J Endocrinol. Invest. 13: 155-159, 1990
Concentrations of somatomedin-C and triiodothyronine in patients with thyroid dysfunction and nonthyroidal illnesses M. Valimaki*, Liewendahl** ****, S.-L. Karonen **, T. Helenius****, and A.-M. Suikkari*** * Third Department of Medicine, ** Department of Clinical Chemistry, *** First Department of Obstetrics and Gynecology, University of Helsinki, and **** Minerva Foundation Institute, Helsinki, Finland
ABSTRACT. We studied the possibility of an association between serum somatomedin-C (Sm-C) and thyroid hormone concentrations. For this purpose 34 hyperthyroid patients, 39 patients with primary hypothyroidism, 36 patients with severe nonthyroidal illnesses (NTI), and 63 euthyroid healthy control subjects were examined. The mean concentration of serum dialyzable free triiodothyronine (FT3) was 26.6 ± 15.4 pmol/l (± SD) in hyperthyroidism, 2.8 ± 1.2 in hypothyroidism, 4.2 ± 1.1 in NTI, and 5.3 ± 0.7 in controls. The lowest mean concentration of serum Sm-C (10.1 ± 3.0 nmol/l) was found in the NTI group and the highest in the hyperthyroid group (16.8 ± 3.2): these con-
centrations differed Significantly from the mean control level (12.2 ± 2.2). In NTI patients the serum FT3 and T3 levels correlated significantly with the serum Sm-C levels (r 0.63; p < 0.001, r 0.65; p < 0.001, respectively). In hypothyroid patients there was a weak correlation between the serum FT3 and Sm-C levels (r = 0.36; P < 0.05), but no correlations were found in hyperthyroid and healthy subjects. We conclude that the lowered Sm-C levels in NTI do not reflect a hypothyroid state, as normal Sm-C levels were found in hypothyroidism, and that impaired nutritional state of the patients is the most likely explanation for the association between Sm-C and FT3 (and T3) in NT!.
INTRODUCTION
one somatomedin, somatomedin-C (Sm-C), in subjects with various thyroid states. In addition, we determined Sm-C and total and free triiodothyronine (T 3) in serum from patients with severe nonthyroidal illnesses (NTI) because in NTlthe Sm-C (11) and T3 (12) concentrations in serum are often low but it is not known if these changes are interrelated. In order to account for the possibility of a more complex interaction between the production of Sm-C and thyroid function in NTI a number of blood components known to affect the concentration of SmC or to be changed in NTI were also studied.
=
The regulation of the concentration of somatomedins (Sm) in blood is multifactorial (1 ). Growth hormone (GH) acts through somatomedins and is the main regulator of the serum somatomedin activity. Nutritional factors are also known to influence the level of somatomedins in blood (2). As to thyroid hormones, studies on experimental animals have shown that they have a synergistic effect on the GH-mediated somatomedin production (3). Controversy, however, exists on blood somatomedin levels in patients with thyroid dysfunction. In hypothyroid patients they have been either low (4-7) or normal (8-10). Correspondingly, in hyperthyroidism either high (5) or normal (10) somatomedin levels have been reported. To shed light on the existing controversy we measured the concentrations of
=
MATERIALS AND METHODS Assays of serum Sm-C and thyroid hormones were performed on serum specimens from 34 hyperthyroid patients (aged 20 to 80 yr; mean 44), 39 patients with primary hypothyroidism (aged 27 to 74 yr; mean 53), 36 patients with NTI (aged 19 to 89 yr; mean 61), and 63 euthyroid healthy controls (aged 21 to 65 yr; mean 42). Out of NTI patients 11 had severe chronic heart failure, 3 acute myocardial infarction, 6 diabetic ketoacidosis, 7 end-stage malignancy, 7 acute bacterial infection and 2 patients anorexia
Key-words: Somafomedin-C, thyroid hormones, nonthyroidal illnesses, hyperthyroidism, hypothyroidism. Correspondence: Dr. Matti Valimaki, Third Department of Medicine, University of Helsinki. Meilahti Hospital, SF-00290 Helsinki, Finland. Received June 2, 1989; accepted November 15, 1989.
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M. Valimaki, K. Liewendahl, s.-L. Karonen, et al.
20
nervosa. The serum concentrations of 34K insulinlike growth factor binding protein (IGF-BP), growth hormone (GH) and cortisol were measured in 25 NTI patients, and the concentration of testosterone in 13 male NTI patients. The patients and controls were not known to be taking drugs that interfere pharmacologically or analytically with the assays of this study. Serum free triiodothyronine (FT3) was measured by a direct equilibrium dialysis procedure (13), serum T3 by an in-house radioimmunoassay (RIA), and serum reverse T3 (rT3) by a RIA kit from Mallinckrodt Corp. (Oietzenbach, FRG). Commercial RIA kits were employed for the assay of serum Sm-C (Immuno Nuclear Corporation, Stillwater, Minn., USA), GH (International CIS, Gif-Sur-Yvette, France), testosterone (Nordiclab, Oulu, Finland), and cortisol (Farmos Oiagnostica, Turku, Finland). The serum 34K IGF binding protein (IGF-BF) (14) concentrations were determined by a previously described radioimmunoassay (15). Serum IGF-BP values were not altered by addition of IGF-I (Sm-C) in vitro, and porcine insulin (Sigma Chemical Co., S1. Louis, MO) or recombinant (Thr59 ) IGF-I (Amersham, Bucks, U.K.) did not interfere in the RIA (15). Interassay coefficients of variation (%) for these assays were: FT3 4.7, T3 5.3, rT3 7.6, Sm-C 10.1, GH 8.8, testosterone 9.1, cortisol 6.9 and IGF-BP 14. The results are given as means ± SO. Statistical testing was performed by Spearman's test and Student's t test for unpaired groups of unequal size.
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concentrations in 36 patients with various non thyroidal illnesses (r = 0.63; P 0.001).
Concentrations of somatomedin-C and triiodothyronine in patients with thyroid dysfunction and nonthyroidal illnesses M. Valimaki*, Liewendahl** ****, S.-L. Karonen **, T. Helenius****, and A.-M. Suikkari*** * Third Department of Medicine, ** Department of Clinical Chemistry, *** First Department of Obstetrics and Gynecology, University of Helsinki, and **** Minerva Foundation Institute, Helsinki, Finland
ABSTRACT. We studied the possibility of an association between serum somatomedin-C (Sm-C) and thyroid hormone concentrations. For this purpose 34 hyperthyroid patients, 39 patients with primary hypothyroidism, 36 patients with severe nonthyroidal illnesses (NTI), and 63 euthyroid healthy control subjects were examined. The mean concentration of serum dialyzable free triiodothyronine (FT3) was 26.6 ± 15.4 pmol/l (± SD) in hyperthyroidism, 2.8 ± 1.2 in hypothyroidism, 4.2 ± 1.1 in NTI, and 5.3 ± 0.7 in controls. The lowest mean concentration of serum Sm-C (10.1 ± 3.0 nmol/l) was found in the NTI group and the highest in the hyperthyroid group (16.8 ± 3.2): these con-
centrations differed Significantly from the mean control level (12.2 ± 2.2). In NTI patients the serum FT3 and T3 levels correlated significantly with the serum Sm-C levels (r 0.63; p < 0.001, r 0.65; p < 0.001, respectively). In hypothyroid patients there was a weak correlation between the serum FT3 and Sm-C levels (r = 0.36; P < 0.05), but no correlations were found in hyperthyroid and healthy subjects. We conclude that the lowered Sm-C levels in NTI do not reflect a hypothyroid state, as normal Sm-C levels were found in hypothyroidism, and that impaired nutritional state of the patients is the most likely explanation for the association between Sm-C and FT3 (and T3) in NT!.
INTRODUCTION
one somatomedin, somatomedin-C (Sm-C), in subjects with various thyroid states. In addition, we determined Sm-C and total and free triiodothyronine (T 3) in serum from patients with severe nonthyroidal illnesses (NTI) because in NTlthe Sm-C (11) and T3 (12) concentrations in serum are often low but it is not known if these changes are interrelated. In order to account for the possibility of a more complex interaction between the production of Sm-C and thyroid function in NTI a number of blood components known to affect the concentration of SmC or to be changed in NTI were also studied.
=
The regulation of the concentration of somatomedins (Sm) in blood is multifactorial (1 ). Growth hormone (GH) acts through somatomedins and is the main regulator of the serum somatomedin activity. Nutritional factors are also known to influence the level of somatomedins in blood (2). As to thyroid hormones, studies on experimental animals have shown that they have a synergistic effect on the GH-mediated somatomedin production (3). Controversy, however, exists on blood somatomedin levels in patients with thyroid dysfunction. In hypothyroid patients they have been either low (4-7) or normal (8-10). Correspondingly, in hyperthyroidism either high (5) or normal (10) somatomedin levels have been reported. To shed light on the existing controversy we measured the concentrations of
=
MATERIALS AND METHODS Assays of serum Sm-C and thyroid hormones were performed on serum specimens from 34 hyperthyroid patients (aged 20 to 80 yr; mean 44), 39 patients with primary hypothyroidism (aged 27 to 74 yr; mean 53), 36 patients with NTI (aged 19 to 89 yr; mean 61), and 63 euthyroid healthy controls (aged 21 to 65 yr; mean 42). Out of NTI patients 11 had severe chronic heart failure, 3 acute myocardial infarction, 6 diabetic ketoacidosis, 7 end-stage malignancy, 7 acute bacterial infection and 2 patients anorexia
Key-words: Somafomedin-C, thyroid hormones, nonthyroidal illnesses, hyperthyroidism, hypothyroidism. Correspondence: Dr. Matti Valimaki, Third Department of Medicine, University of Helsinki. Meilahti Hospital, SF-00290 Helsinki, Finland. Received June 2, 1989; accepted November 15, 1989.
155
M. Valimaki, K. Liewendahl, s.-L. Karonen, et al.
20
nervosa. The serum concentrations of 34K insulinlike growth factor binding protein (IGF-BP), growth hormone (GH) and cortisol were measured in 25 NTI patients, and the concentration of testosterone in 13 male NTI patients. The patients and controls were not known to be taking drugs that interfere pharmacologically or analytically with the assays of this study. Serum free triiodothyronine (FT3) was measured by a direct equilibrium dialysis procedure (13), serum T3 by an in-house radioimmunoassay (RIA), and serum reverse T3 (rT3) by a RIA kit from Mallinckrodt Corp. (Oietzenbach, FRG). Commercial RIA kits were employed for the assay of serum Sm-C (Immuno Nuclear Corporation, Stillwater, Minn., USA), GH (International CIS, Gif-Sur-Yvette, France), testosterone (Nordiclab, Oulu, Finland), and cortisol (Farmos Oiagnostica, Turku, Finland). The serum 34K IGF binding protein (IGF-BF) (14) concentrations were determined by a previously described radioimmunoassay (15). Serum IGF-BP values were not altered by addition of IGF-I (Sm-C) in vitro, and porcine insulin (Sigma Chemical Co., S1. Louis, MO) or recombinant (Thr59 ) IGF-I (Amersham, Bucks, U.K.) did not interfere in the RIA (15). Interassay coefficients of variation (%) for these assays were: FT3 4.7, T3 5.3, rT3 7.6, Sm-C 10.1, GH 8.8, testosterone 9.1, cortisol 6.9 and IGF-BP 14. The results are given as means ± SO. Statistical testing was performed by Spearman's test and Student's t test for unpaired groups of unequal size.
.......
•
c c
'5 Q)
10
E 0
«i
E 0
en
5
4
2
concentrations in 36 patients with various non thyroidal illnesses (r = 0.63; P 0.001).
