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Adrenocortical function in vitiligo
Clinica Chimica Acta, 113 (1981) 325-327 Elsevier/North-Holland Biomedical Press
CCA
325
1802
Short
communication
Adrenocortical SK.
function in vitiligo
Pal a**, K.K. Ghosh a, R.K. and P.K. Banerjee ’
Panja
’
UDepartment of Biochemisrv und RIA Unit, Institute of Post-Graduate Medrcul Educurlon and Research, h Dermaiology Umt, Calcutta Medicul College, and ’ Depurtment of Physiology, Dr. B. C. Rqv Post Gruduate Institute of Basrc Medical Sciences, Calcu~ru (Indra) (Received
July IOth, 1980)
In our earlier studies with vitiligo patients we observed hypothyroidism which was shown by TSH stimulation test to be secondary [ 11. From studies of TSH response to TRH we subsequently suggested that the hypothyroidism in such cases was secondary to some defect at the suprahypophyseal level [2]. It is now well established that both ACTH, through its action on adrenal cortex, and glucocorticoids influence thyroid function. Administration of glucocorticoids reduces serum TSH in hypothyroid patients. This action is believed to be mediated through inhibition of TRH release. It has also been shown that the rate of turnover of cortisol is decreased in hypothyroidism due to a decrease in the rate of oxidation of cortisol [3]. These observations led us to study adrenocortical function in vitiligo by estimating the levels of plasma cortisol and ACTH and also by assessing adrenocortical response to ACTH. Materials and methods 20 Male vitiligo (idiopathic in nature) patients, age ranging between 24 and 46 years, were selected. Clinical examinations were carried out to exclude disorders of adrenal cortex which are associated with Addison’s disease, Cushing’s disease, etc. The patients were not obese and no sign of hyperpigmentation was evident. Blood pressure in all the patients was normal. Routine biochemical tests such as blood sugar, urea, cholesterol, electrolytes, etc. were performed and these were found to be within normal ranges. Hashimoto’s thyroiditis was excluded on the basis of absence of thyroid antibodies. Diabetes mellitus and pernicious anaemia were excluded by oral G.T.T. and haematological studies, respectively. The patients were administered no medications for at least one month prior to our studies. 20 Normal healthy males of the same age group were taken as controls. Blood samples were obtained by venepuncture at 8 a.m. after overnight fasting. Plasma was separated and preserved according to the method of Orth [4] till the assay was done. Plasma cortisol and ACTH were estimated by radioimmunoassay techniques according to the methods of Vecsei [5] and Orth [4], respectively. From
* Correspondence
to: SK.
Pal, 16A Shibdas
0 009-898 l/8 1/OOO& 0000/$02.50
Bhaduri
Street, Calcutta-700004,
0 Elsevier/North-Holland
Biomedical
Press
India
326
these 20 patients, 5 (age range 32-46 yr) were then selected at random and were administered 40 U. of Acthar Gel Corticotrophin (Armour Company Ltd., U.K.) intravenously at 8 a.m. Blood samples were obtained by an indwelling catheter at 0, 30 and 60 min after the injection. Plasma cortisol was estimated in each of these samples. This test was also carried out in 5 normal healthy subjects of the same age group. Results and discussion From Table I it is evident that cortisol is significantly higher and ACTH significantly lower in vitiligo patients as compared to controls. It may seem from Table I that the cortisol values in the control group are somewhat lower than the values quoted by other workers. This could be explained by the fact that we estimated cortisol by radioimmunoassay, which is specific for cortisol. Therefore, the results may not be comparable with those done by fluorimetric methods which are nonspecific and as such would give falsely high values. Our laboratory normal for cortisol (8 a.m. samples) in adults (500 cases) is from 220 to 415 (nmol/l) with a mean of 318. This adds further support for the notion that the values found in vitiligo patients are higher than normal. It has been shown that high levels of both ACTH and glucocorticoids, separately, can alter thyroid function by suppressing pituitary TSH secretion [3]. It is also established that the higher the level of cortisol-like steroids, the lower the ACTH secretion [6]. In our earlier studies [l] we have observed hypothyroidism in vitiligo patients which was thought to be secondary in nature. The results obtained from this study are in agreement with our previous findings as well as with the studies relevant to hypothyroidism caused by ACTH and glucocorticoids. There has been some controversy regarding the role of cortisol in the pigmentation process but experimental studies by Snell [7] have suggested that probably cortisol inhibits the release of ACTH although itself it has no direct action on mammalian epidermal melanocytes. As to the effects of ACTH on pigmentation it has been shown that pure ACTH can cause dispersion of melanin granules in frog melanophores [8] and injection of ACTH into a negro woman caused hyperpigmentation of skin and buccal mucous membrane [9]. Thus the findings of high cortisol and low, ACTH in vitiligo are consistent with the clinical and experimental studies with ACTH. From the data presented in Table I questions may be raised as to whether or not there is some primary adrenocortical alteration. From clinical observations no such abnormality could be found. We were then interested to find out the adrenocortical response to ACTH in order to investigate
TABLE LEVELS
I OF CORTISOL
(nmol/l)
AND ACTH
(mu/l)
Cortisol
Control Vitiligo
IN PLASMA
ACTH
range
mean k S.E.M.
range
mean 2 S.E.M.
225-410 405-685
313_t 10.9 592 i 22.3
2.0-6.3 1.0-3.9
4.2 k 0.26 2.6t0.18
p
327 TABLE PLASMA
II CORTISOL
Time (min)
RESPONSE
TO ACTH
Vitiligo
Control
0 30 60 p
(nmoI/l)
range
mean -C S.E.M.
range
mcan_f
245- 415 495- 890 645- I100
324i21.8 687 i 47.2 868 ? 56.3
440- 710 760- 1300 1220- 2050
581% 35.4 10251 67.1 16422 107.3
S.E.M.
in all three observations
alteration of adrenocortical function, if any, in vitiligo patients. From Table II it is seen that there is significantly higher response to ACTH in vitiligo as compared to controls. It is difficult to explain this exaggerated response from our studies. It may be presumed that the effect is due to some stress and/or derangement in the pituitary-thyroid-adrenal axis. References Pal, SK., Ghosh. K.K. and Banerjee. P.K. (1980) Thyroid function in vitiligo. Clin. Chim. Acta 106. 331-332 Pal, SK., Ghosh, K.K.. Panja, R.K. and Banejee, P.K. (1981) TSH response to TRH in vitiligo. Clin. Chim. Acta 110, 335-336 Ingbar, S.H. and Woeber, K.A. (1974) The thyroid gland. In: Textbook of Endocrinology (Williams, R.H., ed.), pp. 125, 195, W.B. Saunders, Philadelphia Orth, D.N. (1974) Adrenocorticotropic hormone and melanocyte stimulating hormone. In: Methods of Hormone Radioimmunoassay (Jaffe, B.M. and Behrman, H.R., eds.). pp. 125- 159, Academic Press. New York Vecsei, P. (1974) Glucocorticoids: cortisol, corticosterone and compound S. In: Methods of Hormone Radioimmunoassay (Jaffe, B.M. and Behrman, M.R.. eds.), pp. 393-415 Liddle, G.W. and Melmon, K.L. (1974) The adrenals. In: Textbook of Endocrinology (Williams. R.H.. ed.), pp. 240, W.B. Saunders, Philadelphia Snell. R.S. (1966) Effect of hydrocortisone and adrenalectomy on the activity of mammalian epidermal melanocytes. J. Endocrinol. 35, 355-361 Shepherd, R.G., Howard, K.S., Bell, P.H., Cacciola, A.R., Child, R.G.. Davies, M.C., English, J.P.. Finn, B.M., Meisenhelder, J.H., Moyer, A.W. and Van der Scheer, J. (1966) Studies with corticotropin. Isolation, purification and properties of beta-corticotropin. J. Am. Chem. Sot. 78, 5051-5059 Lemer, A.B. and McGuire, J.S. (1964) Melanocyte stimulating hormone and adrenocorticotrophic hormone. New Engl. J. Med. 270, 539-546
CCA
325
1802
Short
communication
Adrenocortical SK.
function in vitiligo
Pal a**, K.K. Ghosh a, R.K. and P.K. Banerjee ’
Panja
’
UDepartment of Biochemisrv und RIA Unit, Institute of Post-Graduate Medrcul Educurlon and Research, h Dermaiology Umt, Calcutta Medicul College, and ’ Depurtment of Physiology, Dr. B. C. Rqv Post Gruduate Institute of Basrc Medical Sciences, Calcu~ru (Indra) (Received
July IOth, 1980)
In our earlier studies with vitiligo patients we observed hypothyroidism which was shown by TSH stimulation test to be secondary [ 11. From studies of TSH response to TRH we subsequently suggested that the hypothyroidism in such cases was secondary to some defect at the suprahypophyseal level [2]. It is now well established that both ACTH, through its action on adrenal cortex, and glucocorticoids influence thyroid function. Administration of glucocorticoids reduces serum TSH in hypothyroid patients. This action is believed to be mediated through inhibition of TRH release. It has also been shown that the rate of turnover of cortisol is decreased in hypothyroidism due to a decrease in the rate of oxidation of cortisol [3]. These observations led us to study adrenocortical function in vitiligo by estimating the levels of plasma cortisol and ACTH and also by assessing adrenocortical response to ACTH. Materials and methods 20 Male vitiligo (idiopathic in nature) patients, age ranging between 24 and 46 years, were selected. Clinical examinations were carried out to exclude disorders of adrenal cortex which are associated with Addison’s disease, Cushing’s disease, etc. The patients were not obese and no sign of hyperpigmentation was evident. Blood pressure in all the patients was normal. Routine biochemical tests such as blood sugar, urea, cholesterol, electrolytes, etc. were performed and these were found to be within normal ranges. Hashimoto’s thyroiditis was excluded on the basis of absence of thyroid antibodies. Diabetes mellitus and pernicious anaemia were excluded by oral G.T.T. and haematological studies, respectively. The patients were administered no medications for at least one month prior to our studies. 20 Normal healthy males of the same age group were taken as controls. Blood samples were obtained by venepuncture at 8 a.m. after overnight fasting. Plasma was separated and preserved according to the method of Orth [4] till the assay was done. Plasma cortisol and ACTH were estimated by radioimmunoassay techniques according to the methods of Vecsei [5] and Orth [4], respectively. From
* Correspondence
to: SK.
Pal, 16A Shibdas
0 009-898 l/8 1/OOO& 0000/$02.50
Bhaduri
Street, Calcutta-700004,
0 Elsevier/North-Holland
Biomedical
Press
India
326
these 20 patients, 5 (age range 32-46 yr) were then selected at random and were administered 40 U. of Acthar Gel Corticotrophin (Armour Company Ltd., U.K.) intravenously at 8 a.m. Blood samples were obtained by an indwelling catheter at 0, 30 and 60 min after the injection. Plasma cortisol was estimated in each of these samples. This test was also carried out in 5 normal healthy subjects of the same age group. Results and discussion From Table I it is evident that cortisol is significantly higher and ACTH significantly lower in vitiligo patients as compared to controls. It may seem from Table I that the cortisol values in the control group are somewhat lower than the values quoted by other workers. This could be explained by the fact that we estimated cortisol by radioimmunoassay, which is specific for cortisol. Therefore, the results may not be comparable with those done by fluorimetric methods which are nonspecific and as such would give falsely high values. Our laboratory normal for cortisol (8 a.m. samples) in adults (500 cases) is from 220 to 415 (nmol/l) with a mean of 318. This adds further support for the notion that the values found in vitiligo patients are higher than normal. It has been shown that high levels of both ACTH and glucocorticoids, separately, can alter thyroid function by suppressing pituitary TSH secretion [3]. It is also established that the higher the level of cortisol-like steroids, the lower the ACTH secretion [6]. In our earlier studies [l] we have observed hypothyroidism in vitiligo patients which was thought to be secondary in nature. The results obtained from this study are in agreement with our previous findings as well as with the studies relevant to hypothyroidism caused by ACTH and glucocorticoids. There has been some controversy regarding the role of cortisol in the pigmentation process but experimental studies by Snell [7] have suggested that probably cortisol inhibits the release of ACTH although itself it has no direct action on mammalian epidermal melanocytes. As to the effects of ACTH on pigmentation it has been shown that pure ACTH can cause dispersion of melanin granules in frog melanophores [8] and injection of ACTH into a negro woman caused hyperpigmentation of skin and buccal mucous membrane [9]. Thus the findings of high cortisol and low, ACTH in vitiligo are consistent with the clinical and experimental studies with ACTH. From the data presented in Table I questions may be raised as to whether or not there is some primary adrenocortical alteration. From clinical observations no such abnormality could be found. We were then interested to find out the adrenocortical response to ACTH in order to investigate
TABLE LEVELS
I OF CORTISOL
(nmol/l)
AND ACTH
(mu/l)
Cortisol
Control Vitiligo
IN PLASMA
ACTH
range
mean k S.E.M.
range
mean 2 S.E.M.
225-410 405-685
313_t 10.9 592 i 22.3
2.0-6.3 1.0-3.9
4.2 k 0.26 2.6t0.18
p
327 TABLE PLASMA
II CORTISOL
Time (min)
RESPONSE
TO ACTH
Vitiligo
Control
0 30 60 p
(nmoI/l)
range
mean -C S.E.M.
range
mcan_f
245- 415 495- 890 645- I100
324i21.8 687 i 47.2 868 ? 56.3
440- 710 760- 1300 1220- 2050
581% 35.4 10251 67.1 16422 107.3
S.E.M.
in all three observations
alteration of adrenocortical function, if any, in vitiligo patients. From Table II it is seen that there is significantly higher response to ACTH in vitiligo as compared to controls. It is difficult to explain this exaggerated response from our studies. It may be presumed that the effect is due to some stress and/or derangement in the pituitary-thyroid-adrenal axis. References Pal, SK., Ghosh. K.K. and Banerjee. P.K. (1980) Thyroid function in vitiligo. Clin. Chim. Acta 106. 331-332 Pal, SK., Ghosh, K.K.. Panja, R.K. and Banejee, P.K. (1981) TSH response to TRH in vitiligo. Clin. Chim. Acta 110, 335-336 Ingbar, S.H. and Woeber, K.A. (1974) The thyroid gland. In: Textbook of Endocrinology (Williams, R.H., ed.), pp. 125, 195, W.B. Saunders, Philadelphia Orth, D.N. (1974) Adrenocorticotropic hormone and melanocyte stimulating hormone. In: Methods of Hormone Radioimmunoassay (Jaffe, B.M. and Behrman, H.R., eds.). pp. 125- 159, Academic Press. New York Vecsei, P. (1974) Glucocorticoids: cortisol, corticosterone and compound S. In: Methods of Hormone Radioimmunoassay (Jaffe, B.M. and Behrman, M.R.. eds.), pp. 393-415 Liddle, G.W. and Melmon, K.L. (1974) The adrenals. In: Textbook of Endocrinology (Williams. R.H.. ed.), pp. 240, W.B. Saunders, Philadelphia Snell. R.S. (1966) Effect of hydrocortisone and adrenalectomy on the activity of mammalian epidermal melanocytes. J. Endocrinol. 35, 355-361 Shepherd, R.G., Howard, K.S., Bell, P.H., Cacciola, A.R., Child, R.G.. Davies, M.C., English, J.P.. Finn, B.M., Meisenhelder, J.H., Moyer, A.W. and Van der Scheer, J. (1966) Studies with corticotropin. Isolation, purification and properties of beta-corticotropin. J. Am. Chem. Sot. 78, 5051-5059 Lemer, A.B. and McGuire, J.S. (1964) Melanocyte stimulating hormone and adrenocorticotrophic hormone. New Engl. J. Med. 270, 539-546