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Surgical Anatomy and Technique of Neck Exploration for Primary Hyperparathyroidism
Symposium on Head and Neck Surgery I
Surgical Anatomy and Technique of Neck Exploration for Primary Hyperparathyroidism I .1 !;. :. 1
Anthony J. Edis, M.D.
Primary hyperparathyroidism is much more common than previously suspected, occurring frequently in an asymptomatic form without complications. The increase in frequency of diagnosis can be attributed mainly to the wide-scale use of multichannel biochemical screening as part of the general medical examination. 31 Cervical exploration for primary hyperparathyroidism has become quite commonplace and is no longer restricted to a few major institutions with a special interest in the disease. Often the operation is so easy that the uninitiated surgeon wonders what all the fuss is about. However, there are many pitfalls and an unsuccessful exploration may have serious and far-reaching consequences. Reoperation on the neck to find a missed parathyroid tumor is difficult and fraught with hazard to the recurrent laryngeal nerves and any remaining normal glands. Therefore, it is important that anyone undertaking parathyroid surgery be thoroughly familiar with the anatomy and pathology of the parathyroids and with the many nuances of technique which may make the difference between success or failure. Indications for Operation Of course the diagnosis of hyperparathyroidism should be firmly established before surgical exploration is undertaken. In the usual case, elevation of serum calcium is the major criterion for diagnosis. Now that a reliable radioimmunoassay for parathormone (PTH) 2 is available, my colleagues and I almost routinely confirm the diagnosis by measurement of the serum PTH level-all patients with primary hyperparathyroidism should have inappropriately elevated concentrations of serum PTH. The criteria we have adopted for operative intervention in patients with primary hyperparathyroidism are summarized in Table 1. 31 The question is often asked, should one operate on patients with asymptomatic hyperparathyroidism and serum calcium levels consistently less than 11 mg/dl ("biochemical" hyperparathyroidism)? To answer this, the natural history of asymptomatic, biochemical primary hyperparathyroidism was recently studied prospectively at the Mayo Clinic. 30•31 After 5 years, 20% of the original group of 146 patients had Surgical Clinics of North America-Vol. 57, No. 3, June 1977
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Table 1. Criteria for Surgical Treatment in Primary Hyperparathyroidism 1. Mean serum calcium above 11 mg/dl (normal: 8.9-10.1) 2. Roentgenologic evidence of bone disease (usually osteitis fibrosa, but sometimes severe osteoporosis) 3. Impairment of renal function 4. Metabolically active or infected renal stones 5. Gastrointestinal complications (peptic ulcer disease, pancreatitis) 6. Impracticality of prolonged observation
come to operation-usually because of progression of their disease, evidenced by increase in serum calcium above 11 mg/dl, development of renal stones or bone disease, or decrease in renal function. It was also plain from this study that careful medical follow-up of these patients is time-consuming, expensive, and sometimes extremely taxing. As one might expect, asymptomatic patients often tend to discount the seriousness of their disease and drop out of follow-up, sometimes despite heroic efforts to bring them back. Accordingly, our current practice is to recommend surgical treatment for patients with biochemical hyperparathyroidism whenever the patient does not express interest and a great willingness to participate in a prolonged period of systematic and regular observation. Having made the decision to operate, two questions confront the surgeon: where are the parathyroids, and how many are diseased?
Anatomic Considerations Notwithstanding many op1n10ns to the contrary, a normal parathyroid gland in the adult is rather easily recognizable grossly at surgery. Perhaps its most characteristic feature is its yellow-brown color. Thyroid tissue is more red, lymph nodes are paler and more pink, and thymic tissue is a pale grayish-yellow. Parathyroid glands may have various shapes and dimensions: oval, spherical, pyriform or leaf-like when suspended in loose areolar tissue, fat, or thymus; and flattened or stretched to resemble a disk or pancake 4 •14•39 when situated deep to the surgical capsule of the thyroid (as is often true of upper glands). A parathyroid gland is soft and pliable in contrast to lymph nodes and thyroid nodules, which are relatively firm. Blood-stained lobules of fat may resemble parathyroid tissue closely in color and texture; but parathyroid tissue will sink in normal saline, whereas a fatty globule will float. 39 The usual weight of a normal parathyroid gland is 35 to 40 mg;L 18•39A 2 but normal glands weighing up to 78 mg have been described in autopsy series, 39 and we have encountered incidentally a normal parathyroid gland weighing 130 mg during the course of thyroidectomy for benign goiter in a eucalcemic patient. Each parathyroid is supplied by a single small artery that enters at a definite hilus and radiates out over the capsule of the gland in a fem-like pattem. 1 • 14 The inferior thyroid artery is of predominant importance for
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Figure 1. Location of parathyroid glands: posterior view. (From Edis AJ, Ayala LA, Egdahl RH: Manual of Endocrine Surgery. Springer-Verlag New York, 1975. By permission.)
the vascular supply of the parathyroids, always supplying at least one of the parathyroids on each side and supplying both upper and lower glands in approximately 80% of cases. 1 The usual number of parathyroids is four. In a detailed account of 352 cases, Alveryd found five parathyroids in 3.7%, four in 90.6%, three in 5.1 %, and 2 in 0.6%. In only one of the cases with two or three parathyroids identified was the combined weight of the glands sufficiently high to suggest that none had been overlooked; and Alveryd concluded that four or more parathyroids probably occur in almost every case. Several careful autopsy studiesL 18 •39•42 have shown that the anatomy of the parathyroids is reasonably constant. The glands are placed symmetrically on opposite sides of the neck in 80% of cases. 12•32•37 The upper pair develop in association with the lateral thyroid from the fourth branchial pouch. They are almost invariably behind the upper pole or at the cricothyroid junction (Figs. 1 and 2). From the embryologic standpoint, the upper parathyroid should not be outside the zone
Figure 2. Location of parathyroid glands: right lateral view, patient supine, thyroid retracted. Note the ectopic inferior parathyroid gland imbedded in cervical thymus-a common finding. (From Edis AJ, Ayala LA, Egdahl RH: Manual of Endocrine Surgery. SpringerVerlag New York, 1975. By permission.)
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bounded by the upper border of the larynx and the lower border of the thyroid. The lower pair of parathyroids are somewhat more widely distributed than the upper pair, but they are almost always in the immediate vicinity of the lower pole of the thyroid. In about half of cases, the lower parathyroid is found on the anterolateral or posterolateral surface of the lower pole of the thyroid, near one of the terminal branches of the inferior thyroid artery (see Figs. 1 and 2). If not in this position, the lower gland is located usually (42% of cases in Wang's series)39 within a tongue of thymic tissue that extends up into the neck from the main body of the thymus to reach the lower thyroid pole. By gentle probing of the thymus, the parathyroid c~ be manipulated to the surface, where it can be seen just beneath the capsule as a darker body immersed in the grayishyellow thymic tissue. This close association with the thymus is not surprising, given that both the lower parathyroid and the thymus develop from the third branchial complex. Occasionally a lower gland descends with the thymus all the way into the mediastinum, or it may be left high in the neck as a result of early developmental arrest. The identity of one of these so-called undescended lower glands is often suggested by the presence of a closely associated thymic remnant.l 4 •39 Such is the proximity of the lower parathyroid to the thymus that Weller4 1 called it the "parathymus" gland. In sum, although it is very unusual not to find the gland in close proximity to the lower pole of the thyroid, the lower parathyroid may be found anywhere from the angle of the jaw to the pericardium. 39 Besides developmental aberrations, a parathyroid, if enlarged, may be displaced caudally (probably in much the same manner as a low-lying adenoma of the thyroid which becomes intrathoracic). If the gland was originally an upper one, and therefore situated well posteriorly, its displacement will be down along the tracheoesophageal groove into the posterior mediastinum. A lower gland will be displaced either into the anterior or posterior mediastinum, according to whether it was originally situated in an anterior or posterior plane (Fig. 3). Wang39 has pointed out that those glands which are situated deep to the surgical capsule of the thyroid usually remain in place when enlarged, expanding within the confines of the capsule.
Pathologic Considerations At the present time, there is much confusion regarding the pathology of primary hyperparathyroidism. Difficulties exist not only in distinguishing hyperplasia from adenoma but also in distinguishing abnormal from normal glands. 6 •33 Lack of precise pathologic criteria has led to a wide variation in the reported incidence of single-gland and multiplegland disease, and this has engendered a great deal of controversy regarding the appropriate surgical treatment of patients with primary hyperparathyroidism (Table 2). The extent of surgery obviously depends on the pathologic entity believed to be present: single-gland disease should require resection of only one gland for cure; multiple-gland disease will require resection of
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Figure 3. Displacement of parathyroid tumors, caudad, toward anterior or posterior mediastinum. (From Edis AJ, Ayala LA, Egdahl RH: Manual of Endocrine Surgery. Springer-Verlag New York, 1975. By permission.)
more than one gland. Some groups currently report 50 to 60% incidence of parathyroid hyperplasia in their series and advocate subtotal parathyroidectomy in every case. 3·20·27·28 This is a radical departure from traditionally accepted practice, which is predicated on the belief that only 10 to 20% of cases have multiple-gland disease or hyperplasia. On this basis, removal of just a single enlarged gland has been considered sufficient for cure in 80 to 90% of cases.19,2s.ao.a2.as A review of the literature7.9· 11•24- 26·32·40 finds little or no evidence to substantiate the view that removal of only one enlarged gland (adenoma)
Table 2. Relative Frequency of Parathyroid Adenoma, Hyperplasia, and Carcinoma in Reported Series %PRIMARY
NO. OF AUTHOR AND YEAR
Goldman et al., 1971 19 Krementz et al., 197123 Hoehn et al., 196922 Davies, 1974 15 Palmer et al., 19752• Satava et al., 197534 Myers, 197425 Werner et al., 197443 Wang, 196638 Romanus et al., 197332 Block et al., 19747 Bruining, 1971 9 Haff and Armstrong, 19742" Eselstyn et al., 1974 17 Haff and Ballinger, 1971 2' Paloyan et al., 19732•
PATIENTS
300 100 788 350 250 307 185 129 431 274 121 242 35 100 74 84
%
ADENOMA
96 96 93 90 90 90 82 84 82 81 80 60 57 51 50 33
HYPERPLASIA
3 3 6 7 9 10 11
14 14 19 20 40 43 49 50 65
%
CARCINOMA
1 1
3 <1 1
4
2
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allows a high incidence of recurrent hyperparathyroidism. 28 Indeed, the converse appears to be true, with recurrence rates of less than 1% in the majority of reported series. It seems very hazardous to advise subtotal parathyroidectomy as a routine procedure solely on theoretic grounds. Perhaps the most serious objection to this radical policy is that it will inevitably result in a higher incidence of postoperative tetany. As Cope 13 has emphasized recently, "Hypoparathyroidism even of mild degree can be miserable: not just the tetany but the anxiety that accompanies slight hypocalcemia." One should not lose sight of the fact that many patients coming to operation today have few, if any, symptoms. To create a significant medical disability where previously none was apparent is deplorable.
Operative Strategy In view of the uncertainty surrounding the histologic diagnosis of parathyroid disease, the surgeon must depend ultimately upon the gross findings at operation, correlated with his knowledge of the clinical history and laboratory data, to distinguish between single-gland and multiple-gland disease and to form his decision regarding specific surgical treatment. The strategy of the operation is based on the probability that the patient has four parathyroids, and the immediate aim of the exploration is their methodical identification. Care must be taken to prevent bleeding, since the characteristic color of the parathyroids is readily obscured by diffusion of blood through the areolar tissue and fat. In the usual case, one of the four glands will be replaced by an adenoma, the size of the adenoma being roughly proportional to the level of serum calcium.l 4 •31 If at least one other normal-sized parathyroid is found, the surgeon can be reasonably sure that he is not dealing with hyperplasia. From a practical point of view, the extent ofthe dissection is governed by the need to find a missing gland or glands. A reasonable effort should be made to exclude a second adenoma or the unlikely possibility of asymmetric hyperplasia of other glands; however, we consider it unwise to prolong the dissection unnecessarily in the majority for the exception. We agree with Cope that unnecessary exploration only endangers the integrity of the undiseased parathyroids and recurrent nerves. 12 Biopsy of glands that appear grossly normal in size and color is indicated infrequently; and rarely, if ever, should it be necessary to remove intentionally a gland believed to be normal. 5 • 14• 19 Of course, if one is in doubt as to whether a piece of tissue is parathyroid, a specimen should be removed for biopsy; and in those cases where a lesion has not been found, biopsy of uninvolved glands becomes necessary to remove all doubt concerning the nature of the glands provisionally identified grossly. Thus biopsy usually is performed only late in the dissection, to provide some guidance for extending the search into other regions of the neck to find a missing gland. In order to avoid destruction of the parathyroid, great care must be taken not to disturb its fragile blood
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supply. When biopsying a gland, one should steady the gland by holding the surrounding fat and take only a minute specimen from the antihilar tip. A pathologist able to recognize parathyroid tissue by examination of fresh-frozen sections is essential to the conduct of the operation.
Technical Aspects The mid compartment of the neck and posterior superior mediastinum in which the parathyroids may be found can be explored adequately under direct vision through a conventional collar incision in the lower neck. The platysma is elevated with skin flaps and the deep cervical fascia is incised in the midline. We have not found it necessary to divide the strap muscles for exposure; indeed, the tension imparted to the cervical areolar tissue by lateral traction of the straps appears to facilitate the dissection. Beginning on either the right or left side, a thyroid lobe is elevated and rotated medially. The areolar tissue is carefully cleared from around the lobe, the inferior thyroid artery, and the middle thyroid veins; and the latter vessels are carefully divided and ligated. If it becomes necessary to extend the dissection into the vicinity of the recurrent laryngeal nerve, we expose the nerve from its entrance into the operative field to the adherent zone of the thyroid in the belief that it is safer to expose the important anatomy than to avoid it. The dissection can be carried distally under direct vision into the posterior mediastinum if necessary. In the usual case, when these steps have been followed on both sides of the neck, an adenoma will have been encountered and the dissection will have been sufficiently extensive to exclude with reasonable certainty enlargement of any other glands. If preliminary bilateral dissection fails to reveal an adenoma, biopsy specimens are taken from all glands provisionally identified by gross inspection and then the exploration is systematically widened. The dissection is extended as far as possible under direct vision into the anterior and posterior mediastinum. If a vascular pedicle arises from the inferior thyroid artery and extends into the mediastinum, it may be a clue to the presence of a displaced adenoma. The retroesophageal and retropharyngeal space may harbor a parathyroid tumor, and it should be examined next. If still no adenoma has been found, the region above the upper pole of the thyroid is opened as high as the hyoid bone in search of an "undescended" inferior parathyroid. The areolar tissue as far lateral as the carotid sheath should also be explored, and the carotid sheath itself opened and inspected. If the exploration thus far has proved fruitless, serious consideration should be given to bisecting that lobe of the thyroid on the side of the missing gland or even removing it subtotally. Intrathyroid parathyroid tumors are rare, but a definite possibility. 36 If an extended search of the neck does not reveal a parathyroid lesion, it is probably best not to proceed with sternotomy and a formal mediastinal exploration unless the patient is in parathyroid crisis. The preferred course is to reconfirm the diagnosis and perform localizing
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studies (parathyroid arteriography with or without selective small vein catheterization and PTH assay) 16 before undertaking a mediastinal dissection. Interestingly, there have been several reports of patients who were cured after negative cervical exploration5 •34-presumably because there was critical interference to the blood supply of the missing tumor during the course of dissection. A formal mediastinal exploration has been required in less than 2% of all surgical cases of primary hyperparathyroidism at the Mayo Clinic.
Extent of Resection, Based on Operative Findings When an adenoma is found and normal glands are identified, only the adenoma need be removed for cure. Biopsy of one normal gland is optional in this situation, but routine biopsy of all three remaining glands or removal of normal glands is undesirable in our opinion. If a parathyroid tumor is hard and whitish and is firmly fixed to surrounding tissue, the possibility of carcinoma should be considered. Degenerative changes in a benign adenoma may lead to adhesions, but the benign lesion usually is less hard and less firmly fixed than an infiltrating carcinoma. If carcinoma is suspected, wide excision is indicated, including the lobe of the thyroid and possibly even the recurrent laryngeal nerve without breaking into the lesion. Rupture of the adherent capsule has been followed by implantations difficult to eradicate by secondary operations .14 If four hyperplastic glands are identified, three are removed completely and about 35 to 50 mg of the fourth gland is left in situ. The gland to be preserved in part should be selected before any of the parathyroids are removed, so that the surgeon has several more chances to obtain a viable remnant if the gland chosen first is badly injured. The parathyroid remnant is tagged with a long silk suture to facilitate its identification should reoperation be required. Nearly all patients will a familial history of hyperparathyroidism or with multiple endocrine neoplasia have chief cell hyperplasia. In our experience, there has been a significant incidence of recurrent hypercalcemia when less than three or three and one-half glands have been removed. Subtotal parathyroidectomy is probably indicated in all these cases even if only a single gland is enlarged. When four normal glands have been found (and their identity proved by biopsy), there is some divergence of opinion about the best course to follow. Block et al. 8 have recommended removal of three and one-half glands on the grounds that microscopic hyperplasia may be present. However, with four normal-sized glands in the neck there may be an adenoma of the supernumerary gland elsewhere in the neck or in the mediastinum: 5 of 14 patients with mediastinal parathyroid adenomas described by Scholz et al. 35 had four glands previously identified in the neck. When four normal-sized parathyroids are found and biopsy reveals a normal histologic pattem, a possible asymmetric fifth gland should be sought. If none is found, it would be reasonable in our opinion to leave the glands in situ, marking them with long silk sutures for future iden-
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ti:fication. If subsequent study failed to reveal a mediastinal tumor or an aberrant tumor in the neck, reoperation with combined mediastinal and neck exploration could be undertaken with planned subtotal parathyroidectomy.
REFERENCES 1. Alveryd A: Parathyroid glands in thyroid surgery. I. Anatomy of parathyroid glands. II. Postoperative hypoparathyroidism: identification and autotransplantation of parathyroid glands. Acta Chir Scand Suppl 389:1-120, 1968 2. Arnaud CD, Tsao HS, Littledike T: Radioimmunoassay of human parathyroid hormone in serum. J Clin Invest 50:21-34, 1971 3. Ballinger WF, Haff RC: Hyperparathyroidism: increased frequency of diagnosis. South Med J 63:571-575, 1970 4. Black EM: Hyperparathyroidism. Springfield, Illinois, Charles C Thomas, Publisher, 1953 5. Black EM, Zimmer JF: Hyperparathyroidism, with particular reference to treatment. Arch Surg 72:830--837, 1956 6. Black WC III, Utley JR: The differential diagnosis of parathyroid adenoma and chief cell hyperplasia. Am J Clin Pathol 49:761-775, 1968 7. Block MA, Frame B, Jackson CE, et al: The extent of operation for primary hyperparathyroidism. Arch Surg 109:798-801, 1974 8. Block MA, Frame B, Jackson CE, et al: Primary diffuse microscopical hyperplasia of the parathyroid glands. Arch Surg 111:348-353, 1976 9. Bruining HA: Surgical Treatment of Hyperparathyroidism With an Analysis of 267 Cases. Springfield, Illinois, Charles C Thomas, Publisher, 1971 10. Clark OH, Taylor S: Osteoclastoma of the jaw and multiple parathyroid tumors. Surg Gynecol Obstet 135:188-192, 1972 11. Clark OH, Way LW, Hunt TK: Recurrent hyperparathyroidism. Ann Surg 184:391-399, 1976 12. Cope 0: Hyperparathyroidism: diagnosis and management. Am J Surg 99:394-403, 1960 13. Cope 0: Hyperparathyroidism: too little, too much surgery? (editorial). N Engl J Med 295:100-102, 1976 14. Cope 0: Surgery of hyperparathyroidism: the occurrence of parathyroids in the anterior mediastinum and the division of the operation into two stages. Ann Surg 114:706-731, 1941 15. Davies DR: The surgery of primary hyperparathyroidism. Clin Endocrinol Metabol 3:253-265, 1974 16. Doppman JL, Mallette LE, Marx SJ, et al: The localization of abnormal mediastinal parathyroid glands. Radiology 115:31-36, 1975 17. Esselstyn CB Jr, Levin HS, Eversman JJ, et al: Reappraisal of parathyroid pathology in hyperparathyroidism. Surg Clin North Am 54:443-447, 1974 18. Gilmour JR: The gross anatomy of the parathyroid glands. J Pathol Bacteriol46: 133-149, 1938 19. Goldman L, Gordan GS, Roof BS: The parathyroids: progress, problems and practice. Curr Probl Surg August 1971, pp 1-64 20. Haff RC, Armstrong RG: Trends in the current management of primary hyperparathyroidism. Surgery 75:715-719, 1974 21. Haff RC, Ballinger WF: Causes of recurrent hypercalcemia after parathyroidectomy for primary hyperparathyroidism. Ann Surg 173:884-889, 1971 22. Hoehn JG, Beahrs OH, Woolner LB: Unusual surgical lesions of the parathyroid gland. Am J Surg 118:770-778, 1969 23. Krementz ET, Yeager R, Hawley W, et al: The first 100 cases of parathyroid tumor from Charity Hospital of Louisiana. Ann Surg 173:872-883, 1971 24. Muller H: True recurrence of hyperparathyroidism: proposed criteria of recurrence. Br J Surg 62:556-559, 1975 25. Myers RT: Followup study of surgically-treated primary hyperparathyroidism. Ann Surg 179:729-732, 1974 26. Palmer JA, Brown WA, Kerr WH, et al: The surgical aspects of hyperparathyroidism. Arch Surg 110:1004-1006, 1975
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27. Paloyan E, Lawrence AM, Baker WH, et al: Near-total parathyroidectomy. Surg Clin North Am 49:43-48, 1969 28. Paloyan E, Lawrence AM, Straus FH: Hyperparathyroidism. New York, Grune & Stratton, 1973 29. Paloyan E, Paloyan D, Pickleman JR: Hyperparathyroidism today. Surg Clin North Am 53:211-220, 1973 30. Pumell DC, Scholz DA, Smith LH, et al: Treatment of primary hyperparathyroidism. Am J Med 56:800-809, 1974 31. Pumell DC, Smith LH, Scholz DA, et al: Primary hyperparathyroidism: a prospective clinical study. Am J Med 50:670-678, 1971 32. Roman us R, Heimann P, Nilsson 0, et al: Surgical treatment of hyperparathyroidism. Prog Surg 12:22-76, 1973 33. Roth Sl: Recent advances in parathyroid gland pathology. Am J Med 50:612-622, 1971 34. Satava RM Jr, Beahrs OH, Scholz DA: Success rate of cervical exploration for hyperparathyroidism. Arch Surg 110:625-627, 1975 35. Scholz DA, Pumell DC, Woolner LB, et al: Mediastinal hyperfunctioning parathyroid tumors: review of 14 cases. Ann Surg 178:173-178, 1973 36. Spiegel AM, Marx SJ, Doppman JL, et al: lntrathyroidal parathyroid adenoma or hyperplasia: an occasionally overlooked cause of surgical failure in primary hyperparathyroidism. JAMA 234:1029-1033, 1975 37. Vail AD, Coller FC: The number and location of parathyroid glands recovered from 202 routine autopsies. Mo Med 63:347-350, 1966 38. Wang C-A: Surgery of the parathyroid glands. Adv Surg 5:109-127, 1966 39. Wang C-A: The anatomic basis of parathyroid surgery. Ann Surg 183:271-275, 1976 40. Watanabe M, Baxter S, Beck JC: Hyperparathyroidism due to late recurrence of parathyroid adenoma. Am J Med 31:498-504, 1961 41. Weller GL Jr: Development of the thyroid, parathyroid and thymus glands in man. In Contributions to Embryology. Vol24, No 141. Camegie Institution of Washington, September 1933, pp 93-139 42. Welsh DA: Conceming the parathyroid glands: a critical, anatomical, and experimental study. J Anat Physiol 32:292-307; 380-402, 1898 43. Werner S, Hjem B, Sjoberg HE: Primary hyperparathyroidism: analysis of findings in a series of 129 patients. Acta Chir Scand 140:618-625, 1974
Mayo Clinic Rochester, Minnesota 55901
Surgical Anatomy and Technique of Neck Exploration for Primary Hyperparathyroidism I .1 !;. :. 1
Anthony J. Edis, M.D.
Primary hyperparathyroidism is much more common than previously suspected, occurring frequently in an asymptomatic form without complications. The increase in frequency of diagnosis can be attributed mainly to the wide-scale use of multichannel biochemical screening as part of the general medical examination. 31 Cervical exploration for primary hyperparathyroidism has become quite commonplace and is no longer restricted to a few major institutions with a special interest in the disease. Often the operation is so easy that the uninitiated surgeon wonders what all the fuss is about. However, there are many pitfalls and an unsuccessful exploration may have serious and far-reaching consequences. Reoperation on the neck to find a missed parathyroid tumor is difficult and fraught with hazard to the recurrent laryngeal nerves and any remaining normal glands. Therefore, it is important that anyone undertaking parathyroid surgery be thoroughly familiar with the anatomy and pathology of the parathyroids and with the many nuances of technique which may make the difference between success or failure. Indications for Operation Of course the diagnosis of hyperparathyroidism should be firmly established before surgical exploration is undertaken. In the usual case, elevation of serum calcium is the major criterion for diagnosis. Now that a reliable radioimmunoassay for parathormone (PTH) 2 is available, my colleagues and I almost routinely confirm the diagnosis by measurement of the serum PTH level-all patients with primary hyperparathyroidism should have inappropriately elevated concentrations of serum PTH. The criteria we have adopted for operative intervention in patients with primary hyperparathyroidism are summarized in Table 1. 31 The question is often asked, should one operate on patients with asymptomatic hyperparathyroidism and serum calcium levels consistently less than 11 mg/dl ("biochemical" hyperparathyroidism)? To answer this, the natural history of asymptomatic, biochemical primary hyperparathyroidism was recently studied prospectively at the Mayo Clinic. 30•31 After 5 years, 20% of the original group of 146 patients had Surgical Clinics of North America-Vol. 57, No. 3, June 1977
495
496
ANTHONY
J. Ems
Table 1. Criteria for Surgical Treatment in Primary Hyperparathyroidism 1. Mean serum calcium above 11 mg/dl (normal: 8.9-10.1) 2. Roentgenologic evidence of bone disease (usually osteitis fibrosa, but sometimes severe osteoporosis) 3. Impairment of renal function 4. Metabolically active or infected renal stones 5. Gastrointestinal complications (peptic ulcer disease, pancreatitis) 6. Impracticality of prolonged observation
come to operation-usually because of progression of their disease, evidenced by increase in serum calcium above 11 mg/dl, development of renal stones or bone disease, or decrease in renal function. It was also plain from this study that careful medical follow-up of these patients is time-consuming, expensive, and sometimes extremely taxing. As one might expect, asymptomatic patients often tend to discount the seriousness of their disease and drop out of follow-up, sometimes despite heroic efforts to bring them back. Accordingly, our current practice is to recommend surgical treatment for patients with biochemical hyperparathyroidism whenever the patient does not express interest and a great willingness to participate in a prolonged period of systematic and regular observation. Having made the decision to operate, two questions confront the surgeon: where are the parathyroids, and how many are diseased?
Anatomic Considerations Notwithstanding many op1n10ns to the contrary, a normal parathyroid gland in the adult is rather easily recognizable grossly at surgery. Perhaps its most characteristic feature is its yellow-brown color. Thyroid tissue is more red, lymph nodes are paler and more pink, and thymic tissue is a pale grayish-yellow. Parathyroid glands may have various shapes and dimensions: oval, spherical, pyriform or leaf-like when suspended in loose areolar tissue, fat, or thymus; and flattened or stretched to resemble a disk or pancake 4 •14•39 when situated deep to the surgical capsule of the thyroid (as is often true of upper glands). A parathyroid gland is soft and pliable in contrast to lymph nodes and thyroid nodules, which are relatively firm. Blood-stained lobules of fat may resemble parathyroid tissue closely in color and texture; but parathyroid tissue will sink in normal saline, whereas a fatty globule will float. 39 The usual weight of a normal parathyroid gland is 35 to 40 mg;L 18•39A 2 but normal glands weighing up to 78 mg have been described in autopsy series, 39 and we have encountered incidentally a normal parathyroid gland weighing 130 mg during the course of thyroidectomy for benign goiter in a eucalcemic patient. Each parathyroid is supplied by a single small artery that enters at a definite hilus and radiates out over the capsule of the gland in a fem-like pattem. 1 • 14 The inferior thyroid artery is of predominant importance for
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Figure 1. Location of parathyroid glands: posterior view. (From Edis AJ, Ayala LA, Egdahl RH: Manual of Endocrine Surgery. Springer-Verlag New York, 1975. By permission.)
the vascular supply of the parathyroids, always supplying at least one of the parathyroids on each side and supplying both upper and lower glands in approximately 80% of cases. 1 The usual number of parathyroids is four. In a detailed account of 352 cases, Alveryd found five parathyroids in 3.7%, four in 90.6%, three in 5.1 %, and 2 in 0.6%. In only one of the cases with two or three parathyroids identified was the combined weight of the glands sufficiently high to suggest that none had been overlooked; and Alveryd concluded that four or more parathyroids probably occur in almost every case. Several careful autopsy studiesL 18 •39•42 have shown that the anatomy of the parathyroids is reasonably constant. The glands are placed symmetrically on opposite sides of the neck in 80% of cases. 12•32•37 The upper pair develop in association with the lateral thyroid from the fourth branchial pouch. They are almost invariably behind the upper pole or at the cricothyroid junction (Figs. 1 and 2). From the embryologic standpoint, the upper parathyroid should not be outside the zone
Figure 2. Location of parathyroid glands: right lateral view, patient supine, thyroid retracted. Note the ectopic inferior parathyroid gland imbedded in cervical thymus-a common finding. (From Edis AJ, Ayala LA, Egdahl RH: Manual of Endocrine Surgery. SpringerVerlag New York, 1975. By permission.)
498
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bounded by the upper border of the larynx and the lower border of the thyroid. The lower pair of parathyroids are somewhat more widely distributed than the upper pair, but they are almost always in the immediate vicinity of the lower pole of the thyroid. In about half of cases, the lower parathyroid is found on the anterolateral or posterolateral surface of the lower pole of the thyroid, near one of the terminal branches of the inferior thyroid artery (see Figs. 1 and 2). If not in this position, the lower gland is located usually (42% of cases in Wang's series)39 within a tongue of thymic tissue that extends up into the neck from the main body of the thymus to reach the lower thyroid pole. By gentle probing of the thymus, the parathyroid c~ be manipulated to the surface, where it can be seen just beneath the capsule as a darker body immersed in the grayishyellow thymic tissue. This close association with the thymus is not surprising, given that both the lower parathyroid and the thymus develop from the third branchial complex. Occasionally a lower gland descends with the thymus all the way into the mediastinum, or it may be left high in the neck as a result of early developmental arrest. The identity of one of these so-called undescended lower glands is often suggested by the presence of a closely associated thymic remnant.l 4 •39 Such is the proximity of the lower parathyroid to the thymus that Weller4 1 called it the "parathymus" gland. In sum, although it is very unusual not to find the gland in close proximity to the lower pole of the thyroid, the lower parathyroid may be found anywhere from the angle of the jaw to the pericardium. 39 Besides developmental aberrations, a parathyroid, if enlarged, may be displaced caudally (probably in much the same manner as a low-lying adenoma of the thyroid which becomes intrathoracic). If the gland was originally an upper one, and therefore situated well posteriorly, its displacement will be down along the tracheoesophageal groove into the posterior mediastinum. A lower gland will be displaced either into the anterior or posterior mediastinum, according to whether it was originally situated in an anterior or posterior plane (Fig. 3). Wang39 has pointed out that those glands which are situated deep to the surgical capsule of the thyroid usually remain in place when enlarged, expanding within the confines of the capsule.
Pathologic Considerations At the present time, there is much confusion regarding the pathology of primary hyperparathyroidism. Difficulties exist not only in distinguishing hyperplasia from adenoma but also in distinguishing abnormal from normal glands. 6 •33 Lack of precise pathologic criteria has led to a wide variation in the reported incidence of single-gland and multiplegland disease, and this has engendered a great deal of controversy regarding the appropriate surgical treatment of patients with primary hyperparathyroidism (Table 2). The extent of surgery obviously depends on the pathologic entity believed to be present: single-gland disease should require resection of only one gland for cure; multiple-gland disease will require resection of
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Figure 3. Displacement of parathyroid tumors, caudad, toward anterior or posterior mediastinum. (From Edis AJ, Ayala LA, Egdahl RH: Manual of Endocrine Surgery. Springer-Verlag New York, 1975. By permission.)
more than one gland. Some groups currently report 50 to 60% incidence of parathyroid hyperplasia in their series and advocate subtotal parathyroidectomy in every case. 3·20·27·28 This is a radical departure from traditionally accepted practice, which is predicated on the belief that only 10 to 20% of cases have multiple-gland disease or hyperplasia. On this basis, removal of just a single enlarged gland has been considered sufficient for cure in 80 to 90% of cases.19,2s.ao.a2.as A review of the literature7.9· 11•24- 26·32·40 finds little or no evidence to substantiate the view that removal of only one enlarged gland (adenoma)
Table 2. Relative Frequency of Parathyroid Adenoma, Hyperplasia, and Carcinoma in Reported Series %PRIMARY
NO. OF AUTHOR AND YEAR
Goldman et al., 1971 19 Krementz et al., 197123 Hoehn et al., 196922 Davies, 1974 15 Palmer et al., 19752• Satava et al., 197534 Myers, 197425 Werner et al., 197443 Wang, 196638 Romanus et al., 197332 Block et al., 19747 Bruining, 1971 9 Haff and Armstrong, 19742" Eselstyn et al., 1974 17 Haff and Ballinger, 1971 2' Paloyan et al., 19732•
PATIENTS
300 100 788 350 250 307 185 129 431 274 121 242 35 100 74 84
%
ADENOMA
96 96 93 90 90 90 82 84 82 81 80 60 57 51 50 33
HYPERPLASIA
3 3 6 7 9 10 11
14 14 19 20 40 43 49 50 65
%
CARCINOMA
1 1
3 <1 1
4
2
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allows a high incidence of recurrent hyperparathyroidism. 28 Indeed, the converse appears to be true, with recurrence rates of less than 1% in the majority of reported series. It seems very hazardous to advise subtotal parathyroidectomy as a routine procedure solely on theoretic grounds. Perhaps the most serious objection to this radical policy is that it will inevitably result in a higher incidence of postoperative tetany. As Cope 13 has emphasized recently, "Hypoparathyroidism even of mild degree can be miserable: not just the tetany but the anxiety that accompanies slight hypocalcemia." One should not lose sight of the fact that many patients coming to operation today have few, if any, symptoms. To create a significant medical disability where previously none was apparent is deplorable.
Operative Strategy In view of the uncertainty surrounding the histologic diagnosis of parathyroid disease, the surgeon must depend ultimately upon the gross findings at operation, correlated with his knowledge of the clinical history and laboratory data, to distinguish between single-gland and multiple-gland disease and to form his decision regarding specific surgical treatment. The strategy of the operation is based on the probability that the patient has four parathyroids, and the immediate aim of the exploration is their methodical identification. Care must be taken to prevent bleeding, since the characteristic color of the parathyroids is readily obscured by diffusion of blood through the areolar tissue and fat. In the usual case, one of the four glands will be replaced by an adenoma, the size of the adenoma being roughly proportional to the level of serum calcium.l 4 •31 If at least one other normal-sized parathyroid is found, the surgeon can be reasonably sure that he is not dealing with hyperplasia. From a practical point of view, the extent ofthe dissection is governed by the need to find a missing gland or glands. A reasonable effort should be made to exclude a second adenoma or the unlikely possibility of asymmetric hyperplasia of other glands; however, we consider it unwise to prolong the dissection unnecessarily in the majority for the exception. We agree with Cope that unnecessary exploration only endangers the integrity of the undiseased parathyroids and recurrent nerves. 12 Biopsy of glands that appear grossly normal in size and color is indicated infrequently; and rarely, if ever, should it be necessary to remove intentionally a gland believed to be normal. 5 • 14• 19 Of course, if one is in doubt as to whether a piece of tissue is parathyroid, a specimen should be removed for biopsy; and in those cases where a lesion has not been found, biopsy of uninvolved glands becomes necessary to remove all doubt concerning the nature of the glands provisionally identified grossly. Thus biopsy usually is performed only late in the dissection, to provide some guidance for extending the search into other regions of the neck to find a missing gland. In order to avoid destruction of the parathyroid, great care must be taken not to disturb its fragile blood
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501
supply. When biopsying a gland, one should steady the gland by holding the surrounding fat and take only a minute specimen from the antihilar tip. A pathologist able to recognize parathyroid tissue by examination of fresh-frozen sections is essential to the conduct of the operation.
Technical Aspects The mid compartment of the neck and posterior superior mediastinum in which the parathyroids may be found can be explored adequately under direct vision through a conventional collar incision in the lower neck. The platysma is elevated with skin flaps and the deep cervical fascia is incised in the midline. We have not found it necessary to divide the strap muscles for exposure; indeed, the tension imparted to the cervical areolar tissue by lateral traction of the straps appears to facilitate the dissection. Beginning on either the right or left side, a thyroid lobe is elevated and rotated medially. The areolar tissue is carefully cleared from around the lobe, the inferior thyroid artery, and the middle thyroid veins; and the latter vessels are carefully divided and ligated. If it becomes necessary to extend the dissection into the vicinity of the recurrent laryngeal nerve, we expose the nerve from its entrance into the operative field to the adherent zone of the thyroid in the belief that it is safer to expose the important anatomy than to avoid it. The dissection can be carried distally under direct vision into the posterior mediastinum if necessary. In the usual case, when these steps have been followed on both sides of the neck, an adenoma will have been encountered and the dissection will have been sufficiently extensive to exclude with reasonable certainty enlargement of any other glands. If preliminary bilateral dissection fails to reveal an adenoma, biopsy specimens are taken from all glands provisionally identified by gross inspection and then the exploration is systematically widened. The dissection is extended as far as possible under direct vision into the anterior and posterior mediastinum. If a vascular pedicle arises from the inferior thyroid artery and extends into the mediastinum, it may be a clue to the presence of a displaced adenoma. The retroesophageal and retropharyngeal space may harbor a parathyroid tumor, and it should be examined next. If still no adenoma has been found, the region above the upper pole of the thyroid is opened as high as the hyoid bone in search of an "undescended" inferior parathyroid. The areolar tissue as far lateral as the carotid sheath should also be explored, and the carotid sheath itself opened and inspected. If the exploration thus far has proved fruitless, serious consideration should be given to bisecting that lobe of the thyroid on the side of the missing gland or even removing it subtotally. Intrathyroid parathyroid tumors are rare, but a definite possibility. 36 If an extended search of the neck does not reveal a parathyroid lesion, it is probably best not to proceed with sternotomy and a formal mediastinal exploration unless the patient is in parathyroid crisis. The preferred course is to reconfirm the diagnosis and perform localizing
502
ANTHONY
J. Ems
studies (parathyroid arteriography with or without selective small vein catheterization and PTH assay) 16 before undertaking a mediastinal dissection. Interestingly, there have been several reports of patients who were cured after negative cervical exploration5 •34-presumably because there was critical interference to the blood supply of the missing tumor during the course of dissection. A formal mediastinal exploration has been required in less than 2% of all surgical cases of primary hyperparathyroidism at the Mayo Clinic.
Extent of Resection, Based on Operative Findings When an adenoma is found and normal glands are identified, only the adenoma need be removed for cure. Biopsy of one normal gland is optional in this situation, but routine biopsy of all three remaining glands or removal of normal glands is undesirable in our opinion. If a parathyroid tumor is hard and whitish and is firmly fixed to surrounding tissue, the possibility of carcinoma should be considered. Degenerative changes in a benign adenoma may lead to adhesions, but the benign lesion usually is less hard and less firmly fixed than an infiltrating carcinoma. If carcinoma is suspected, wide excision is indicated, including the lobe of the thyroid and possibly even the recurrent laryngeal nerve without breaking into the lesion. Rupture of the adherent capsule has been followed by implantations difficult to eradicate by secondary operations .14 If four hyperplastic glands are identified, three are removed completely and about 35 to 50 mg of the fourth gland is left in situ. The gland to be preserved in part should be selected before any of the parathyroids are removed, so that the surgeon has several more chances to obtain a viable remnant if the gland chosen first is badly injured. The parathyroid remnant is tagged with a long silk suture to facilitate its identification should reoperation be required. Nearly all patients will a familial history of hyperparathyroidism or with multiple endocrine neoplasia have chief cell hyperplasia. In our experience, there has been a significant incidence of recurrent hypercalcemia when less than three or three and one-half glands have been removed. Subtotal parathyroidectomy is probably indicated in all these cases even if only a single gland is enlarged. When four normal glands have been found (and their identity proved by biopsy), there is some divergence of opinion about the best course to follow. Block et al. 8 have recommended removal of three and one-half glands on the grounds that microscopic hyperplasia may be present. However, with four normal-sized glands in the neck there may be an adenoma of the supernumerary gland elsewhere in the neck or in the mediastinum: 5 of 14 patients with mediastinal parathyroid adenomas described by Scholz et al. 35 had four glands previously identified in the neck. When four normal-sized parathyroids are found and biopsy reveals a normal histologic pattem, a possible asymmetric fifth gland should be sought. If none is found, it would be reasonable in our opinion to leave the glands in situ, marking them with long silk sutures for future iden-
503
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ti:fication. If subsequent study failed to reveal a mediastinal tumor or an aberrant tumor in the neck, reoperation with combined mediastinal and neck exploration could be undertaken with planned subtotal parathyroidectomy.
REFERENCES 1. Alveryd A: Parathyroid glands in thyroid surgery. I. Anatomy of parathyroid glands. II. Postoperative hypoparathyroidism: identification and autotransplantation of parathyroid glands. Acta Chir Scand Suppl 389:1-120, 1968 2. Arnaud CD, Tsao HS, Littledike T: Radioimmunoassay of human parathyroid hormone in serum. J Clin Invest 50:21-34, 1971 3. Ballinger WF, Haff RC: Hyperparathyroidism: increased frequency of diagnosis. South Med J 63:571-575, 1970 4. Black EM: Hyperparathyroidism. Springfield, Illinois, Charles C Thomas, Publisher, 1953 5. Black EM, Zimmer JF: Hyperparathyroidism, with particular reference to treatment. Arch Surg 72:830--837, 1956 6. Black WC III, Utley JR: The differential diagnosis of parathyroid adenoma and chief cell hyperplasia. Am J Clin Pathol 49:761-775, 1968 7. Block MA, Frame B, Jackson CE, et al: The extent of operation for primary hyperparathyroidism. Arch Surg 109:798-801, 1974 8. Block MA, Frame B, Jackson CE, et al: Primary diffuse microscopical hyperplasia of the parathyroid glands. Arch Surg 111:348-353, 1976 9. Bruining HA: Surgical Treatment of Hyperparathyroidism With an Analysis of 267 Cases. Springfield, Illinois, Charles C Thomas, Publisher, 1971 10. Clark OH, Taylor S: Osteoclastoma of the jaw and multiple parathyroid tumors. Surg Gynecol Obstet 135:188-192, 1972 11. Clark OH, Way LW, Hunt TK: Recurrent hyperparathyroidism. Ann Surg 184:391-399, 1976 12. Cope 0: Hyperparathyroidism: diagnosis and management. Am J Surg 99:394-403, 1960 13. Cope 0: Hyperparathyroidism: too little, too much surgery? (editorial). N Engl J Med 295:100-102, 1976 14. Cope 0: Surgery of hyperparathyroidism: the occurrence of parathyroids in the anterior mediastinum and the division of the operation into two stages. Ann Surg 114:706-731, 1941 15. Davies DR: The surgery of primary hyperparathyroidism. Clin Endocrinol Metabol 3:253-265, 1974 16. Doppman JL, Mallette LE, Marx SJ, et al: The localization of abnormal mediastinal parathyroid glands. Radiology 115:31-36, 1975 17. Esselstyn CB Jr, Levin HS, Eversman JJ, et al: Reappraisal of parathyroid pathology in hyperparathyroidism. Surg Clin North Am 54:443-447, 1974 18. Gilmour JR: The gross anatomy of the parathyroid glands. J Pathol Bacteriol46: 133-149, 1938 19. Goldman L, Gordan GS, Roof BS: The parathyroids: progress, problems and practice. Curr Probl Surg August 1971, pp 1-64 20. Haff RC, Armstrong RG: Trends in the current management of primary hyperparathyroidism. Surgery 75:715-719, 1974 21. Haff RC, Ballinger WF: Causes of recurrent hypercalcemia after parathyroidectomy for primary hyperparathyroidism. Ann Surg 173:884-889, 1971 22. Hoehn JG, Beahrs OH, Woolner LB: Unusual surgical lesions of the parathyroid gland. Am J Surg 118:770-778, 1969 23. Krementz ET, Yeager R, Hawley W, et al: The first 100 cases of parathyroid tumor from Charity Hospital of Louisiana. Ann Surg 173:872-883, 1971 24. Muller H: True recurrence of hyperparathyroidism: proposed criteria of recurrence. Br J Surg 62:556-559, 1975 25. Myers RT: Followup study of surgically-treated primary hyperparathyroidism. Ann Surg 179:729-732, 1974 26. Palmer JA, Brown WA, Kerr WH, et al: The surgical aspects of hyperparathyroidism. Arch Surg 110:1004-1006, 1975
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27. Paloyan E, Lawrence AM, Baker WH, et al: Near-total parathyroidectomy. Surg Clin North Am 49:43-48, 1969 28. Paloyan E, Lawrence AM, Straus FH: Hyperparathyroidism. New York, Grune & Stratton, 1973 29. Paloyan E, Paloyan D, Pickleman JR: Hyperparathyroidism today. Surg Clin North Am 53:211-220, 1973 30. Pumell DC, Scholz DA, Smith LH, et al: Treatment of primary hyperparathyroidism. Am J Med 56:800-809, 1974 31. Pumell DC, Smith LH, Scholz DA, et al: Primary hyperparathyroidism: a prospective clinical study. Am J Med 50:670-678, 1971 32. Roman us R, Heimann P, Nilsson 0, et al: Surgical treatment of hyperparathyroidism. Prog Surg 12:22-76, 1973 33. Roth Sl: Recent advances in parathyroid gland pathology. Am J Med 50:612-622, 1971 34. Satava RM Jr, Beahrs OH, Scholz DA: Success rate of cervical exploration for hyperparathyroidism. Arch Surg 110:625-627, 1975 35. Scholz DA, Pumell DC, Woolner LB, et al: Mediastinal hyperfunctioning parathyroid tumors: review of 14 cases. Ann Surg 178:173-178, 1973 36. Spiegel AM, Marx SJ, Doppman JL, et al: lntrathyroidal parathyroid adenoma or hyperplasia: an occasionally overlooked cause of surgical failure in primary hyperparathyroidism. JAMA 234:1029-1033, 1975 37. Vail AD, Coller FC: The number and location of parathyroid glands recovered from 202 routine autopsies. Mo Med 63:347-350, 1966 38. Wang C-A: Surgery of the parathyroid glands. Adv Surg 5:109-127, 1966 39. Wang C-A: The anatomic basis of parathyroid surgery. Ann Surg 183:271-275, 1976 40. Watanabe M, Baxter S, Beck JC: Hyperparathyroidism due to late recurrence of parathyroid adenoma. Am J Med 31:498-504, 1961 41. Weller GL Jr: Development of the thyroid, parathyroid and thymus glands in man. In Contributions to Embryology. Vol24, No 141. Camegie Institution of Washington, September 1933, pp 93-139 42. Welsh DA: Conceming the parathyroid glands: a critical, anatomical, and experimental study. J Anat Physiol 32:292-307; 380-402, 1898 43. Werner S, Hjem B, Sjoberg HE: Primary hyperparathyroidism: analysis of findings in a series of 129 patients. Acta Chir Scand 140:618-625, 1974
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