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Parathyroid surgery for inherited endocrinopathies
Operative Techniques in Otolaryngology (]]]]) ], ]]]–]]]
Parathyroid surgery for inherited endocrinopathies Joshua Davies, MD, Gerard M. Doherty, MD, FACS From the Department of Surgery, Boston Medical Center, Boston, Massachusetts KEYWORDS Parathyroid; Surgery; Heritable; Endocrinopathy; MEN-1
Hyperparathyroidism presents as a component of selected familial endocrinopathies including multiple endocrine neoplasia types 1 and 2. These people develop multiple parathyroid adenomas that often present synchronously and can require operative intervention. The goals of the operation are to reduce the functional parathyroid mass to a point that normalizes the serum parathyroid hormone level, to avoid hypoparathyroidism, and to leave the residual parathyroid tissue in a place that can be safely accessed at the time of recurrent hyperparathyroidism. Recurrence is highly likely, as any residual parathyroid tissue has the propensity to develop subsequent adenomatous growth. The 2 main alternatives to accomplish these goals are to either remove all of the evident parathyroid tissue from the neck, and to move it to an accessible position, such as the forearm, as an autograft (total parathyroidectomy and autograft), or to remove nearly all of the parathyroid tissue from the neck, leaving a single focus of well-vascularized, carefully located tissue in the neck (subtotal parathyroidectomy). r 2016 Elsevier Inc. All rights reserved.
Introduction Primary hyperparathyroidism is caused by resistance of parathyroid tissue to serum calcium suppression of parathyroid hormone secretion. This results in parathyroid hormone levels that are abnormally elevated for the serum level of calcium, and as the excess serum calcium is cleared by the kidneys, the bone stores of calcium are mobilized to maintain the abnormally high serum calcium levels. The net effect is loss of bone calcium through urinary excretion. The effects of primary hyperparathyroidism are (1) gradually diminished bone density; (2) systemic effects of elevated serum levels of calcium, including those due to muscle relaxation such as gastroesophageal reflux, constipation, and leg weakness, as well as the effects on the nervous system, such as fatigue, lethargy, mental fogginess, and depression; (3) diminished renal function due to nephrocalcinosis; and Address reprint requests and correspondence: Gerard M. Doherty, MD, FACS, Boston Medical Center, 88 East Newton St, Collamore Ste 500, Boston, MA 02118. E-mail address: [email protected]@bu.edu http://dx.doi.org/10.1016/j.otot.2016.06.010 1043-1810/r 2016 Elsevier Inc. All rights reserved.
(4) renal stones due to calcium precipitation in the renal collecting system. Most primary hyperparathyroidism is caused by single parathyroid adenoma, and removal of the single adenoma is curative. Some heritable neoplastic syndromes include primary hyperparathyroidism as a part of the syndrome. The most common and typical is multiple endocrine neoplasia type 1 (MEN-1), but primary hyperparathyroidism also occurs in multiple endocrine neoplasia type 2 (MEN-2) and hyperparathyroidism-jaw tumor syndrome.1 In each of these syndromes, susceptible tissues, including the parathyroid glands, have an increased rate of development of neoplasms. As time passes, they risk development of multiple parathyroid adenomas within single glands, and in separate glands. As initiation of the tumors occurs at separate times in each parathyroid gland, patients often have multiple involved parathyroid glands (a decreasing number of normal glands with patient age), with tumors of different sizes in each one.2 This led to the historical misnomer, “asymmetrical hyperplasia.” These glands are not hyperplastic, and it would be coincidental for them to be symmetric. In addition, because all parathyroid tissue is at risk of
2 developing tumors, these people can develop adenomas in rests of ectopic parathyroid tissue that are normally found in the thymus or carotid sheath. These rests are rarely clinically evident or significant, unless they develop a parathyroid adenoma in the setting of one of these clinical syndromes, or, rarely, as a sporadic event. This set of circumstances leads to the necessary considerations for managing primary hyperparathyroidism in MEN-1 (which will be used as the prototypical example of heritable primary hyperparathyroidism for this discussion). If these people develop primary hyperparathyroidism, and an indication for intervention, then the planned operation must address each of the parathyroid glands and cervically accessible sites of ectopic parathyroid tissue, must anticipate that any parathyroid tissue left in place will eventually develop additional neoplasms and lead to recurrent hyperparathyroidism, and must recognize that hypoparathyroidism is a significant functional deficit for a patient.3,4 Opting to risk permanent hypoparathyroidism for a decreased rate of recurrence is not a good option for patients.
Clinical presentation Patients with MEN-1 hyperparathyroidism present with the same clinical features as those with sporadic disease. There are no distinguishing biochemical features. For patients who are known to be members of MEN-1 kindreds, and who undergo regular biochemical screening, hypercalcemia often develops in the third or fourth decade of life. This can present earlier or later, and it can be the presenting feature for many people. For those who present without known MEN-1, the features that can make one suspicious include young patient age with multiple gland disease and some features in the family history that suggest possible MEN-1 components.5,6
Operative Techniques in Otolaryngology, Vol ], No ], Month ]]]]
Imaging Preoperative imaging has become common as a part of the operative planning for sporadic hyperparathyroidism. However, it is not useful, in general, for planning of initial cervical operations in familial disease. Because each parathyroid gland must be identified in the operating room for these patients anyway, the imaging does not limit the planned exploration as it does for focused procedures in the sporadic setting. For reoperations, imaging may be helpful to identify the site of recurrence and to plan the operation.
Surgical exploration The operative exploration for a patient with known MEN-1 hyperparathyroidism proceeds in a standard fashion, no matter the selected operative strategy for maintaining parathyroid function while preparing for the expected later recurrence. A typical incision (Figure 1) over the isthmus of the thyroid gland provides access to the central neck (region bounded by the carotid sheaths from submandibular glands to upper mediastinum) where abnormal parathyroid tissue is likely to reside. The length of the incision can be determined by the patient's body shape and by the size of the thyroid gland. Subplatysmal flaps (Figure 2) can be raised to enable a smaller incision to provide access to adjacent parts of the neck. The tracheoesophageal groove is exposed sequentially on each side as diagramed (Figure 3), demonstrating all of
Patient selection The indications for intervention in primary hyperparathyroidism associated with MEN-1 are the same as for those without the familial basis for the disease. If the patient has symptoms attributable to the hyperparathyroidism (fatigue, lethargy, depression, renal stone, and fragility fractures), then they should strongly consider operation. If they do not have clear symptoms, then criteria that were first introduced after a National Institutes of Health consensus conference in 1990 are generally used. Those criteria include young age (less than 50 years), markedly elevated serum calcium (41 mg/dL above the upper limit of normal), or end-organ effects (osteoporosis by dual energy X-ray absorptiometry scan, or renal function impairment with elevated serum level of creatinine). For recurrent disease in this setting, the criteria are generally stricter, with evidence of functional impairment by symptoms or end-organ effect being most convincing. Once a decision to intervene is settled, then the operative strategy can be selected.
Figure 1 With the patient position supine, neck extended, and upper body raised above the level of the abdomen (“beach chair”), a transverse incision is made over the isthmus of the thyroid gland, or within a nearby skin crease. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGraw-Hill Companies, 2010.) (Color version of figure is available online.)
Davies and Doherty
Parathyroid Surgery for Inherited Endocrinopathies
Figure 2 Subplatysmal flaps can be raised in the plane superficial to the anterior jugular veins. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGraw-Hill Companies, 2010.) (Color version of figure is available online.)
the soft tissues that are likely to contain parathyroid glands along the medial aspect of the dissection on each side of the neck. The upper parathyroid glands (Figure 4) are often identified first, as they tend to be deeper in the neck, and so starting the dissection there keeps the more superficial tissues intact. The lower parathyroid glands can then be dissected (Figure 5) within the tissues of the thyrothymic
Figure 3 The foundation of the exploration is set by following the posterior surface of the sternothyroid muscle laterally to the carotid sheath, and then following the plane of the medial aspect of the carotid sheath posteriorly to the spine. Completing this dissection of the medial aspect of the carotid sheath along its entire accessible length ensures that the primary typical and ectopic locations of the parathyroid glands all remain attached to the central tissues attached to the thyroid gland and larynx. This then safely focuses the exploration on these medial tissues, obviating the need to survey both medially and laterally to identify the parathyroid glands. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGraw-Hill Companies, 2010.) (Color version of figure is available online.)
3
Figure 4 The upper parathyroid glands are typically located deep in the neck, superior to the inferior thyroid artery trunk and posterior to the recurrent laryngeal nerve insertion to the larynx. Their blood supply is usually from the upper branches of the inferior thyroid artery, and if the gland has descended inferiorly along the lateral border of the esophagus, the vessels are at the superior end, and pass posterior to the inferior artery trunk. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGrawHill Companies, 2010.) (Color version of figure is available online.)
ligament, often but not always quite close to the lower pole of the thyroid gland. Finally, missing or additional glands should be sought, with knowledge of the typical ectopic pathways of the glands (Figure 6).
Figure 5 The lower parathyroid glands are typically located more anteriorly in the neck in the thyrothymic ligament. They are generally anterior to the recurrent laryngeal nerve and inferior to the inferior thyroid artery trunk. Their position is more variable than the superior glands. (Color version of figure is available online.)
4
Operative Techniques in Otolaryngology, Vol ], No ], Month ]]]]
Subtotal parathyroidectomy
Figure 6 The parathyroid glands can form in, or enlarge into, ectopic positions, usually in predictable directions as demonstrated. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGraw-Hill Companies, 2010.) (Color version of figure is available online.)
Operative strategies There are 2, essentially equivalent alternative strategies for managing MEN-1 hyperparathyroidism. They have been compared in a randomized trial and each is found to have advantages and disadvantages, and probably both have roles in different patients.7-9 The total parathyroidectomy with autograft strategy has a slightly higher hypoparathyroidism risk, but a simpler reoperation procedure. Some experienced surgeons prefer this option for patients more likely to require reoperation (younger patients, more diffusely affected larger glands, and prior recurrence). The subtotal parathyroidectomy strategy has less risk of hypoparathyroidism, but it requires reoperation in the neck for recurrence.
Subtotal parathyroidectomy, commonly termed a “threeand-a-half” gland parathyroidectomy, is better thought of as a “half-and-three” gland procedure. Once all parathyroid glands have been identified, one is selected to be the remnant. The criteria for this are that it should be a more “normal” looking gland in size, shape, and color, and it should be accessible at a subsequent operation if need be. A portion of this gland is removed, leaving approximately 100 mg attached to grossly intact vasculature. This should bleed freely. The remnant can then be inspected, and only once some time has passed, and it is clear that the remnant is viable, the remaining parathyroid glands are removed. If the remnant does not remain viable, then another gland is selected, and a new remnant is created. This avoids the awkward circumstance of removing the 3 “nonremnant” glands and then devascularizing the intended remnant.
Postoperative care These patients are often relatively hypoparathyroid postoperatively and may have significant bone hunger if they have had significant bone disease. They generally require calcium replacement and may need supplementation with activated forms of vitamin D (such as calcitriol) to enhance the gastrointestinal calcium absorption.
Follow-up and natural history As long as these patients have parathyroid tissue in place, they have a lifetime risk of recurrent hyperparathyroidism. They should be followed annually for recurrence as a part of their MEN-1 surveillance program.
Disclosure Total parathyroidectomy and autograft Once all the parathyroid tissue has been identified and confirmed (either by definitive gross examination or by intraoperative pathology consultation), the resection strategy can be implemented. One option is to remove all parathyroid tissue from the neck and place it into an ice bath in sterile saline. A portion, usually estimated at approximately 100 mg, can then be trimmed from one of the glands, minced into small pieces, and reimplanted into individual pockets in a convenient position. The nondominant forearm is often chosen as it allows low-morbidity access for reoperation to treat future graft-dependent recurrence. This position also enables demonstration of graft dependence of future recurrence through “transient parathyroidectomy”— measuring contralateral arm parathyroid hormone before and after occlusion of the venous drainage above the graft.
The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.
References 1. Doherty GM: Multiple endocrine neoplasia type 1. J Surg Oncol 89 (3):143-150, 2005 2. Doherty GM, Lairmore TC, DeBenedetti MK: Multiple endocrine neoplasia type 1 parathyroid adenoma development over time. World J Surg 28(11):1139-1142, 2004 3. Yavuz S, Simonds WF, Weinstein LS, et al: Sleeping parathyroid tumor: Rapid hyperfunction after removal of the dominant tumor. J Clin Endocrinol Metab 97(6):1834-1841, 2012 4. Norton JA, Venzon DJ, Berna MJ, et al: Prospective study of surgery for primary hyperparathyroidism (HPT) in multiple endocrine neoplasiatype 1 and Zollinger-Ellison syndrome: Long-term outcome of a more virulent form of HPT. Ann Surg 247(3):501-510, 2008
Davies and Doherty
Parathyroid Surgery for Inherited Endocrinopathies
5. Glascock MJ, Carty SE: Multiple endocrine neoplasia type 1: Fresh perspective on clinical features and penetrance. Surg Oncol 11(3): 143-150, 2002 6. Yip L, Ogilvie JB, Challinor SM, et al: Identification of multiple endocrine neoplasia type 1 in patients with apparent sporadic primary hyperparathyroidism. Surgery 144(6):1002-1006. [discussion 1006–1007], 2008 7. Lairmore TC, Govednik CM, Quinn CE, et al: A randomized, prospective trial of operative treatments for hyperparathyroidism in
5
patients with multiple endocrine neoplasia type 1. Surgery 156(6): 1326-1334. [discussion 1334–1325], 2014 8. Elaraj DM, Skarulis MC, Libutti SK, et al: Results of initial operation for hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Surgery 134(6):858-864. [discussion 864–855], 2003 9. Hubbard JG, Sebag F, Maweja S, et al: Subtotal parathyroidectomy as an adequate treatment for primary hyperparathyroidism in multiple endocrine neoplasia type 1. Arch Surg 141(3):235-239, 2006
Parathyroid surgery for inherited endocrinopathies Joshua Davies, MD, Gerard M. Doherty, MD, FACS From the Department of Surgery, Boston Medical Center, Boston, Massachusetts KEYWORDS Parathyroid; Surgery; Heritable; Endocrinopathy; MEN-1
Hyperparathyroidism presents as a component of selected familial endocrinopathies including multiple endocrine neoplasia types 1 and 2. These people develop multiple parathyroid adenomas that often present synchronously and can require operative intervention. The goals of the operation are to reduce the functional parathyroid mass to a point that normalizes the serum parathyroid hormone level, to avoid hypoparathyroidism, and to leave the residual parathyroid tissue in a place that can be safely accessed at the time of recurrent hyperparathyroidism. Recurrence is highly likely, as any residual parathyroid tissue has the propensity to develop subsequent adenomatous growth. The 2 main alternatives to accomplish these goals are to either remove all of the evident parathyroid tissue from the neck, and to move it to an accessible position, such as the forearm, as an autograft (total parathyroidectomy and autograft), or to remove nearly all of the parathyroid tissue from the neck, leaving a single focus of well-vascularized, carefully located tissue in the neck (subtotal parathyroidectomy). r 2016 Elsevier Inc. All rights reserved.
Introduction Primary hyperparathyroidism is caused by resistance of parathyroid tissue to serum calcium suppression of parathyroid hormone secretion. This results in parathyroid hormone levels that are abnormally elevated for the serum level of calcium, and as the excess serum calcium is cleared by the kidneys, the bone stores of calcium are mobilized to maintain the abnormally high serum calcium levels. The net effect is loss of bone calcium through urinary excretion. The effects of primary hyperparathyroidism are (1) gradually diminished bone density; (2) systemic effects of elevated serum levels of calcium, including those due to muscle relaxation such as gastroesophageal reflux, constipation, and leg weakness, as well as the effects on the nervous system, such as fatigue, lethargy, mental fogginess, and depression; (3) diminished renal function due to nephrocalcinosis; and Address reprint requests and correspondence: Gerard M. Doherty, MD, FACS, Boston Medical Center, 88 East Newton St, Collamore Ste 500, Boston, MA 02118. E-mail address: [email protected]@bu.edu http://dx.doi.org/10.1016/j.otot.2016.06.010 1043-1810/r 2016 Elsevier Inc. All rights reserved.
(4) renal stones due to calcium precipitation in the renal collecting system. Most primary hyperparathyroidism is caused by single parathyroid adenoma, and removal of the single adenoma is curative. Some heritable neoplastic syndromes include primary hyperparathyroidism as a part of the syndrome. The most common and typical is multiple endocrine neoplasia type 1 (MEN-1), but primary hyperparathyroidism also occurs in multiple endocrine neoplasia type 2 (MEN-2) and hyperparathyroidism-jaw tumor syndrome.1 In each of these syndromes, susceptible tissues, including the parathyroid glands, have an increased rate of development of neoplasms. As time passes, they risk development of multiple parathyroid adenomas within single glands, and in separate glands. As initiation of the tumors occurs at separate times in each parathyroid gland, patients often have multiple involved parathyroid glands (a decreasing number of normal glands with patient age), with tumors of different sizes in each one.2 This led to the historical misnomer, “asymmetrical hyperplasia.” These glands are not hyperplastic, and it would be coincidental for them to be symmetric. In addition, because all parathyroid tissue is at risk of
2 developing tumors, these people can develop adenomas in rests of ectopic parathyroid tissue that are normally found in the thymus or carotid sheath. These rests are rarely clinically evident or significant, unless they develop a parathyroid adenoma in the setting of one of these clinical syndromes, or, rarely, as a sporadic event. This set of circumstances leads to the necessary considerations for managing primary hyperparathyroidism in MEN-1 (which will be used as the prototypical example of heritable primary hyperparathyroidism for this discussion). If these people develop primary hyperparathyroidism, and an indication for intervention, then the planned operation must address each of the parathyroid glands and cervically accessible sites of ectopic parathyroid tissue, must anticipate that any parathyroid tissue left in place will eventually develop additional neoplasms and lead to recurrent hyperparathyroidism, and must recognize that hypoparathyroidism is a significant functional deficit for a patient.3,4 Opting to risk permanent hypoparathyroidism for a decreased rate of recurrence is not a good option for patients.
Clinical presentation Patients with MEN-1 hyperparathyroidism present with the same clinical features as those with sporadic disease. There are no distinguishing biochemical features. For patients who are known to be members of MEN-1 kindreds, and who undergo regular biochemical screening, hypercalcemia often develops in the third or fourth decade of life. This can present earlier or later, and it can be the presenting feature for many people. For those who present without known MEN-1, the features that can make one suspicious include young patient age with multiple gland disease and some features in the family history that suggest possible MEN-1 components.5,6
Operative Techniques in Otolaryngology, Vol ], No ], Month ]]]]
Imaging Preoperative imaging has become common as a part of the operative planning for sporadic hyperparathyroidism. However, it is not useful, in general, for planning of initial cervical operations in familial disease. Because each parathyroid gland must be identified in the operating room for these patients anyway, the imaging does not limit the planned exploration as it does for focused procedures in the sporadic setting. For reoperations, imaging may be helpful to identify the site of recurrence and to plan the operation.
Surgical exploration The operative exploration for a patient with known MEN-1 hyperparathyroidism proceeds in a standard fashion, no matter the selected operative strategy for maintaining parathyroid function while preparing for the expected later recurrence. A typical incision (Figure 1) over the isthmus of the thyroid gland provides access to the central neck (region bounded by the carotid sheaths from submandibular glands to upper mediastinum) where abnormal parathyroid tissue is likely to reside. The length of the incision can be determined by the patient's body shape and by the size of the thyroid gland. Subplatysmal flaps (Figure 2) can be raised to enable a smaller incision to provide access to adjacent parts of the neck. The tracheoesophageal groove is exposed sequentially on each side as diagramed (Figure 3), demonstrating all of
Patient selection The indications for intervention in primary hyperparathyroidism associated with MEN-1 are the same as for those without the familial basis for the disease. If the patient has symptoms attributable to the hyperparathyroidism (fatigue, lethargy, depression, renal stone, and fragility fractures), then they should strongly consider operation. If they do not have clear symptoms, then criteria that were first introduced after a National Institutes of Health consensus conference in 1990 are generally used. Those criteria include young age (less than 50 years), markedly elevated serum calcium (41 mg/dL above the upper limit of normal), or end-organ effects (osteoporosis by dual energy X-ray absorptiometry scan, or renal function impairment with elevated serum level of creatinine). For recurrent disease in this setting, the criteria are generally stricter, with evidence of functional impairment by symptoms or end-organ effect being most convincing. Once a decision to intervene is settled, then the operative strategy can be selected.
Figure 1 With the patient position supine, neck extended, and upper body raised above the level of the abdomen (“beach chair”), a transverse incision is made over the isthmus of the thyroid gland, or within a nearby skin crease. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGraw-Hill Companies, 2010.) (Color version of figure is available online.)
Davies and Doherty
Parathyroid Surgery for Inherited Endocrinopathies
Figure 2 Subplatysmal flaps can be raised in the plane superficial to the anterior jugular veins. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGraw-Hill Companies, 2010.) (Color version of figure is available online.)
the soft tissues that are likely to contain parathyroid glands along the medial aspect of the dissection on each side of the neck. The upper parathyroid glands (Figure 4) are often identified first, as they tend to be deeper in the neck, and so starting the dissection there keeps the more superficial tissues intact. The lower parathyroid glands can then be dissected (Figure 5) within the tissues of the thyrothymic
Figure 3 The foundation of the exploration is set by following the posterior surface of the sternothyroid muscle laterally to the carotid sheath, and then following the plane of the medial aspect of the carotid sheath posteriorly to the spine. Completing this dissection of the medial aspect of the carotid sheath along its entire accessible length ensures that the primary typical and ectopic locations of the parathyroid glands all remain attached to the central tissues attached to the thyroid gland and larynx. This then safely focuses the exploration on these medial tissues, obviating the need to survey both medially and laterally to identify the parathyroid glands. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGraw-Hill Companies, 2010.) (Color version of figure is available online.)
3
Figure 4 The upper parathyroid glands are typically located deep in the neck, superior to the inferior thyroid artery trunk and posterior to the recurrent laryngeal nerve insertion to the larynx. Their blood supply is usually from the upper branches of the inferior thyroid artery, and if the gland has descended inferiorly along the lateral border of the esophagus, the vessels are at the superior end, and pass posterior to the inferior artery trunk. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGrawHill Companies, 2010.) (Color version of figure is available online.)
ligament, often but not always quite close to the lower pole of the thyroid gland. Finally, missing or additional glands should be sought, with knowledge of the typical ectopic pathways of the glands (Figure 6).
Figure 5 The lower parathyroid glands are typically located more anteriorly in the neck in the thyrothymic ligament. They are generally anterior to the recurrent laryngeal nerve and inferior to the inferior thyroid artery trunk. Their position is more variable than the superior glands. (Color version of figure is available online.)
4
Operative Techniques in Otolaryngology, Vol ], No ], Month ]]]]
Subtotal parathyroidectomy
Figure 6 The parathyroid glands can form in, or enlarge into, ectopic positions, usually in predictable directions as demonstrated. (Modified with permission from Doherty GM, Minter RM (eds): Current Procedures Surgery. New York, NY, McGraw-Hill Companies, 2010.) (Color version of figure is available online.)
Operative strategies There are 2, essentially equivalent alternative strategies for managing MEN-1 hyperparathyroidism. They have been compared in a randomized trial and each is found to have advantages and disadvantages, and probably both have roles in different patients.7-9 The total parathyroidectomy with autograft strategy has a slightly higher hypoparathyroidism risk, but a simpler reoperation procedure. Some experienced surgeons prefer this option for patients more likely to require reoperation (younger patients, more diffusely affected larger glands, and prior recurrence). The subtotal parathyroidectomy strategy has less risk of hypoparathyroidism, but it requires reoperation in the neck for recurrence.
Subtotal parathyroidectomy, commonly termed a “threeand-a-half” gland parathyroidectomy, is better thought of as a “half-and-three” gland procedure. Once all parathyroid glands have been identified, one is selected to be the remnant. The criteria for this are that it should be a more “normal” looking gland in size, shape, and color, and it should be accessible at a subsequent operation if need be. A portion of this gland is removed, leaving approximately 100 mg attached to grossly intact vasculature. This should bleed freely. The remnant can then be inspected, and only once some time has passed, and it is clear that the remnant is viable, the remaining parathyroid glands are removed. If the remnant does not remain viable, then another gland is selected, and a new remnant is created. This avoids the awkward circumstance of removing the 3 “nonremnant” glands and then devascularizing the intended remnant.
Postoperative care These patients are often relatively hypoparathyroid postoperatively and may have significant bone hunger if they have had significant bone disease. They generally require calcium replacement and may need supplementation with activated forms of vitamin D (such as calcitriol) to enhance the gastrointestinal calcium absorption.
Follow-up and natural history As long as these patients have parathyroid tissue in place, they have a lifetime risk of recurrent hyperparathyroidism. They should be followed annually for recurrence as a part of their MEN-1 surveillance program.
Disclosure Total parathyroidectomy and autograft Once all the parathyroid tissue has been identified and confirmed (either by definitive gross examination or by intraoperative pathology consultation), the resection strategy can be implemented. One option is to remove all parathyroid tissue from the neck and place it into an ice bath in sterile saline. A portion, usually estimated at approximately 100 mg, can then be trimmed from one of the glands, minced into small pieces, and reimplanted into individual pockets in a convenient position. The nondominant forearm is often chosen as it allows low-morbidity access for reoperation to treat future graft-dependent recurrence. This position also enables demonstration of graft dependence of future recurrence through “transient parathyroidectomy”— measuring contralateral arm parathyroid hormone before and after occlusion of the venous drainage above the graft.
The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.
References 1. Doherty GM: Multiple endocrine neoplasia type 1. J Surg Oncol 89 (3):143-150, 2005 2. Doherty GM, Lairmore TC, DeBenedetti MK: Multiple endocrine neoplasia type 1 parathyroid adenoma development over time. World J Surg 28(11):1139-1142, 2004 3. Yavuz S, Simonds WF, Weinstein LS, et al: Sleeping parathyroid tumor: Rapid hyperfunction after removal of the dominant tumor. J Clin Endocrinol Metab 97(6):1834-1841, 2012 4. Norton JA, Venzon DJ, Berna MJ, et al: Prospective study of surgery for primary hyperparathyroidism (HPT) in multiple endocrine neoplasiatype 1 and Zollinger-Ellison syndrome: Long-term outcome of a more virulent form of HPT. Ann Surg 247(3):501-510, 2008
Davies and Doherty
Parathyroid Surgery for Inherited Endocrinopathies
5. Glascock MJ, Carty SE: Multiple endocrine neoplasia type 1: Fresh perspective on clinical features and penetrance. Surg Oncol 11(3): 143-150, 2002 6. Yip L, Ogilvie JB, Challinor SM, et al: Identification of multiple endocrine neoplasia type 1 in patients with apparent sporadic primary hyperparathyroidism. Surgery 144(6):1002-1006. [discussion 1006–1007], 2008 7. Lairmore TC, Govednik CM, Quinn CE, et al: A randomized, prospective trial of operative treatments for hyperparathyroidism in
5
patients with multiple endocrine neoplasia type 1. Surgery 156(6): 1326-1334. [discussion 1334–1325], 2014 8. Elaraj DM, Skarulis MC, Libutti SK, et al: Results of initial operation for hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Surgery 134(6):858-864. [discussion 864–855], 2003 9. Hubbard JG, Sebag F, Maweja S, et al: Subtotal parathyroidectomy as an adequate treatment for primary hyperparathyroidism in multiple endocrine neoplasia type 1. Arch Surg 141(3):235-239, 2006