- Email: [email protected]
ADRENAL SUPPRESSION AFTER SHORT-TERM CORTICOSTEROID THERAPY
1030 anti-human IgG antibody to placental tissue previously treated with human c.M.v. antibody (see figure). This procedure is essentially the same as the commercially available indirect fluorescent antibody test for detection of c.M.v. antibody in human serum. The method can be done on frozen sections or, more conveniently, with tissue routinely processed in paraffin blocks.6 and Pediatrics Services, Oklahoma Children’s Memorial Hospital, Oklahoma City, Oklahoma 73126, U.S.A.
Pathology
a constituent of human Paneth cell secretory it is of rat granules, and this species difference granules means that the rat is probably not a suitable model for zincdeficiency studies on Paneth cells. A short period of severe zinc deficiency in weanling rats produces no Paneth cell abnormalities.5 Microprobe analysis of human Paneth cell granules in patients with acrodermatitis enteropathica and zinc deficiency should prove of value in the investigation of the xtiology of the abnormal inclusion bodies.
to
MARY ANNE MCCAFFREE GEOFFREY ALTSHULER
J. G. J. is supported by the Welsh Scheme for the Development of Health and Social Research. We thank J. A. Chandler for assistance with the microprobe analyses.
SiR,—The letter by Dr Suzuki and colleagues (March 31, p. 734) on inclusion bodies in Paneth cells in zinc deficiency will be of great interest to those interested in Paneth cell structure and function. These bodies had been found previously only in patients with acrodermatitis enteropathica, and it was not certain whether they were caused by the disease process or by the consequent zinc deficiency,.1 Zinc has been associated with Paneth cells since it was detected histochemically in rat Paneth cells by Okamato in
of Pathology, Welsh National School of Medicine, Cardiff CF4 4XN
Department
MARGARET E. ELMES
J. GWYN JONES
ADRENAL SUPPRESSION AFTER SHORT-TERM CORTICOSTEROID THERAPY
SIR,-Dr Spiegel and colleagues (March 24, p. 630) ask high-dose corticosteroid therapy causes hypothalamic-pituitary-adrenal (H.P.A.) suppression. This has been the subject of three previous studiesl-3 also on patients receiving corticosteroids and cytotoxic drugs. The insulin-induced hypoglycxmia test is generally accepted as the best way of assessing the H.P.A. axis. We reported2 the results of insulin tests and corticotropin-stimulation tests in ten patients treated with intermittent high-dose prednisolone
whether short-term
1942.2 Studies on rat Paneth cells have shown that dithizonereactive zinc is not present in all Paneth cells and that it is absent in severely zinc-deficient animals.3 MICROANALYSIS,
major
as
as
INCLUSION BODIES IN PANETH CELLS
ZINC LEVELS DETERMINED BY X-RAY
be
IN PARTS
PER MILLION
..=not done
Studies on human Paneth cells have shown a marked species difference in that samples of jejunum and ileum from 43 patients, none of which demonstrated features of zinc deficiency, contained no histochemically detectable zinc by the dithizone method.4 X-ray microanalysis of the zinc content of human Paneth cells has been done on the A.E.I. ’EMMA4’ instrument (Tenovus Institute, Cardiff) and compared with goblet cells which are not dithizone-reactive in either man or rat, and the’ preliminary results are shown in the table. These results indicate that in patients D and F there was noI appreciable difference in the zinc content of the secretory granules of Paneth cells and goblet cells. In the jejunum zinc levels in Paneth cell granules were of the same order in three patients. However, there was a large variation in the ileum between patients, which may be due to differences in zinc status or to inter-regional variation in the ileum. Regional variations in dithizone reactivity are common in the rat. Technical problems have prevented our doing satisfactory microanalyses of rat Paneth cells. However, zinc does not seem ’
and cytotoxic drugs. Tests were done 36 h after the last dose of prednisolone and repeated 10 days to 1 year later. Plasmaadrenocorticotropin (A.C.T.H.) responses were subnormal in all patients during the first insulin tests and corresponding plasma-corticosteroid responses were subnormal in five. However, three of these five patients had normal plasma-corticosteroid responses to corticotropin stimulation. It therefore seems incorrect to assume that a normal corticotropin response will be associated with a normal stress response in this situation. The corticotropin test, while providing a safe and reliable assessment of adrenal reserve, does not measure hypothalamicpituitary function, even indirectly. We have shown that hypothalamic-pituitary suppression occurred in all patients whereas unequivocal adrenal suppression by our response criteria occurred in only two. Nevertheless all patients had greater responses to corticotropin stimulation in subsequent tests, suggesting some degree of secondary adrenal suppression in each. Seven patients had impaired plasma-A.c.T.H. responses during insulin tests done up to 1 year later indicating prolonged partial anterior pituitary suppression. However, all plasmacorticosteroid responses during insulin tests and to corticotropin were in the normal range as early as 10 days after cessation
of therapy. Short-term high-dose corticosteroid therapy suppresses hypothalamic-pituitary function which may remain subnormal for many months. Suppression at the hypothalamic-pituitary level with or without secondary adrenal suppression accounts for impaired stress responses which can return to normal within 10 days. Cancer
Clinic, University Hospital, Saskatoon, Saskatchewan S7N 0W8, Canada
KENNETH S. WILSON
Department of Hæmatology, Royal Infirmary, Edinburgh
ALISTAIR C. PARKER
5. Elmes, M. E., Gwyn Jones, J. J. Path. (in the press). 1. Wilson, K. S., Gray, C. E., Cameron, E. H. D., Seth,
J., Parker, A C
1976, i, 610. 2. Wilson, K. S., Gray, C. E., Lidgard, C. E., Parker, A. C. Postgrad
Lan-
cet,
1. Elmes, M. E. Lancet, 1975, ii, 549 2. Okamato, K Trans. Soc. Path. Jap. 1942, 32, 3. Elmes, M. E. J. Path. 1976, 118, 183. 4. Midorikawa, O., Eder, M. Histochemie, 1962,
99.
2, 444.
1977,53,745. 3. Naysmith, A., Hancock, Lancet, 1976, i, 715.
B.
med
J
W., Cullen, D. R., Richmond, J, Wilde, C E
Pathology
a constituent of human Paneth cell secretory it is of rat granules, and this species difference granules means that the rat is probably not a suitable model for zincdeficiency studies on Paneth cells. A short period of severe zinc deficiency in weanling rats produces no Paneth cell abnormalities.5 Microprobe analysis of human Paneth cell granules in patients with acrodermatitis enteropathica and zinc deficiency should prove of value in the investigation of the xtiology of the abnormal inclusion bodies.
to
MARY ANNE MCCAFFREE GEOFFREY ALTSHULER
J. G. J. is supported by the Welsh Scheme for the Development of Health and Social Research. We thank J. A. Chandler for assistance with the microprobe analyses.
SiR,—The letter by Dr Suzuki and colleagues (March 31, p. 734) on inclusion bodies in Paneth cells in zinc deficiency will be of great interest to those interested in Paneth cell structure and function. These bodies had been found previously only in patients with acrodermatitis enteropathica, and it was not certain whether they were caused by the disease process or by the consequent zinc deficiency,.1 Zinc has been associated with Paneth cells since it was detected histochemically in rat Paneth cells by Okamato in
of Pathology, Welsh National School of Medicine, Cardiff CF4 4XN
Department
MARGARET E. ELMES
J. GWYN JONES
ADRENAL SUPPRESSION AFTER SHORT-TERM CORTICOSTEROID THERAPY
SIR,-Dr Spiegel and colleagues (March 24, p. 630) ask high-dose corticosteroid therapy causes hypothalamic-pituitary-adrenal (H.P.A.) suppression. This has been the subject of three previous studiesl-3 also on patients receiving corticosteroids and cytotoxic drugs. The insulin-induced hypoglycxmia test is generally accepted as the best way of assessing the H.P.A. axis. We reported2 the results of insulin tests and corticotropin-stimulation tests in ten patients treated with intermittent high-dose prednisolone
whether short-term
1942.2 Studies on rat Paneth cells have shown that dithizonereactive zinc is not present in all Paneth cells and that it is absent in severely zinc-deficient animals.3 MICROANALYSIS,
major
as
as
INCLUSION BODIES IN PANETH CELLS
ZINC LEVELS DETERMINED BY X-RAY
be
IN PARTS
PER MILLION
..=not done
Studies on human Paneth cells have shown a marked species difference in that samples of jejunum and ileum from 43 patients, none of which demonstrated features of zinc deficiency, contained no histochemically detectable zinc by the dithizone method.4 X-ray microanalysis of the zinc content of human Paneth cells has been done on the A.E.I. ’EMMA4’ instrument (Tenovus Institute, Cardiff) and compared with goblet cells which are not dithizone-reactive in either man or rat, and the’ preliminary results are shown in the table. These results indicate that in patients D and F there was noI appreciable difference in the zinc content of the secretory granules of Paneth cells and goblet cells. In the jejunum zinc levels in Paneth cell granules were of the same order in three patients. However, there was a large variation in the ileum between patients, which may be due to differences in zinc status or to inter-regional variation in the ileum. Regional variations in dithizone reactivity are common in the rat. Technical problems have prevented our doing satisfactory microanalyses of rat Paneth cells. However, zinc does not seem ’
and cytotoxic drugs. Tests were done 36 h after the last dose of prednisolone and repeated 10 days to 1 year later. Plasmaadrenocorticotropin (A.C.T.H.) responses were subnormal in all patients during the first insulin tests and corresponding plasma-corticosteroid responses were subnormal in five. However, three of these five patients had normal plasma-corticosteroid responses to corticotropin stimulation. It therefore seems incorrect to assume that a normal corticotropin response will be associated with a normal stress response in this situation. The corticotropin test, while providing a safe and reliable assessment of adrenal reserve, does not measure hypothalamicpituitary function, even indirectly. We have shown that hypothalamic-pituitary suppression occurred in all patients whereas unequivocal adrenal suppression by our response criteria occurred in only two. Nevertheless all patients had greater responses to corticotropin stimulation in subsequent tests, suggesting some degree of secondary adrenal suppression in each. Seven patients had impaired plasma-A.c.T.H. responses during insulin tests done up to 1 year later indicating prolonged partial anterior pituitary suppression. However, all plasmacorticosteroid responses during insulin tests and to corticotropin were in the normal range as early as 10 days after cessation
of therapy. Short-term high-dose corticosteroid therapy suppresses hypothalamic-pituitary function which may remain subnormal for many months. Suppression at the hypothalamic-pituitary level with or without secondary adrenal suppression accounts for impaired stress responses which can return to normal within 10 days. Cancer
Clinic, University Hospital, Saskatoon, Saskatchewan S7N 0W8, Canada
KENNETH S. WILSON
Department of Hæmatology, Royal Infirmary, Edinburgh
ALISTAIR C. PARKER
5. Elmes, M. E., Gwyn Jones, J. J. Path. (in the press). 1. Wilson, K. S., Gray, C. E., Cameron, E. H. D., Seth,
J., Parker, A C
1976, i, 610. 2. Wilson, K. S., Gray, C. E., Lidgard, C. E., Parker, A. C. Postgrad
Lan-
cet,
1. Elmes, M. E. Lancet, 1975, ii, 549 2. Okamato, K Trans. Soc. Path. Jap. 1942, 32, 3. Elmes, M. E. J. Path. 1976, 118, 183. 4. Midorikawa, O., Eder, M. Histochemie, 1962,
99.
2, 444.
1977,53,745. 3. Naysmith, A., Hancock, Lancet, 1976, i, 715.
B.
med
J
W., Cullen, D. R., Richmond, J, Wilde, C E