J. Endocrinol. Invest. 13: 667 -670, 1990
CASE REPORT
Asymptomatic parathyroid adenoma manifested by intratumoral hemorrhage A. Paracchi*, E. Reschini**, C. Ferrari*, and R. Macchi* *Ospedale Fatebenefratelli, and **Ospedale Maggiore, Milano, Italy ABSTRACT. A 48-year-old woman whose past history was unrevealing presented with sudden swelling of the neck with pain and dysphonia. Neck ultrasonography suggested the possibility of hemorrhage in a parathyroid adenoma. Surgical
exploration revealed a hemorrhagic parathyroid adenoma of the chief cell type. This event is exceedingly rare, but should be considered in the differential diagnosis of suddenly appearing masses of the neck region.
INTRODUCTION The possibility of hemorrhage in thyroid nodules or cysts causing sudden swelling of the anterior neck is well known. The same phenomenon may occur also in parathyroid adenomas, but this complication is exceedingly rare, only eleven cases having been reported to date (1-11). We report here on a case of sudden swelling of the neck due to bleeding in a previously unrecognized parathyroid adenoma.
laryngoscopy showed paresis of the left vocal cord, Ultrasonography of the neck disclosed a 3x5 cm mass interpreted as hemorrhagic collection of the left lower thyroid pole. Fine needle biopsy resulted in the aspiration of 7ml of blood and little cellular material considered suggestive of follicular thyroid proliferation. Thyroid scintigraphy with pertechnetate was normal (Fig. 1). This unexpected result prompted us to obtain another echographic examination by a sonographer (Dr. L. Solbiati, Busto Arsizio, Italy) with particular experience in neck pathology (12, 13). On that occasion the mass was clearly demonstrated as being separated from the thyroid lobe (Fig. 2). The sonographer could not exclude the thyroid origin of the mass, but raised the suspicion of a parathyroid adenoma, Concomitant fine needle biopsy resulted in the aspiration of 3 ml of blood without analyzable cells. Serum calcium level was then measured for the first time, about two months after the onset of symptoms and was slightly subnormal (2.04 mmol/l); normal 2.24-2.62); serum phosphate was normal (1.13 mmol/l; normal 0.96-1.45). There were no clinical signs of hypocalcemia. There was no radiological evidence of bone disease. Renal function was normal. Surgical exploration was decided and at operation a mass of about 4x2 cm was found in the position of the left lower parathyroid gland. There was an inflammatory reaction with scar tissue causing dense adhesions between the mass, the prethyroid muscles, the trachea and the left thyroid
CASE REPORT A 48-year-old woman, whose past history was unrevealing, presented complaining sudden swelling on the left side of the lower anterior neck since a few days. In the days immediately preceding the onset of symptoms she had assumed aspirin by self prescription for headache. The neck swelling was accompanied by local pain and dysphonia, without dysphagia. Local examination revealed a hard swelling in the region of the lower pole of the left thyroid lobe, tender at palpation; the right lobe was not palpable. Tentative diagnostic hypotheses were subacute thyroiditis or hemorrhage in a previously unrecognized thyroid nodule. Initial laboratory findings included normal thyroid hormone levels and normal erythrocyte sedimentation rate. Indirect Key-words: Parathyroid adenoma, parathyroid hemorrhage, neck swelling. Correspondence. Dr. A. Paracchi, Via Ie Campania 40, 20133 Milano, Italy. Received January 8, 1990; accepted April 20, 1990.
667
E. Reschini, C. Ferrari, et al.
A. Paracchi,
Ii
I
I
,, I
I
I
I
I ': I' , \ 11'1
II
I Fig. 3 - Histological sections of the removed mass. A: Parathyroid
tissue composed of chief cells. There is a large area of hemorrhage in organization phase (original magnification x 100). B: Particular view at stronger magnification showing trabecular cell pattern and including a dilated vessel (original magnification x 400). The tissue was stained with hematoxylin and eosin.
Fig. 1 - Pertechnetate thyroid scintigraphy showing essentially
normal results.
course was uneventful. Dysphonia resolved rapidly and all110st completely. Three weeks later serum calcium and phosphate levels were normal (2.44 and 1.32 mmol/I, respectively). The patient was last seen 5 months after operation and was in good health.
lobe. The surgeon elected to excise the mass en bloc with the left thyroid lobe. At gross examination after section the mass contained several areas of hemorrhage. Histologic examination revealed a chief cell parathyroid adenoma with cystic and hemorrhagic component (Fig. 3). The day after surgery serum calcium was 2.12 mmol/1. Postoperative
DISCUSSION Among the 11 previously reported cases of symptomatic bleeding in a parathyroid adenoma, 4 were already known as hypercalcemic at the moment of the hemorrhage (4, 5, 9, 11), while in the other 7 cases the swelling of the adenoma caused the presenting symptoms of the disease (1-3, 6-8, 10). The local signs varied from simple swelling of the neck with moderate dysphagia and pain, to severe signs simulating aortic dissecting aneurysm, depending on the size and location of the swollen adenomas, 3 of which were intrathoracic (4-6). In the cases in which the hemorrhage became extracapsular, ecchymoses appeared on neck and/or chest (4, 5, 7, 9,11). Serum calcium was elevated in all previous cases but one (10) at the time of diagnosis and 2 of them developed, coincident with the hemorrhagic episode, a hypercalcemic crisis ascribed to massive release of parathyroid hormone from the tumor (2, 3). In 2 patients (8, 11) serum calcium normalized
Fig. 2 - Ultrasonography of the neck showing a mass with predominantly liquid content adjacent to the caudal pole of the left thyroid lobe.
668
Hemorrhage in parathyroid adenoma
spontaneously before operation and in another one (3) an episode clinically strongly suggestive of a hypercalcemic crisis with hemorrhage in a parathyroid adenoma subsided spontaneously and relapsed 10 months later. It can be speculated that in these cases a partial necrosis of the adenoma caused the spontaneous remissions. In our case there were no clinical signs suggestive of hyperparathyroidism and the serum calcium levels were measured only at about 2 months from the onset of symptoms, after ultrasonography had raised the suspicion of parathyroid involvement. The moderate hypocalcemia then registered may have been the consequence of hemorrhagic necrosis of the adenoma, although this is only speculative. In our case the hemorrhage remained mainly intracapsular, but some extravasation must have occurred, insufficient to cause subcutaneous ecchymoses but sufficient to cause firm adhesions between the adenoma and the adjacent structures. The aspirin assumed in the days preceding the episode may have played a role in promoting hemorrhage through its anticoagulation properties; an identical history was reported also for another patient (8). When a parathyroid adenoma is suspected, it can be identified non invasively in a high proportion of cases by thallium- technetium scintigraphy (14, 15) and/or ultrasonography (12, 15). Among hemorrhagic adenomas, one case was identified by scintigraphy (9); echography was performed in 2 cases (8, 10), but did not suggest clearly the parathyroid nature of the mass, although in one case (8) it was identified as extrathyroid. Our case is the first one in which the sonographer was able to suggest the parathyroid origin of the neck hemorrhage. The rate of success of ultrasonography in identifying parathyroid pathology is probably highly dependent on the experience of the operator. The long term management of asymptomatic hyperparathyrOidism is a matter of dispute. The erT)ployed strategies varied from simple follow-up (16, 17) to systematic surgical treatment (18). If followup is decided, the physician should be aware that hemorrhage is a possible complication. It should be remembered that massive hemorrhage can occur not only in adenomatous but also in hyperplastic parathyroid glands (19). Apart from the follow-up of hypercalcemic patients, hemorrhage in an abnormal parathyroid gland should be kept in mind in the differential diagnosis of sudden swelling of the neck and mediastinum.
ACKNOWLEDGMENTS We thank Dr. N. Paracchi, Como, Italy, who referred the patient to us, and Dr. L. Solbiati, Busto Arsizio, Italy, for the sonographic study.
REFERENCES 1. Lemann J., Donatelli AA Calcium intoxication due to primary hyperparathyroidism. Ann. Intern. Med. 60: 447, 1964. 2. Chodack P., Attie J.N., Groder M.G. Hypercalcemic crisis coincidental with hemorrhage in parathyroid adenoma. Arch. Intern. Med. 116: 416, 1965.
3. De Groote JW. Acute intermittent hyperparathyroidism with hemorrhage into a parathyroid adenoma. JAMA 208: 2160, 1969. 4.
Berry B.E., Carpenter P.C., Fulton A.E., Danielson G.K. Mediastinal hemorrhage from parathyroid adenoma simulating dissecting aneurysm. Arch. Surg. 108: 740, 1974.
5.
Santos G.H., Tseng C.L., Frater RW.M. Ruptured intrathoracic parathyroid adenoma. Chest 68: 844, 1975.
6.
Gamondes J.P., Maret G., Berger G., Brune J., Joud A. Adenome parathyro"idien du mediastin superieur avec kyste hematique suffocant. Nouv. Presse Med. 7: 4149, 1978.
7. Jordan FT., Harness J.K., Thompson NW. Spontaneous cervical hematoma: A rare manifestation of parathyroid adenoma. Surgery 89: 697, 1981. 8.
Bacourt F., Brun J.G., Lacombe P., Dupuy P., Parlier H. Adenome parathyro"idien revele par une hemorrhagie sous-capsulaire massive. Presse Med. 13: 669, 1984.
9. Dick JA, Brame K.G., Owen W.J. Spontaneous bleeding into a parathyroid cyst. Sr. J. Surg. 72: 693, 1985. 10. Ghisotti E., Cimino F., Ferrero D., Cardesi E., Anselmetti G.C. Adenoma paratiroideo rilevato da una emorragia sottocapsulare. Minerva Chir. 41: 165, 1986. 11. Hotes L.S., Barzilay J., Cloud L.P., Rolla A.A. Spontaneous hematoma of a parathyroid adenoma. Am. J. Med. Sci. 297: 331, 1989.
669
A. Paracchi, E. Reschini, C. Ferrari, et al.
99m pertechnetate subtraction sCintigraphy and high-resolution ultrasonography. Radiology 155: 231, 1985.
12. Solbiati L., Montali G., Croce F., Bellotti E., Giangrande A., Ravetto C. Parathyroid tumors detected by fine-needle aspiration biopsy under ultrasonic guidance. Radiology 148: 793, 1983.
16. Scholz DA, Purnell D.C. Asymptomatic primary hyperparathyroidism. 1O-year prospective study. Mayo Clin. Proc. 56: 473, 1981.
13. Solbiati L., Volterrani L., Rizzatto G., Bazzocchi M., Busilacchi P., Candiani F., Ferrari F., Giuseppetti G., Maresca G., Mirk P., Rubaltelli L., Zappasodi F. The thyroid gland with low uptake lesions: Evaluation by ultrasound. Radiology 155: 187, 1985.
17. Van't Hoff W., Ballardie FW., Bicknell E.J. Primary hyperparathyroidism: the case for medical management. Br. Med. J. 287: 1605, 1983. 18. Russell C.F., Edis A.J. Surgery of primary hyperparathyroidism: experience with 500 consecutive cases and evaluation of the role of surgery in the asymptomatic patient. Br. J. Surg. 69: 244, 1982.
14. Ferlin G., Borsato N., Camerani M., Conte N., Zotti D. New perspectives in localizing enlarged parathyroids by technetium-thallium subtraction scan. J. Nucl. Med. 24: 438, 1983.
19. Hedman I., Hansson G., Romanus R., Tisell L.E., Zachrisson B.F. Massive parathyroid hemorrhage in a case of waterclear cell hyperplasia. Acta Chir. Scand. 144: 541, 1978.
15. Winzelberg G.G., Hydovitz J.D., O'Hara K.R., Anderson K.M., Turbiner E., Danowski T.S., Lippe R.D., Melada GA, Harrison A.M. Parathyroid adenomas evaluated by TI-201 / Tc-
670
CASE REPORT
Asymptomatic parathyroid adenoma manifested by intratumoral hemorrhage A. Paracchi*, E. Reschini**, C. Ferrari*, and R. Macchi* *Ospedale Fatebenefratelli, and **Ospedale Maggiore, Milano, Italy ABSTRACT. A 48-year-old woman whose past history was unrevealing presented with sudden swelling of the neck with pain and dysphonia. Neck ultrasonography suggested the possibility of hemorrhage in a parathyroid adenoma. Surgical
exploration revealed a hemorrhagic parathyroid adenoma of the chief cell type. This event is exceedingly rare, but should be considered in the differential diagnosis of suddenly appearing masses of the neck region.
INTRODUCTION The possibility of hemorrhage in thyroid nodules or cysts causing sudden swelling of the anterior neck is well known. The same phenomenon may occur also in parathyroid adenomas, but this complication is exceedingly rare, only eleven cases having been reported to date (1-11). We report here on a case of sudden swelling of the neck due to bleeding in a previously unrecognized parathyroid adenoma.
laryngoscopy showed paresis of the left vocal cord, Ultrasonography of the neck disclosed a 3x5 cm mass interpreted as hemorrhagic collection of the left lower thyroid pole. Fine needle biopsy resulted in the aspiration of 7ml of blood and little cellular material considered suggestive of follicular thyroid proliferation. Thyroid scintigraphy with pertechnetate was normal (Fig. 1). This unexpected result prompted us to obtain another echographic examination by a sonographer (Dr. L. Solbiati, Busto Arsizio, Italy) with particular experience in neck pathology (12, 13). On that occasion the mass was clearly demonstrated as being separated from the thyroid lobe (Fig. 2). The sonographer could not exclude the thyroid origin of the mass, but raised the suspicion of a parathyroid adenoma, Concomitant fine needle biopsy resulted in the aspiration of 3 ml of blood without analyzable cells. Serum calcium level was then measured for the first time, about two months after the onset of symptoms and was slightly subnormal (2.04 mmol/l); normal 2.24-2.62); serum phosphate was normal (1.13 mmol/l; normal 0.96-1.45). There were no clinical signs of hypocalcemia. There was no radiological evidence of bone disease. Renal function was normal. Surgical exploration was decided and at operation a mass of about 4x2 cm was found in the position of the left lower parathyroid gland. There was an inflammatory reaction with scar tissue causing dense adhesions between the mass, the prethyroid muscles, the trachea and the left thyroid
CASE REPORT A 48-year-old woman, whose past history was unrevealing, presented complaining sudden swelling on the left side of the lower anterior neck since a few days. In the days immediately preceding the onset of symptoms she had assumed aspirin by self prescription for headache. The neck swelling was accompanied by local pain and dysphonia, without dysphagia. Local examination revealed a hard swelling in the region of the lower pole of the left thyroid lobe, tender at palpation; the right lobe was not palpable. Tentative diagnostic hypotheses were subacute thyroiditis or hemorrhage in a previously unrecognized thyroid nodule. Initial laboratory findings included normal thyroid hormone levels and normal erythrocyte sedimentation rate. Indirect Key-words: Parathyroid adenoma, parathyroid hemorrhage, neck swelling. Correspondence. Dr. A. Paracchi, Via Ie Campania 40, 20133 Milano, Italy. Received January 8, 1990; accepted April 20, 1990.
667
E. Reschini, C. Ferrari, et al.
A. Paracchi,
Ii
I
I
,, I
I
I
I
I ': I' , \ 11'1
II
I Fig. 3 - Histological sections of the removed mass. A: Parathyroid
tissue composed of chief cells. There is a large area of hemorrhage in organization phase (original magnification x 100). B: Particular view at stronger magnification showing trabecular cell pattern and including a dilated vessel (original magnification x 400). The tissue was stained with hematoxylin and eosin.
Fig. 1 - Pertechnetate thyroid scintigraphy showing essentially
normal results.
course was uneventful. Dysphonia resolved rapidly and all110st completely. Three weeks later serum calcium and phosphate levels were normal (2.44 and 1.32 mmol/I, respectively). The patient was last seen 5 months after operation and was in good health.
lobe. The surgeon elected to excise the mass en bloc with the left thyroid lobe. At gross examination after section the mass contained several areas of hemorrhage. Histologic examination revealed a chief cell parathyroid adenoma with cystic and hemorrhagic component (Fig. 3). The day after surgery serum calcium was 2.12 mmol/1. Postoperative
DISCUSSION Among the 11 previously reported cases of symptomatic bleeding in a parathyroid adenoma, 4 were already known as hypercalcemic at the moment of the hemorrhage (4, 5, 9, 11), while in the other 7 cases the swelling of the adenoma caused the presenting symptoms of the disease (1-3, 6-8, 10). The local signs varied from simple swelling of the neck with moderate dysphagia and pain, to severe signs simulating aortic dissecting aneurysm, depending on the size and location of the swollen adenomas, 3 of which were intrathoracic (4-6). In the cases in which the hemorrhage became extracapsular, ecchymoses appeared on neck and/or chest (4, 5, 7, 9,11). Serum calcium was elevated in all previous cases but one (10) at the time of diagnosis and 2 of them developed, coincident with the hemorrhagic episode, a hypercalcemic crisis ascribed to massive release of parathyroid hormone from the tumor (2, 3). In 2 patients (8, 11) serum calcium normalized
Fig. 2 - Ultrasonography of the neck showing a mass with predominantly liquid content adjacent to the caudal pole of the left thyroid lobe.
668
Hemorrhage in parathyroid adenoma
spontaneously before operation and in another one (3) an episode clinically strongly suggestive of a hypercalcemic crisis with hemorrhage in a parathyroid adenoma subsided spontaneously and relapsed 10 months later. It can be speculated that in these cases a partial necrosis of the adenoma caused the spontaneous remissions. In our case there were no clinical signs suggestive of hyperparathyroidism and the serum calcium levels were measured only at about 2 months from the onset of symptoms, after ultrasonography had raised the suspicion of parathyroid involvement. The moderate hypocalcemia then registered may have been the consequence of hemorrhagic necrosis of the adenoma, although this is only speculative. In our case the hemorrhage remained mainly intracapsular, but some extravasation must have occurred, insufficient to cause subcutaneous ecchymoses but sufficient to cause firm adhesions between the adenoma and the adjacent structures. The aspirin assumed in the days preceding the episode may have played a role in promoting hemorrhage through its anticoagulation properties; an identical history was reported also for another patient (8). When a parathyroid adenoma is suspected, it can be identified non invasively in a high proportion of cases by thallium- technetium scintigraphy (14, 15) and/or ultrasonography (12, 15). Among hemorrhagic adenomas, one case was identified by scintigraphy (9); echography was performed in 2 cases (8, 10), but did not suggest clearly the parathyroid nature of the mass, although in one case (8) it was identified as extrathyroid. Our case is the first one in which the sonographer was able to suggest the parathyroid origin of the neck hemorrhage. The rate of success of ultrasonography in identifying parathyroid pathology is probably highly dependent on the experience of the operator. The long term management of asymptomatic hyperparathyrOidism is a matter of dispute. The erT)ployed strategies varied from simple follow-up (16, 17) to systematic surgical treatment (18). If followup is decided, the physician should be aware that hemorrhage is a possible complication. It should be remembered that massive hemorrhage can occur not only in adenomatous but also in hyperplastic parathyroid glands (19). Apart from the follow-up of hypercalcemic patients, hemorrhage in an abnormal parathyroid gland should be kept in mind in the differential diagnosis of sudden swelling of the neck and mediastinum.
ACKNOWLEDGMENTS We thank Dr. N. Paracchi, Como, Italy, who referred the patient to us, and Dr. L. Solbiati, Busto Arsizio, Italy, for the sonographic study.
REFERENCES 1. Lemann J., Donatelli AA Calcium intoxication due to primary hyperparathyroidism. Ann. Intern. Med. 60: 447, 1964. 2. Chodack P., Attie J.N., Groder M.G. Hypercalcemic crisis coincidental with hemorrhage in parathyroid adenoma. Arch. Intern. Med. 116: 416, 1965.
3. De Groote JW. Acute intermittent hyperparathyroidism with hemorrhage into a parathyroid adenoma. JAMA 208: 2160, 1969. 4.
Berry B.E., Carpenter P.C., Fulton A.E., Danielson G.K. Mediastinal hemorrhage from parathyroid adenoma simulating dissecting aneurysm. Arch. Surg. 108: 740, 1974.
5.
Santos G.H., Tseng C.L., Frater RW.M. Ruptured intrathoracic parathyroid adenoma. Chest 68: 844, 1975.
6.
Gamondes J.P., Maret G., Berger G., Brune J., Joud A. Adenome parathyro"idien du mediastin superieur avec kyste hematique suffocant. Nouv. Presse Med. 7: 4149, 1978.
7. Jordan FT., Harness J.K., Thompson NW. Spontaneous cervical hematoma: A rare manifestation of parathyroid adenoma. Surgery 89: 697, 1981. 8.
Bacourt F., Brun J.G., Lacombe P., Dupuy P., Parlier H. Adenome parathyro"idien revele par une hemorrhagie sous-capsulaire massive. Presse Med. 13: 669, 1984.
9. Dick JA, Brame K.G., Owen W.J. Spontaneous bleeding into a parathyroid cyst. Sr. J. Surg. 72: 693, 1985. 10. Ghisotti E., Cimino F., Ferrero D., Cardesi E., Anselmetti G.C. Adenoma paratiroideo rilevato da una emorragia sottocapsulare. Minerva Chir. 41: 165, 1986. 11. Hotes L.S., Barzilay J., Cloud L.P., Rolla A.A. Spontaneous hematoma of a parathyroid adenoma. Am. J. Med. Sci. 297: 331, 1989.
669
A. Paracchi, E. Reschini, C. Ferrari, et al.
99m pertechnetate subtraction sCintigraphy and high-resolution ultrasonography. Radiology 155: 231, 1985.
12. Solbiati L., Montali G., Croce F., Bellotti E., Giangrande A., Ravetto C. Parathyroid tumors detected by fine-needle aspiration biopsy under ultrasonic guidance. Radiology 148: 793, 1983.
16. Scholz DA, Purnell D.C. Asymptomatic primary hyperparathyroidism. 1O-year prospective study. Mayo Clin. Proc. 56: 473, 1981.
13. Solbiati L., Volterrani L., Rizzatto G., Bazzocchi M., Busilacchi P., Candiani F., Ferrari F., Giuseppetti G., Maresca G., Mirk P., Rubaltelli L., Zappasodi F. The thyroid gland with low uptake lesions: Evaluation by ultrasound. Radiology 155: 187, 1985.
17. Van't Hoff W., Ballardie FW., Bicknell E.J. Primary hyperparathyroidism: the case for medical management. Br. Med. J. 287: 1605, 1983. 18. Russell C.F., Edis A.J. Surgery of primary hyperparathyroidism: experience with 500 consecutive cases and evaluation of the role of surgery in the asymptomatic patient. Br. J. Surg. 69: 244, 1982.
14. Ferlin G., Borsato N., Camerani M., Conte N., Zotti D. New perspectives in localizing enlarged parathyroids by technetium-thallium subtraction scan. J. Nucl. Med. 24: 438, 1983.
19. Hedman I., Hansson G., Romanus R., Tisell L.E., Zachrisson B.F. Massive parathyroid hemorrhage in a case of waterclear cell hyperplasia. Acta Chir. Scand. 144: 541, 1978.
15. Winzelberg G.G., Hydovitz J.D., O'Hara K.R., Anderson K.M., Turbiner E., Danowski T.S., Lippe R.D., Melada GA, Harrison A.M. Parathyroid adenomas evaluated by TI-201 / Tc-
670
