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Functional cystic parathyroid adenoma
Functional Cystic Parathyroid Adenoma LTC. JERRY M. EARLL, MC, USA, Honolulu, Hawaii COL. ARTHUR COHEN, MC, USA, San Francisco, California LTC. GEORGE D. LUN’DBERG, MC, USA, Los Angeles, California
Primary hyperparathyroidism commonly results in symptoms related to the urinary tract, skeleton, or gastrointestinal tract, and the manifestations of the disease may vary from an extremely chronic nature to acute medical and surgical emergencies. Although the local signs of most tumors are usually emphasized as contributing to the appropriate diagnosis, this aspect has been de-emphasized in relation to parathyroid tumors to the point of misleading the unwary clinician. It used to be axiomatically suggested that if a patient with hyperparathyroidism had a lump in the neck, the lump was not a parathyroid tumor [1,21. The need to consider parathyroid adenoma in the differential diagnosis of tumors of the neck was emphasized in a recent review of 106 cases in which a mass in the neck was palpable [31. In almost one fourth of these the mass was the presenting symptom, but the parathyroid tusurprise.” Parathyroid mor was a “surgical cysts which are clinically apparent are extremely rare. The preoperative diagnosis has been made in only three cases [&s]. This report describes a patient with an unusually large cystic, functioning parathyroid adenoma which was additionally unique in that it presented as a rapidly enlarging mass after hemorrhage into the cyst. The importance of preoperative serum calcium determinations which allowed the correct diagnosis to be made and the relationship of hypercalcemia and hypertension are illustrated. Case Report A thirty-seven year old Caucasian man was first noted to have hypertension in January 1963. From the Department of Surgery, eral Hospital. El Paso. Texas. 100
William
Beaumont
Gen-
Before therapy, blood pressure ranged from 150/ 100 to 1701116 mm. Hg. After hospitalization and thorough evaluation, his diagnosis remained essential hypertension. Therapy with variable doses of chlorothiazide and reserpine controlled the hypertension in a range of 130/90 to 160/115 mm. Hg over the ensuing two years. In March 1966 a mass appeared suddenly in the left side of the neck and was slightly tender. The mass measured 7 by 5 cm. in diameter and was quite firm. It was initially believed that this represented hemorrhage into a thyroid cyst. Chest roentgenogram revealed deviation of the trachea. Protein-bound iodine and radioactive iodine uptake studies gave normal results. The thyroid scan revealed a “cold” area in the left lobe compatible with a thyroid cyst. (Fig. 1.) Thyroid suppression with exogenous thyroid was associated with some regression in the size of the lesion. Surgical excision was elected because of the large persisting mass. He was admitted to the hospital on May 9, 1965. Blood pressure was 142/88 mm. Hg and physical examination was within normal limits except for the mass in the left side of the neck and a rather dull mentation. Routine preoperative serum caIcium was 15.0 mg./lOO ml. (normal 8.5 to 10.5 mg.1100 ml.) and serum phosphorus was 2.2 mg./lOO ml., indicating the presence of hyperparathyroidism and implicating the palpable neck mass. All other electrolyte levels were normal. The electrocardiogram revealed a shortened Q-T interval compatible with hypercalcemia. Review of the original electrocardiogram taken in 1963 also demonstrated this abnormality. Roentgenograms revealed early demineralization of the skull and early bony resorption of the phalanges. The lamina dura was intact. Despite a low calcium diet, large fluid intake, and required ambulation, the serum calcium was 17.6 mg.1100 ml. with a serum phosphorus of 2.3 mg./lOO ml. on May 12. Further delay in surgery in the hope of lowering the serum calcium level seemed unwise. With continuous electrocardiographic monitoring, removal of a large The American
Journal of Surgery
Functional Cystic Parathyroid
Fig. 1. ““I thyroid scintigram demonstrating area of decreased function in the left lobe. Small round dot indicates center of the palpable mass. cystic adenoma of the left inferior parathyroid gland was accomplished without complication on May 13. The specimen consisted of an 85 gm. ovoid mass measuring ‘7 by 5 by 3 cm. with a smooth, shining red surface. (Fig. 2.) On cross section, 67 ml. of cloudy, red-brown fluid escaped from a single, large, central cystic cavity. (Fig. 3.) The wall of the cyst was red-brown interspersed with bright yellow and averaged 0.4 cm. in thickness. On microscopic examination (Fig. 4)) the tumor consisted of masses of uniform compact chief cells which only rarely displayed an acinar arrangement. Nuclei were small and round and cytoplasm was sparse with indistinct cystoplasmic borders. Mitotic figures were not seen. The stroma was scant and delicately fibrous with abundant small blood vessels. A few thick fibrous strands were present. Free and phagocytized hemosiderin pigment was scattered throughout the mass, representing resolving hemorrhage. The cyst was lined by cells identical to those comprising the remainder of the mass. Normal appearing parathyroid tissue
2 Fig. 2. shining
The gross specimen of the tumor surface measuring 7 by 5 by 3 cm.
On cross section the predominantly Fig. 3. arrows outline the cystic cavity. Vol.
118,July 1969
Adenoma
Photomicrograph of the tumor demonstrating a homogeneous pattern of uniform chief cells in a delicate fibrovascular stroma. (Hematoxylin and eosin stain; original magnification x 185.) Fig. 4.
was present outside the capsule and was compressed by the adenoma. Immediately after surgery, the serum calcium was 17.5 mg./lOO ml. and serum phosphorus 2.6 mg./lOO ml. The serum calcium level fell steadily to 8.0 mg./lOO ml. with phosphorus 4.0 mg./lOO ml. by May 16, 1965. Oral calcium was briefly required to maintain a normal serum calcium level and the electrocardiogram reverted to normal. Postoperative blood pressure ranged from 130/80 to 140/88 mm. Hg without medication. The patient remained normotensive and was transferred to the care of his referring physician ten weeks later.
Comments This case was unusual in several aspects which are worthy of emphasis. It has already been pointed out that the old axiom of a pal-
.~_.--._.-.--------_
3
illustrating
its ovoid shape and smooth
cystic nature
of the mass is evident;
101
Eat-II, Cohen, and Lundberg
pable mass in the neck not being a parathyroid adenoma needs to be discarded [9]. Clinically significant macroscopic parathyroid cysts are uneommon and the cysts are not usually associated with dysfunction of the parathyroids. Diagnosis of this very large functioning cystic adenoma was made even more confusing by hemorrhage into the cyst. This misled us into considering the more common diagnosis of hemorrhage into a thyroid cyst. The thyroid scan supported this diagnosis, and it was tempting to attribute some of the reduction in size to the exogenous thyroid therapy. The possibility of a parathyroid adenoma presenting as a “cold” thyroid nodule must always be considered [ 7’1.Accepting the concept that palpable masses in the neck may well be parathyroid adenomas, the decision to obtain preoperative serum calcium determinations is obvious and should reduce the number of “surgical surprises” [3]. As emphasized by this patient, the preoperative diagnosis is not just of academic interest but is very important to insure that preoperative preparation is optimal, and the anesthetist can be aware of the problem and prepared to cope with the increased risk of the hypercalcemic patient. The critical level of serum calcium is 17 to 18 mg./lOO ml., and over this, life-threatening parathyroid crisis commonly develops. Rising levels of calcium, phosphorus, and nonprotein nitrogen with a decrease in urinary volume are indications for immediate exploratory surgery [&!I. Electrolyte abnormalities are to be corrected as promptly as possible to avoid dehydration, acidosis which increases the percentage of ionized calcium, and alkalosis which can result in calcium precipitation. If the usual duration of symptoms is considered with the evidence that a diagnosis of hyperparathyroidism should be made in about 1 in 1,200 new patients [9], it is apparent that the diagnosis is commonly delayed or missed. The mere listing of some of the symptoms associated with only one complication such as hypercalcemia assists in explaining the difficulties in suspecting the diagnosis. Hypertension has rarely been emphasized and yet may be present in one third of patients with hypercalcemia [10,11]. In retrospect, the electrocardiogram in our patient suggested that hypercalcemia was present two years earlier. This hypertension was greatly improved by correction of the hypercalcemia. There is adequate basic re102
search to indicate that the calcium ion has a direct role in increasing vascular resistance 1121, and otherwise normal patients have been noted to become severely hypertensive during calcium infusion tests [IS]. Changes in renal function and structural renal damage in association with hypercalcemia are well documented [141 but the rapidity of onset of hypertension [IS], the reversibility [10,11], and the ability to produce hypertension in the isolated perfused limb Cl.21 suggest a more direct mechanism. Hypercalcemia should be added to the list of correctible types of hypertension. Summary An unusual case of hyperparathyroidism associated with an 85 gm. cystic functioning adenoma is described. The mass had enlarged suddenly and presented as a hemorrhagic thyroid cyst. Thyroid scintigram was compatible with a “cold” nodule of the thyroid gland. The correct diagnosis was made when a high serum calcium level was obtained in the immediate preoperative workup. Clinically palpable parathyroid adenomas occur often enough to justify routine serum calcium and phosphorus determinations in patients who present with masses in the neck, and hypercalcemia should be considered in the differential diagnosis in hypertensive patients. References 1.
2.
ALBRIGHT,F. Further experience in the diagnosis of hyperparathyroidism including a discussion of cases with a minimal degree of hyperparathyroidism. Am. J. M. Sci., 193: 800,1937. SCHNEIDER,R. W. and ROBINETT,A. H. Diag-
nosis
of
Cleveland
3.
obscure Clin. Quart.,
SOLOMON,M. Palpable J. Louieiccna
hyperparathyroidism. 18 : 66, 1951. parathyroid
M. SOL. 116
tumors.
: 214. 1964.
4.
SHIELDS,T. W. and ST~LEY,C. J. Functioning ;;ac;thyroid cysts. Arch. Surg., 82: 937,
5.
WEEKS, P. M. Clinically significant para& thyroid cysts: case report and review of literature. Am. Surgeon, 31: 366,1965. MCCORMACK,K. R. An unusual “thyroid” nodule “cold” to scintiscan. California Med.,
6.
103:
7.
8. 9.
282,1966.
ARNAIJD, C. D., WALKER, J. A., and EWER, R. W. Primary hyperparathyroidism associated with a cystic lesion in the neck: probable parathyroid cyst. J. Clin. Endocrinol., 21: 833, 1961. HENLEY, R. B. Management of the parathyroid crisis. Am. J. Smg., 108: 183, 1964. HUTH, E. J. Primary hyperparathyroidism: The American
Journal of
Surgery
Functional Cystic Parathyroid Adenoma
10. 11. 12.
problems for clinician and chemist. Ann. Znt. Med., 57: 1062,1962. COPE, 0. Hyperparathyroidism : diagnosis and management. Am. J. Sura.. _ I 99: 394, 1960. EAIU, J. M., KURTZMAN,N. A., and MOSER, R. H. Hvnercalcemia and hvnertension. Ann. Znt. %ed., 64: 378,1966. ”_ HADDY, F. J., SCOTT, J. B., FLORIO, M., DAUGHERTY, R. M., JR., and HUIZENGA,
Vol. 118, July 1969
13. 14.
J. N. Local vascular effects of hypokalemia, alkalosis, hypercalcemia, and hypomagnesemia. Am. J. Physiol., 204: 202,1963. MOORE,W. T. and SMITH, L. H., JR. Experience with a calcium infusion test in narathyroid disease. Metabolism, 12: 447, 1963. BELLMAN.S. and ENGFELDT.B. Kidnev lesions in experimental hypervitaminosis D. A microradiographic and microangiographic study. Am. J. Roentgenol., 74: 288, 1955.
103
Primary hyperparathyroidism commonly results in symptoms related to the urinary tract, skeleton, or gastrointestinal tract, and the manifestations of the disease may vary from an extremely chronic nature to acute medical and surgical emergencies. Although the local signs of most tumors are usually emphasized as contributing to the appropriate diagnosis, this aspect has been de-emphasized in relation to parathyroid tumors to the point of misleading the unwary clinician. It used to be axiomatically suggested that if a patient with hyperparathyroidism had a lump in the neck, the lump was not a parathyroid tumor [1,21. The need to consider parathyroid adenoma in the differential diagnosis of tumors of the neck was emphasized in a recent review of 106 cases in which a mass in the neck was palpable [31. In almost one fourth of these the mass was the presenting symptom, but the parathyroid tusurprise.” Parathyroid mor was a “surgical cysts which are clinically apparent are extremely rare. The preoperative diagnosis has been made in only three cases [&s]. This report describes a patient with an unusually large cystic, functioning parathyroid adenoma which was additionally unique in that it presented as a rapidly enlarging mass after hemorrhage into the cyst. The importance of preoperative serum calcium determinations which allowed the correct diagnosis to be made and the relationship of hypercalcemia and hypertension are illustrated. Case Report A thirty-seven year old Caucasian man was first noted to have hypertension in January 1963. From the Department of Surgery, eral Hospital. El Paso. Texas. 100
William
Beaumont
Gen-
Before therapy, blood pressure ranged from 150/ 100 to 1701116 mm. Hg. After hospitalization and thorough evaluation, his diagnosis remained essential hypertension. Therapy with variable doses of chlorothiazide and reserpine controlled the hypertension in a range of 130/90 to 160/115 mm. Hg over the ensuing two years. In March 1966 a mass appeared suddenly in the left side of the neck and was slightly tender. The mass measured 7 by 5 cm. in diameter and was quite firm. It was initially believed that this represented hemorrhage into a thyroid cyst. Chest roentgenogram revealed deviation of the trachea. Protein-bound iodine and radioactive iodine uptake studies gave normal results. The thyroid scan revealed a “cold” area in the left lobe compatible with a thyroid cyst. (Fig. 1.) Thyroid suppression with exogenous thyroid was associated with some regression in the size of the lesion. Surgical excision was elected because of the large persisting mass. He was admitted to the hospital on May 9, 1965. Blood pressure was 142/88 mm. Hg and physical examination was within normal limits except for the mass in the left side of the neck and a rather dull mentation. Routine preoperative serum caIcium was 15.0 mg./lOO ml. (normal 8.5 to 10.5 mg.1100 ml.) and serum phosphorus was 2.2 mg./lOO ml., indicating the presence of hyperparathyroidism and implicating the palpable neck mass. All other electrolyte levels were normal. The electrocardiogram revealed a shortened Q-T interval compatible with hypercalcemia. Review of the original electrocardiogram taken in 1963 also demonstrated this abnormality. Roentgenograms revealed early demineralization of the skull and early bony resorption of the phalanges. The lamina dura was intact. Despite a low calcium diet, large fluid intake, and required ambulation, the serum calcium was 17.6 mg.1100 ml. with a serum phosphorus of 2.3 mg./lOO ml. on May 12. Further delay in surgery in the hope of lowering the serum calcium level seemed unwise. With continuous electrocardiographic monitoring, removal of a large The American
Journal of Surgery
Functional Cystic Parathyroid
Fig. 1. ““I thyroid scintigram demonstrating area of decreased function in the left lobe. Small round dot indicates center of the palpable mass. cystic adenoma of the left inferior parathyroid gland was accomplished without complication on May 13. The specimen consisted of an 85 gm. ovoid mass measuring ‘7 by 5 by 3 cm. with a smooth, shining red surface. (Fig. 2.) On cross section, 67 ml. of cloudy, red-brown fluid escaped from a single, large, central cystic cavity. (Fig. 3.) The wall of the cyst was red-brown interspersed with bright yellow and averaged 0.4 cm. in thickness. On microscopic examination (Fig. 4)) the tumor consisted of masses of uniform compact chief cells which only rarely displayed an acinar arrangement. Nuclei were small and round and cytoplasm was sparse with indistinct cystoplasmic borders. Mitotic figures were not seen. The stroma was scant and delicately fibrous with abundant small blood vessels. A few thick fibrous strands were present. Free and phagocytized hemosiderin pigment was scattered throughout the mass, representing resolving hemorrhage. The cyst was lined by cells identical to those comprising the remainder of the mass. Normal appearing parathyroid tissue
2 Fig. 2. shining
The gross specimen of the tumor surface measuring 7 by 5 by 3 cm.
On cross section the predominantly Fig. 3. arrows outline the cystic cavity. Vol.
118,July 1969
Adenoma
Photomicrograph of the tumor demonstrating a homogeneous pattern of uniform chief cells in a delicate fibrovascular stroma. (Hematoxylin and eosin stain; original magnification x 185.) Fig. 4.
was present outside the capsule and was compressed by the adenoma. Immediately after surgery, the serum calcium was 17.5 mg./lOO ml. and serum phosphorus 2.6 mg./lOO ml. The serum calcium level fell steadily to 8.0 mg./lOO ml. with phosphorus 4.0 mg./lOO ml. by May 16, 1965. Oral calcium was briefly required to maintain a normal serum calcium level and the electrocardiogram reverted to normal. Postoperative blood pressure ranged from 130/80 to 140/88 mm. Hg without medication. The patient remained normotensive and was transferred to the care of his referring physician ten weeks later.
Comments This case was unusual in several aspects which are worthy of emphasis. It has already been pointed out that the old axiom of a pal-
.~_.--._.-.--------_
3
illustrating
its ovoid shape and smooth
cystic nature
of the mass is evident;
101
Eat-II, Cohen, and Lundberg
pable mass in the neck not being a parathyroid adenoma needs to be discarded [9]. Clinically significant macroscopic parathyroid cysts are uneommon and the cysts are not usually associated with dysfunction of the parathyroids. Diagnosis of this very large functioning cystic adenoma was made even more confusing by hemorrhage into the cyst. This misled us into considering the more common diagnosis of hemorrhage into a thyroid cyst. The thyroid scan supported this diagnosis, and it was tempting to attribute some of the reduction in size to the exogenous thyroid therapy. The possibility of a parathyroid adenoma presenting as a “cold” thyroid nodule must always be considered [ 7’1.Accepting the concept that palpable masses in the neck may well be parathyroid adenomas, the decision to obtain preoperative serum calcium determinations is obvious and should reduce the number of “surgical surprises” [3]. As emphasized by this patient, the preoperative diagnosis is not just of academic interest but is very important to insure that preoperative preparation is optimal, and the anesthetist can be aware of the problem and prepared to cope with the increased risk of the hypercalcemic patient. The critical level of serum calcium is 17 to 18 mg./lOO ml., and over this, life-threatening parathyroid crisis commonly develops. Rising levels of calcium, phosphorus, and nonprotein nitrogen with a decrease in urinary volume are indications for immediate exploratory surgery [&!I. Electrolyte abnormalities are to be corrected as promptly as possible to avoid dehydration, acidosis which increases the percentage of ionized calcium, and alkalosis which can result in calcium precipitation. If the usual duration of symptoms is considered with the evidence that a diagnosis of hyperparathyroidism should be made in about 1 in 1,200 new patients [9], it is apparent that the diagnosis is commonly delayed or missed. The mere listing of some of the symptoms associated with only one complication such as hypercalcemia assists in explaining the difficulties in suspecting the diagnosis. Hypertension has rarely been emphasized and yet may be present in one third of patients with hypercalcemia [10,11]. In retrospect, the electrocardiogram in our patient suggested that hypercalcemia was present two years earlier. This hypertension was greatly improved by correction of the hypercalcemia. There is adequate basic re102
search to indicate that the calcium ion has a direct role in increasing vascular resistance 1121, and otherwise normal patients have been noted to become severely hypertensive during calcium infusion tests [IS]. Changes in renal function and structural renal damage in association with hypercalcemia are well documented [141 but the rapidity of onset of hypertension [IS], the reversibility [10,11], and the ability to produce hypertension in the isolated perfused limb Cl.21 suggest a more direct mechanism. Hypercalcemia should be added to the list of correctible types of hypertension. Summary An unusual case of hyperparathyroidism associated with an 85 gm. cystic functioning adenoma is described. The mass had enlarged suddenly and presented as a hemorrhagic thyroid cyst. Thyroid scintigram was compatible with a “cold” nodule of the thyroid gland. The correct diagnosis was made when a high serum calcium level was obtained in the immediate preoperative workup. Clinically palpable parathyroid adenomas occur often enough to justify routine serum calcium and phosphorus determinations in patients who present with masses in the neck, and hypercalcemia should be considered in the differential diagnosis in hypertensive patients. References 1.
2.
ALBRIGHT,F. Further experience in the diagnosis of hyperparathyroidism including a discussion of cases with a minimal degree of hyperparathyroidism. Am. J. M. Sci., 193: 800,1937. SCHNEIDER,R. W. and ROBINETT,A. H. Diag-
nosis
of
Cleveland
3.
obscure Clin. Quart.,
SOLOMON,M. Palpable J. Louieiccna
hyperparathyroidism. 18 : 66, 1951. parathyroid
M. SOL. 116
tumors.
: 214. 1964.
4.
SHIELDS,T. W. and ST~LEY,C. J. Functioning ;;ac;thyroid cysts. Arch. Surg., 82: 937,
5.
WEEKS, P. M. Clinically significant para& thyroid cysts: case report and review of literature. Am. Surgeon, 31: 366,1965. MCCORMACK,K. R. An unusual “thyroid” nodule “cold” to scintiscan. California Med.,
6.
103:
7.
8. 9.
282,1966.
ARNAIJD, C. D., WALKER, J. A., and EWER, R. W. Primary hyperparathyroidism associated with a cystic lesion in the neck: probable parathyroid cyst. J. Clin. Endocrinol., 21: 833, 1961. HENLEY, R. B. Management of the parathyroid crisis. Am. J. Smg., 108: 183, 1964. HUTH, E. J. Primary hyperparathyroidism: The American
Journal of
Surgery
Functional Cystic Parathyroid Adenoma
10. 11. 12.
problems for clinician and chemist. Ann. Znt. Med., 57: 1062,1962. COPE, 0. Hyperparathyroidism : diagnosis and management. Am. J. Sura.. _ I 99: 394, 1960. EAIU, J. M., KURTZMAN,N. A., and MOSER, R. H. Hvnercalcemia and hvnertension. Ann. Znt. %ed., 64: 378,1966. ”_ HADDY, F. J., SCOTT, J. B., FLORIO, M., DAUGHERTY, R. M., JR., and HUIZENGA,
Vol. 118, July 1969
13. 14.
J. N. Local vascular effects of hypokalemia, alkalosis, hypercalcemia, and hypomagnesemia. Am. J. Physiol., 204: 202,1963. MOORE,W. T. and SMITH, L. H., JR. Experience with a calcium infusion test in narathyroid disease. Metabolism, 12: 447, 1963. BELLMAN.S. and ENGFELDT.B. Kidnev lesions in experimental hypervitaminosis D. A microradiographic and microangiographic study. Am. J. Roentgenol., 74: 288, 1955.
103