The mechanism of pituitary ACTH secration under various conditions and various endocrine disorders was studied by a synthetic lysine vasopressin (L-8-V) which was re-ported to possess a corticotrophin releasing factor-like activity. Variations in the level of the plasma cortisol were used as an index of ACTH release. Blood samples were drawn before, 15 and 30 minutes after the injection of L-8-V and the concentration of plasma cortisol was determined by a fluorescence method.
Concerning the response of plasma cortisol to various doses of L-8-V, it was revealed that the intravenous injection of 4 units of L-8-V produced a great response, as compared with the intravenous injection of 3 and 2 units respectively and the intramuscular injection of 10 units. Therefores, plasma cortisol response to the intravenous injection of 4 units of L-8-V was standardised as a pituitary function test.
The results of the clincal investigations are summaresed as follows :
L-8-V dose not seem to possess an ACTH-like activity, since no plasme cortisol response was produced in the subjets treated with L-8-V during the infusion of 4 mg of dexamethasone. No response to L-8-V was observed in patients with idiopathic hypopituitarism, patient with acromegaly and patients with craniopharyngioma, though a plasma cortisol response to ACTH was still maintained in those patients.. Although it is un-known whether the L-8-V-induced ACTH release is based on its CRF-like activity, or mediated by the stimulation of CRF secretion, L-8-V is thought to be a kind of stress from its side effects.
A study was made on the effect of an administration of L-8-V as a corticotropin releaser during various times of the circadian rhythm of the plasma cortisol. The material was administered at 10 : 00 a.m. 4 : 00 p.m. and 10 : 00 p.m.
The response to 4 units of L-8-V at 10 : 00 a.m. in 11 subjects resulted in a rise of the plasma cortisol from a mean of 8.8±2.6μg/dl to levels of 14.1±1.9μg/dl at 15 minutes, 14.6±2.5μg/di at 30 minutes;at 4 : 00 p.m. in 5 subjects, from a mean of 6.2±2.8μg/dl to levels of 12.1±2.9 μg/dl at 15 minutes, 14.2±4.7 μg/dl at 30 minutes; at 10 : 00 p.m. in 9 subjects, from a mean of 4.9±1.5μg/sl to levels of 11.6±3.7μg/dl at 15 minutes, 11.9±4.6 μg/dl at 30 minutes.
The response to 250 μg of synthetic ACTH at 10 : 00 a.m. in 7 subjects resulted in a rise of the plasma cortisol from a mean of 10.7±4.1 μg/dl to level of 18.4±4.1 μg/dl at 90 minutes ; at 9 : 00 p.m. in 8 subjects from a mean of 4.4±2.1μg/dl to level of 17.8±3.7μg/dl at 90 minutes.
These data suggest that responsiveness to both L-8-V and ACTH was not significantly different at night from day time. It was assumed that too much ACTH exceedeing the asrenal capacity acted on the adrenal cortex during a short time in both cases.
A study was made on the effect of L-8-V in patients with pituitary adrenal function suppressed by a small dose of dexamethasone. In one group of patients who received 0.5 mg of dexamethasone at midnight, there was a significant rise of plasma cortisol level by the stimulation with L-8-V given at 8 : 00 a.m. However, in the other group of pattients who received 0.5 mg of dexamethasone at 8 : 00 a.m. there was no response to L-8-V given at 4 : 00 p.m. By the pretreatment with 1.5 mg at midnight, the response to L-8-V at 8 : 00 a.m. was suppressed. The result indicates that the responsiveness to L-8-V was greater in the morning than in the evening under the condition of the incomplete pituitary adrenal function caused by the administration of 0.5 mg of dexamethasone. This suggests that a pituitary ACTH secretion in response to stress is more active in the morning than in the evening.

抄録全体を表示

The author has tried to establish a convenient and accurate bioassay method for the determination of C.R.F. (corticotrophin relasing factor) activity of the hypothalamic extract. The principle of the method lies in the combination of two in vitro techniques. In the first step three pituitary halves taken from the freshly sacrified female rats were incubated in vitro for the liberation of ACTH into the incubation medium. In the second step the expected ACTH secretion into the medium was determined by the in vitro assay technique of ACTH-like activity following the description of Tsuji and Yasui, which is characterised through its specificity, high sensitivity and reproductbility (Folia Endo-crinologica Japonica. 41 : 643, 1965).
The method and the results obtained are summarized as follows :
1) As the first test, tissue for the liberation of ACTH three pituitary halves taken from three different rats were placed in two flasks and used in the form of pooled samples. One flask served as test and the other flask as the control. Preincubation of pituitary halves for 60 minutes brought about high sensitivity and well standardized reactivity of the pooled pituitary tissues. After preincubation for sixty minutes three halves of the above-described pituitary halves were placed in the fresh incubation medium after tho-rough washing. A standardized portion of the rat hypothalamus encircling the median eminence was cut out with a razor blade and crude extract was placed with cold galcial acetic acid following the description of Vernikos-Danellis. This extract (henceforth abr. M.M.E.) was added to the incubation medium, in which 3 halves of rat pituitary halves are placed. After final incubation for 60 minutes the expected ACTH secretion in the medium was determined after Tsuji-Yasui's bioassay method of ACTH. The characteris-tic of this last step lies in the use of pooled samples of four beef adrenocortical slices weigh-ing about 100 mg in total as test material. The two-step procedures made it possible to determine the C.R.F. activity of M.E.E. qualitatively and even semi-quantitatively. The sensitivity of the method for C.R.F. activity was in the level of M.E.E. prepared from one animal.
2) At first the author has tried to verify the specifictiy of this assay technique through the exclusion of possible sources of error originating from this M.E.E.
The following points were checked : i) No ACTH-like activity was observed in the M.E.E. ii) No ACTH destroying or potentiating effect was observed in the M.E.E. iii) C.R.F. contained in the M.E.E. was stable for heating up to 100°C for 30 minutes, henceforth all experiments were carried out using M.E.E. heated to 100°C for 30 minutes. This procedure excludes various enzymic actions. iv) No C.R.F. activity was shown in the crude extract of brain cortex. v) It was proved that the M.E.E. acts directly upon the incubated pituitary tissues and induces the release of ACTH. The simultaneous examination of ACTH content of the incubated pituitary tissues revealed the decrease of the ACTH content in the tissue.
3) To verify the presence of ACTH itself in the incubation medium, in which pituitary tissues were placed, a 4 point assay was carried out with the incubation medium and ACTH (Third international standard preparation of ACTH). There was always a 'exact parallelism. In the following experiments for the assay of expected ACTH secretion in the incubation medium two control flasks with two concentrations of ACTH standard preparation, i.e, 10^-2 and 10^-3 mU/flask were incubated simultaneously for the guarantee of the ACTH assay.
4) The specificity of this assay system for the determination of C.R.F. activity was clearly demonstrated in the comparative studies, in which crude extract from brain cortex, serotonin, pitressin, histamine, acetylcholin and bradykinin were used as the test material.

抄録全体を表示

A 32-year-old housewife was admitted to our hospital on March 8, 1965 with the complaints of obesity, fatigability, edema, polyuria and polydipsia. Hypertention and hypokalemia were noted by a physician.
Physical examination revealed a round plethoric face, truncal obesity, crevicodorsal hump, mild hirsutism and purplish striae on the hip and thigh. Biochemical examina-tions showed mild diabetes mellitus and the elevated alkaline phosphatase. Radiological studies showed slight widening of the upper mediastinum and abnormal osteoplastic shadows which were scattered in almost all bones. The skull was normal. Both adrenal glands were considered to be normal in size by retroperitoneal pneumography.
Urinary 17-OHCS levels ranged from 12.2 to 14.8 mg/24 hr. and urinary 17-KS levels were 5.3-12.1 mg/24 hr. Plasma 11-OHCS levels were elevated with the absence of the normal diurnal variation (28.5-34.5 μg/dl.). ACTH test was hyperresponsive while Metopirone (SU-4885) test was normal. Dexamethasone suppression test in doses of 8 mg/day failed to suppress the urinary 17-OHCS.
During her hospitalization, tremor, muscular weakness, irritability and pigmentation of skin appeared. Severe hypokalemia was always present after her admission (2.2-3.3 mEq/L.) and was not improved by treatment. On June 22, she suddenly fell into a coma associated with marked hyperglycemia and hypokalemic alkalosis. (blood sugar levels 400 mg/dl, serum potassium 2.4 mEq/L, blood pH 7.62, Pco₂ 35.0 mmHg.) After recovering from the coma high remittent fever continued without remission. She died on July 16.
Autopsy revealed a malignant thymoma and bilateral adrenocortical hyperplasia. Crooke's change was found microscopically in the pituitary gland. The metastases of the thymoma were found in many bones. Miliary tuberculosis was present. ACTH activity was detected in the malignant tissue (0.45 mU/gm.) with decreased ACTH activity of pituitary gland (Lipscomb & Nelson's method).
It is strongly suggested that thymoma caused Cushing's syndrome.
This case seems to be the second report in Japan of Cushing's syndrome caused by nonendocrine tumors in which the bioassay of ACTH activity was performed.

抄録全体を表示

An attempt was made to clarify the mechanism of biosynthesis and release of ACTH.
According to the method of Wool et al, the isolated rat anterior pituitary glands were incubated with ¹⁴C-phenylalanine, and the redioactivities incorporated into corticotropin (ACTH) and pituitary protein were measured.
The corticosterone in rat plasma was determined by the fluorometric method of De Moor et al.
The following results were obtained.
1) The rate of incorporation of ¹⁴C-phenylalanine and ¹⁴C-alanine into ACTH fraction in the pituitary glands increased after adrenalectomy, but the rate of incorporation of ¹⁴C-isoleucine into ACTH fraction was not affected by the operation.
It is known that isoleucine is not a component of amino acid residues of ACTH.
Thus, the above-mentioned result does give support for identification of the isolated radioactive material with ACTH, although this is not evidence that ACTH and the radioactivity are identical.
2) Puromycin, an inhibitor of protein biosynthesis, inhibited in vitro both ACTH and protein biosynthesis in rat anterior pituitary glands to the same degree.
On the other hand, it was found that protein biosynthesis was far more suppressed by actinomycin C, an inhibitor of DNA dependent RNA bio-synthesis, in vitro than ACTH biosynthesis, and the difference was statistically significant. ACTH biosynthesis in the anterior pituitaries of rats that had been adrenalectomized 1 week before, was inhibited as well as that of normal rat pituitaries by either puromycin or actinomycin C.
These results indicate that the biosynthesis of ACTH seems to involve the participation of polysome, as found in protein formation, although RNA specific for ACTH biosynthesis seems to undergo a slower turnover than RNA for protein biosynthesis, and that the similarity seems to exist between the mechanisms of ACTH biosynthesis in anterior pituitaries of normal and adrenalectomized rats.
3) The rate of incorporation of ¹⁴C-phenylalanine into ACTH fraction in the pituitary glands increased after adrenalectomy and decreased by the treatment with prednisolone. However, protein biosynthesis in the pituitary glands was not affected either by adrenalectomy or by the treatment with prednisolone. Furthermore the addition of prednisolone in vitro failed to affect the incorporation of ¹⁴C-phenylalanine into ACTH fraction in the pituitary glands.
It is generally accepted that biosynthesis and release of ACTH are controled by the concentration of glucocorticoids in blood through the feed-back mechanism.
The above-mentioned results provide evidence that the biosynthesis of ACTH was specifically controled through the feed-back mechanism, irrelevant to protein biosynthe-sis in the pituitary gland, and the target point of the feed-back action of glucocorticoids might not be in the pituitary gland but in the hypothalamus.
4) The concentration of corticosterone in the blood of rats elevated significantly in 30 minutes after intravenous injections of synthetic lysine-vasopressin or the peptide factor (s) extracted from the hypothalamus of rats. However, an extract of rat cerebral cortices by the same procedures as hypothalamic extracts did not cause elevation of corticosterone in the blood of rats.
The biosynthesis of ACTH in the pituitary glands was increased only by the treatment with the peptide factor (s) from the hypothalamus.
Synthetic lysine-vasopressin and peptide fraction from cerebral cortex had no effect on the biosynthesis of ACTH.
Thus, it is considered that there is the peptide factor (s) which is different from vasopressin, and which posesses ACTH biosynthesizing and releasing activities in the rat hypothalamus.
Further studies are required to elucidate whether this factor (s) and corticotropin releasing factor (CRF) are identical or not.

抄録全体を表示

Steroid binding protein in human serum was analyzed with the technique of gel filtration and radio-immunoelectrophoresis.
“Transcortin” which we have named as high affinity for the binding of corticosteroid, may be associated with α₁-glycoprotein.
Serum of twety normal adults and five patients of uterine cancer was analyzed for steroid binding protein. After incubation of C¹⁴-steroid with serum in vitro at 4°C for 40 min., protein fraction of each serum was collected by gel filtration, then concentrated by dialysis using cellulose tube in vacuo. Aliquot of sample was carried out immunoelectrophoresis ; horse anti-human serum (prepared by our Research Institute) was used.
Radioautograms in normal serum revealed the 5 distinct traces of radioactivity associated with the arcs ofρ₁ albumin, α₁-, α₂-lipoprotein, α₁-glycoprotein, but only 3 traces (α₁-, α₂-lipoprotein, and albumin) in cases of hypoproteinemia were observed.
And these results were obtained in each experiment of cortisol, progesterone and estradiol.
From these observations, it is considered that “Transcortin” does not mean only a single protein fraction but involves α₁-, α₂-lipoprotein and α₁-glycoprotein.

抄録全体を表示

The present study was undertaken in order to observe the excretion of I-containing compounds in the urine after oral administration of radioiodide in therapeutic amounts for treatment of thyrotoxicosis. In the literature it is generally agreed that a large portion of iodine excreted in the urine is inorganic iodide. Since the amount of organic radioiodine compounds excreted in the urine is much lower than inorganic iodide, identifi cation of those compounds is difficult. In order to study these minor components, inorganic iodide in the urine collected at 8 hours' intervals for 24 hours was removed as much as possible by passing through an Amberlite IR 120 column. The affluent was concentrated under N₂ atmosphere in order to avoid spontaneous transformation to iodide. High voltage paper electrophoresis and radioautography of the concentrated extracts.
were carried out as described in the previous papers.^{1) '2) '3) '4) '} Each band was identified by RJ values (ratio of mobility of ¹³¹I components/mobility of inorganic iodide) measured from the radioautograms. The paper strips were cut into appropriate sections for counting radioactivity in a well-type scintillation counter. Radioactivity in each section was expressed as percentage of total ¹³¹I compounds. The black bands corresponding to the ¹³¹I-compounds developed by HVPE-radioautography of those extracts were classified into 9 fractions in respect to their RJ values. By referring to the RJ values of known Icontaining compounds under similar conditions, the bands 1, 5, 6, 7 and 8' were assigned to I-, monoiodo-tyrosine (MIT), diiodo-tyrosine (DIT), triiodo-thyronine (T₃) and diiodo-thyronine (T₂). To confirm these identities, the extracts of each section were chromato-graphed by two different solvents. A correlation was found between the percentage of each ¹³¹I compound and BMR of the patients with diverse states of thyroidal function. Fig. 12 shows that the percentage of DIT in the urine increases with accelation of BMR. However, percentage values of T₃, T₂ and MIT decrease when BMR increases as illustrated in Fig. 11, 13 and 14. DIT may arise by metabolism of thyroxine (T₄) as shown by Albert⁵⁾ and Rall⁶⁾ , and hence T₄ is present in circulation, DIT may appear in the urine. It is known that the quantity of T₄ in circulating blood of the patients with thyrotoxicosis is increased. In addition, the fractional turnover of T₄ is abnormally high in the experimental thyrotoxicosis as reported by Ingbar et al⁷⁾ . From these facts the present results can be explained in this maner that the percentage of DIT of urine after ¹³¹I-therapy for thyrotoxicosis increases when BMR is elevated. Urinary T₃ could be derived from free T₃ in circulation as reported by Inada⁸⁾ who also found that the fractional turnover of T₃ was considerably high and that a major proportion of the iodine excreted in the urine was in the form of inorganic iodide in the patients with hyperthyroidism. The present results are consistent with Inada's report. The origin of the urinary T₂ and MIT remains to be solved in the future.

抄録全体を表示

The presence of thyroid autoantibodies in Hashimoto's disease and experimentally induced thyroiditis in animals makes it seem most possible that the lesions in the thyroid gland result from an autoimmune process. Since Rose and Witebsky (1956) many workers have described now they could induce the autoimmune thyroiditis in the dog, rabbit and guinea pig by immunization with homologous thyroid extract with Freund's adjuvant.
These investigations have had a considerable bearing upon the mechanisms underlying the pathogenesis of Hashimoto's thyroiditis. Mackay et al. described the concept of “autoclasia” that the leak of thyroglobulin, and possibly of other thyroid antigens from its follicle might stimulate the formation of autoantibodies in lymphoid tissue and then damage thyroid constituents in situ, thereby releasing more thyroglobulin : thus chain reaction might ensue, culminating in eventual destruction of the gland, but to clarify this concept further investigations may be required.
In 1961 Jones and Roitt showed that marked thyroiditis could be evoked consistently in the rat by immunization with homologous or heterologous thyroid extract or thyrogloblin in Freund's adjuvant, and that tissue destruction was mediated primarily by the invading inflammatory cells, and serum antibody might be implicated, perhaps in a synergistic role.
Following this lead, Wistar strain rats were injected with homologous thyroid suspensions in complete Freund's adjuvant. The present investigation was made in the course of immunization of rats, using serologic and histologic methods. The results obtained were as follows :
1) Wistar strain rats weighing 200 gm. were immunized by injecting 0.1 ml. of the thyroid emulsion mixed with an equal volume of complete Freund's adjuvant (Difco) intradermally in 2 divided doses in each food pad every two weeks. Four animals given a mixture of Freund's adjuvant and saline only (saline emulsion) served as controls.
2) The thyroid glands were removed at 3, 4, 6 and 8 weeks after immunization and their histologic changes were examined. Three weeks later the initial change appeared consisting of a decrease of colloid and sparse infiltration of inflammatory cells. Six weeks later more advanced damage occurred consisting of dense infiltration of inflammatory cells, disruption of colloid, and desquamation of the lying follicle epithelial cells. Eight weeks later severe damage appeared; there were islet-like follicles due to the distortion of the normal thyroid architecture by dense infiltration of inflammatory cells into the interstitial tissue, the presence of germinal centers and occasionally, the leakage of colloid into the interstitium; and furthermore, the development of fibrosis.
3) Circulating thyroid autoantibodies were measured by Oudin or BDB test. BDB hemagglutinating antibodies showed generally a remarkably higher level, compared with precipitating antibodies. Three weeks later circulating thyroid autoantibodies appeared. BDB antibody reached its maximum level (4096) 8 weeks later, and thereafter decreased gradually. An Ouchterlony test, using purified thyroglobulin and microsomal preparation sshowed the presence of anti-thyroglobulins and anti-microsomal antibodies in the serum of rats with severe thyroiditis.
4) In order to investigate the localization of autoantibody in the thyroid gland of rat autoimmune thyroiditis, the fluorescent antibody technique was used, and the following results were obtained : the result of applying a fluorescent antirat gamma globulin to the frozen section of rat thyroid gland with extensive lesions demonstrated that the fluorescein conjugate was present mainly within the follicles, and sometimes in the cells of the follicular epithelium; the staining pattern of intrafollicular colloid was homogeneous or follicular-type. In addition, specific fluorescence (gamma globulin) was also present in the cytoplasm of inflammatory cells.

抄録全体を表示

In spite of many investigations on experimental autoimmune thyroiditis, the exact relationship between circulating and cellular antibodies and thyroiditis in autoimmunized animals remains to be determined. It seems that it is necessary to make an electron microscopic study of experimental thyroiditis to clarify the precise mechanism of tissue damage, but there has been no report on the ultrastructure of experimental thyroiditis, except for that of Sobel and Geller (1965)
On Hashimoto thyroiditis, Irvine and Muir (1963) have recently made an electron microscopic styudy of human chronic thyroiditis and described the presence of the intimate interreaction between invading lymphocytes and the epithelial cells of the thyroid follicles.
The present electron microscopic study on rat autoimmune thyroiditis was carried out to reconfirm their observations. In addition, in order to investigate the localization of autoantibody in the thyroid gland to rat autoimmune thyroiditis, the immunoelectron microscopy was used, and the following results were obtained :
1) Electron micrographs of the thyroid gland, taken 8 weeks later, showed a marked expansion and an extensive confluence of the ergastoplasmic sacs, degeneration and tumefaction of mitochondria, nuclear abnormalities, invasion of dense inflammatory cells, distortion and loss of microvilli; and furthermore, in areas of severe cellular necrosis, disruption of plasma membrane or basement membrane of follicular cells appeared. As a very interesting evidence, it was ovserved that tenuous processes of epithelial cells connect intimately with those of invading lymphocytes. This observation, we believe, is in accord with the finding of Irvine and Muir (1963).
2) To investigate the results obtained by fluorescent antibody technique also at subcellular level, immunoelectron microscopic studies of thyroiditis were made.
First, the result of applying a ferritin conjugate (ferroglobulin) of a globulin fraction of rat serum with severe thyroiditis to the sections of rat thyroid gland with extensive lesions, revealed localization of the antibody in colloid, in ergastoplasmic sacs and on their membranes, and in the perinuclear space.
Second, the incubation of the same thyroid tissue sections with a ferritin conjugate of a globulin fraction of rabbit antirat gamma globulin antibody showed localization of ferritin granules (host gamma globulin) in the same regions observed in the first experiment. It was ascertained that ferritin granules (thyroid autoantibody) were also present in the cytoplasm of invading lymphocytes into thyroid follicle. It seems likely that lymphoid cells infiltrating the thyroid gland of rat thyroiditis may be synthesizing globulins -presumably antibody to the thyroid components.
These studies have shown that tissue damage in experimental thyroiditis may be mediated by the infiltrating inflammatory cells; especially, the presence of germinal centers may be implicated in the production of autoantibody which reacted damagingly with thyroid constituents in situ, thereby releasing more thyroglobulin, and this in turn may provoke further antibody production (“vicious cycle”). In addition, one can suggest also the possibility that the intimate contact between follicular epithelial cells and invading lymphocytes may allow the direct transfer of lymphocyte-bound thyroid autoantibody to the follicular cells, as described by Irvine and Muir (1963). As Koffler and Friedman (1964) and Koffler and Paronetto (1963) have postulated previously, humoral antibody, especially cytotoxic antibody may be of significance in the pathogenesis of experimental thyroiditis, a synergistic role of serum antibody may also not be excluded.

抄録全体を表示

The effect of massive doses of synthetic corticoids, with an initial dose equivalent to 200 mg/day prednisolone, on the hypothalamo-pituitary adrenocortical function and its reserve in the acute leukemic patients was studied. On the basis of results obtained, the adequacy of massive administration of corticoids was discussed.
The cases employed in the study were a total of 26 patients (31 therapeutic courses). They were determined for the daily urinary excretion of Porter-Silber chromogens, Zimmermann chromogens and 17-KGS and then for their consequent response to i. m. injection of 25 unit ACTH-Z or to oral administration of 3 gm SU 4885, before and after treatment. In postmedication follow-ups the 7th day of discontinuance of treatment was taken as Day 1.
i) Both the daily urinary excretion of corticosteroids and the response to ACTH-Z & SU 4885 of the patients with acute leukemia before treatment showed no significant difference from those of the control group, though varied considerably. This means that there generally is no demonstrable dysfunction of the hypothalamo-pituitary adrenocortical system in acute leukemia.
ii) Since, however, there was evidence of dysfunction of the hypothalamo-pituitary adrenocortical system and of reduction in its reserve in some cases, the possible influences of clinical factors on them were studied. The clinical factors examined included age, sex, bleeding tendency, high fever, hepatic enlargement, hepatic insufficiency, A/G ratio, hematocrit, platelet count, WBC & NCC. On each of these factors, the patients were divided into 2 groups as in Fig. 5 to determine whether there is statistically any significant difference in urinary excretion of corticosteroids and response to ACTH-Z between both groups. None of these factors were found to have any conspicuous effect on them.
iii) The 24 hours' urinary excretion of corticosteroids following treatment with massive doses of corticoids in the acute leukemic patients showed no significant difference from that before treatment or of the control group. This is presumably due to our careful reduction of dosage with subsequent tapering at 5 mg daily for two weeks.
iv) The response to ACTH-Z after treatment, as compared to that before treatment or of the control group, was reduced with a significant difference (P<0.05), indicating a reduced adrenocortical reserve following treatment with massive doses of corticoids. Similarly, the response to SU 4885 was found significantly reduced (P<0.05) after treatment as compared to that before treatment or of the control group. But it is impossible to determine whether this change is of hypothalamo-pituitary or of adrenocortical origin.
v) Throughout the therapeutic courses, no clinical and laboratory findings suggestive of hypothalamo-pituitary adrenocortical insufficiency were obtained in any instance.
vi) There was no inverse correlation between the 24 hours' excretion as well as response to ACTH-Z or SU-4885 of urinary corticosteroids after treatment and the sum of administered doses of corticoids as prednisolone or duration (days) of corticoid therapy. It is unlikely, therefore, that the hypothalamo-pituitary adrenocortical function and its reserve reduce with increasing doses and with a longer duration of administration, which is given within the dosage range employed in the present study.
vii) The recovery of the adrenocortical reserve appears to be somewhat retarded after treatment with “massive” doses than with “ordinary” ones. However, the reduction in the adrenocortical reserve produced by treatment with massive doses is by no means irreversible, the reserve being found normalized after 8 months in all instances.
It has been generally accepted that corticoids, when used not as a replacement therapy but for their pharmacologic effects, produce the suppression of the hypothalamo-pituitary adrenocortical system. These results, however,

抄録全体を表示