å¡ CASE REPORT å¡ Multiple Endocrine Neoplasia Type 2A Hiroyuki Shimizu, Yuuji Ueda, Katsutoshi Makino, Hirofumi Fujioka, Masayuki Hamada, Masayasu Kanamaru, Tetsuya Murata*, Masaki Fujioka**, Tokuji Konishi and Takeshi Nakano A 40-year-old woman was admitted with complaints of headache, palpitation and diaphore sis. She had undergone right hemithyroidectomy 12 years previously. Histological reexamination of the operative specimen revealed a medullary thyroid carcinoma. Abdominal ultrasonography, CT scan and angiography showed bilateral adrenal tumors. Serum catecholamine levels in both adrenalexamination veins were high. Basedthe on diagnosis these data,ofbilateral adrenalectomyAfter was performed. Histological confirmed pheochromocytomas. operation, serum calcitonin and urinary noradrenaline levels were still high. Further examination by 131Imetaiodobenzylguanidine (MIBG) scintigraphy is planned. (Internal Medicine 31: 798-802, 1992) Key words: pheochromocytoma, medullary thyroid carcinoma, MEN 2A
Introduction
diaphoresis. The attacks had increased in frequency from April 1990. She was admitted to our hospital for The association with medullary thyroid carcinoma further evaluation in August 1990. and pheochromocytoma was reported by Sipple in Physical examination revealed a thin female with a 1961 (1). Since then about 100 patients in 40 families blood pressure of 220/120mmHg and a regular pulse have been reported in Japan. We report here a case of rate of 114/min. There was sweating of head, chest and multiple endocrine neoplasia type 2A (MEN 2A) as back, but the extremities were cold. The tongue and lips sociated with pheochromocytomas 12 years after right were normal. The right hemithyroidectomy scar was hemithyroidectomy. present and no mass in the left thyroid lobe was palpable. No cervical lymph nodes were palpable. The chest was Case Report clear to percussion and auscultation. Abdomen was soft and flat. No palpable abdominal masses or organomegaly A 40-year-old woman was admitted with complaints were noted. Neurological examination was non-focal. of headache, palpitation and diaphoresis. Her family Urinalysis showed positive tests for glucose and history revealed that her father had diabetes mellitus protein. Laboratory evaluation revealed leukocytosis and her mother had died of cerebral bleeding at the age and erythrocytosis. Glucose tolerance test (75 gm) was of 34. Her three children were referred to our medical borderline (Table 1). Twenty-four hour urinary cat unit for screening for MEN 2A. Her oldest son aged 18 echolamine assay showed definite elevations of adrena had normal urinary catecholamines (adrenaline 10.6 fig/ line, noradrenaline, metanephrine, normetanephrine day, noradrenaline 92.8 /^g/day, dopamine 220.1 /xg/day) and vanillylmandelic acid; serum calcitonin was also elevated serum calcitonin (280 pg/ml) and enlarged right elevated (Table 2). An electrocardiogram and chromo adrenal gland (60 x 41 x 10mm). Tetragastrin test was somal analysis were normal. Funduscopic examination attempted, but discontinued due to side effects. Further revealed severe hypertensive changes. Abdominal At the age of years this patient had undergone evaluation is 28 planned. ultrasonography and CT scan showed a left adrenal right hemithyroidectomy, but at that the histological mass of ll x 7cm including necrotic tissue with a de examination was misdiagnosed. In the summer of 1989 fined margin and slightly enlarged right adrenal gland she began to have attacks of headache, palpitation and (Figs. 1 , 2). Adrenal arteriography revealed a left adrenal tumor stainHospital, of llcm inSuzuka diameter an enlarged right From the Department of Internal Medicine and ^Pathology, Chusei General andand **the First Department of Internal Med Mie University School of Medicine, Tsu Received for publication October 2, 1991; Accepted for publication February 18, 1992 Reprint requests should be addressed to Dr. Hiroyuki Shimizu, the Department of Internal Medicine, Chusei General Hospital, 8-28-30 K Suzuka 513, Japan 798
Internal
Medicine
Vol. 31, No. 6 (June
1992)
Multiple Table 1.
Laboratory
Findings
Urinalysis Protein (2+ ) Glucose (3 + ) Hematological data WB C 23 ,000/mm3 RBC 616 x 104/mm3 Hb 17.8 g/dl Ht 54.9% Platelet 30.2 x 104/mm3 Erythrocyte sedimentation rate 2 mm/h Serological data C-reactive protein O.O mg/dl Tumor marker Carcinoembryonic antigen 2.9 ng/ml 75 g Glucose tolerance test B S Insulin pre 113 4.9 30 min 194 9.8 60 min 181 43.9 90 min 147 57.6 120 min 128 32.4
Table 2.
Endocrine Neoplasia
Type 2A
on Admission
Chemistry TP 8.9 g/dl Alb 4.9 g/dl GOT 30 IU/1 GPT 22 IU/1 LDH 847 IU/1 CPK 245 IU/1 ALP 287 IU/1 y-GTP 38 IU/1 Ch-E 1.46APH T-C 219 mg/dl FBS 112 mg/dl BUN 12 mg/dl Cr l.l mg/dl Creatinine clearance 101.8 ml/min Na 144 mEq/l K 4.8 mEq/l Cl lOO mEq/1 Ca 9.1 mg/dl P 3.9mg/dl
Fig. 1.
Abdominal
ultrasonography
showing a left adrenal
mass.
Endocrine Function Tests
preop S e ru m N o ra d re n a lin e A d r e n a lin e U ri n e N o ra d re n a lin e A d re n a lin e D o p am in e N o rm eta n e p h ri n e M e ta n ep h rin e V a n illy lm a n d elic a cid S eru m c aicito n in P a ra th y ro id h o rm o n e C -fra g m e n t R e n in A ld o ste ro n e C o rtiso l A d re n o co rtic o tro p ic h o rm o n e F re e -T 3 F re e -T 4 T h y ro id stim u la tin g h o rm o n e
4 1 .0 3 1 6 .4 0 > 2 0 0 0 .0 > 2 0 0 .0 6 3 6 .3 3 0 .3 4 4 6 .9 6 1 .0 13 0 0 .5 7 .9 790 6 2 .0 46 3 .1 1 .3 1 5 .7
postop 0 .2 9 n g /m l < 0 .0 1 n g /m J 2 9 7 .5 w g /d 0 .5 /ig /d 2 2 2 5 .3 u g /d 0 .7 3 m g /d 0 .0 1 m g /d 5 .4 m g /d l l O p g /m l 0 .3 n g /m l - n g /m l/h < 1 0 p g /m l < 1 .0 /ig /d l - p g /m l 3 .2 p g /m l 1 .2 0 n g /d l 4 .4 w U /m l
adrenal medulla (Fig. 3). Bilateral adrenal venous blood samplings yielded high values of adrenaline and nor adrenaline (Fig. 4). A small pheochromocytoma was suspected in the right adrenal gland. Thyroid radiography showed no calcifications within the left lobe. Thyroid scintigraphy by 99mTechnetium demonstrated no cold nodules. Ultrasonography and CT scan of the left thyroid lobe showed a cystic tumor, 8mm in diameter. The fine needle aspiration cytology of this tumor was negative for malignant cells. Reviewing the right thyroid specimen taken 12 years previously, that the Internal Medicine Vol. 31, No. it6 was (June discovered 1992)
Fig. 2. CT scan ofthe abdomen showing a left adrenal mass including necrotic tissue with a defined margin and slightly enlarged right adrenal gland. medium sized tumor cells were arranged in sheets. The stroma was abundant, eosinophilic and hyalinized. The cells had hyperchromatic nuclei and a lightly stained cytoplasm (Fig.data, 5). MEN 2A accompanied with Based on these medullary thyroid carcinoma and pheochromocytoma was diagnosed, ar-blockade and ^-blockade therapy was started, but it was difficult control theOn hypertension. Bilateral adrenalectomy wastoperformed. examination of the operative specimen, the left adrenal tumor was solid, 10.0x7.Ox5.8cm in size encapsulated with fibrous tissue, and the sectioned surface was red-brown. The right adrenal medulla was slightly enlarged. On histological examination of the operative specimen, large polygonal tumor cells were arranged in sheets supported by a vascular connective tissue stroma (Fig. 6). The cytoplasm was eosinophilic. Multinuclear giant 799
Shimizu et al
Fig. 3. Adrenal arteriography showing enlarged right adrenal medulla (left) and left adrenal tumor stain (right).
Fig. 4. The measurement of adrenaline (A) and noradrenaline (NA) (ng/ml) at the first time (left) and the second time (right). IVC: inferior vena cava, LAV: left adrenal vein, LRV: left renal vein, RAV: right adrenal vein, RRV: right renal vein. cells and hemorrhagic necrosis were sporadically seen. On microscopic examination, the diagnosis of pheo chromocytoma was confirmed. The right adrenal tumor was borderline between adrenal medullary hyperplasia and pheochromocytoma. After the operation, transient hypoglycemic attacks
1,300pg/ml after intravenous injection of tetragastrin. Medullary carcinoma in the left thyroid lobe is suspected, and thus thyroidectomy is being contemplated.
were well controlled by glucose replacement therapy. Intravenous hydrocortisone administration was started with an initial dose of 600 mg daily and tapered of within 15 days. Subsequently, 20mg of oral hydrocortisone administration was started as a maintenance therapy. Serum calcitonin level was increased from HOpg/ml to
MEN 2A has been reported to be either familial or sporadic type. The familial type is transmitted as an autosomal dominant trait with a high degree of pen etrance. Sporadic cases show the possibility of new mutations. In the present case, according to the family screening examination, her oldest son was suspected
800
Discussion
Internal
Medicine
Vol. 31, No. 6 (June
1992)
Multiple
Endocrine Neoplasia
Type 2A
corticosteroid replacement therapy is necessary after bilateral adrenalectomy, it is thought that the con tralateral adrenal gland should be preserved. Tibblin et al reported that tumors exceeding 5cm in diameter carry a greater risk for bilateral involvement (5). In these patients, bilateral adrenalectomy should be considered as the first surgical intervention. In the present case, the tumor involvement in the right adrenal gland was unclear, thus the decision of whether or not to remove the right adrenal gland was controversial. From the re sults of the bilateral adrenal venous blood catecholamine levels, we considered that the pheochromocytomas oc curred bilaterally and therefore performed bilateral Fig. 5. Microscopic observation of thyroid specimen showing adrenalectomy. Medullary hyperplasia may be an early medium sized tumor cells arranged in sheets. The stroma is large and manifestation of pheochromocytoma in NEN 2A and hyalinized (HE x lOO). may develop into pheochromocytoma in the course of time (6). In the present case the right adrenal gland was histologically diagnosed as borderline between Extra-adrenal medullary hyperplasia pheochromocytomas and pheochromocytoma. lack the enzyme If no adrenalectomy which converts had noradrenaline been performed to adrenaline, , pheochromocytoma therefore in adrenal the urinary adrenaline would havepheochromocytoma developed. level is high. On the other hand, in extra-adrenal pheo chromocytoma theofurinary noradrenaline level is high. The measurement adrenaline and noradrenaline can determine the localization of the tumor to some degree. In this case after adrenalectomy, only the urinary noradrenaline level was high. It may be considered a compensatory change, but the coexistence of extra adrenal pheochromocytoma cannot be denied. 131I Fig. 6. Histologically, the large polygonal tumor cells are arranged metaiodobenzylguanidine (MIBG) is structurally similar in sheets supported by vascular connective tissue stroma (HE X200). to noradrenaline and guanethidine and MIBG uptake by a tumor can be accepted as the evidence for a neuro of MEN 2A due to the high value of serum calcitonin endocrine tumor (7). Recently, the localization of extra and enlargement of the right adrenal gland. Likewise adrenal or metastatic pheochromocytoma is probably therefore, the present patient was considered to be best achieved by MIBG scintigraphy. This technique familial MEN 2A. Her mother died of cerebral bleeding facilitates screening of the whole body with a high spe at the young age of 34. It appears that MEN 2A was cificity for this tumor (8, 9). In the present patient, the inherited from her mother. This patient had been mis fine-needle aspiration cytology of the left thyroid mass diagnosed as papillary thyroid carcinoma 12 years earlier, was negative, but based on the elevated serum calcitonin so thus did not undergo the screening for MEN 2A after level and the response to the tetragastrin test, medullary the hemithyroidectomy. The pheochromocytomas were thyroid carcinoma is strongly suspected. In patients with According discoveredto12previous years after reports, hemithyroidectomy thyroid carcinoma as a pro MEN 2A, MIBG scintiscan is useful not only in detecting gression of the natural course of found the disease. and pheochromocytoma can be to coexist (2). associated pheochromocytoma, but also in diagnosing When the two occur at different times, the discovery medullary thyroid carcinoma (10). MIBG scintigraphy References of the medullary thyroid carcinoma precedes that of is planned for the present patient in the near future. pheochromocytoma more frequently (2). Pheochromo Sipple JH. The association of pheochromocytoma with carcinoma of the thyroid gland. Am J Med 31: 163, 1961. cytoma is bilateral in about 70% of MEN 2A (3). Surgical Yamanaka Y, Yamasaki S, Hikita T, Matsuura K, Araki K, treatment of pheochromocytoma involves unilateral Ogata T. A case of multiple endocrine neoplasia type Ha. J Jpn Pract Surg Soc 48(7): 935, 1987 (in Japanese). adrenalectomy, subtotal adrenalectomy leaving the healthy portion, or bilateral adrenalectomy (4). Because Internal
Medicine
Vol. 31, No. 6 (June
1992)
801
Multiple Endocrine Neoplasia Type 2A 3) Morimoto S. 3 cases report and review of 62 cases in Japanese zylguanidine. J Nucl Med 26: 897, 1985. literature. 8) Chatal JF, Endocr Charbonnel Surg 4(2): B. Comparison 183, 1987 (inofJapanese). iodobenzylguanidine 4) imaging Shima with M, Watanabe computedH,tomography Igari D, et al. in locating Six casespheochromo of Sipple's syndrome. Shindan to Chiryou 62:61: 1059, (in Japanese). cytoma. J Clin Endocrinol Metab 769,1974 1985. 5) Shapiro 9) Tibblin S, B,Berg CoppM, JE,Ingemansson Sisson JC, Eyre S. Surgical PL, Wallis treatment J, Beierwaltes of pheochromocytoma WH. Iodine-131 inmetaiodobenzylguanidine MEN IIA. World J Surg 5:for 458, the1981. locating of 6) Carney JA, Sizemore GW, Sheps SG. Adrenal disease suspected pheochromocytoma: experience in 400medullary cases. J Nucl in multiple endocrine Med 26: 576, 1985. neoplasia, type 2. Pheochromocytoma and its precursors. 10) Baulieu JL,Am Guilloteau J Clin Pathol D, Delisle 66: 279, MJ,1976. et al. Radioiodinated 7) Tobes MC, Jaques S, Wieland Sisson JC. Effectcancer. of uptake metaiodobenzylguanidine uptakeDM, in medullary thyroid one inhibitors Cancer 60: 2189, on the 1987. uptake of norepinephrine and metaiodoben-
802
Internal
Medicine
Vol. 31, No. 6 (June
1992)
Introduction
diaphoresis. The attacks had increased in frequency from April 1990. She was admitted to our hospital for The association with medullary thyroid carcinoma further evaluation in August 1990. and pheochromocytoma was reported by Sipple in Physical examination revealed a thin female with a 1961 (1). Since then about 100 patients in 40 families blood pressure of 220/120mmHg and a regular pulse have been reported in Japan. We report here a case of rate of 114/min. There was sweating of head, chest and multiple endocrine neoplasia type 2A (MEN 2A) as back, but the extremities were cold. The tongue and lips sociated with pheochromocytomas 12 years after right were normal. The right hemithyroidectomy scar was hemithyroidectomy. present and no mass in the left thyroid lobe was palpable. No cervical lymph nodes were palpable. The chest was Case Report clear to percussion and auscultation. Abdomen was soft and flat. No palpable abdominal masses or organomegaly A 40-year-old woman was admitted with complaints were noted. Neurological examination was non-focal. of headache, palpitation and diaphoresis. Her family Urinalysis showed positive tests for glucose and history revealed that her father had diabetes mellitus protein. Laboratory evaluation revealed leukocytosis and her mother had died of cerebral bleeding at the age and erythrocytosis. Glucose tolerance test (75 gm) was of 34. Her three children were referred to our medical borderline (Table 1). Twenty-four hour urinary cat unit for screening for MEN 2A. Her oldest son aged 18 echolamine assay showed definite elevations of adrena had normal urinary catecholamines (adrenaline 10.6 fig/ line, noradrenaline, metanephrine, normetanephrine day, noradrenaline 92.8 /^g/day, dopamine 220.1 /xg/day) and vanillylmandelic acid; serum calcitonin was also elevated serum calcitonin (280 pg/ml) and enlarged right elevated (Table 2). An electrocardiogram and chromo adrenal gland (60 x 41 x 10mm). Tetragastrin test was somal analysis were normal. Funduscopic examination attempted, but discontinued due to side effects. Further revealed severe hypertensive changes. Abdominal At the age of years this patient had undergone evaluation is 28 planned. ultrasonography and CT scan showed a left adrenal right hemithyroidectomy, but at that the histological mass of ll x 7cm including necrotic tissue with a de examination was misdiagnosed. In the summer of 1989 fined margin and slightly enlarged right adrenal gland she began to have attacks of headache, palpitation and (Figs. 1 , 2). Adrenal arteriography revealed a left adrenal tumor stainHospital, of llcm inSuzuka diameter an enlarged right From the Department of Internal Medicine and ^Pathology, Chusei General andand **the First Department of Internal Med Mie University School of Medicine, Tsu Received for publication October 2, 1991; Accepted for publication February 18, 1992 Reprint requests should be addressed to Dr. Hiroyuki Shimizu, the Department of Internal Medicine, Chusei General Hospital, 8-28-30 K Suzuka 513, Japan 798
Internal
Medicine
Vol. 31, No. 6 (June
1992)
Multiple Table 1.
Laboratory
Findings
Urinalysis Protein (2+ ) Glucose (3 + ) Hematological data WB C 23 ,000/mm3 RBC 616 x 104/mm3 Hb 17.8 g/dl Ht 54.9% Platelet 30.2 x 104/mm3 Erythrocyte sedimentation rate 2 mm/h Serological data C-reactive protein O.O mg/dl Tumor marker Carcinoembryonic antigen 2.9 ng/ml 75 g Glucose tolerance test B S Insulin pre 113 4.9 30 min 194 9.8 60 min 181 43.9 90 min 147 57.6 120 min 128 32.4
Table 2.
Endocrine Neoplasia
Type 2A
on Admission
Chemistry TP 8.9 g/dl Alb 4.9 g/dl GOT 30 IU/1 GPT 22 IU/1 LDH 847 IU/1 CPK 245 IU/1 ALP 287 IU/1 y-GTP 38 IU/1 Ch-E 1.46APH T-C 219 mg/dl FBS 112 mg/dl BUN 12 mg/dl Cr l.l mg/dl Creatinine clearance 101.8 ml/min Na 144 mEq/l K 4.8 mEq/l Cl lOO mEq/1 Ca 9.1 mg/dl P 3.9mg/dl
Fig. 1.
Abdominal
ultrasonography
showing a left adrenal
mass.
Endocrine Function Tests
preop S e ru m N o ra d re n a lin e A d r e n a lin e U ri n e N o ra d re n a lin e A d re n a lin e D o p am in e N o rm eta n e p h ri n e M e ta n ep h rin e V a n illy lm a n d elic a cid S eru m c aicito n in P a ra th y ro id h o rm o n e C -fra g m e n t R e n in A ld o ste ro n e C o rtiso l A d re n o co rtic o tro p ic h o rm o n e F re e -T 3 F re e -T 4 T h y ro id stim u la tin g h o rm o n e
4 1 .0 3 1 6 .4 0 > 2 0 0 0 .0 > 2 0 0 .0 6 3 6 .3 3 0 .3 4 4 6 .9 6 1 .0 13 0 0 .5 7 .9 790 6 2 .0 46 3 .1 1 .3 1 5 .7
postop 0 .2 9 n g /m l < 0 .0 1 n g /m J 2 9 7 .5 w g /d 0 .5 /ig /d 2 2 2 5 .3 u g /d 0 .7 3 m g /d 0 .0 1 m g /d 5 .4 m g /d l l O p g /m l 0 .3 n g /m l - n g /m l/h < 1 0 p g /m l < 1 .0 /ig /d l - p g /m l 3 .2 p g /m l 1 .2 0 n g /d l 4 .4 w U /m l
adrenal medulla (Fig. 3). Bilateral adrenal venous blood samplings yielded high values of adrenaline and nor adrenaline (Fig. 4). A small pheochromocytoma was suspected in the right adrenal gland. Thyroid radiography showed no calcifications within the left lobe. Thyroid scintigraphy by 99mTechnetium demonstrated no cold nodules. Ultrasonography and CT scan of the left thyroid lobe showed a cystic tumor, 8mm in diameter. The fine needle aspiration cytology of this tumor was negative for malignant cells. Reviewing the right thyroid specimen taken 12 years previously, that the Internal Medicine Vol. 31, No. it6 was (June discovered 1992)
Fig. 2. CT scan ofthe abdomen showing a left adrenal mass including necrotic tissue with a defined margin and slightly enlarged right adrenal gland. medium sized tumor cells were arranged in sheets. The stroma was abundant, eosinophilic and hyalinized. The cells had hyperchromatic nuclei and a lightly stained cytoplasm (Fig.data, 5). MEN 2A accompanied with Based on these medullary thyroid carcinoma and pheochromocytoma was diagnosed, ar-blockade and ^-blockade therapy was started, but it was difficult control theOn hypertension. Bilateral adrenalectomy wastoperformed. examination of the operative specimen, the left adrenal tumor was solid, 10.0x7.Ox5.8cm in size encapsulated with fibrous tissue, and the sectioned surface was red-brown. The right adrenal medulla was slightly enlarged. On histological examination of the operative specimen, large polygonal tumor cells were arranged in sheets supported by a vascular connective tissue stroma (Fig. 6). The cytoplasm was eosinophilic. Multinuclear giant 799
Shimizu et al
Fig. 3. Adrenal arteriography showing enlarged right adrenal medulla (left) and left adrenal tumor stain (right).
Fig. 4. The measurement of adrenaline (A) and noradrenaline (NA) (ng/ml) at the first time (left) and the second time (right). IVC: inferior vena cava, LAV: left adrenal vein, LRV: left renal vein, RAV: right adrenal vein, RRV: right renal vein. cells and hemorrhagic necrosis were sporadically seen. On microscopic examination, the diagnosis of pheo chromocytoma was confirmed. The right adrenal tumor was borderline between adrenal medullary hyperplasia and pheochromocytoma. After the operation, transient hypoglycemic attacks
1,300pg/ml after intravenous injection of tetragastrin. Medullary carcinoma in the left thyroid lobe is suspected, and thus thyroidectomy is being contemplated.
were well controlled by glucose replacement therapy. Intravenous hydrocortisone administration was started with an initial dose of 600 mg daily and tapered of within 15 days. Subsequently, 20mg of oral hydrocortisone administration was started as a maintenance therapy. Serum calcitonin level was increased from HOpg/ml to
MEN 2A has been reported to be either familial or sporadic type. The familial type is transmitted as an autosomal dominant trait with a high degree of pen etrance. Sporadic cases show the possibility of new mutations. In the present case, according to the family screening examination, her oldest son was suspected
800
Discussion
Internal
Medicine
Vol. 31, No. 6 (June
1992)
Multiple
Endocrine Neoplasia
Type 2A
corticosteroid replacement therapy is necessary after bilateral adrenalectomy, it is thought that the con tralateral adrenal gland should be preserved. Tibblin et al reported that tumors exceeding 5cm in diameter carry a greater risk for bilateral involvement (5). In these patients, bilateral adrenalectomy should be considered as the first surgical intervention. In the present case, the tumor involvement in the right adrenal gland was unclear, thus the decision of whether or not to remove the right adrenal gland was controversial. From the re sults of the bilateral adrenal venous blood catecholamine levels, we considered that the pheochromocytomas oc curred bilaterally and therefore performed bilateral Fig. 5. Microscopic observation of thyroid specimen showing adrenalectomy. Medullary hyperplasia may be an early medium sized tumor cells arranged in sheets. The stroma is large and manifestation of pheochromocytoma in NEN 2A and hyalinized (HE x lOO). may develop into pheochromocytoma in the course of time (6). In the present case the right adrenal gland was histologically diagnosed as borderline between Extra-adrenal medullary hyperplasia pheochromocytomas and pheochromocytoma. lack the enzyme If no adrenalectomy which converts had noradrenaline been performed to adrenaline, , pheochromocytoma therefore in adrenal the urinary adrenaline would havepheochromocytoma developed. level is high. On the other hand, in extra-adrenal pheo chromocytoma theofurinary noradrenaline level is high. The measurement adrenaline and noradrenaline can determine the localization of the tumor to some degree. In this case after adrenalectomy, only the urinary noradrenaline level was high. It may be considered a compensatory change, but the coexistence of extra adrenal pheochromocytoma cannot be denied. 131I Fig. 6. Histologically, the large polygonal tumor cells are arranged metaiodobenzylguanidine (MIBG) is structurally similar in sheets supported by vascular connective tissue stroma (HE X200). to noradrenaline and guanethidine and MIBG uptake by a tumor can be accepted as the evidence for a neuro of MEN 2A due to the high value of serum calcitonin endocrine tumor (7). Recently, the localization of extra and enlargement of the right adrenal gland. Likewise adrenal or metastatic pheochromocytoma is probably therefore, the present patient was considered to be best achieved by MIBG scintigraphy. This technique familial MEN 2A. Her mother died of cerebral bleeding facilitates screening of the whole body with a high spe at the young age of 34. It appears that MEN 2A was cificity for this tumor (8, 9). In the present patient, the inherited from her mother. This patient had been mis fine-needle aspiration cytology of the left thyroid mass diagnosed as papillary thyroid carcinoma 12 years earlier, was negative, but based on the elevated serum calcitonin so thus did not undergo the screening for MEN 2A after level and the response to the tetragastrin test, medullary the hemithyroidectomy. The pheochromocytomas were thyroid carcinoma is strongly suspected. In patients with According discoveredto12previous years after reports, hemithyroidectomy thyroid carcinoma as a pro MEN 2A, MIBG scintiscan is useful not only in detecting gression of the natural course of found the disease. and pheochromocytoma can be to coexist (2). associated pheochromocytoma, but also in diagnosing When the two occur at different times, the discovery medullary thyroid carcinoma (10). MIBG scintigraphy References of the medullary thyroid carcinoma precedes that of is planned for the present patient in the near future. pheochromocytoma more frequently (2). Pheochromo Sipple JH. The association of pheochromocytoma with carcinoma of the thyroid gland. Am J Med 31: 163, 1961. cytoma is bilateral in about 70% of MEN 2A (3). Surgical Yamanaka Y, Yamasaki S, Hikita T, Matsuura K, Araki K, treatment of pheochromocytoma involves unilateral Ogata T. A case of multiple endocrine neoplasia type Ha. J Jpn Pract Surg Soc 48(7): 935, 1987 (in Japanese). adrenalectomy, subtotal adrenalectomy leaving the healthy portion, or bilateral adrenalectomy (4). Because Internal
Medicine
Vol. 31, No. 6 (June
1992)
801
Multiple Endocrine Neoplasia Type 2A 3) Morimoto S. 3 cases report and review of 62 cases in Japanese zylguanidine. J Nucl Med 26: 897, 1985. literature. 8) Chatal JF, Endocr Charbonnel Surg 4(2): B. Comparison 183, 1987 (inofJapanese). iodobenzylguanidine 4) imaging Shima with M, Watanabe computedH,tomography Igari D, et al. in locating Six casespheochromo of Sipple's syndrome. Shindan to Chiryou 62:61: 1059, (in Japanese). cytoma. J Clin Endocrinol Metab 769,1974 1985. 5) Shapiro 9) Tibblin S, B,Berg CoppM, JE,Ingemansson Sisson JC, Eyre S. Surgical PL, Wallis treatment J, Beierwaltes of pheochromocytoma WH. Iodine-131 inmetaiodobenzylguanidine MEN IIA. World J Surg 5:for 458, the1981. locating of 6) Carney JA, Sizemore GW, Sheps SG. Adrenal disease suspected pheochromocytoma: experience in 400medullary cases. J Nucl in multiple endocrine Med 26: 576, 1985. neoplasia, type 2. Pheochromocytoma and its precursors. 10) Baulieu JL,Am Guilloteau J Clin Pathol D, Delisle 66: 279, MJ,1976. et al. Radioiodinated 7) Tobes MC, Jaques S, Wieland Sisson JC. Effectcancer. of uptake metaiodobenzylguanidine uptakeDM, in medullary thyroid one inhibitors Cancer 60: 2189, on the 1987. uptake of norepinephrine and metaiodoben-
802
Internal
Medicine
Vol. 31, No. 6 (June
1992)
