with removal of the adenoma .
patients with doubtful lesion or nonlocalized lesions underwent bilateral neck exploration , and all parathyroid glands were examined with the removal of 3 glands .
statistical analysis was done on pc windows using statistical package for social sciences ( spss ) , version 11.5.0 , from spss inc .
pearson 's chi - square method was used for comparing proportions and percentages , whereas student 's t - test was used for comparing continuous variables .
anova was used wherever needed . where the data were not uniformly distributed nonparametric test such as mann 
smirnov z - test , or kruskal  wallis h - test was used . a p < 0.05 was taken as statistically significant .
in patients in whom a single parathyroid adenoma was localized on tc sestamibi scan , unilateral neck exploration was performed with removal of the adenoma .
patients with doubtful lesion or nonlocalized lesions underwent bilateral neck exploration , and all parathyroid glands were examined with the removal of 3 glands .
statistical analysis was done on pc windows using statistical package for social sciences ( spss ) , version 11.5.0 , from spss inc .
pearson 's chi - square method was used for comparing proportions and percentages , whereas student 's t - test was used for comparing continuous variables .
anova was used wherever needed . where the data were not uniformly distributed nonparametric test such as mann 
smirnov z - test , or kruskal  wallis h - test was used . a p < 0.05 was taken as statistically significant .
the clinical characteristics of patients are shown in table 1 . an overwhelming majority ( 67/78 ; 85.7% ) of the patients were females giving a male : female ratio of 1:6 .
the mean age of patients was 44.72  12.46 with a median of 45 years and a range of 1670 years .
nephrolithiasis and/or nephrocalcinosis [ figure 1 ] was the most common presentation , seen in 50 ( 64.10% ) patients followed by bone pain in 26 ( 44.1% ) , abdominal pain in 24 ( 39% ) , constipation in 16 ( 26% ) , and myopathy in 11 ( 14.10% ) .
skeletal involvement ( osteopenia , sub - periosteal resorption , pathological fractures , salt and pepper appearance of skull , brown tumors ) was present in 31 ( 39.74% ) patients ; 8 ( 10.25% ) had fractures [ figure 2 ] .
about one - fourth ( 19 ; 24.38% ) of our patients had both renal and skeletal manifestations .
clinical characteristics of 78 patients with primary hyperparathyroidism ( a ) radiograph of abdomen showing extensive bilateral nephrolithiasis ; ( b ) striking improvement after successful parathyroid surgery radiograph showing advanced bone disease . ( a ) fracture of femur ; ( b ) brown tumor of tibia out of fifty patients with nephrolithiasis , 15 ( 30% ) had a past history of at least one surgery for renal stones prior to the diagnosis of phpt , and another four patients had received extracorporeal shock wave lithotripsy at least once prior to diagnosis of phpt .
the mean serum calcium level was 12.5  1.7 mg / dl , ( median12 , range 10.719 ) .
the mean serum ipth level was 377.6  386.1 pg / ml ( median 224.5 , range 701900 ) .
hypophosphatemia ( serum inorganic phosphorus < 2.5 mg / dl ) was documented in 54 ( 69.23% ) patients .
the mean serum inorganic phosphorus level was 2.2  0.6 mg / dl ( median 2.2 ) .
hypercalciuria ( 24 h urinary calcium 4 mg / kg ) was present in 41 ( 52.56% ) patients .
the mean serum alp was 255.1  336.8 iu / l ( median 154 ) . biochemical variables of 78 patients with primary hyperparathyroidism serum 25-ohd was available for 54 patients .
the mean 25-ohd level was 37.2  58.1 ng / ml ( median 22.8 , range 4.3312 ) .
we did not find any correlation between vitamin d status and biochemical parameters ( serum calcium and ipth ) or adenoma weight .
two females ; aged 25 and 23 years had phpt and microprolactinoma , whereas a 58-year - old female patient had phpt and acromegaly .
two of our patients had associated adrenal incidentalomas causing sub - clinical cushing 's syndrome in one of them . a 27-year - old female patient presented in postpartum period with nephrogenic diabetes insipidus as the sole manifestation of phpt , which settled immediately after parathyroid surgery .
all our patients underwent usg neck and tc-99 m sestamibi scan for localization of parathyroid adenoma . in our series , the sensitivity of usg and tc-99 m sestamibi scan for the localization of adenoma was 89.8% and 95.3% , respectively . at the time of surgery ,
single adenoma was involved in 69 ( 88.46% ) double adenomas in 6 ( 8.57% ) and more than 2 gland involvement in 3 ( 4.28% ) patients . among the 69 patients with single adenoma ,
right inferior gland was involved most often ( 40 ; 57.97% ) , followed by left inferior ( 22 ; 31.88% ) and right superior ( 7 ; 0.14% ) ; none of the patients had involvement of left superior gland .
on histopathology , adenoma was found in 75 ( 94.44% ) , hyperplasia in 3 ( 3.79% ) patients .
the mean parathyroid gland weight was 2.05  3.03 g ( median 1.05 ; range 0.113.8 ) . using pearson 's correlation coefficient ,
the mean postoperative serum ipth level was 61.8  43.8 pg / ml ( range : 10.7154 ) .
postoperative hungry bone syndrome ( hbs ) was observed in 8 ( 10.12% ) patients .
this was managed with oral calcium and calcitriol in five patients , whereas three patients needed parenteral calcium gluconate infusion .
permanent hypoparathyroidism was observed in a single patient , and postoperative pancreatitis was documented in one patient .
no patient sustained permanent vocal cord paralysis , wound infection , or sepsis . the surgical success ( cure ) for phpt is defined by the maintenance of eucalcemia at the arbitrarily accepted interval of 6 months after surgery .
based on this definition , the overall cure rate in our series was 96.15% ( 75 out of our 78 patients achieved cure ) .
one of these patients had men-1 ( phpt and acromegaly ) ; she underwent the removal of all four parathyroid glands .
the second patient was a young male in whom preoperatively left inferior adenoma was localized but had a persistent disease ; however , he achieved cure after second surgery .
out of 75 patients who achieved cure , long - term follow - up ( more than one year , range 19 years ) was available for 41 patients . during this follow - up period , none had recurrence of phpt .
at the time of surgery , single adenoma was involved in 69 ( 88.46% ) double adenomas in 6 ( 8.57% ) and more than 2 gland involvement in 3 ( 4.28% ) patients . among the 69 patients with single adenoma ,
right inferior gland was involved most often ( 40 ; 57.97% ) , followed by left inferior ( 22 ; 31.88% ) and right superior ( 7 ; 0.14% ) ; none of the patients had involvement of left superior gland .
on histopathology , adenoma was found in 75 ( 94.44% ) , hyperplasia in 3 ( 3.79% ) patients .
the mean parathyroid gland weight was 2.05  3.03 g ( median 1.05 ; range 0.113.8 ) . using pearson 's correlation coefficient ,
the mean postoperative serum ipth level was 61.8  43.8 pg / ml ( range : 10.7154 ) .
postoperative hungry bone syndrome ( hbs ) was observed in 8 ( 10.12% ) patients .
this was managed with oral calcium and calcitriol in five patients , whereas three patients needed parenteral calcium gluconate infusion .
permanent hypoparathyroidism was observed in a single patient , and postoperative pancreatitis was documented in one patient .
no patient sustained permanent vocal cord paralysis , wound infection , or sepsis . the surgical success ( cure ) for phpt is defined by the maintenance of eucalcemia at the arbitrarily accepted interval of 6 months after surgery .
based on this definition , the overall cure rate in our series was 96.15% ( 75 out of our 78 patients achieved cure ) .
one of these patients had men-1 ( phpt and acromegaly ) ; she underwent the removal of all four parathyroid glands .
the second patient was a young male in whom preoperatively left inferior adenoma was localized but had a persistent disease ; however , he achieved cure after second surgery .
out of 75 patients who achieved cure , long - term follow - up ( more than one year , range 19 years ) was available for 41 patients . during this follow - up period ,
the traditional age of presentation of phpt in india is in the 4 decade . in our study ,
our results reflect a shift in the presentation of phpt from fourth to fifth decade in india .
however , our patients continue to be much younger than patients from the developed countries .
comparison of present study with other indian studies renal stone disease ( 50:64.10% patients ) was the most common presentation in our series .
the prevalence of renal stones has fallen from 57% to < 5% in the west due to the detection of more and more asymptomatic cases .
thirty percent of our patients with renal stones had a past history of at least one surgery for renal stones and another four patients ( 8% ) had received lithotripsy prior to diagnosis of phpt .
surprisingly , in none of these patients serum calcium estimation had been advised during previous evaluation .
this significant delay in the diagnosis of phpt reflects the lack of awareness among urologists , nephrologists , and general practitioners regarding phpt .
mishra et al . in 2001 in a study of 29 patients reported osteitis fibrosa cystica in all of them and fractures in 57% of the patients .
in a study of 52 patients reported bone disease in 67% and fractures in 48% patients .
a systematic review of phpt in india has reported fractures in 40% and brown tumors in 42% patients .
a recent indian study reported fractures in 25.8% of phpt patients and brown tumors in none . in our study , fractures were present only in 10.25% and brown tumors in 6.41% patients .
this is the lowest prevalence of fractures in a cohort of phpt patients from india .
our results reflect a changing trend in the presentation of phpt in india wherein the overt skeletal disease in the form of fractures and brown tumors is on the decline .
the remarkably low prevalence of fractures in our series probably is due to earlier diagnosis of phpt for last few years ( more than half of our subjects were enrolled from 2013 onwards ) .
the improvement in vitamin d nutrition is reflected by the mean serum 25-ohd of 37.2 ng / ml in our patients .
the frequency of specific radiological manifestations of phpt in the united states declined from 23% in the 1960s to a remarkably low 2% in the 1990s .
the difference in the severity of skeletal disease in phpt between western and eastern populations is determined by calcium and vitamin d nutrition , but additional factors also play a role .
previous data from india report that 1213% patients with phpt have pancreatitis . in our series ,
the mechanisms of phpt induced pancreatitis include hypercalcemia - induced activation of trypsinogen to trypsin , ductal obstruction due to pancreatic calculi , and finally genetic risk factors .
all our patients had hypercalcemia and their mean serum calcium level was 12.5 mg / dl , which is remarkably similar to that reported by other indian studies .
a previous indian study has reported hypophosphatemia in 65% patients with phpt , but another indian study has reported a normal mean serum phosphorus in phpt patients .
the mean serum ipth level in our patients was 377.6 pg / ml , which is lower than that reported by previous indian studies .
elevated alp has been consistently reported by other indian series due to high prevalence of bone disease in phpt patients .
the mean parathyroid weight ( 2.05  3.03 g ) in our study is markedly lower than that reported by other indian studies [ table 3 ] .
we found a strong correlation of parathyroid gland weight with serum calcium and ipth , as has been reported previously .
the mean serum 25-ohd ( 37.2  58.1 ng / ml ) in our study was higher than that reported by previous indian studies ; however , vitamin d deficiency was present in 38% of our patients .
an inverse correlation between serum 25-ohd concentration and parathyroid gland weight has been reported previously .
we did not find any correlation between vitamin d status and biochemical parameters ( serum calcium and ipth ) or adenoma weight .
the likely reason is the possibility of prior vitamin d treatment and uncertainty about its timing and amount , which could have confounded the 25-ohd measurements at the time of presentation .
in addition , vitamin d may not be the only significant factor in the development of bone disease in phpt patients , other factors could be playing a significant role .
the preoperative localization of an abnormal parathyroid gland can reduce operative time , postoperative morbidity , and the need for repeat surgery .
the imaging methods for localization include high - resolution usg , tc sestamibi scan , computerized tomography , and magnetic resonance imaging .
the sensitivity of usg to localize the adenoma has been reported as 6577% , whereas the sensitivity of tc sestamibi scan has been reported as 86.9100% . in our series , the sensitivity of usg and tc sestamibi scan for localization of adenoma was 89.8% and 95.3% , respectively . with a sensitivity of 89.8%
, we conclude that usg is an effective localization modality as it is inexpensive and is widely available .
mishra et al . , in a study of 29 patients reported a cure rate of 100% .
previous indian studies have reported postoperative hbs in a large proportion of patients from 24% to 82% . in our study ,
our results are in agreement with a recent indian study in which postoperative hbs was seen in only four patients ( 8% ) out of fifty .
our policy to treat all patients with preoperative serum 25-ohd level < 30 ng / ml with vitamin d is in all probability , responsible for much lower prevalence of postoperative hbs in our series .
consistent with the data about recurrent phpt on long - term follow - up revealing recurrence rates of zero to 41.6% , none of the 41 patients in our series on whom follow - up was available for 19 years , had recurrence of phpt .
the strengths of our study include its large size and largely prospective nature with about two - thirds ( 62% ) of the subjects evaluated prospectively .
lack of data on bone mineral density and for many patients , on vitamin d status are the limitations of the study .
in conclusion , our study reflects a changing trend in the clinical profile of phpt in india .
there is a shift in the age of presentation of phpt from fourth to fifth decade .
renal stone disease is emerging , the most common presentation , whereas overt skeletal disease in the form of fractures and brown tumors is on the decline .
 background : although primary hyperparathyroidism ( phpt ) has become an asymptomatic disease in the west , in india , phpt is still an uncommonly diagnosed , overtly symptomatic disease with skeletal , muscular , and renal manifestations.aims:to describe the profile and surgical outcome of 78 consecutive phpt patients over a period of two decades at a single center.materials and methods : all patients who underwent evaluation and surgery for phpt from january 1996 to december 2015 were included . 
 evaluation included measurement of serum total calcium , inorganic phosphorus , alkaline phosphatase , intact parathyroid hormone , 25-hydroxy vitamin d , 24 hour urinary calcium and radiological survey . 
 ultrasonography neck and technetium-99 m sestamibi scan were used for preoperative localization.results:a total of 78 patients were identified during the two decades of whom 29 patients were studied retrospectively and 49 patients prospectively . 
 mean age of patients was 44.72  12.46 , and male : female ratio was 1:6 . 
 the most common presenting features were nephrolithiasis and/or nephrocalcinosis ( 64.10% ) , bone pain ( 44.1% ) , abdominal pain ( 39% ) , constipation ( 26% ) , and myopathy ( 14.10% ) . 
 fractures were present only in 10.25% , and brown tumors in 6.41% patients . 
 the cure rate in our series was 96.15% . 
 the mean parathyroid gland weight was 2.05  3.03 g. none of the 41 patients in whom long - term follow - up was available , had recurrence of phpt.conclusions:the profile of phpt is changing with older age at presentation , and emergence of renal stone disease and decline in overt skeletal disease as common presentation . 
 the parathyroid weight in our study resembles that reported from developed countries . 
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Parathyroid surgery
Statistical analysis
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Operative findings and pathological features
Postoperative course
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Financial support and sponsorship
Conflicts of interest