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Parathyroid autotransplantation with total thyroidectomy for thyroid carcinoma: Long-term follow-up of grafted parathyroid function
Parathyroid autotransplantation with total thyroidectomy for thyroid carcinoma: Long-term follow-up of grafted parathyroid function Toyone Kikumori, MD, Tsuneo Imai, MD, Yuji Tanaka, MD, Mikinao Oiwa, MD, Takahiro Mase, MD, and Hiroomi Funahashi, MD, Nagoya, Japan
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 µg of 1α-vitamin D3. Four hypoparathyroid patients were normocalcemic with 2 µg of 1α-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. (Surgery 1999;125:504-8.) From the Department of Surgery II, Nagoya University School of Medicine, Nagoya, Japan
PERMANENT HYPOPARATHYROIDISM IS A DISTRESSING complication of thyroidectomy that has been reported in 0% to 20% of patients who underwent this procedure.1-5 Much has been written regarding operative strategies to cope with these difficulties, yet no clearly superior approach has been established. Many authors agree that preservation of parathyroid glands in situ during thyroidectomy is desirable, if possible. However, it is frequently not technically feasible with total thyroidectomy,
Accepted for publication Jan 22, 1999. Reprint requests: Hiroomi Funahashi, MD, Department of Surgery II, Nagoya University School of Medicine, 65 Tsurumaicho, Showa-ku, Nagoya, 466-8550 Japan. Copyright © 1999 by Mosby, Inc. 0039-6060/99/$8.00 + 0
504 SURGERY
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and the blood supply to the parathyroid glands is easily compromised by aggressive neck dissection. Parathyroid autotransplantation is cited as another solution. Although several reports are available on the results of parathyroid autotransplantation,1,4,6,7 most of them are based on clinical assessment or biochemical analysis of the serum calcium concentration. However, the serum calcium concentration does not necessarily reflect the parathyroid function because it is readily affected by supplementation of calcium or vitamin D. We have previously reported successful parathyroid autotransplantation in patients with thyroid carcinoma and have documented the function of the grafted tissue during a short postoperative course.8 Here we present results of long-term follow-up of patients with the serum intact PTH concentration used as an index of parathyroid graft
Kikumori et al 505
Surgery Volume 125, Number 5 Table I. Number of autotransplanted glands No. of glands 2 3 4 Preservation in situ Total
Table II. Incidence of hypoparathyroidism
No. of patients 18 33 33 20 104
function. Our results indicate that autotransplantation of parathyroid glands is technically feasible and that grafted tissue functions in the long term. SUBJECTS AND METHODS One hundred four patients having total thyroidectomy because of thyroid differentiated carcinoma at the Department of Surgery II, Nagoya University School of Medicine, from January 1992 to December 1996 were investigated. The patients whose serum intact PTH, calcium, and phosphorus concentrations had been measured for more than 1 year were considered eligible. Seven patients were not eligible for the current study because one of them had undergone reoperation and the remainder were lost to follow-up within 1 year postoperatively. The mean follow-up was 34 months. Total thyroidectomy along with bilateral modified neck dissection was performed by 3 instructors (H. F., T. I., and Y. T.) or by senior surgical fellows under the supervision of these instructors. Twenty of these patients who underwent only total thyroidectomy because of multiple nodular goiter that at operation turned out to encompass incidental carcinomas postoperatively were assigned to the control group. Their parathyroid glands were preserved in situ. Data were collected regarding patient demographics, histopathologic diagnoses, number of autotransplanted glands (Table I), and postoperative courses. There were 88 female (85%) and 16 male (15%) patients in this series. The average age of the patients was 46.8 years (range 9 to 82 years) among female patients and 55.4 years (range 27 to 72 years) among male patients. Histopathologic analysis of resected thyroid specimens showed papillary carcinoma in 100 cases, follicular carcinoma in 3 cases, and medullary carcinoma in 1 case. Of 84 patients who underwent lymph node resection, 70 had positive nodes. (Control group was assigned to “unknown.”) In 29 (28%) of 104 cases the lesions were multifocal. All the patients were autotransplanted with 2 or more parathyroid glands. The term “hypoparathyroidism” is defined as a condition in which supplementation of calcium or vita-
No. of glands 2 3 4 Total Preservation in situ
No. with hypoparathyroidism/ No. of patients 3/18 (17%) 1/33 (3%) 0/33 (0%) 3/84 (5%) 0/20 (0%)
min D is required to maintain normocalcemia and the serum intact parathyroid hormone (PTH) concentration is below the normal range during observation. Two-site immunoradiometric assay was used to measure the serum intact PTH concentration.9 The normal range of the serum intact PTH concentration is between 10 and 65 pg/mL. Operative technique. Surgical procedures were previously described in detail.8 Briefly, our procedure is as follows. Removed parathyroid glands were minced into pieces to obtain a gel-like consistency. Each parathyroid tissue was immediately autotransplanted to the separate pockets excavated in the pectoralis major muscle, which was readily exposed by retraction of the caudal side of the skin incision. The pockets were closed with nylon sutures. Postoperative evaluation and follow-up. Postoperative evaluation of all patients included daily clinical evaluation for symptoms and signs of hypocalcemia. All patients had serum intact PTH, serum phosphorus, and serum calcium concentrations adjusted by serum albumin measured preoperatively, on the first, third, and seventh days and at 2 weeks and 1 month postoperatively and every 6 months at the outpatient department. All patients with autotransplantation were first administered 7.5 g of oral calcium lactate and 2 µg of 1α-vitamin D3 a day to prevent the occurrence of hypocalcemic symptoms on the day after surgery. If they did not have symptoms or signs of hypocalcemia, calcium and vitamin D supplementations were tapered off and discontinued along with confirmation of recovery of serum intact PTH, calcium, and phosphorus within 1 month after the procedure. The patients whose serum intact PTH concentrations did not recover to the normal range and who had symptoms or signs of hypocalcemia continued to take 1α- vitamin D3. Statistical analysis. Results from each group were subjected to 1-way analysis of variance, and Student’s t test was used to evaluate statistical significance. P values <.05 were considered significant. RESULTS None of 20 control patients had transient or permanent hypoparathyroidism. In all patients under-
506 Kikumori et al
Fig 1. Profile of serum intact PTH concentration in patients stratified by number of autotransplanted parathyroid glands. Data represent mean of each group ± SE (2 glands: open squares, n = 18; 3 glands: open diamonds, n = 33; 4 glands: open circles, n = 33; preservation in situ: open triangles, n = 20). Asterisk, P < .01 versus 2, 3, and 4 glands; dagger, P < .05 versus 4 glands; double dagger, P < .05 versus 2, 3 glands. Hatched area, Normal range. POD, Postoperative day.
going parathyroid autotransplantation, the 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 follow-up in 80 (95%) of 84 patients. Seventy-eight of 80 patients with normal intact PTH values were normocalcemic without any treatment, and 2 patients were normocalcemic with 1 µg of 1α-vitamin D3. Four hypoparathyroid patients were normocalcemic with 2 µg of 1α-vitamin D3. None of the patients required the administration of oral calcium to maintain normocalcemia. The serum intact PTH concentration of the control group varied within the normal range throughout most of the postoperative course (Fig 1). The average postoperative serum intact PTH concentration seemed to be correlated with the number of autotransplanted parathyroid glands. However, this correlation was not statistically significant except in patients with 2 autotransplanted glands. Similar to our previous report,8 the serum intact PTH concentration of all those patients who underwent total thyroidectomy and bilateral neck dissection fell transiently below the detectable limit between the first and the third day postoperatively. This suggested that our procedure virtually removed all parathyroid glands. There were 4 patients (5%) with failure in auto-
Surgery May 1999
Fig 2. Profile of serum calcium concentration in patients stratified by number of autotransplanted parathyroid glands. Data represent mean of each group ± SE (2 glands: open squares, n = 18; 3 glands: open diamonds, n = 33; 4 glands: open circles, n = 33; preservation in situ: open triangles, n = 20). Asterisk, P < .01 vs 2, 3, and 4 glands. Hatched area, Normal range. POD, Postoperative day.
transplantation. The incidence of hypoparathyroidism was apparently higher in the group with a smaller number of grafts (Table II). There were no patients with “late hypoparathyroidism” in which a successfully implanted graft lost its function later. The occurrence of postoperative complications such as chylorrhea or hematoma at the recipient sites did not adversely affect the postoperative grafted parathyroid function. The reason for the smaller number of grafts was attributed to the extensive lymph node metastases (data not shown). The serum calcium concentration fell transiently in the early postoperative period in all groups and recovered to the preoperative value 1 month postoperatively. Thereafter there was no significant difference among the different graft groups (Fig 2). Likewise, the serum phosphorus concentration fluctuated reciprocally in relationship to the calcium concentration and there was no significant difference among the different graft groups (Fig 3). No other remarkable sequelae were encountered in this series. DISCUSSION We previously reported that our methods for parathyroid autotransplantation were feasible for at least a short period.8 There have been many reports on parathyroid autotransplantation during thyroidectomy.1,4-7 These reports, however, included various operative methods (eg, total thyroidectomy or lobectomy, various numbers of grafts, and
Surgery Volume 125, Number 5
autotransplantation alone or in combination with preservation in situ), and there have been few consistent series of patients or techniques. In previous reports describing parathyroid autotransplantation in humans1,4,6,7 assessment of parathyroid autotransplantation performed during thyroidectomy was considerably impractical in terms of confirming aparathyroidism and the various numbers of resected parathyroid glands. Most of these results are based on clinical assessment or biochemical analyses such as measurement of the serum calcium concentration. However, we demonstrated that the serum calcium level did not always reflect parathyroid function (eg, the calcium concentration was not necessarily lower in the patients who had lower intact PTH concentrations). We showed in this study that all the patients who underwent parathyroid autotransplantation transiently had virtual aparathyroidism, and most patients were successfully weaned from supplemental calcium and vitamin D within 3 weeks of thyroidectomy. This means all parathyroid glands, including supranumeric glands that are frequently found in thymus, were removed during the procedure, and the serum intact PTH value in all patients who underwent autotransplantation could depend on parathyroid graft function. In the earlier series we did not administer calcium and vitamin D to the patients until overt symptoms of hypocalcemia such as tetany emerged because we supposed that supplementation by calcium and vitamin D would interfere with engraftment. However, we previously confirmed that supplementation of vitamin D did not interfere with engraftment of human parathyroid glands in nude mice10 and humans.11,12 Therefore we routinely administer calcium and vitamin D to prevent the occurrence of tetany in the early postoperative course. Four hypoparathyroid patients in this series have required long-term vitamin D supplementation to maintain normocalcemia. Overall, parathyroid autotransplantation was successful in 80 (95%) of 84 patients and resulted in a 5% incidence of hypoparathyroidism after parathyroid autotransplantation. The investigators who routinely use parathyroid autotransplantation reported an incidence of hypoparathyroidism of less than 6%.1,3-5 Our results compare favorably with the results of these previous reports. There were no patients with failure in the control group. Thyroidectomy alone without central bilateral neck dissection harbors a lower risk for the vascular supply of the parathyroid glands than does thyroidectomy combined with bilateral central neck dissection, which is part of a radical cancer surgery and modified neck dissection. Therefore this might not be an optimal control group.
Kikumori et al 507
Fig 3. Profile of serum phosphorus concentration in patients stratified by number of autotransplanted parathyroid glands. Data represent mean of each group ± SE (2 glands: open squares, n = 18; 3 glands: open diamonds, n = 33; 4 glands: open circles, n = 33; preservation in situ: open triangles, n = 20). Asterisk, P < .01 versus preserved in situ; dagger, P < .05 vs 2, 3, and 4 glands. Hatched area, Normal range. POD, Postoperative day.
Patients with only 2 parathyroid glands grafted had a lower concentration of intact PTH and a higher incidence of hypoparathyroidism. This implies that the amount of grafted tissue is critical for the maintenance of postoperative parathyroid function. It also suggests that autotransplantation of 3 or more parathyroid glands is desirable for maintaining postoperative parathyroid function and that autotransplantation of 4 glands is best. It is preferable that the parathyroid glands be left in situ if the cancerous lesion can be removed without total parathyroidectomy. In this series we routinely removed all parathyroid glands to complete thorough neck dissection. However, we are of the opinion that hereafter we try to perform neck dissection in a technique compatible with parathyroid preservation in situ. Another aspect of the current study is the method of autotransplantation. In most of the previous reports the resected parathyroid glands were sliced and engrafted into the sternocleidomastoid muscle. However, the technique for slicing the parathyroid glands takes considerable time, and the blood supply for the sternocleidomastoid muscle is easily compromised during neck dissection, whereas mincing the parathyroid glands is simple to perform and the pectoralis major muscle is easily accessible from the collar incision. Although there is still room for improvement in the technique for identifying parathyroid glands,
508 Kikumori et al
our method for mincing the glands can be performed easily. The feasibility of this procedure depends on the number of identified parathyroid glands during thyroidectomy and neck dissection. We think there may be no difference in outcome among surgeons if our method is used. Our method should be also taken into consideration in case of insufficient blood supply to the parathyroid glands, which the surgeon should try to preserve in situ. In summary, our method offers a solution to make total thyroidectomy and bilateral neck dissection compatible with parathyroid function. We have shown that the function of autotransplanted parathyroid glands can be maintained in the long term. REFERENCES 1. Salander H, Tisell LE. Incidence of hypoparathyroidism after radical surgery for thyroid carcinoma and autotransplantation of parathyroid glands. Am J Surg 1977;134:358-62. 2. Wingert DJ, Friesen SR, Iliopoulos JI, Pierce GE, Thomas JH, Hermreck AS. Post-thyroidectomy hypocalcemia: incidence and risk factors. Am J Surg 1986;152:606-10. 3. Shaha AR, Burnett C, Jaffe BM. Parathyroid autotransplantation during thyroid surgery. J Surg Oncol 1991;46:21-4. 4. Olson JA Jr, DeBenedetti MK, Baumann DS, Wells SA Jr. Parathyroid autotransplantation during thyroidectomy: results of long-term follow-up. Ann Surg 1996;223:472-80.
Surgery May 1999 5. Skinner MA, Norton JA, Moley JF, DeBenedetti MK, Wells SJ. Heterotopic autotransplantation of parathyroid tissue in children undergoing total thyroidectomy. J Pediatr Surg 1997;32:510-3. 6. Ohman U, Granberg PO, Lindell B. Function of the parathyroid glands after total thyroidectomy. Surg Gynecol Obstet 1978;146:773-8. 7. Walker RP, Paloyan E, Kelley TF, Gopalsami C, Jarosz H. Parathyroid autotransplantation in patients undergoing a total thyroidectomy: a review of 261 patients. Otolaryngol Head Neck Surg 1994;111:258-64. 8. Funahashi H, Satoh Y, Imai T, Ohno M, Narita T, Katoh M, et al. Our technique of parathyroid autotransplantation in operation for papillary thyroid carcinoma. Surgery 1993;114:92-6. 9. Nussbaum SR, Zahradnik RJ, Lavigne JR, Brennan GL, Nozawa-Ung K, Kim LY, et al. Highly sensitive two-side immunoradiometric assay of parahthyrin, and its clinical utility in evaluating patients with hypercalcemia. Clin Chem 1987;33:1364-7. 10. Funahashi H, Tanaka Y, Imai T, Wada M, Tsukamura K, Hayakawa Y, et al. Parathyroid hormone suppression by 22oxacalcitriol in the severe parathyroid hyperplasia. J Endocrinol Invest 1998;21:43-7. 11. Ueda M, Funahashi H, Satoh Y, Kato M, Takagi H. Evaluation on our procedure for autotransplantation of parathyroid glands by the intact-PTH. Nippon Geka Gakkai Zasshi 1993;94:840-6. 12. Imai T, Tanaka Y, Kikumori T, Ohiwa M, Matsuura N, Funahashi H. Surgical management of preclinical medullary thyroid carcinoma in MEN2A. Thyroidol Clin Exp 1998;10:143-7.
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 µg of 1α-vitamin D3. Four hypoparathyroid patients were normocalcemic with 2 µg of 1α-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. (Surgery 1999;125:504-8.) From the Department of Surgery II, Nagoya University School of Medicine, Nagoya, Japan
PERMANENT HYPOPARATHYROIDISM IS A DISTRESSING complication of thyroidectomy that has been reported in 0% to 20% of patients who underwent this procedure.1-5 Much has been written regarding operative strategies to cope with these difficulties, yet no clearly superior approach has been established. Many authors agree that preservation of parathyroid glands in situ during thyroidectomy is desirable, if possible. However, it is frequently not technically feasible with total thyroidectomy,
Accepted for publication Jan 22, 1999. Reprint requests: Hiroomi Funahashi, MD, Department of Surgery II, Nagoya University School of Medicine, 65 Tsurumaicho, Showa-ku, Nagoya, 466-8550 Japan. Copyright © 1999 by Mosby, Inc. 0039-6060/99/$8.00 + 0
504 SURGERY
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and the blood supply to the parathyroid glands is easily compromised by aggressive neck dissection. Parathyroid autotransplantation is cited as another solution. Although several reports are available on the results of parathyroid autotransplantation,1,4,6,7 most of them are based on clinical assessment or biochemical analysis of the serum calcium concentration. However, the serum calcium concentration does not necessarily reflect the parathyroid function because it is readily affected by supplementation of calcium or vitamin D. We have previously reported successful parathyroid autotransplantation in patients with thyroid carcinoma and have documented the function of the grafted tissue during a short postoperative course.8 Here we present results of long-term follow-up of patients with the serum intact PTH concentration used as an index of parathyroid graft
Kikumori et al 505
Surgery Volume 125, Number 5 Table I. Number of autotransplanted glands No. of glands 2 3 4 Preservation in situ Total
Table II. Incidence of hypoparathyroidism
No. of patients 18 33 33 20 104
function. Our results indicate that autotransplantation of parathyroid glands is technically feasible and that grafted tissue functions in the long term. SUBJECTS AND METHODS One hundred four patients having total thyroidectomy because of thyroid differentiated carcinoma at the Department of Surgery II, Nagoya University School of Medicine, from January 1992 to December 1996 were investigated. The patients whose serum intact PTH, calcium, and phosphorus concentrations had been measured for more than 1 year were considered eligible. Seven patients were not eligible for the current study because one of them had undergone reoperation and the remainder were lost to follow-up within 1 year postoperatively. The mean follow-up was 34 months. Total thyroidectomy along with bilateral modified neck dissection was performed by 3 instructors (H. F., T. I., and Y. T.) or by senior surgical fellows under the supervision of these instructors. Twenty of these patients who underwent only total thyroidectomy because of multiple nodular goiter that at operation turned out to encompass incidental carcinomas postoperatively were assigned to the control group. Their parathyroid glands were preserved in situ. Data were collected regarding patient demographics, histopathologic diagnoses, number of autotransplanted glands (Table I), and postoperative courses. There were 88 female (85%) and 16 male (15%) patients in this series. The average age of the patients was 46.8 years (range 9 to 82 years) among female patients and 55.4 years (range 27 to 72 years) among male patients. Histopathologic analysis of resected thyroid specimens showed papillary carcinoma in 100 cases, follicular carcinoma in 3 cases, and medullary carcinoma in 1 case. Of 84 patients who underwent lymph node resection, 70 had positive nodes. (Control group was assigned to “unknown.”) In 29 (28%) of 104 cases the lesions were multifocal. All the patients were autotransplanted with 2 or more parathyroid glands. The term “hypoparathyroidism” is defined as a condition in which supplementation of calcium or vita-
No. of glands 2 3 4 Total Preservation in situ
No. with hypoparathyroidism/ No. of patients 3/18 (17%) 1/33 (3%) 0/33 (0%) 3/84 (5%) 0/20 (0%)
min D is required to maintain normocalcemia and the serum intact parathyroid hormone (PTH) concentration is below the normal range during observation. Two-site immunoradiometric assay was used to measure the serum intact PTH concentration.9 The normal range of the serum intact PTH concentration is between 10 and 65 pg/mL. Operative technique. Surgical procedures were previously described in detail.8 Briefly, our procedure is as follows. Removed parathyroid glands were minced into pieces to obtain a gel-like consistency. Each parathyroid tissue was immediately autotransplanted to the separate pockets excavated in the pectoralis major muscle, which was readily exposed by retraction of the caudal side of the skin incision. The pockets were closed with nylon sutures. Postoperative evaluation and follow-up. Postoperative evaluation of all patients included daily clinical evaluation for symptoms and signs of hypocalcemia. All patients had serum intact PTH, serum phosphorus, and serum calcium concentrations adjusted by serum albumin measured preoperatively, on the first, third, and seventh days and at 2 weeks and 1 month postoperatively and every 6 months at the outpatient department. All patients with autotransplantation were first administered 7.5 g of oral calcium lactate and 2 µg of 1α-vitamin D3 a day to prevent the occurrence of hypocalcemic symptoms on the day after surgery. If they did not have symptoms or signs of hypocalcemia, calcium and vitamin D supplementations were tapered off and discontinued along with confirmation of recovery of serum intact PTH, calcium, and phosphorus within 1 month after the procedure. The patients whose serum intact PTH concentrations did not recover to the normal range and who had symptoms or signs of hypocalcemia continued to take 1α- vitamin D3. Statistical analysis. Results from each group were subjected to 1-way analysis of variance, and Student’s t test was used to evaluate statistical significance. P values <.05 were considered significant. RESULTS None of 20 control patients had transient or permanent hypoparathyroidism. In all patients under-
506 Kikumori et al
Fig 1. Profile of serum intact PTH concentration in patients stratified by number of autotransplanted parathyroid glands. Data represent mean of each group ± SE (2 glands: open squares, n = 18; 3 glands: open diamonds, n = 33; 4 glands: open circles, n = 33; preservation in situ: open triangles, n = 20). Asterisk, P < .01 versus 2, 3, and 4 glands; dagger, P < .05 versus 4 glands; double dagger, P < .05 versus 2, 3 glands. Hatched area, Normal range. POD, Postoperative day.
going parathyroid autotransplantation, the 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 follow-up in 80 (95%) of 84 patients. Seventy-eight of 80 patients with normal intact PTH values were normocalcemic without any treatment, and 2 patients were normocalcemic with 1 µg of 1α-vitamin D3. Four hypoparathyroid patients were normocalcemic with 2 µg of 1α-vitamin D3. None of the patients required the administration of oral calcium to maintain normocalcemia. The serum intact PTH concentration of the control group varied within the normal range throughout most of the postoperative course (Fig 1). The average postoperative serum intact PTH concentration seemed to be correlated with the number of autotransplanted parathyroid glands. However, this correlation was not statistically significant except in patients with 2 autotransplanted glands. Similar to our previous report,8 the serum intact PTH concentration of all those patients who underwent total thyroidectomy and bilateral neck dissection fell transiently below the detectable limit between the first and the third day postoperatively. This suggested that our procedure virtually removed all parathyroid glands. There were 4 patients (5%) with failure in auto-
Surgery May 1999
Fig 2. Profile of serum calcium concentration in patients stratified by number of autotransplanted parathyroid glands. Data represent mean of each group ± SE (2 glands: open squares, n = 18; 3 glands: open diamonds, n = 33; 4 glands: open circles, n = 33; preservation in situ: open triangles, n = 20). Asterisk, P < .01 vs 2, 3, and 4 glands. Hatched area, Normal range. POD, Postoperative day.
transplantation. The incidence of hypoparathyroidism was apparently higher in the group with a smaller number of grafts (Table II). There were no patients with “late hypoparathyroidism” in which a successfully implanted graft lost its function later. The occurrence of postoperative complications such as chylorrhea or hematoma at the recipient sites did not adversely affect the postoperative grafted parathyroid function. The reason for the smaller number of grafts was attributed to the extensive lymph node metastases (data not shown). The serum calcium concentration fell transiently in the early postoperative period in all groups and recovered to the preoperative value 1 month postoperatively. Thereafter there was no significant difference among the different graft groups (Fig 2). Likewise, the serum phosphorus concentration fluctuated reciprocally in relationship to the calcium concentration and there was no significant difference among the different graft groups (Fig 3). No other remarkable sequelae were encountered in this series. DISCUSSION We previously reported that our methods for parathyroid autotransplantation were feasible for at least a short period.8 There have been many reports on parathyroid autotransplantation during thyroidectomy.1,4-7 These reports, however, included various operative methods (eg, total thyroidectomy or lobectomy, various numbers of grafts, and
Surgery Volume 125, Number 5
autotransplantation alone or in combination with preservation in situ), and there have been few consistent series of patients or techniques. In previous reports describing parathyroid autotransplantation in humans1,4,6,7 assessment of parathyroid autotransplantation performed during thyroidectomy was considerably impractical in terms of confirming aparathyroidism and the various numbers of resected parathyroid glands. Most of these results are based on clinical assessment or biochemical analyses such as measurement of the serum calcium concentration. However, we demonstrated that the serum calcium level did not always reflect parathyroid function (eg, the calcium concentration was not necessarily lower in the patients who had lower intact PTH concentrations). We showed in this study that all the patients who underwent parathyroid autotransplantation transiently had virtual aparathyroidism, and most patients were successfully weaned from supplemental calcium and vitamin D within 3 weeks of thyroidectomy. This means all parathyroid glands, including supranumeric glands that are frequently found in thymus, were removed during the procedure, and the serum intact PTH value in all patients who underwent autotransplantation could depend on parathyroid graft function. In the earlier series we did not administer calcium and vitamin D to the patients until overt symptoms of hypocalcemia such as tetany emerged because we supposed that supplementation by calcium and vitamin D would interfere with engraftment. However, we previously confirmed that supplementation of vitamin D did not interfere with engraftment of human parathyroid glands in nude mice10 and humans.11,12 Therefore we routinely administer calcium and vitamin D to prevent the occurrence of tetany in the early postoperative course. Four hypoparathyroid patients in this series have required long-term vitamin D supplementation to maintain normocalcemia. Overall, parathyroid autotransplantation was successful in 80 (95%) of 84 patients and resulted in a 5% incidence of hypoparathyroidism after parathyroid autotransplantation. The investigators who routinely use parathyroid autotransplantation reported an incidence of hypoparathyroidism of less than 6%.1,3-5 Our results compare favorably with the results of these previous reports. There were no patients with failure in the control group. Thyroidectomy alone without central bilateral neck dissection harbors a lower risk for the vascular supply of the parathyroid glands than does thyroidectomy combined with bilateral central neck dissection, which is part of a radical cancer surgery and modified neck dissection. Therefore this might not be an optimal control group.
Kikumori et al 507
Fig 3. Profile of serum phosphorus concentration in patients stratified by number of autotransplanted parathyroid glands. Data represent mean of each group ± SE (2 glands: open squares, n = 18; 3 glands: open diamonds, n = 33; 4 glands: open circles, n = 33; preservation in situ: open triangles, n = 20). Asterisk, P < .01 versus preserved in situ; dagger, P < .05 vs 2, 3, and 4 glands. Hatched area, Normal range. POD, Postoperative day.
Patients with only 2 parathyroid glands grafted had a lower concentration of intact PTH and a higher incidence of hypoparathyroidism. This implies that the amount of grafted tissue is critical for the maintenance of postoperative parathyroid function. It also suggests that autotransplantation of 3 or more parathyroid glands is desirable for maintaining postoperative parathyroid function and that autotransplantation of 4 glands is best. It is preferable that the parathyroid glands be left in situ if the cancerous lesion can be removed without total parathyroidectomy. In this series we routinely removed all parathyroid glands to complete thorough neck dissection. However, we are of the opinion that hereafter we try to perform neck dissection in a technique compatible with parathyroid preservation in situ. Another aspect of the current study is the method of autotransplantation. In most of the previous reports the resected parathyroid glands were sliced and engrafted into the sternocleidomastoid muscle. However, the technique for slicing the parathyroid glands takes considerable time, and the blood supply for the sternocleidomastoid muscle is easily compromised during neck dissection, whereas mincing the parathyroid glands is simple to perform and the pectoralis major muscle is easily accessible from the collar incision. Although there is still room for improvement in the technique for identifying parathyroid glands,
508 Kikumori et al
our method for mincing the glands can be performed easily. The feasibility of this procedure depends on the number of identified parathyroid glands during thyroidectomy and neck dissection. We think there may be no difference in outcome among surgeons if our method is used. Our method should be also taken into consideration in case of insufficient blood supply to the parathyroid glands, which the surgeon should try to preserve in situ. In summary, our method offers a solution to make total thyroidectomy and bilateral neck dissection compatible with parathyroid function. We have shown that the function of autotransplanted parathyroid glands can be maintained in the long term. REFERENCES 1. Salander H, Tisell LE. Incidence of hypoparathyroidism after radical surgery for thyroid carcinoma and autotransplantation of parathyroid glands. Am J Surg 1977;134:358-62. 2. Wingert DJ, Friesen SR, Iliopoulos JI, Pierce GE, Thomas JH, Hermreck AS. Post-thyroidectomy hypocalcemia: incidence and risk factors. Am J Surg 1986;152:606-10. 3. Shaha AR, Burnett C, Jaffe BM. Parathyroid autotransplantation during thyroid surgery. J Surg Oncol 1991;46:21-4. 4. Olson JA Jr, DeBenedetti MK, Baumann DS, Wells SA Jr. Parathyroid autotransplantation during thyroidectomy: results of long-term follow-up. Ann Surg 1996;223:472-80.
Surgery May 1999 5. Skinner MA, Norton JA, Moley JF, DeBenedetti MK, Wells SJ. Heterotopic autotransplantation of parathyroid tissue in children undergoing total thyroidectomy. J Pediatr Surg 1997;32:510-3. 6. Ohman U, Granberg PO, Lindell B. Function of the parathyroid glands after total thyroidectomy. Surg Gynecol Obstet 1978;146:773-8. 7. Walker RP, Paloyan E, Kelley TF, Gopalsami C, Jarosz H. Parathyroid autotransplantation in patients undergoing a total thyroidectomy: a review of 261 patients. Otolaryngol Head Neck Surg 1994;111:258-64. 8. Funahashi H, Satoh Y, Imai T, Ohno M, Narita T, Katoh M, et al. Our technique of parathyroid autotransplantation in operation for papillary thyroid carcinoma. Surgery 1993;114:92-6. 9. Nussbaum SR, Zahradnik RJ, Lavigne JR, Brennan GL, Nozawa-Ung K, Kim LY, et al. Highly sensitive two-side immunoradiometric assay of parahthyrin, and its clinical utility in evaluating patients with hypercalcemia. Clin Chem 1987;33:1364-7. 10. Funahashi H, Tanaka Y, Imai T, Wada M, Tsukamura K, Hayakawa Y, et al. Parathyroid hormone suppression by 22oxacalcitriol in the severe parathyroid hyperplasia. J Endocrinol Invest 1998;21:43-7. 11. Ueda M, Funahashi H, Satoh Y, Kato M, Takagi H. Evaluation on our procedure for autotransplantation of parathyroid glands by the intact-PTH. Nippon Geka Gakkai Zasshi 1993;94:840-6. 12. Imai T, Tanaka Y, Kikumori T, Ohiwa M, Matsuura N, Funahashi H. Surgical management of preclinical medullary thyroid carcinoma in MEN2A. Thyroidol Clin Exp 1998;10:143-7.