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Difficulties in the Treatment of Hyperparathyroidism
Difficulties In the Treatment of Hyperparathyroidism B. MARDEN BLACK, M.D.
IN HYPERPARATHYROIDISM, the usual adenoma is of sufficiently large size and distinctive color to permit certain identification grossly. Variation in the number of glands and in their locations is much less frequent than was thought formerly. Difficulties occasionally do arise, however; and in all explorations performed because of hyperparathyroidism there is the inherent problem of finding the parathyroid glands. Extensive, detailed discussions of treatment have appeared in the past2-5· 7 and need not be repeated. Instead, certain aspects of treatment, particularly the type of dissection indicated when a lesion is not found, will be reviewed. SURGICAL EXPLORATION IN EQUIVOCAL CASES
One of the principles of treatment emphasized by Churchill and Cope almost 30 years ago is that the diagnosis of hyperparathyroidism should be established firmly before surgical exploration is undertaken. Although the rule still is extremely sound, equivocal cases are encountered in which cervical dissection seems indicated. In cases of renal lithiasis with serum calcium values in the uppermost range of normal, it may be quite impossible to distinguish between isoparathyroidism and minimal hyperparathyroidism by means of currently available diagnostic tests. In some rare cases, other hypercalcemic conditions cannot be differentiated from hyperparathyroidism. A more subtle problem is posed by the patient who clearly has another condition characterized by hypercalcemia but may have hyperparathyroidism also. If stone formation is sufficiently serious to damage a kidney or endanger the patient's life, exploration of the parathyroids probablY is justified. These explorations were undertaken in such cases at the Clinic only after internists and surgeons had had much experience with hyperparathyroidism. Occasionally, adenomas have been found and removed; in other cases, hyperparathyroidism has been disproved to a reasonable degree by the finding of four parathyroid glands o(normal appearance. Much too often, however, the results of exploration were inconclusive 1115
1116
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MARDEN BLACK
in that neither was a lesion found nor was hyperparathyroidism excluded by the finding of four glands. The mediastinum has not been explored as yet at the Clinic in any case in which the diagnosis was uncertain. Failure to find an adenoma at cervical exploration has been accepted as final evidence that hyperparathyroidism was not present. It is becoming increasingly evident that cervical exploration is a very uncertain method of establishing the diagnosis of hyperparathyroidism. By necessity, however, exploration probably will continue to be advised at the Clinic in certain unusual cases until more precise diagnostic tests become available. PROBLEMS OF CERVICAL EXPLORATION
In treating hyperparathyroidism, cases inevitably will be encountered in which an adenoma is not found on completion of the usual bilateral dissection. Indeed, it is because of such cases that the immediate aim of the dissection is identification of each of the parathyroids. Bloodless dissection is essential, not so much for fear that the color of an adenoma may be obscured but because of the possibility that a normal gland may be lost to sight in the blood-stained tissues. The extent of the dissection is governed by the need to find a missing gland or glands. The superior gland most often is located far medially on the dorsal surface of the lobe of the thyroid at the level of the junction of the middle and upper thirds. Occasionally it is medial to the thyroid at approximately the same level on the inferior constrictor of the pharynx. If in neither place, the gland is likely to be cephalad to its usual location, closely associated with the superior pole of the thyroid or with the superior thyroid vessels as they approach the lobe. The inferior gland is somewhat less constant in position than the superior. It is usually in one of two places: on the capsule of the thyroid near the terminal branches of the inferior thyroid artery, or closely associated with-even within-the cervical extension of the thymus. The larger the cervical thymus, the more commonly the parathyroid will be found in its immediate vicinity. If in neither place, it may be in the plane of the inferior thyroid veins somewhere between its two more usual locations. The gland, of course, may have descended into the anterior superior mediastinum during the developmental period; and in such cases it cannot be exposed through the cervical incision. If the lesion still is not found after the dissection has been extended as indicated by the missing gland, the possibility of postdevelopmental or adult displacement of the adenoma should be considered. The likelihood of displacement may be judged by the calcium concentration in the serum: The correlation between the size of the adenoma and this value is sufficiently good to justify some estimate of the size of the
Difficulties in the Treatment of Hyperparathyroidism
1117
adenoma; and large adenomas tend to be displaced, while smaller lesions tend to remain in the original location of the parent gland. With a calcium value higher than 12.5 mg. per 100 ml. of serum, the adenoma probably is large enough to have become displaced. The enlarged superior gland descends along the tracheoesophageal groove toward or into the posterior superior part of the mediastinum. It never is deep within the posterior region of the mediastinum, and almost always it can be exposed through the cervical incision. Invariably there is a pedicle leading from the thyroidal vessels to the displaced adenoma. The adenoma arising in an inferior gland descends into either the anterior or the posterior region of the mediastinum (usually the former), depending on the original location of the parent gland. A pedicle mayor may not be present, since the inferior gland may have descended into the mediastinal region during the developmental period before its vascular attachments had become established. If the calcium value is high, the dissection is carried into that part of the superior mediastinal region indicated by which gland is absent and a careful search is made for pedicles. The vascular pedicle is surprisingly large if the adenoma has attained more than small size. Traction on the pedicle may permit the removal, under direct vision, of lesions well within the mediastinum. Conversely, in minimal hypercalcemia the likelihood of adult displacement is remote; and the dissection therefore should be extended particularly into regions where the missing gland occasionally is located. If the lesion is not found after search of the regions just described, resection of the thyroid in order to expose or devascularize the missing adenoma should be considered. At this time arises the necessity of proving by exclusion that the adenoma is not in the neck but is in the mediastinum. When two glands have been found on one side and one gland is missing from the other side, the lobe of the thyroid on the side of the missing gland should be removed totally. When a gland is missing on both sides, the decision to carry out total thyroidectomy is more difficult-which emphasizes again the importance of finding normal glands. Again some help in arriving at the proper decision is provided by the concentration of calcium in the serum. It is unlikely that a normal-sized lobe of the thyroid could conceal completely a large adenoma. Hence, in cases in which the value for serum calcium is high, one lobe of the thyroid may be split rather than removed, thus avoiding the necessity of total thyroidectomy. In cases of minimal hypercalcemia, the decision to remove the entire thyroid should depend on the likelihood of preserving at least one viable parathyroid. If one or more parathyroids can be preserved with an intact vascular supply, or if one or both inferior glands are contiguous to the cervical projections of the thymus, the thyroid probably should be
1118
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removed totally. Otherwise, some compromise would seem in order and one lobe or possibly a portion of one lobe of the thyroid should be saved. It is only after dissections of this extent that there can be any certainty that the missing adenoma is within the anterior superior part of the mediastinum. To remove all doubt concerning the nature of the glands found, the tissues provisionally identified grossly as parathyroids should be proved by biopsy. Tiny fragments of each gland are taken and no effort is made to control the slight resultant oozing. Uninvolved glands should not be biopsied unless absolutely necessary, for fear of destroying them. Therefore, biopsy is indicated only late in the dissection and practically never in cases in which the lesion already has been found. If there is one common error in treating hyperparathyroidism, it is the premature and erroneous conclusion that the lesion is in the anterior superior part of the mediastinum. In less than 2 per cent of the almost 500 cases in the Clinic series has mediastinotomy been necessary to reveal and to remove the lesion. In many other cases the lesion could have been considered as anatomically within the mediastinum, but removal under direct vision through the cervical incision was possible. The chance that small adenomas are deep within the anterior mediastinal region is even more remote. The parathyroids, after all, are cervical organs; the superior glands do not descend into the chest embryologically, and the descent of an inferior gland to this level is rare. OTHER DIFFICULTIES
So-called fused glands should cause little difficulty. The two glands on one side may be located in close proximity or may have coalesced. The resulting enlarged gland is twice the size of a normal gland and is located between the usual sites of the two glands on that side. The size and location should suggest the possibility of a fused gland. A gland of this kind does not require removal any more than does a normal one. If an adenoma is not found, however, and if at least one parathyroid has been found on the opposite side, it may be advisable to remove the enlarged gland to prove that an adenoma is not present within it. Otherwise, dependence should be placed on biopsy. A more formidable problem is presented by parathyroids whose color approaches that of the surrounding fat. Adenoma usually retains its characteristic brownish tint, at least to a degree that is recognizable. In such cases the surgeon often must be content to remove the lesion without identifying the other parathyroids. Uninvolved glands do not, as a rule, atrophy so much that they cannot be recognized. The entire question of supposed atrophy of uninvolved glands is somewhat confused. Usually glands of essentially normal appearance are found in cases of hyperparathyroidism. It is now thought that an atrophic gland is not materially smaller than a normal gland but rather that there is an increased proportion of fat to parenchyma, so that the color of the
I
Ii
Difficulties in the Treatment of Hyperparathyroidism
1119
parenchyma is affected by that of the fat. The change in color is usually no greater than the variation in color of normal parathyroids. The presence of a goiter adds materially to the difficulty of finding parathyroid glands. Not only may the glands be displaced, but also they are more difficult to expose-particularly without causing bleeding. An attempt should be made to find the parathyroids before resecting the enlarged lobe of the thyroid. If the thyroid is resected first, unrecognized parathyroids may be removed or the tissues may become stained with blood. Sizable goiters, however, may require removal before the parathyroids can be exposed. Essentially the same objection may be made to mobilization of the superior pole as an aid to exposure of the superior gland. The superior gland, as remarked previously, is often in the immediate vicinity of the superior pole of the thyroid or of the superior thyroid vessels. The gland may be crushed or its vascular supply may be destroyed by ligation or division of the vessels. There is also the possibility that bleeding, if it occurs, will conceal the gland. PROBLEMS ARISING FROM LESIONS OF THE PARATHYROIDS
The only difficulties that may be encountered in finding solitary adenomas are those arising from size and aberrant location, which have been discussed already. The same considerations apply to the search for a second adenoma, which may be expected in approximately 5 per cent of cases. Wasserhelle or primary clear-cell hyperplasia usually is easy to recognize on gross inspection. Occasionally the enlargement of one or more of the glands-most often the inferior glands-is so slight that grossly they seem not to be involved. The correct diagnosis is established readily from fresh-frozen sections. Treatment has not proved so hard as was anticipated initially, although the preservation of enough viable tissue to prevent tetany is somewhat difficult. A fragment of tissue approximately three times the size of a normal gland immediately adjacent to the hilus should be saved. The vascular supply to the fragment is least endangered when a portion of the smaller gland is retained. PRIMARY CHIEF-CELL HYPERPLASIA OR ADENOMATOSIS
A definite, recently recognized pathologic entity 6 -primary chief-cell hyperplasia (adenomatosis)-may be expected in cases of polyendocrine adenomas,s in cases of Zollinger-Ellison syndrome with hyperparathyroidism, in cases of hyperparathyroidism in which there is a strong family history, and, finally, in cases of hyperparathyroidism with peptic ulcer in which there is a family history of peptic ulcer. Similar, if not identical, pathologic changes may be found in the parathyroids when
1120
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hyperparathyroidism is complicated by renal insufficiency. In cases of the latter type, the lesions conceivably may be a combination of primary and secondary hyperplasia. Treatment has proved rather unsatisfactory in that persistence and recurrence of hyperparathyroidism as well as tetany have occurred far too commonly. Subtotal resection of all parathyroid tissue except for a viable fragment, as in treatment of wasserhelle hyperplasia, is the treatment most commonly advised at present. If four parathyroids are not found, an extended dissection such as that described for cases of missing adenoma should be considered carefully. I am beginning to have some doubts about preservation of any parathyroid tissue in cases of this type. Recurrences in two cases and spontaneous recovery from tetany in a third case suggest strongly that the remnants are capable of causing recurrent hyperparathyroidism. Conversely, tetany has ensued in cases in which a presumably adequate amount of viable tissue was saved. CARCINOMA
There have been no developments that might be expected to improve the results of treatment of parathyroidal carcinoma. Practically all patients in whom metastasis was present-even limited metastasis to regional lymph nodes-have died. l Death has resulted most commonly from recurrent hyperparathyroidism. In the few cases of survivors with locally invasive disease, the diagnosis often was in doubt. The possibility of cancer should be considered carefully if the lesion seems to be fixed to surrounding structures. Biopsy should not be attempted because of the undoubtedly real danger of seeding. The mass should be resected as radically as possible. External irradiation has proved entirely useless. Most fortunately, the lesions are uncommon, not more than one or two cases being reported each year. SUMMARY
In equivocal cases of hyperparathyroidism, cervical exploration probably is justified if a life or a kidney is endangered. In the majority of cases, the lesion causing the hyperparathyroidism is found without particular difficulty provided the dissection is carried out properly. When no lesion is found, the extension of the dissection is determined by which of the parathyroids are missing. With minimal hypercalcemia, the adenoma is likely to be small and in the usual location of a parathyroid; with severe hypercalcemia, it is likely to be large and displaced toward or into the mediastinum. Total thyroid lobectomy on one or even on both sides is indicated occasionally in a final effort to find an adenoma, or to prove that the lesion is in fact in the mediastinum. Primary chief-cell hyperplasia or adenomatosis (which may be predicted clinically) and
Difficulties in the Treatment oj Hyperparathyroidism
1121
carcinoma have proved difficult to treat satisfactorily. Lesions of the latter type, fortunately, are extremely rare. REFERENCES 1. Black, B. K. and Ackerman, L. V.: Tumors of parathyroid: A review of twenty-
three cases. Cancer 3: 415-444 (May) 1950. 2. Black, B. M.: Hyperparathyroidism. Springfield, Illinois, Charles C Thomas, 1953. 3. Black, B. M. and Zimmer, J. F.: Hyperparathyroidism: With particular reference to treatment. A.M.A. Arch. Surg. 72: 830-837 (May) 1956. 4. Churchill, E. D. and Cope, 0.: Parathyroid tumors associated with hyperparathyroidism: Eleven cases treated by operation. Surg., Gynec. & Obst. 58: 255-271 (Feb. 15) 1934. 5. Cope, 0.: Surgery of hyperparathyroidism: Occurrence of parathyroids in anterior mediastinum and division of operation into two stages. Ann. Surg. 114: 706733 (Oct.) 1941. 6. Cope, 0., Keynes, W. M., Roth, S. 1. and Castleman, B.: Primary chief-cell hyperplasia of parathyroid glands: A new entity in surgery of hyperparathyroidism. Ann. Surg. 148: 375-387 (Sept.) 1958. 7. Rienhoff, W. F., Jr.: Surgical treatment of hyperparathyroidism: With report of 27 cases. Ann. Surg. 131: 917-943 (June) 1950. 8. Underdahl, L. 0., Woolner, L. B. and Black, B. M.: Multiple endocrine adenomas: Report of 8 cases in which parathyroids, pituitary and pancreatic islets were involved. J. Clin. Endocrinol. 13: 20-47 (Jan.) 1953.
IN HYPERPARATHYROIDISM, the usual adenoma is of sufficiently large size and distinctive color to permit certain identification grossly. Variation in the number of glands and in their locations is much less frequent than was thought formerly. Difficulties occasionally do arise, however; and in all explorations performed because of hyperparathyroidism there is the inherent problem of finding the parathyroid glands. Extensive, detailed discussions of treatment have appeared in the past2-5· 7 and need not be repeated. Instead, certain aspects of treatment, particularly the type of dissection indicated when a lesion is not found, will be reviewed. SURGICAL EXPLORATION IN EQUIVOCAL CASES
One of the principles of treatment emphasized by Churchill and Cope almost 30 years ago is that the diagnosis of hyperparathyroidism should be established firmly before surgical exploration is undertaken. Although the rule still is extremely sound, equivocal cases are encountered in which cervical dissection seems indicated. In cases of renal lithiasis with serum calcium values in the uppermost range of normal, it may be quite impossible to distinguish between isoparathyroidism and minimal hyperparathyroidism by means of currently available diagnostic tests. In some rare cases, other hypercalcemic conditions cannot be differentiated from hyperparathyroidism. A more subtle problem is posed by the patient who clearly has another condition characterized by hypercalcemia but may have hyperparathyroidism also. If stone formation is sufficiently serious to damage a kidney or endanger the patient's life, exploration of the parathyroids probablY is justified. These explorations were undertaken in such cases at the Clinic only after internists and surgeons had had much experience with hyperparathyroidism. Occasionally, adenomas have been found and removed; in other cases, hyperparathyroidism has been disproved to a reasonable degree by the finding of four parathyroid glands o(normal appearance. Much too often, however, the results of exploration were inconclusive 1115
1116
B.
MARDEN BLACK
in that neither was a lesion found nor was hyperparathyroidism excluded by the finding of four glands. The mediastinum has not been explored as yet at the Clinic in any case in which the diagnosis was uncertain. Failure to find an adenoma at cervical exploration has been accepted as final evidence that hyperparathyroidism was not present. It is becoming increasingly evident that cervical exploration is a very uncertain method of establishing the diagnosis of hyperparathyroidism. By necessity, however, exploration probably will continue to be advised at the Clinic in certain unusual cases until more precise diagnostic tests become available. PROBLEMS OF CERVICAL EXPLORATION
In treating hyperparathyroidism, cases inevitably will be encountered in which an adenoma is not found on completion of the usual bilateral dissection. Indeed, it is because of such cases that the immediate aim of the dissection is identification of each of the parathyroids. Bloodless dissection is essential, not so much for fear that the color of an adenoma may be obscured but because of the possibility that a normal gland may be lost to sight in the blood-stained tissues. The extent of the dissection is governed by the need to find a missing gland or glands. The superior gland most often is located far medially on the dorsal surface of the lobe of the thyroid at the level of the junction of the middle and upper thirds. Occasionally it is medial to the thyroid at approximately the same level on the inferior constrictor of the pharynx. If in neither place, the gland is likely to be cephalad to its usual location, closely associated with the superior pole of the thyroid or with the superior thyroid vessels as they approach the lobe. The inferior gland is somewhat less constant in position than the superior. It is usually in one of two places: on the capsule of the thyroid near the terminal branches of the inferior thyroid artery, or closely associated with-even within-the cervical extension of the thymus. The larger the cervical thymus, the more commonly the parathyroid will be found in its immediate vicinity. If in neither place, it may be in the plane of the inferior thyroid veins somewhere between its two more usual locations. The gland, of course, may have descended into the anterior superior mediastinum during the developmental period; and in such cases it cannot be exposed through the cervical incision. If the lesion still is not found after the dissection has been extended as indicated by the missing gland, the possibility of postdevelopmental or adult displacement of the adenoma should be considered. The likelihood of displacement may be judged by the calcium concentration in the serum: The correlation between the size of the adenoma and this value is sufficiently good to justify some estimate of the size of the
Difficulties in the Treatment of Hyperparathyroidism
1117
adenoma; and large adenomas tend to be displaced, while smaller lesions tend to remain in the original location of the parent gland. With a calcium value higher than 12.5 mg. per 100 ml. of serum, the adenoma probably is large enough to have become displaced. The enlarged superior gland descends along the tracheoesophageal groove toward or into the posterior superior part of the mediastinum. It never is deep within the posterior region of the mediastinum, and almost always it can be exposed through the cervical incision. Invariably there is a pedicle leading from the thyroidal vessels to the displaced adenoma. The adenoma arising in an inferior gland descends into either the anterior or the posterior region of the mediastinum (usually the former), depending on the original location of the parent gland. A pedicle mayor may not be present, since the inferior gland may have descended into the mediastinal region during the developmental period before its vascular attachments had become established. If the calcium value is high, the dissection is carried into that part of the superior mediastinal region indicated by which gland is absent and a careful search is made for pedicles. The vascular pedicle is surprisingly large if the adenoma has attained more than small size. Traction on the pedicle may permit the removal, under direct vision, of lesions well within the mediastinum. Conversely, in minimal hypercalcemia the likelihood of adult displacement is remote; and the dissection therefore should be extended particularly into regions where the missing gland occasionally is located. If the lesion is not found after search of the regions just described, resection of the thyroid in order to expose or devascularize the missing adenoma should be considered. At this time arises the necessity of proving by exclusion that the adenoma is not in the neck but is in the mediastinum. When two glands have been found on one side and one gland is missing from the other side, the lobe of the thyroid on the side of the missing gland should be removed totally. When a gland is missing on both sides, the decision to carry out total thyroidectomy is more difficult-which emphasizes again the importance of finding normal glands. Again some help in arriving at the proper decision is provided by the concentration of calcium in the serum. It is unlikely that a normal-sized lobe of the thyroid could conceal completely a large adenoma. Hence, in cases in which the value for serum calcium is high, one lobe of the thyroid may be split rather than removed, thus avoiding the necessity of total thyroidectomy. In cases of minimal hypercalcemia, the decision to remove the entire thyroid should depend on the likelihood of preserving at least one viable parathyroid. If one or more parathyroids can be preserved with an intact vascular supply, or if one or both inferior glands are contiguous to the cervical projections of the thymus, the thyroid probably should be
1118
B. MARDEN BLACK
removed totally. Otherwise, some compromise would seem in order and one lobe or possibly a portion of one lobe of the thyroid should be saved. It is only after dissections of this extent that there can be any certainty that the missing adenoma is within the anterior superior part of the mediastinum. To remove all doubt concerning the nature of the glands found, the tissues provisionally identified grossly as parathyroids should be proved by biopsy. Tiny fragments of each gland are taken and no effort is made to control the slight resultant oozing. Uninvolved glands should not be biopsied unless absolutely necessary, for fear of destroying them. Therefore, biopsy is indicated only late in the dissection and practically never in cases in which the lesion already has been found. If there is one common error in treating hyperparathyroidism, it is the premature and erroneous conclusion that the lesion is in the anterior superior part of the mediastinum. In less than 2 per cent of the almost 500 cases in the Clinic series has mediastinotomy been necessary to reveal and to remove the lesion. In many other cases the lesion could have been considered as anatomically within the mediastinum, but removal under direct vision through the cervical incision was possible. The chance that small adenomas are deep within the anterior mediastinal region is even more remote. The parathyroids, after all, are cervical organs; the superior glands do not descend into the chest embryologically, and the descent of an inferior gland to this level is rare. OTHER DIFFICULTIES
So-called fused glands should cause little difficulty. The two glands on one side may be located in close proximity or may have coalesced. The resulting enlarged gland is twice the size of a normal gland and is located between the usual sites of the two glands on that side. The size and location should suggest the possibility of a fused gland. A gland of this kind does not require removal any more than does a normal one. If an adenoma is not found, however, and if at least one parathyroid has been found on the opposite side, it may be advisable to remove the enlarged gland to prove that an adenoma is not present within it. Otherwise, dependence should be placed on biopsy. A more formidable problem is presented by parathyroids whose color approaches that of the surrounding fat. Adenoma usually retains its characteristic brownish tint, at least to a degree that is recognizable. In such cases the surgeon often must be content to remove the lesion without identifying the other parathyroids. Uninvolved glands do not, as a rule, atrophy so much that they cannot be recognized. The entire question of supposed atrophy of uninvolved glands is somewhat confused. Usually glands of essentially normal appearance are found in cases of hyperparathyroidism. It is now thought that an atrophic gland is not materially smaller than a normal gland but rather that there is an increased proportion of fat to parenchyma, so that the color of the
I
Ii
Difficulties in the Treatment of Hyperparathyroidism
1119
parenchyma is affected by that of the fat. The change in color is usually no greater than the variation in color of normal parathyroids. The presence of a goiter adds materially to the difficulty of finding parathyroid glands. Not only may the glands be displaced, but also they are more difficult to expose-particularly without causing bleeding. An attempt should be made to find the parathyroids before resecting the enlarged lobe of the thyroid. If the thyroid is resected first, unrecognized parathyroids may be removed or the tissues may become stained with blood. Sizable goiters, however, may require removal before the parathyroids can be exposed. Essentially the same objection may be made to mobilization of the superior pole as an aid to exposure of the superior gland. The superior gland, as remarked previously, is often in the immediate vicinity of the superior pole of the thyroid or of the superior thyroid vessels. The gland may be crushed or its vascular supply may be destroyed by ligation or division of the vessels. There is also the possibility that bleeding, if it occurs, will conceal the gland. PROBLEMS ARISING FROM LESIONS OF THE PARATHYROIDS
The only difficulties that may be encountered in finding solitary adenomas are those arising from size and aberrant location, which have been discussed already. The same considerations apply to the search for a second adenoma, which may be expected in approximately 5 per cent of cases. Wasserhelle or primary clear-cell hyperplasia usually is easy to recognize on gross inspection. Occasionally the enlargement of one or more of the glands-most often the inferior glands-is so slight that grossly they seem not to be involved. The correct diagnosis is established readily from fresh-frozen sections. Treatment has not proved so hard as was anticipated initially, although the preservation of enough viable tissue to prevent tetany is somewhat difficult. A fragment of tissue approximately three times the size of a normal gland immediately adjacent to the hilus should be saved. The vascular supply to the fragment is least endangered when a portion of the smaller gland is retained. PRIMARY CHIEF-CELL HYPERPLASIA OR ADENOMATOSIS
A definite, recently recognized pathologic entity 6 -primary chief-cell hyperplasia (adenomatosis)-may be expected in cases of polyendocrine adenomas,s in cases of Zollinger-Ellison syndrome with hyperparathyroidism, in cases of hyperparathyroidism in which there is a strong family history, and, finally, in cases of hyperparathyroidism with peptic ulcer in which there is a family history of peptic ulcer. Similar, if not identical, pathologic changes may be found in the parathyroids when
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B. MARDEN BLACK
hyperparathyroidism is complicated by renal insufficiency. In cases of the latter type, the lesions conceivably may be a combination of primary and secondary hyperplasia. Treatment has proved rather unsatisfactory in that persistence and recurrence of hyperparathyroidism as well as tetany have occurred far too commonly. Subtotal resection of all parathyroid tissue except for a viable fragment, as in treatment of wasserhelle hyperplasia, is the treatment most commonly advised at present. If four parathyroids are not found, an extended dissection such as that described for cases of missing adenoma should be considered carefully. I am beginning to have some doubts about preservation of any parathyroid tissue in cases of this type. Recurrences in two cases and spontaneous recovery from tetany in a third case suggest strongly that the remnants are capable of causing recurrent hyperparathyroidism. Conversely, tetany has ensued in cases in which a presumably adequate amount of viable tissue was saved. CARCINOMA
There have been no developments that might be expected to improve the results of treatment of parathyroidal carcinoma. Practically all patients in whom metastasis was present-even limited metastasis to regional lymph nodes-have died. l Death has resulted most commonly from recurrent hyperparathyroidism. In the few cases of survivors with locally invasive disease, the diagnosis often was in doubt. The possibility of cancer should be considered carefully if the lesion seems to be fixed to surrounding structures. Biopsy should not be attempted because of the undoubtedly real danger of seeding. The mass should be resected as radically as possible. External irradiation has proved entirely useless. Most fortunately, the lesions are uncommon, not more than one or two cases being reported each year. SUMMARY
In equivocal cases of hyperparathyroidism, cervical exploration probably is justified if a life or a kidney is endangered. In the majority of cases, the lesion causing the hyperparathyroidism is found without particular difficulty provided the dissection is carried out properly. When no lesion is found, the extension of the dissection is determined by which of the parathyroids are missing. With minimal hypercalcemia, the adenoma is likely to be small and in the usual location of a parathyroid; with severe hypercalcemia, it is likely to be large and displaced toward or into the mediastinum. Total thyroid lobectomy on one or even on both sides is indicated occasionally in a final effort to find an adenoma, or to prove that the lesion is in fact in the mediastinum. Primary chief-cell hyperplasia or adenomatosis (which may be predicted clinically) and
Difficulties in the Treatment oj Hyperparathyroidism
1121
carcinoma have proved difficult to treat satisfactorily. Lesions of the latter type, fortunately, are extremely rare. REFERENCES 1. Black, B. K. and Ackerman, L. V.: Tumors of parathyroid: A review of twenty-
three cases. Cancer 3: 415-444 (May) 1950. 2. Black, B. M.: Hyperparathyroidism. Springfield, Illinois, Charles C Thomas, 1953. 3. Black, B. M. and Zimmer, J. F.: Hyperparathyroidism: With particular reference to treatment. A.M.A. Arch. Surg. 72: 830-837 (May) 1956. 4. Churchill, E. D. and Cope, 0.: Parathyroid tumors associated with hyperparathyroidism: Eleven cases treated by operation. Surg., Gynec. & Obst. 58: 255-271 (Feb. 15) 1934. 5. Cope, 0.: Surgery of hyperparathyroidism: Occurrence of parathyroids in anterior mediastinum and division of operation into two stages. Ann. Surg. 114: 706733 (Oct.) 1941. 6. Cope, 0., Keynes, W. M., Roth, S. 1. and Castleman, B.: Primary chief-cell hyperplasia of parathyroid glands: A new entity in surgery of hyperparathyroidism. Ann. Surg. 148: 375-387 (Sept.) 1958. 7. Rienhoff, W. F., Jr.: Surgical treatment of hyperparathyroidism: With report of 27 cases. Ann. Surg. 131: 917-943 (June) 1950. 8. Underdahl, L. 0., Woolner, L. B. and Black, B. M.: Multiple endocrine adenomas: Report of 8 cases in which parathyroids, pituitary and pancreatic islets were involved. J. Clin. Endocrinol. 13: 20-47 (Jan.) 1953.