17-OHCS Levels Research Articles

Analysis of RIG-I-mediated innate immune response in rats with Kidney-Yang Deficiency Syndrome and its change following Yougui pill administration

Kidney-Yang Deficiency Syndrome (KYDS) is closely bound up with the immune response of immunocompromised patients. The study is to investigate whether retinoic acid-inducible gene-I (RIG-I)-mediated innate immune responseparticipates in the development of KYDS in rats and evaluate the effect of Yougui pill (YGP) on the response in KYDS rats. KYDS rats were induced by intramuscular injection of hydrocortisone at the dose of 10 mg/kg/d for 15 days. YGP at concentrations of 2.43 g/kg/d and 4.86 g/kg/d were administered intragastrically to KYDS rats for 30 days. The results showed that the body weight, urinary 17-hydroxycorticosteroid (17-OHCS) level, spleen size and spleen index in KYDS rats were significantly decreased compared with healthy control rats, while YGP treatment reversed them towards normal level in a dose-dependent manner. Moreover, KYDS challenge not only strikingly increased the mRNA and protein expression levels of RIG-I, tripartite motif containing 25 (TRIM25), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) but also markedly enhanced the endogenous RIG-I polyubiquitination levels. Whereas, YGP treatment effectively reversed this tendency in a dose-dependent manner. In conclusion, these findings revealed that RIG-I-mediated innate immune response was closely bound up with the development of KYDS. And YGP exhibited certain anti-inflammatory effects on KYDS rats via inhibiting the RIG-I-mediated innate immune response.

A CASE OF ADRENAL ADENOMATOID TUMOR DIAGNOSED BY IMMUNOHISTOCHEMICAL EVALUATION.

An adenomatoid tumor is a benign tumor of mesothelial derivation, typically found in the genital track. However, though extremely rare, an adenomatoid tumor can be found in the adrenal gland, making it difficult to clinically and radiologically differentiate it from an adrenocortical tumor or a pheochromocytoma prior to surgery. We encountered a-52-year old man with an adenomatoid tumor in the adrenal gland, who presented with an incidentally discovered left adrenal mass revealed by PET-CT from his regular health examinations. He had been diagnosed with paroxysmal hypertension two years before and was being treated with a hypolipidemic agent. Abdominal computed tomography revealed a left adrenal mass measuring 25 × 15 mm, and the findings were different from the typical adrenocortical adenoma or pheochromocytoma. Although laboratory examinations of his blood samples indicated normal adrenal function, 24-hour urine specimens revealed high levels of 17-OHCS, 17-KS, and catecholamine. Both 131I-MIBG scintigraphy and phentolamine tests showed negative findings. The patient underwent a laparoscopic left adrenalectomy. The cut surface of the left adrenal gland weighing 21 g contained a white, solid mass measuring 25 × 15 × 20 mm within the adrenocortical tissue. Histologically, the tumor was composed of small tubules lined by eosinophilic tumor cells. The tumor cells were immunohistochemically positive for cytokeratins and calretinin, but negative for steroidogenic factor-1. Therefore, based on these findings, we diagnosed this tumor as an adrenal adenomatoid tumor. Histopathologically, the adrenal adenomatoid tumor may be difficult to distinguish from an adrenocortical adenoma, carcinoma, lymphangioma, hemangioma, angiosarcoma, or metastatic adenocarcinoma. Under these conditions, immunohistochemical examination is useful for definite diagnosis.

Biomarkers for cancer-related fatigue and adverse reactions to chemotherapy in lung cancer patients.

This study was conducted to investigate the biomarkers that appear to be correlated with cancer-related fatigue (CRF) and the adverse reactions (ADRs) to chemotherapy. A total of 100 lung cancer patients were selected and CRF prior to and following chemotherapy was evaluated. The plasma levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1 and the level of 17-hydroxycorticosteroid (17-OHCS) in the urine were analyzed and correlated with CRF and the ADRs associated with chemotherapy. The incidence of CRF was found to be 88.0% and ADRs following chemotherapy occurred in 15.0% of the patients. An increase in the TNF-α and IL-1 levels was detected in patients with CRF. The level of 17-OHCS in the urine was found to be elevated in cases that experienced ADRs following chemotherapy. In conclusion, CRF is closely correlated with increased plasma levels of TNF-α and IL-1. Furthermore, an abnormally elevated 17-OHCS level in the urine may be an important indicator predicting ADR development following chemotherapy.

Study relationship between the value of 17-OHP and the value of testosterone in monitoring for congenital adrenal hyperplasia

Deficiency of 21-hydroxylase (21-OHD) is present in 90–95% cases of congenital adrenal hyperplasia (CAH), an autosomal recessive disorder. CAH affects severely on the physical development and reproductive function. In monitoring the disease and evaluating treatment outcome, presentation of salt wasting, electrolyte disturbance, androgenism, cushingoid features, plasma levels of 17-OHP, testosterone, Δ4-androstenedione, urinary levels of 17-OHCS, 17-CS, and bone age were used. We aimed to study relationship between the value of the plasma 17–OHP and the value of the plasma testosterone levels to monitor treatment of CAH. The study was prospective. We collected 82 CAH Vietnamese patients who were diagnosed of 21-OHD. The have been treated and monitored at the Vietnam National Hospital of Pediatrics. Hanoi, Vietnam in the period of 1/2007- 1/2010. The value of plasma levels of 17-OHP and testosterone were measured in combination with clinical symptoms every 6 months. In 82 study’s CAH patients aged 1-15 years old, the group aged < 10 years old occupied 82.9%. The salt – wasting form occupied 75.6%; the simple virilizing form 24.4%. 59/82 of patients (71.1%) had successful treatment with the mean plasma level 17-OHP of 0.02-5.67 nmol/l and the mean levels of testosterone of 0.01- 8.02 nmol/l according to groups'ages. The mean levels of plasma 17-OHP and testosterone also increased with age and sex in the group of patients having failed treatment. It confirmed a positive relationship between the value of plasma 17 – OHP and levels of the testosterone with 95% significant confidence. Each time of patient examination, besides clinical symptoms and plasma levels of 17-OHP should be done to evaluate treatment.

Change of aquaporin-1 in rat models of kidney-yang-deficiency syndrome

To explore the material foundation of kidney-yang-deficiency syndrome. Two kinds of rat models of deficiency of kidney-yang were induced by adenine intragastric administration (model I) and hydrocortisone intramuscular injection (model II). One hundred rats were randomly divided into normal control group, model I group, low-dose model II group, medium-dose model II group and high-dose model II group. After model establishment, contents of serum creatinine (SCr), blood urea nitrogen (BUN), and urine creatinine (UCr) were detected by automatic biochemistry analyzer; freezing point method was used for 24-hour urinary osmotic pressure (Uosm) testing and kaolinite method was used to detect the content of urinary 17-hydroxycorticosteroid (17-OHCS). Expression of aquaporin-1 in renal tissue was observed by using real time reverse transcription polymerase chain reaction. The rats of model groups had the characteristics of kidney-yang deficiency syndrome. The contents of SCr and BUN were significantly higher in model I group than in normal control group and three model II groups (P<0.05), and UCr and Uosm were significantly lower (P<0.05). The level of urinary 17-OHCS and expression of aquaporin-1 in renal tissue were decreased in the model I group (P<0.05) as compared with the normal control group. Compared with the normal control group, the content of SCr was increased and urinary 17-OHCS was decreased in the medium-dose model II group, but the expression of aquaporin-1 was increased in three model II groups with a dose-dependent manner. Aquaporin-1 may be one of the material foundations of kidney-yang-deficiency syndrome.

Comprehensive study of urinary cortisol metabolites in hyperthyroid and hypothyroid patients

To further analyse the significance and mutual relationship of thyroid function-linked alterations in cortisol metabolism that have been separately and variously reported. Twenty-four-hour urine samples from 21 patients with hyperthyroidism (Graves' disease), 16 patients with hypothyroidism (Hashimoto's thyroiditis), 21 healthy age- and sex-matched controls for hyperthyroidism, and 16 healthy age- and sex-matched controls for hypothyroidism were evaluated for 6beta-hydroxycortisol (6beta-OHF), tetrahydrocortisol (THF), tetrahydrocortisone (THE), allo-tetrahydrocortisol (allo-THF), urinary free cortisol (UFF), urinary free cortisone (UFE) and 17-hydroxycorticosteroid (17-OHCS). Urinary 17-OHCS, THE and allo-THF levels increased considerably in hyperthyroid patients compared to the controls, while UFF and THF showed no difference between the two groups. Urinary 6beta-OHF was significantly lower in the hyperthyroid patients than in the controls. Both the urinary allo-THF + THF/THE and the UFF/UFE ratios were significantly lower in the hyperthyroid patients than in the controls, whereas only the former was significantly higher in the hypothyroid patients than in the controls. The urinary allo-THF/THF ratio was significantly higher in the hyperthyroid patients and significantly lower in the hypothyroid patients than in the controls. In an analysis of pooled subjects including all groups (n = 64), free T4 levels correlated negatively (P < 0.0001) with the urinary allo-THF + THF/THE ratio but not with the UFF/UFE ratio. The serum levels of free T4 correlated positively (P < 0.0001) with the urinary allo-THF/THF ratio. The thyroid hormones seem to affect the total 11beta-HSD activity (allo-THF + THF/THE) more strongly than the renal 11beta-HSD2 activity (UFF/UFE). 5alpha-reductase activity (allo-THF/THF) is also enhanced in hyperthyroidism, while the reduction of urinary 6beta-OHF in hyperthyroidism might be a secondary effect of the altered activity of the total 11beta-HSD and 5alpha-reductase.

The biochemical study of intermaxillary fixation (IMF) stress in oral surgery inpatients.

Although intermaxillary fixation (IMF) is performed to treat the patients with maxillary fracture, this procedure is very stressful to the patients. IMF has been reported to increase noradrenaline (NA) release in the brain and elevate plasma corticosterone contents in the rat. These changes were significantly attenuated by diazepam, an anxiolytic of the benzodiazepine family. These results suggest that IMF could greatly affect the pituitary-adrenal system as a stress. In the present study, in order to examine the influence of IMF on the human body function, we measured levels of 17-hydrocorticosteroids (17-OHCS) and 17-ketosteroid (17-KS), which are metabolites of the adreno-cortical hormone cortisol, in the urine of inpatients undergoing IMF. The subjects were requested to fill out a questionnaire on irritableness caused by IMF. In these patients, urinary 17-OHCS levels were significantly increased after IMF and well correlated to the results of the questionnaire. The finding suggested that urinary 17-OHCS levels reflect stress related to IMF, and that such stress mainly causes an irritated feeling. Natural killer cell activity (NK activity), which is considered to be related to stress, was measured in these patients. The relationship between 17-OHCS levels and NK activity was examined in reference to the results of the questionnaire. Questionnaire showed that most patients noted insomnia and an irritated feeling during IMF. To examine the influence of anxiolytic agents on stress related to IMF, an anxiolytic agent, ethyl loflazepate, was administered during IMF, and urinary 17-OHCS levels were measured. There was no correlation between 17-OHCS levels and NK activity in the patients. Furthermore, no correlation was observed between visual analogue scale (VSA) and NK activity. Increases in 17-OHCS levels in the group treated with ethyl loflazepate, an anxiolytic of the benzodiazepine family, were significantly lower than in the untreated group. This suggests that ethyl loflazepate reduced stress responses to IMF. It has been reported that NK activity is reduced inpatients with depression or chronic fatigue syndrome. However, NK activity may not be affected by mechanical stress such as IMF. The finding that an anxiolytic agent, ethyl loflazepate, inhibited stress responses to IMF further suggests that anxiolytic drugs are very useful for treatment of irritated feeling of the patients undergoing IMF.

Adrenal incidentalomas showing unilateral concordant visualization by adrenocortical scintigraphy: Comparison with adenomas in Cushing’s syndrome

An adrenocortical adenoma causing Cushing's syndrome (Cushing's adenoma) produces a unilateral concordant visualization (UCV) imaging pattern in which the adenoma is only visualized on radioiodocholesterol adrenocortical scintigraphy. But because this imaging pattern is also noted in some patients with adrenal incidentalomas, we examined whether the UCV-incidentaloma was essentially identical with Cushing's adenoma and would develop Cushing's syndrome. The subjects were 9 patients with UCV-incidentalomas (mean size, 30 mm; range, 20-45 mm) and 6 patients with Cushing's adenomas (mean size, 28 mm; range, 25-35 mm). Endocrinological evaluations showed several abnormalities including blunted diurnal rhythm of plasma cortisol within the normal range, low plasma ACTH and/or high 24-hr urinary 17-OHCS levels in 8 of 9 patients with UCV-incidentalomas, but these abnormalities did not meet the diagnostic criteria of Cushing's syndrome. Adrenal uptake of the tracer in the patients with UCV-incidentalomas was not statistically different from that in the patients with Cushing's adenomas and had no relationship with hormonal values in either patient group. Tumor size on CT correlated with the levels of 24-hr urinary 17-OHCS (r = 0.75, p = 0.02) and plasma cortisol at 7:00 (r = 0.82, p = 0.007) in the patients with UCV-incidentalomas, but not in the patients with Cushing's adenomas. Although 3 UCV-incidentalomas increased slightly in size, none of 9 patients with UCV-incidentalomas has developed Cushing's syndrome for 4 to 52 months. These results suggest that the UCV-incidentaloma may be essentially different from the Cushing's adenoma and unlikely to develop Cushing's syndrome.

Study on Alpiniae Fructus. I. Pharmacological evidence of efficacy of Alpiniae Fructus on ancient herbal literature

Pharmacological effects on anti-diuresis, anti-ulceration, anti-dementia and learning function of 50% ethanolic extract (AO-ext) from Alpiniae Fructus (fruit of Alpinia oxyphylla) removed seed vessel were investigated in order to prove the evidence of the efficacy of Alpiniae Fructus on the ancient herbal literature. AO-ext showed the effects of anti-diuresis, anti-ulceration, anti-dementia and on increase in the learning function in animals. And also, AO-ext exhibited the increasing effect on the serum 11-hydroxycorticosteroid (11-OHCS) level in the above-described experimental animals and in intact and hypophysectomized rats.

Unconsciousness due to Hyponatremia in a Patient of Short Stature with Panhypopituitarism

An unconscious woman of short stature (141 cm) was admitted to our hospital in March, 1994. She had hyponatremia (120 mEq/l) and had experienced massive bleeding during delivery. No increment of either plasma ACTH or cortisol levels was observed after insulin-induced hypoglycemia. However, urinary 17OHCS levels gradually increased after repeated intramuscular injections of ACTH. Plasma free T3 and free T4 levels were low. Neither plasma TSH nor prolactin (PRL) levels increased after an intravenous injection of TRH. Basal plasma LH, FSH and growth hormone (GH) levels were low and there were no observable responses to any of the stimulation tests. A magnetic resonance image (MRI) of her pituitary gland showed an empty sella. These results showed that she had a panhypopituitarism with primary empty sella. Replacement therapy with glucocorticoid was started and serum sodium levels normalized immediately. Levothyroxine was also administered. The possibility of pituitary dwarfism during her youth and a gradual postpartum reduction of other pituitary hormones may have caused an impairment of the hypothalamo-pituitary-adrenal axis.

AN ATYPICAL CASE OF CUSHING SYNDROME

A 44-year-old woman was admitted to the hospital because of lumbago and muscular weakness of the lower extremities. X-P of the thoracic and lumbar vertebrae revealed multiple compression fracture. Blood cortisol and urine 17-OHCS levels were as high as 22.7mmg/dl and 11.8mg/day, respectively. ACTH level was in the lower normal limit, 4.4pg/ml. A probable diagnosis of Cushing syndrome due to an adrenal tumor was supposed. With ultrasonography, CT, MRI, and angiography the left adrenal tomor was identified. Under left subcostal laparotomy the mobilization of the pancreatic tail and spleen was performed and the tumor was extirpated. The extirpated tumor was 3.5×2.5×2.5cm in size and 13 g in weight. The section presented canary yellow. Histological findings indicated adrenal adenoma. After the operation mellitus and hypertension improved. Blood cortisol and urine 17-OHCS levels decreased. ACTH increased, because it was released from the negative feedback.

HETEROGENEITY OF URINARY STEROID PROFILES IN CHILDREN WITH ADRENAL TUMORS

Adrenocortical tumors in children are rare but inportant causes of virilization and/or Cushing's syndrome. Other symptoms, including feminization and hyperaldosteronism, are less frequent. We present steroid urine profiles in 8 girls with adrenocortical tumors. Assessment of the urinary steroid pattern reveals its heterogeneity and makes it possible to: 1)follow the patients after surgery in terms of possible recurrence of the tumor, 2)exclude CAH as a cause of virilization (cases 6, 7, 8), 3)confirm the diagnosis of adrenal tumor in patients with only marginally elevated 17-KS but elevated 11β-OHAN (cases 6 & T), 4)detect patients with adrenal tumor with unusual steroid patterns (case 8). Steroid profiling in urine by capillary gas chromatography has an advantage over the traditional assays of 17-KS, 17-OHCS or serum levels of DHA, DHAS, testosterone, cortisol, 17OH-progesterone for the diagnosis and management of adrenal tumors.

Urinary Cortisol Metabolites in the Assessment of Peripheral Thyroid Hormone Action: Application for Diagnosis of Resistance to Thyroid Hormone

Urinary cortisol metabolites are altered both quantitatively and qualitatively in thyroid dysfunction. This study was conducted to elucidate the usefulness of urinary cortisol metabolites in the assessment of peripheral thyroid hormone action, particularly in the patients with inappropriate thyrotropin secretion. Twenty-four hour urinary 17-hydroxycorticosteroid (17-OHCS) level and gas chromatographical steroid profile were studied in 25 hyperthyroid, 18 hypothyroid, and 24 euthyroid control subjects. Five patients with generalized thyroid hormone resistance and two patients with thyrotropin secreting pituitary tumor were also studied. The ratio of urinary tetrahydrocortisone to tetrahydrocortisol (THE/THF) was significantly elevated in hyperthyroidism (4.58 +/- 1.49) and depressed in hypothyroidism (1.31 +/- 0.55) compared to control (1.93 +/- 0.35). There were good correlations between THE/THF and serum thyroid hormone levels, especially in hypothyroidism. THE/THF can be a good biochemical indicator for deficiency of peripheral thyroid hormone action. Two patients with thyrotropin-secreting tumor showed high THE/THF, which reflected thyroid hormone excess. In contrast, THE/THF in the patients with generalized thyroid hormone resistance was low as compared to high serum thyroid hormone levels. Similar findings were demonstrated with 17-OHCS but discrimination of thyroid hormone resistance was insufficient. Thus, the ratio of the urinary concentrations of cortisol metabolites, THE/THF, appears to be a good marker for peripheral thyroid hormone resistance.

Elevated urinary free cortisol in patients with dementia

Urinary free cortisol (UFC), 17-hydroxycorticosteroids (17-OHCS) in urine and dexamethasone suppression test (DST) were examined in patients with dementia of Alzheimer type (DAT) and multi-infarct dementia (MID), and nondemented elderly. Eight of 19 patients (42.1%) were DST nonsuppressor. UFC was significantly elevated in patients with dementia, compared with that in nondemented elderly. There was no difference in UFC levels between DAT and MID. The UFC level correlated with post-DST plasma cortisol level at 1600 in demented patients. The mean level of 17-OHCS in demented patients was increased, although the difference was not significant statistically. In demented patients, UFC levels, not 17-OHCS levels in urine were correlated with Mini-Mental State Examination scores. These results suggest that a hypothalamo-pituitary-adrenal axis function is activated in demented patients and that this activation relates generally to dementation itself, not to an etiology of dementia. Measurement of UFC might be a biological marker of dementia and may have a value in diagnosis of dementia.

Presidential Lecture delivered on the 63th Autumn Congress of Japan Endocrine Society

We followed up 21 Cushing's disease patients (16 females and 5 males) aged 15 to 46 years, treated with reserpine (R) plus pituitary irradiation (PI). Mean duration of R administration and mean dose of PI were 24.5 +/- 10.8 (mean +/- SD) months and 54.0 +/- 9.8 Gy, respectively. Of them, four patients did not respond, one who received 66 Gy had brain necrosis and panhypopituitarism, and the other 16 patients (78%, 16/21) achieved initial remission. Of these 16 patients, there were 10 (aged 15 to 46 years) who were irradiated with 50 Gy or less (mean, 45.5 +/- 6.9 Gy), and 7 of them had initial response. As previously demonstrated effectiveness of the present regimen (R plus PI) could be evaluated by subjecting the patients to R-test, higher rate of remission was obtained among R-test responders (J. Clin. Endocrinol. Metab. 41:511, 1975). Eleven of our R-test responders in the present study showed an early onset of remission (6.9 +/- 5.7 months) as compared with 5 R-test non-responders (17.0 +/- 9.1, p less than 0.05). In addition, the response time positively correlated with the ratio of the difference between basal plasma cortisol (11-OHCS) levels before and after midnight administration of 8 mg dexamethasone (delta D8) divided by the difference between 24-h urinary excretion of 17-OHCS for 3 successive days before, during metyrapone (3.0 g/day, 6 divided dose, 2 days) administration and one day after (delta M). The sixteen patients were followed up until 1990 for a mean of 12.4 years (2.2 to 25.2 years). Among them, one died of unrelated illness with this regimen 4 years after achieving remission, 4 relapsed between 5 to 7 years follow-up, and the remaining 11 (52%, 11/21) had long-term remission for a mean of 15.7 +/- 9.0 years (2.2 to 25.2 years). Of them, there were 5 patients who were treated with PI with 50 Gy or less, and had long-term remission (5.8 to 24.4 with a mean of 17.6 +/- 7.6 years). During the long-term follow-up period of these 11 patients, endocrine assessment was carried out while off therapy. Basal urinary excretion of cortisol or 17-OHCS were were normal in all of the 11 patients, and 8 of 9 showed normal diurnal rhythm of plasma cortisol. Nine of 10 patients tested showed normal suppressibility by overnight 1 mg dexamethasone test and 6 of 9 showed normal response to CRH.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of Long Term Exposure to Infrasound on Growth, Activity, and Urinary 17-OHCS Levels in Rats

To clarify the physiological effects of infrasound, 42 day-old male Wistar rats were exposed to 16Hz infrasound at 120 B for 28 days. We measured body weight, spontaneous running activity, and urinary 17-OHCS levels. The exposure group was exposed to infrasound in the exposure chamber and the control group was housed in the same chamber without exposure. Each group was further subdivided into two subgroups, a sedentary group and an exercise group. The exercise group was housed with a rotating wheel cage adjoining the feed cage. It was found that: The growth was slower in the exposure group than in the control group. Spontaneous running activity of the exposure group increased significantly from 20 days after the start of infrasound exposure. Urinary 17-OHCS levels increased in 3 days after the start of infrasound exposure. These results suggested that infrasound acted as a stressor.

Adrenal cortex hormones in male epileptic patients before and during a 2-year phenytoin treatment.

Serum levels of progesterone, cortisol and phenytoin as well as the excretion of 17-OHCS were determined in 45 male epileptics before and during 24 months of the therapy. A significant decrease of the hormones was found in untreated patients. Phenytoin administration caused further decrease of cortisol and its metabolite 17-OHCS levels and a compensation of progesterone serum concentration.

STUDIES ON ADRENOCORTICAL FUNCTION IN TEN CHILDREN WITH SEVERE ATOPIC DERMATITIS

We examined adrenocortical function in ten children with severe atopic dermatitis who were treated with topical corticosteroid preparations for an average of 4 years and 11 months.The ACTH stimulation test was performed with an intravenous drip of ACTH (0.003mg/kg in one hour). Observation was carried out 2 hours later. A rising incline index in cortisol or 11-OHCS per hour was used.In children with atopic dermatitis, the rising incline index was significantly smaller than in control patients who did not receive prolonged topical corticosteroid therapy (p<0.01). No differences in basal cortisol or 11-OHCS levels were noted. For 4 patients, their heights were less than -2 SD.The results suggest that topical corticosteroid therapy for atopic dermatitis may cause adrenal suppression and also stunted growth and a permanent short stature. The mode of topical therapy shoud be changed to alternating or daily administration in the morning in patients with insufficient responsiveness to ACTH stimulation.

Dehydroepiandrosterone-Sulphate-Secretion and State of Adrenal Function in the Rat

After more than one month under growth-restraining feeding conditions the influence of undernutrition (50% feed restriction) on dehydroepiandrosterone sulphate (DHEA-S) and 11-OHCS (corticosterone) secretion was investigated in male Wistar rats. Diet-restricted (DR) rats, untreated before the taking of blood samples, showed clearly elevated 11-OHCS plasma levels in the morning (lights-on) compared to ad libitum-fed (AL) control rats, whereas the evening (lights-off) 11-OHCS levels were almost identical in both groups. The corresponding DHEA-S blood concentrations were equal under both feeding schedules in the morning as well as in the evening. However DHEA-S response to adrenocorticotropic hormone (ACTH) administration was significantly elevated in DR rats compared with AL rats. No such difference was detectable for ACTH-stimulated 11-OHCS blood levels. Measurement of total adrenal cholesterol content revealed a markedly higher concentration of this hormone precursor in the glands of untreated DR rats than in the adrenals of the AL control group, thus clearly indicating the existence of a chronically elevated endogenous ACTH secretion under dietary restriction, since continued in vivo ACTH stimulation is known to increase the cholesterol content of the adrenal cortex. Furthermore the occurrence of a nutritional stress is obviously reflected by the elevated 11-OHCS levels in the circulation of DR rats at “lights-on.” The observations in DR rats coupled with the findings in ACTH-pretreated rats under metyrapone treatment (J. Clin. Biochem. Nutr., 2, 141-152, 1987) strongly support our already proposed concept that stress or stimulation of the cortico adrenal activity provokes an increase in the capacity for secretion of DHEA-S measurable after an appropriate stimulation. Contrary to a recently published hypothesis undernutrition appears to be not necessarily associated with a suppression of enzymes involved in DHEA-S formation.

Single-dose metyrapone test at 06.00 h: an accurate method for assessment of pituitary-adrenal reserve.

One dose of metyrapone (1.5g) administered at 06.00 h, with subsequent measurement of 11-deoxycortisol and 17-hydroxycorticosteroid (17-OHCS) levels in plasma at 12.00 and 14.00 h, allowed accurate assessment of the pituitary-adrenal reserve. Normal response was defined as achieving a serum 17-OHCS level of more than 10.0 micrograms/100 ml and a 11-deoxycortisol level of more than 6.0 micrograms/100 ml at either 12.00 or 14.00 h. These criteria are based on a group of 18 persons with normal pituitary-adrenal axis, and 86 additional cases responded in this normal range. In this group of 104 subjects, 11-deoxycortisol levels rose to 9.2 +/- 3.5 micrograms/100 ml at noon and 17-OHCS levels to 15.4 +/- 4.7 micrograms/100 ml at 14.00 h. Post-metyrapone 17-OHCS levels were significantly higher than normal cortisol levels at these times (P less than 0.001) and than those observed at 08.00 h on the day of the test, demonstrating stimulation of adrenal corticoid production in addition to blockade of cortisol production by metyrapone. Thirty-one patients found to suffer from secondary adrenal failure showed impaired response. All these patients had limited pituitary-adrenal reserve, either proven by other pituitary-adrenal tests or implicated by severe pituitary disease.