World J. Surg. 14, 342-348, 1990
World Journal of Surgery 9 1990 by the Soci~t~ Intemationale de Chirurgie
Undescended Parathyroid Adenoma: An Important Etiology for Failed Operations for Primary Hyperparathyroidism Douglas L. Fraker, M.D., John L. Doppman, M.D., Thomas H. Shawker, M.D., Stephen J. Marx, M.D., Allen M. Spiegel, M.D., and Jeffrey A. Norton, M.D. Surgery Branch, National Cancer Institute; Diagnostic Radiology Department, and the Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, U.S.A. From July, 1982 to April, 1989, a total of 145 patients with persistent or recurrent primary hyperparathyroidism (HPT) were explored; 105 patients had an adenoma as the cause of HPT, and in 9 patients (9%), the abnormal gland was located at or superior to the carotid bifurcation (undescended parathyroid gland). These 9 patients had 14 prior explorations for HPT including 4 median sternotomies and 5 thyroidectomies. Each of the 9 patients was symptomatic of HPT, including bone disease in 8 of 9 patients and renal stones in 4 of 9 patients. Seven patients had an undescended parathyroid adenoma correctly localized preoperatively by ultrasound (n = 5), angiography (n = 5), venous sampling (n = 1), or computed tomography scan (n = 4). These 7 patients with accurate preoperative localization were explored by an incision anterior to the sternodeidomastoid muscle high in the neck that avoided the previous operative fidd and allowed rapid resection of the parathyroid adenoma. In the 2 patients who did not have accurate preoperative localization, the undescended adenoma was found after long tedious exploration including median sternotomy in 1 patient. Each patient (n = 9) who had an undescended parathyroid adenoma removed was cured of hypercaicemia, and 5 patients required postoperative 1,25-dihydroxy vitamin D3 for hypocaicemia. We conclude that undescended parathyroid adenomas comprise a significant proportion (9%) of adenomas during reoperations for persistent HPT. The majority of these glands (78%) can be accurately imaged preoperatively and, when imaged, can be easily resected by a rapid, direct, surgical approach.
Concomitant with the well-recognized improved ability to determine the common occurrence of primary hyperparathyroidism (3-5/1,000 population) and secondary to automated laboratory screening [1] is a resultant associated increase in the number of initial operations for primary hyperparathyroidism (HPT), and subsequently, the number of failed initial operations for HPT [2]. The literature of the past decade contains several clinical series of reoperations for HPT delineating the technical difficulties as well as the increased risk of complications secondary to scarring and distortion of normal tissue planes [2-10]. The reported success rates of reoperations for HPT in recent Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989. Reprint requests: Jeffrey A. Norton, M.D., Head, Surgical Metabolism Section, Building 10, Room 2B07, Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, U.S.A.
reports from large referral centers is approximately 90% [3, 7, 8] while other investigators report overall success rates as low as 65% [2]. Reasons for failure include misdiagnosis failure to identify supernumerary glands, and incomplete resection of abnormal parathyroid tissue in hyperplasia [11]. Patients with "missed parathyroid adenomas" comprise the majority of patients with failed operations for persistent primary hyperparathyroidism. These patients have biochemical characteristics of HPT, biopsy, or excision of one or more histologically-proven normal parathyroid glands, and failure to identify any abnormal parathyroid tissue despite extensive neck explorations, mediastinal explorations, and often thymectomy and/or thyroidectomy. The unidentified parathyroid adenoma is presumably located in an unusual or ectopic site. An undescended inferior parathyroid gland may comprise a significant proportion of these missed adenomas. Edis and associates [12], in 1979, described an undescended parathyroid adenoma in 7 patients as a gland located high in the neck at the level of the angle of the mandible. The present series reports the finding of an undescended parathyroid adenoma in 9 patients undergoing reoperation for primary hyperparathyroidism. The ability to localize preoperatively an undescended parathyroid adenoma, and the unique operative approach to these patients are also described. Methods
From July, 1982 to April, 1989, a total of 145 patients with biochemical evidence of HPT underwent reoperation for persistent or recurrent HPT at the Clinical Center of the National Institutes of Health (NIH). Of these 145 patients, 33 had multiglandular disease and 7 had parathyroid carcinoma. Five of the remaining 105 patients had evidence of locally-recurrent parathyroid adenomas secondary to incomplete resection at the initial operation (3 patients), local seeding of an adenoma (1 patient), or a recurrent autografted adenoma (1 patient). The final 100 patients had persistent primary hyperparathyroidism following an initial unsuccessful exploration due to a missed parathyroid adenoma. Nine of these 100 patients were eventu-
D.L. Fraker et al.: Hyperparathyroidism
343
Results
Characteristics and Symptoms of Patients with Undescended Adenoma There were 5 female and 4 male patients with a median age of 51 years of age (Table 1). Each patient had clear biochemical evidence of HPT. Each patient was symptomatic with at least 1 symptom typical for primary hyperparathyroidism. The majority of the patients had renal stones (88%) and bone pain (44%), while the remainder had gastrointestinal or constitutional complaints.
Initial Operation 9
\
Fig. 1. Sketch of the neck, showing placement of the skin incision.
ally shown to have an undescended inferior parathyroid adenoma and these 9 patients comprise the population presented in the present study. Each patient had primary hyperparathyroidism documented by serially elevated serum levels of calcium and parathyroid hormone. Each patient underwent 2 or more noninvasive parathyroid-imaging studies consisting of a neck ultrasound, 99m technetium-thallium scan, or computed tomography (CT) [13]. Based on the certainty of the results of the noninvasive studies, a subgroup of patients had selective arteriography including the injection of the inferior thyroid artery, the superior thyroid artery, and the internal mammary artery [14]. If arteriogram was not helpful, then patients underwent selective venous catheterization for selective determination of venous parathyroid hormone levels [14]. Each patient underwent at least 1 prior operation at an outside institution before referral to the NIH. Outside pathology slides and operative reports were obtained and reviewed in each case. Patients were explored on the basis of the records from the initial exploration and the preoPerative localization studies. Patients with negative localization studies were explored via a standard cervical approach through the previous transverse neck incision. Dissection was developed medial to the carotid sheath to focus on the retrothyroidal paraesophageal areas. Patients with preoperative radiographic evidence of undescended parathyroid adenoma were explored by making a transverse or longitudinal incision over the medial border of the sternocleidomastoid muscle high in the neck at the approximate region of the hyoid bone or the carotid bifurcation (Fig. 1).
The 9 patients with undescended parathyroid adenomas had undergone 14 prior exploratory operations at outside institutions (5 patients had had 1 operation; 3 patients had had 2 operations; and 1 patient had had 3 operations) (Table 2). Seven of 14 operations in 4 of 9 patients had been performed at institutions that would have been recognized as referral centers or teaching institutions, and all of these operations had taken place within the past decade. The extent of the initial exploration was reflected by the types of procedures performed and the complications that ensued. Six patients (nos. 2, 3, 4, 6, 7, 9) had undergone thyroid resection in hopes of excising an intrathyroidal or subcapsular gland [15] including 5 patients (nos. 2, 3, 4, 7, 9) with a subtotal or total thyroidectomy. Four patients (nos. 4, 6, 7, 8) had had negative mediastinal exploration via median sternotomy. Two (nos. 2 and 6) of the 9 patients had suffered a recurrent laryngeal nerve injury including 1 patient with a bilateral nerve injury requiring tracheostomy. In every patient, at least 1 parathyroid gland was biopsied and, in 7 patients, more than 1 parathyroid was excised or biopsied. All previously removed parathyroid tissue was identified as normal by the pathologists. Following each of the outside operations, serum levels of calcium and parathyroid hormone (Table 1) remained elevated indicating persistent primary hyperparathyroidism.
Localizing Studies Each of 9 patients underwent noninvasive preoperative localizing studies including ultrasound and 99m technetium-thallium scan, and 8 patients underwent a CT scan (Table 3). Both CT scan and ultrasound correctly imaged approximately 50% of the undescended parathyroid adenomas (Fig. 2); however, these 2 studies appeared to image the same abnormal glands as each patient (nos. 2, 3, 4, 8) with a positive CT scan also had a positive ultrasound. One patient (no. 6) had ultrasound evidence of an undescended parathyroid adenoma and had an aspiration performed under ultrasound guidance that contained high levels of parathyroid hormone and did not undergo CT scanning. Technetium-thallium scans were not as useful as ultrasound or CT and only identified 2 (22%) of 9 undescended abnormal glands; however, 1 patient (no. 9) had a positive technetium-thallium scan and a negative ultrasound and CT scan. Overall, the noninvasive studies identified 6 (67%) of 9 undescended parathyroid glands correctly. Of the 7 patients who had a selective angiogram, 5 patients had the abnormal
344
World
J. Surg. Vol.
14, No. 3, May/June
1990
Table 1. Patient characteristics and symptoms in patients with undescended parathyroid adenoma. Symptoms Patient no.
Age (yr)
!
2 3 4 5 6 7 8 9
Biochemistry
Sex
Renal stones
Bone disease
Fatigue
PUD
Hypertension
22
F
+
+
-
64 68 43 61 46 33 51 60
F M M M M F F F
+ + + + + + +
+ . + . + -
+ -
+
+ -
+ -
+ +
-
+ -
.
.
.
+ .
.
.
+
Serum Ca meq/L
Serum PTH (nl range)
5.4 5.8 5.7 5.7 6.8 6.1 6.2 6.5 6.2
0.61 0.59 0.53 0.47 0.97 0.44 311 456 370
(
World Journal of Surgery 9 1990 by the Soci~t~ Intemationale de Chirurgie
Undescended Parathyroid Adenoma: An Important Etiology for Failed Operations for Primary Hyperparathyroidism Douglas L. Fraker, M.D., John L. Doppman, M.D., Thomas H. Shawker, M.D., Stephen J. Marx, M.D., Allen M. Spiegel, M.D., and Jeffrey A. Norton, M.D. Surgery Branch, National Cancer Institute; Diagnostic Radiology Department, and the Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, U.S.A. From July, 1982 to April, 1989, a total of 145 patients with persistent or recurrent primary hyperparathyroidism (HPT) were explored; 105 patients had an adenoma as the cause of HPT, and in 9 patients (9%), the abnormal gland was located at or superior to the carotid bifurcation (undescended parathyroid gland). These 9 patients had 14 prior explorations for HPT including 4 median sternotomies and 5 thyroidectomies. Each of the 9 patients was symptomatic of HPT, including bone disease in 8 of 9 patients and renal stones in 4 of 9 patients. Seven patients had an undescended parathyroid adenoma correctly localized preoperatively by ultrasound (n = 5), angiography (n = 5), venous sampling (n = 1), or computed tomography scan (n = 4). These 7 patients with accurate preoperative localization were explored by an incision anterior to the sternodeidomastoid muscle high in the neck that avoided the previous operative fidd and allowed rapid resection of the parathyroid adenoma. In the 2 patients who did not have accurate preoperative localization, the undescended adenoma was found after long tedious exploration including median sternotomy in 1 patient. Each patient (n = 9) who had an undescended parathyroid adenoma removed was cured of hypercaicemia, and 5 patients required postoperative 1,25-dihydroxy vitamin D3 for hypocaicemia. We conclude that undescended parathyroid adenomas comprise a significant proportion (9%) of adenomas during reoperations for persistent HPT. The majority of these glands (78%) can be accurately imaged preoperatively and, when imaged, can be easily resected by a rapid, direct, surgical approach.
Concomitant with the well-recognized improved ability to determine the common occurrence of primary hyperparathyroidism (3-5/1,000 population) and secondary to automated laboratory screening [1] is a resultant associated increase in the number of initial operations for primary hyperparathyroidism (HPT), and subsequently, the number of failed initial operations for HPT [2]. The literature of the past decade contains several clinical series of reoperations for HPT delineating the technical difficulties as well as the increased risk of complications secondary to scarring and distortion of normal tissue planes [2-10]. The reported success rates of reoperations for HPT in recent Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989. Reprint requests: Jeffrey A. Norton, M.D., Head, Surgical Metabolism Section, Building 10, Room 2B07, Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, U.S.A.
reports from large referral centers is approximately 90% [3, 7, 8] while other investigators report overall success rates as low as 65% [2]. Reasons for failure include misdiagnosis failure to identify supernumerary glands, and incomplete resection of abnormal parathyroid tissue in hyperplasia [11]. Patients with "missed parathyroid adenomas" comprise the majority of patients with failed operations for persistent primary hyperparathyroidism. These patients have biochemical characteristics of HPT, biopsy, or excision of one or more histologically-proven normal parathyroid glands, and failure to identify any abnormal parathyroid tissue despite extensive neck explorations, mediastinal explorations, and often thymectomy and/or thyroidectomy. The unidentified parathyroid adenoma is presumably located in an unusual or ectopic site. An undescended inferior parathyroid gland may comprise a significant proportion of these missed adenomas. Edis and associates [12], in 1979, described an undescended parathyroid adenoma in 7 patients as a gland located high in the neck at the level of the angle of the mandible. The present series reports the finding of an undescended parathyroid adenoma in 9 patients undergoing reoperation for primary hyperparathyroidism. The ability to localize preoperatively an undescended parathyroid adenoma, and the unique operative approach to these patients are also described. Methods
From July, 1982 to April, 1989, a total of 145 patients with biochemical evidence of HPT underwent reoperation for persistent or recurrent HPT at the Clinical Center of the National Institutes of Health (NIH). Of these 145 patients, 33 had multiglandular disease and 7 had parathyroid carcinoma. Five of the remaining 105 patients had evidence of locally-recurrent parathyroid adenomas secondary to incomplete resection at the initial operation (3 patients), local seeding of an adenoma (1 patient), or a recurrent autografted adenoma (1 patient). The final 100 patients had persistent primary hyperparathyroidism following an initial unsuccessful exploration due to a missed parathyroid adenoma. Nine of these 100 patients were eventu-
D.L. Fraker et al.: Hyperparathyroidism
343
Results
Characteristics and Symptoms of Patients with Undescended Adenoma There were 5 female and 4 male patients with a median age of 51 years of age (Table 1). Each patient had clear biochemical evidence of HPT. Each patient was symptomatic with at least 1 symptom typical for primary hyperparathyroidism. The majority of the patients had renal stones (88%) and bone pain (44%), while the remainder had gastrointestinal or constitutional complaints.
Initial Operation 9
\
Fig. 1. Sketch of the neck, showing placement of the skin incision.
ally shown to have an undescended inferior parathyroid adenoma and these 9 patients comprise the population presented in the present study. Each patient had primary hyperparathyroidism documented by serially elevated serum levels of calcium and parathyroid hormone. Each patient underwent 2 or more noninvasive parathyroid-imaging studies consisting of a neck ultrasound, 99m technetium-thallium scan, or computed tomography (CT) [13]. Based on the certainty of the results of the noninvasive studies, a subgroup of patients had selective arteriography including the injection of the inferior thyroid artery, the superior thyroid artery, and the internal mammary artery [14]. If arteriogram was not helpful, then patients underwent selective venous catheterization for selective determination of venous parathyroid hormone levels [14]. Each patient underwent at least 1 prior operation at an outside institution before referral to the NIH. Outside pathology slides and operative reports were obtained and reviewed in each case. Patients were explored on the basis of the records from the initial exploration and the preoPerative localization studies. Patients with negative localization studies were explored via a standard cervical approach through the previous transverse neck incision. Dissection was developed medial to the carotid sheath to focus on the retrothyroidal paraesophageal areas. Patients with preoperative radiographic evidence of undescended parathyroid adenoma were explored by making a transverse or longitudinal incision over the medial border of the sternocleidomastoid muscle high in the neck at the approximate region of the hyoid bone or the carotid bifurcation (Fig. 1).
The 9 patients with undescended parathyroid adenomas had undergone 14 prior exploratory operations at outside institutions (5 patients had had 1 operation; 3 patients had had 2 operations; and 1 patient had had 3 operations) (Table 2). Seven of 14 operations in 4 of 9 patients had been performed at institutions that would have been recognized as referral centers or teaching institutions, and all of these operations had taken place within the past decade. The extent of the initial exploration was reflected by the types of procedures performed and the complications that ensued. Six patients (nos. 2, 3, 4, 6, 7, 9) had undergone thyroid resection in hopes of excising an intrathyroidal or subcapsular gland [15] including 5 patients (nos. 2, 3, 4, 7, 9) with a subtotal or total thyroidectomy. Four patients (nos. 4, 6, 7, 8) had had negative mediastinal exploration via median sternotomy. Two (nos. 2 and 6) of the 9 patients had suffered a recurrent laryngeal nerve injury including 1 patient with a bilateral nerve injury requiring tracheostomy. In every patient, at least 1 parathyroid gland was biopsied and, in 7 patients, more than 1 parathyroid was excised or biopsied. All previously removed parathyroid tissue was identified as normal by the pathologists. Following each of the outside operations, serum levels of calcium and parathyroid hormone (Table 1) remained elevated indicating persistent primary hyperparathyroidism.
Localizing Studies Each of 9 patients underwent noninvasive preoperative localizing studies including ultrasound and 99m technetium-thallium scan, and 8 patients underwent a CT scan (Table 3). Both CT scan and ultrasound correctly imaged approximately 50% of the undescended parathyroid adenomas (Fig. 2); however, these 2 studies appeared to image the same abnormal glands as each patient (nos. 2, 3, 4, 8) with a positive CT scan also had a positive ultrasound. One patient (no. 6) had ultrasound evidence of an undescended parathyroid adenoma and had an aspiration performed under ultrasound guidance that contained high levels of parathyroid hormone and did not undergo CT scanning. Technetium-thallium scans were not as useful as ultrasound or CT and only identified 2 (22%) of 9 undescended abnormal glands; however, 1 patient (no. 9) had a positive technetium-thallium scan and a negative ultrasound and CT scan. Overall, the noninvasive studies identified 6 (67%) of 9 undescended parathyroid glands correctly. Of the 7 patients who had a selective angiogram, 5 patients had the abnormal
344
World
J. Surg. Vol.
14, No. 3, May/June
1990
Table 1. Patient characteristics and symptoms in patients with undescended parathyroid adenoma. Symptoms Patient no.
Age (yr)
!
2 3 4 5 6 7 8 9
Biochemistry
Sex
Renal stones
Bone disease
Fatigue
PUD
Hypertension
22
F
+
+
-
64 68 43 61 46 33 51 60
F M M M M F F F
+ + + + + + +
+ . + . + -
+ -
+
+ -
+ -
+ +
-
+ -
.
.
.
+ .
.
.
+
Serum Ca meq/L
Serum PTH (nl range)
5.4 5.8 5.7 5.7 6.8 6.1 6.2 6.5 6.2
0.61 0.59 0.53 0.47 0.97 0.44 311 456 370
(
