Normocalcemic primary hyperparathyroidism with fractures

Normocalcemic primary hyperparathyroidism is an uncommon condition usually found among patients with urinary stones. To the best of our knowledge, this is the first case of a patient with normocalcemic primary hyperparathyroidism presenting with bilateral femoral neck fracture. A 45-year-old man had pain both hip joints and limping in for several months. Vertical fractures of bilateral femoral necks were found by radiographs. Laboratory findings showed a normal value of total serum calcium but elevated serum ionized calcium. Serum parathyroid hormone and alkaline phosphatase levels were elevated. The patient was treated with subtrochanteric valgus osteotomy fixed with a dynamic hip screw and total parathyroidectomy. Histopathologic examination showed hyperplasia of the parathyroid glands. At 1-year follow-up, the patient was doing well clinically.     

Tertiary hyperparathyroidism: histologic patterns of disease and results of parathyroidectomy

HYPOTHESIS: Patients with tertiary hyperparathyroidism (THPT) commonly have parathyroid hyperplasia and should have a bilateral neck exploration with subtotal or total parathyroidectomy with autotransplantation to obtain long-term cure. DESIGN: A retrospective cohort study. SETTING: Tertiary referral medical center. PATIENTS: Thirty-four consecutive patients (21 women and 13 men; mean age, 48 years) who underwent neck exploration for THPT. MAIN OUTCOME MEASURES: Sites and histologic pattern of parathyroid disease, and postoperative normalization of serum calcium and parathyroid hormone levels. RESULTS: Twenty-seven patients underwent initial bilateral neck exploration and 7 patients underwent repeat neck exploration for persistent or recurrent THPT. The mean serum total calcium level was 11.2 mg/dL (2.8 mmol/L) (range, 10.3-13.5 mg/dL [2.6-3.4 mmol/L]) and the mean intact parathyroid hormone level was 355 ng/L (range, 95-1236 ng/L). The THPT was due to 4-gland hyperplasia in 33 patients and a single adenoma in only 1 patient. The parathyroid glands were in the normal position in 23 patients and in ectopic locations in 11 patients (8 intrathymic, 1 carotid sheath, 1 tracheoesophageal groove, and 1 intramuscular). Preoperative localizing studies did not identify ectopic or supernumerary glands in any of the patients (ultrasonography, 14 patients; technetium Tc 99m sestamibi, 15; and magnetic resonance imaging, 7). Persistent (n = 5) and recurrent (n = 2) THPT was more common in patients who had an initial 1- or 2-gland excision instead of subtotal or total parathyroidectomy with autotransplantation (P<.001). Four patients had transient hypocalcemia (<8.0 mg/dL [<2.0 mmol/L]), and no other permanent complications or deaths occurred. Biochemical cure was achieved in 94% of patients with a mean follow-up of 4.8 years. CONCLUSIONS: Tertiary hyperparathyroidism is usually due to multiple hyperplastic parathyroid glands, and patients who have initial limited parathyroidectomy have a higher risk of persistent or recurrent THPT.     

Hyperparathyroidism and gastroenteropancreatic hormone levels

The diagnosis of multiple endocrine neoplasia (MEN) in patients with presumed hyperparathyroidism has important ramifications for patient management especially since as many as 20% of patients with hyperparathyroidism may have associated MEN. Gut hormone levels were measured before and after surgery in 28 patients who underwent resection of a single parathyroid adenoma for biochemical or clinical evidence of hyperparathyroidism. The mean serum calcium level was 11.9 +/- 0.2 mg/dl before surgery and 9.3 +/- 0.3 mg/dl after surgery (p less than 0.001). Two or more hormone levels were elevated in 32% of patients before surgery and 21% after surgery. The same hormone abnormalities (pancreatic polypeptide [PP] and gastrin) occurred 56% of the time. Of elevated preoperative levels of PP, 91% were in the normal range after surgery. In patients with elevated preoperative PP levels, the postoperative level of PP decreased by an average of 64% of the preoperative level. In 27% of patients the level increased more than double the preoperative value. In two of four patients with high levels of PP after surgery the serum calcium level failed to fall. Of 18 patients whose PP levels fell, 17 had a fall in serum calcium levels. Of six patients whose PP levels rose, four had a significant fall in calcium levels. There was no correlation between the absolute levels or the decremental change of calcium and the change in PP. Several abnormalities in gut hormone secretion occur in patients with primary hyperparathyroidism and a parathyroid adenoma. An elevated serum level of PP does not signify MEN syndrome and must be reevaluated after resection of the parathyroid adenoma. Failure of adequate tumor resection is attended by persistent elevation of serum calcium and PP levels.     

Measurement of intraoperative parathyroid hormone predicts long-term operative success

HYPOTHESIS: A decrease in the intraoperative parathyroid hormone (PTH) level predicts long-term operative success. DESIGN: A case series of consecutive patients undergoing parathyroidectomy with intraoperative PTH measurement. SETTING: A university hospital. PATIENTS AND INTERVENTION: One hundred two patients with sporadic primary hyperparathyroidism underwent parathyroidectomy according to the principles of unilateral exploration with intraoperative PTH measurement. MAIN OUTCOME MEASURES: Longitudinal effects on levels of serum calcium and PTH. RESULTS: In 94 of 98 patients who underwent primary exploration because of a solitary adenoma, intraoperative PTH decreased at least 60% 15 minutes after gland excision. The 4 cases in which PTH fell to less than 60% were classified as false negatives. Patients examined for multiglandular disease (n = 4) were correctly predicted not to have an adenoma. Twenty-two patients (22%) were unavailable for 5-year follow-up. These patients were followed up for 2 months to 48 months (median, 24 months), and none developed recurrent primary hyperparathyroidism. Of the remaining 80 patients (78%), all but 1 patient had normal or slightly decreased serum calcium levels (mean +/- SD, 9.24 +/- 0.4 mg/dL [2.31 +/- 0.10 mmol/L]) at 5-year follow-up. One patient with hypercalcemia (10.6 mg/dL [2.65 mmol/L]) was interpreted to have developed renal failure with secondary hyperparathyroidism. Thirty-four patients had elevated serum PTH levels at least once during the postoperative study period, with normal or slightly decreased calcium concentrations. The prediction of late postoperative normocalcemia by means of intraoperative PTH measurement had an overall accuracy of 95%. CONCLUSIONS: The measurement of intraoperative PTH during surgery for primary hyperparathyroidism accurately differentiates between single- and multiple-gland disease and ensures good long-term results.     

Lack of effect of parathyroidectomy or calcium channel blockade on serum gastrin concentration and gastric acid secretion in a patient with hyperparathyroidism and Zollinger-Ellison syndrome

Management of patients with multiple endocrine neoplasia type I (Wermer's syndrome) who have concurrent hypercalcemia and hypergastrinemia is controversial. The usual therapeutic approach has been to perform parathyroidectomy first before surgery for ulcer disease in an effort to decrease serum calcium concentration and presumably remove one of the stimuli for both gastrin and gastric acid secretion. We present the history of a 48-year-old man with primary hyperparathyroidism and Zollinger-Ellison syndrome who underwent acid secretory studies and secretin stimulation tests before and after parathyroidectomy. We also studied the effect of calcium channel blockade on gastrin and gastric acid secretion, since calcium influx into endocrine cells, such as the gastrinoma cell, is thought to be critical in hormone secretion. Although parathyroidectomy reduced serum calcium and parathormone levels to normal, basal serum gastrin concentration and basal acid output remained unchanged. The peak rise in serum gastrin concentration after secretin injection was less after parathyroidectomy than before parathyroidectomy but was still abnormal. During administration of verapamil, a calcium channel antagonist, no change was seen in the serum gastrin concentration, secretin test response, or acid secretion. Basal acid output was 45.4 mmol/hr before parathyroidectomy or verapamil and 54.0 and 50.4 mmol/hr after parathyroidectomy or verapamil, respectively. In contrast, a small but significant decrease (p less than 0.05) in serum parathormone concentration occurred during treatment with verapamil, an observation that to the best of our knowledge has not been previously reported in humans.     

Long-term management and outcome of parathyroidectomy for sporadic primary multiple-gland disease

HYPOTHESIS: For a specific subset of patients with sporadic primary multiple-gland parathyroid disease, subtotal parathyroidectomy results in long-term normocalcemia in the majority of patients, with a minimal complication rate. DESIGN: Retrospective analysis of outcomes in patients undergoing parathyroidectomy performed by a single surgeon (A.E.G.) between 1984 and 1999. SETTING: A multidisciplinary endocrine service based at a tertiary referral center. PATIENTS: Patients undergoing subtotal parathyroidectomy for primary hyperparathyroidism due to sporadic multiple-gland disease identified from a single surgeon's operative records (A.E.G.). MAIN OUTCOME MEASURES: Data analyzed included demographic factors, operative and pathologic findings, and postoperative and long-term clinical and laboratory results, including calcium and intact parathyroid hormone levels. RESULTS: Of 379 patients undergoing parathyroidectomy for hyperparathyroidism between 1984 and 1999, 49 (13%) had sporadic multiple-gland disease. Median preoperative calcium and intact parathyroid hormone (iPTH) levels were 2.7 mmol/L (10.8 mg/dL) and 11.79 pmol/L, respectively. Postoperative calcium and iPTH levels were available in 39 patients, and median values were 2.28 mmol/L (9.1 mg/dL) and 2.84 pmol/L, respectively. Long-term follow-up was available for 36 patients (73%), and duration ranged from 6 to 180 months (median, 44 months). Median calcium and iPTH levels at follow-up were 2.3 mmol/L (9.2 mg/dL) and 3.26 pmol/L, respectively, with 3 (8%) of 36 patients having evidence of persistent or recurrent hyperparathyroidism. No patient had biochemical evidence of hypoparathyroidism at long-term follow-up. Five patients (14%) had persistent elevated iPTH levels (range, 8.11-10.95 pmol/L) and normal calcium levels. CONCLUSIONS: Subtotal parathyroidectomy for sporadic primary multiple-gland disease resulted in a long-term normocalcemia rate of 92%, with minimal complications. Selective subtotal parathyroidectomy can yield excellent long-term results in patients with multiple-gland disease.     

Health-related quality of life in hyperparathyroidism measurably improves after parathyroidectomy

BACKGROUND: Hyperparathyroidism is associated with subjective feelings of fatigue and depression as well as limitations in physical activity from musculoskeletal complaints. These quality of life symptoms are not widely accepted as an indication for parathyroidectomy. This study quantifies and compares subjective symptoms of patients with hyperparathyroidism before and after surgery. METHODS: Between February 2001 and June 2002, 61 patients (14 males and 47 females, mean age of 60.8+/-14.4 years) underwent parathyroidectomy. There were 45 patients with single-gland adenomas, 9 patients with double adenomas, 3 patients with primary hyperparathyroidism from 4-gland hyperplasia, 3 patients with secondary hyperparathyroidism, and 1 patient with tertiary hyperparathyroidism. Patients filled out a 53-question survey based on the Health Outcomes Institute Health Status Questionnaire 2.0 before surgery, 1 month postoperatively, and 3-24 months postoperatively. The survey included questions on overall health, daily activities, mood, and medical conditions. Surveys were analyzed for changes in symptoms attributable to parathyroidectomy. Serum calcium and intact parathyroid hormone levels were obtained preoperatively and at 1- and 3-month follow-up visits. RESULTS: At both postoperative evaluations, patients' perception of general health, muscle strength, energy level, and mood significantly improved (P<.05). Moreover, there was a significant correlation between the changes in serum calcium and intact parathyroid hormone levels and improvement in symptoms. CONCLUSIONS: Parathyroidectomy for hyperparathyroidism is associated with significant improvement in patient quality of life. These subjective symptoms represent a valid indication for parathyroidectomy.     

Parathyroidectomy for tertiary hyperparathyroidism associated with X-linked dominant hypophosphatemic rickets

BACKGROUND: X-linked dominant hypophosphatemic rickets (XLHR) is a hereditary metabolic bone syndrome that is only beginning to be understood and is rarely associated with progression to irreversible tertiary hyperparathyroidism. We report our surgical experience with 6 patients with XLHR who underwent parathyroidectomy for associated autonomous parathyroid hyperfunction. HYPOTHESIS: Parathyroidectomy can successfully treat tertiary hyperparathyroidism in the setting of XLHR, although an understanding of expected operative findings and postoperative complications is essential. DESIGN: The study group comprised 6 patients with XLHR identified from our endocrine surgery database. Presentation, surgical procedure, parathyroid pathologic findings, and subsequent outcome are outlined. RESULTS: There were 4 women and 2 men. All were exposed to long-term vitamin D and phosphate supplementation therapy. All had persistently elevated preoperative levels of parathyroid hormone and serum calcium. The patients were treated as follows: 3 had total parathyroidectomy, 2 had 3 parathyroid glands identified and resected, and 1 had 2 abnormal parathyroid glands resected with 2 normal-appearing parathyroid glands left in situ. One patient subsequently required completion parathyroidectomy for recurrent disease. Pathologic examination results revealed hyperplasia of all resected parathyroid glands in 4 of 6 patients. One patient had a single adenoma with 3-gland hyperplasia, and 1 patient had a double adenoma. The principal complication of this procedure was profound symptomatic hypocalcemia requiring intravenous calcium infusion. Hungry bone syndrome was also observed in most subjects. Long-term, all patients achieved normocalcemia. CONCLUSION: Tertiary hyperparathyroidism is a rare but recognized complication of XLHR. Parathyroidectomy effectively treats this complication caused by autonomous parathyroid hyperfunction, but profound postoperative hypocalcemia necessitates careful management.     

Early biochemical response to parathyroidectomy for primary hyperparathyroidism and its predictive value for recurrent hypercalcemia and recurrent primary hyperparathyroidism

BackgroundThe traditional definition of cure after parathyroidectomy (PTX) for primary hyperparathyroidism is normocalcemia. Our hypothesis was that early postoperative levels of serum calcium and parathyroid hormone after PTX would have predictive value for later recurrence.MethodsWe performed a retrospective study of 1,146 patients with primary hyperparathyroidism who underwent PTX and had long-term biochemical follow-up. The first postoperative serum level of calcium and parathyroid hormone values were used to categorize patients into the following four early biochemical response groups: (1) complete response (normal calcium and normal parathyroid hormone), (2) partial response with hyperparathormonemia (normal calcium and increased parathyroid hormone), (3) partial response with hypercalcemia (increased calcium and normal parathyroid hormone), and (4) non-response (increases in both calcium and parathyroid hormone). Incidences of recurrent hypercalcemia and recurrent primary hyperparathyroidism >6 months after operation were then analyzed.ResultsThe overall rate of any elevated serum levels of calcium and any increase in serum levels of parathyroid hormone during >6-month follow-up was 9.8% (112 of 1146), with 6.6% (57 of 861) for group 1, 27% (35 of 129) for group 2, and 16% (20 of 127) for group 3 (P < .02). Partial biochemical responses with either increased serum calcium or increased parathyroid hormone levels were the strongest predictors of any episode of increased serum levels of calcium after 6 months and was associated with 2.7× to 4.3× the risk of recurrent primary hyperparathyroidism, respectively.ConclusionThis study demonstrates the importance of measuring parathyroid hormone in the early postoperative period to better predict later recurrent primary hyperparathyroidism.     

Parathyroid Adenomas versus Four-gland Hyperplasia as the Cause of Primary Hyperparathyroidism in Patients with Prolonged Lithium Therapy

Chronic lithium therapy in patients with affective psychiatric disorders has been implicated as the cause of hypercalcemia and primary hyperparathyroidism. Our objective was to evaluate whether primary hyperparathyroidism was caused by an adenoma or four-gland hyperplasia. The medical records of 15 patients with affective psychiatric disorders who were treated with chronic lithium therapy from 1982 to 1997, all of whom were operated on for primary hyperparathyroidism, were reviewed. Data on age, symptoms, duration of lithium therapy, pre- and postoperative calcium levels, and parathyroid hormone levels were collected. Parathyroid histology for each patient was independently and blindly reviewed. The mean age was 58 +/- 10 years, the mean duration of lithium therapy 10.7 +/- 6 years, and the mean preoperative calcium level 11.7 +/- 0.5 mg/dl. All patients underwent bilateral neck exploration with selective resection of enlarged glands. Of the 15 patients, 14 (92%) had adenomas (11 single, 3 double), and 1 (8%) had four-gland hyperplasia. All patients were rendered eucalcemic, with a postoperative calcium level of 9.2 +/- 0.5 mg/dl ( p < 0.005). All patients resumed their lithium therapy, with 1 of 15 patients developing recurrent hyperparathyroidism 2 years following the first operation; this patient required reexploration, at which time an adenoma was resected. In our experience hyperparathyroidism in patients who have undergone prolonged therapy with lithium is associated with a high incidence of parathyroid adenomas versus four-gland hyperplasia. This suggests that lithium selectively stimulates growth of parathyroid adenomas in susceptible patients, who are best treated with adenoma excision rather than subtotal parathyroidectomy.     

Hypercalcemic hyperparathyroidism and hypophosphatemic osteomalacia complicating neurofibromatosis

Summary Neurofibromatosis is sometimes complicated by impaired renal tubular reabsorption of phosphate, hypophosphatemia, and osteomalacia. Hyperparathyroidism has also been reported in patients with neurofibromatosis. When hypercalcemia and elevated levels of parathyroid hormone are found in osteomalacia, however, it may be difficult to determine if the hyperparathyroidism was primary or tertiary. We describe a patient with neurofibromatosis, hypercalcemic hyperparathyroidism, hypophosphatemic osteomalacia, vitamin D deficiency, and clear-cell hyperplasia of all four parathyroid glands. Serial biomechanical, bone biopsy, and densitometric studies confirmed that treatment with ergocalciferol, calcium, and phosphate supplements significantly improved the osteomalacia but caused increased parathyroid overactivity. After subtotal parathyroidectomy, the parathyroid hormone concentration became normal and the bone mineral content increased at the spine and hip, but inappropriate phosphaturia persisted. The findings indicate that hyperparathyroidism, osteomalacia, and vitamin D deficiency adversely affect each other.     

Plasma and parathyroid tumor tissue gastrin and hyperparathyroidism.

Hyperparathyroidism has been associated with an increased incidence of duodenal ulcer, increased acid secretion, and increased plasma gastrin levels. A relationship between these changes, increased serum calcium levels, and the increased incidence of peptic ulceration has been suggested, especially since increased plasma gastrin levels, serum calcium levels, and gastric acid secretion decrease after parathyroidectomy. We have previously suggested that the decrease in plasma gastrin levels after parathyroidectomy may suggest an extragastric source of gastrin, whereas others using immunofluorescent studies have suggested that the parathyroid adenomas themselves might be the source of this gastrin. We prospectively studied in fifteen patients with primary hyperparathyroidism, plasma gastrin and serum calcium levels before and after parathyroidectomy, as well as the gastrin content of parathyroid tumor tissue. The mean basal plasma gastrin level before operation was significantly greater than that of a control group and decreased insignificantly after operation, in contrast to serum calcium levels. No positive correlation could be found between plasma gastrin and serum calcium levels before and after operation. Parathyroid tumor tissue was assayed for gastrin content by radioimmunoassay and no detectable amounts of gastrin could be recovered from any tumor. The results do not support the concept that the extragastric source of gastrin in patients with hyperparathyroidism is the parathyroid adenoma itself.     

Parathyroidectomy can improve bone mineral density in patients with symptomatic secondary hyperparathyroidism

HYPOTHESIS: The recovery of osteoporosis or bone mineral density (BMD) after parathyroidectomy and autotransplantation can be improved in patients with symptomatic secondary hyperparathyroidism. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Forty-five patients with symptomatic secondary hyperparathyroidism who underwent total parathyroidectomy and autotransplantation were included. They were divided into an osteoporotic group (n = 20) and a nonosteoporotic group (n = 25) according to preoperative T scores less than -2.5 at either the lumbar spine (L1-L4) or the femoral neck (FN). INTERVENTIONS: Serum levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were checked before surgery and 1 day, 1 week, and 3 months after surgery. The BMDs of the FN and L1-L4 were measured using dual-energy x-ray absorptiometry before surgery and 6 months after surgery. RESULTS: Patients with osteoporosis were older (mean +/- SD, 50.2 +/- 14.0 years) than those without osteoporosis (42.7 +/- 9.1 years) (P =.04). Except for bone fractures found in 2 women in the osteoporotic group, there were no significant differences between the 2 groups in sex, clinical manifestations, duration of dialysis, weight of removed parathyroid tissue, and types of dialysis. Also, serum levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were similar in both groups. Both 1 day and 1 week after total parathyroidectomy and autotransplantation, serum levels of calcium and intact parathyroid hormone decreased rapidly and then gradually increased 3 months later; however, serum levels of alkaline phosphatase increased rapidly and then gradually decreased 3 months later. Six months after parathyroidectomy, BMD, T score, and Z score at L1-L4 and the FN increased significantly (P<.001). The increment was much better in the osteoporotic group than in the nonosteoporotic group (P<.001). Also, osteopenia or osteoporosis improved significantly after parathyroidectomy at both L1-L4 and the FN (P<.001 for both). CONCLUSION: Parathyroidectomy and autotransplantation can improve BMD of symptomatic secondary hyperparathyroidism at L1-L4 and the FN.     

Inhibition of gastrin release and gastric secretion by calcitonin in patients with peptic ulcer

We studied the effect of an intravenous infusion of calcitonin (2 MRCU/kg) on gastric secretion and serum gastrin and serum calcium levels in eight normal subjects, six patients with duodenal ulcer disease, three patients with primary hyperparathyroidism, six patients with histologically proved Zollinger-Ellison syndrome, and three patients with the Zollinger-Ellison syndrome and hyperparathyroidism. Gastric secretion was greatly inhibited in all groups of patients. Serum calcium was significantly diminished only in patients with hypercalcemia. Serum gastrin levels were depressed in all patients with elevated basal gastrin levels (DU, HPT, Z-E, and ZE + HPT). In normal subjects calcitonin inhibited strongly the serum gastrin response to food. These findings suggest that calcitonin may have a regulatory function in the release or catabolism of the hormone gastrin.     

Plasma and tumor gastrin in patients with primary hyperparathyroidism

It is well known that primary hyperparathyroidism is often associated with peptic ulcer. The purpose of this study is to confirm the relationship between the gastrin-levels before and after parathyroidectomy in fourteen patients with primary hyperparathyroidism, and to determine the localization of gastrin in the surgically resected parathyroid tumor. The results obtained were as follows: 1) Three patients had peptic ulcer (gastric ulcer and duodenal ulcer), the incidence being 21%. 2) The basal serum gastrin levels were 123.0% +/- 68.1 pg/ml before operation and decreased to 90.2 +/- 44.5 pg/ml after operation. In the 3 patients with slightly elevated gastrin levels, the mean level before operation was 209.1 +/- 61.2 pg/ml. The gastrin level decreased to 116.4 +/- 62.0 pg/ml after operation. 3) Gastrin immunoreactivity was detected in 10 out of 14 tumors and its localization was at the periphery of tumor cells. From these results, we conclude that extragastric gastrin secretion from parathyroid tumors may be one of the cause of peptic ulcer in patients with primary hyperparathyroidism.     

Lethal post-transplantation calcinosis.

The case studies of four patients with post-transplantation calcinosis are presented. Three of the four patients died of inanition and sepsis secondary to infection of extensive soft tissue ulcers and diffuse cutaneous vascular calcification with gangrene. The fourth patient survived following removal of all four parathyroid glands and autografting of approximately one-half of one gland. Common to the patients was secondary hyperparathyroidism, elevated mean serum calcium levels after transplantation, and radiographic evidence of small and medium vessel calcification. No other differences could be found between these patients and other patients with post-transplantation hyperparathyroidism without calcinosis. In the face of apparently minor complaints of lower extremity discomfort, elevated parathyroid hormone levels (PTH) and positive xerography may indicate subtotal parathyroidectomy regardless of the serum calcium level.     

Parathyroid exploration for primary hyperparathyroidism

Parathyroidectomy was studied retrospectively in 107 patients with primary hyperparathyroidism. This condition was diagnosed by measuring both the total serum calcium and ultrafilterable calcium (non-protein-bound) levels. The identification of ultrafilterable calcium is an important adjunct to parathyroid surgery as it allows the diagnosis of hyperparathyroidism when the total serum calcium level is normal. The surgical technique for selective parathyroidectomy and multiple biopsies was uniform. Parathyroid adenoma was discovered in 73 patients, diffuse hyperplasia in 26 and combined disease in 8. Postoperatively, two patients suffered from permanent hypocalcemia and three had hypercalcemia.     

Serum calcium, parathyroid hormone, and urinary cyclic adenosine monophosphate after parathyroidectomy

In specific cases of primary hyperparathyroidism (HPT), an intraoperative measure of parathyroid function might aid the surgeon. Ideally this would permit the surgeons to recognize that sufficient parathyroid tissue had been removed to cure the patient, but that viable glandular tissue remains. This study was designed to evaluate the efficacy of urinary cyclic adenosine monophosphate (cAMP) concentrations as such a determinant. We studied serum calcium and parathyroid hormone concentrations and urinary cAMP levels in 11 control patients undergoing thyroid and non-neck operations and in 22 persons undergoing parathyroidectomy for primary HPT. The serum calcium and parathyroid hormone concentrations were normal in control patients and elevated in each person with primary HPT. Changes of these parameters after successful parathyroidectomy took too long either to occur or to be measured to be clinically useful intraoperatively. Basal urinary cAMP concentrations were normal in 10 of 11 control patients and remained so during their operations. Elevations of basal urinary cAMP levels were found in 78% of those with primary HPT. At 30 minutes after removal of all abnormal parathyroid tissue, urinary cAMP levels remained high in 41% of those in whom it as elevated in the basal state. However, by 60 minutes all urinary cAMP values were normal or low. Plasma cAMP values were normal in three of four patients with primary HPT and did not change within 90 minutes after operation despite the performance of a successful parathyroidectomy. As expected, urinary cAMP levels returned to normal in each of these individuals. Intraoperative changes of urinary cAMP levels do reflect changes in parathyroid status. However, because of the delay of 40 to 60 minutes before urinary cAMP normalizes after parathyroidectomy and because of the sophisticated technology necessary for rapid determination of this cyclic nucleotide, its present clinical applicability is limited.     

Intact parathyroid hormone in primary hyperparathyroidism

In 49 patients with primary hyperparathyroidism, intact parathyroid hormone (PTH) was measured with a recently developed immunoradiometric assay, and midregional PTH fragments (sequence 44-68) were measured with an established radioimmunoassay technique. In 47 normal subjects, the concentration of intact PTH ranged from 2.0 to 6.8 pmol/l, and in 49 patients with primary hyperparathyroidism it ranged from 6.4 to 80.0 pmol/l. In contrast, midregional PTH fragments were normal in seven of 49 patients with primary hyperparathyroidism. In five healthy controls and in 12 patients with surgically confirmed primary hyperparathyroidism and serum calcium levels below 3.0 mmol/l, a rapid calcium loading test was performed. In healthy controls, intact PTH was in the low normal to subnormal range within 2.5-5.0 min, and had recovered within 15 min of calcium infusion. In patients with primary hyperparathyroidism, the calcium infusion also led to a 30-50 per cent decrease in intact PTH levels within 5.0-7.5 min after injection, with a slow recovery after 10-15 min. In six of the patients with only slightly elevated basal intact PTH, a suppression to the normal range was observed. In 24 patients (16 patients with a solitary adenoma and eight patients with four-gland hyperplasia) the intact PTH levels were followed intraoperatively during parathyroidectomy, revealing a significantly different rate of decline for single adenomas compared with hyperplasia during the first 15 min after removal of the primary enlarged gland. Intact PTH values remained constantly elevated in one patient with primary hyperparathyroidism and an unsuccessful neck exploration. These results confirm that (a) the measurement of intact PTH in patients with primary hyperparathyroidism is superior to the measurement of midregional fragments; (b) PTH secretion in primary hyperparathyroidism is not totally autonomous; and (c) intraoperative monitoring of intact PTH values could be used to monitor the success of surgery.     

Hyperparathyroidism associated with thyroid pathology

BACKGROUND: The pathological association between thyroid and parathyroid gland disease is here discussed. The multiphase analyzer has revealed a new type of subclinical primary hyperparathyroidism (HPP) and the role of surgery in these cases is not clear. METHODS: This is a prospective study of all cases of thyroid disease in association with parathyroid disease treated surgically in our Institute from July 1999 to June 2001. RESULTS: Of the 221 thyroidectomies carried out, 29 patients had an elevated preoperative serum level of parathyroid hormone (PTH). An ultrasonography examination was performed on all patients and a preoperative scanning with 99Tc-MIBI on 11 of 29 patients. We examined intraoperatively 19 cases of HPP (14 parathyroid adenoma, 5 hyperplasia). In 10 cases we observed a normal size of the parathyroid gland and we did not perform a parathyroidectomy. CONCLUSIONS: All patients with elevated serum parathyroid hormone and serum calcium levels before thyroidectomy should be considered candidates also for surgery to the parathyroid glands. The pathological association between thyroid and parathyroid gland diseases is not rare. We must conduct an accurate neck exploration in all these cases.