Is routine 24-hour urine calcium measurement useful during the evaluation of primary hyperparathyroidism?

BACKGROUND: Primary hyperparathyroidism and familial hypocalciuric hypercalcemia have similar biochemical profiles, and calcium-to-creatinine-clearance ratio helps distinguish the two. Additionally, 24-hour urine calcium >400 mg/day indicates surgery and guidelines recommend obtaining 24-hour urine calcium preoperatively. Our aim was to assess how 24-hour urine calcium altered care in the evaluation of suspected primary hyperparathyroidism. METHODS: Consecutive patients assessed for primary hyperparathyroidism from 2018 to 2020 were reviewed. Primary hyperparathyroidism was diagnosed by 2016 American Association of Endocrine Surgeons Parathyroidectomy Guidelines criteria. 24-hour urine calcium-directed change in care was defined as familial hypocalciuric hypercalcemia diagnosis, surgical deferment for additional testing, or 24-hour urine calcium >400 mg/day as the sole surgical indication. RESULTS: Of 613 patients, 565 (92%) completed 24-hour urine calcium and 477 (84%) had concurrent biochemical testing to calculate calcium-to-creatinine-clearance ratio. 24-hour urine calcium was <100 mg/day in 9% (49/565) and calcium-to-creatinine-clearance ratio was <0.01 in 17% (82/477). No patient had confirmed familial hypocalciuric hypercalcemia, although 1 had a CASR variant of undetermined significance. When calcium-to-creatinine-clearance ratio was <0.01, familial hypocalciuric hypercalcemia was excluded by 24-hour urine calcium >100 mg/day (56%), prior normal calcium (16%), renal insufficiency (11%), absence of familial hypercalcemia (3%), normal repeat 24-hour urine calcium (10%), or interfering diuretic (1%). 24-hour urine calcium-directed change in care occurred in 25 (4%), including 4 (1%) who had genetic testing. Four-gland hyperplasia was more common with calcium-to-creatinine-clearance ratio <0.01 (17% vs calcium-to-creatinine-clearance ratio ≥ 0.01, 4%, P < .001), but surgical failure rates were equivalent (P = .24). CONCLUSION: 24-hour urine calcium compliance was high, and results affected management in 4%, including productive identification of hypercalciuria as the sole surgical indication in 2 patients. When calcium-to-creatinine-clearance ratio <0.01, clinical assessment was sufficient to exclude familial hypocalciuric hypercalcemia and only 1% required genetic testing. 24-hour urine calcium should be ordered judiciously during primary hyperparathyroidism assessment.

Parathyroidectomy improves hypercalciuria in patients with primary hyperparathyroidism.

BACKGROUND: Hypercalciuria is an important manifestation of primary hyperparathyroidism and may contribute to the risk of nephrolithiasis. This study examined the impact of parathyroidectomy on 24-hour urinary calcium (24-hour UCa) levels and rates of resolution of hypercalciuria after surgery. METHODS: A retrospective cohort study was performed of patients who underwent curative parathyroidectomy for primary hyperparathyroidism from 2007 to 2017. Baseline and postoperative urine and serum biochemistry levels were analyzed. The relationship between preoperative 24-hour UCa levels and the absolute decrease in postoperative UCa excretion was assessed using Spearman's rank correlation coefficient. RESULTS: Of 110 patients, 84 (76.4%) experienced a ≥20% decrease in 24-hour UCa level postoperatively. These patients had a higher baseline median 24-hour UCa level (293.5 vs 220.5 mg/24-hour; P = .001), higher baseline mean serum parathyroid hormone (106.5 vs 83; P = .05) and were more likely to have single gland disease (85.7% vs 65.4%, P = .04) compared with patients in whom 24-hour UCa excretion did not improve. Of the 28 patients (25%) who were hypercalciuric (24-hour UCa >400 mg/day) at baseline, 22 (79%) became normocalciuric postoperatively. A linear correlation was observed between preoperative 24-hour UCa levels and the decline in 24-hour UCa excretion after surgery (R2 = 0.59, P < .0001) such that the degree of improvement could be predicted using the following equation: absolute decrease in postoperative 24-hour UCa = 0.68 × preoperative 24-hour UCa-68. CONCLUSION: Parathyroidectomy reduces 24-hour UCa excretion in the majority of patients with PHPT and restores normocalciuria in 79% of patients with hypercalciuria at baseline.

Hypomagnesuria is Associated With Nephrolithiasis in Patients With Asymptomatic Primary Hyperparathyroidism.

CONTEXT: The pathogenesis of nephrolithiasis in primary hyperparathyroidism (PHPT) remains to be elucidated. The latest guidelines suggest parathyroidectomy in patients with asymptomatic PHPT with hypercalciuria (> 400 mg/d) and increased stone risk profile. OBJECTIVE: The objective of this work is to evaluate the association of urinary stone risk factors and nephrolithiasis in patients with asymptomatic sporadic PHPT and its clinical relevance. DESIGN: A total of 157 consecutive patients with sporadic asymptomatic PHPT were evaluated by measurement of serum and 24-hour urinary parameters and kidney ultrasound. RESULTS: Urinary parameters were tested in the univariate analysis as continuous and categorical variables. Only hypercalciuria and hypomagnesuria were significantly associated with nephrolithiasis in the univariate and multivariate analysis adjusted for age, sex, body mass index, estimated glomerular filtration rate, parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and urine volume (odds ratio, OR 2.14 [1.10-4.56]; P = .04; OR 3.06 [1.26-7.43]; P = .013, respectively). Hypomagnesuria remained associated with nephrolithiasis in the multivariate analysis (OR 6.09 [1.57-23.5], P = .009) even when the analysis was limited to patients without concomitant hypercalciuria. The urinary calcium/magnesium (Ca/Mg) ratio was also associated with nephrolithiasis (univariate OR 1.62 [1.27-2.08]; P = .001 and multivariate analysis OR 1.74 [1.25-2.42], P = .001). Hypomagnesuria and urinary Ca/Mg ratio had a better, but rather low, positive predictive value compared with hypercalciuria. CONCLUSIONS: Hypomagnesuria and urinary Ca/Mg ratio are each associated with silent nephrolithiasis and have potential clinical utility as risk factors, besides hypercalciuria, for kidney stones in asymptomatic PHPT patients. The other urinary indices that have been commonly thought to be associated with kidney stones in PHPT are not supported by our results.

Hyperparathyroidism in patients over 75: Clinical characteristics and outcome. Is conservative treatment a safe alternative?

OBJECTIVE: With the current aging of the world's population, primary hyperparathyroidism (PHPT) is increasingly detected in the elderly. Yet data on the presentation and outcome of PHPT in this group are scarce. The objective was to describe a cohort of patients aged 75 years or more with PHPT observed in our endocrine clinic. STUDY DESIGN: A retrospective analysis of medical records in an endocrine clinic at a tertiary hospital. We evaluated 182 patients with PHPT, aged 75 years or more at their last follow-up, all diagnosed at age 65 or more. Laboratory data were compared at diagnosis and last follow-up. RESULTS: Mean age at diagnosis was 73 ± 4 years, last follow-up was at 83 ± 4 years, and mean follow-up was 11.3 ± 5.5 years. Osteoporosis, fractures, and nephrolithiasis were diagnosed in 114(63 %), 84(46 %), and 43(24 %) patients, respectively. Overall, 150 patients had an indication for surgery; of them, the 29 who underwent parathyroidectomy were younger than the non-operated patients and had higher rates of hypercalciuria. During the follow-up of the 141 patients who did not undergo operation, serum and urinary calcium levels significantly had decreased, and vitamin D level had increased at last visit (10.4 ± 0.5 mg/dl, 161 ± 70 mg/24 h, 69 ± 17 nmol/l, p < 0.01 respectively) compared with levels at diagnosis (10.6 ± 0.2 mg/dl, 223 ± 95 mg/24 h, 53 ± 15 nmol/l, respectively, p = 0.001). Overall, 38 of the 182 patients (20 %) died during follow-up; these patients were significantly older at diagnosis (76 ± 5 vs. 72 ± 4 years) but there were no differences in laboratory variables. CONCLUSIONS: While most patients had a formal indication for surgery, few underwent parathyroidectomy. Serum and urinary calcium significantly decreased during follow-up in patients who did not undergo surgery. Our data are reassuring and support at least the consideration of conservative treatment for these patients.

Circulating IL-17A Levels in Postmenopausal Women with Primary Hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common cause of secondary osteoporosis in postmenopausal women. Th17 lymphocytes and the released cytokine IL-17A play an important role in bone metabolism. Th17 cells have been shown to be activated by PTH, and peripheral blood T cells from patients affected with PHPT express higher levels of IL-17A mRNA than controls. AIM: To investigate circulating levels of IL-17A and the ratio RANKL/OPG, as markers of osteoclastogenesis, in 50 postmenopausal PHPT women compared with postmenopausal osteoporotic non-PHPT women (n = 20). RESULTS: Circulating levels of IL-17A were similarly detectable in most PHPT and non-PHPT osteoporotic women (12.9 (8.4-23.1) vs. 11.3 (8.3-14.3) pg/ml, median (range interquartile), P = 0.759), at variance with premenopausal women where IL-17A was undetectable. In PHPT women, any significant correlations could be detected between circulating IL-17A levels and PTH levels. Nonetheless, significant negative correlations between circulating IL-17A and ionized calcium levels (r = -0.294, P = 0.047) and urine calcium excretions (r = -0.300, P = 0.045) were found. Moreover, PHPT women were characterized by positive correlations between IL-17A levels and femur neck (r = 0.364, P = 0.021) and total hip (r = 0.353, P = 0.015) T-scores. Circulating IL-17A levels did not show any significant correlation with sRANKL, OPG, and sRANKL/OPG ratio in PHPT women. CONCLUSIONS: In postmenopausal PHPT women, circulating IL-17A levels were similar to those detected in postmenopausal non-PHPT women, showing a disruption of the relationship observed in postmenopausal osteoporosis among circulating PTH, sRANKL, OPG, IL-17A, and bone demineralization in postmenopausal PHPT women. The data support an osteogenic effect of IL-17A in postmenopausal PHPT women.

Investigating subtle kidney injury in primary hyperparathyroidism by means of sensitive and specific biomarkers.

OBJECTIVE: Kidney involvement is a common complication in primary hyperparathyroidism (PHPT). No study so far has assessed the prevalence of kidney injury developing before the reduction in glomerular filtration rate (GFR) in PHPT. The study was aimed at establishing the potential role of biomarkers of kidney injury in detecting subtle renal damage in patients with PHPT. DESIGN: Cross-sectional study. PATIENTS: A total of 69 postmenopausal patients with PHPT and 41 healthy age- and sex-matched subjects were studied. Exclusion criteria were as follows: GFR < 30 mL/min, chronic inflammatory disease, nephrotic syndrome, infection, malignancy, heart failure, recent exposure to iodinated contrast media or nonsteroidal anti-inflammatory drugs. MEASUREMENTS: We measured a panel of sensitive biomarkers of kidney injury in PHPT vs controls. RESULTS: Mean FGF23 and Klotho were higher in PHPT (72 ± 48 and 811 ± 366 pg/mL, respectively) than controls (53 ± 23.5 and 668.6 ± 17; P < .02 and P < .05). Urine KIM-1/uCr was significantly higher in PHPT (1.4-6  ± 1.3-6 ) than controls (9.2-7  ± 7-7 ; P < .05); this was particularly evident in the CrCl 60-89 mL/min category (1.36  ± 97 vs 8.2-7  ± 3.6-7 ; P < .02). Mean values of urine NGAL/uCr were higher in PHPT with (n = 28) compared to those without kidney stones (n = 35; 1.8-5  ± 1.4-5 and 1-5  ± 8-6 ; P < .0001). We found significant positive associations between urine NGAL/uCr and Ca (R = .292, P < .02) and urine KIM1/uCr and PTH (R = .329, P < .01). CONCLUSIONS: We propose the utilization of these molecules, particularly urine KIM-1/uCr and urine NGAL/uCr ratios for the assessment of subtle kidney injury in patients with PHPT. These molecules are elevated in tubular necrosis and have potential role in the development of kidney damage in PHPT, according to the severity of the disease.

The Abdominal Aortic Intima-Media Thickness Increases in Patients with Primary Hyperparathyroidism.

BACKGROUND: We aimed to determine whether there is an increase in aortic intima-media thickness values measured from the abdominal aorta in addition to the traditional carotid intima-media thickness in patients with primary hyperparathyroidism and to determine the parameters closely related to aortic intima-media thickness. METHODS: This perspective study included 65 primary hyperparathyroidism patients and 30 healthy-controls. Routine laboratory tests for the diagnosis of hyperparathyroidism and vascular ultrasound examinations were performed. Common carotid, internal carotid, and abdominal aortic intima media thickness were measured. The participants of the study was divided into 3 groups as the control (Group-I), the medical treatment (Group-II) due to primary hyperparathyroidism, and the planned surgery (group-III). RESULTS: Aortic intima-media thickness, serum urea, creatinine, glucose, uric acid, hs-CRP, parathyroid hormone, calcium and urine calcium levels increased significantly from Group-I to Group-III and T-scores and serum phosphorus in levels decreased significantly. Carotid intima-media thicknesses were not significantly different between the groups. Serum and urinary calcium levels were independently associated with aortic intima-media thickness. Aortic intima-media thickness, serum phosphorus, parathyroid hormone, T-scores, serum and urinary calcium levels are independent indicators for Group-III. When the cut-off value of aortic intima-media thickness was taken as 1.5 mm, 80.6% sensitivity and 89.1% specificity were determined for patients who would go to surgery. CONCLUSION: Serum and urine calcium levels were independently associated with aortic intima-media thickness. Aortic intima-media thickness is more useful than carotid intima-media thickness in showing vascular organ involvement in patients with primary hyperparathyroidism.

Current opinions on nephrolithiasis associated with primary hyperparathyroidism.

Nephrolithiasis is a common urological disease and could be secondary to primary hyperparathyroidism (PHPT). PHPT is traditionally characterised with hypercalcaemia. Recently, a normocalcemic PHPT has been officially recognised at the International Workshops. Regarding this new phenotype, nephrolithiasis is frequently found in studies that evaluate low bone mass. However, until now, no study on aetiology of nephrolithiasis considered normocalcemic PHPT. Hypercalciuria related to PHPT is considered as an important risk factor of stone formation in hypercalcemic PHPT, but the precise relationships between hypercalcemic PHPT and nephrolithiasis and between normocalcemic PHPT and nephrolithiasis remain unclear. In patients with hypercalcemic PHPT, after a surgical cure of PHPT, the renal calcium excretion and stone recurrence rate reduce but remain higher above health controls. This finding implies that abnormalities not caused by PHPT also probably affect stone formation. According to the new guideline, the presence of stones indicates the need for parathyroidectomy in patients with either hypercalcemic or normocalcemic PHPT unless contraindications exist. Patients with contraindications for parathyroidectomy or those who do not want to receive parathyroidectomy should be monitored for signs of disease progression and given of medical management. Moreover, due to decreased but significantly higher frequency of nephrolithiasis above those of healthy controls, patients with nephrolithiasis associated with PHPT after parathyroidectomy still should be motivated to explore strategies to prevent stone occurrence.

Sporadic primary hyperparathyroidism and stone disease: a comprehensive metabolic evaluation before and after parathyroidectomy.

OBJECTIVES: To characterize the stone risk and the impact of parathyroidectomy on the metabolic profile of patients with primary hyperparathyroidism (PHPT) and urolithiasis. PATIENTS AND METHODS: We analysed the prospectively collected charts of patients treated at our stone clinic between January 2001 and January 2016 searching for patients with PHPT and urolithiasis. Imaging evaluation of the kidneys, bones and parathyroid glands was assessed. We analysed the demographic data, serum and urinary variables before and after parathyroidectomy. We used a paired t-test, Fisher's test, Spearman's test and anova in the statistical analysis. RESULTS: A total of 51 patients were included. The mean patient age was 57.1 ± 12.1 years and 82.4% were women. Before parathyroidectomy, mean calcium and parathyroid hormone (PTH) levels were 11.2 ± 1.0 mg/dL and 331 ± 584 pg/dL, respectively. Hypercalcaemia was present in 84.3% of patients. All eight patients with normal calcium levels had elevated PTH levels. Only two patients did not have PTH above the normal range, although both had elevated calcium levels. The most common urinary disorders were low urinary volume (64.7%), hypercalciuria (60.8%), high urinary pH (41.2%) and hypocitraturia (31.4%). After parathyroidectomy, the number of patients with hypercalcaemia (n = 4; 7.8%), elevated PTH (n = 17; 33.3%) and hypophosphataemia (n = 3; 5.9%) significantly decreased (P < 0.001). The number of urinary abnormalities decreased and there was a reduction in urinary calcium (P < 0.001), pH (P = 0.001) and citrate levels (P = 0.003). CONCLUSION: Individuals with PHPT and nephrolithiasis frequently have elevated baseline PTH and calcium levels. Low volume, hypercalciuria, high urinary pH, and hypocitraturia are the most frequent urinary disorders. Parathyroidectomy is effective in normalizing serum calcium and PTH levels, although other urinary metabolic may persist. Patients should be monitored for the need for citrate supplementation.

Factors influencing pre-operative urinary calcium excretion in primary hyperparathyroidism.

OBJECTIVE: Normal or elevated 24-hour urinary calcium (Ca) excretion is a diagnostic marker in primary hyperparathyroidism (PHPT). It is used to distinguish familial hypocalciuric hypercalcaemia (FHH) from PHPT by calculating the Ca/creatinine clearance ratio (CCCR). The variance of CCCR in patients with PHPT is considerable. The aim of this study was to analyse the parameters affecting CCCR in patients with PHPT. DESIGN: The data were collected prospectively. Patients with sporadic PHPT undergoing successful surgery were included in a retrospective analysis. PATIENTS: The analysis covered 381 patients with pre-operative workup 2 days before removal of a solitary parathyroid adenoma. MEASUREMENTS: The impact of serum Ca and 25-hydroxyvitamin D3 (25-OH D3) on CCCR. RESULTS: The coefficient of determination (R2 ) in the multivariable model for CCCR consisting of age, Ca, 25-OH D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), testosterone (separately for males and females), intact parathyroid hormone (iPTH) and osteocalcin was 25.8%. The only significant parameters in the multivariable analysis were 1,25-(OH)2 D3 and osteocalcin with a drop in R2 of 15.4% (P<.001) and 2.4% (P=.006), respectively. Bone mineral densities at the lumbar spine, distal radius and left femoral neck were not associated with CCCR (r=-.08, r=-.10 and r=-0.09). CONCLUSIONS: In multivariable analysis, 1,25-(OH)2 D3 and osteocalcin were the only factors correlating with CCCR. Vitamin D3 replacement may therefore impair the diagnostic value of CCCR and increase the importance of close monitoring of urinary Ca excretion during treatment.

Low 24-hour urine calcium levels in patients with sporadic primary hyperparathyroidism: is further evaluation warranted prior to parathyroidectomy?

BACKGROUND: Low 24-hour urine calcium (uCa) levels in patients with primary hyperparathyroidism (pHPT) raise concern for familial hypocalciuric hypercalcemia. This study evaluated patients with a low 24-hour uCa level for potential differences that may guide the extent of preoperative evaluation needed. METHODS: A retrospective review was conducted of 1,139 sporadic pHPT patients who underwent parathyroidectomy between December 1999 and May 2011. RESULTS: Of the 54 (5%) patients with greater than or equal to one low 24-hour uCa (<100 mg), 28 (52%) patients had only one low level, 9 (17%) had multiple low levels, and 17 (31%) had a repeat 24-hour uCa greater than 100. In the latter group, 4 of the 9 (53%) patients were on a thiazide and had normalization after cessation. Among the groups, differences existed only in serum creatinine (P = .0011) and glomerular filtration rate (P = .0007). CONCLUSION: This study suggests that sporadic pHPT patients with low 24-hour uCa levels may not require further evaluation with genetic testing for familial hypocalciuric hypercalcemia, especially if previous eucalcemia is documented.

Laboratory approaches for the diagnosis and assessment of hypercalcemia.

Calcium, the fifth most common element in the body, plays major physiological functions. Measurement of blood calcium is one of the most commonly ordered laboratory tests in assessments of calcium homeostasis and disease diagnosis. Hypercalcemia is an increased level of calcium in the blood. This disorder is most commonly caused by primary hyperparathyroidism and malignancy. However, other less common causes of elevated calcium levels need to be considered when making a differential diagnosis. This review is intended to provide readers with a better understanding of calcium homeostasis and the causes and pathophysiology of hypercalcemia. Most importantly, this review describes useful approaches for laboratory scientists and clinicians to appropriately diagnose and assess hypercalcemia.

Factors associated with vertebral fracture risk in patients with primary hyperparathyroidism.

OBJECTIVE: To examine factors, in addition to bone mineral density (BMD), such as the common calcium-sensing receptor (CASR) gene polymorphisms, associated with vertebral fracture (VFx) risk in primary hyperparathyroidism (PHPT). DESIGN AND METHODS: A cross-sectional analysis of 266 Caucasian PHPT seen as outpatients. Serum calcium (sCa) phosphate metabolism parameters were measured. BMD was assessed by dual-energy X-ray absorptiometry (expressed as Z-score) at lumbar spine (Z-LS) and femoral neck, morphometric VFx by radiograph, and CASR A986S/R990G genotypes by PCR amplification and genomic DNA sequencing. RESULTS: Fractured patients (n=100, 37.6%) had lower sCa (10.8±0.7 mg/dl) and Z-LS BMD (-1.0±1.44), higher age (61±10 years), and prevalence (51%) of ≥1 S alleles of the CASR A986S single-nucleotide polymorphism (SNP; AS/SS), than those not fractured (n=166, 11.2±1.0 mg/dl, -0.57±0.97, 58±13 years, and 38% AS/SS, respectively, P<0.05 for all comparisons). Logistic regression, with VFx as dependent variable, showed independent risks associated with increased age (OR 1.03, 95% CI 1.01-1.06, P=0.006), decreased sCa (OR 1.86, 95% CI 1.28-2.7, P=0.001), and Z-LS BMD (OR 1.4, 95% CI 1.12-1.7, P=0.002) and presence of AS/SS (OR 1.8, 95% CI 1.1-2.9, P=0.05). The presence of two out of three factors (age ≥58 years, sCa <10.8 and Z-LS BMD≤-1.0, and AS/SS genotype) gave an overall OR of 4.2 (95% CI 2.25-7.85, P<0.0001). CONCLUSIONS: In PHPT, VFx is associated positively with age, negatively with sCa and spinal BMD, and presence of at least one copy of the CASR A986S SNP.

Coexisting primary hyperparathyroidism and sarcoidosis cause increased angiotensin-converting enzyme and decreased parathyroid hormone and phosphate levels.

CONTEXT: Primary hyperparathyroidism (PHPT) and sarcoidosis may separately contribute to abnormal calcium and phosphate metabolism via different mechanisms, and their coexistence is infrequently reported. OBJECTIVE: We sought to characterize a group of 50 patients with coexisting PHPT and sarcoidosis in our institution to evaluate their clinical and laboratory characteristics. DESIGN AND SETTING: This was a retrospective observational study of patients with both disorders at our institution between January 1980 and December 2011. OUTCOME: A cohort of 50 patients was identified, with mean ± SD age 59.6 ± 13.9 years and 86% women. Serum calcium in the cohort was 11.1 ± 1.1 mg/dL, phosphate was 3.3 ± 0.6 mg/dL, and PTH was 76 ± 42 pg/mL. Serum 25-hydroxyvitamin D was 25 ± 9 ng/mL, and serum 1,25-dihydroxyvitamin D was 51 ± 20 pg/mL; 24-hour urine calcium was 275 ± 211 mg. In subjects with sarcoidosis, serum angiotensin-converting enzyme (ACE) was 47.2 ± 37.4 U/L. Sarcoidosis was diagnosed first in 50% of patients, PHPT was diagnosed first in 16% of patients, and sarcoidosis and PHPT were both diagnosed within 6 months of each other in 30% of patients. The interval between the 2 diagnoses when sarcoidosis was diagnosed first was 15.5 ± 12.4 years and was 5.5 ± 6.0 years when PHPT was diagnosed first. Patients with PHPT who had active sarcoidosis had higher serum ACE levels (60.9 ± 38.1 vs 20.2 ± 14.0 U/L, P <.0001), lower PTH levels (60 ± 24 vs 96 ± 41 pg/mL, P = .01), and lower phosphate levels (2.7 ± 0.6 vs 3.2 ± 0.5 mg/dL, P = .02). CONCLUSIONS: Fifty patients with coexisting PHPT and sarcoidosis are described, with patients with PHPT coexisting with clinically active sarcoidosis having increased serum ACE levels and decreased serum PTH and phosphate levels compared with those with inactive sarcoidosis.

24-hour urinary calcium in primary hyperparathyroidism.

OBJECTIVE: To establish whether urinary and serum calcium levels are correlated in patients with primary hyperparathyroidism (PHPT) and to evaluate related factors including serum levels of parathyroid hormone (PTH) and vitamin D, age, gender and renal function. DESIGN: Retrospective review on patients undergoing a parathyroidectomy for PHPT from 2000- 2008. Data collected included: age, sex, preoperative serum calcium (ionized and total), creatinine, PTH, postoperative ionized calcium, vitamin D, and 24-hour urine calcium and creatinine. Data were evaluated by standard descriptive statistics. RESULTS: Of the 214 patients evaluated, preoperative 24-hour urinary calcium was available for 150 patients (70%). 24-hour urine calcium levels did not correlate significantly with preoperative total serum or ionized calcium, PTH, vitamin D, or postoperative serum ionized calcium. There were significant correlations (P<0.0001) of 24-hour urinary calcium with age, serum creatinine, and urine creatinine. Secondary analysis grouped subjects by urinary calcium level greater or less than 400 mg/24 hours. Age and urinary creatinine were significantly different between the two groups. CONCLUSIONS In patients with PHPT who underwent parathyroidectomy, there was little correlation between preoperative 24-hour urine calcium and preoperative serum calcium, PTH, or vitamin D levels. 24-hour urine calcium levels were correlated with renal function and age, but these correlations are likely to occur in the general population and are not specific to this disease group.

Persistence of hypercalciuria after successful surgical treatment for primary hyperparathyroidism.

UNLABELLED: Primary hyperparathyroidism (PHPT) causes hypercalciuria and stone disease in a subset of patients. Hypercalciuria typically normalizes after surgery, although the risk of stone formation may persist up to 10 years. There are few reports in the literature that show persistent hypercalciuria despite normalization of serum calcium after parathyroid surgery. We retrospectively analyzed 111 patients with PHPT from the osteoporosis, and stone clinics seen between 1999 and 2006. We selected only patients who had a complete metabolic profile that included 24-hour collections before and at least 3 months after parathyroidectomy. We excluded patients who had creatinine clearance <60 ml/min/1.73 m(2). Fifty-four patients were selected for further analysis, 46 with baseline hypercalciuria and 8 with normocalciuria. Changes in filtered load of calcium and fractional excretion of calcium were evaluated before and after parathyroid surgery. Total and ionized calcium and phosphorus normalized in all patients after surgery (24 ± 19 months); fractional excretion of calcium decreased, but did not normalize. Hypercalciuria persisted after surgery in 30.7% (n = 12/39) of the women and 50% (n = 4/8) of men. Of the patients in whom calciuria normalized after parathyroidectomy, 43.3% (n = 13/30) had kidney stones before surgery, whereas kidney stones were present in 87.5% (n = 14/16) in those in whom hypercalciuria persisted postsurgery. In hypercalciuric men and women before surgery in whom hypercalciuria persisted after surgery, fractional excretion of calcium was significantly higher than that in patients with normocalciuria. CONCLUSIONS: Persistently increased fractional excretion of calcium could explain the sustained increased risk of stone disease in patients with PHPT for many years after successful parathyroidectomy.

Urinary parameters as predictors of primary hyperparathyroidism in patients with nephrolithiasis.

PURPOSE: Serum calcium and parathyroid hormone levels are the primary means of evaluating patients for hyperparathyroidism. Whether there are differences in urinary parameters between stone formers with and those without hyperparathyroidism is controversial. In this study we identify urinary parameters that predict primary hyperparathyroidism. MATERIALS AND METHODS: From 2001 to 2010 a total of 1,190 adult, noncystine stone forming patients underwent urinary metabolic stone evaluation. Of these patients 34 (3%) underwent parathyroidectomy for primary hyperparathyroidism. Urinary parameters were evaluated as predictors of primary hyperparathyroidism. The most accurate combination of serum and urinary tests and their cutoffs were determined. RESULTS: Stone forming patients with primary hyperparathyroidism were more likely to be women and had higher urinary calcium excretion. Hypercalciuria (aOR 4.38), supersaturation calcium oxalate greater than 10 (aOR 4.27), supersaturation calcium phosphate greater than 2 (aOR 3.64), calcium per kg greater than 4 mg/kg (aOR 8.03) and calcium-to-creatinine ratio greater than 150 mg/gm (aOR 7.07) were significant predictors of primary hyperparathyroidism in separate multivariate models after adjustment. The best accuracy was determined using serum calcium and parathyroid hormone levels with our laboratory cutoffs (AUC 0.984) with a sensitivity of 87%, specificity of 99%, positive predictive value of 79% and negative predictive value of 99.5%. No other factor(s) improved diagnostic accuracy or could replace parathyroid hormone level. CONCLUSIONS: Greater urinary calcium excretion predicted primary hyperparathyroidism. Serum calcium with parathyroid hormone level was the most accurate test for primary hyperparathyroidism. No other serum or urinary parameter improved diagnostic accuracy or could replace parathyroid hormone. There were no obvious cutoffs for any of the urinary parameters that reliably differentiated cases of hyperparathyroidism.