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Thyrotropin stimulating hormone response to thyrotropin releasing hormone in patients with panic disorder
Psychoneuroendocrinology 24 (1999) 155 – 160
Thyrotropin stimulating hormone response to thyrotropin releasing hormone in patients with panic disorder Ras¸it Tu¨kel a,*, Kaan Kora a, Nezih Hekim b, Harika Og˘uz c, Faruk Alago¨l c a
Department of Psychiatry, Istanbul Faculty of Medicine, Istanbul Uni6ersity, Istanbul, Turkey b Dr Pakize Tarzi, Biochemistry and Hormone Laboratories, Istanbul, Turkey c Department of Internal Medicine, Endocrinology Unit, Istanbul Faculty of Medicine, Istanbul Uni6ersity, Istanbul, Turkey Received 3 March 1998; accepted 24 August 1998
Abstract Objective: The aim of this study is to assess thyrotropin stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in patients with panic disorder (PD). Method: The effects of TRH administration on the release of TSH were examined in 15 patients who met DSM-III-R criteria for PD and compared their test results with those of 15 normal control subjects. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. Results: Dmax TSH values were lower in the panic disorder patients than in the control subjects. Using the criterion of Dmax TSH 57 mlU/l, nine of the 15 panic disorder patients and four of the 15 control subjects had a blunted TSH response to TRH. Conclusions: These results confirm the findings from earlier reports that patients with PD show blunted TSH response to TRH which is similar to that seen in depressed patients. © 1999 Elsevier Science Ltd. All rights reserved. © 1999 Elsevier Science Ltd. All rights reserved. Keywords: Panic disorder; TRH; TSH
* Corresponding author. Tel.: +90-212-534-0050; fax: +90-212-631-2400. 0306-4530/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PII S0306-4530(98)00067-5
156
R. Tu¨kel et al. / Psychoneuroendocrinology 24 (1999) 155–160
1. Introduction The thyrotropin (TSH) responses to prothyrelin (TRH) has been extensively studied to assess abnormalities in hypothalamo-pituitary-thyroid (HPT) axis activity in patients with major depressive disorder (MDD) (Asnis et al., 1980; Baumgartner et al., 1988; Gold et al., 1980; Kirkegaard et al., 1978; Loosen et al., 1978; Rubin et al., 1987). In numerous studies, decreased TSH responses to TRH were obtained in 25 – 30% of patients with MDD (Loosen and Prange, 1982). TSH responses to TRH were studied also in patients with panic disorder (PD). In one study (Hamlin and Pottash, 1986) 40% and in two other studies (Castellani et al., 1988; Roy-Byrne et al., 1986), 33% of patients with PD, showed decreased TSH responses (57 mlU/ml), similar to the patients with MDD. In these studies (Castellani et al., 1988; Hamlin and Pottash, 1986; Roy-Byrne et al., 1986), the TSH responses were found significantly lower than the control groups. On the other hand, another study reported that no significant difference could be found in TSH response to TRH between patients with PD and healthy controls (Stein and Uhde, 1991). Blunted TSH response to TRH in patients with PD has not been so evident as it is in patients with MDD depending on the results that have been reported in a few studies. The purpose of the present study was to examine the function of the HPT axis in PD by conducting a study of TSH responses to TRH in a sample of patients with PD who were compared to normals.
2. Method
2.1. Subjects and procedure A total of 15 patients who met DSM-III-R criteria for PD were included in the study. None of the patients met concurrent DSM-III-R criteria for major depressive epizode. The control group consisted of 15 healthy volunteers matched by age and sex who did not have any past or present psychiatric problems. The matching for age included9 1 year difference. In the panic group, the mean age was 33.67 (SD 7.95), and in the control group, was 33.80 (SD 7.93). There were seven women and eight men in both groups. In PD group, the mean age of onset was 28.3 (SD 6.10), the mean duration of the disorder was 66.21 (months) (SD 90.40), the longest period free of panic attacks since the onset was 16.81 (months) (SD 30.07), and the mean number of attacks in the previous month was 17.00 (SD 24.83). The mean Beck Depression Inventory (BDI) score in this group was 23.36 (SD 12.60) and the mean Hamilton Rating Scale for Anxiety (HRSA) score was 30.79 (SD 7.04). Detailed medical histories were taken from all of the subjects in both groups and all of them underwent a thorough physical examination by an internist, to exclude subjects with any kind of organic disorder in the past or present. Both groups had 2 weeks in which all of their medications were discontinued prior to the administration of the neuroendocrine tests. Written informed consent was obtained from all of the patients and the healthy controls after the procedures had been fully explained.
R. Tu¨kel et al. / Psychoneuroendocrinology 24 (1999) 155–160
157
The diagnosis of PD was made by structured clinical interview for DSM-III-R (SCID) (Spitzer et al., 1987). PD patients were given a semi-structured interview form prepared by the authors, the BDI (Beck et al., 1961) and the HRSA (Hamilton, 1959) during the day before TRH testing. After an overnight fast, the subjects were instructed to relax for 20 min before the test. At 0900h, 400 mg TRH was given with slow injection in 1 min via IV route. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. Serums collected by centrifuging blood samples were stored at −70°C until all of the samples were ready for the measurements. TSH levels were measured by ‘chemiluminescent immunoassay’ method (SANOFI/Pasteur USA). Analytical sensitivity was 0.006 mlU/l and the intra-assay coefficients of variation were 3.61 – 4.94 for TSH.
2.2. Statistical analysis We compared the TSH values measured initially (baseline) and as responses to TRH using Mann – Whitney U-test. In the view of the literature (Castellani et al., 1988; Hamlin and Pottash, 1986; Roy-Byrne et al., 1986), Dmax TSH5 7 mlU/l was taken as blunted TSH response (Dmax =peak value−baseline value). We also used an arbitrary threshold for Dmax TSH of 5 mIU/l to dichotomize the patients as ‘blunted’ and ‘not blunted’. Using x 2 test, we compared the blunted TSH response rates. When necessary, Pearson’s r-test was used to examine the relationships among selected measures.
3. Results There was no significant difference observed in baseline TSH values between patients with PD and control subjects (Table 1). The TSH values (represented as Table 1 TSH responses to TRH in panic disorder and control groupsa Panic disorder group
Control group
Baseline TSH (mlU/l)
1.079.66 (15)
1.26 9 .52 (15)
Dmax TSH (mlU/l)
7.1295.03 (15)
Blunted TSH response (Dmax57 mlU/l) Blunted TSH response (DmaxTSH55 mlU/l)
9/15 (60%)
Mann–Whitney-U= 91.0, z=−.89 11.09 95.44 (15) Mann–Whitney-U= 64.0, z =−2.02** 4/15 (26.6%) x 2 =3.39*
6/15 (40%)
1/15 (6.7%)
Values on the table, mean 9 SD (case number). * pB.1. ** pB.05. a
x 2 =4.66**
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R. Tu¨kel et al. / Psychoneuroendocrinology 24 (1999) 155–160
difference values between the baseline and the three time points) at 30 and 60 min were found to be significantly lower than the control group (for 30 min, Mann– Whitney U-test =66.0, z= − 1.93, p = .05; for 60 min, Mann–Whitney U-test= 62.5, z= −2.07, p B .05). Dmax TSH values in the PD group were found to be significantly lower than the control group (Table 1). Using the criterion of Dmax TSH5 7 mlU/l, nine out of 15 PD patients (60%) and four out of 15 control subjects (26.6%) had blunted TSH responses to TRH (x 2 test, p B.1). When we arbitrarily defined a blunted TSH response as Dmax TSH 5 5 mlU/l, we have found TSH blunting in six of 15 (40%) PD patients and one of 15 (6.7%) control subjects (x 2 test, pB .05) (Table 1). There was significant negative correlation between HRSA scores and Dmax TSH values in the PD group (r= − .57, p B.05). There was no significant correlation between Dmax TSH values and BDI scores (r= − .36, NS). Dmax TSH values are significantly correlated with the longest period free of panic attacks (r= .61, pB .05). No significant correlation was found between Dmax TSH values and the number of attacks in the previous month, although there was a trend (r= − .46, pB .1).
4. Discussion The results of our study, namely the TSH responses to TRH at 30 and 60 min being significantly lower in the PD group than the control group support the findings of Roy-Byrne et al. (1986) and Castellani et al. (1988). Castellani et al. (1988) have found Dmax TSH values to be significantly lower than the values in control group. According to the study of Stein and Uhde (1991), Dmax TSH values were not significantly different between the PD group and the control group. In our study, we have estimated Dmax TSH values in PD group to be significantly lower than the control group. Blunted TSH response rate (Dmax TSH5 7 mlU/l as the accepted value) in the PD group which we have found to be 60% in our study is higher than the rates (12–40%) found in other studies (Castellani et al., 1988; Hamlin and Pottash, 1986; Roy-Byrne et al., 1986; Stein and Uhde, 1991). Another finding different from other studies is the blunted TSH response rate of 27% in the control group. In other four studies, there were no subjects in the control group with blunted TSH responses. Gillette et al. (1989) have reported decreased TSH responses (DTSH30 B 7 mU/ml) in 23 subjects out of 106 healthy controls (22%), a finding corresponding to ours. With using the criterion of Dmax TSH5 5 mlU/l in our study, the rates for both groups were more like those obtained in other studies. With the limited number of data available, it seems impracticable to interpret whether the unexpectedly high rates of blunted TSH responses in both of the groups are characteristics of our society. In two studies, different results have been obtained concerning the relation of TSH response to TRH with depression and anxiety levels (Roy-Byrne et al., 1986;
R. Tu¨kel et al. / Psychoneuroendocrinology 24 (1999) 155–160
159
Stein and Uhde, 1991). Roy-Byrne et al. (1986) have reported that they have not observed any correlation between TSH response to TRH and the levels of anxiety and depression in patients with PD. Stein and Uhde (1991) have found that BDI scores, but none of the behavioral measures of anxiety and Hamilton Rating Scale for Depression (HRSD) scores, was negatively correlated with Dmax TSH in the patients with PD. According to these authors, HRSD scores tend to reflect psychic and somatic anxiety levels rather than depression in patients with PD. In our study, in patients with PD, significant negative correlation has been observed between Dmax TSH and anxiety rates measured by HRSA (r= − .57); a similar finding has not been replicated with the scores on the BDI. Therefore, a different conclusion than that of Stein and Uhde (1991) has been reached in our study that the TSH response to TRH can be more closely related to the level of anxiety rather than of depression in PD. Another finding supporting this view comes from a study which has compared depressive patients with and without panic attacks. Gillette et al. (1989) have found lower mean TSH response to TRH in depressive patients with panic attacks compared to the depressive patients without panic attacks and normal controls. A significant positive correlation was estimated between Dmax TSH values and the longest period free of panic attacks. The blunted TSH response is explained by chronic TRH hypersecretion, leading hyporesponsiveness of pituitary, possibly due to down regulation of pituitary receptors (Loosen and Prange, 1982). It has been suggested that the duration and the severity of the illness cause more intensive and/or prolonged hypersecretion of TRH and subsequent down-regulation of the pituitary receptors (Castellani et al., 1988). The finding that Dmax TSH values decrease as the scores in HRSA (which is the indicator of the severity of the disorder) increase and that they increase as the length of the attack free period increases has been in accord with this hypothesis. This was a small study, and conclusions are therefore limited. The results of this study demonstrate that PD patients have a lower mean Dmax TSH than control subjects. The findings also indicate that Dmax TSH values are negatively related to HRSA scores, and positively related to longest period free of panic attacks in PD patients. We see that there are only a few studies present in the current literature investigating TSH responses to TRH in patients with PD. Despite some contradicting results, the significant findings in terms of TSH responses demonstrated in available studies, emphasize the need for further studies on this subject.
Acknowledgements The authors acknowledge Dr Pakize Tarzi Biochemistry and Hormone Laboratories for their contribution in performing the assays on blood samples and Erkim Drug Co. for supplying TRH ampuls.
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R. Tu¨kel et al. / Psychoneuroendocrinology 24 (1999) 155–160
References Asnis, G. M., Nathan, R. S., Halbreich, U., Halpern, F. S., Sachar, E. J., 1980. TRH tests in depression. Lancet 1, 424–425. Baumgartner, A., Graff, K. J., Kurten, I., Meinhold, H., 1988. The hypothalamic-pituitary-thyroid axis in psychiatric patients and healthy subjects, I – IV. Psychiatry Research 24, 271 – 332. Beck, A. T., Ward, C. H., Mendelson, M., Mock, J., Erbaugh, J., 1961. An inventory for measuring depression. Archives of General Psychiatry 4, 561 – 571. Castellani, S., Quillen, M. A., Vaughan, D. A., Hund, M. A., Ho, L., Ziegler, M. G., Le Vine, W. R., 1988. TSH and catecholamine response to TRH in panic disorder. Biological Psychiatry 24, 87 – 90. Gillette, G. M., Garbutt, J. C., Quade, D. E., 1989. TSH response to TRH in depression with and without panic attacks. American Journal of Psychiatry 146, 743 – 748. Gold, M. S., Pottash, A. L. C., Ryan, N., Sweeney, D. R., Davies, R. K., Martin, D. M., 1980. TRH induced TSH response in unipolar, bipolar, and secondary depressions: possible utility in clinical assessment and differential diagnosis. Psychoneuroendocrinology 5, 147 – 155. Hamilton, M., 1959. The assessment of anxiety states by rating. British Journal of Medical Psychology 32, 50 – 55. Hamlin, C. L., Pottash, A. L. C., 1986. Evaluation of anxiety disorders. In: Gold, M. S., Pottash, A. L. C. (Eds.), Diagnostic and Laboratory Testing in Psychiatry. Plenum, New York, pp. 215 – 233. Kirkegaard, C., Bjorum, N., Cohn, D., Lauridsen, U. B., 1978. Thyrotropin releasing hormone (TRH) stimulation test in manic depressive illness. Archives of General Psychiatry 35, 1017 – 1021. Loosen, P. T., Prange, A. J., Wilson, I. C., 1978. Influence of cortisol on TRH-induced TSH response in depression. American Journal of Psychiatry 135, 244 – 246. Loosen, P. T., Prange, A. J., 1982. Serum thyrotropin response to thyrotropin-releasing hormone in psychiatric patients: a review. American Journal of Psychiatry 139, 405 – 416. Roy-Byrne, P. P., Uhde, T. W., Rubinow, D. R., Post, R. M., 1986. Reduced TSH and prolactin responses to TRH in patients with panic disorder. American Journal of Psychiatry 143, 503 – 507. Rubin, R. T., Poland, R. E., Lesser, I. M., Martin, D. J., 1987. Neuroendocrine aspects of primary endogenous depression IV. Pituitary-thyroid axis activity in patients and matched control subjects. Psychoneuroendocrinology 12, 333–347. Spitzer, R. L., Williams, J. B. W., Gibbon, M., 1987. Structured Clinical Interview for DSM-III-R. American Psychiatric Press, Washington DC. Stein, M. B., Uhde, T. W., 1991. Endocrine, cardiovascular and behavioral effects of intravenous protirelin in patients with panic disorder. Archives of General Psychiatry 48, 148 – 156.
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Thyrotropin stimulating hormone response to thyrotropin releasing hormone in patients with panic disorder Ras¸it Tu¨kel a,*, Kaan Kora a, Nezih Hekim b, Harika Og˘uz c, Faruk Alago¨l c a
Department of Psychiatry, Istanbul Faculty of Medicine, Istanbul Uni6ersity, Istanbul, Turkey b Dr Pakize Tarzi, Biochemistry and Hormone Laboratories, Istanbul, Turkey c Department of Internal Medicine, Endocrinology Unit, Istanbul Faculty of Medicine, Istanbul Uni6ersity, Istanbul, Turkey Received 3 March 1998; accepted 24 August 1998
Abstract Objective: The aim of this study is to assess thyrotropin stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in patients with panic disorder (PD). Method: The effects of TRH administration on the release of TSH were examined in 15 patients who met DSM-III-R criteria for PD and compared their test results with those of 15 normal control subjects. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. Results: Dmax TSH values were lower in the panic disorder patients than in the control subjects. Using the criterion of Dmax TSH 57 mlU/l, nine of the 15 panic disorder patients and four of the 15 control subjects had a blunted TSH response to TRH. Conclusions: These results confirm the findings from earlier reports that patients with PD show blunted TSH response to TRH which is similar to that seen in depressed patients. © 1999 Elsevier Science Ltd. All rights reserved. © 1999 Elsevier Science Ltd. All rights reserved. Keywords: Panic disorder; TRH; TSH
* Corresponding author. Tel.: +90-212-534-0050; fax: +90-212-631-2400. 0306-4530/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PII S0306-4530(98)00067-5
156
R. Tu¨kel et al. / Psychoneuroendocrinology 24 (1999) 155–160
1. Introduction The thyrotropin (TSH) responses to prothyrelin (TRH) has been extensively studied to assess abnormalities in hypothalamo-pituitary-thyroid (HPT) axis activity in patients with major depressive disorder (MDD) (Asnis et al., 1980; Baumgartner et al., 1988; Gold et al., 1980; Kirkegaard et al., 1978; Loosen et al., 1978; Rubin et al., 1987). In numerous studies, decreased TSH responses to TRH were obtained in 25 – 30% of patients with MDD (Loosen and Prange, 1982). TSH responses to TRH were studied also in patients with panic disorder (PD). In one study (Hamlin and Pottash, 1986) 40% and in two other studies (Castellani et al., 1988; Roy-Byrne et al., 1986), 33% of patients with PD, showed decreased TSH responses (57 mlU/ml), similar to the patients with MDD. In these studies (Castellani et al., 1988; Hamlin and Pottash, 1986; Roy-Byrne et al., 1986), the TSH responses were found significantly lower than the control groups. On the other hand, another study reported that no significant difference could be found in TSH response to TRH between patients with PD and healthy controls (Stein and Uhde, 1991). Blunted TSH response to TRH in patients with PD has not been so evident as it is in patients with MDD depending on the results that have been reported in a few studies. The purpose of the present study was to examine the function of the HPT axis in PD by conducting a study of TSH responses to TRH in a sample of patients with PD who were compared to normals.
2. Method
2.1. Subjects and procedure A total of 15 patients who met DSM-III-R criteria for PD were included in the study. None of the patients met concurrent DSM-III-R criteria for major depressive epizode. The control group consisted of 15 healthy volunteers matched by age and sex who did not have any past or present psychiatric problems. The matching for age included9 1 year difference. In the panic group, the mean age was 33.67 (SD 7.95), and in the control group, was 33.80 (SD 7.93). There were seven women and eight men in both groups. In PD group, the mean age of onset was 28.3 (SD 6.10), the mean duration of the disorder was 66.21 (months) (SD 90.40), the longest period free of panic attacks since the onset was 16.81 (months) (SD 30.07), and the mean number of attacks in the previous month was 17.00 (SD 24.83). The mean Beck Depression Inventory (BDI) score in this group was 23.36 (SD 12.60) and the mean Hamilton Rating Scale for Anxiety (HRSA) score was 30.79 (SD 7.04). Detailed medical histories were taken from all of the subjects in both groups and all of them underwent a thorough physical examination by an internist, to exclude subjects with any kind of organic disorder in the past or present. Both groups had 2 weeks in which all of their medications were discontinued prior to the administration of the neuroendocrine tests. Written informed consent was obtained from all of the patients and the healthy controls after the procedures had been fully explained.
R. Tu¨kel et al. / Psychoneuroendocrinology 24 (1999) 155–160
157
The diagnosis of PD was made by structured clinical interview for DSM-III-R (SCID) (Spitzer et al., 1987). PD patients were given a semi-structured interview form prepared by the authors, the BDI (Beck et al., 1961) and the HRSA (Hamilton, 1959) during the day before TRH testing. After an overnight fast, the subjects were instructed to relax for 20 min before the test. At 0900h, 400 mg TRH was given with slow injection in 1 min via IV route. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. Serums collected by centrifuging blood samples were stored at −70°C until all of the samples were ready for the measurements. TSH levels were measured by ‘chemiluminescent immunoassay’ method (SANOFI/Pasteur USA). Analytical sensitivity was 0.006 mlU/l and the intra-assay coefficients of variation were 3.61 – 4.94 for TSH.
2.2. Statistical analysis We compared the TSH values measured initially (baseline) and as responses to TRH using Mann – Whitney U-test. In the view of the literature (Castellani et al., 1988; Hamlin and Pottash, 1986; Roy-Byrne et al., 1986), Dmax TSH5 7 mlU/l was taken as blunted TSH response (Dmax =peak value−baseline value). We also used an arbitrary threshold for Dmax TSH of 5 mIU/l to dichotomize the patients as ‘blunted’ and ‘not blunted’. Using x 2 test, we compared the blunted TSH response rates. When necessary, Pearson’s r-test was used to examine the relationships among selected measures.
3. Results There was no significant difference observed in baseline TSH values between patients with PD and control subjects (Table 1). The TSH values (represented as Table 1 TSH responses to TRH in panic disorder and control groupsa Panic disorder group
Control group
Baseline TSH (mlU/l)
1.079.66 (15)
1.26 9 .52 (15)
Dmax TSH (mlU/l)
7.1295.03 (15)
Blunted TSH response (Dmax57 mlU/l) Blunted TSH response (DmaxTSH55 mlU/l)
9/15 (60%)
Mann–Whitney-U= 91.0, z=−.89 11.09 95.44 (15) Mann–Whitney-U= 64.0, z =−2.02** 4/15 (26.6%) x 2 =3.39*
6/15 (40%)
1/15 (6.7%)
Values on the table, mean 9 SD (case number). * pB.1. ** pB.05. a
x 2 =4.66**
158
R. Tu¨kel et al. / Psychoneuroendocrinology 24 (1999) 155–160
difference values between the baseline and the three time points) at 30 and 60 min were found to be significantly lower than the control group (for 30 min, Mann– Whitney U-test =66.0, z= − 1.93, p = .05; for 60 min, Mann–Whitney U-test= 62.5, z= −2.07, p B .05). Dmax TSH values in the PD group were found to be significantly lower than the control group (Table 1). Using the criterion of Dmax TSH5 7 mlU/l, nine out of 15 PD patients (60%) and four out of 15 control subjects (26.6%) had blunted TSH responses to TRH (x 2 test, p B.1). When we arbitrarily defined a blunted TSH response as Dmax TSH 5 5 mlU/l, we have found TSH blunting in six of 15 (40%) PD patients and one of 15 (6.7%) control subjects (x 2 test, pB .05) (Table 1). There was significant negative correlation between HRSA scores and Dmax TSH values in the PD group (r= − .57, p B.05). There was no significant correlation between Dmax TSH values and BDI scores (r= − .36, NS). Dmax TSH values are significantly correlated with the longest period free of panic attacks (r= .61, pB .05). No significant correlation was found between Dmax TSH values and the number of attacks in the previous month, although there was a trend (r= − .46, pB .1).
4. Discussion The results of our study, namely the TSH responses to TRH at 30 and 60 min being significantly lower in the PD group than the control group support the findings of Roy-Byrne et al. (1986) and Castellani et al. (1988). Castellani et al. (1988) have found Dmax TSH values to be significantly lower than the values in control group. According to the study of Stein and Uhde (1991), Dmax TSH values were not significantly different between the PD group and the control group. In our study, we have estimated Dmax TSH values in PD group to be significantly lower than the control group. Blunted TSH response rate (Dmax TSH5 7 mlU/l as the accepted value) in the PD group which we have found to be 60% in our study is higher than the rates (12–40%) found in other studies (Castellani et al., 1988; Hamlin and Pottash, 1986; Roy-Byrne et al., 1986; Stein and Uhde, 1991). Another finding different from other studies is the blunted TSH response rate of 27% in the control group. In other four studies, there were no subjects in the control group with blunted TSH responses. Gillette et al. (1989) have reported decreased TSH responses (DTSH30 B 7 mU/ml) in 23 subjects out of 106 healthy controls (22%), a finding corresponding to ours. With using the criterion of Dmax TSH5 5 mlU/l in our study, the rates for both groups were more like those obtained in other studies. With the limited number of data available, it seems impracticable to interpret whether the unexpectedly high rates of blunted TSH responses in both of the groups are characteristics of our society. In two studies, different results have been obtained concerning the relation of TSH response to TRH with depression and anxiety levels (Roy-Byrne et al., 1986;
R. Tu¨kel et al. / Psychoneuroendocrinology 24 (1999) 155–160
159
Stein and Uhde, 1991). Roy-Byrne et al. (1986) have reported that they have not observed any correlation between TSH response to TRH and the levels of anxiety and depression in patients with PD. Stein and Uhde (1991) have found that BDI scores, but none of the behavioral measures of anxiety and Hamilton Rating Scale for Depression (HRSD) scores, was negatively correlated with Dmax TSH in the patients with PD. According to these authors, HRSD scores tend to reflect psychic and somatic anxiety levels rather than depression in patients with PD. In our study, in patients with PD, significant negative correlation has been observed between Dmax TSH and anxiety rates measured by HRSA (r= − .57); a similar finding has not been replicated with the scores on the BDI. Therefore, a different conclusion than that of Stein and Uhde (1991) has been reached in our study that the TSH response to TRH can be more closely related to the level of anxiety rather than of depression in PD. Another finding supporting this view comes from a study which has compared depressive patients with and without panic attacks. Gillette et al. (1989) have found lower mean TSH response to TRH in depressive patients with panic attacks compared to the depressive patients without panic attacks and normal controls. A significant positive correlation was estimated between Dmax TSH values and the longest period free of panic attacks. The blunted TSH response is explained by chronic TRH hypersecretion, leading hyporesponsiveness of pituitary, possibly due to down regulation of pituitary receptors (Loosen and Prange, 1982). It has been suggested that the duration and the severity of the illness cause more intensive and/or prolonged hypersecretion of TRH and subsequent down-regulation of the pituitary receptors (Castellani et al., 1988). The finding that Dmax TSH values decrease as the scores in HRSA (which is the indicator of the severity of the disorder) increase and that they increase as the length of the attack free period increases has been in accord with this hypothesis. This was a small study, and conclusions are therefore limited. The results of this study demonstrate that PD patients have a lower mean Dmax TSH than control subjects. The findings also indicate that Dmax TSH values are negatively related to HRSA scores, and positively related to longest period free of panic attacks in PD patients. We see that there are only a few studies present in the current literature investigating TSH responses to TRH in patients with PD. Despite some contradicting results, the significant findings in terms of TSH responses demonstrated in available studies, emphasize the need for further studies on this subject.
Acknowledgements The authors acknowledge Dr Pakize Tarzi Biochemistry and Hormone Laboratories for their contribution in performing the assays on blood samples and Erkim Drug Co. for supplying TRH ampuls.
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