Primary hyperparathyroidism: the case for medical management.

Thirty two patients with primary hyperparathyroidism were followed up medically for a mean of 4.2 years. One patient had an operation because of a rise in plasma calcium concentration. There was no significant change in the mean plasma calcium and creatinine concentrations or in blood pressure during the period of follow up. The progress of these patients who were managed medically was compared with that of a group of 60 patients who had had successful operations for primary hyperparathyroidism. There was no significant change in mean plasma creatinine concentration or in blood pressure in the group who had had operations during a mean follow up period of 5.9 years. The natural history of mild asymptomatic hyperparathyroidism is probably different from and better than that of the type of hyperparathyroidism that was usually seen before the advent of routine chemical screening. It is suggested that patients over the age of 60 with mild asymptomatic hyperparathyroidism, and perhaps even younger patients, may not require operation.     

Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1: comparison with sporadic parathyroid adenomas.

A prospective study on the natural course of primary hyperparathyroidism has recently been reported. Since hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is genetically distinct from most forms of sporadic hyperparathyroidism, it is important to know the natural course of hyperparathyroidism in MEN 1 for better clinical management. For this purpose, we retrospectively reviewed clinical parameters of patients with MEN 1 when they were diagnosed as having hyperparathyroidism, and compared them with those of patients with sporadic primary hyperparathyroidism. In patients with MEN 1: 1) levels of intact PTH (i-PTH) gradually increased with age, which accelerated over 40 years; 2) compared to the steep rise in i-PTH levels in aged patients, increase in serum calcium or decrease of serum inorganic phosphate concentration was relatively mild, and 3) the high concentrations of i-PTH in aged patients were not due to renal insufficiency. These features were not observed in patients with sporadic primary parathyroid adenomas. Clinical features of untreated hyperparathyroidism in MEN 1 may be significantly affected by the age of the patient. The effect, if any, of age-dependent deterioration on recurrence rate after subtotal or total parathyroidectomy requires further elucidation.     

Primary Hyperparathyroidism

ObjectiveTo review primary hyperparathyroidism and the key issues that are relevant to the practicing endocrinologist.MethodsThe latest information on the presentation, diagnosis, and traditional and nontraditional aspects of primary hyperparathyroidism is reviewed.ResultsThe diagnosis of primary hyperparathyroidism is straightforward when the traditional hypercalcemic patient is documented to have an elevated parathyroid hormone (PTH) level. Commonly, patients are identified who have normal serum calcium levels but elevated PTH levels in whom no secondary causes for hyperparathyroidism can be confirmed. Traditional target organs of primary hyperparathyroidism—the skeleton and the kidneys—continue to be a focus in the patient evaluation. Bone mineral density shows a typical pattern of involvement with the distal one-third radius being selectively reduced compared with the lumbar spine in which bone mineral density is generally well maintained. Neurocognitive and cardiovascular aspects of primary hyperparathyroidism, while a focus of recent interest, have not been shown to definitively aid in the decision for or against surgery. The recommendation for surgery in primary hyperparathyroidism is based on guidelines that focus on the serum calcium level, renal function, bone mineral density, and age. In patients who do not meet guidelines, a nonsurgical management approach has merit.ConclusionsPrimary hyperparathyroidism is continuing to show changes in its clinical profile, with normocalcemic primary hyperparathyroidism being a topic of great interest. Skeletal and renal features of primary hyperparathyroidism drive, in most cases, the decision to recommend surgery. In patients who do not meet any criteria for surgery, a conservative approach with appropriate monitoring is acceptable. (Endocr Pract. 2012;18:781-790)     

Long term follow up of untreated primary hyperparathyroidism.

Fourteen patients with primary hyperparathyroidism and whose initial serum calcium concentrations were 2.75 mmol/l (11.0 mg/100 ml) or more were followed up for five to 23 years without operative treatment. One had osteitis fibrosa when seen and died with a fibrosarcoma 22 years later. The remaining 13 patients, who were followed up for a mean of 10 years, came to little obvious harm from not being operated on. Their serum calcium concentrations did not rise and there was no evidence of progressive renal impairment. In four patients who presented originally with renal calculi there were three further episodes of renal colic in 54 patient years of follow up. Conservative management of primary hyperparathyroidism is not an unreasonable option, and patients who do not have symptoms need not necessarily be pressed to accept surgery.     

The suppression of TSH in the presence of the normal PRL responses to TRH out of 26 patients with primary hyperparathyroidism

The responses of TSH and PRL to intravenous doses of 500 micrograms of TRH were investigated in 26 patients with primary hyperparathyroidism. Fourteen patients (54%) showed low responses of TSH with peak values of less than 5 microU/ml (Group A). Twelve patients showed normal responses of TSH to TRH (Group B). Among the 26, 12 cases belonging to Group A and eight in Group B were reexamined after the correction of serum calcium level by parathyroidectomy. After successful treatment, the responses of TSH to TRH in six of the 12 patients in Group A returned to normal, whereas those in the remaining six were unchanged. The responses in the eight patients in Group B after surgery were not changed when compared to those before treatment. The basal values of PRL and the responses of PRL to TRH were normal in all patients and did not change after treatment. We showed that patients with primary hyperparathyroidism have a high incidence (54%) of suppressed TSH response to TRH. Hypercalcemia was obviously one of the causative factors in inducing this abnormality in six patients. However, persistently suppressed responses of TSH to TRH were observed in the other six patients in Group A even after the correction of the serum calcium level by surgery. This finding suggests a primary failure of the TSH-regulatory mechanism in some cases of primary hyperparathyroidism.     

Primary hyperparathyroidism and familial hypocalciuric hypercalcemia: relationships and clinical implications

ObjectiveTo discuss the unusual occurrence of both familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism in the same patient and to explore potential mechanisms of association and issues related to clinical management.MethodsWe discuss the diagnosis, compare the clinical presentations of FHH and primary hyperparathyroidism, review the literature regarding patients who have presented with both disorders, and discuss management considerations. We also describe 2 patients who have both FHH (confirmed by genetic testing for a mutation in the gene encoding the calcium-sensing receptor [CASR]) and primary hyperparathyroidism.ResultsThe occurrence of both FHH and primary hyperparathyroidism in the same patient has been reported in a few cases, including 2 patients described here, one of whom was documented to have a novel CASR mutation. Inthose with clinical sequelae of hyperparathyroidism, parathyroidectomy has led to reduction, but not normalization, of serum calcium levels.ConclusionsThe coexistence of FHH and primary hyperparathyroidism should be considered in patients with hypercalcemia, hypophosphatemia, frankly elevated parathyroid hormone levels, and low urinary calcium excretion. Genetic testing for inactivating CASR gene mutations can confirm the diagnosis of FHH. Although surgical intervention does not resolve hypercalcemia, it may be beneficial by reducing the degree of hypercalcemia, alleviating the symptoms, and preventing potential complications of hyperparathyroidism. (Endocr Pract. 2012;18:412-417)     

Albumin-Corrected Calcium and the Prevalence and Categories of Hypercalcemia in Hospitalized Patients With 1-Year Follow-Up of Undiagnosed Cases

ObjectiveTo assess the impact of using corrected calcium versus total calcium on hypercalcemia case detection in hospitalized patients.MethodsPatients hospitalized from June 2012 to June 2017 with a corrected calcium level of ≥10.5 mg/dL were identified by medical record review. One-year follow-up data through June 2018 were acquired. Albumin-corrected calcium level was calculated: (4 − albumin concentration in g/dL) × 0.8 + total serum calcium in mg/dL.ResultsA group of 1067 patients had a corrected calcium level of ≥10.5 mg/dL. The prevalence of hypercalcemia was 0.73% with total calcium and 1.09% with corrected calcium, respectively, with a 49% relative increase. Most patients (62%) had mild hypercalcemia (10.5-11.9 mg/dL); 3.7% had severe hypercalcemia (>14 mg/dL). With corrected calcium, the most common categories of hypercalcemia were malignancy (35.4%), hypercalcemia that was not further evaluated (31.1%), and hyperparathyroidism (22.4%). All patients in the unidentified category had albumin levels <2.8 g/dL. At the 1-year follow–up, 63% of the unidentified cases had normal calcium levels, and 26.8% had mild persistent hypercalcemia. Of those with persisting hypercalcemia at 1 year, 16.8% were diagnosed with hyperparathyroidism.ConclusionUsing albumin-corrected calcium resulted in an ∼50% increase in the detection of hypercalcemia cases. Although hypercalcemia resolved in majority of the undiagnosed cases at 1 year, a number of these remained abnormal. Detecting hypercalcemic disorders by correcting for low albumin level can help identify conditions such as hyperparathyroidism. Adding auto-calculated albumin-corrected calcium to routine laboratory tests could be a cost-effective intervention to improve the detection of hypercalcemic disorders.     

Calcium,Parathyroid Hormone,and Vitamin D in Patients with Primary Hyperparathyroidism: Normograms Developed from 10000 Cases

ObjectiveTo better define the typical and atypical biochemical profiles of patients with surgically proven primary hyperparathyroidism.MethodsIn this single-center, prospectively conducted study of consecutive patients with surgically proven primary hyperparathyroidism over a 7-year period, we analyzed serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations.ResultsA total of 10 000 patients were included, and more than 210 000 calcium, parathyroid hormone, and 25-hydroxyvitamin D values were evaluated. Both calcium and parathyroid hormone levels demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/mL. The average highest calcium and parathyroid hormone concentrations were 11.4 ± 0.7 mg/dL and 115.3 ± 50 pg/mL, respectively. At least 1 calcium value of 11.0 mg/dL was seen in 87% of patients, but only 21% had 1 or more calcium value above 11.5 mg/dL. Only 7% had a single serum calcium level reaching 12.0 mg/dL. Normocalcemic hyperparathyroidism was seen in just under 3% of patients who had identical findings at surgery. An average parathyroid hormone concentration less than 65 pg/mL was seen in 16%, with 10% of patients who had no high parathyroid hormone values. The average 25-hydroxyvitamin D concentration was 22.4 ± 9 ng/mL, with levels decreasing as calcium levels increased (P < .001); 36% had 25-hydroxyvitamin D levels below 20 ng/mL.ConclusionsPatients with PHPT present with a number of distinct biochemical profiles, but as a group, they present with a near-normal Gaussian distribution of both calcium and parathyroid hormone levels. Either serum calcium or parathyroid hormone remained normal in 13% of patients, yet the findings at surgery are similar to those of patients with elevated calcium or parathyroid hormone. Low 25-hydroxyvitamin D is an expected finding in patients with PHPT, decreasing as serum calcium levels increase. (Endocr Pract. 2011;17:384-394)     

Renal Effects of Calcitonin

Porcine calcitonin in a slow-release gelatin vehicle was given by intramuscular injection to 10 patients—four with primary hyperparathyroidism, four with Paget''s disease, and two with carcinoma of the breast and hypercalcaemia. All cases showed a fall in serum calcium with an immediate rise in urine calcium. All except three patients with primary hyperparathyroidism showed a fall in serum phosphorus, but an immediate rise in urine phosphorus occurred in all cases. Urine hydroxyproline output fell in three patients with severe Paget''s disease. Urine sodium rose in all cases, but the effects on potassium, magnesium, water, and pH were not appreciably different from results obtained in four control subjects who were given the gelatin vehicle alone.The data suggest that calcitonin caused a decrease in the tubular resorption of calcium and phosphorus. The hypocalcaemic effect appeared to be due to a decrease in bone resorption in the patients with Paget''s disease but in the remaining cases could be accounted for in part or entirely by the rise in urine calcium.     

Echocardiographic Findings in Patients With Normocalcemic Primary Hyperparathyroidism Compared With Findings in Hypercalcemic Primary Hyperparathyroid Patients and Control Subjects

ObjectiveThere are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls.MethodsSeventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation.ResultsPatients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction).ConclusionIn a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls.     

Failure of cyproheptadine to affect calcium homoeostasis and PTH levels in primary hyperparathyroidism

In this study we evaluated the influence of cyproheptadine treatment on serum PTH values, as well as serum Ca, Mg and P levels in patients with primary hyperparathyroidism. For this purpose, cyproheptadine was given in a dose of 4 mg orally every 4 hours during 10 consecutive days to six patients with primary hyperparathyroidism. Control fasting blood samples for PTH, Ca, Mg and P were obtained every other day for a week. Afterwards cyproheptadine treatment was applied as mentioned above. Then blood samples were taken on the 4th, 6th, and 10th day of treatment to determine serum PTH, Ca, Mg and P. Before treatment the mean PTH (+/- SE) values were 22.95 +/- 1.4 mlU/ml and during cyproheptadine treatment were 23.06 +/- 0.9, 22.95 +/- 0.8, 22.32 +/- 0.8 mlU/ml, respectively. There were no significant changes in serum PTH levels before and during treatment (P greater than 0.05). Also serum Ca, Mg and P levels remained unchanged. Our data suggest that cyproheptadine treatment does not affect calcium homoeostasis and serum PTH levels in primary hyperparathyroidism.     

Safety of Immediate Discharge after Parathyroidectomy: A Prospective Study of 3,000 Consecutive Patients

ObjectiveTo evaluate the safety of immediate discharge after parathyroidectomy and to establish a protocol for the amount and duration of supplemental orally administered calcium for patients with varied clinical presentations of primary hyperparathyroidism.MethodsA 40-months, prospective, single institution, cohort study of 3,000 consecutive patients undergoing parathyroidectomy and discharged within 2.5 hours after the operation is reviewed. The amount of oral calcium supplementation prescribed postoperatively varied according to a protocol that considered the degree of serum calcium elevation preoperatively as well as the intraoperative findings (hyperplasia versus adenoma). Symptoms of hypocalcemia were tracked, and all surgical outcomes were monitored.ResultsWith use of the reported protocol, less than 7% of patients had postoperative symptoms of hypocalcemia, most of whom were successfully selftreated with additional orally administered calcium. Only 6 patients (0.2%) required a visit to the emergency department for intravenous calcium infusion, all occurring on postoperative day 3 or later, and none of these patients required rehospitalization. Postoperative calcium requirements varied on the basis of the degree of serum calcium elevation preoperatively, number of parathyroid glands removed or subjected to biopsy, presence of morbid obesity, and presence of severe osteoporosis.ConclusionPatients with primary hyperparathyroidism can be sent home immediately after successful parathyroidectomy, provided specific measures are taken regarding postoperative oral calcium supplementation. Use of a specific calcium dosing protocol that considers several patient variables will prevent the postoperative development of symptomatic hypocalcemia in 93% of patients, identify patients at high risk of hypocalcemia, and allow most patients who develop symptoms of hypocalcemia to self-medicate in a simple and predictable fashion. Routine monitoring of postoperative serum calcium levels in the hospital can be safely eliminated if the details of this protocol are followed. (Endocr Pract. 2007;13:105-113)     

Familial hypocalciuric hypercalcaemia and acute pancreatitis.

Four families with familial hypocalciuric hypercalcaemia were studied. The probands presented with abdominal pain, which in three was due to acute pancreatitis; in two the condition was life threatening. Serum concentrations of calcium, magnesium, phosphate, and immunoassayable parathyroid hormone, urinary calcium excretion, and the rate of renal tubular reabsorption of phosphate were measured; the findings were compared with results in 10 patients with primary hyperparathyroidism matched for serum calcium concentration to establish differences between the diseases. Familial hypocalciuric hypercalcaemia should be suspected in patients with hypercalcaemia in whom daily urinary calcium excretion is below 5 mmol (200 mg) provided renal insufficiency, vitamin D deficiency, and ingestion of drugs that reduce calcium excretion have been excluded. Most cases appear to run a benign course, but some may suffer considerable morbidity. Surgical treatment should be reserved for patients with severe complications, when all parathyroid tissue should be removed.     

Increased Serum Calcium is not Common in Hospitalized Patients with Primary Hyperparathyroidism: A Retrospective,Observational Study

Objective: Serum calcium levels often decrease during acute illness in patients with an intact calcium-regulating system. However, the dynamics of serum calcium levels in hospitalized patients with primary hyperparathyroidism (PHPT) have not yet been described.Methods: Clinical and laboratory data were retrospectively retrieved from the electronic medical records of patients with PHPT before, during, and after hospitalization for various reasons (excluding parathyroid surgery).Results: There were 99 nonselected patients with asymptomatic, hypercalcemic PHPT, hospitalized for various reasons; 42% were admitted for apparent infectious or septic conditions, and 58% were admitted for noninfectious conditions. Total serum calcium increased >0.5 mg/dL in 7.4% of the patients: 10.9% and 2.5% of the patients with noninfectious and infectious conditions, respectively. In 65.7% of the patients, the mean total serum calcium (TsCa), but not albumin-corrected calcium (corrCa), decreased significantly during hospitalization, down to below the upper limit of the reference range. Although prehospitalization TsCa and corrCa were similar in patients with infectious and noninfectious conditions, during hospitalization, TsCa was lower in patients with infectious conditions (P = .02). Both TsCa and albumin returned to prehospitalization levels after recovery.Conclusion: TsCa increases in a minority of hospitalized PHPT patients. In the majority of hospitalized patients with PHPT, TsCa, but not corrCa, decreases to within the normal reference range, more so in patients with infectious conditions, obscuring the major characteristic of PHPT. Therefore, it is prudent to follow calcium and corrCa during hospitalization in patients with PHPT.Abbreviations: corrCa = albumin-corrected serum calcium; IQR = interquartile range; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TsCa = total serum calcium     

Suppressibility of Parathyroid Hormone in Primary Hyperparathyroidism

ObjectiveTo describe an unusual case of pathologically confirmed primary hyperparathyroidism in a patient presenting with severe hypercalcemia and an undetectable parathyroid hormone (PTH) level.MethodsWe present a detailed case report and outline the serial laboratory findings. In addition, the possible causes of low serum PTH levels in the setting of primary hyperparathyroidism are discussed.ResultsA 16-year-old female patient presented with severe epigastric pain, found to be attributable to acute pancreatitis. At hospital admission, her serum calcium concentration was high (14.0 mg/dL); the patient also had a normal serum phosphorus level of 3.6 mg/dL and an undetectable PTH level (< 0.2 pmol/L). An evaluation for non-PTH-mediated causes of hypercalcemia revealed a partially suppressed thyroid-stimulating hormone concentration and a below normal 1,25-dihydroxyvitamin D level, consistent with her suppressed PTH. One week after the patient was dismissed from the hospital, repeated laboratory studies showed a serum calcium value of 11.1 mg/dL, a serum phosphorus level of 2.8 mg/dL, and an elevated PTH concentration of 11.0 pmol/L, consistent with primary hyperparathyroidism. A repeated 1,25-dihy-droxyvitamin D measurement was elevated. A parathyroid scan showed a parathyroid adenoma in the left lower neck area, and she subsequently underwent successful surgical resection of a pathologically confirmed parathyroid adenoma.ConclusionThis case demonstrates that the serum PTH level can be suppressed in patients with primary hyperparathyroidism. Moreover, it emphasizes the need for careful evaluation of the clinical context in which the PTH measurement is determined. Consideration should be given to repeating measurement of PTH and serum calcium levels when the initial laboratory evaluation of hypercalcemia is unclear because dynamic changes in calcium metabolism may occur in the presence of secondary contributing factors. (Endocr Pract. 2007;13:785-789)     

Significance of Elevated Parathyroid Hormone After Parathyroidectomy

ObjectiveTo review the prevalence of parathyroid hormone elevation after parathyroidectomy for primary hyperparathyroidism and to discuss possible mechanisms.MethodsA Medline search of the English-language literature published between 1990 and 2009 was performed using the search terms “elevated PTH after parathyroidectomy.” All of the identified articles reported either prospective or retrospective studies without control groups. Studies that included patients with secondary or tertiary hyperparathyroidism were not reviewed.ResultsWithin 1 week to 5 years after parathyroidectomy, 9% to 62% of patients with a normal serum calcium concentration are reported to have an elevated parathyroid hormone concentration. No evidence suggests that postoperative normocalcemic parathyroid hormone elevation is an indication of surgical failure and recurrent hypercalcemia. Preoperative findings in patients with postoperative parathyroid hormone elevation include lower vitamin D concentration, higher concentrations of bone turnover markers, and higher parathyroid hormone concentration. Potential mechanisms for parathyroid hormone elevation in the setting of normocalcemia include vitamin D deficiency, hungry bone syndrome, and parathyroid hormone resistance. Study findings suggest a possible benefit of postoperative calcium and vitamin D supplementation, but no randomized trials have been done.ConclusionElevation of parathyroid hormone commonly occurs after parathyroidectomy for primary hyperparathyroidism, although the underlying mechanism remains unclear. (Endocr Pract. 2010;16:112-117)     

Normal responsiveness of serum parathyroid hormone to beta-adrenergic blockade in patients with secondary hyperparathyroidism

Infusion of calcium gluconate (15 mg Ca++/kg body weight in 4 h) to 6 patients with secondary hyperparathyroidism (due to mild renal insufficiency) decreased serum parathyroid hormone (PTH) levels to the same degree (on a percent basis) as in normal subjects. Serum PTH values at 4 h were 60 +/- 4.5 (SEM)% of baseline in the patients and 59 +/- 2.9% of baseline in the normal subjects. Infusion of propranolol (1 mg i.v. bolus followed by an infusion of 60 micrograms/min for 2 h) to 7 additional patients with secondary hyperparathyroidism also decreased serum PTH to the same degree as in normal subjects. Serum PTH values at 2 h were 68 +/- 10.4% of baseline in the patients and 68 +/- 3.3% of baseline in the normal subjects. The studies indicate normal responsiveness of serum PTH to calcium or beta-adrenergic blockade in secondary hyperparathyroidism due to mild renal insufficiency.     

Simple test of intestinal calcium absorption measured by stable strontium.

A clinical test of intestinal calcium absorption has been developed using non-radioactive stable strontium as a calcium tracer. In nine elderly subjects there was a close correlation between the fractional absorption of strontium and radioactive calcium (45Ca) during a five hour period after the simultaneous oral administration of the two tracers. Comparable precision was achieved with each tracer in six subjects in whom the test was repeated after two weeks. The effect of food on strontium absorption was examined in a further 33 normal subjects (age 21-60 years), and the administration of the strontium with a standard breakfast was shown to reduce the variance at individual time points. A simplified test in which serum strontium concentration was measured four hours after the oral dose given with a standard breakfast was adopted as the routine procedure. The normal range (mean (2 SD], established over 97 tests in 53 patients, was 7.0-18.0% of the dose in the extracellular fluid. A further 30 patients with possible disorders of calcium absorption (10 with primary hyperparathyroidism and 20 with coeliac disease) were studied by this standard test. In both groups of patients the mean four hour strontium values were significantly different from normal. This standard strontium absorption test allows assessment of calcium absorption with sufficient sensitivity and precision to have a wide application in clinical practice.     

Drug treatment of primary hyperparathyroidism: use of clodronate disodium.

Clodronate disodium (dichloromethylene diphosphonate), a specific inhibitor of bone resorption, was given by mouth (1.0-3.2 g daily) to nine patients with primary hyperparathyroidism for two to 32 weeks so that its clinical and metabolic effects could be evaluated. Bone resorption decreased in all patients as judged by a fall in the fasting urinary calcium to creatinine and hydroxyproline to creatinine ratios. Serum calcium concentration was increased in all patients before treatment and fell in response to treatment to values near the upper end of the normal range. Hypercalcaemia and hypercalciuria recurred when treatment was stopped. In three patients treated for longer than 19 weeks clodronate failed to sustain the reduction in serum calcium concentration but the concentration remained below pretreatment values. These results suggest that clodronate may be of use in the medical management of primary hyperparathyroidism, particularly in patients in whom suppression of bone disease is desirable before surgery or in whom surgery is contraindicated.     

Surgical treatment of primary hyperparathyroidism in the elderly.

Twelve patients aged over 70 with primary hyperparathyroidism (persistent hypercalcaemia and raised serum parathyroid hormone concentrations) underwent parathyroidectomy, which was well tolerated by all. After operation serum calcium concentrations returned to normal and the commonest symptoms before operation (muscle weakness, malaise, and mild to severe dementia), although not related in severity to the degree of hypercalcaemia, improved. Mental function was greatly improved. The findings suggest that primary hyperparathyroidism should be sought in any elderly patient with hypercalcaemia and that more such patients with the diagnosis should be considered for parathyroidectomy irrespective of age.