Solitary parathyroid microadenoma

In our experience with operations for primary hyperparathyroidism, a recurring problem centers on patients whose solitary adenomas are too small to be appreciated at the initial exploration. We have seen four patients with parathyroid microadenomas, which we define as lesions less than 6 mm in diameter in externally undeformed parathyroid glands. Two such patients were fortuitously cured at the initial exploration even though the operative findings were inconclusive. One, a 25-year-old man, underwent excision of an externally normal gland that contained a 3 by 2 by 2 mm microadenoma. He is eucalcemic since the operation. The other patient, a 70-year-old woman with hypercalcemia, responded to prednisone. She then underwent a neck exploration at which the diagnosis of sarcoidosis was confirmed by lymph node biopsy examination. A 4 by 2 by 2 mm parathyroid microadenoma was incidentally removed. The patient is normocalcemic receiving low-dose steroid treatment since the operation. In a third patient, a 34-year-old practical nurse, three explorations were needed to find a parathyroid gland, which was negative for adenoma on frozen-section microscopy. The solitary adenoma, 6 by 3 by 3 mm, was appreciated only on permanent sections. The majority of oxyphil microadenomas should be suspected to be nonfunctioning, as in a 59-year-old woman in whom the lesion coexisted with primary chief cell parathyroid hyperplasia. The hyperparathyroidism responded well to three and a half-gland resection. The 2 by 2 by 2 mm oxyphil adenoma was also removed. Solitary parathyroid adenomas can be subtle and small. Appraisal of parathyroid disease at the operating table is not always straightforward. As more patients with early hyperparathyroidism appear on routine calcium screening, we may expect to see increasing numbers of challenging solitary parathyroid microadenomas.     

Early postoperative function of suppressed parathyroid glands with microscopic hyperplasia

Calcium-parathyroid hormone (Ca-PTH) relationships were studied perioperatively in 35 patients with primary hyperparathyroidism. Twenty-nine patients had solitary adenomas that caused preoperative hypercalcemia; those patients whose remaining glands were subjected to biopsy were classified as having either microscopic evidence of suppression in those glands (15 patients) or no evidence of suppression (less than or equal to 30% stromal fat on biopsy cross sections, 11 patients). Before surgery, all patients showed the expected positive slopes for Ca-PTH linear regression curves. After surgery, all patients with adenomas showed an immediate and sustained shift of the Ca-PTH regression to the right; this shift achieved statistical significance only in those patients whose remaining glands showed microscopic evidence of suppression (greater than 30% fat, p less than 0.05). Moreover, the slope of the Ca-PTH regression curve for these patients assumed a negative value 1 month after surgery. All patients with adenomas were eucalcemic after surgery, regardless of the cellularity of the remaining in situ glands. We conclude that the absence of microscopic suppression in grossly suppressed parathyroid glands at the time of adenoma resection for hyperparathyroidism does not affect postoperative results. However, the presence of microscopic hyperplasia in macroscopically normal or suppressed glands may represent a persistent alteration in biologic function, evidenced by failure of these glands to achieve negative calcium regulation.     

Distribution of solitary parathyroid adenoma over the parathyroid glands and its surgical management

Objective: To determine the distribution of solitary parathyroid adenoma over the parathyroid glands in a group of patients with primary hyperparathyroidism Design: A case-series. Place and Duration of Study: Departments of Surgery and Pathology at Shariati Hospital, Tehran, Iran, between the years 1981 and 2003. Patients and Methods: A retrospective review of surgery reports of 118 patients with primary hyperparathyroidism was performed. All of the patients had solitary parathyroid adenoma and the anatomical location of each adenoma was clearly defined during operation. Serum calcium, phosphorus and parathormone levels along with clinical characteristics were also included. Results: The distribution of adenomas over the superior and inferior parathyroid glands showed a significant higher incidence of adenoma in the lower parathyroids (p < 0.001). The right to left distribution of adenomas was not significant (p=0.4). Conclusion: Surgical exploration for primary hyperparathyroidism should be initiated from the lower parathyroid glands provided that pre-operative localization scans are not helpful.     

Double parathyroid adenomas. Clinical and biochemical characteristics before and after parathyroidectomy.

OBJECTIVE: There is considerable debate about whether double parathyroid adenomas are a discrete entity or represent hyperplasia with parathyroid glands of varying sizes. This distinction is important because it impacts on the extent of parathyroid resection and the success of the parathyroid operation. SUMMARY BACKGROUND DATA: Double parathyroid adenomas have been reported to occur in 1.7% to 9% of patients with primary hyperparathyroidism (HPT). It is important for surgeons to differentiate between double adenoma and hyperplasia with glands of varying sizes using gross examination during the initial procedure because microscopic findings of a small biopsy specimen at frozen-section examination may not be diagnostic. METHODS: From 1982 to 1992, 416 unselected patients (309 women and 107 men) with primary HPT without familial HPT or multiple endocrine neoplasia (MEN) were treated by one surgeon at the University of California at San Francisco. Double adenoma occurred in 49 patients, solitary adenoma in 309 patients, and hyperplasia in 58 patients. The authors analyzed the clinical manifestations, the preoperative and postoperative serum levels of calcium, phosphate, and parathyroid hormone (PTH), and the success rate and outcome after parathyroidectomy and compared their results in 49 patients with double adenomas to the results for patients with solitary adenomas or hyperplasia. RESULTS: Ten of the patients with double adenomas (20.4%) were referred for persistent HPT after removal of one abnormal parathyroid gland. The ages of the patients with double adenoma, single adenoma, and hyperplasia were 61 +/- 14, 56 +/- 15, and 58 +/- 7 years, respectively. Fatigue, muscle weakness, and bone pain were common in patients with double adenomas, whereas nephrolithiasis occurred more frequently in patients with solitary adenoma (p = 0.0001). Serum calcium and PTH levels (per cent of upper limit of normal) fell from 11.5 +/- 1.2 mg/dL and 487% to 9.5 +/- 0.8 mg/dL and 61% for patients with double adenomas; from 11.9 +/- 0.9 mg/dL and 378% to 9.3 +/- 1.4 mg/dL and 101% for patients with single adenoma; and from 10.9 +/- 0.5 mg/dL and 418% to 9.1 +/- 0.7 mg/dL and 94% for patients with hyperplasia, respectively. There was no recurrence in the patients with double adenomas with a mean follow-up time of 5.8 years. CONCLUSIONS: Double adenomas are a discrete entity and occur more often in older patients. Patients with double adenomas can be successfully treated by removal of the two abnormal glands.     

Multiple parathyroid adenomas: report of thirty-three cases

An increasing number of patients with primary hyperparathyroidism are found to have two or three enlarged parathyroid glands. Of 865 patients successfully operated on by one surgeon (J.N.A.), multiple enlarged parathyroid glands (adenomas) were found and resected in 33 cases (3.8%), with resulting normocalcemia lasting from 1 to 22 years (mean 5.8). Twenty-nine patients had two adenomas and four had three adenomas. In 28 patients the multiple adenomas were synchronous. Twenty-five patients underwent removal of all of the enlarged parathyroid glands in one operation; in three patients one adenoma was removed, reoperation for persistent hypercalcemia was performed, and a second adenoma was resected with cure. In five patients one adenoma was removed, normocalcemia ensued for 3 to 18 years, and a second (metachronous) adenoma occurred and was resected successfully. Although 10 of 70 enlarged parathyroid glands removed were labeled hyperplasia, cure in all but one of our patients by selective resection of only enlarged parathyroid glands emphasizes the unreliability of histologic criteria in differentiating between parathyroid adenoma and hyperplasia. Based on this study, we support the existence of multiple adenomas and advocate removal of only macroscopically enlarged parathyroid glands in patients with primary hyperparathyroidism.     

Parathyroidectomy in familial hypercalcemia with clinical characteristics of primary hyperparathyroidism and familial hypocalciuric hypercalcemia

BACKGROUND: Familial primary hyperparathyroidism is associated with tumor-susceptibility syndromes, which are unrelated to mutations in the calcium receptor gene. This study describes parathyroidectomy in a kindred with hypercalcemia due to a heterozygous point mutation in the calcium receptor gene. METHODS: Seventeen family members were studied, and postoperative follow-up averaged 5.1 years. RESULTS: Radical parathyroid resection with total parathyroid remnants of 10 to 20 mg or total parathyroidectomy with autotransplantation normalized the serum calcium and parathyroid hormone values in 12 family members. Persistent hypercalcemia was noted in 3 of 5 patients subjected to less radical procedures. Diffuse to nodular hyperplasia and microscopic findings, interpreted incorrectly as a single adenoma, were found. Weight of the parathyroid tissue increased with the age of the patients (P <.05), and almost one third of them (29%) had 1 to 3 atypically located glands. There were no patients with recurrent hypercalcemia during follow-up. CONCLUSIONS: The heterozygous inactivating mutation of the calcium receptor gene of this family is accompanied by mild increases in parathyroid gland x weight and diffuse parathyroid hyperplasia with possibly secondary genetic events causing nodule formation. Radical parathyroid resection is advocated in this hypercalcemic disorder, which may represent an intermediary stage between primary hyperparathyroidism and familial hypocalciuric hypercalcemia.     

Influence of 1,25-dihydroxycholecalciferol on parathyroid activity in patients with primary hyperparathyroidism.

Parathyroid morphology and blood chemistry were studied in five patients with primary hyperparathyroidism treated with 1,25-dihydroxycholecalciferol (1,25-DHCC) for 2 to 11 days before planned operation. Before the institution of treatment all patients were hypercalcemic, whereas the serum immunoreactive parathyroid hormone (iPTH) concentration either was elevated or normal. During the treatment the urinary phosphate excretion was significantly increased, whereas the calcium excretion and the serum concentrations of calcium and phosphate were unaffected or only slightly changed. Serum iPTH decreased during the first days of treatment, but returned then to increased levels close to the pretreatment ones. The treatment was tolerated well by the patients. Light and electron microscopy of the removed parathyroid glands disclosed one adenoma in each of the five patients, the other glands exhibiting either a slight hyperplasia or a normal appearance. Both the adenomatous and the non-adenomatous parathyroid tissue showed a predominance of dark chief cells and three of the adenomas exhibited a varying number of atrophic and oxyphil cells. The non-adenomatous glands were composed of atrophic and dark chief cells. Signs of low functional activity were ultrastructurally observed in the parathyroid parenchymal cells. It is suggested that 1,25-DHCC treatment of patients with primary hyperparathyroidism inhibits parathyroid hormone secretion.     

Nonautonomy of parathyroid hormone and urinary cyclic AMP in primary hyperparathyroidism.

This study demonstrates that appreciable changes in serum parathyroid hormone and urinary cyclic AMP occur during experimentally induced hyper- and hypocalcemia in almost all patients with primary hyperparathyroidism regardless of histology. A single patient with tertiary hyperparathyroidism also demonstrated a significant elevation of serum parathyroid hormone and urinary cyclic AMP in response to EDTA induced reduction in ionized calcium. Thus, total autonomy of hormone secretion was not present in the great majority of the patients with a parathyroid adenoma, parathyroid hyperplasia, or the single patient with tertiary hyperparathyroidism. Therefore, preoperative evaluation of the rsponse of urinary cyclic AMP and serum parapthyroid hormone to EDTA or calcium infusion will not distinguish parathyroid adenomas from hyperplasia on the basis of total autonomy of hormone secretion. If a difference in secretory control is present between parathyroid adenomas and parathyroid hyperplasia, it is more subtle than total autonomy for adenomas and nonautonomy for hyperplasia.     

Surgical approaches to solitary parathyroid adenoma: state of the art. Our early experience with intraoperative parathyroid hormone measurement

We report our early experience with focused radioguided parathyroidectomy with intraoperative parathyroid hormone measurement in patients affected by primary hyperparathyroidism. Over a period of 2 months we performed 4 consecutive focused parathyroidectomies with intraoperative parathyroid hormone measurement, 3 of which radioguided. All patients had a preoperative localization of single gland disease by sestamibi scanning and/or ultrasound. Blood samples for parathyroid hormone measurement were taken at baseline (induction of anaesthesia), 10 minutes after adenoma excision and the day after surgery. Three of the 4 patients were discharged within 24 hours. In all cases a solitary adenoma was successfully identified and removed. As predicted by the appropriate fall in intraoperative parathyroid hormone levels, all patients were considered cured on the basis of normal levels of calcium and parathyroid hormone at 1-month follow-up. Targeted parathyroidectomy can be successfully performed in patients with preoperatively localized solitary adenoma. The appropriate decrease in intraoperative parathyroid hormone levels assures a curative operation. The use of radioguidance should be recommended when difficulties with gland identification are foreseen.     

Surgery for parathyroid adenoma and hyperplasia: Relationship of histology to outcome

Recent histopathologic evidence challenges the teaching that enlargement of a solitary parathyroid gland is invariably caused by an adenoma, whereas multiple gland enlargement results from hyperplasia. We have re-examined the parathyroid tissue obtained from 152 consecutive patients undergoing surgery for primary hyperparathyroidism and compared it with their clinical outcome. Our approach was to excise enlarged glands and biopsy the remainder. In 124 patients (82%) at least three glands were biopsied or removed. The ratio of adenoma to hyperplasia was reversed by our histologic re-examination; adenomas were found in only 27 patients (25 single, two double), whereas hyperplasia was found in 117 patients (one gland, 87 patients; two glands, 16 patients; three glands, five patients; four glands, nine patients). Normal tissue only was reported in eight patients. During a 2-year follow-up, five patients (3%) developed hypocalcemia and none developed recurrent hypercalcemia. Our results indicate that a full neck exploration with removal of all enlarged glands is more important than the histologic diagnosis in planning a successful surgical strategy for 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.     

Unexpected parathyroid disease discovered at thyroidectomy in irradiated patients

Eight of 23 patients undergoing total thyroidectomy for radiation-associated nodular thyroid disease were found to have unsuspected parathyroid hyperplasia or adenoma at operation. The total serum calcium level was normal preoperatively in each patient. Serum ionized calcium and parathyroid hormone levels were measured in five patients preoperatively and were normal in each case. These pathologic findings in normocalcemic patients may represent a preclinical form of hyperparathyroidism, which would be further evidence linking radiation to the pathogenesis of hyperparathyroidism. The parathyroid glands should be evaluated both preoperatively and at operation in all patients who have a history of radiation and require thyroidectomy.     

Primary hyperparathyroidism. Preoperative evaluation and correlation with surgical findings

The clinical and operative findings in 101 patients with the diagnosis of primary hyperparathyroidism are reviewed, with particular emphasis on the current methods of preoperative evaluation.Of these patients seventy-two (72 per cent) underwent neck exploration. The twenty-nine patients who did not have an operation either refused operative treatment or were not granted an operation because of medical reasons (multiple system disease in elderly patients). Fourteen of the surgical patients (20 per cent) required re-exploration. Two patients had negative neck explorations.Preoperative evaluation included routine serum calcium (X3), serum phosphorus, and alkaline phosphatase determinations, and appropriate radiologic evaluation. Urinary cyclic AMP levels were helpful in differentiating primary hyperparathyroidism from nonparathyroid hypercalcemia.Phosphorus clearance studies were helpful as were twenty-four hour urinary calcium determinations. Parathyroid scans and arteriography were not helpful diagnostically and intravenous toluidine blue was of no benefit intraoperatively.Eleven patients had selective neck vein catheterizations for parathyroid hormone immunoassays with 63 per cent localization.Of seventy patients with positive surgical findings, eleven had chief cell hyperplasia, six had adenomatous hyperplasia, and fifty-three had adenoma(s).     

Functioning oxyphil cell adenomas of the parathyroid gland. A study of 15 cases

Parathyroid adenomas composed predominantly of chief cells are the most frequent cause of primary hyperparathyroidism. Until as recently as 1978, the rare oxyphil cell parathyroid adenoma was generally considered nonfunctioning. A retrospective review of 500 consecutive patients at the Massachusetts General Hospital with a diagnosis of hyperparathyroidism associated with parathyroid adenoma during the years 1979-1987 yielded 15 (3.0%) oxyphil cell adenomas. A total of 65 case reports of hyperparathyroidism associated with a diagnosis of oxyphil cell adenomas were reviewed, applying the same diagnostic criteria used in case selection for the present series. These criteria include: (a) at least 90% composition of the adenoma by oxyphil cells; (b) biopsy or excision of a second histologically normal parathyroid gland to help rule out hyperplasia; and (c) postoperative alleviation of hypercalcemia. More than 50% of the previously reported cases did not conform to these criteria. The findings in the present study further document the entity of hyperparathyroidism caused by oxyphil cell parathyroid adenomas and suggest criteria guidelines for this rare diagnosis.     

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??Hypercalcemia??Differential diagnosis, surgical treatment and evaluation CHU Cheng-yu, WANG Hong-ying, ZOU Qiang. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
Corresponding author: ZOU Qiang, E-mail: zouqiang003@aliyun.com
Abstract Surgery remains the main therapeutic approach in treating the hypercalcemia caused by hyperparathyroidism??HPT??. Most cases of primary HPT are due to a solitary parathyroid adenoma. Qualitative diagnosis may depend on elevated parathyroid hormone (PTH)??hypercalcemia and hypophosphatemia. Pre-operative imaging examination, including scintigraphy and ultrasonography??may help to locate the lesion. The resection of adenoma is the choice forthe operation and extensive exploration is unnecessary. Characterized by parathyroid hyperplasia, renal HPT is diagnosed on the basis of long-term renal failure and hemodialysis. Elevated PTH with elevated calcium and phosphorus as well as ultrasonography may be used in the qualitative identification and localization respectively. Parathyroidectomy may be indicated when the medical therapies are inefficient. Total parathyroidectomy with partial autotransplantation of parathyroid tissue is recommended.     

Studies in patients with hyperparathyroidism using a new two-site immunochemiluminometric assay for circulating intact (1-84) parathyroid hormone

A recently developed chemiluminescent immunoassay for 1-84 intact parathyroid hormone (PTH) demonstrated increased specificity by virtue of two-site antibody binding and increased sensitivity by use of a chemiluminescent technique. Basal PTH levels were measured in three groups of subjects: (1) normal (n = 82), (2) hyperparathyroidism (n = 31), and (3) patients with hypercalcemia of malignancy (n = 16). There was good discrimination between normal (1.2 to 9.4 pmol/L) and hyperparathyroid subjects (9.2 to 53.4 pmol/L). In persons with hypercalcemia of malignancy all PTH levels were within the normal range (0.8 to 5.2 pmol/L) or suppressed. PTH release was stimulated by the intramuscular injection of 100 IU salmon calcitonin in 6 normal controls, 10 patients with primary hyperparathyroidism due to adenoma, and 5 with four-gland hyperplasia. There was no significant rise in PTH concentration and out of the normal range in the control subjects, but the adenoma patients demonstrated a mean rise of 24.4%, 26%, and 33%, and hyperplasia patients, a mean rise of 37%, 47%, and 37% over basal levels at 120, 180, and 240 minutes. The mean absolute rise in PTH concentration was 13.4 +/- 7.7 pmol/gm of parathyroid tissue in the adenomas and 27.2 +/- 9.5 pmol/gm of parathyroid tissue in the hyperplastic glands; this difference was significant (p less than 0.05). Serial blood samples from a central vein were taken at surgery for hyperparathyroidism, and the rate of decay of the intact hormone was studied in 9 patients after removal of the parathyroid tissue. This decay was rapid with a half-life of 300 seconds. We conclude that this new specific and sensitive intact PTH assay will provide a valuable means of investigating dynamic aspects of parathyroid physiology.     

Long-term evaluation of patients with primary parathyroid hyperplasia managed by total parathyroidectomy and heterotopic autotransplantation.

Since 1973, we have performed total parathyroidectomy and forearm parathyroid autotransplantation in 36 patients with generalized (four gland) primary parathyroid hyperplasia. Twenty (56%) patients had nonfamilial parathyroid hyperplasia (NFPH) and 16 (44%) patients had familial parathyroid hyperplasia (FPH). Twenty-one patients (Group A) were undergoing operation for the first time and 15 (Group B) were having either second, third or fourth re-explorations for persistent hyperparathyroidism. All patients in Group A and nine patients in Group B had parathyroid resection and immediate autotransplantation as a single procedure. Six Group B patients had hyperfunctioning parathyroid tissue resected, cryopreserved, and subsequently grafted when it was evident that they had been rendered aparathyroid. A sustained differential elevation (13.7 fold +/- 2.7) of parathyroid hormone was detected in the antecubital vein of the grafted compared to the nongrafted arm in 35 (97%) patients. Two (5.6%) of the 36 patients (both with FPH; one Group A and one Group B) required permanent oral calcium and vitamin D replacement therapy and one (3%) patient (NFPH: Group A) had persistent hypercalcemia postoperatively, presumably due to a supernumerary gland. The remaining 33 (92%) patients became normocalcemia after surgery and 23 (70%) of them remained so. Ten (30%) of the 33 patients developed recurrent graft dependent hyperparathyroidism. Eight patients were from the group with FPH (8/14, 57%) and two were from the group with NFPH (2/19, 11%)(FPH vs. NFPH, p < 0.005). Because of symptoms of hypercalcemia or a serum calcium concentration exceeding 11 mg/dl, partial graft resection was performed in five patients and four became normocalcemic. Patients with generalized primary parathyroid hyperplasia may be difficult to cure, especially if the disease is familial. The technique of total parathyroidectomy and heterotopic autotransplantation of fresh or cryopreserved parathyroid tissue offers distinct advantages over alternative techniques.     

Correlation of biochemical parameters with single parathyroid adenoma weight and volume

OBJECTIVE: To determine the relationship of the biochemical parameters serum phosphate, serum calcium, and serum parathyroid hormone levels with respect to parathyroid adenoma weight and volume in primary hyperparathyroidism. STUDY DESIGN: Retrospective review of 63 cases of primary hyperparathyroidism from 1992 to 1998. METHODS: Single parathyroid adenomas were identified from surgical pathology reports. Preoperative calcium, phosphate, and parathyroid hormone levels were collected from charts. The volume of the adenoma was calculated using a mathematical equation for the volume of an ellipsoid object. The data were analyzed using a multiple analysis of variance, and a correlation coefficient was calculated. The level of significance was set at p < or = .05. RESULTS: With respect to adenoma volume, there was a significant correlation with serum calcium and parathormone levels (p = .0001 and p = .0001, respectively). There was no significant correlation between serum phosphate and adenoma volume. With respect to adenoma weight, there was a significant correlation with serum calcium and parathormone levels (p = .0001 and p = .0001, respectively). There was no significant correlation between serum phosphate and adenoma weight. CONCLUSIONS: Preoperative serum calcium and parathormone levels may be able to predict adenoma weight and volume in primary hyperparathyroidism for a single adenoma.     

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.