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Elevated serum angiotensin-converting enzyme in hyperthyroidism
Elevated Serum Angiotensin-Converting Enzyme in Hypetthyroidism
EMANUEL SILVERSTEIN, M.D., Ph.D. GEORGE C. SCHUSSLER, M.D. JOAN FRIEDLAND, Ph.D. Brooklyn. New York
Serum angiotensin-converting enzyme was elevated In patients with hyperthyroidism (72 f 31 nmol/minute/ml, n = 12, p
Fromthe Departmentof Medicine,StateUniversity of New York, DownstateMedical Center, Brooklyn, New York. Requests for reprints should be addressed to Dr. Emanuel Silverstein, Department of Medicine, State University of New York, Downstate Medical Center, Box 112, Brooklyn, New York 11203. This work was supported by Grants HL 12599 and GM 18453 from the National Institutes of Health, Bethesda, Maryland. Manuscript accepted November 4. 1982.
The diagnoses of hyperthyroidism, hypothyroidism, and euthyroidism were made on the basis of clinical characteristics, serum thyroxine concentration values, and triiodothyronine resin uptake. Thyroiditis was diagnosed on the basis of a palpable goiter and elevated thyroid antibody titer. None of the patients had sarcoidosis, Gaucher disease, liver or renal disease, diabetes, or leprosy. Blood bank donors were used as healthy control subjects. Blood was allowed to clot for one to two hours before separation of serum after centrifugation. Serum samples were stored at -80% for up to three weeks before assay. Serum angiotensin-converting enzyme was assayed fluorimetrically with the substrate hippuryl-L-histidyl-L-leucine [21]. Rabbit alveolar macrophages were collected, cultured in the presence or absence
August 1983
The American Journal of Medicine
Volume 75
233
ANGIOTENSIN-CONVERTINGENZYME IN HYPERTHYROIDISM-SILVERSTEIN ET AL
TABLE I
Elevation of Serum Angiotensin-Converting Enzyme In Hyperthyroidism Number
Groups Patients with hyperthyroidism Patients with hypothyroidism Patients with thyroiditis Euthyroid control subjects Blood bank control subjects
T4’ (pg/dl)
12 3 1 6 58
19.9 f 5.0 1.9 f 0.9 6.2 9.2 f 2.6
TBRIJ’ (%)
SACE’ (nmol/minute/ml)
44 f 7 24 f 2 37 29 f 4
72 f 31’ 38 f 3 26 36f 14 32.2 f 10
Normal range: T4 (serum thyroxine) 4.7 to 12.2 pg/dl; TIRU (triiodothyronine resin uptake) 25 to 35 percent: SACE (serum angiotensinconverting enzyme) 12.2 to 52.2 nmollminute/ml. + p
values.
subjects (32.2 f 10, p
RESULTS
COMMENTS
Serum angiotensin-converting enzyme was elevated in 12 patients with hyperthyroidism (72 f 31 nmol/ minute/ml) in comparison with 58 healthy control
Our results indicate that serum angiotensin-converting enzyme tends to be elevated in patients with hyperthyroidism, in agreement with other observations 1201, but is not altered from the normal range in patients with hypothyroidism and probably thyroiditis. The elevation in serum angiotensin-converting enzyme is significantly correlated with the elevated circulating thyroid hormone.
of dexamethasone
[ 151 or 3,5,3’-triiodo-L-thyronine
in me-
for angiotensin-converting enzyme and protein as previously described. Peripheral blood monocytes from a normal subject were isolated by histopaque centrifugation [ 161. Residual red blood cells in the monocyte preparation were lysed by treatment with 10 mM potassium bicarbonate and 155 mM ammonium chloride, pH 7.4, without EDTA [22]. The cells were washed three times by centrifugation for 10 minutes at 400 g and plated [ 161 at 8 X lo6 cells per plate in RPM1 medium with 10 percent autologous serum and cultured for seven days. Triicdothyronine (1 mg/ml) was dissolved in dilute sodium hydroxide (3 to 4 ~1 of 1N sodium hydroxide per 1 ml of water), sterilized by filtration through a 0.22 p millipore filter, diluted 1:IO into 9 ml of RPM1 1640 medium containing 30 ~1 of 1N sodium hydroxide, and then serially diluted l/l0 (IO pg/ml), and l/100 (1 pg/ml) in RPMI 1640 medium without alteration in pH. dium RPM
Statistical Student t
1640 for three days, and assayed
significance
was determined
by means
of the
test. The standarddeviation is noted following mean
TABLE II
Effect of Triiodothyronine Bnd Dexamethasone on the AngiotensinConverting Enzyme Concentration in Rabbit Alveolar Macrophages in Culture*
MacrophageCondition
Number
Not incubated Ethanol vehicle control Triiiyronine, 0.15 p M Dexamethasone, 7.3 nM Dexamethasone. 7.3 nM + triiodothyronine, 15 PA4
1 2 2 3 3
AngiotensinConvertingEnzyme (nmollmimdelmg protein) 0.26 0.70 f 0.85 f 23f 15 f p
0.02+ 0.09 1 0 <0.001t
Rabbit alveolar macrophages were cultured for 90 hours in 5 percent carbon dioxide at 37“C. Triiodothyronine and/or dexamethasone were present during the last 68 hours of incubation. + Standard deviation. * In comparison with dexamethasone alone. l
234
August 1993
TABLE III
Effect of Triiodothyronine on the Synthesis of Angiotensin-ConvertinI( Enzyme in Human Monocytes in Cufture’ AngiotensinConvertingEnzyme Number
Control Triiodothyronine, 1.5 PM Triiodothyronine, 15 j&f
(nmol/mlnute/mgpfokin)
3 3
9.2 f 0.3+ 9.1 f 0.8
3
7.7 f 0.2
* Cultures were for seven days in 5 percent 37OC. + Standard deviation.
The American Journal of Medicine Volume 79
p <0.005
carbon dioxide at
ANGIOTENSIN-CONVERTING
ENZYME IN HYPERTHYROIDISM-SILVERSTEIN
ET AL
Yotsumoto et al [ 201 have observed that a decrease in serum thyroxine and triiodothyronine in patients undergoing treatment for hyperthyroidism with methylmercaptoimidazole was paralleled by a decrease in serum angiotensin-converting enzyme. Triiodothyronine at higher than physiologic levels failed to initiate or enhance induction of angiotensinconverting enzyme in mononuclear phagocytes. There is thus no evidence for the possibility that increased serum angiotensin-converting enzyme in patients with hyperthyroidism is due to increased angiotensin-convetting enzyme synthesis caused directly by an increased triiodothyronine concentration. Increased levels of thyroid hormone are associated with an alteration in the levels of activity of various enzymes, including elevated serum ribonuclease, gamma glutamyltranspeptidase, and N-acetyl-betahexosaminidase, thought to be mainly due to induction of enzyme synthesis [23-311. It is possible that the increased level of serum angiotensin-converting enzyme in patients with hyperthyroidism is an indirect effect of increased thyroid hormone, which may alter enzymes affecting the level of soluble circulating an-
giotensin-converting enzyme. We have observed that soluble angiotensin-converting enzyme, similar in properties to serum angiotensin-converting enzyme, can be produced from cellular particulate angiotensin-converting enzyme by treatment with a proteolytic enzyme such as trypsin [32]. It is conceivable that an altered proteolytic enzyme concentration brought about by increased concentrations of thyroid hormone might increase the production of soluble, circulating angiotensin-converting enzyme from cellular sources such as endothelial cells [ 10,111. Triiodothyronine is an inducer of chymotrypsin-like esteroproteases [ 271 and may have other similar effects. Elevated serum angiotensin-converting enzyme may be a useful, rapidly available, nonspecific marker of thyrotoxicosis. The possibility of hypet-thyroidismmust be considered in the evaluation of serum angiotensinconverting enzyme in the diagnosis and management of patients with sarcoidosis.
Lieberman J: Elevation of serum angiotensin-converting enzvme (ACE) level in sarcoidosis. Am J f&d 1975; 59: 365-372. 2. Silverstein E, Friedland J, Lyons HA, Gourin A: Markedly elevated angiotensin converting enzyme in lymph nodes containing nonnecrotizing granulomas in sarcoidosis. Proc Natl Acad Sci USA 1976; 73: 2137-2141. Lieberman J, Seutler E: Elevation of serum angiotensin-converting enzyme in Gaucher’s disease. N Engl J Med 1976; 294: 1442-1444. Silverstein E, Friedland J: Elevated serum and spleen angiotensinconverting enzyme and serum lysozyme in Gaucher’s disease. Clin Chem Acta 1977; 74: 21-25. Schweisfuth H, Wernze H: Changs of serum angiotensin I converting enzyme in patients with viral hepatitis and liver cirrhosis. Acta Hepatogastroenterol 1979; 26: 207-210. Borowsky SA, Lieberman J, Strorne S, Sastre A: Elevation of serum angiotensin-convertingenzyme level. Dccwrence in alcoholic liver disease. Arch Intern Med 1962; 142: 893-895. 7. Lieberman J, Rea TH: Serum angiotensinconverting enzyme in leprosy and coccidioidomycosis. Ann Intern Med 1977; 87: 422-425. 6. Studdy P, Bird R. Geraint James D. Sherlock S: Serum angiotensin converting enzyme (SACE) in sarcoidosis and other granulomatous disorders. Lancet 1978; II: 13311334. 9. Silverstein E. Brunswick J, Rao TK, Friedland J: Increased serum angiotensin converting enzyme in chronic renal disease. Nephron (in press). Ryan JW, Ryan US, Schultz DR, Whitaker C, Chung A, Dorer 10. FE: Subcellular localization of pulmonary angiotensinconverting enzyme (kininase II). Biochem J 1975; 146: 497-499. 11. Caldwell PRB, Seegal BC, Hsu KC, Das M, Soffer RL: Angio-
tensin-converting enzyme: vascular endothelial localization. Science 1976; 191: 1050-1051. Wigger HJ, Stalcup SA: Distribution and development of angiotensin converting enzyme in the fetal and newborn rabbit. An immunofluorescent study. Lab Invest 1978; 38: 581-585. Silverstein E, Pertschuk LP, Friedland J: lmmunofluorescent localization of angiotensin converting enzyme in epltheliold and giant cells of sarcoidosis granulomas. Proc Natl Acad Sci USA 1979; 76: 6646-6648. Silverstein E, Pertschuk LP, Friedland J: lmmunofluorescent detection of angiotensin-converting enzyme in Gaucher cells. Am J Med 1980; 69: 408-410. Friedland J, Setton C, Silverstein E: Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophases in culture. Science 1977; 197: 64-65. Friedland J, Setton C, Silverstein E: Induction of angiotensin converting enzyme in human monocytes in culture. Biothem Biophys Res Commun 1978; 83: 843-849. Silverstein E, Friedland J, Kitt M, Lyons HA: Increased serum angiotensin converting enzyme activity in sarcoidosis. Isr J Med Sci 1977: 13: 995-1000. Silverstein E, Friedland J, Lyons HA: Angiotensin converting enzyme in sarcoidosis. Clinical significance. Isr J Med Sci 1977; 13: 1001-1006. DeRemee RA, Rohrbach MS: Serum angiotensin converting enzyme activity in evaluating the clinical course of sarcoidosis. Ann Intern Med 1980; 92: 361-365. Yotsumoto H, lmai Y, Kuzuya N, Uchimura H, Matsuzaki F: Increased levels of serum angiotensin-converting enzyme activity in hyperthyroidism. Ann Intern Med 1982: 96: 326-328. Friedland J, Silverstein E: A sensitive fluorimetric assay for serum angiotensin-converting enzyme. Am J Clin Pathol 1976; 86: 416-424.
ACKNOWLEDGMENT We thank Charlotte Setton for capable technical assistance.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
August 1983
The American Journal of Medicine
Volume 75
235
ANGIOTENSIN-CONVERTING
22.
23. 24.
25.
26. 27.
236
ENZYME IN HYPERTHYROIDISM-SILVERSTEIN
Roos D, Loos JA: Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes I. Stimulation by phytohemagglutinin.Biochim Biophys Acta 1970; 222: 565-582. Lamberg BA: Thyroid function tests. Acta Endocrinol 1967; 124(suppl): 153-182. Snyder LM, Reddy WJ: Mechanism of action of thyroid hormones on erythrocyte 2, 3diphosphoglyceric acid synthesis. J Clin Invest 1970; 49: 1993-1998. Goodridge AG: Regulation of fatty acid synthesis in isolated hepatocytes prepared from the livers of neonatal chicks. J Biol Chem 1973; 248: 1924-1931. Leeper RD: Effect of thyroid hormone on human serum ribonuclease. J Clin Endocrinol Metab 1963; 23: 426-432. Takuma T, lchida T, Kumegawa M: Hormonal regulation of chymotrypsin-like esteroproteases in the mouse submandibular gland. Histochem 1981; 73: 477-480.
August 1963
The American Journal of Medicine
Volume 75
ET AL
28. 29.
30.
31.
32.
Azizi F: Gamma glutamyl transpeptidase levels in thyroid disease. Arch Intern Med 1982; 142: 79-81. Davis PJ, Davis FB, Blas SD: Studies on the mechanism of thyroid hormone stimulation in vitro of human red-cell Ca*+-ATPase activity. Life Sci 1982; 30: 675682. Oberkotter LV, Tenore A, Koldovsky 0: Changes in serum N-acetyl-beta-hexosaminidase levels after treatment of hypothyroid and hyperthyroid individuals with L-thyroxine and propylthiouracil. Clin Chem Acta 1980; 108: 61-66. Roti E. Bandini P, Robuschi G, et al: Serum concentrations of myoglobin, creatine kinase, lactate dehydrogenase and cardiac isoenzymes in euthyroid. hypothyroid and hyperthyroid subjects. La Ricerca Clin Lab 1980; 10: 609617. Friedland J, Silverstein E: Properties of soluble and particulate angiotensin-converting enzymes of rabbit lung, induced macrophage and serum. lnternat J Biochem (in press).
EMANUEL SILVERSTEIN, M.D., Ph.D. GEORGE C. SCHUSSLER, M.D. JOAN FRIEDLAND, Ph.D. Brooklyn. New York
Serum angiotensin-converting enzyme was elevated In patients with hyperthyroidism (72 f 31 nmol/minute/ml, n = 12, p
Fromthe Departmentof Medicine,StateUniversity of New York, DownstateMedical Center, Brooklyn, New York. Requests for reprints should be addressed to Dr. Emanuel Silverstein, Department of Medicine, State University of New York, Downstate Medical Center, Box 112, Brooklyn, New York 11203. This work was supported by Grants HL 12599 and GM 18453 from the National Institutes of Health, Bethesda, Maryland. Manuscript accepted November 4. 1982.
The diagnoses of hyperthyroidism, hypothyroidism, and euthyroidism were made on the basis of clinical characteristics, serum thyroxine concentration values, and triiodothyronine resin uptake. Thyroiditis was diagnosed on the basis of a palpable goiter and elevated thyroid antibody titer. None of the patients had sarcoidosis, Gaucher disease, liver or renal disease, diabetes, or leprosy. Blood bank donors were used as healthy control subjects. Blood was allowed to clot for one to two hours before separation of serum after centrifugation. Serum samples were stored at -80% for up to three weeks before assay. Serum angiotensin-converting enzyme was assayed fluorimetrically with the substrate hippuryl-L-histidyl-L-leucine [21]. Rabbit alveolar macrophages were collected, cultured in the presence or absence
August 1983
The American Journal of Medicine
Volume 75
233
ANGIOTENSIN-CONVERTINGENZYME IN HYPERTHYROIDISM-SILVERSTEIN ET AL
TABLE I
Elevation of Serum Angiotensin-Converting Enzyme In Hyperthyroidism Number
Groups Patients with hyperthyroidism Patients with hypothyroidism Patients with thyroiditis Euthyroid control subjects Blood bank control subjects
T4’ (pg/dl)
12 3 1 6 58
19.9 f 5.0 1.9 f 0.9 6.2 9.2 f 2.6
TBRIJ’ (%)
SACE’ (nmol/minute/ml)
44 f 7 24 f 2 37 29 f 4
72 f 31’ 38 f 3 26 36f 14 32.2 f 10
Normal range: T4 (serum thyroxine) 4.7 to 12.2 pg/dl; TIRU (triiodothyronine resin uptake) 25 to 35 percent: SACE (serum angiotensinconverting enzyme) 12.2 to 52.2 nmollminute/ml. + p
values.
subjects (32.2 f 10, p
RESULTS
COMMENTS
Serum angiotensin-converting enzyme was elevated in 12 patients with hyperthyroidism (72 f 31 nmol/ minute/ml) in comparison with 58 healthy control
Our results indicate that serum angiotensin-converting enzyme tends to be elevated in patients with hyperthyroidism, in agreement with other observations 1201, but is not altered from the normal range in patients with hypothyroidism and probably thyroiditis. The elevation in serum angiotensin-converting enzyme is significantly correlated with the elevated circulating thyroid hormone.
of dexamethasone
[ 151 or 3,5,3’-triiodo-L-thyronine
in me-
for angiotensin-converting enzyme and protein as previously described. Peripheral blood monocytes from a normal subject were isolated by histopaque centrifugation [ 161. Residual red blood cells in the monocyte preparation were lysed by treatment with 10 mM potassium bicarbonate and 155 mM ammonium chloride, pH 7.4, without EDTA [22]. The cells were washed three times by centrifugation for 10 minutes at 400 g and plated [ 161 at 8 X lo6 cells per plate in RPM1 medium with 10 percent autologous serum and cultured for seven days. Triicdothyronine (1 mg/ml) was dissolved in dilute sodium hydroxide (3 to 4 ~1 of 1N sodium hydroxide per 1 ml of water), sterilized by filtration through a 0.22 p millipore filter, diluted 1:IO into 9 ml of RPM1 1640 medium containing 30 ~1 of 1N sodium hydroxide, and then serially diluted l/l0 (IO pg/ml), and l/100 (1 pg/ml) in RPMI 1640 medium without alteration in pH. dium RPM
Statistical Student t
1640 for three days, and assayed
significance
was determined
by means
of the
test. The standarddeviation is noted following mean
TABLE II
Effect of Triiodothyronine Bnd Dexamethasone on the AngiotensinConverting Enzyme Concentration in Rabbit Alveolar Macrophages in Culture*
MacrophageCondition
Number
Not incubated Ethanol vehicle control Triiiyronine, 0.15 p M Dexamethasone, 7.3 nM Dexamethasone. 7.3 nM + triiodothyronine, 15 PA4
1 2 2 3 3
AngiotensinConvertingEnzyme (nmollmimdelmg protein) 0.26 0.70 f 0.85 f 23f 15 f p
0.02+ 0.09 1 0 <0.001t
Rabbit alveolar macrophages were cultured for 90 hours in 5 percent carbon dioxide at 37“C. Triiodothyronine and/or dexamethasone were present during the last 68 hours of incubation. + Standard deviation. * In comparison with dexamethasone alone. l
234
August 1993
TABLE III
Effect of Triiodothyronine on the Synthesis of Angiotensin-ConvertinI( Enzyme in Human Monocytes in Cufture’ AngiotensinConvertingEnzyme Number
Control Triiodothyronine, 1.5 PM Triiodothyronine, 15 j&f
(nmol/mlnute/mgpfokin)
3 3
9.2 f 0.3+ 9.1 f 0.8
3
7.7 f 0.2
* Cultures were for seven days in 5 percent 37OC. + Standard deviation.
The American Journal of Medicine Volume 79
p <0.005
carbon dioxide at
ANGIOTENSIN-CONVERTING
ENZYME IN HYPERTHYROIDISM-SILVERSTEIN
ET AL
Yotsumoto et al [ 201 have observed that a decrease in serum thyroxine and triiodothyronine in patients undergoing treatment for hyperthyroidism with methylmercaptoimidazole was paralleled by a decrease in serum angiotensin-converting enzyme. Triiodothyronine at higher than physiologic levels failed to initiate or enhance induction of angiotensinconverting enzyme in mononuclear phagocytes. There is thus no evidence for the possibility that increased serum angiotensin-converting enzyme in patients with hyperthyroidism is due to increased angiotensin-convetting enzyme synthesis caused directly by an increased triiodothyronine concentration. Increased levels of thyroid hormone are associated with an alteration in the levels of activity of various enzymes, including elevated serum ribonuclease, gamma glutamyltranspeptidase, and N-acetyl-betahexosaminidase, thought to be mainly due to induction of enzyme synthesis [23-311. It is possible that the increased level of serum angiotensin-converting enzyme in patients with hyperthyroidism is an indirect effect of increased thyroid hormone, which may alter enzymes affecting the level of soluble circulating an-
giotensin-converting enzyme. We have observed that soluble angiotensin-converting enzyme, similar in properties to serum angiotensin-converting enzyme, can be produced from cellular particulate angiotensin-converting enzyme by treatment with a proteolytic enzyme such as trypsin [32]. It is conceivable that an altered proteolytic enzyme concentration brought about by increased concentrations of thyroid hormone might increase the production of soluble, circulating angiotensin-converting enzyme from cellular sources such as endothelial cells [ 10,111. Triiodothyronine is an inducer of chymotrypsin-like esteroproteases [ 271 and may have other similar effects. Elevated serum angiotensin-converting enzyme may be a useful, rapidly available, nonspecific marker of thyrotoxicosis. The possibility of hypet-thyroidismmust be considered in the evaluation of serum angiotensinconverting enzyme in the diagnosis and management of patients with sarcoidosis.
Lieberman J: Elevation of serum angiotensin-converting enzvme (ACE) level in sarcoidosis. Am J f&d 1975; 59: 365-372. 2. Silverstein E, Friedland J, Lyons HA, Gourin A: Markedly elevated angiotensin converting enzyme in lymph nodes containing nonnecrotizing granulomas in sarcoidosis. Proc Natl Acad Sci USA 1976; 73: 2137-2141. Lieberman J, Seutler E: Elevation of serum angiotensin-converting enzyme in Gaucher’s disease. N Engl J Med 1976; 294: 1442-1444. Silverstein E, Friedland J: Elevated serum and spleen angiotensinconverting enzyme and serum lysozyme in Gaucher’s disease. Clin Chem Acta 1977; 74: 21-25. Schweisfuth H, Wernze H: Changs of serum angiotensin I converting enzyme in patients with viral hepatitis and liver cirrhosis. Acta Hepatogastroenterol 1979; 26: 207-210. Borowsky SA, Lieberman J, Strorne S, Sastre A: Elevation of serum angiotensin-convertingenzyme level. Dccwrence in alcoholic liver disease. Arch Intern Med 1962; 142: 893-895. 7. Lieberman J, Rea TH: Serum angiotensinconverting enzyme in leprosy and coccidioidomycosis. Ann Intern Med 1977; 87: 422-425. 6. Studdy P, Bird R. Geraint James D. Sherlock S: Serum angiotensin converting enzyme (SACE) in sarcoidosis and other granulomatous disorders. Lancet 1978; II: 13311334. 9. Silverstein E. Brunswick J, Rao TK, Friedland J: Increased serum angiotensin converting enzyme in chronic renal disease. Nephron (in press). Ryan JW, Ryan US, Schultz DR, Whitaker C, Chung A, Dorer 10. FE: Subcellular localization of pulmonary angiotensinconverting enzyme (kininase II). Biochem J 1975; 146: 497-499. 11. Caldwell PRB, Seegal BC, Hsu KC, Das M, Soffer RL: Angio-
tensin-converting enzyme: vascular endothelial localization. Science 1976; 191: 1050-1051. Wigger HJ, Stalcup SA: Distribution and development of angiotensin converting enzyme in the fetal and newborn rabbit. An immunofluorescent study. Lab Invest 1978; 38: 581-585. Silverstein E, Pertschuk LP, Friedland J: lmmunofluorescent localization of angiotensin converting enzyme in epltheliold and giant cells of sarcoidosis granulomas. Proc Natl Acad Sci USA 1979; 76: 6646-6648. Silverstein E, Pertschuk LP, Friedland J: lmmunofluorescent detection of angiotensin-converting enzyme in Gaucher cells. Am J Med 1980; 69: 408-410. Friedland J, Setton C, Silverstein E: Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophases in culture. Science 1977; 197: 64-65. Friedland J, Setton C, Silverstein E: Induction of angiotensin converting enzyme in human monocytes in culture. Biothem Biophys Res Commun 1978; 83: 843-849. Silverstein E, Friedland J, Kitt M, Lyons HA: Increased serum angiotensin converting enzyme activity in sarcoidosis. Isr J Med Sci 1977: 13: 995-1000. Silverstein E, Friedland J, Lyons HA: Angiotensin converting enzyme in sarcoidosis. Clinical significance. Isr J Med Sci 1977; 13: 1001-1006. DeRemee RA, Rohrbach MS: Serum angiotensin converting enzyme activity in evaluating the clinical course of sarcoidosis. Ann Intern Med 1980; 92: 361-365. Yotsumoto H, lmai Y, Kuzuya N, Uchimura H, Matsuzaki F: Increased levels of serum angiotensin-converting enzyme activity in hyperthyroidism. Ann Intern Med 1982: 96: 326-328. Friedland J, Silverstein E: A sensitive fluorimetric assay for serum angiotensin-converting enzyme. Am J Clin Pathol 1976; 86: 416-424.
ACKNOWLEDGMENT We thank Charlotte Setton for capable technical assistance.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
August 1983
The American Journal of Medicine
Volume 75
235
ANGIOTENSIN-CONVERTING
22.
23. 24.
25.
26. 27.
236
ENZYME IN HYPERTHYROIDISM-SILVERSTEIN
Roos D, Loos JA: Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes I. Stimulation by phytohemagglutinin.Biochim Biophys Acta 1970; 222: 565-582. Lamberg BA: Thyroid function tests. Acta Endocrinol 1967; 124(suppl): 153-182. Snyder LM, Reddy WJ: Mechanism of action of thyroid hormones on erythrocyte 2, 3diphosphoglyceric acid synthesis. J Clin Invest 1970; 49: 1993-1998. Goodridge AG: Regulation of fatty acid synthesis in isolated hepatocytes prepared from the livers of neonatal chicks. J Biol Chem 1973; 248: 1924-1931. Leeper RD: Effect of thyroid hormone on human serum ribonuclease. J Clin Endocrinol Metab 1963; 23: 426-432. Takuma T, lchida T, Kumegawa M: Hormonal regulation of chymotrypsin-like esteroproteases in the mouse submandibular gland. Histochem 1981; 73: 477-480.
August 1963
The American Journal of Medicine
Volume 75
ET AL
28. 29.
30.
31.
32.
Azizi F: Gamma glutamyl transpeptidase levels in thyroid disease. Arch Intern Med 1982; 142: 79-81. Davis PJ, Davis FB, Blas SD: Studies on the mechanism of thyroid hormone stimulation in vitro of human red-cell Ca*+-ATPase activity. Life Sci 1982; 30: 675682. Oberkotter LV, Tenore A, Koldovsky 0: Changes in serum N-acetyl-beta-hexosaminidase levels after treatment of hypothyroid and hyperthyroid individuals with L-thyroxine and propylthiouracil. Clin Chem Acta 1980; 108: 61-66. Roti E. Bandini P, Robuschi G, et al: Serum concentrations of myoglobin, creatine kinase, lactate dehydrogenase and cardiac isoenzymes in euthyroid. hypothyroid and hyperthyroid subjects. La Ricerca Clin Lab 1980; 10: 609617. Friedland J, Silverstein E: Properties of soluble and particulate angiotensin-converting enzymes of rabbit lung, induced macrophage and serum. lnternat J Biochem (in press).