Surgical treatment of parathyroid disease: A review

Since the first parathyroidectomy was performed by Mandl in 1925, there have been many advances in our understanding of the parathyroid gland and its related disorders of calcium homeostasis. Our ability to establish the diagnosis of parathyroid neoplasia and locate the source of autonomous parathormone production has also dramatically improved. Nevertheless, it was the advent of the routine calcium and phosphate screening done on the sequential multiple analyzer (SMA-12) that has caused a tremendous increase in the number of patients who are diagnosed to have hyperparathyroidism and who therefore present for surgical treatment. Essential for successful and uncomplicated treatment of this disorder is a thorough understanding of the anatomy, physiology, and pathology of the parathyroid glands. This review will consider the parathyroid glands in their normal state, as well as the diagnosis and management of the various disorders associated with them.     

Parathyroid autotransplantation in total thyroidectomy

Although parathyroid autotransplantation during the course of thyroidectomy was first described by Halsted in 1907, it is only during the past 20 years that this simple and effective method of preserving parathyroid function is being used by an increasing number of surgeons. Our group has autotransplanted normal parathyroids since 1965, whenever these glands could not be preserved in situ with adequate blood supply. With increasing experience, we find it much simpler to autotransplant parathyroid glands attached to the thyroid, than to dissect their precarious blood supply, hoping they will survive postoperative edema and fibrosis. Furthermore, it is our impression that in operations for thyroid carcinoma, attempts to preserve the blood supply to the parathyroids may compromise the completeness of the thyroidectomy or of the dissection of cervical nodes in the tracheoesophageal groove. In a review of our experience during the past four years (January 1, 1984 to December 31, 1988), 87 patients underwent total thyroidectomy. Parathyroid glands that could not be saved in situ were biopsied to confirm their identity by frozen section and autotransplanted in the ipsilateral sternocleidomastoid muscle. Among the 87 patients undergoing total thyroidectomy, 34 required no autotransplantation, whereas 52 had one to three glands autotransplanted, and one had four glands autotransplanted. Postoperatively, 23 patients (26 percent) developed hypocalcemia, whereas 18 required CaCO3 and five required vitamin D in addition. All patients (98%) except two had normal parathyroid function at four-month follow-up and thereafter, as judged by serum calcium, phosphorus and parathormone, when indicated.     

Parathyroid sonography in secondary hyperparathyroidism: correlation with clinical findings

We present the results of ultrasonic neck examination in 72 patients (47 males, 25 females) on chronic haemodialysis, with clinical and biochemical signs of increased function of the parathyroid glands. The findings of the ultrasonic examination performed using linear transducers of 5 and 7.5 MHz for the surface tissue are compared with the duration of haemodialysis treatment, biochemical parameters (calcium, phosphate, parathormone, alkaline phosphatase) and skeleton X-ray findings. In 18 patients parathyroid glands were not visible, in 30 patients there were one or two enlarged (i.e. abnormal) parathyroid glands, and in the remaining 24 patients three or four of the glands were enlarged. Abnormal parathyroid glands were more often found in patients who had been dialysed for a longer period of time, as well as in those with a higher parathormone level in the blood. It is concluded that ultrasonic examination of the neck is very useful in the diagnosis of enlarged parathyroid glands, and helpful in the management of patients on chronic haemodialysis.     

Risk of hypoparathyroidism after surgery for carcinoma of the thyroid

The reported incidence of postoperative hypoparathyroidism varies from 3% to 32%, and many surgeons are reluctant to perform a total thyroidectomy because of the risk of permanent damage to the parathyroid glands. We prospectively studied three groups of patients for evidence of acute parathyroid damage: group A consisted of 29 patients with total thyroidectomies; group B, 21 controls with partial thyroidectomies; and group C, 29 patients with total thyroidectomies that had been performed several months to years earlier. Functional status of the glands was measured by serum parathormone, calcium, and phosphorus levels. Although these levels fell postoperatively, they remained within normal limits. None of the long-term follow-up patients (group C) was found to have hypoparathyroidism, leading us to conclude that this risk may be overstated in the literature.     

The rationale against routine subtotal parathyroidectomy for primary hyperparathyroidism

Our therapeutic approach to the treatment of primary hyperparathyroidism has been the resection of only the abnormally enlarged parathyroid gland, the normal-appearing parathyroids being left intact. During the past twenty-five years we have operated on 292 patients with primary hyperparathyroidism. In all cases the serum calcium levels returned to within normal limits during the immediate postoperative period, and there were no instances of permanent hypoparathyroidism. To determine the long-term efficacy of this therapeutic approach, a retrospective study of 101 patients operated on for primary hyperparathyroidism during a nine year period from July 15, 1965 through June 30, 1974 was made. Of the 101 patients, eight were dead and nine could not be located. Of the remaining eighty-four patients, only two required reoperation because of recurrent hypercalcemia; one had MEA-I and eventually three and a half glands were removed, and the other had recurrent hypercalcemia after a three year normocalcemic interval, and after a second operation with resection of an enlarged parathyroid gland, he has remained normocalcemic. The other eighty-two patients (97 per cent of those reevaluated and 82 per cent of the total operated on) have remained symptom-free and normocalcemic for periods ranging from three to twelve years. Only one patient (if we exclude the patient with MEA-I) has elevated serum parathormone levels with borderline levels of serum calcium. Our results suggest that the optimal surgical treatment of primary hyperparathyroidism, except for cases of MEA, is resection of only the abnormally enlarged parathyroid glands after exploration and identification of all four glands in every case. If all four glands are enlarged, three and a half should be resected.     

Prospective study of parathyroid graft function in patients with renal hyperparathyroidism after total parathyroidectomy and heterotopic autotransplantation by measurement of the intact parathyroid hormone concentrations in both antecubital veins.

OBJECTIVE: Evaluation of the value of gradients for intact parathyroid hormone after total parathyroidectomy and heterotopic autotransplantation for renal hyperparathyroidism. DESIGN: Prospective long-term follow-up study. SETTING: Teaching hospital, Germany. SUBJECTS: A total of 115 patients operated on for renal hyperparathyroidism between 1 August 1987 to 15 August 1997. INTERVENTIONS: 100/115 had total parathyroidectomy with autotransplantation. MAIN OUTCOME MEASURES: Analyses of serum calcium, alkaline phosphatase, and intact parathormone in serum 1, 4, 8, 12, 18 and 24 months postoperatively and annually thereafter. Parathormone gradients were calculated as the ratio of the parathormone concentrations in the antecubital venous blood of the grafted and the non-grafted arm. RESULTS: During follow-up (mean 32 months, range 1 month to 9 years), 111 of the 115 patients had one to 10 re-examinations (mean: 4) and in the patients who had had total parathyroidectomy with autotransplantation a total of 437 gradients could be calculated, 91% of which were < or =20. Postoperative hypocalcaemia caused by calcium deficiency of the skeleton led to an increase in parathormone secretion and gradients. Increasing parathormone gradients during follow-up as a result of excessive parathormone secretion in the grafted-arm indicated graft-dependent recurrence. In 6 of the 9 patients with graft-dependent recurrences the gradients exceeded 20. CONCLUSION: The combined sequential assessment of gradients for intact parathyroid hormone and of serum calcium concentrations permits objective evaluation of parathyroid graft function.     

Intraoperatives Parathormonmonitoring bei der Halsexploration wegen renalem Hyperparathyreoidismus?

Introduction. In operations for renal hyperparathyroidism the value of intraoperative parathormone monitoring was investigated. Patients and methods. Intraoperative intact parathyroid hormone levels were determined (PTH Quick assay) in 40 patients undergoing first cervical exploration and in two patients with graft-dependent recurrence of renal hyperparathyroidism. Results. In 33 patients, total parathyroidectomy with autotransplantation was carried out. The median parathormone levels decreased from 652 pg/ml to 120 pg/ml (19% of initial level) 5 min after total parathyroidectomy. In seven patients, fewer than 4 parathyroid glands each were identified during cervical exploration and “total parathyroidectomy (?)” without autotransplantation was performed. Intraoperatively median parathormone level decreased from 1193 pg/ml to 116 pg/ml (10% of initial level). In one of these seven patients, hyperparathyroidism persisted due to an ectopic fourth gland within the carotid sheath. In two of these patients, hypoparathyroidism occurred and a delayed autotransplantation of cryopreserved parathyroid tissue was carried out. On the first day after total parathyroidectomy with autotransplantation and “total parathyroidectomy (?)”, median levels of intact parathyroid hormone were 1.9 pg/ml and 82.5 pg/ml, respectively. Conclusion. Intraoperative monitoring is not useful in first cervical exploration for renal hyperparathyroidism because it cannot predict complete resection of parathyroid tissue. The parathormone level on the first postoperative day allows precise evaluation of the efficacy of the surgical procedure.     

Unusual problems in parathyroid surgery

Although parathyroid surgery is difficult because of the smallness of the glands and the variability in their location and number, a surgeon who is well versed in the embryology, gross anatomy, pathology of the glands, and the fine points of gross identification of normal and abnormal tissue should be able to identify these glands in most instances. In a review of 122 cases during a two year period, pathologic change was found in 96 per cent, even though 11 per cent were secondary cervical explorations and the mediastinum was entered by a sternal split approach in only two cases. Although the abnormal glands were found in varying locations and ten were outside the usual areas of search, all were consistent with failure to descend or excessive descent and with a relationship to anatomic structures having similar embryologic origin. Sophisticated localizing procedures such as arteriography and selective venous sampling for parathormone are rarely necessary.     

Blood Supply and Parathyroid Hormone Secretion in Pathological Parathyroid Glands

The blood supply of pathologic parathyroid glands and the relation between parathyroid hormone secretion and parathyroid blood perfusion was studied during surgery for hyperparathyroidism. Blood flow in 39 single adenomas and 20 glands classified as primary or secondary hyperplasia were studied intraoperatively with laser Doppler flowmetry. The ipsilateral inferior thyroid artery was occluded during continuous flowmetry recording, which resulted in a 40% reduction of parathyroid blood flow in both groups. In 12 patients with single adenomas, intact parathormone (iPTH) was measured intraoperatively before and during occlusion of the ipsilateral inferior thyroid artery and after extirpation of the adenoma. During occlusion the iPTH levels were mainly unchanged despite blood flow reduction of up to 80%. After removal of the adenoma the iPTH normalized within 15 minutes. In a control group of eight single adenomas, iPTH was measured similarly without vascular occlusion, demonstrating comparable iPTH levels. This study demonstrates similar routes of vascularization for single adenomas and hyperplastic glands, as was earlier seen for normal parathyroid glands. The increased parathyroid hormone secretion from single adenomas appears to remain mainly unchanged during significant blood flow reduction.     

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.     

Parathyroid function in persistent hyperparathyroidism: relationship to gland size

The release of parathyroid hormone in experimental animals is related inversely to the plasma calcium concentration. The relevance, though, of these observations to the dynamics of parathyroid function in normal and hyperparathyroid humans is uncertain. We assessed the in vivo parathyroid hormone response to changes in extracellular calcium in 8 normal subjects and 15 patients with persistent hyperparathyroidism following renal transplantation. In 12 hyperparathyroid patients, the hormone response was related to their total gland size measured at the time of their parathyroidectomy. Plasma ionized calcium, magnesium, and parathyroid hormone concentrations were measured in the basal state and during a 2-hr infusion of EDTA (50 mg/kg), and a 4-hr calcium infusion (15 mg/kg). The parathyroid function curves of both groups of subjects (P less than 0.001) fit a log-linear relationship. The slopes of the respective parathyroid function curves were similar, although the hyperparathyroid curve was shifted to the right (P less than 0.0001). Gland size was not predicted by basal PTH levels; however, it did correlate with changes in parathyroid hormone induced by EDTA (P less than 0.001) and calcium (P less than 0.001). We conclude that the in vivo sensitivity of hyperplastic glands to changes in plasma calcium is maintained. The excessive secretion of immunoreactive parathyroid hormone in chief cell hyperplasia primarily reflects total gland mass. Our results indicate that the assessment of the dynamics of parathyroid response, rather than measurements of static plasma parathyroid hormone and calcium concentrations, should be further investigated as a more rational application of radioimmunoassays in the evaluation of the parathyroid axis.     

Total parathyroidectomy without autotransplantation in dialysis patients and renal transplant recipients, long-term follow-up evaluation

Background

Persistent secondary hyperparathyroidism not responding to medication is treated successfully with surgical excision of parathyroid glands (total parathyroidectomy [PTX]). PTX without autotransplantation of parathyroid glands excludes the risk for recurrence of hyperparathyroidism.

Methods

During the years 2002 to 2005, 36 total parathyroidectomies were performed in 33 patients: 21 dialysis patients because of end-stage renal disease and 12 renal transplant recipients.

Results

PTX without autotransplantation was performed successfully in 33 patients, whereas 3 patients were reoperated for remaining parathyroid glands. Immediate improvement of clinical symptoms and a decrease of serum calcium and parathormone levels were observed after surgical procedures. Oral replacement treatment with vitamin D (1a-calcidiol) and calcium was commenced and long-term follow-up evaluation (23.5 ± 7.6 mo) showed that calcium homeostasis was controlled adequately.

Conclusions

PTX without autotransplantation is a safe and effective surgical procedure for the treatment of resistant secondary hyperparathyroidism with immediate response of clinical symptoms. Replacement treatment with vitamin D and calcium provides satisfactory coverage of individual needs.     

精细化被膜解剖法在甲状腺全切手术中的应用

目的探讨精细化被膜解剖法在甲状腺全切手术中的应用。方法回顾性分析四川省肿瘤医院头颈外科2012年1月至12月118例应用精细化被膜解剖法行甲状腺全切术患者的临床资料。结果所有病例术中均发现并保留l～4枚甲状旁腺。其中16例未发现明确的下旁腺;术中发现上甲状旁腺197枚,其中42枚由甲状腺上动脉分支供血,131枚由甲状腺下动脉上行支供血;下甲状旁腺163枚,明确的下动脉分支血管供血的136枚。术后有62例（52.5%）甲状腺激素（PTH）值低于正常值（一过性甲状旁腺功能低下）,其中56例于术后第7天恢复正常,其余6例于术后2～4周恢复正常;23例有暂时性低钙血症症状的患者,术后4 d～1月都恢复正常,无永久性低钙血症。所有病例术中均解剖并显露双侧喉返神经,除术前喉返神经受侵或损伤的患者,其余患者均未发生永久性喉返神经损伤。结论采用精细化被膜解剖法行甲状腺全切除术,能较好地原位保留甲状旁腺及其血供、避免喉返神经损伤的发生,减少甲状腺全切除术的并发症。     

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 autotransplantation with total thyroidectomy for thyroid carcinoma: long-term follow-up of grafted parathyroid function.

BACKGROUND: Permanent hypoparathyroidism is a major complication of thyroidectomy. Autotransplantation of parathyroid glands has been attempted to prevent this complication. However, no direct data have been available to assess grafted parathyroid function after long-term follow-up in terms of the serum intact parathyroid hormone (PTH) concentration. METHODS: Eighty-four consecutive patients with differentiated thyroid carcinoma who underwent total thyroidectomy and bilateral modified neck dissection from 1992 to 1996 were enrolled. They concomitantly underwent total parathyroidectomy and autotransplantation of all parathyroid glands to the pectoralis major muscle. The serum intact PTH concentration was periodically measured as an index of grafted parathyroid function. RESULTS: The mean follow-up was 34 months. In all autotransplanted patients serum intact PTH concentrations fell below detectable limits immediately after surgery. They were restored to the normal range within 1 month postoperatively and were maintained during observation in 80 (95%) of 84 patients. Seventy-eight of 80 patients with normal intact PTH values were normocalcemic without any treatment and the remainder were normocalcemic with 1 microgram of 1 alpha-vitamin D3. Four hypoparathyroid patients were normocalcemic with 2 micrograms of 1 alpha-vitamin D3. The postoperative average serum intact PTH concentration of patients having more than 2 autotransplanted parathyroid glands was almost equal to that of patients with preservation of the parathyroid glands in situ. The incidence of permanent hypoparathyroidism was inversely correlated with the number of autotransplanted parathyroid glands. CONCLUSIONS: The recovery patterns of the intact PTH concentration indicate that the glands were grafted successfully and functioned for a long period. This feasible method of parathyroid autotransplantation bears comparison with the previous reports in terms of the incidence of permanent postoperative hypoparathyroidism, and it can be performed simply and is reproducible.     

Oral calcium load test: diagnostic and physiologic implications in hyperparathyroidism

An oral calcium load test (CLT) (1 gm Ca/50 kg) was administered to 11 control subjects and 35 patients with overt hyperparathyroidism to assess its efficacy in diagnosis of hyperparathyroidism. All participants were placed on a low-calcium diet 3 days before the CLT. Intact parathormone and ionized calcium (Cai) levels were measured 0, 1, 2, and 3 hours after CLT. Initial Cai and parathormone (mean +/- SE) were 1.22 +/- 0.01 mmol/L and 2.94 +/- 0.03 pmol/L in the control group compared with 1.43 +/- 0.02 mmol/L and 10.6 +/- 2.2 pmol/L in the group with hyperparathyroidism. Both groups had a similar percent increase in Cai values (control, 5.9% +/- 0.8%; hyperparathyroidism, 6.3% +/- 0.6% (p greater than 0.1). A decline in parathormone levels of 47.6% +/- 2.8% in patients with hyperparathyroidism was significantly less than the 75.3% +/- 5.3% decline observed in control subjects (p less than 0.025). Three hours after CLT, parathormone was suppressed in control subjects, whereas a rebound occurred in patients with hyperparathyroidism. Postoperative CLT demonstrated a higher mean percent Cai increase and percent parathormone decline (Cai, 8.9% +/- 1.1%; parathormone, 67.9% +/- 1.8%) compared with preoperative values (Cai, 6.0% +/- 1.0%; PTH, 49.6% +/- 4.3%) (p less than 0.025), and 3 hours after calcium intake, parathormone remained suppressed, similar to control subjects. After surgery, three patients had elevated parathormone and low normal Cai levels and parathormone response to a CLT confirmed the diagnosis of secondary hyperparathyroidism. In conclusion, a CLT (1) can confirm the diagnosis of hyperparathyroidism and successful parathyroidectomy, (2) distinguished postoperative secondary from persistent primary hyperparathyroidism, (3) demonstrated nonautonomy of abnormal parathyroid glands with a parathormone response to a calcium load characterized by an earlier nadir, decreased suppressibility, and more rapid recovery, and (4) produced dynamic changes that did not distinguish patients with hyperparathyroidism from control subjects or hyperplasia from adenoma.     

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.     

Enlarged parathyroid glands discovered in normocalcemic patients during thyroid surgery

BACKGROUND: This is a retrospective study analyzing data of normocalcemic patients with enlarged parathyroid glands discovered during thyroid surgery and comparing it with data of patients operated on for proved primary hyperparathyroidism. METHODS: The records of patients with enlarged parathyroid glands (group 1) and those with primary hyperparathyroidism (group 2) were reviewed. RESULTS: There were 11 patients in group 1 and 123 patients in group 2. Enlarged parathyroid glands identified at thyroid surgery were lighter and developed in younger patients. Biochemistry and pathology revealed that these were less hyperfunctioning. Sex, number of diseased glands per patient, and cell type were not statistically different between the 2 groups. CONCLUSIONS: Enlarged parathyroid glands discovered at the time of surgery are mildly hyperfunctioning. They may represent an early pathologic stage responsible for overt primary hyperparathyroidism. We recommend removal of enlarged parathyroid glands found during thyroid operation in normocalcemic patients as long as at least 1 normal parathyroid gland remains.     

原发性甲状旁腺功能亢进症临床分析（附138例报告）

目的 总结原发性甲状旁腺功能亢进症的诊治体会。方法 回顾性分析本院普通外科2015年1月至2017年11月经手术治疗的138例原发性甲状旁腺功能亢进症病人的临床资料。结果 138例病人,男30例,女108例,均行手术治疗,其中甲状旁腺危象5例,1例行急诊手术治疗。切除病变甲状旁腺150枚。术后病理检查显示：123枚（82.0%）为甲状旁腺腺瘤,9枚（6.0%）为甲状旁腺增生,4枚（2.7%）为甲状旁腺癌,10枚（6.6%）为甲状旁腺囊肿,4枚（2.7%）为甲状旁腺非典型腺瘤。术后第1天甲状旁腺素（parathyroid hormone, PTH）均降至正常,血钙下降。其中48例术后出现低血钙症状,经补充活性维生素D和葡萄糖酸钙,恢复正常。无喉返神经损伤等并发症发生。结论 血钙和PTH可作为原发性甲状旁腺功能亢进的初步诊断方法。甲状旁腺切除术是有效治疗手段。术前准确定位有助于缩小探查范围。对于甲状旁腺危象,给予水化利尿及双膦酸盐降钙治疗、及时早期行甲状旁腺切除术,可取得良好治疗效果。     

Phosphatemia is related to chromosomal aberrations of parathyroid glands in patients with hyperparathyroidism

BACKGROUND AND AIMS: It has been well documented that gene and DNA alterations occur frequently in benign primary parathyroid adenomas as well as in parathyroid glands with secondary hyperplasia. However, it has not been shown whether a correlation exists between somatic DNA aberrations and clinical data. METHODS: We analyzed the frequency of chromosomal aberrations in adenomas obtained from 25 patients with primary hyperparathyroidism (pHPT) and 60 parathyroid nodules from 20 uremic patients with secondary hyperparathyroidism (sHPT). The relation of chromosomal aberrations to parathyroid hormone, as well as calcium and phosphate serum concentrations, was assessed. Allelic changes were evaluated by microsatellite allelotyping using 105 polymorphic markers. RESULTS: Somatic chromosomal aberrations were found in 23 out of 25 adenomas, in hyperplastic lesions from 16 out of 20 patients. In pHPT as well as in sHPT a positive correlation was found between the number of chromosomal alterations and serum phosphate concentration (tau=0.270, p=0.05; and tau=0.362, p=0.03, respectively). Only in pHPT was a negative correlation of borderline significance between serum parathormone (PTH) and number of aberrated chromosomes noticed (tau=-0.258, p=0.07). There was no correlation between the number of DNA changes and serum concentration of calcium or tumor volume. CONCLUSION: Hyperphosphatemia may increase the risk of specific and random chromosomal aberrations due to increasing proliferation rate of parathyroid cells in patients with sHPT.