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Original Research |
1 Department of Diagnostic Imaging, The Warren Alpert Medical School of Brown
University and Rhode Island Hospital, 593 Eddy St., Providence, RI
02903.
2 Department of Surgery, The Warren Alpert Medical School of Brown University
and Rhode Island Hospital, Providence, RI.
Received September 13, 2007;
accepted after revision March 11, 2008.
Address correspondence to J. J. Cronan
(jcronan{at}lifespan.org).
Abstract
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MATERIALS AND METHODS. We retrospectively reviewed the renal sonograms of 271 patients with surgically proven primary hyperparathyroidism. All patients had undergone renal imaging within 6 months before parathyroid surgery. Our control group consisted of 500 age-matched subjects who had right upper quadrant sonograms obtained for various reasons.
RESULTS. Nineteen (7.0%) of the 271 patients with primary hyperparathyroidism had renal stones, and eight (1.6%) of the 500 subjects in the control group had stones. Pearson's chi-square analysis showed that this difference in prevalence is significant (p < 0.0001).
CONCLUSION. Our results showed a fourfold increased prevalence of asymptomatic renal stone disease in patients with surgically proven primary hyperparathyroidism compared with subjects not affected by the disorder. The National Institutes of Health consensus conference on asymptomatic primary hyperparathyroidism recommended that patients with renal stone disease undergo parathyroid surgery. These patients should undergo surgery even if they have minimal or no elevation of the total serum calcium value and no other metabolic manifestations of hyperparathyroidism. The finding of nephrocalcinosis or nephrolithiasis is, therefore, a significant finding in evaluating patients for parathyroid surgery. Routine imaging of the kidneys is necessary when primary hyperparathyroidism is documented.
Keywords: hypercalcemia • hyperparathyroidism • nephrocalcinosis • nephrolithiasis • parathyroid gland • renal stones • sonography
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The signs and symptoms of hyper parathyroidism reflect the combined effects of increased parathyroid hormone secretion and hypercalcemia [5]. Primary hyper para thyroidism has traditionally been associated with a constellation of symptoms including "painful bones, renal stones, abdominal groans, and psychic moans." Barium swallow was the principal diagnostic imaging study used to preoperatively localize para thyroid adenomas in the 1970s. The lesions were found in a late stage of clinical pre sentation: The parathyroid adenomas were sufficiently large and were often distorting the esophagus (Fig. 1).
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We collected the records and images of a con trol group to assess the prevalence of renal calculi in patients not being evaluated for hyperparathyroidism. The control cohort con sisted of right upper quadrant sonography scans obtained from July 1, 2006, to September 29, 2006, for various reasons (e.g., upper abdominal pain, cholelithi asis, abnormal liver function studies) in 500 pa tients 36 years old or older (212 men and 288 women; mean age, 59 years; age range, 36–91 years).
Renal sonography was performed using 3–7-MHz transducers in an attempt to image with the highest-frequency transducer that would permit assessment of the entire kidney. Renal length, renal echogenicity, the presence or absence of hydronephrosis, and the presence or absence of renal stones were noted. If a renal stone was detected, color Doppler imaging was used to assess for the presence of twinkling artifact.
Right upper quadrant sonography included complete scanning of the liver, gallbladder, and right kidney. The right kidney was specifically interrogated with a 3–7-MHz transducer and, in each instance, renal length, renal masses (if present), hydronephrosis, and renal echogenicity were assessed. Within the kidney, any echogenic focus thought to be a stone was noted and Doppler assessment for the "twinkle sign" sought.
The sonography images were initially inter preted by reviewing the original radiology report for each examination. The findings in the reports were classified as positive or as negative for renal calculi. Positive cases were reevaluated by a board-certified reviewer to confirm stones because it is well documented in the literature that blood ves sels may be misinterpreted as calculi on sono graphy [8]. For definitive diag nosis, stones must show echogenicity (i.e., echo difference), pos terior acoustic shadowing, or a positive twinkle sign [9, 10]. We did not evaluate the bladder in either study group.
Statistical Analysis
Pearson's chi-square test was used to determine the relationship between
primary hyper parathyroidism and the presence of renal calculi. A p
value of < 0.05 was considered significant.
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In the control group, 13 kidney stones were detected in the 500 subjects who underwent imaging because of abdominal pain, cholelithiasis, or abnormal liver function studies. After performing the same review protocol as that performed in the patient group, we confirmed eight cases as definitive stones and eliminated five false-positive cases. The final prevalence of renal calculi in the control group was 1.6% (Table 1). We also noted two kidneys with mild hydronephrosis. In neither case of hydronephrosis was a stone detected. In both study groups, stones varied in size from 3 to 20 mm (Table 2).
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We noted a fourfold increased prevalence of renal stones in patients with primary hyperparathyroidism compared with those not affected by the disorder. Chi-square analysis confirmed the significance of this finding. Pearson's chi-square value was 15.23 (p < 0.0001).
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In addition to a decrease in the prevalence of renal calculi, the size of the detected renal stones has also decreased. Abdominal radiographs showing large staghorn calculi filling the entire collecting system were typical in patients with hyperparathyroidism in the 1950s. Sonography now shows very small calculi of at least 5 mm with the twinkle sign [9–12] (Table 2).
Modern diagnostic tools for recognizing hypercalcemia and serum concentrations of parathyroid hormone have had a dramatic impact on the frequency with which primary hyperparathyroidism is diagnosed, especially in older people (> 18 years) with nonspecific symptoms of the disease. Renal stone disease is considered a less frequent complication of primary hyperparathyroidism by some investigators, although others have reported that up to 75% of patients undergoing surgical treatment for primary hyper para thyroidism present with nephrolithiasis [4]. The results of a study by Mollerup et al. [13] showed that the risk of renal stone disease in patients with primary hyperparathyroidism not only is greater but also remains elevated 10 years after surgery. If the underlying cause is not found and treated, painful renal stones may recur and cause permanent kidney damage [13]. Patients with recurrent nephrolithiasis and nephrocalcinosis may develop urinary tract obstruction, infection, and loss of renal function.
In 1990, the NIH presented a consensus statement [6] about the indications for parathyroidectomy; the statement explained that the term "asymptomatic primary hyper parathyroidism" should be used to describe "the clinical profile of patients with documented primary HPT [hyper para thyroidism] without symptoms or signs commonly attributable to the disease" [6]. Some patients may have one or several indistinct and nonspecific symptoms that cannot be definitively at trib uted to primary hyperparathyroidism. In contrast, patients who present with significant bone, renal, neuromuscular, or gastrointestinal symptoms typical of primary hyper para thyroidism are defined as symptomatic and require surgery [5].
Imaging studies are crucial in the care of patients with kidney stones. Many radiologic techniques are available today including abdominal radiography, sonography, CT, and MRI. Imaging can be used to establish the diagnosis of renal stones, assess the disease burden, determine distribution of stones within the kidney, identify pelvicaliceal anatomy, and evaluate kidney function [14]. The best method for diagnosing renal stones remains debatable [15]. We used sonography for renal stone assessment because it is the test of choice of our referring clinicians. It is recognized that small stones less than 5 mm may be problematic to detect on sonography when obscured by fat or bowel gas [10]. CT appears to have greater sensitivity than sonography in detecting stones but has the disadvantage of using ionizing radiation.
Sonography is easily used but has limited specificity for the detection of renal calculi because of confusion related to small stones and arcuate arteries [8]. In fact, we noted that 16 of 35 cases originally interpreted as stones on the basis of sonography findings were determined to be false-positives related to blood vessels. In the literature [8], researchers have reported that the arcuate arteries are often misinterpreted as renal calculi. In our study, we eliminated 16 false-positives in the patient cohort and five false-positives in the control group. We found that punctate echogenicity at the cortico medullary junction was often mistaken for calculi. The previously reported higher pro bability of renal stone disease in patients with primary hyperparathyroidism leads to a higher positive interpretative rate.
In conclusion, we found a fourfold increased prevalence of renal stones in patients with primary hyperparathyroidism compared with subjects not affected by the disorder. Although reduced in prevalence, nephrolithiasis and nephrocalcinosis remain the most common clinical manifestations of the disorder. Routine evaluation of the kidneys remains necessary even in asymptomatic patients with hyperpara thyroidism because asymptomatic renal stone disease is an indication for parathyroid surgery. Patients with primary hyper para thyroidism should be evaluated with carefully performed sono graphy to determine whether renal stone disease is present.
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