J. Endocrinol. Invest. 14: 499-502, 1991
CASE REPORT
Association of athyrotropin-secreting pituitary adenoma and athyroid follicular carcinoma A.L. Calle-Pascual*, E. Yuste*, P. Martin*, T. Aramendi**, M.L. Garcia-Maurino**, J. Argente***, M.J. Catalan***, J. Uria****, J.A. Cabranes*****, and A.L. Charro***** *Unidad de Endocrinologia y Nutricion, **Seccion de Anatomia Patologica, and ***Unidad de Neurologia, Hospital Ntra Sra de Sonsoles, Avila, Universidad de Salamanca; ****Servicio de Neurocirugia, Clinica Puerta de Hierro, and *****Servicio de Endocrinologia y Medicina Nuclear, Hospital Clinico San Carlos, Madrid, Spain ABSTRACT. The different factors involved as etiological agents in thyroid cancer have in common long term thyroid follicle stimulation. On this base, a patient with a TSH-producing pituitary adenoma could be at high risk for developing thyroid cancer. A patient consulting for a single thyroid nodule was
studied in our unit. He was diagnosed as having a TSH-producing pituitary adenoma and the Thyroid nodule was shown to be a follicular carcinoma following removed. We speculate that elevated TSH levels could have contributed to neoplastic transformation of the thyroid in this patient.
INTRODUCTION
THYROID HORMONE ASSAYS
Although the etiology of thyroid cancer remains unknown, several factors have been considered to be related to its onset and development. Among others, these include iodine deficiency, prolonged administration of goitrogens, and external radiation or radioactive iodine (1). A common factor to these conditions could be chronic TSH stimulation ·of the thyroid. After long-term stimulation and given the heterogeneity of thyroid follicular cells (2), hyperplasia, adenoma and carcinoma could be a rational sequence. Several facts support this theory: the exposure to goitrogens can produce tumoral cellular clones (3); the tumor relapses disappear following inhibition of TSH by L-T4 administration (4), and medical suppression of TSH secretion is the mainstay of treatment for most cases of differentiated thyroid carcinoma (5). We have recently had the opportunity to study a patient in whom a TSH-producing pituitary adenoma.and a thyroidal follicular carcinoma coincided.
TSH was measured by immunoradiometric assay using a commercial kit, ELSA 2 TSH (CIS bioindustries, France). ELSA 2 TSH is a solid-phase two sites immunoradiometric assay. Two mouse monoclonal anti b-TSH antibodies were prepared against sterically remote antigenic sites on the molecule. The antibodies used in the test do not present any crossreaction with structurally related substances (LH, FSH, HCG). The sensitivity was 0.02 IlUI/ml. The intraassay variations coefficient at 0.9 IlUI/ml level was 3.5% and at 8.3 IlUI/ml level was 2.9%. Interassay variations were 3.8% and 4.6%, respectively. Radioimmunoassays of total T4 and total T3 were done using commercial kits provided from Abbott Cientifica SA, Madrid, Spain and from Diagnostic Products Corporation, Los Angeles, CA, U.S.A. Intraassay variation coefficients were 5.8% for T4 and 6% for T3, and the interassay variation coefficients were 3.5% and 7% respectively. The Free T41ndex (FT41) was done using T3 resin uptake. CASE REPORT V.B.G. was a 55 years old man who had been sent to the Endocrinology and Nutrition Unit for further studies of an enlarged sella turcica and a single thyroid nodule. He had been diagnosed and treated by the neu-
Key-Words: TSH pituitary adenoma, thyroid cancer. Correspondence: A.L. Calle-Pascual, Servicio de Endocrinologia y Nutricion, Hospital Clinico de San Carlos, Plaza de Cristo Rey sIn. 28040 Madrid, Spain. Received September 6, 1990; accepted February 28, 1991 .
499
A.L. Calle-Pascual, E. Yuste, P. Martin, et al.
99mTc thyroid scan revealed a cold area in the left thyroid lobe coinciding with the palpated nodule. Thyroid hormones, taken to another laboratory, were: T4 =207.69 nmol/I (N, 56-155) T3 =3.9 ng/ml (N , 0.82.1), FT4 1=192.2 (N,64-155) and TSH=4.9 mUI/1 (N, 0.45-6.2). In our laboratory were: T4 =183.2 nmol/I (N , 65-170), T3= 3.4 ng/ml (N, 0.8-1.9), FT4 1=172 (N, 68154) and TSH=3.5 miU/1 (N, 0.3-3.6). Cytology after fine needle aspiration was suspicious of thyroid follicular carcinoma. Skull X-rays revealed a generalized increase of sellar size without changes of its wall. Contrast sella CT scan showed a hypophyseal mass with suprasellar extension (Fig. 1). A pituitary reserve study was performed using four stimuli : a) GRF (100 /J-g), b) GnRH (100 /J-g), c) TRH (300 /J-g) , and d) 0.1 IU regular insulin/kg body weight. Basal HGH (N, 010) rose from 1.1 /J-g/I to 9.3 /J-g/1. Basal LH (N, 525) increased from 2.2 IU/I to 5.3 IU/I and basal FSH (N, 5-20) from 3 IU/I to 3.7 IU/I. ACTH (N , 1580 pg/ml) was undetectable and did not vary. Basal cortisol (N, 160-700) rose from 62.3 nmol/I to 112.8 nmol/I, basal TSH from 6.3 miU/1 to 9.9 miU/1 and PRL levels (N, 5-20 /J-g/I) of 25 /J-g/I remained constant. GRF (100 /J-g), TRH (300 /J-g) and somatostatin (infusion of 500 /J-g from time 0 to 120 min .) tests were performed during three nonconsecutive days, in order to evaluate PRL and TSH responses. These results are displayed in Table 1. The patient underwent a total thyroidectomy. The 102 g total thyroidectomy specimen consisted of the left lobe, the isthmus and the right lobe. The thyroid parenchima in the 7x5.5x5 cm . left lobule was almost entirely replaced by a soft, pale, partially necrotic well encapsulated 4x4x5 cm nodule. The nodule was composed of small size follicles with variable amount of colloid . Considerable variation in the size and shape of the cells was seen in focal areas. Small areas of necrosis were identified. Focal capsular invasion was demonstrated. The diagnostic of follicular carcinoma of the thyroid was estab-
Fig. 1 - Sellar CT scan with contrast media shows an intrasellar mass, that takes up the contrast in an inhomogeneous way and that grows outside the limits of the sella anteriorly and towards the right side.
rologist for Parkinson's disease. He had lived in a non-goiter-endemic area. Since the last year, he complained of weight loss (9 kg) , increase of his resting tremor, sleeping difficulties, and acceleration of his bowel habits . During two previous months he had noticed a nodule on the anterior region of the neck, with no other symptoms. The patient had to increase the doses of L-Dopa needed to control his Parkinson 's disease. The physical examination revealed a weight of 46 kg, height of 156 cm, 108 beats per minute and a blood pressure of 140/95 mmHg (supine). There were no signs of infiltrative ophthalmopathy . A 3x3 cm nodule was found occupying the left thyroid lobe. There were no adenopathies. The cardiovascular examination revealed rhythmic tachycardia. The abdomen was normal. His extremities displayed either a fine distal tremor or a gross tremor rest. Chest X-ray showed right tracheal displacement. A
Table 1 - PRL and TSH responses to administration of a bolus of GRF (100 I1g) and TRH (300l1g), and an infusion of somatostatin (500l1g from time 0 to 120 min), during three non consecutive days.
Stimulus GRF
TRH
Somatostatin
Hormone
-30
0
15
30
45
60
90
120
min
PRL
57
42
49
47
47
43
45
42
TSH
3.4
3.0
4.0
4.2
4.6
4.4
4.3
3.9
miU/1
PRL
59
41
50
49
49
43
48
fig/I
TSH
3.1
2.9
3.4
3.4
3.6
3.3
3.1
miU/1
I1g/1
PRL
45
46
43
43
60
49
45
42
I1g/1
TSH
3.0
3.2
2.9
3.0
3.1
2.8
2.8
2.9
miU/1
500
TSH pituitary adenoma and thyroid carcinoma
lished (Fig. 2a). Twenty-five days later, (T3 0.41 ng/ml, T4 64.5 nmol/I and TSH 27 mIU/I), 131 1 scan revealed a minimal eutopic uptake (6,000 cpm) having undetectable thyroglobulin levels, and the patient received a dose of 35 mCi of 1311. Fifteen days later the pituitary mass was excised by transsphenoidal route; the tumor showed a sinusoidal pattern with pseudorosette formation and palisading along vessels. The cells appeared chromophobic with HE enclosing few or no discernible granules with PAS stain (Fig. 2b). The patient remained asymptomatic with replacement therapy (hydrocortisone 10 mg q 8 h, levothyroxine 100 )lg q day, and a combination of carbidopa 25 mg and levodopa 100 mg q day). Six months later, on replacement therapy, T4 was 126.4 nmol/l, T3 was 0.7 ng/ml and TSH and thyroglobulin levels were undetectable. A triple stimuli (iv GnRH 100 )lg, GRF 100 )lg, and TRH 300 )lg) exhibited the following pattern: FSH rose from 4.0 lUll to 5.8 lUll; LH from 2.3 lUll to 6.1 lUll; HGH from undetectable to 2 )lg/l; PRL from 13.2 )lg/l to 22.8 )lg/l; TSH from undetectable to 0.9 mlU/I. The patient, one year after his initial surgery, continues asymptomatic and on replacement therapy with hydrocortisone and levothyroxine.
In addition he was diagnosed as having thyroidal follicular carcinoma after thyroidectomy specimen study. This association has never been reported in the literature. The order of surgery has not been established. In our patient, surgery on the thyroid was performed initially, permitting body scan without the need for exogenous TSH stimulation, facility ablative 131 1 doses. Forty days after thyroidectomy, when transsphenoidal surgery was performed, no evidence of accelerated pituitary tumor growth was observed. Our case supports the hypothesis that lengthy TSH stimulation of the thyroid can induce growth of susceptible follicular cells (2) until achieving malignant neoplastic transformation (3). A TSH-secreting pituitary adenoma is rare. There are few series in the literature (6-8) the largest being of nine patients (8), and association with carcinoma of the thyroid is not described. However, published evidence, pointing to the influence of high TSH levels in promoting thyroid cancer (1), as well as the regression of tumor relapses after suppression of TSH (4), induced us to consider that the association of TSH-producing adenoma and thyroid carcinoma found in our patient, could be more than coincidence. In addition, increased biologic activity of TSH molecules secreted by tumorous thyrotroph has been reported (8). The scant number of cases of TSH-secreting pituitary adenomas have responded rather poorly to transsphenoidal surgery (6-8). In order to prevent subsequent hyperthyroidism, 131 1, beta blockers, or total or subtotal thyroidectomy are usually needed, and various pharmacological agents have been studied to control neoplastic TSH hypersecretion, (6, 7). In these series, TSH control by somatostatin analogues was efficient. In our case transsphe-
COMMENTS
Our patient met the following criteria for neoplastic inappropriate secretion of TSH: measurable (or elevated) serum levels of TSH in the presence of increased total and free serum thyroid hormone concentrations, as well as clinical features consistent with hyperthyroidism. Moreover, he had radiologic evidence of a pituitary tumor by sellar computed tomography.
Fig. 2 - (a) Encapsulated follicular carcinoma showing invasion of thick capsule. (b) Pituitary adenoma showing a sinusoidal pattern.
501
A.L. Calle-Pascual, E. Yuste, P. Martin, et a/.
3. Thomas GA, Williams D., Williams E.D. The demonstration of tissue clomality by X-linked enzyme histochemistry. J. Pathol. 155: 101,1988. 4. Mazzaferri E. Papillary thyroid carcinoma: Factors influencing prognosis and current therapy. Sem. Oncology 14: 315, 1987. 5. Benker G., Olbricht Th., Reinwein D., Reiners Chr., Sauerwein W., Krause U., Mlynek M.L., Hirche H. Survival rates in patients with differentiated thyroid carcinoma. Cancer 65: 1517,1990. 6. Comi R.J., Gesundheit N., Murray L., Gorden P., Weintraub B.D. Response of thyrotropin-secreting pituitary pituitary adenoma to a long-acting somatostatin analogue. N. Engl. J. Med. 317: 12,1987. 7. Lamberts SW.J. The role of somatostatine in the regulation of anterior pituitary hormone secretion and the use of its analogs in the treatment of human pituitary tumors. Endocr. Rev. 9: 417,1988. 8. Gesundheit N., Petrick PA, Nissim M., Dahlberg P.A., Doppman J.L., Emerson Ch. H., Braverman L.E., Oldfield E.H., Weintraub B.D. Thyrotropin-secreting pituirary adenomas: Clinical and biochemical heterogeneity. Ann. Intern. Med. 111: 827, 1989.
noidal surgery removed all visible tumor tissue, as revealed by postsurgical CT as well as low TSH levels. As our patient presented a flat TSH response to TRH, with normal peripheral T3 and T4 levels, no additional therapy to suppress TSH was needed. In summary, we have studied a patient in whom a TSH-producing pituitary adenoma and thyroidal follicular carcinoma coincided. Surgery on the thyroid was performed initially in order to permit body scan and facilitate ablative 131 1 doses application without the need for exogenous TSH stimulation. We think that elevated TSH levels could have contributed to neoplastic transformation of the thyroid in this patient.
REFERENCES 1. DeGroot L.J., Sridama V. Thyroid neoplasia. In: DeGroot L.J. (Ed.), Endocrinology. W.B. Saunders Company, Philadelphia, 1989, p. 758. 2. Studer H., Peter H.J., Gerber H. Natural heterogeneity of thyroid cells: The basis for understanding thyroid function and nodular goiter growth. Endocr. Rev. 10: 125, 1989.
502
CASE REPORT
Association of athyrotropin-secreting pituitary adenoma and athyroid follicular carcinoma A.L. Calle-Pascual*, E. Yuste*, P. Martin*, T. Aramendi**, M.L. Garcia-Maurino**, J. Argente***, M.J. Catalan***, J. Uria****, J.A. Cabranes*****, and A.L. Charro***** *Unidad de Endocrinologia y Nutricion, **Seccion de Anatomia Patologica, and ***Unidad de Neurologia, Hospital Ntra Sra de Sonsoles, Avila, Universidad de Salamanca; ****Servicio de Neurocirugia, Clinica Puerta de Hierro, and *****Servicio de Endocrinologia y Medicina Nuclear, Hospital Clinico San Carlos, Madrid, Spain ABSTRACT. The different factors involved as etiological agents in thyroid cancer have in common long term thyroid follicle stimulation. On this base, a patient with a TSH-producing pituitary adenoma could be at high risk for developing thyroid cancer. A patient consulting for a single thyroid nodule was
studied in our unit. He was diagnosed as having a TSH-producing pituitary adenoma and the Thyroid nodule was shown to be a follicular carcinoma following removed. We speculate that elevated TSH levels could have contributed to neoplastic transformation of the thyroid in this patient.
INTRODUCTION
THYROID HORMONE ASSAYS
Although the etiology of thyroid cancer remains unknown, several factors have been considered to be related to its onset and development. Among others, these include iodine deficiency, prolonged administration of goitrogens, and external radiation or radioactive iodine (1). A common factor to these conditions could be chronic TSH stimulation ·of the thyroid. After long-term stimulation and given the heterogeneity of thyroid follicular cells (2), hyperplasia, adenoma and carcinoma could be a rational sequence. Several facts support this theory: the exposure to goitrogens can produce tumoral cellular clones (3); the tumor relapses disappear following inhibition of TSH by L-T4 administration (4), and medical suppression of TSH secretion is the mainstay of treatment for most cases of differentiated thyroid carcinoma (5). We have recently had the opportunity to study a patient in whom a TSH-producing pituitary adenoma.and a thyroidal follicular carcinoma coincided.
TSH was measured by immunoradiometric assay using a commercial kit, ELSA 2 TSH (CIS bioindustries, France). ELSA 2 TSH is a solid-phase two sites immunoradiometric assay. Two mouse monoclonal anti b-TSH antibodies were prepared against sterically remote antigenic sites on the molecule. The antibodies used in the test do not present any crossreaction with structurally related substances (LH, FSH, HCG). The sensitivity was 0.02 IlUI/ml. The intraassay variations coefficient at 0.9 IlUI/ml level was 3.5% and at 8.3 IlUI/ml level was 2.9%. Interassay variations were 3.8% and 4.6%, respectively. Radioimmunoassays of total T4 and total T3 were done using commercial kits provided from Abbott Cientifica SA, Madrid, Spain and from Diagnostic Products Corporation, Los Angeles, CA, U.S.A. Intraassay variation coefficients were 5.8% for T4 and 6% for T3, and the interassay variation coefficients were 3.5% and 7% respectively. The Free T41ndex (FT41) was done using T3 resin uptake. CASE REPORT V.B.G. was a 55 years old man who had been sent to the Endocrinology and Nutrition Unit for further studies of an enlarged sella turcica and a single thyroid nodule. He had been diagnosed and treated by the neu-
Key-Words: TSH pituitary adenoma, thyroid cancer. Correspondence: A.L. Calle-Pascual, Servicio de Endocrinologia y Nutricion, Hospital Clinico de San Carlos, Plaza de Cristo Rey sIn. 28040 Madrid, Spain. Received September 6, 1990; accepted February 28, 1991 .
499
A.L. Calle-Pascual, E. Yuste, P. Martin, et al.
99mTc thyroid scan revealed a cold area in the left thyroid lobe coinciding with the palpated nodule. Thyroid hormones, taken to another laboratory, were: T4 =207.69 nmol/I (N, 56-155) T3 =3.9 ng/ml (N , 0.82.1), FT4 1=192.2 (N,64-155) and TSH=4.9 mUI/1 (N, 0.45-6.2). In our laboratory were: T4 =183.2 nmol/I (N , 65-170), T3= 3.4 ng/ml (N, 0.8-1.9), FT4 1=172 (N, 68154) and TSH=3.5 miU/1 (N, 0.3-3.6). Cytology after fine needle aspiration was suspicious of thyroid follicular carcinoma. Skull X-rays revealed a generalized increase of sellar size without changes of its wall. Contrast sella CT scan showed a hypophyseal mass with suprasellar extension (Fig. 1). A pituitary reserve study was performed using four stimuli : a) GRF (100 /J-g), b) GnRH (100 /J-g), c) TRH (300 /J-g) , and d) 0.1 IU regular insulin/kg body weight. Basal HGH (N, 010) rose from 1.1 /J-g/I to 9.3 /J-g/1. Basal LH (N, 525) increased from 2.2 IU/I to 5.3 IU/I and basal FSH (N, 5-20) from 3 IU/I to 3.7 IU/I. ACTH (N , 1580 pg/ml) was undetectable and did not vary. Basal cortisol (N, 160-700) rose from 62.3 nmol/I to 112.8 nmol/I, basal TSH from 6.3 miU/1 to 9.9 miU/1 and PRL levels (N, 5-20 /J-g/I) of 25 /J-g/I remained constant. GRF (100 /J-g), TRH (300 /J-g) and somatostatin (infusion of 500 /J-g from time 0 to 120 min .) tests were performed during three nonconsecutive days, in order to evaluate PRL and TSH responses. These results are displayed in Table 1. The patient underwent a total thyroidectomy. The 102 g total thyroidectomy specimen consisted of the left lobe, the isthmus and the right lobe. The thyroid parenchima in the 7x5.5x5 cm . left lobule was almost entirely replaced by a soft, pale, partially necrotic well encapsulated 4x4x5 cm nodule. The nodule was composed of small size follicles with variable amount of colloid . Considerable variation in the size and shape of the cells was seen in focal areas. Small areas of necrosis were identified. Focal capsular invasion was demonstrated. The diagnostic of follicular carcinoma of the thyroid was estab-
Fig. 1 - Sellar CT scan with contrast media shows an intrasellar mass, that takes up the contrast in an inhomogeneous way and that grows outside the limits of the sella anteriorly and towards the right side.
rologist for Parkinson's disease. He had lived in a non-goiter-endemic area. Since the last year, he complained of weight loss (9 kg) , increase of his resting tremor, sleeping difficulties, and acceleration of his bowel habits . During two previous months he had noticed a nodule on the anterior region of the neck, with no other symptoms. The patient had to increase the doses of L-Dopa needed to control his Parkinson 's disease. The physical examination revealed a weight of 46 kg, height of 156 cm, 108 beats per minute and a blood pressure of 140/95 mmHg (supine). There were no signs of infiltrative ophthalmopathy . A 3x3 cm nodule was found occupying the left thyroid lobe. There were no adenopathies. The cardiovascular examination revealed rhythmic tachycardia. The abdomen was normal. His extremities displayed either a fine distal tremor or a gross tremor rest. Chest X-ray showed right tracheal displacement. A
Table 1 - PRL and TSH responses to administration of a bolus of GRF (100 I1g) and TRH (300l1g), and an infusion of somatostatin (500l1g from time 0 to 120 min), during three non consecutive days.
Stimulus GRF
TRH
Somatostatin
Hormone
-30
0
15
30
45
60
90
120
min
PRL
57
42
49
47
47
43
45
42
TSH
3.4
3.0
4.0
4.2
4.6
4.4
4.3
3.9
miU/1
PRL
59
41
50
49
49
43
48
fig/I
TSH
3.1
2.9
3.4
3.4
3.6
3.3
3.1
miU/1
I1g/1
PRL
45
46
43
43
60
49
45
42
I1g/1
TSH
3.0
3.2
2.9
3.0
3.1
2.8
2.8
2.9
miU/1
500
TSH pituitary adenoma and thyroid carcinoma
lished (Fig. 2a). Twenty-five days later, (T3 0.41 ng/ml, T4 64.5 nmol/I and TSH 27 mIU/I), 131 1 scan revealed a minimal eutopic uptake (6,000 cpm) having undetectable thyroglobulin levels, and the patient received a dose of 35 mCi of 1311. Fifteen days later the pituitary mass was excised by transsphenoidal route; the tumor showed a sinusoidal pattern with pseudorosette formation and palisading along vessels. The cells appeared chromophobic with HE enclosing few or no discernible granules with PAS stain (Fig. 2b). The patient remained asymptomatic with replacement therapy (hydrocortisone 10 mg q 8 h, levothyroxine 100 )lg q day, and a combination of carbidopa 25 mg and levodopa 100 mg q day). Six months later, on replacement therapy, T4 was 126.4 nmol/l, T3 was 0.7 ng/ml and TSH and thyroglobulin levels were undetectable. A triple stimuli (iv GnRH 100 )lg, GRF 100 )lg, and TRH 300 )lg) exhibited the following pattern: FSH rose from 4.0 lUll to 5.8 lUll; LH from 2.3 lUll to 6.1 lUll; HGH from undetectable to 2 )lg/l; PRL from 13.2 )lg/l to 22.8 )lg/l; TSH from undetectable to 0.9 mlU/I. The patient, one year after his initial surgery, continues asymptomatic and on replacement therapy with hydrocortisone and levothyroxine.
In addition he was diagnosed as having thyroidal follicular carcinoma after thyroidectomy specimen study. This association has never been reported in the literature. The order of surgery has not been established. In our patient, surgery on the thyroid was performed initially, permitting body scan without the need for exogenous TSH stimulation, facility ablative 131 1 doses. Forty days after thyroidectomy, when transsphenoidal surgery was performed, no evidence of accelerated pituitary tumor growth was observed. Our case supports the hypothesis that lengthy TSH stimulation of the thyroid can induce growth of susceptible follicular cells (2) until achieving malignant neoplastic transformation (3). A TSH-secreting pituitary adenoma is rare. There are few series in the literature (6-8) the largest being of nine patients (8), and association with carcinoma of the thyroid is not described. However, published evidence, pointing to the influence of high TSH levels in promoting thyroid cancer (1), as well as the regression of tumor relapses after suppression of TSH (4), induced us to consider that the association of TSH-producing adenoma and thyroid carcinoma found in our patient, could be more than coincidence. In addition, increased biologic activity of TSH molecules secreted by tumorous thyrotroph has been reported (8). The scant number of cases of TSH-secreting pituitary adenomas have responded rather poorly to transsphenoidal surgery (6-8). In order to prevent subsequent hyperthyroidism, 131 1, beta blockers, or total or subtotal thyroidectomy are usually needed, and various pharmacological agents have been studied to control neoplastic TSH hypersecretion, (6, 7). In these series, TSH control by somatostatin analogues was efficient. In our case transsphe-
COMMENTS
Our patient met the following criteria for neoplastic inappropriate secretion of TSH: measurable (or elevated) serum levels of TSH in the presence of increased total and free serum thyroid hormone concentrations, as well as clinical features consistent with hyperthyroidism. Moreover, he had radiologic evidence of a pituitary tumor by sellar computed tomography.
Fig. 2 - (a) Encapsulated follicular carcinoma showing invasion of thick capsule. (b) Pituitary adenoma showing a sinusoidal pattern.
501
A.L. Calle-Pascual, E. Yuste, P. Martin, et a/.
3. Thomas GA, Williams D., Williams E.D. The demonstration of tissue clomality by X-linked enzyme histochemistry. J. Pathol. 155: 101,1988. 4. Mazzaferri E. Papillary thyroid carcinoma: Factors influencing prognosis and current therapy. Sem. Oncology 14: 315, 1987. 5. Benker G., Olbricht Th., Reinwein D., Reiners Chr., Sauerwein W., Krause U., Mlynek M.L., Hirche H. Survival rates in patients with differentiated thyroid carcinoma. Cancer 65: 1517,1990. 6. Comi R.J., Gesundheit N., Murray L., Gorden P., Weintraub B.D. Response of thyrotropin-secreting pituitary pituitary adenoma to a long-acting somatostatin analogue. N. Engl. J. Med. 317: 12,1987. 7. Lamberts SW.J. The role of somatostatine in the regulation of anterior pituitary hormone secretion and the use of its analogs in the treatment of human pituitary tumors. Endocr. Rev. 9: 417,1988. 8. Gesundheit N., Petrick PA, Nissim M., Dahlberg P.A., Doppman J.L., Emerson Ch. H., Braverman L.E., Oldfield E.H., Weintraub B.D. Thyrotropin-secreting pituirary adenomas: Clinical and biochemical heterogeneity. Ann. Intern. Med. 111: 827, 1989.
noidal surgery removed all visible tumor tissue, as revealed by postsurgical CT as well as low TSH levels. As our patient presented a flat TSH response to TRH, with normal peripheral T3 and T4 levels, no additional therapy to suppress TSH was needed. In summary, we have studied a patient in whom a TSH-producing pituitary adenoma and thyroidal follicular carcinoma coincided. Surgery on the thyroid was performed initially in order to permit body scan and facilitate ablative 131 1 doses application without the need for exogenous TSH stimulation. We think that elevated TSH levels could have contributed to neoplastic transformation of the thyroid in this patient.
REFERENCES 1. DeGroot L.J., Sridama V. Thyroid neoplasia. In: DeGroot L.J. (Ed.), Endocrinology. W.B. Saunders Company, Philadelphia, 1989, p. 758. 2. Studer H., Peter H.J., Gerber H. Natural heterogeneity of thyroid cells: The basis for understanding thyroid function and nodular goiter growth. Endocr. Rev. 10: 125, 1989.
502
