Geront. clin. 17: 89-95 (1975)
Circadian Rhythm of Plasma Cortisol in the Aged (Cosinor Method)1 C. F. C o l u c c i , B. D ’A lessandro , A. B ellastella and N. M ontalbetti S. Maria della Pace Hospital, 00. RR. di Napoli, Institute of Medical Semeiotics, University of Naples, and Magenta Hospital, Magenta
Abstract. Plasma cortisol circadian rhythm was investigated in 18 apparently healthy elderly subjects, in 11 elderly patients affected by cerebrovascular hemiplegia and in 11 otherwise healthy blind elderly subjects. Results were microscopically analyzed by the least squares and Cosinor methods. The circadian rhythm of plasma cortisol was present and normal both in elderly subjects and in elderly patients with cerebrovascular hemiple gia. By contrast, a plasma cortisol rhythm was not found in blind elderly subjects.
1 This paper has been read at the meeting of the European Clinical Section of the International Association of Gerontology, held in Manchester, 1974.
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Frequent anomalies of circadian rhythm concerning the urinary excretion of corticosteroids catabolites have been found in old age [10, 12], and yet plasma cortisol rhythm seems to remain normal [2, 13-16], Circadian adrenocortical rhythm is usually present in localized or diffuse cerebral lesions unless they specifically involve neuroendocrine structures regulating corticotrophic releasing factor (CRF) and ACTH [2, 6], However, different findings have been reported in the literature on adrenocortical rhythm in blind subjects [1, 5, 7, 9, 11, 17, 18]. For many years we have investigated the circadian rhythm of plasma cortisol in the aged by a macrosopic analysis [1,2,13], and recently the data collected by us have been evaluated by means of the microscopic analysis carried out in the Cronobiology laboratories of Minneapolis, Minn., using the Cosinor method as suggested by H alberg et al. [3, 4], These authors have set up a technique for the study of biorhythms by computer, this technique is now widely accepted and used in chronobiological research.
C olucci/D ’A lessan» ro/B ellastella,M ontalbetti
90
Material and Methods We studied 40 male volunteers hospitalized in a long-term geriatric hospital. They were grouped as follows: (1) a control group consisting of 18 apparently healthy subjects aged 62-88 (average 73.11); (2) 11 patients, aged 62-83 (average 67.09), having suffered from cerebrovascular arteriosclerotic hemiplegia from 1 to 5 years. They were free from any endocrine, metabolic, hepatic or renal diseases which might have interfered with the plasma cortisol levels, and (3) 11 apparently healthy but totally blind subjects aged 65-93 (average 74.27). The blindness had been present from 4 to 12 years and had been caused by bilateral glaucoma (cases 1, 2, 5, 6, 8), bilateral cataract (cases 9, 10), panophthalmitis (cases 4,7) and trauma (cases 3, 11). During the experiment none of the subjects were affected by intercurrent acute illness, fever, pains and other episodic symptoms which might have interfered with the validity of the results. All subjects had a 6-7 h sleep rhythm per day, approximately from 10-11 p.m. to 5-6 a.m. Meals were given at 7.30 a.m., 1 p.m. and 6.30 p.m. Blood was sampled through a needle-catheter every 3 or 6 h, starting at 6 a.m. and for a period of 24 or 48 h. Plasma cortisol was assessed by means of the fluorimetric method of M attingly [8]. Results have been microscopically analyzed by the least squares and Cosinor methods consisting in the fitting of a cosine curve in order to find the curve with the least square error from the original data, and in the computation of a sum vector of individual phases and ampli tudes with the confidential limits.
Results Results are summarized in table 1-1V and in figure I. Data show that both in the control group and in the hemiplegic patients the circadian
number
subject
Age
6 a.m.
12 noon
6 p.m.
midnight
6 a.m.
1 2 3 4 5 6 7 8 9 10 11
C. A. V. L. F. L. V. M. B. M. D. B. G. A. P. M. C. V. G. C. T. G.
64 62 63 63 66 66 67 70 71 72 83
18.1 20.7 26.8 9.3 29.0 15.0 8.7 9.8 7.3 28.7 20.0
4.0 14.7 16.0 11.3 15.5 2.3 5.0 12.7 8.7 26.0 14.5
3.5 0 12.0 5.3 8.2 2.7 4.1 4.9 4.0 18.3 4.3
0 0 0 6.7 5.0 0 0 5.7 3.3 4.8 0
19.8 17.8 24.0 9.3 26.6 11.3 9.6 8.7 8.1 30.2 22.5 Downloaded by: King's College London 137.73.144.138 - 11/22/2017 4:22:49 PM
Table I. Circadian rhythm of plasma cortisol (ng%) in the clinically healthy aged subjects
Circadian Rhythm of Plasma Cortisol in the Aged
91
Fig. I. Cosinor representation of the cortisol circadian rhythm in the aged. C ontrols;------ = hemiplegic patients;------ = blind subjects.
rhythm of plasma cortisol is present and its characteristics are similar to those referred in the literature for normal adult subjects. By contrast, a circadian rhythm of plasma cortisol was not found in the blind subjects. Figure 1 shows that in the control and hemiplegic groups the error ellipse does not overlap the origin of the circle. This is significance of a rhythm (p = 0.0001). In the blind subjects, however, the error ellipse covers the origin of the circle, therefore there is no evidence of a statistically significant rhythm (p = 0.150).
These results confirm the occurrence of a normal plasma cortisol rhythm in the clinically healthy aged and in aged patients with cerebral lesions which do not specifically involve neuroendocrine structures regulating CRF and ACT FI [2, 6, 14, 16].
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Discussion
92
Colucci/D ’A lessandro/B ellastella/M ontalbetti
Table II. Circadian rhythm of plasma cortisol number subject
Age
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
88 62 79 62 76 63 71 71 75 75 78 73 71 73 71 75 75 78
A. S. I. G. L. M. P. I. F .G . R. A. R .C . F. B. C.L. P. M. C. C. F .G . F. P. S. M. I. F. C. G. C. A. F. G.
6 a.m.
_ 28.5 -
21.3 20.0 13.4 8.0 15.7 -
32.0 17.8 -
28.0 30.7
9 a.m.
noon
3 p.m.
4.5 14.3
5.3 9.7 10.5 7.6 7.0 12.3 4.7 6.7 10.7 17.5 7.3 21.0 2.2 10.2 5.4 6.7 20.1 24.0
2.0
-
7.5 -
-
15.0 9.5 5.0 -
6.6 7.1 -
-
-
8.1 -
6.0 -
16.4 10.0 -
1.5 -
4.4 8.1 -
-
6 p.m. 5.0 7.4 12.5 0 4.6 24.2 2.0 2.7 5.6 12.0 7.5 12.3 5.5 7.2 6.3 3.7 14.5 10.0
9 p.m. 0 -
6.5 -
2.2 -
12.4 4.4 -
1.0 -
4.4 2.8 -
-
Table III. Circadian rhythm of plasma cortisol Age
1 2 3 4 5 6 7 8 9 10 11
65 73 70 65 67 65 73 73 93 93 80
T. G. T. L. B. G. T. L. R. M. B. A. S. A. D. B. R. G. R. A. E. L.
6 a.m.
-
9.0 -
20.2 9.5 -
26.0
9 a.m.
noon
3 p.m.
6 p.m.
9 p.m.
6.8 11.3 10.1
4.6 15.2 9.5 4.8 4.0 18.5 14.8 25.3 8.5 18.5 9.7
6.9 9.2 11.4
5.8 6.0 14.5 5.8 11.2 24.5 15.6 6.0 7.3 14.2 8.9
13.5 3.1 11.4
-
9.1 -
16.0 -
11.5 12.0
-
8.3 -
12.5 -
17.0 -
17.5
-
1.7 -
6.5 -
13.1 -
14.5
To explain our findings on the blind subjects three hypotheses are suggest ed: (1) a loss of synchronizer light stimuli over a long period, particularly of light-darkness alternating stimuli; (2) presence of free-running rhythms with slightly different periods in the different subjects [11], and (3) circannual
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number subject
93
Circadian Rhythm of Plasma Cortisol in the Aged (ng%) in the aged affected by hemiplegia midnight
6 a.m.
0 4.8 3.4 0 1.0 16.0 0 1.3 3.3 3.5 0 4.0 0 7.8
6.8 29.0 17.0 18.2 9.5 22.0 15.0 6.2 ¡3.8 16.5 11.5 27.5 17.8 16.6 8.0 15.9 31.2 30.3
1 .0
1.2 4.7 4.0
9 a.m.
noon
3 p.m.
6 p.m. 9 p.m.
_
_
_
_
__
-
-
-
-
-
18.5
18.0
10.2
9.0
6.3
midnight 1.5 -
2.8
6 a.m. 3.9 -
15.1
-
-
-
-
-
-
-
7.5
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
13.0 8.4 -
5.6
13.4 8.0 -
3.5
-
9.0 8.5
-
-
-
-
3.5
-
2.5 0 1 .0
-
14.3 12.0 -
14.1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
(ng%) in the elderly blind subjects 6 a.m.
18.0 0 9.3 18.2 2.0 18.0 8.9 0 6.9 16.8 8.3
10.0 8.7 11.0 10.0 12.3 22.2 9.5 8.7 17.2 24.2 18.0
9 a.m.
noon
_
_
-
-
-
-
-
-
14.5 -
5.0 -
10.3
11.0
3 p.m.
_ 13.7
6 p.m.
9 p.m.
_
_
-
-
-
17.4 -
-
-
-
-
-
-
-
-
-
6 a.m.
_ -
5.2
-
-
_
-
-
-
7.4
midnight
6.8 -
-
desynchronization where the phase differences of the circannual rhythm might have overlaid the circadian rhythm variations. Our data are inadequate to exclude or to accept any of the above-mentioned hypotheses. Longitudinal studies on various subjects for an adequate span of time ( = o r > to 30 r)
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midnight
94
C o l u c c i /D 'A lessan dro /B e l l a s t e l l a /M o n t a lb e t t i
Table IV. Analysis of circadian rhythm of plasma cortisol in the aged by Cosinor method1 n
Age
Rhythm PR2 detection
Amplitude ± SE
Acrophase3
Controls
18
62-88 (73,11)
p 0.001
66.8
6.00 ± 2.53
-1 2 3 (-1 0 8 , -139)
Subjects affected by hemiplegia
11
62-83 (67.09)
p 0.001
81.9
7.70 ± 3.03
-1 2 5 (-1 1 1 , -141)
Blind subjects
11
65-93 (74.27)
p 0.150
53.4
1.65 ± 2.65
-148
1 Investigation carried out using the least square method and the Cosinor method in the Cronobiology Laboratories of University of Minneapolis, Minn. 2 Percent variability in relation to the adapted curve. 3 Local midnight.
and transversal studies repeated throughout the year would be needed in order to assess or exclude the presence of free-running rhythms and circannual components. The few available reports in the literature on the circadian rhythm of plasma cortisol in blind people are only based on macroscopic investigation and show conflicting data [5. 7, 9, 11, 18].
1 Bellastella, A. ; C olucci, C. F. e D 'A lessandro, B. : Comportamento del ritmo circadiano del cortisolo plasmatico nel soggetto anziano affetto da cecità totale. Boll. Soc. ital. Biol. sper. 48: 592 (1972). 2 C olucci, C. F . ; D 'A lessandro, B. e Bellastella, A.: Comportamento del ritmo circadiano del cortisolo plasmatico nell’anziano con osenzaesiti di apoplessia cerebrale. Boll. Soc. ital. Biol. sper. 48: 184 (1972). 3 H alberg, F. ; E ngeli, M.; H amburger, C., and H illmann, D.: Spectral resolution of low-frequency, small-amplitude rhythms in excreted 17-ketosteroids; probable andro gen-induced circaseptan desynchronization. Acta endocr., Copenh. 50: suppl. 103, p. I (1965). 4 H alberg, F .; T ong , Y. L., and Johnson, E. A.: Circadian system phase. An aspect of temporal morphology; procedures and illustration examples; in M ayersbach The cellular aspects of biorhythms, pp. 20-48 (Springer, Berlin 1967). 5 H ollwich , F. and D ieckhues, B.: Endocrine system and blindness. Germ. med. mon. /; 122(1971).
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References
Circadian Rhythm of Plasma Cortisol in the Aged
95
Dr. C. F. Colucci, S. Maria della Pace Hospital, 00. RR. di Napoli, 80078 Pozznoli, Napoli (Italy)
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6 K rieger, D. T. and K rieger, H. P.: Circadian variation of plasma 17-hydroxycorticosteroids in central nervous system disease. J. clin. Endocr. 26: 929 (1966). 7 K rieger, D. T. and Rizzo, F.: Circadian periodicity of plasma 11-hydroxycorticosteroids in subjects with partial and absent light perception. Neuroendocrinology 8: 1965 (1971). 8 M attingly, D.: A simple fluorimetric method for the estimation of free 11-hydroxycorticosteroids in human plasma. J. clin. Path. 15 : 374 (1962). 9 M igeon, C. J.; T ylon, F. H .; M ahoney, J. P.; F lorentin, A. R.; C astle, H.; Bliss, E. L., and Samuels, L. T. : The diurnal variation of plasma levels and urinary excretion of 17-hydroxycorticosteroids in normal subjects, night workers and blind subjects. J. clin. Endocr. 16: 622 (1956). 10 M ontalbetti, N.; Bonanoni, L. e Bonini, P. A.: 11 ritmo circadiano della funzione glucocortocoidea surrenalica nell’età senile. Scritti in onore di G. Pellegrini (Viscontea, Pavia 1966). 1 1 O rth , D. N. and Island, D. P. : Light synchronization of the circadian rhythm in plasma cortisol (17-OHCS) concentration in man. J. clin. Endocr. 29: 479 (1969). 12 P incus, G.; R omanoff, L. P., and C arlo, J.: A diurnal rhythm in the excretion of neutral reducing lipids by man and its relation to the 17-ketosteroids rhythm. J. clin. Endocr. 8: 221 (1948). 13 P iotti, L. E.; F errari, E.; M ontalbetti, N. et M azzi, C .: Etude dynamique des fonctions androgène et glycoactive corticosurrénaliennes chez le vieillard; dans Actualités endocrinologiques, La Pitié 1964, p 297 (L’Expansion, Paris 1964). 14 S erio, M.; Piolanti, P.; R omano, S.; D e M aoistris, L., and G iusti, G.: The circa dian rhythm of plasma cortisol in subjects over 70 years of age. J. Geront. 25:95 (1970). 15 S holiton, L. J.; W ork , E. E., and M arnell, R. T.: Diurnal variation of adreno cortical function in non-endocrine disease states. Metabolism 10: 632 (1961). 16 S ilveberg, A.; Rizzo, F., and K rieger, D. T.: Nyctemerale periodicity of plasma 17-OHCS levels in elderly subjects. J. clin. Endocr. 28: 1661 (1968). 17 W f.itzman , E. D. ; N ogeire, C. ; P erlow , M. ; F ukushima, D. ; Sassin, J. ; M c G regor, P. ; G allagher, T. F., and H ellman, L. : Effects of a prolonged 3-hour sleep-wake cycle on sleep stages, plasma cortisol, growth hormone and body temperature in man. J. clin. Endocr. 38: 1018 (1974). 18 W eitzman, E. D.; P erlow , M.; Sassin, J. F .; F ukushima, D.; Burack , B., and H ellman, L. : Persistence of the twenty-four hour patlcrn of episodic cortisol secretion and growth hormone release in blind subjects. Trans. Am. Neurol. Ass. 97: 197 (1972).
Circadian Rhythm of Plasma Cortisol in the Aged (Cosinor Method)1 C. F. C o l u c c i , B. D ’A lessandro , A. B ellastella and N. M ontalbetti S. Maria della Pace Hospital, 00. RR. di Napoli, Institute of Medical Semeiotics, University of Naples, and Magenta Hospital, Magenta
Abstract. Plasma cortisol circadian rhythm was investigated in 18 apparently healthy elderly subjects, in 11 elderly patients affected by cerebrovascular hemiplegia and in 11 otherwise healthy blind elderly subjects. Results were microscopically analyzed by the least squares and Cosinor methods. The circadian rhythm of plasma cortisol was present and normal both in elderly subjects and in elderly patients with cerebrovascular hemiple gia. By contrast, a plasma cortisol rhythm was not found in blind elderly subjects.
1 This paper has been read at the meeting of the European Clinical Section of the International Association of Gerontology, held in Manchester, 1974.
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Frequent anomalies of circadian rhythm concerning the urinary excretion of corticosteroids catabolites have been found in old age [10, 12], and yet plasma cortisol rhythm seems to remain normal [2, 13-16], Circadian adrenocortical rhythm is usually present in localized or diffuse cerebral lesions unless they specifically involve neuroendocrine structures regulating corticotrophic releasing factor (CRF) and ACTH [2, 6], However, different findings have been reported in the literature on adrenocortical rhythm in blind subjects [1, 5, 7, 9, 11, 17, 18]. For many years we have investigated the circadian rhythm of plasma cortisol in the aged by a macrosopic analysis [1,2,13], and recently the data collected by us have been evaluated by means of the microscopic analysis carried out in the Cronobiology laboratories of Minneapolis, Minn., using the Cosinor method as suggested by H alberg et al. [3, 4], These authors have set up a technique for the study of biorhythms by computer, this technique is now widely accepted and used in chronobiological research.
C olucci/D ’A lessan» ro/B ellastella,M ontalbetti
90
Material and Methods We studied 40 male volunteers hospitalized in a long-term geriatric hospital. They were grouped as follows: (1) a control group consisting of 18 apparently healthy subjects aged 62-88 (average 73.11); (2) 11 patients, aged 62-83 (average 67.09), having suffered from cerebrovascular arteriosclerotic hemiplegia from 1 to 5 years. They were free from any endocrine, metabolic, hepatic or renal diseases which might have interfered with the plasma cortisol levels, and (3) 11 apparently healthy but totally blind subjects aged 65-93 (average 74.27). The blindness had been present from 4 to 12 years and had been caused by bilateral glaucoma (cases 1, 2, 5, 6, 8), bilateral cataract (cases 9, 10), panophthalmitis (cases 4,7) and trauma (cases 3, 11). During the experiment none of the subjects were affected by intercurrent acute illness, fever, pains and other episodic symptoms which might have interfered with the validity of the results. All subjects had a 6-7 h sleep rhythm per day, approximately from 10-11 p.m. to 5-6 a.m. Meals were given at 7.30 a.m., 1 p.m. and 6.30 p.m. Blood was sampled through a needle-catheter every 3 or 6 h, starting at 6 a.m. and for a period of 24 or 48 h. Plasma cortisol was assessed by means of the fluorimetric method of M attingly [8]. Results have been microscopically analyzed by the least squares and Cosinor methods consisting in the fitting of a cosine curve in order to find the curve with the least square error from the original data, and in the computation of a sum vector of individual phases and ampli tudes with the confidential limits.
Results Results are summarized in table 1-1V and in figure I. Data show that both in the control group and in the hemiplegic patients the circadian
number
subject
Age
6 a.m.
12 noon
6 p.m.
midnight
6 a.m.
1 2 3 4 5 6 7 8 9 10 11
C. A. V. L. F. L. V. M. B. M. D. B. G. A. P. M. C. V. G. C. T. G.
64 62 63 63 66 66 67 70 71 72 83
18.1 20.7 26.8 9.3 29.0 15.0 8.7 9.8 7.3 28.7 20.0
4.0 14.7 16.0 11.3 15.5 2.3 5.0 12.7 8.7 26.0 14.5
3.5 0 12.0 5.3 8.2 2.7 4.1 4.9 4.0 18.3 4.3
0 0 0 6.7 5.0 0 0 5.7 3.3 4.8 0
19.8 17.8 24.0 9.3 26.6 11.3 9.6 8.7 8.1 30.2 22.5 Downloaded by: King's College London 137.73.144.138 - 11/22/2017 4:22:49 PM
Table I. Circadian rhythm of plasma cortisol (ng%) in the clinically healthy aged subjects
Circadian Rhythm of Plasma Cortisol in the Aged
91
Fig. I. Cosinor representation of the cortisol circadian rhythm in the aged. C ontrols;------ = hemiplegic patients;------ = blind subjects.
rhythm of plasma cortisol is present and its characteristics are similar to those referred in the literature for normal adult subjects. By contrast, a circadian rhythm of plasma cortisol was not found in the blind subjects. Figure 1 shows that in the control and hemiplegic groups the error ellipse does not overlap the origin of the circle. This is significance of a rhythm (p = 0.0001). In the blind subjects, however, the error ellipse covers the origin of the circle, therefore there is no evidence of a statistically significant rhythm (p = 0.150).
These results confirm the occurrence of a normal plasma cortisol rhythm in the clinically healthy aged and in aged patients with cerebral lesions which do not specifically involve neuroendocrine structures regulating CRF and ACT FI [2, 6, 14, 16].
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Discussion
92
Colucci/D ’A lessandro/B ellastella/M ontalbetti
Table II. Circadian rhythm of plasma cortisol number subject
Age
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
88 62 79 62 76 63 71 71 75 75 78 73 71 73 71 75 75 78
A. S. I. G. L. M. P. I. F .G . R. A. R .C . F. B. C.L. P. M. C. C. F .G . F. P. S. M. I. F. C. G. C. A. F. G.
6 a.m.
_ 28.5 -
21.3 20.0 13.4 8.0 15.7 -
32.0 17.8 -
28.0 30.7
9 a.m.
noon
3 p.m.
4.5 14.3
5.3 9.7 10.5 7.6 7.0 12.3 4.7 6.7 10.7 17.5 7.3 21.0 2.2 10.2 5.4 6.7 20.1 24.0
2.0
-
7.5 -
-
15.0 9.5 5.0 -
6.6 7.1 -
-
-
8.1 -
6.0 -
16.4 10.0 -
1.5 -
4.4 8.1 -
-
6 p.m. 5.0 7.4 12.5 0 4.6 24.2 2.0 2.7 5.6 12.0 7.5 12.3 5.5 7.2 6.3 3.7 14.5 10.0
9 p.m. 0 -
6.5 -
2.2 -
12.4 4.4 -
1.0 -
4.4 2.8 -
-
Table III. Circadian rhythm of plasma cortisol Age
1 2 3 4 5 6 7 8 9 10 11
65 73 70 65 67 65 73 73 93 93 80
T. G. T. L. B. G. T. L. R. M. B. A. S. A. D. B. R. G. R. A. E. L.
6 a.m.
-
9.0 -
20.2 9.5 -
26.0
9 a.m.
noon
3 p.m.
6 p.m.
9 p.m.
6.8 11.3 10.1
4.6 15.2 9.5 4.8 4.0 18.5 14.8 25.3 8.5 18.5 9.7
6.9 9.2 11.4
5.8 6.0 14.5 5.8 11.2 24.5 15.6 6.0 7.3 14.2 8.9
13.5 3.1 11.4
-
9.1 -
16.0 -
11.5 12.0
-
8.3 -
12.5 -
17.0 -
17.5
-
1.7 -
6.5 -
13.1 -
14.5
To explain our findings on the blind subjects three hypotheses are suggest ed: (1) a loss of synchronizer light stimuli over a long period, particularly of light-darkness alternating stimuli; (2) presence of free-running rhythms with slightly different periods in the different subjects [11], and (3) circannual
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number subject
93
Circadian Rhythm of Plasma Cortisol in the Aged (ng%) in the aged affected by hemiplegia midnight
6 a.m.
0 4.8 3.4 0 1.0 16.0 0 1.3 3.3 3.5 0 4.0 0 7.8
6.8 29.0 17.0 18.2 9.5 22.0 15.0 6.2 ¡3.8 16.5 11.5 27.5 17.8 16.6 8.0 15.9 31.2 30.3
1 .0
1.2 4.7 4.0
9 a.m.
noon
3 p.m.
6 p.m. 9 p.m.
_
_
_
_
__
-
-
-
-
-
18.5
18.0
10.2
9.0
6.3
midnight 1.5 -
2.8
6 a.m. 3.9 -
15.1
-
-
-
-
-
-
-
7.5
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
13.0 8.4 -
5.6
13.4 8.0 -
3.5
-
9.0 8.5
-
-
-
-
3.5
-
2.5 0 1 .0
-
14.3 12.0 -
14.1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
(ng%) in the elderly blind subjects 6 a.m.
18.0 0 9.3 18.2 2.0 18.0 8.9 0 6.9 16.8 8.3
10.0 8.7 11.0 10.0 12.3 22.2 9.5 8.7 17.2 24.2 18.0
9 a.m.
noon
_
_
-
-
-
-
-
-
14.5 -
5.0 -
10.3
11.0
3 p.m.
_ 13.7
6 p.m.
9 p.m.
_
_
-
-
-
17.4 -
-
-
-
-
-
-
-
-
-
6 a.m.
_ -
5.2
-
-
_
-
-
-
7.4
midnight
6.8 -
-
desynchronization where the phase differences of the circannual rhythm might have overlaid the circadian rhythm variations. Our data are inadequate to exclude or to accept any of the above-mentioned hypotheses. Longitudinal studies on various subjects for an adequate span of time ( = o r > to 30 r)
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midnight
94
C o l u c c i /D 'A lessan dro /B e l l a s t e l l a /M o n t a lb e t t i
Table IV. Analysis of circadian rhythm of plasma cortisol in the aged by Cosinor method1 n
Age
Rhythm PR2 detection
Amplitude ± SE
Acrophase3
Controls
18
62-88 (73,11)
p 0.001
66.8
6.00 ± 2.53
-1 2 3 (-1 0 8 , -139)
Subjects affected by hemiplegia
11
62-83 (67.09)
p 0.001
81.9
7.70 ± 3.03
-1 2 5 (-1 1 1 , -141)
Blind subjects
11
65-93 (74.27)
p 0.150
53.4
1.65 ± 2.65
-148
1 Investigation carried out using the least square method and the Cosinor method in the Cronobiology Laboratories of University of Minneapolis, Minn. 2 Percent variability in relation to the adapted curve. 3 Local midnight.
and transversal studies repeated throughout the year would be needed in order to assess or exclude the presence of free-running rhythms and circannual components. The few available reports in the literature on the circadian rhythm of plasma cortisol in blind people are only based on macroscopic investigation and show conflicting data [5. 7, 9, 11, 18].
1 Bellastella, A. ; C olucci, C. F. e D 'A lessandro, B. : Comportamento del ritmo circadiano del cortisolo plasmatico nel soggetto anziano affetto da cecità totale. Boll. Soc. ital. Biol. sper. 48: 592 (1972). 2 C olucci, C. F . ; D 'A lessandro, B. e Bellastella, A.: Comportamento del ritmo circadiano del cortisolo plasmatico nell’anziano con osenzaesiti di apoplessia cerebrale. Boll. Soc. ital. Biol. sper. 48: 184 (1972). 3 H alberg, F. ; E ngeli, M.; H amburger, C., and H illmann, D.: Spectral resolution of low-frequency, small-amplitude rhythms in excreted 17-ketosteroids; probable andro gen-induced circaseptan desynchronization. Acta endocr., Copenh. 50: suppl. 103, p. I (1965). 4 H alberg, F .; T ong , Y. L., and Johnson, E. A.: Circadian system phase. An aspect of temporal morphology; procedures and illustration examples; in M ayersbach The cellular aspects of biorhythms, pp. 20-48 (Springer, Berlin 1967). 5 H ollwich , F. and D ieckhues, B.: Endocrine system and blindness. Germ. med. mon. /; 122(1971).
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References
Circadian Rhythm of Plasma Cortisol in the Aged
95
Dr. C. F. Colucci, S. Maria della Pace Hospital, 00. RR. di Napoli, 80078 Pozznoli, Napoli (Italy)
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6 K rieger, D. T. and K rieger, H. P.: Circadian variation of plasma 17-hydroxycorticosteroids in central nervous system disease. J. clin. Endocr. 26: 929 (1966). 7 K rieger, D. T. and Rizzo, F.: Circadian periodicity of plasma 11-hydroxycorticosteroids in subjects with partial and absent light perception. Neuroendocrinology 8: 1965 (1971). 8 M attingly, D.: A simple fluorimetric method for the estimation of free 11-hydroxycorticosteroids in human plasma. J. clin. Path. 15 : 374 (1962). 9 M igeon, C. J.; T ylon, F. H .; M ahoney, J. P.; F lorentin, A. R.; C astle, H.; Bliss, E. L., and Samuels, L. T. : The diurnal variation of plasma levels and urinary excretion of 17-hydroxycorticosteroids in normal subjects, night workers and blind subjects. J. clin. Endocr. 16: 622 (1956). 10 M ontalbetti, N.; Bonanoni, L. e Bonini, P. A.: 11 ritmo circadiano della funzione glucocortocoidea surrenalica nell’età senile. Scritti in onore di G. Pellegrini (Viscontea, Pavia 1966). 1 1 O rth , D. N. and Island, D. P. : Light synchronization of the circadian rhythm in plasma cortisol (17-OHCS) concentration in man. J. clin. Endocr. 29: 479 (1969). 12 P incus, G.; R omanoff, L. P., and C arlo, J.: A diurnal rhythm in the excretion of neutral reducing lipids by man and its relation to the 17-ketosteroids rhythm. J. clin. Endocr. 8: 221 (1948). 13 P iotti, L. E.; F errari, E.; M ontalbetti, N. et M azzi, C .: Etude dynamique des fonctions androgène et glycoactive corticosurrénaliennes chez le vieillard; dans Actualités endocrinologiques, La Pitié 1964, p 297 (L’Expansion, Paris 1964). 14 S erio, M.; Piolanti, P.; R omano, S.; D e M aoistris, L., and G iusti, G.: The circa dian rhythm of plasma cortisol in subjects over 70 years of age. J. Geront. 25:95 (1970). 15 S holiton, L. J.; W ork , E. E., and M arnell, R. T.: Diurnal variation of adreno cortical function in non-endocrine disease states. Metabolism 10: 632 (1961). 16 S ilveberg, A.; Rizzo, F., and K rieger, D. T.: Nyctemerale periodicity of plasma 17-OHCS levels in elderly subjects. J. clin. Endocr. 28: 1661 (1968). 17 W f.itzman , E. D. ; N ogeire, C. ; P erlow , M. ; F ukushima, D. ; Sassin, J. ; M c G regor, P. ; G allagher, T. F., and H ellman, L. : Effects of a prolonged 3-hour sleep-wake cycle on sleep stages, plasma cortisol, growth hormone and body temperature in man. J. clin. Endocr. 38: 1018 (1974). 18 W eitzman, E. D.; P erlow , M.; Sassin, J. F .; F ukushima, D.; Burack , B., and H ellman, L. : Persistence of the twenty-four hour patlcrn of episodic cortisol secretion and growth hormone release in blind subjects. Trans. Am. Neurol. Ass. 97: 197 (1972).
