Methods
Study Subjects
PHPT Patients. We performed a retrospective analysis of a case series of PHPT patients admitted to the Division of Endocrinology of Santa Croce Hospital, Cuneo, Italy, from 2003 to 2011. Among 234 patients diagnosed with PHPT, only those with neither symptoms nor a history of renal stones entered the study.
PHPT was diagnosed in the presence of persistent hypercalcemia and inappropriately normal or elevated PTH concentrations. The screening protocol for evaluation of our PHPT patients included: (1) complete family and personal medical history; (2) physical examination, including body mass index (BMI) and blood pressure; (3) fasting biochemical evaluation of general blood and urinary parameters, including serum levels of total and ionized calcium, phosphate, creatinine, immunoreactive intact PTH, 25-hydroxyvitamin D3 (25[OH]D3), glucose, uric acid, and urinary calcium; (4) dual energy X-ray absorptiometry for assessment of mineral density at the lumbar spine, femoral neck, and one-third of the distal forearm; (5) neck US and parathyroid scintigraphy; and (6) routinely abdominal US. All charts were reviewed for age, sex, BMI, biochemical assay data (calcium, phosphate, PTH, creatinine, and uric acid blood levels, urinary calcium), and medical history of diabetes mellitus and arterial hypertension. Reports of abdominal US were classified as positive or negative for nephrolithiasis. The following characteristics of renal stones were reported: number, size (diameter ≤ or > than 5 mm), and mono- or bilateral renal involvement.
Patients were classified for surgical indication according to the most recent guidelines:
symptomatic patients were defined by the presence of nephrolithiasis, osteitis fibrosa cystica, symptoms of hypercalcemia;
asymptomatic patients with serum calcium at least 1 mg/dL above the normal reference range, renal impairment (creatinine clearance reduced to <60 mL/min), bone mineral density >2.5 standard deviations below peak bone mass (T-score less than −2.5), age younger than 50 years.
Control Group. The control group consisted of 315 consecutive subjects undergoing abdomen US at the Department of Radiology of Santa Croce Hospital, from January 2012 to September 2012. They had a short clinical evaluation before US to collect data regarding age, sex, BMI, history of diabetes, and hypertension. Subjects who underwent US for typical renal colic pain and those with a history of nephrolithiasis or hyperparathyroidism were excluded. The remaining control subjects were matched with PHPT patients on the basis of age and sex, using a 1:1 frequency technique. US findings as well as biochemical data (serum levels of calcium, PTH, 25(OH)D3, and creatinine, if evaluated during the previous 6 months) were retrieved from hospital records.
Biochemical Data
Serum levels of total calcium, phosphate, creatinine, and 24-hour urinary calcium were analyzed by a standard autoanalyzer using colorimetric and enzymatic methods, whereas ionized serum calcium was analyzed using a specific probe after correction for pH.
Serum 25(OH)D3 levels were measured by radioimmunoassay (RIA, DIAsource 25OH-VitD3-Ria-CT Kit, DIAsource ImmunoAssays S.A., Nivelles, Belgium), with a detection limit of 0.6 ng/mL (1.5 nmol/L) and inter- and intraassay coefficients of variation of 5.3 and 4.7%, respectively. Serum immunoreactive intact PTH was measured using a second-generation immunochemiluminometric assay (DPC, Los Angeles, CA) with intra- and interassay coefficients of variation of 4.2 to 5.7 and 6.3 to 8.8%, respectively. This assay reacts with the long fragments of human PTH that represent up to 50% of PTH immunoreactivity in renal failure patients. Glomerular filtration rate (GFR) was assessed using the "modification of diet in renal disease" formula reexpressed for use with a standardized creatinine assay as follows:
GFR = 175 × standardized Scr × age × 1.212(if black) × 0.742 (if female).
In this equation, GFR is expressed as mL/min/1.73 m, serum creatinine (Scr) is expressed as mg/dL, and age is expressed as years.
US Scanning
All patients and controls had standard renovesical sonogram performed by 2 skilled radiologists at Santa Croce Hospital, using a 2- to 5-MHz-wide band convex transducer. For definitive diagnosis of stones our radiologists looked for hyperechogenic spots more than 2 mm in diameter with multiplanar evaluation of specific signs as echogenicity, posterior acoustic shadowing, or positive twinkle sign.
Statistical Analysis
Variables were tested for normal distribution with the Shapiro-Wilks' W test. Data are expressed as mean (SD) or median and interquartile range or percentage, as appropriate. The Mann-Whitney U test or Student's t test for independent samples was used to compare continuous variables for data with a nonnormal or normal distribution, respectively. Differences in categorical variables between groups were evaluated using the χ or Fisher's test, as appropriate. The level of statistical significance was set at P<.05. Calculations were performed using Statistica for Windows, release 5.1 (Statsoft Inc, Tulsa, OK).