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The objective evaluation of Psychoneuroendocrinological effects of music is performed in listening and performing. Subjects were classified into 3 groups; a control group and performance/listening groups voluntarily in each 10 subjects. Urine 17-KS-S (abbreviated S) and 17-OHCS (abbreviated OH) were measured before (phase I), after the experiments (phase II) and on the following morning (phase III). They enjoyed listening to their favorite music by stereo sets or performing favorite music instruments. No directions were done on the quality of music. OH showed decreasing effects in both control and performance/listening groups. S showed significant increase in listening group. From a rise of S/OH a wear and tear by stress and a skewness of balance of restoration were corrected. Music is considered that it contributed to relaxation from stress and a wear and tear by the stress and correction of balance of restoration. The fact that the efficacy persisted until the morning of the following day indicates the efficacy persists for a relatively long period of time.

DHEA-S (dehydroepiandrosterone sulfate) has many roles in human body as comprehensive vital power, whose metabolite is urine 17-KS-S (abbreviated S), having function of anti-cortisol. The metabolite of cortisol is urine 17-OHCS (abbreviated OH). DHEA-S is produced not only in adrenal glands but in brain. In order to examine the effects of logotherapy, urine S and OH were examined. Subjects were chronic low back pain patients treated by loxoprofen sodium (NSAID). In Group 1 (n = 11) logotherapy was not added, but in Group 2 (n = 10) it was added. Before the treatment, both groups showed low S and high OH. After 3 weeks, Group 2 showed higher S and lower OH than Group 1. After 18 weeks, 4 cases (40%) were relapsed in Group 2, and 10 (90.9%) were in Group 1 (p < 0.05). Group 2 was divided into 2 groups; relapsed group (n = 4) and non-relapsed group (n = 6). S, OH, S/OH were examined between 2 groups of Group 2 and Group 1. Relapsed group of Group 2 and Group 1 showed lower S and higher OH than non-relapsed group of Group 2. [Discussion] Logotherapy is a method to activate comprehensive human vital power. This is the mechanism through stimulating and activating human brain function.

In terms of adaptability, unlike inanimate objects, living organisms exist in a dynamic balance between "wear and tear" and "repair and recovery". We regarded 17-hydroxycorticosteroids (17-OHCS) as a compound related to tissue "wear and tear" (Hans Selye) and sought for a compound related to tissue "repair and recovery". This led us to the discovery of 17-ketosteroid sulfates (17-KS-S) in urine. Elderly persons, unlike young adults, show low levels in 17-KS-S and little diurnal changes. In an elderly person 17-KS-S can decrease on significant life events (e.g. a spouse's death) and remain at low levels for a long time. Elderly persons with frailty need to improve their lifestyle (meals, exercise, rest, sleep, etc.) qualitatively and quantitatively to adapt themselves to stress adequately. Increased 17-KS-S levels were to be related to improvement in lifestyle.

Urinary DHEA and its metabolites in healthy young female were measured by capillary gas chromatography. The subjects achieved normal pubertal development, and their adrenal DHEA secretions had reached to the stable state. The diurnal variation, fluctuation during the menstrual cycle and seasonal variation of urinary DHEA excretion in each subject were relatively low compared with between-subject variability. We analyzed the urine of the follicular phase in the morning because of the high correlation to the daily urinary pattern. The distribution of the urinary DHEA excretion in follicular phase of the subjects was in the broad range, 80% distributed in the low levels and 20% in the high level. The scattered diagram of the ratio of DHEA to deoxy17KS was separated to 2 groups. Each of them had a high correlation coefficient. The one group had high DHEA ratio to deoxy17KS, and the other group had a low ratio. These findings suggest that the urinary DHEA excretion pattern is highly specific in each subject and may be used as a measure to see the distinction from the others.

Traditional oriental medicine tells us that everything is interrelated and consists of combinations of opposing factors, "Yin-Yang". So we need to evaluate the normal state and pathologic condition from the perspective of dynamic hormone balance between cortisol and DHEA which are opposing and physiologically very important. Cortisol has a more functional side and is considered Yang, while DHEA has a more material side and is considered Yin. We tried to explain the concepts of KAMPO which include SHO (Yin-Yang. Excess-Deficiency), the 6 Stages of Disease and Deficiency of the Kidney, by measuring urinary 17-OHCS and 17-KS-S, metabolites of cortisol and DHEA. We think our effort may develop a good objective indicator of KAMPO's diagnosis and be useful for selecting of treatment.

We found an association between low levels of 17-Ketosteroid Sulfates (17-KS-S) in subjects under psychosocial stress. Stress associated with overwork and lack of sleep resulted in decreased levels of 17-KS-S and an increase in 17-Hydroxycorticosteroids (17-OHCS) levels. Alleviation of stress condition was associated with a restoration of the ratio of 17-KS-S/17-OHCS resulting from a slow increase in 17-KS-S and a decrease in 17-OHCS. In subjects with severe mental stress the ratio of 17-KS-S/17-OHCS showed markedly reduced values with a transient marked increase in 17-OHCS. There was a decrease in the levels of 17-KS-S in depressives, which was more pronounced during severe depression. There was no significant difference in 17-OHCS levels. In a cohort experiencing bereavement, there was a reduction in the levels of 17-KS-S, which remained low for about 50 days. With time, the level of 17-KS-S returned to the basal level established prior to spousal death. In this case, there was no significant change in the levels of 17-OHCS. Persistent severe stress over several months in a physician, led to a Herpes Zoster outbreak and Arrhythmia, resulting in hospital admission. The levels of 17-KS-S gradually decreased over this time reaching 1/3 of the normal baseline value, while 17-OHCS levels remained within normal ranges. These results suggest that measurement of 17-KS-S is indispensable for current research on psychosocial stress.

We examined availability of urinary 17-KS-S to evaluate work and job strain by presented the results in two field research and one experiment. It became clear that urinary S/OH was a comprehensive parameter of thermal strain, under the combined load condition of temperature and exercise, and as an additional factor, under the various load conditions of air velocity. Significant changes of urinary S/OH before and after the rest break and holiday suggested that the findings reflected fatigue conditions. This suggestion was strongly supported by the finding that the values of urinary S/OH on the first day-off after a mid-night shift and those 1 to 3 days later were not able to recover to the value before the night shift. A ratio between urinary 17-KS-S and 17-OHCS, S/OH, suggests a method of evaluating the degree of strain and the condition of fatigue and over-fatigue by measuring these parameters and thus clarifying the work conditions and work-place environment.

In order to evaluate QOL from the perspective of comprehensive medicine, a self-rated QOL Questionnaire and urine 17-KS-S (abbreviated S), 17-OHCS (OH), S/OH were examined in 268 patients (including 11 terminally ill cancer patients) and 31 nurses. Lower S and S/OH were observed in both groups, but OH was higher in patients' group and lower in the nurses' group. Total QOL score was lower in patients' group, but higher in nurses' group. The correlation of each parameter, S, OH and S/OH was related to QOL items. Among terminally ill cancer patients, supplementary treatments were performed. During the course, the elevation of S were observed. In conclusion, S, OH and S/OH were related to QOL and they were considered an objective method of evaluating QOL.

We attempted to determine compounds in human urine which, differing from 17-OHCS, show high values in healthy individuals, decrease with failing health, clearly decline with advancing disease and finally reach very low values in severe disease. We have initially established that 17-ketosteroid sulfates (17-KS-S) are the compound we were searching for. Hans Selye regarded stress as the rate of wear and tear and 17-OHCS as its indicator, but we considered that, differing from inanimate objects, living organisms consume energy to cope with stress and "repair" "wear and tear" of the tissue "and recover" its function. This concept led us to determine the organism's requirements for two mechanisms: "Wear and tear" which could be represented by the secretion of 17-OHCS (Selye), and "repair and recovery", which could be determined by the amounts of 17-KS-S (Nishikaze) derived from dehydroepiandrosterone sulfate (DHEA-S), a product of the adrenal cortex, which enhances neuronal survival, long-term memory, maintains the function of peripheral tissues (skin, bone-muscle, gastro-intestinal and vascular system etc.), increases lipid metabolism, protein anabolism (antiobesity, antiatherosclerosis etc.) and stimulates the immune system. We hold that the stress response is a series of biological processes, beginning with CRH.ACTH and Catecholamines, Cortisol (17-OHCS), followed by Insulin, acting as an anabolic agent and finally DHEA-S (17-KS-S) induces tissue repair utilizing the energy produced. Low levels of urinary 17-KS-S are observed not only in cases of low cortisol or catecholamines secretion, but also when these are elevated. Normalization of these levels is followed by an increase in 17-KS-S excretion. Balanced changes of hormones, such as 17-KS-S, 17-OHCS, Cortisol, Catecholamines and Insulin are seen in a normal organism under healthy lifestyles and disruption of the balance induces an apparent reduction in 17-KS-S. From this perspective, we hope to research the interrelations between biologically antagonistic 17-KS-S and 17-OHCS as well as other agents, focusing particularly on 17-KS-S, which represents a contact point for mind and body, which is kept in healthy balance by appropriate sleeping and exercise programs along with adequate food intake.

Adrenal tumors showing no clinical manifestations (incidentaloma) are frequently encountered during imaging analysis upon routine examinations. These tumors are sometimes associated with hypertension and/or diabetes mellitus (DM). We have examined six cases of incidentalomas with these symptoms in this study. All patients underwent endocrinological evaluation by measuring plasma cortisol and aldosterone levels to assess adrenocortical function. The levels of urinary 17-hydroxysteroids, 17-ketosteroids and catecholamines were also measured. Imaging analysis were performed by using 131I-adosterol scintigraphy, computed tomography and magnetic resonance imaging. Whereas one case was diagnosed as having an adrenal adenoma without the examination of a surgical specimen, other cases underwent surgical removal of the tumor, and final diagnoses were made by pathohistological examination of the tumors. Three cases were diagnosed as having adrenocortical adenomas (one was functioning and others were non-functioning) and one case was diagnosed as having a functional adrenocortical carcinoma. Adenomas were found to produce either non-functional steroids or a small amount of functional steroid hormones. The adenoma patients all suffered hypertension, whereas one of the adenoma patients and the carcinoma patient showed signs of DM. By contrast, of the six cases, one case was diagnosed as having an adrenal cyst, and one case was diagnosed with myelolipoma. Although these two cases suffered DM and hypertension, respectively, it seemed to be unlikely that these clinical symptoms were caused by the adrenal disease. Thus, the present analysis of the six incidentaloma patients suggests that once an adrenal incidentaloma patient with hypertension and/or DM is found, both endocrinological and imaging examinations are necessary to determine the indication of surgical treatment. This analysis supports the present consensus that non-functional adenomas whose sizes are 3cm or less and whose sizes do not change at any reevaluation period, as well as adrenal cysts and myelolipoma should not be surgically removed.

At our medical center we have seen 151 patients who have undergone adrenalectomy from 1971 up until June 1992. There has been a recent increase in the number of cases since 99 patients have been seen in the last eight years from 1985. This increase is related to the increase in the number of incidental tumors. Of those 99, 26 have been incidental tumors. Twenty-four of those have been endocrine inactive tumors, and the remaining 2, both active endocrinologically, were pheochromocytoma. We propose that our tentative indications for surgical treatment of incidental tumors are 1) tumors of diameter 3.5 cm or greater, 2) tumors undeniably malignant by imaging diagnosis, 3) tumors that tend to increase in size with every six-month re-examination, even though the original size is less than 3.5 cm in diameter, and 4) tumors endocrinologically active. The main purpose of this study was to make a differential diagnosis of malignant tumors among incidental tumors. Diagnostic modalities included 1) imaging diagnosis such as echography, CT, MRI, and angiography, 2) analysis of DNA ploidy and BrdU uptake utilizing flow cytometry of excised adrenal tumor tissues, and 3) analysis of urinary steroid fraction. It is generally thought that there are currently no methods by which malignant tumors can be differentiated with certainty, even with modern diagnostic technology, and review of the literature, finds approval or disapproval with regard to the methods we selected to evaluate tumors. What has aroused interest in our results is urinary 17KS fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

We conducted research to determine compounds in human urine which show high values in healthy individuals, decrease with failing health (or bodily decay), clearly decline with advancing illness and finally reach very low values during terminal and severe illness. We have initially established that 17-ketosteroid sulfates (17-KS-S) are the substances we were searching for. Hans Selye regarded stress as the rate of wear and tear and 17-OHCS (cortisol) as its indicator. He further considered that stress is distinct from aging: There is no difference in the stress of ordinary life between young and old people, and there is no difference in 17-OHCS levels between the two. Aging is, however, accompanied by decreased adaptability. In terms of adaptability, we consider that, different from inanimate objects, energy transforming live organisms exist in a dynamic balance between "wear and tear" and "repair and recovery". This shows the need to determine the organism's adaptability to at least these two factors. We regarded 17-OHCS as a compound related to tissue "wear and tear" and searched for a compound related to tissue "repair and recovery", leading us to an identification of 17-KS-S. In other words, we have been considering the relation between "repair and recovery" and "wear and tear". The measurement of 17-KS-S which decreases with failing health, when combined with 17-OHCS, may make it possible to evaluate distortion of adaptation in a Yin-Yang like fashion, which can demonstrate the presence of illness, susceptibility to illness and progress of disease in individuals. It further adds a new dimension to clinical diagnostic acumen in an objective evaluation of psychosocial stress where results of routine clinical tests are often within normal limits, thus facilitating the monitoring of health and illness.

A previously unknown HPLC peak was recently observed in urine samples from patients with Cushing's syndrome and disease. We analysed dansylated derivatives of 17keto steroid glucuronides in urine samples from patients with Cushing's syndrome, Cushing disease and from healthy subjects using high-performance liquid chromatography (HPLC) on reversed-phase Cap Cell PakC8. All urine samples from patients with Cushing's syndrome caused by adrenal adenoma and Cushing's disease showed an unknown large peak at the point between [110HE-G] and [110HA-G] peaks and at a retention time of 25.4 min. The same unknown peak was also observed in urine samples from a patient with asymptomatic cortisol-producing adrenal adenoma and two patients with ectopic ACTH-producing tumor, though the peak height was low for the former and one of the latter but high for the second of the two patients. In contrast, healthy male and female urine only showed a very small peak at the same retention time. Urine samples from a Cushing disease treated with op'DDD and Cushing's syndrome bilaterally adrenalectomized and treating with cortisol showed no such peak. The retention time of this unknown peak is clearly different from that of seven 17keto steroid standard glucuronide conjugates. The structure of this substance may be closely related to [110HE-G] or [110HA-G].

We have conducted research to determine the compounds in human urine which have high values in healthy individuals, decrease with failing health (or bodily decay) and decline rapidly with advancing illness to reach very low values in severe illnesses. We initially established that 17-ketosteroid sulfates (17-KS-S) have the highest values in healthy individuals. Stress was regarded by Hans Selye as the rate of wear and tear and 17-OHCS as its indicator, but we considered that, different from inanimate things, energy transforming live organisms exist in a dynamic balance between "wear and tear" and "repair and recovery". Here it becomes important to determine the organism's adaptability at least to two factors. We regarded 17-OHCS as a compound related to tissue "wear and tear", and a search for a compound related to "repair and recovery", led us to the identification of 17-KS-S. In other words, we considered the relation between "repair and recovery" and "wear and tear". The measurement of 17-KS-S, which decreases with failing health, when combined with 17-OHCS, may make it possible to evaluate distortions in the organism (disturbance of adaptability), which bring the presence of illness or the susceptibility to illness in each person to our notice. Further adding a new dimension to clinical diagnostic acumen in an objective evaluation of psychosocial stress (emotional imbalance, dejection, depression, etc. due to the burden of a heavy debt, dismissal, urgent mental work against a deadline, transfer, inter-personal friction, parent-child relationship, etc.) where results of clinical routine tests are often within normal limits, and in the monitoring of health and illness.

With the recent increase in number of patients with stress, the search is continuing for health-indicators that can be used to determine stress reliably and quickly. These indicators rely on subjective evaluations, and the establishment of an objective method of determining stress is necessary. We have developed a method involving the determination of the 17-Ketosteroid sulfates (17-KS-S) which has proved valuable for stress research. By simultaneous measurement of both 17-KS-S and 17-hydroxycorticosteroids (17-OHCS), which have different biological significance, and which originate from the adrenal gland, an organic Yin-Yang evaluation of the adrenocortical function can be made. The two values (mainly the 17-KS-S values) are closely correlated to the biological stress state as evaluated from psychosocial factors. This method should prove to be valuable in the clinic as an objective method of determining stress.

In primary care, the management of stress-related diseases occupies a wide spectrum of prevention and treatment, from holistic health care to final cure, centered on medical health and an organic integration of body, mind, and social parameters. Inquiries are being made at examinations and interviews to obtain information on the health condition of the patient, but, they are inadequate. There is a need for an objective indicator to help in the diagnosis. With the introduction of the Stress Barometer (measurements of 17-ketosteroid sulfates and 17-hydroxy-corticosteroids) it has become possible to obtain critical information on a patient in a very short time. This method allows early detection of stress, depression state and tiredness from work which is not presently possible from blood tests. It then becomes possible to call the patient's attention to these matters and to work at increasing awareness, energy levels, and responses to the conditions that are determined in this manner.

A 24-year-old man visited our hospital complaining of hypertension and headache. Endocrinological findings revealed no abnormalities except for a slight decrease in serum adrenocorticotropic hormone (ACTH), a slight increase in urine 17-ketosteroid (17-KS), and a marked increase in serum pregnenolone. Computed tomography and magnetic resonance imaging revealed a 3 x 3 cm mass in the right adrenal area and I131-aldosterol scintigraphy demonstrated a high absorption of the isotope in the right adrenal area. Vena cavography suggested a 2 x 2 cm tumor thrombus originating in the right adrenal. Under the diagnosis of the right adrenocortical carcinoma, adrenalectomy and removal of the tumor thrombus were performed. Both serum pregnenolone and urine 17-KS returned to the normal level within a week after the operation and blood pressure was well controlled without any medication 3 months after the operation. Thus, the tumor seemed to be endocrinologically active.

Newly developed resins and high-performance liquid chromatography (HPLC) with column switching technique have enabled on-line solid-phase extraction, purification and derivatization for highly sensitive determination in recently developed determination methods for serum cortisol, urinary 17-ketosteroids (17-KS), urinary conjugated 17-KS fractions and urinary free catecholamines (CA). These methods are (1) determination of serum cortisol by HPLC with a BSA-ODS column (TSK) and serum sample direct injection, (2) determination of fluorescently derivatized serum cortisol with sulfuric acid and ethanol by column switching HPLC, (3) determination of urinary 17-KS with no need of previous hydrolysis of the conjugated forms, (4) HPLC of conjugated 17-KS fluorescently prelabelled with dansyl hydrazine, (5) HPLC of urinary free catecholamines (CA) with on-line extraction using a cation exchange column and on-line fluorescent derivatization with 1,2-diphenylethylenediamine, (6) ion pair HPLC of urinary free CA with on-line extraction using a hard boric acid gel column and postcolumn trihydroxyindole derivatization, and (7) HPLC of urinary free CA with on-line extraction and solid-phase derivatization using a boric acid gel column, o-phthalaldehyde and 2-mercaptoethanol, have achieved no previous or simple sample extraction, more rapid, accurate and higher sensitive determination comparison with ordinary methods for these substances and furthermore, some methods have enabled fully automated analysis.

Hypothalamic-pituitary-adrenocortical function was investigated in 14 patients with anorexia nervosa. Impaired suppression of plasma cortisol by dexamethasone was revealed. In 14 patients with anorexia nervosa, circadian rhythm of plasma cortisol, insulin tolerance test, rapid ACTH test and overnight dexamethasone suppression test were examined. Levels of plasma cortisol were higher than those in control subjects throughout the day, and normal circadian rhythm of plasma cortisol was not observed. Basal levels of plasma ACTH were within normal range. tthe response of plasma cortisol to insulin-induced hypoglycemia was lower than that in control subjects, while the response of plasma cortisol in rapid Acth test was normal. In overnight suppression tests, in which one mg dexamethasone was administered orally, 11 of 14 patients showed no suppression of plasma cortisol and 3 other patients showed incomplete suppression. Elevated levels of plasma cortisol and the absence of normal circadian rhythm in patients with anorexia nervosa and malnutrition have already been reported by other investigators, and these abnormalities were ascribed to the delayed half life of plasma cortisol due to impaired cortisol metabolism. However, according to our investigation, it is difficult to explain the failure of dexamethasone to suppress cortisol only by the delayed half life of plasma cortisol, and it is supposed that some kind of abnormal hypothalamic control is also involved.

A quantitative analysis of seven components of 17-KS in human urine was successfully carried out by GCMS. The sample including deuterated 17-KS was introduced into TMS derivatives by BSTFA in pyridine. The derived TMS derivatives were analysed using the GC-MS system equipped with the column of 0.5% NPGS Chromosorb W AW DMCS, and the temperature was programmed from 180 degrees C to 240 degrees C at 3 degrees C/min. increment. Seven components were well separated, and each fraction was analysed by MS spectrum. Normal human urine was analysed by this method, the result of which is summarized in Table 3.

The effects of ACTH preparations on the pituitary-adrenocortical function remain to be clarified in more respects than those of steroid drugs. In the present study, the author investigated the effect of synthetic ACTH-Z on the pituitary-adrenocortical function in a series of 76 patients under synthetic ACTH-Z therapy using the daily urinary excretion of 17-KGS as an index. The results are summarized as follows: 1) The administration of synthetic ACTH-Z in a dose of 0.25 mg or 0.5 mg q.d. was followed by a gradually declining tendency of the daily urinary excretion of 17-KGS. More particularly, after 1.5 months of synthetic ACTH-Z medication at either of these dosage levels, the response of urinary 17-KGS was found to have decreased to about 1/2 of its level at the beginning of medication. 2) The responsiveness of urinary 17-KGS was well maintained even after 3 months of intermittent doses of 0.25 mg of synthetic ACTH-Z (3 times a week, or every other day). 3) Synthetic ACTH-Z, when used in a smaller dose of 0.125 mg daily, produced a minimal stimulating effect on the adrenal cortex. When administered in a less frequent (twice weekly) dose of 0.25 mg, synthetic ACTH-Z failed to prevent or counterbalance atrophy of the adrenal cortex induced by small doses of steroid drugs (average total dose equivalent to 12.2 mg of prednisolone). 4) With the purpose of activating the steroid-atrophied adrenal cortex, synthetic ACTH-Z was administered in a daily or intermittent (every other day, or 3 times a week) dose of 0.25 mg. With the daily dosage regimen, the atrophied adrenal cortex temporarily exhibited a good response, but its responsiveness soon decreased again, and in the end, synthetic ACTH-Z administered in this mode failed to activate the adrenal cortex. With the intermittent dosage regimen, on the other hand, a tendency toward recovery of adrenocortical responsiveness was observed in half the cases studied. In the remaining half receiving steroids over a prolonged period of time, recovery of adrenocortical responsiveness was not attained to any appreciable extent. These results might be interpreted as suggesting that the administration of synthetic ACTH-Z in an intermittent dose of 0.25 mg or 0.5 mg is advisable for the activation of the atrophied adrenal cortex. If this therapeutic regimen fails to initiate a tendency to recovery of adrenocortical responsiveness in a matter of a month or two, this implies that there is atrophy of the adrenal cortex severe enough to invalidate the therapeutic use of synthetic ACTH-Z. 5) The response of the adrenal cortex of 0.25 mg doses of synthetic ACTH-Z was distinctly suppressed by the concomitant use of steroids in 10 mg doses (as calculated on a prednisolone basis). Likewise, the response of the adrenal cortex of 0.5 mg doses of synthetic ACTH-Z was suppressed to 78%, 46% and 16%, respectively, by the conjoined use of steroids in doses of 20 mg, 30 mg and 40 mg or above...