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.     

The clinical significance and anatomic distribution of parathyroid double adenomas

BACKGROUND: Parathyroid double adenomas are reported to occur in 3% to 12% of cases of primary hyperparathyroidism, but the very existence of double adenomas has been controversial. This study was undertaken to evaluate the clinical significance and anatomic distribution of parathyroid double adenomas. STUDY DESIGN: The medical records of 384 consecutive patients who underwent operation for primary hyperparathyroidism were reviewed. RESULTS: A total of 27 patients (7%) were found to have double parathyroid adenomas. Intraoperative parathyroid hormone (PTH) levels were measured in each case. Two enlarged hypercellular parathyroid glands were identified in 6 possible configurations: 10 both superior, 3 both inferior, 5 both right, 3 both left, 5 right superior and left inferior, and 1 left superior and right inferior. There was preferential distribution to the bilateral superior position (p = 0.008). In all patients intraoperative PTH levels dropped by at least 50% from baseline and into the normal range after removal of both abnormal parathyroid glands. All patients remain normocalcemic 1 to 26 months postoperatively. Two patients have persistently elevated PTH values with normal serum calcium levels. CONCLUSIONS: The drop in intraoperative PTH levels and maintenance of normocalcemia postoperatively confirm previous reports that double adenomas do exist and are not simply missed cases of four-gland hyperplasia. Their incidence is more than would be expected by chance alone. The preferential occurrence of bilateral superior double adenomas suggests the possibility that these may represent hyperplasia of parathyroids arising from the fourth branchial pouch rather than isolated neoplastic events.     

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.     

Primary hyperparathyroidism associated with two enlarged parathyroid glands

An increasingly recognized although small percentage of patients with primary hyperparathyroidism have enlargement of two parathyroid glands. We have treated nine patients with primary hyperparathyroidism associated with such double parathyroid gland enlargement. In four of these patients, marked asymmetry of the two enlarged glands was noted and the failure to recognize and excise a second enlarged parathyroid gland resulted in persistent or recurrent hyperparathyroidism. In one of these patients, the second enlargement was present in a super-numerary mediastinal gland. The subsequent excision of the second enlarged parathyroid gland resulted in normocalcemia in each instance. This contrasts with five patients in whom initial excision of two enlarged glands resulted in normocalcemia with no recurrence of hypercalcemia. Only three patients fulfilled the histologic criteria of true double adenomas. The remainder showed multiglandular hypercellularity. This experience supports identifying all parathyroid glands and recognizing that even minimal enlargement of a gland may be important pathophysiologically, regardless of its histopathologic classification. Excision of both enlarged glands, even if asymmetric, is appropriate.     

Microfluorometric measurements of cytoplasmic calcium in chief and oxyphil parathyroid cells of adenomatous and hyperplastic glands and of normal-sized glands associated with adenomas

The effects of extracellular calcium on the cytoplasmic Ca2+ concentration (Ca2+i) were studied by dual-wavelength microfluorometry in individual human parathyroid cells obtained from adenomatous glands and normal-sized glands associated with adenomas in hypercalcemic hyperparathyroidism (HPT), as well as from enlarged glands of patients with uremia with HPT. In comparison with the normal parathyroid tissue, chief cells of the adenomatous and hyperplastic glands showed significantly lower Ca2+, and also right-shifted responses of Ca2+i to increases in the extracellular calcium concentration within the 0.5 to 3.0 mmol/L range. This pathophysiologic disturbance apparently was independent of the cell size. Oxyphil cells of nodules from the hyperplastic glands had lower Ca2+i and responded less to increments in extracellular Ca2+ than the chief cells from the surrounding parts of the same glands. Also the chief cells from the normal-sized glands associated with single adenomas exhibited a disturbance of the regulation of Ca2+i, which was less pronounced than that in the cells of the adenomas. These findings support the presence of relative calcium insensitivity of Ca2+i in chief and oxyphil parathyroid cells from adenomatous and hyperplastic glands. This derangement may also be found in all parathyroid glands of individuals with adenomatous HPT.     

Histopathological study of the parathyroid gland in renal hyperparathyroidism

From July 1973 to July 1984, 50 patients underwent parathyroidectomy because of secondary hyperparathyroidism due to chronic renal failure. One hundred fifty-eight excised parathyroid glands in 41 of these patients were submitted to the histopathological examinations in the relations to their clinical features which revealed the following findings. Inspite of secondary hyperparathyroidism, eleven of 41 patients showed four unevenly enlarged parathyroid glands with one or two glands weighing less than 100mg. The glands were divided into three adenomas, 101 diffusely and 54 nodulary hyperplastic glands. The nodular type hyperplasia, which had a greater proportion of clear chief cells, vacuolated chief cells, transitional oxyphil cells and oxyphil cells, was more hyperplastic than the diffuse type. The patients with the nodular type showed more advanced clinical features in the secondary hyperparathyroidism.     

Incidental preclinical hyperparathyroidism identified during thyroid operations.

The entity of preclinical hyperparathyroidism has never been clearly investigated. The authors believe that the incidence of pathologic abnormalities of the parathyroid glands before the development of any symptoms or hypercalcemia (serum calcium > 12.0 mg/dl) is more frequent than has been reported. Over a 14-year period, parathyroid glands were examined during thyroid operations in over 800 patients. Serum calcium and phosphorous levels were measured in all patients preoperatively. Thirty-six patients had additional parathyroid operations for a preclinical form of hyperparathyroidism, defined by abnormal appearing parathyroid glands at the time of thyroid surgery. None of the 36 patients had symptoms of hyperparathyroidism preoperatively. Nine patients had borderline hypercalcemia (serum calcium 10.6 to 12.0 mg/dl), and the remainder were considered normocalcemic. The average age was 53 (range 21 to 75) with a male to female ratio of 1:3. Nine of the 36 patients had thyroid cancer. There were eight patients with parathyroid adenoma and 28 patients with parathyroid hyperplasia. Of 13 patients who had a history of neck irradiation, five had parathyroid adenoma and eight had parathyroid hyperplasia. Only two patients with parathyroid hyperplasia remain on calcium medication. Since preoperative normocalcemia does not preclude the presence of parathyroid pathology, the authors urge careful identification and examination of the parathyroid glands during thyroid operations. It adds little time to the procedure. Excision of parathyroid disease along with the thyroid gland can be performed safely and prevents the need for further operation with its associated morbidity.     

Parathyroid metabolism after operative treatment of hypercalcemic (primary) hyperparathyroidism

Parathyroidectomy is usually followed by a decrease in serum calcium, a lessening of symptoms, and a normocalcemic state that continues for years. Evaluation of parathyroid gland function after parathyroidectomy over a protracted period showed a continued hypersecretory state in many normocalcemic patients and is reported here for the first time. Patients identified with parathyroid hyperplasia (more than one gland excised) and patients who later developed mild renal failure were excluded. Seventy-seven patients undergoing parathyroidectomy with only one enlarged gland removed and the other normal-sized glands viewed or examined by biopsy were followed up from 5 to 16 years. Two patients developed recurrent hypercalcemia at 4 and 9 years after surgery. Seventy-five patients are considered "cured" and have normal serum calcium values. However, 28 (37%) of these normocalcemic patients have persistent elevations of parathyroid hormone. This increased parathyroid gland function suggests a continuing stimulation of the remaining glands. The rarity of clinical recurrence may be related to effective adaptations that prevent overt hypercalcemia. Many parathyroid adenomas appear to represent nonneoplastic disease.     

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.     

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.     

Primary hyperparathyroidism: four- to eight-year postoperative follow-up demonstrating persistent functional insignificance of microscopic parathyroid hyperplasia and decreased autonomy of parathyroid hormone release.

Thirty-nine patients with primary hyperparathyroidism were studied four to eight years after their initial operation. In six patients, both the pathologist and surgeon agreed on the diagnosis of solitary adenoma; in 16 patients, the surgeon diagnosed solitary adenoma and the pathologist parathyroid hyperplasia (microscopic hyperplasia). In 16 patients, primary chief cell hyperplasia was agreed upon by the pathologist and surgeon. In the 16 patients with microscopic hyperplasia, there have been no long-term recurrences of hypercalcemia, but, in two patients, plasma parathyroid hormone levels are high. Parathyroid hormone--total calcium regression curves demonstrate significant preoperative correlation in solitary adenoma, p less than 0.01, and primary chief cell hyperplasia, p less than 0.05. After operation, significant correlations were not found between parathyroid hormone and total calcium. T-testing slope differences of pre- and postoperative parathyroid hormone--total calcium regression curves demonstrates a significant (p less than 0.01) shift to the right of the microscopic hyperplasia patients after operation, moving them to a broader range of total calcium per picogram parathyroid hormone. We conclude that 1) in primary hyperparathyroidism, positive regulation of total calcium by autonomously released parathyroid hormone exists in patients with solitary adenoma and chief cell hyperplasia; 2) autonomously functioning parathyroid tissue has been removed by operation for solitary adenoma with coexistent microscopic parathyroid hyperplasia. In this four- to eight-year follow-up period, it is clear that microscopic parathyroid hyperplasia is not associated with recurrent hypercalcemia. Two functionally distinct forms of parathyroid suppression are suggested; positively regulated microscopic hyperplasia and negatively regulated pathologically suppressed glands.     

Calcium infusion in suspected hyperparathyroidism: changes in parathyroid hormone concentration related to histopathological findings.

Changes in parathormone, total and free calcium concentrations in serum were studied in 27 patients with suspected hyperparathyroidism (25 with normocalcemia judged from CaT). Six patients were classified as normals. In 21 patients neck explorations was performed. Patients with definite pathology in the parathyroid glands had higher parathormone, total and free calcium levels than patients with borderline pathology or normal glands. The mean parathormone concentration fell significantly during calcium infusion in patients with histologically normal parathyroid glands. In patients with definitely pathological glands the parathormone concentration remained unchanged during the calcium infusion.     

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.     

Intracellular lipid droplets in functioning transitional parathyroid oxyphil adenomas. A caveat.

Histochemical demonstration of intracellular lipid droplets on frozen section has been used to distinguish normal parathyroid tissue from that of adenoma and chief cell hyperplasia. Differentiation is based on the observation that the cells of adenoma and chief-cell hyperplasia largely lack intracellular lipid, which is present in the suppressed chief cells of normal glands in patients with adenoma. We present two functional transitional oxyphil adenomas that contained abundant intracellular lipid. Failure to recognize that transitional oxyphilic adenomas may contain focal accumulation of intracellular lipid droplets could lead to confusion in histologic interpretation.     

Late results of operation for primary hyperparathyroidism in 441 patients

The late results of operation for primary hyperparathyroidism (HPT) were analyzed in 441 patients operated on 4 to 27 years earlier (mean follow-up time, 7.7 years). A conservative surgical approach was mainly used, attempting if possible to visualize all four parathyroid glands and extirpate only the enlarged glands. Subtotal resection was performed in patients with hyperplasia. The histopathologic diagnosis was adenoma in 77% and hyperplasia in 18%. In 5% of the patients, the histopathologic classification was uncertain. Hypercalcemia persisted after operation in 8% of all patients. This generally occurred because of an incomplete neck exploration or too limited a resection in the patients with hyperplasia. Recurrent hypercalcemia occurred in 16% of the patients operated on for hyperplasia and was noted 1 to 19 years after surgery. Recurrences were also seen in 3% of the patients with adenomas but not earlier than 9 years after the operation. These findings suggest that primary HPT may even in patients with adenomatous disease, sometimes affect all parathyroid glands. Nevertheless, it was obvious that most of the patients with adenomas would not have benefited from a more radical procedure. On the other hand, it was evidently important to obtain a correct histopathologic diagnosis intraoperatively so that patients with hyperplasia could be identified and adequatley treated.     

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.     

Oxyphil parathyroid carcinomas: a clinicopathologic and immunohistochemical study of 10 cases

Oxyphil parathyroid carcinomas are uncommon neoplasms, and the clinicopathologic features of these tumors are largely unknown. We evaluated the clinicopathologic features of oxyphil parathyroid carcinomas and the expression of cytokeratin 14 (CK14), the high-affinity glucose transporter-4 (Glut-4), as well as the cell cycle proteins p27 and Ki67 and compared these with oxyphil parathyroid adenomas and chief cell parathyroid adenomas and carcinomas. Formalin-fixed, paraffin-embedded archival tissues from primary (n = 6) and recurrent (n = 4) oxyphil carcinomas were analyzed and compared with chief cell parathyroid carcinomas (n = 12), oxyphil parathyroid adenomas (n = 38), and chief cell parathyroid adenomas (n = 17) by immunohistochemistry for CK14, Glut-4, p27, and Ki67 using the avidin-biotin peroxidase system. Patients with primary oxyphil and chief cell carcinoma presented with high levels of serum calcium (n = 15.5 and 13.7 mg/dL, respectively). Approximately half the patients in each group died of disease. The Ki67 labeling index was higher (4.9 vs 1.9) and the p27 index lower (23 vs 66) in primary oxyphil carcinoma compared with primary oxyphil adenomas. CK14 was expressed in most oxyphil adenomas (35 of 38 cases) but not in oxyphil carcinomas (0 of 10 cases). Glut-4 was more commonly expressed in both groups of adenomas compared with carcinomas. These results show that oxyphil parathyroid carcinomas are functional malignancies similar to chief cell carcinomas and are associated with hypercalcemia, recurrence, and death. Expression of CK14 is very different in oxyphil adenomas compared with carcinomas. Although distinction between parathyroid adenomas and carcinomas can only be made by histopathologic and clinical findings, these results suggest that immunostaining for CK14, p27, and Ki67 may provide additional information to help distinguish between difficult cases of parathyroid adenomas and carcinomas. These findings also indicate that the same histopathologic features should be used to diagnose oxyphil and chief cell parathyroid carcinomas.     

Relation of biochemical, cytologic, and morphologic parameters to the result of gammagraphy with technetium 99m sestamibi in primary hyperparathyroidism

The aim of this study was to analyze the possible relation of biochemical, cytologic, and morphologic parameters to the results of parathyroid gammagraphy with Tc 99m sestamibi in primary hyperparathyroidism. We studied 46 consecutive patients with primary hyperparathyroidism who were undergoing surgery. All the patients were given a preoperative parathyroid gammagraphy with Tc 99m sestamibi and a complete preoperative biochemical study. During the surgical intervention we recorded the weight and size of the pathologic glands to calculate the volume of each. We also determined the percentage of the chief and oxyphil cells in the pathologic glands. Tc 99m sestamibi sensitivity is higher in adenomas (91%) than in hyperplasia (67%) or double adenomas (50%). No relation was found between biochemical or cytologic parameters and gammagraphic results. Weight and gland volume were significantly greater for adenomas than for hyperplasia (P < 0.0014 and P < 0.0004, respectively), and statistically significant differences in both of them were observed between the glands with positive and negative sestamibi.     

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.