Increase In Adrenocorticotropic Hormone Levels Research Articles

ODP351 Silent Corticotroph Adenomas – Characteristics and Comparisons to Other Non-functioning Pituitary Adenomas: A Case Series

Abstract Introduction Silent corticotroph adenomas (SCA) are characterised by an absence of cortisol excess yet show positive immunostaining for T-Box transcription factor (TPIT) and frequently adrenocorticotropic hormone (ACTH). Patients with a SCA commonly present with symptoms of mass effect such as headache or visual compromise or are identified incidentally on imaging. SCAs are high risk according to the WHO 2017 classification scheme. Aim To assess our cohort of SCAs for differences in demographics, presenting symptoms and imaging results compared to other non-functioning pituitary adenomas (NFPA). Methods Surgically treated patients with NFPAs seen by endocrinology at an Australian Tertiary Centre between the years 2011-2021 were included in the analysis. SCA was diagnosed based on the absence of clinical and biochemical features of cortisol excess in combination with immunohistochemical staining including positive staining for ACTH. Other NFPA subtypes were defined by immunohistochemical staining and the absence of hormone overproduction. We compared demographic information, symptoms at presentation and tumour size as assessed by magnetic resonance imaging (MRI) between the SCA and all other NFPA groups. Where available, pre- and postoperative ACTH and cortisol levels were compared in the SCA and non-SCA groups. Results 31 patients were identified, 5 with SCA and 26 with other NFPA, all were macroadenomas. All 5 cases of SCA showed ACTH positivity, 2 of 5 cases were stained for TPIT, both were positive. Mean age at surgery for the SCA group was 50.8±10.9 years. Mean non-SCA age was 54.3±15.4 years. 3 of the 5 patients with SCA were women. The most frequent symptoms at presentation were headache (SCA: 40%; non-SCA 36%) and visual disturbances (SCA: 60%; non-SCA 68%). The mean maximal tumour diameter in the SCA group was 31.36±13.61 mm versus 24.65±6.80 mm in the non-SCA group on MRI. Cavernous sinus invasion was present in 60% of the SCA and 38.5% of the non-SCA group. In the SCA group pre-operative ACTH levels were 5.1±2.6 pmol/L (normal <12.1 pmol/L) and dropped to 2.5±1.8 pmol/L postoperatively. Cortisol levels were 344±205 nmol/L (normal 138-650 nmol/L) and dropped to 269±228 nmol/L. In the non-SCA group ACTH levels were 4.5±2.3 pmol/L preoperatively and 4.6±3.8 pmol/L postoperatively. Cortisol levels were and 538±168 nmol/L preoperatively and 403±179 nmol/L postoperatively. Conclusion In this retrospective comparison, compared to other NFPAs the SCA group showed younger age, more frequent headaches, less visual compromise, larger tumour size and increased cavernous sinus invasion. These findings are consistent with the known aggressiveness of SCAs. The reduction in ACTH levels postoperatively support the concept that SCAs produce inactive forms of ACTH. Although this is a small case series, there may be merit in monitoring for relative increases in ACTH levels in patients with a history of SCA. Presentation: No date and time listed

Tumor Shrinkage by Metyrapone in Cushing Disease Exhibiting Glucocorticoid-Induced Positive Feedback.

ContextParadoxical increases in serum cortisol in the dexamethasone suppression test (DST) have been rarely observed in Cushing disease (CD). Its pathophysiology and prevalence remain unclear.Case DescriptionA 62-year-old woman with suspected CD showed paradoxical increases in cortisol after both 1-mg and 8-mg DST (1.95-fold and 2.52-fold, respectively). The initiation of metyrapone paradoxically decreased plasma adrenocorticotropic hormone (ACTH) levels and suppressed cortisol levels. Moreover, the pituitary tumor considerably shrank during metyrapone treatment.Ex Vivo ExperimentsThe resected tumor tissue was enzymatically digested, dispersed, and embedded into Matrigel as 3D cultured cells. ACTH levels in the media were measured. In this tumor culture, ACTH levels increased 1.3-fold after dexamethasone treatment (P < 0.01) while control tumor cultures exhibited no increase in ACTH levels, but rather a 20% to 40% suppression (P < 0.05).Clinical StudyA cross-sectional, retrospective, multicenter study that included 92 patients with CD who underwent both low-dose and high-dose DST from 2014 to 2020 was performed. Eight cases (8.7%) showed an increase in serum cortisol after both low-dose and high-dose DST.ConclusionThis is the first report of a patient with glucocorticoid (GC)-driven positive feedback CD who showed both ACTH suppression and tumor shrinkage by metyrapone. Our cohort study revealed that 8.7% of patients with CD patients possibly possess GC-driven positive-feedback systems, thereby suggesting the presence of a new subtype of CD that is different from the majority of CD cases. The mechanisms exhibiting GC positive feedback in CD and the therapeutic approach for these patients remain to be investigated.

Naltrexone alters alcohol self-administration behaviors and hypothalamic-pituitary-adrenal axis activity in a sex-dependent manner in rats

BackgroundThe mu-opioid antagonist, naltrexone (NTX), is a FDA-approved treatment for alcohol use disorder (AUD); however, the data on whether it differentially affects males vs. females are mixed. NTX increases hypothalamic-pituitary-adrenal (HPA) axis activity that associates with subjective responses to alcohol and craving in individuals with AUD. The present study tested for sex differences in the ability of NTX to decrease appetitive and consummatory behaviors in rats in operant alcohol self-administration. Because the opioid system and HPA axis are sexually dimorphic, we examined NTX's effect on adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels. MethodsMale and female Sprague-Dawley rats (n's = 6–8) were trained to lever press for alcohol (10% v/v) under a fixed-ratio 2 schedule of reinforcement. NTX doses (0, 0.1–10 mg/kg) were assessed in tests conducted under a progressive ratio schedule of reinforcement. Separate groups of alcohol and water drinking rats (n's = 8) were used to assess NTX's (10 mg/kg) effects on HPA axis hormones. ResultsNTX decreased consummatory behaviors for alcohol in a dose-related manner, but not appetitive behaviors in males. In females, NTX decreased appetitive behaviors for alcohol in a dose-dependent manner, but only decreased consummatory behaviors at the highest (10 mg/kg) NTX dose. NTX increased ACTH levels in alcohol drinking females in diestrus, but not in other groups. However, NTX increased CORT levels for longer durations in alcohol drinking males relative to alcohol drinking females in diestrus. ConclusionsOur findings suggest that NTX selectively reduces consummatory behaviors for alcohol in males and appetitive behaviors in females, while also showing differential sex effects on HPA hormones.

Electroacupuncture activates corticotrophin-releasing hormone-containing neurons in the paraventricular nucleus of the hypothalammus to alleviate edema in a rat model of inflammation

BackgroundStudies show that electroacupuncture (EA) has beneficial effects in patients with inflammatory diseases. This study investigated the mechanisms of EA anti-inflammation, using a rat model of complete Freund's adjuvant (CFA)-induced hind paw inflammation and hyperalgesia.DesignFour experiments were conducted on male Sprague-Dawley rats (n = 6–7/per group). Inflammation was induced by injecting CFA into the plantar surface of one hind paw. Experiment 1 examined whether EA increases plasma adrenocorticotropic hormone (ACTH) levels. Experiments 2 and 3 studied the effects of the ACTH and corticotropin-releasing hormone (CRH) receptor antagonists, ACTH(11–24) and astressin, on the EA anti-edema. Experiment 4 determined whether EA activates CRH neurons in the paraventricular nucleus of the hypothalammus. EA treatment, 10 Hz at 3 mA and 0.1 ms pulse width, was given twice for 20 min each, once immediately post and again 2 hr post-CFA. Plasma ACTH levels, paw thickness, and paw withdrawal latency to a noxious thermal stimulus were measured 2 h and 5 h after the CFA.ResultsEA significantly increased ACTH levels 5 h (2 folds) after CFA compared to sham EA control, but EA alone in naive rats and CFA alone did not induce significant increases in ACTH. ACTH(11–24) and astressin blocked EA anti-edema but not EA anti-hyperalgesia. EA induced phosphorylation of NR1, an essential subunit of the N-methyl-D-aspartic acid (NMDA) receptor, in CRH-containing neurons of the paraventricular nucleus.ConclusionThe data demonstrate that EA activates CRH neurons to significantly increase plasma ACTH levels and suppress edema through CRH and ACTH receptors in a rat model of inflammation.

Preliminary Evidence That Hippocampal Volumes in Monkeys Predict Stress Levels of Adrenocorticotropic Hormone

Hippocampal volumes previously determined in monkeys by magnetic resonance imaging are used to test the hypothesis that small hippocampi predict increased stress levels of adrenocorticotropic hormone (ACTH). Plasma ACTH levels were measured after restraint stress in 19 male monkeys pretreated with saline or hydrocortisone. Monkeys were then randomized to an undisturbed control condition or intermittent social separations followed by new pair formations. After 17 months of exposure to the intermittent social manipulations, restraint stress tests were repeated to determine test/retest correlations. Individual differences in postrestraint stress ACTH levels over the 17-month test/retest interval were remarkably consistent for the saline (r(s) = .82, p = .0004) and hydrocortisone (r(s) = .78, p = .001) pretreatments. Social manipulations did not affect postrestraint stress ACTH levels, but monkeys with smaller hippocampal volumes responded to restraint after saline pretreatment with greater increases in ACTH levels with total brain volume variation controlled as a statistical covariate (beta = -.58, p = .031). Monkeys with smaller hippocampal volumes also responded with diminished sensitivity to glucocorticoid feedback determined by greater postrestraint ACTH levels after pretreatment with hydrocortisone (beta = -.68, p = .010). These findings support clinical reports that small hippocampi may be a risk factor for impaired regulation of the hypothalamic-pituitary-adrenal axis in humans with stress-related psychiatric disorders.

Gamma Knife surgery for adrenocorticotropic hormone–producing pituitary adenomas after bilateral adrenalectomy

Patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas may require a bilateral adrenalectomy to treat their Cushing's disease. Approximately one third of these patients, however, will experience progressive enlargement of the residual pituitary adenoma, develop hyperpigmentation, and have an elevated level of serum ACTH. These patients with Nelson's syndrome can be treated with Gamma Knife surgery (GKS). The prospectively collected University of Virginia Gamma Knife database of patients with pituitary adenomas was reviewed to identify all individuals with Nelson's syndrome who were treated with GKS. Twenty-three patients with a minimum of 6 months of follow up were identified in the database. These patients were assessed for tumor control (that is, lack of tumor growth over time) with neuroimaging studies (median follow-up duration 22 months) and for biochemical normalization of their ACTH levels (median follow-up duration 50 months). Neuroimaging follow-up studies were available for 22 patients, and endocrine follow up was available for 15 patients in whom elevation of ACTH levels was documented prior to GKS. In the 22 patients in whom neuroimaging follow-up studies were available, 12 had a decrease in tumor size, eight had no tumor growth, and two had an increase in tumor volume. Ten of 15 patients with elevated ACTH levels prior to GKS showed a decrease in their ACTH levels at last follow up; three of these 10 patients achieved normal ACTH levels (< 50 pg/ml) and the other five patients with initially elevated values had an increase in ACTH levels. Ten patients were thoroughly evaluated for post-GKS pituitary function; four were found to have new pituitary hormone deficiency and six did not have hypopituitarism after GKS. One patient suffered a permanent third cranial nerve palsy and four patients are now deceased. Gamma Knife surgery may control the residual pituitary adenoma and decrease ACTH levels in patients with Nelson's syndrome. Delayed hypopituitarism or cranial nerve palsies can occur after GKS. Patients with Nelson's syndrome require continued multidisciplinary follow-up care. Given the difficulties associated with management of Nelson's syndrome, even the modest results of GKS may be helpful for a number of patients.

Temporary adrenal dysfunction with descending thoracic aortic occlusion

Background. We sought to determine whether descending thoracic aortic occlusion (DTAOC) induced ischemia results in adrenal dysfunction. Methods. Eight pigs underwent DTAOC for 45 min. Six control pigs underwent a sham procedure. Serum cortisol and adrenocorticotropic hormone (ACTH) were measured at baseline, at the end of DTAOC, 30 and 60 min after restoration of flow, and 24 hours later. Statistical analysis was performed using repeated measures ANOVA and t-test. Results. In the study group, cortisol levels decreased during DTAOC (p=0.048) and 30 min after flow restoration (p=0.004). In the control group there was no change in serum cortisol levels. In the study group the drop in serum cortisol was associated with an increase in ACTH levels during DTAOC (p=0.040) and 30 minutes after flow restoration (p=0.070). The increase in ACTH was also significant when compared to the controls during DTAOC (p=0.030) and 30 min after blood flow restoration (p=0.040). Conclusions. There is a transient period of adrenal dysfunction associated with DTAOC that results in stimulation of the pituitary-adrenal axis.

Effects of Mineralocorticoid and Glucocorticoid Receptor Blockade on Hypothalamic–Pituitary–Adrenal Function in Female Rats Prenatally Exposed to Ethanol

Rats prenatally exposed to ethanol (E) exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness, demonstrated by increased and/or prolonged elevations of adrenocorticotropic hormone (ACTH) and/or corticosterone (CORT) in response to stressors. The present study examined the possible role of CORT feedback deficits in mediating this hyperresponsiveness by examining HPA function following mineralocorticoid (MR) and glucocorticoid (GR) receptor blockade. Adult female Sprague-Dawley offspring from E, pair-fed (PF), and control (C) groups were injected subcutaneously with the MR antagonist spironolactone (SPIRO; 30 mg/kg bw), the GR antagonist RU38486 (120 mg/kg bw), or vehicle. One hour postinjection, blood samples (0 minutes) were taken via jugular cannulae to obtain a measure of prestress ACTH and CORT levels. Rats were then loosely restrained for 1 hour, and samples were taken during (15, 30, and 60 minutes) and then 1 hour following stress, for determination of plasma ACTH and CORT levels. Both SPIRO and RU38486 significantly increased prestress ACTH levels in E compared with both PF and C females. In contrast, RU38486 significantly increased ACTH levels in C compared with PF females during stress and in C compared with E females during recovery. CORT levels were increased during stress in E females in response to SPIRO, and RU38486 increased the CORT response during stress in PF and during recovery in E and PF females compared with vehicle. E females showed enhanced HPA responses to both MR and GR blockade compared with PF and C before restraint as well as a different pattern of responsivity during and following restraint. While receptor blockade had some effect on CORT responses in PF females, changes in ACTH appear specific to ethanol. These findings suggest that the balance between HPA drive and feedback may be altered in E compared with C females.

Role of endogenous glucocorticoid metabolism in human acute pancreatitis*

This study aimed to observe how levels of total cortisol, calculated free cortisol, corticosteroid-binding globulin, and adrenocorticotropic hormone change during the early course of human acute pancreatitis and to describe how these changes affect the development of pancreatic necrosis. In a total of 109 consecutive patients with acute pancreatitis (74 with edematous pancreatitis, 35 with necrotizing pancreatitis), serial daily blood monitoring of total and free cortisol, adrenocorticotropic hormone, and corticosteroid-binding globulin was done after hospital admission, up to day 6 after the onset of pain; 30 healthy individuals served as controls. Corticosteroid-binding globulin and total cortisol were measured by immunoassays, and free cortisol was calculated according to Coolens et al. The adrenocorticotropic hormone was measured with an enzyme-linked immunoassay. Initially, highly elevated levels of calculated free cortisol (median, 86.2 ng/mL; quartile ranges, 50.6-106.7 ng/mL) and total cortisol (41.2 microg/dL, 30.4-51.1 microg/dL) and depressed levels of adrenocorticotropic hormone (0.2 pg/mL, 0.1-2.0 pg/mL) and corticosteroid-binding globulin (30.6 microg/mL, 24.1-35.5 microg/mL) were observed. Further, daily measurements revealed increasing adrenocorticotropic hormone levels, whereas cortisol levels decreased. Although an increase in adrenocorticotropic hormone levels is suggested to increase corresponding cortisol levels, cortisol levels decreased during the development of necrotizing acute pancreatitis. This phenomenon, along with the continuously decreasing corticosteroid-binding globulin levels, brings up the hypothesis of a relative adrenal insufficiency, which favors acinar cell apoptosis and hence may trigger the development of necrosis in the initial vulnerable phase of acute pancreatitis.

Stress Augmented Ultraviolet-Irradiation-Induced Pigmentation

It was reported that adrenocorticotropic hormone stimulates melanogenesis in cultured melanocytes. Stress (high population density and restraint stress) induced a significant increase in adrenocorticotropic hormone levels in plasma and skin compared to control. The serum obtained from HR-1 x HR/De F1 female mice subjected to stress showed significantly increased tyrosinase activity in human melanocytes compared to that from nonstressed mice. The increase in tyrosinase activity was inhibited in the presence of 10 nM corticostatin, an adrenocorticotropic hormone inhibitor. The aim of this study was to examine whether adrenocorticotropic hormone released into the circulation under stressful conditions is associated with the regulation of ultraviolet-induced pigmentation. Mice divided into three groups were housed for 22 d under the following conditions: five mice per cage (control); 10 mice per cage (high population density); restraint stress 4 h per d. The animals were exposed to ultraviolet-B irradiation (72 mJ per cm2, thrice per wk). After ultraviolet-B irradiation, delayed tanning was marked in stressed mice. The number of dihydroxyphenylalanine-positive melanocytes also significantly increased in stressed animals. Pretreatment with 100 microg of corticostatin inhibited the augmentation of the stress-induced pigmentary response and the increase in dihydroxyphenylalanine-positive melanocytes after ultraviolet irradiation. Adrenocorticotropic hormone released by stress may activate tyrosinase in melanocytes, resulting in the augmentation of ultraviolet-induced pigmentation. These results suggest that adrenocorticotropic hormone is at least partly responsible for the sensitivity of the pigmentary response after ultraviolet irradiation under stressful conditions.

Effect of opioid receptor antagonists on hypothalamic–pituitary–adrenal activity in rhesus monkeys

Some opioid antagonists increase the release of adrenocorticotropic hormone (ACTH) and cortisol in humans and, therefore, may indicate that endogenous opioids modulate hypothalamic–pituitary–adrenal axis activity. The type of opioid receptor that may be related to these endocrine effects is unknown. The purpose of this experiment was to evaluate the ability of different opioid antagonists to increase ACTH and cortisol plasma levels in rhesus monkeys. Eight monkeys received intramuscular injections of various antagonists: 0.0032–1.0 mg/kg naltrexone, 0.1–3.2 mg/kg naltrindole (delta-selective), 0.032–0.32 mg/kg clocinnamox (mu-selective), and 1–3.2 mg/kg nor-binaltorphimine (kappa-selective). Naltrexone, 0.1–1.0 mg/kg, increased ACTH levels, whereas naltrindole and clocinnamox failed to increase ACTH levels. Nor-binaltorphimine, 1–3.2 mg/kg, increased ACTH concentrations on the day of injection, but not at a time when other assays continue to demonstrate κ-antagonism (24 h). Cortisol concentrations generally followed the same pattern as the ACTH concentrations, but the incremental differences in cortisol release between doses were less clear. Thus, opioid modulation of ACTH and cortisol plasma levels is not clearly associated with a particular opioid receptor. Although the κ-antagonist increased ACTH and cortisol release on the day of injection, some evidence suggests that this endocrine effect may be due to mechanisms other than those mediated by the κ-receptor. Alternatively, the naltrexone-induced increase of ACTH and cortisol plasma levels may be caused by activity at multiple opioid receptors or some uncharacterized receptor. Finally, the increased release of ACTH and cortisol may be a response to naltrexone’s aversive properties.

Glucocorticoid negative feedback on the HPA axis in five inbred rat strains.

The aim of the present work was to study the influence of altering glucocorticoid negative feedback on both basal activity of the hypothalamic-pituitary-adrenal (HPA) axis and its response to acute stress (tail shock) in five inbred rat strains known to differ in some depression-like behaviors: Brown Norway (BN), Fischer 344 (F344), Lewis (Lew), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats. Two complementary approaches were used: 1) enhancement of negative feedback by administration of 0.05 and 0.2 mg/kg dexamethasone (Dex) and 2) attenuation of negative feedback by pharmacological adrenalectomy (PhADX). The results indicate that 1) Lew rats consistently show adrenocorticotropic hormone (ACTH) and corticosterone hyporesponsiveness to stress, 2) interstrain differences in the effect of Dex on the HPA axis were very weak and not related apparently to differences in the metabolism of the steroid, 3) the suppressive effect of the highest dose of Dex on basal corticosterone levels was lower in BN rats than in the other strains, and 4) after PhADX, an increase in ACTH levels was observed in response to acute stress in BN, F344, and WKY but not in Lew and SHR rats, suggesting possible interstrain differences in pituitary sensitivity to neural stimuli induced by stress. In summary, our results indicate that there are differences among the strains with regard to both 1) the suppressive effect of Dex on the HPA axis, BN rats showing a certain degree of resistance, and 2) the capability of PhADX rats to respond to acute stress, which suggests a defective release of ACTH in Lew and SHR rats. The biological meaning of these alterations of corticosteroid negative feedback among the five inbred strains studied remains to be established.

Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs.

To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five awake dogs. Four hours after endotoxin or saline challenge human corticotrophin-releasing hormone (hCRH; 1.0 microgram/kg) was administered. Plasma ACTH and cortisol levels increased considerably in response to endotoxin, from 13 +/- 1 ng/l to 360 +/- 85 ng/l (p < 0.01) and from 60 +/- 20 nmol/l to 710 +/- 80 nmol/l (p < 0.01). Despite a considerable difference in ACTH and cortisol levels prior to CRH administration between both studies (p < 0.01), the absolute increase in ACTH levels induced by hCRH was not different (231 +/ 43 ng/l vs 238 +/- 45 ng/l, control vs endotoxin). Plasma cortisol levels increased significantly in the control study (from 40 +/- 10 nmol/l to 330 +/- 40 nmol/l, p < 0.01), whereas they did not change in the endotoxin study after hCRH administration (from 710 +/- 80 nmol/l to 730 +/- 70 nmol/l, ns). We conclude that the HPA-axis reacts initially to endotoxin in such a way that cortisol, but not ACTH, secretion is maximized. Therefore, a blunted cortisol response to CRH testing is part of the initial response to infection.

Ramipril in angina pectoris: short-term effects on glucose, insulin, C-peptide, adrenocorticotropic hormone, and cortisol levels

We studied the effects of the angiotensin-converting enzyme inhibitor ramipril on plasma levels of adrenocorticotropic hormone (ACTH), cortisol, glucose, insulin, and C-peptide in patients with coronary artery disease. Patients were randomly assigned to treatment with ramipril 5 mg once daily, ramipril 5 mg once daily in combination with 20 mg of the oral nitrate isosorbide dinitrate (ISDN), ISDN alone 20 mg twice daily, or placebo. After a 72-hour washout period from their previous vasoactive medication, 32 patients (1 woman, 31 men) aged 42 to 72 years (mean age, 63.3 years) received a single dose of the study medication. Plasma levels of ACTH, cortisol, glucose, insulin, and C-peptide were measured before drug administration and 1, 2, 3, 4, 5, 6, 8, and 24 hours after drug administration. After the initial 24-hour treatment period, a randomized, double-masked, placebo-controlled, four-way, crossover phase started in which each patient was treated with each study medication for 1 week. Individual treatment phases were separated by weekly washout periods, and plasma levels of insulin, C-peptide, and glucose were assessed in the morning at trough and 3 hours after intake of the study medication. The typical circadian variation was observed for cortisol, without any difference between the four treatment groups. On average, ACTH levels were significantly higher in the patients treated with ISDN alone. No significant effect on glucose, insulin, or C-peptide levels was observed among patients receiving the first dose of ramipril, ISDN, ramipril + ISDN, or placebo, nor between the crossover phases during continued treatment. We conclude that in patients with angina pectoris, a single dose of ramipril has no acute effects on insulin secretion and glucose utilization, nor does multiple dosing of ramipril affect glucose hemeostasis. Ramipril also did not affect circadian cortisol secretion. These findings also pertain to the combination of ramipril and ISDN. In contrast, after administration of a single dose of ISDN alone, a statistically significant increase in ACTH levels was observed. The increase in ACTH levels could be a marker for sympathetic nervous system activation resulting from counterregulation.

Interleukin-1 stimulates aldosterone secretion: involvement of renin, ACTH, and prostaglandins.

Interleukin-1 (IL-1), a cytokine produced during infection and inflammation, mediates some of the endocrinological alterations that parallel these processes. The purpose of this study was to determine whether human recombinant IL-1 (hrIL-1) affects aldosterone output as well as renin and adrenocorticotropic hormone (ACTH) release, two key factors in the regulation of mineralocorticoid secretion. We observed that intravenous administration of hrIL-1 into conscious unrestrained rats elicited a marked and rapid rise in aldosterone plasma levels in a dose-dependent manner. The hrIL-1-induced increase in aldosterone levels was associated with enhanced renin activity and increased ACTH levels in plasma. Furthermore, aldosterone levels of IL-1-injected rats were positively correlated with plasma renin activity (PRA), suggesting that the renin-angiotensin system contributes to the changes observed in the levels of the mineralocorticoid hormone. ACTH seems also to be implicated in the aldosterone response to hrIL-1 because the profile of the kinetic curves of changes in the levels of the pituitary hormone and aldosterone was similar. Pretreatment with the cyclooxygenase inhibitor indomethacin markedly reduced the increase in aldosterone plasma levels and PRA induced by IL-1, indicating that prostaglandins are involved in these effects of the cytokine. These results suggest that IL-1 may play an important role in the control of homeostasis during infectious and inflammatory diseases.

Growth Hormone and Adrenocorticotropic Hormone Levels Increased in a Child with Diencephalic Syndrome

AbstractA Japanese male child with diencephalic syndrome due to suprasellar tumor was treated in our department. There were no symptoms suggestive of hyper‐adrenalism despite an increased adrenocorticotropic hormone (ACTH), nor was there an excessive growth even in the presence of high fasting levels of growth hormone (GH). After radiation therapy, both ACTH and GH levels reverted to normal. Thus, the abnormal hypothalamic control following destruction of a certain area of the diencephalon may have led to increases in the levels of ACTH and GH. This may be the first documentation of increased ACTH levels in a patient with diencephalic syndrome.