β-endorphin and ACTH in plasma during attacks of common and classic migraine

Plasma levels of beta-endorphin and ACTH were measured during and outside migraine attacks in 17 patients with common migraine and 11 patients with classic migraine. Specific radioimmunoassays for beta-endorphin and ACTH were used. The beta-endorphin assay did not cross-react with beta-lipotropin. In common migraine, median plasma beta-endorphin was 3.3 pmol/l (95% confidence limits: 2.5-4.0 pmol/l) during attacks and 2.9 (2.4-3.2) pmol/l in the headache-free period. In classic migraine, plasma beta-endorphin was 3.2 (1.4-4.3) pmol/l during attacks and 2.4 (1.1-3.6) pmol/l outside attacks. ACTH plasma levels were 15 (10.5-20) pmol/l during and 15.7 (13.4-17) pmol/l outside attacks in common migraine. In classic migraine, plasma ACTH was 16 (7-36) pmol/l and 12.3 (8-28) pmol/l respectively. No significant differences were found between attacks and headache-free periods in common or classic migraine. Accordingly, we could not add evidence to the theory of a dysfunction of the endogenous opioid system in migraine.     

Primary headaches: reduced circulating β-lipotropin and β-endorphin levels with impaired reactivity to acupuncture

Eleven patients affected by common migraine (CM), eleven affected by daily chronic headache (DCH), and eight healthy volunteers were studied. Plasma levels of beta-endorphin (beta EP), beta-lipotropin (beta LPH). ACTH and cortisol were measured in basal conditions and after traditional Chinese acupuncture (TCA). Basal beta LPH and beta EP plasma levels (pg/ml) in the DCH patients (57.6 +/- 9.5 and 16.8 +/- 2.5, respectively; M +/- SE) were lower than those found in the controls (83.6 +/- 13.7 and 26.0 +/- 6.1; p less than 0.001), while those found in the CM cases showed inter-mediate values (75.3 +/- 12.0 and 24.4 +/- 5.8). ACTH and cortisol concentrations in both the CM and DCH patients were in the same range as those of the control group. TCA caused an increase in beta LPH and beta EP plasma concentrations in the control group (beta LPH: 117 +/- 16.9; beta EP: 44.1 +/- 6.7). Opioid plasma levels, however, remained unmodified after TCA in both the CM and DCH groups. ACTH plasma levels remained stable after TCA in all three subject groups. Patients suffering from primary headache are characterized by low beta LPH and beta EP plasma levels and by a poor reactivity of circulating opioids to non-stressful stimuli.     

Continuous subcutaneous administration of high-dose salmon calcitonin in bone metastasis: pain control and beta-endorphin plasma levels

This prospective nonrandomized trial was performed to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain related to bone metastasis in cancer patients and the relation of sCT's analgesic efficacy with beta-endorphin blood levels. The study group consisted of 22 cancer patients with bone metastases (male 13 and female 9, age range 38-77 years). Pain control was first achieved by continuous subcutaneous (s.c.) morphine administration. The next increase in pain was managed with continuous s.c. administration of 400 IU/day sCT. Beta-endorphin blood levels were measured before and during sCT administration. The first measurement was taken before sCT administration; subsequent measurement occurred at 12, 24, and 48 hours and 7 days after the commencement of treatment. Pain scores were monitored by a visual analogue scale. A complete blood count and a biochemical screening profile were taken before the administration of calcitonin and also on the seventh and the fifteenth day of the administration. The results showed a satisfactory analgesic effect. The mean pain score before the calcitonin administration was 4.43 and the score on the seventh day was 1.17. The gradual reduction of pain score was associated with an increase in beta-endorphin blood levels (increase to 147.2% of baseline on the seventh treatment day). In three cases, no satisfactory analgesic effect was obtained and pain control was achieved by increasing the continuous s.c. morphine dosage. No significant side effects were observed. These data suggest that sCT in high doses may be a useful adjuvant analgesic when combined with low doses of morphine in continuous s.c. administration for the management of metastatic bone pain.     

Concomitant increase in nociceptive flexion reflex threshold and plasma opioids following transcutaneous nerve stimulation

In order to evaluate the role of endogenous opioids in sustaining analgesia induced by transcutaneous nerve stimulation (TNS), we measured plasma beta-lipotropin (BLPH), beta-endorphin (BEP), ACTH and cortisol changes concomitantly with nociceptive flexion reflex (RIII) threshold after TNS (80 microseconds rectangular waves at 85 Hz) in a group of healthy volunteers (A). The same protocol was carried out in another group of volunteers using placebo stimulation (0.5 Hz) (B). RIII threshold significantly increased 0.5 h after TNS in group A and no changes were recorded in group B. Similarly, both BLPH and BEP plasma levels increased at the end of TNS only in group A. ACTH and cortisol concentrations show only random variations after both high and low frequency TNS. A positive linear correlation was found between the maximum percentage increase of RIII threshold after high frequency TNS and the maximum percentage increase of BLPH plasma levels occurring 20 min beforehand (r = 0.856, P less than 0.001). A less positive correlation was found between RIII and BEP levels (r = 0.574, P less than 0.05). These data indicate that the so-called post-stimulation analgesia could be supported by the enhancement of the endogenous opioid system.     

异位促肾上腺皮质激素综合征合并肺孢子菌肺炎一例及文献复习

  目的  探讨异位促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)综合征合并肺孢子菌肺炎(pneumocystis carinii pneumonia, PCP)患者的临床特征和治疗。  方法  回顾性分析北京协和医院诊治的1例异位ACTH综合征合并PCP患者的临床资料, 并复习相关文献。  结果  患者女性, 52岁, 以向心性肥胖、乏力起病, 血ACTH、总皮质醇显著升高, 诊断异位ACTH综合征, 右肺类癌为分泌异位ACTH的病灶。合并PCP的症状出现于手术切除异位ACTH病灶、血ACTH及总皮质醇明显下降后, 主要症状为发热、咳嗽、气短, 经磺胺、外源性激素治疗后恢复。  结论  PCP是异位ACTH综合征的严重机会性感染类型, 高的血皮质醇水平预示着更高的肺孢子菌感染率, 异位ACTH综合征合并PCP患者的症状出现在开始治疗、血皮质醇水平下降、免疫功能重建时, 尽早明确病原学、预防性治疗对改善异位ACTH综合征合并PCP预后有益。     

Epidural Calcitonin: Does it Provide Better Postoperative Analgesia? An Analysis of the Haemodynamic,Endocrine, and Nociceptive Responses of Salmon Calcitonin and Opioids in Epidural Anesthesia for Hip Arthroplasty Surgery

Abstract: Calcitonin is an endogenous regulator of calcium homeostasis, which acts principally on bone. At present, the principal indications for the therapeutic use of calcitonin are disorders involving hypercalcemia Paget's disease, acute pancreatitis, high‐bone‐turnover osteoporosis, pain associated with osteoporosis or bone metastases, and Sudeck's atrophy. The aim of this study was to compare the analgesic effects on postoperative pain of salmon calcitonin versus opioids administered epidurally. Our prospective study included 53 ASA I‐II patients who were scheduled for total hip arthoplasty under epidural anaesthesia and who did not fulfill 1 or more of the exclusion criteria: a history of pituitary gland dysfunction; diabetes mellitus; obesity; contraindications to performing an epidural block and/or an allergy to calcitonin. These patients were randomly allocated into 3 groups (A, B, and C), each of which received postoperatively a different analgesic epidural mixture of 10 mL to control postoperative pain. Group A was given bupivacaine 0.5% (5 mL) + fentanyl 100 (2 mL) + NaCl 0.9% (3 mL). Group B was given bupivacaine 0.5% (5 mL) + salmon calcitonin 100IU (1 mL) + NaCl 0.9% (4 mL). Group C was given salmon calcitonin 100IU (1 mL) + NaCl 0.9% (9 mL). Perioperatively, 4 blood samples were taken from each patient at the following specific times: 1. Before the induction of anesthesia; 2. At the end of the operation and before the epidural administration of the analgesic mixture; 3. At the end of the first postoperative hour (1 hour after the administration of the analgesic mixture); and 4. At the end of the second postoperative hour (2 hours after the administration of the mixture). In each blood sample, glucose, cortisol, growth hormone, and prolactin plasma levels were determined in order to investigate the changes of these parameters as a result of the endocrine reaction to stress, and to pain relief. The analgesic solution was administered immediately after the second blood sample was taken. At the same time as the 4 blood samples were taken, haemodynamic parameters and pain scores were recorded. Epidural salmon calcitonin in combination with local anaesthetic produces an analgesic effect similar to fentanyl and with stable hemodynamic results. It also eliminates postoperative hyperglycaemia. The cortisol plasma level does not increase during the first postoperative hour, but increases significantly during the second postoperative hour . Growth hormone and prolactin plasma levels were stable in all patients in all 3 groups. This study shows that calcitonin is a suitable alternative for the treatment of acute postoperative pain.     

Distribution of beta-endorphin immunoreactivity in normal human pituitary.

Recent immunohistochemical demonstration of calcitonin in rat pituitary has suggested that calcitonin, in addition to ACTH, endorphins, lipotropins, and melanocyte-stimulating hormones might be derived from a 31,000-dalton glycoprotein percursor molecule. This immunoperoxidase study demonstrates a similar distribution for beta-endorphin and ACTH immunoreactivity in human pituitary; however, the two peptides are not necessarily present in the same cells at all times. Calcitonin could not be demonstrated in human pituitary under conditions suitable for demonstration of the peptide in thyroid C cells. Weakly positive immunostaining could be obtained only with much increase in antiserum concentration and length of incubation, and higher concentrations of calcitonin were needed to abolish staining in preabsorption studies. It thus appears that the immunoreactive calcitonin in human pituitary differs from that in thyroid C cells. Likewise, we could not demonstrate immunoreactive endorphin in any developmental stage of medullary thyroid carcinoma. Our study suggests that caution should be applied in considering a physiologic role for calcitonin in the pituitary and in postulating a common peptide origin for endorphin and calcitonin in humans.     

Endocrine function is altered in chronic migraine patients with medication-overuse

OBJECTIVE: To evaluate the effects of analgesic overuse on endocrine function in patients with chronic migraine and medication-overuse headache (CM-MOH). BACKGROUND: Chronic migraine is frequently associated with an overuse of symptomatic medications. Drugs currently used in acute migraine attacks are associated with several endocrine effects. At present, the endocrine effects of medication overuse in chronic migraine patients are unknown. METHODS: Eighteen patients with CM-MOH, diagnosed according to the ICHD-II criteria, and 18 healthy controls received an intravenous administration of GHRH, hCRH, and TRH. Plasma concentrations of GH, TSH, ACTH, and cortisol were measured for a 90-minute period after administration of the specific releasing hormones. RESULTS: Hormonal basal concentrations were similar in both groups. GH response to GHRH was significantly reduced in patients with CM-MOH in comparison with controls. TRH induced a reduction of TSH concentrations only at the end of the test. After hCRH administration, ACTH and cortisol concentrations were significantly higher in cases than in controls. A significant correlation between duration of the disease and altered hormonal response was found. CONCLUSIONS: Our study shows that both corticotropic and somatotropic functions are significantly impaired in CM-MOH patients and suggests a role for hormones in the development of chronic migraine.     

Calcitonin and Migraine

SYNOPSIS
A group of 30 patients (12 M - 18 F) suffering from migraine underwent salmon calcitonin therapy for a period of one month. All patients were treated at first for 30 days with vehicle administration in a daily i.m. injection, as a control. Calcitonin effectiveness was evaluated in terms of changes in frequency, intensity and duration of the migraine attacks. The results show a significant difference between the observation period (vehicle only) and treatment phase, with improvement during the calcitonin treatment.     

Admission cortisol and adrenocorticotrophic hormone levels in children with meningococcal disease: evidence of adrenal insufficiency?

OBJECTIVE: To measure admission cortisol and adrenocorticotrophic hormone (ACTH) levels in children with meningococcal disease to try and determine the prevalence of adrenal insufficiency. DESIGN: Prospective observational study. SETTING: Pediatric departments of four hospitals in Merseyside, United Kingdom. PATIENTS: Ninety-six children with meningococcal disease; 29 with hypotension, ten of whom died. MEASUREMENTS AND MAIN RESULTS: Admission cortisol, ACTH, and proinflammatory cytokine levels were measured. Serial cortisol levels also were measured during the first 48 hrs. Significantly lower cortisol levels were found in those who died compared with survivors. Significantly higher ACTH levels also were found in those who died. However, no child had a cortisol level <5 microg/dL (<138 nmol/L) implying definite adrenal insufficiency. Three of 29 children with hypotension had plasma cortisol levels implying possible adrenal insufficiency (<18 microg/dL [<497 nmol/L]), but high ACTH levels were only found in one of those three. Cortisol levels decreased significantly after antibiotic treatment, unless steroid therapy was administered. ACTH levels did not correlate with cortisol or proinflammatory cytokine levels. CONCLUSIONS: Children with meningococcal disease have a wide range of initial plasma cortisol levels, with lower levels found in those who die. Many factors may affect cortisol levels, but adrenal insufficiency is probably uncommon.     

Opioid control of the hypothalamus-pituitary-adrenal axis cyclically fails in menstrual migraine

To assess the biological correlates of the precipitation of migraine attacks in the perimenstrual period, plasma beta-endorphin (beta-EP) and cortisol responses to naloxone (8 mg iv) and corticotropin releasing hormone (100 micrograms iv) were evaluated in both the follicular phase and the premenstrual period in 7 patients suffering from menstrual migraine and in 7 healthy, asymptomatic control volunteers. In the controls, naloxone evoked a significant release of both beta-EP (F = 5.86, p less than 0.002) and cortisol (F = 4.43, p less than 0.008), independently of the menstrual cycle phase (F = 0.31 and 1.04, for beta-EP and cortisol, respectively). Menstrual migraine patients, on the other hand, showed a significant hormone response only in the follicular phase, not in the premenstrual period. Corticotropin releasing hormone significantly increased beta-EP and cortisol in both the controls and the menstrual migraine patients, independently of the menstrual cycle phase. In both the naloxone and corticotropin releasing hormone testings, the basal beta-EP levels measured in the premenstrual period were lower than those observed in the follicular phase (p less than 0.02). These data demonstrate a cyclical, premenstrual dysfunction of the hypothalamic control exerted by opioids on the hypothalamus-pituitary-adrenal axis. Impairment of this fundamental adaptive mechanism (involved in stress responses and in pain control) could establish a causal relationship between menstrual-related migraine attacks and premenstrual opioid hyposensitivity.     

Progressive impairment of CSF beta-EP levels in migraine sufferers

Common migraine (CM) is an evolutive disease characterized by a progressive increase in the number of attacks and a consequent reduction in the free periods, eventually reaching a state of continuous migraine with interparoxysmal headache (MIH). To evaluate the role of central pro-opiocortin-related peptides in the pathogenesis of the disease, cerebrospinal fluid (CSF) levels of beta-lipotropin (beta-LPH), beta-endorphin (beta-EP) and ACTH were measured in two groups of migraine sufferers with increasing severity of the disease (CM and MIH), and in healthy controls. ACTH values were similar in the 3 groups, while beta-LPH levels were significantly lower (P less than 0.005) in patients affected by MIH (10.4 +/- 8.6 fmol/ml) than in patients with CM (35.7 +/- 8.3) and in controls (32.9 +/- 15.33). beta-EP levels were closely correlated with the severity of the disease: they decreased significantly from those found in healthy controls (86.1 +/- 37 fmol/ml) to those of CM sufferers (38.5 +/- 3.5; P less than 0.005) and showed a further significant fall (P less than 0.01) to the lowest levels which were found in MIH patients (14.8 +/- 9.8). These data showing that the progressive evolution of migraine is concomitant with a progressive impairment in the CSF levels of beta-EP, sustain the concept that non-organic central pain is related to a reduced activity of the neurons responsible for the CSF content of beta-EP.     

Effects of naloxone on beta-endorphin and cortisol release in sepsis

We investigated the effects of the opiate antagonist naloxone on the release of beta-endorphin and cortisol in rats subjected to sepsis. Sepsis was induced in weanling male Wistar albino rats (3–4 weeks old, 75–90 g) by cecal ligation and double perforation (CLP). Forty animals were randomly allocated to four groups. Group 1 was given naloxone hydrochloride 0.5 mg/kg subcutaneously after CLP and this treatment was repeated at 2-h intervals until the rats were killed. Group 2 rats underwent a sham operation. Group 3 (control group) rats had CLP. Group 4 consisted of nonoperated animals used to establish normal reference values. Eighteen hours after CLP or sham operation, the rats were killed by cervical dislocation and a blood sample was drawn via cardiac puncture to determine the beta-endorphin and cortisol levels. The beta-endorphin levels were significantly higher in the control group than in the sham-operated, naloxone-treated (NT), and nonoperated rats (P<0.05). However, there were no significant differences in plasma beta-endorphin levels between sham-operated, NT and nonoperated rats (P>0.05). Plasma cortisol levels were significantly higher in the control group compared with the other three groups and this difference was more significant in sham-operated and nonoperated rats (P<0.01). However, no difference existed between sham-operated, NT, and nonoperated rats (P>0.05). This study demonstrates that the endogenous opioid system may play a role in the activation of the pituitary-adrenal axis following sepsis, and shows that the increase in beta-endorphin and cortisol could be blocked by naloxone.     

Hypothalamo-pituitary-adrenal axis activity after intracranial catastrophies: what is enough?

This commentary on a paper by Bendel and colleagues in the previous issue of Critical Care describes the difficulty in assessing the sufficiency of adrenal responses to endogenous, stress-induced adrenocorticotropic hormone (ACTH) release by the pituitary or to exogenous ACTH administration in the critically ill patient in general, and after subarachnoid hemorrhage in particular. It is argued that comparisons with responses under circumstances of equal stress as well as assessments of severity of disease are necessary to judge the sufficiency of cortisol responses to endogenous and exogenous ACTH before treatment is considered. There are no universally applicable cutoff values for cortisol levels – and increases in cortisol levels with increasing levels of ACTH – for the diagnosis of relative adrenal insufficiency (or as it is now commonly termed, critical illnes-related corticosteroid insufficiency) following, for example, subarachnoid hemorrhage or other intracranial catastrophes. The paper by Bendel and colleagues is critically discussed in view of these concepts.     

Relation between plasma beta-endorphin and the ventilatory response to hypercapnia in humans

1. Endogenous opioids have been implicated in the control of breathing in neonates, but their role in ventilatory control in adults remains unclear. 2. We studied the relationship between circulating immunoreactive beta-endorphin and the ventilatory and mouth occlusion pressure responses to hypercapnia in 12 healthy male subjects. In addition, we examined the effect of repetitive hypercapnia on plasma beta-endorphin and cortisol levels. 3. A weak but significant negative relationship between the ventilatory response to hypercapnia and basal plasma beta-endorphin levels was observed (r = -0.35, P less than 0.01). A similar negative relationship was noted between mouth occlusion pressure response to hypercapnia and basal plasma beta-endorphin levels (r = -0.36, P less than 0.01). 4. Repetitive hypercapnia prevented the fall in plasma cortisol that occurred under control conditions (P less than 0.02) but had no effect on plasma beta-endorphin. 5. We conclude that plasma beta-endorphin may play a role in the central chemical control of breathing in man.     

Effect of cyproheptadine on episodic ACTH and cortisol secretion

To investigate the effect of cyproheptadine on ACTH and cortisol secretion, we obtained blood samples at 10-min intervals for 24 h in six healthy volunteers under basal conditions and under treatment with 16 mg day⁻¹cyproheptadine. Cyproheptadine caused significant decreases in mean plasma ACTH and cortisol levels in 30% and 19% of samples, respectively, mainly in the afternoon and evening. Analysis of episodic hormone secretion by three different methods demonstrated that the drug did not modulate the frequency but lowered the amplitudes of ACTH and cortisol secretory episodes. ACTH and cortisol responses following ovine CRH injection at 20.00 h were unchanged. We conclude that in the afternoon and evening central serotoninergic mechanisms influence the activity of the hypothalamic–pituitary–adrenal axis at the hypothalamic level by modulating the amplitude of the secretory hormonal bursts, but do not influence the increase in ACTH and cortisol secretion in the morning.     

VENEPUNCTURE CAUSES RAPID RISE IN PLASMA ACTH

SUMMARY Serum cortisol and adrenocorticotropin (ACTH) levels were measured on nine sleeping volunteers at midnight, before and after the stress of being woken and exposed to a single standard venepuncture. In six volunteers, plasma ACTH levels were raised within 90 seconds of venepuncture, while it remained undetectable in the other three. Cortisol levels began to rise within 4 minutes. ACTH and cortisol levels may be greatly altered by the stress of venesection. Plasma ACTH measured after a difficult venesection in a subject with poor venous access may be misleading.     

肾康2号对HPA轴抑制模型大鼠的HPA轴影响的实验研究

目的 通过观察补肾健脾中药肾康2号对HPA轴抑制模型大鼠HPA轴的影响,为其在肾病综合征激素撤减、维持治疗阶段的临床应用提供理论依据.方法 以大剂量糖皮质激素制作大鼠HPA轴抑制模型,在激素撤减至小剂量维持时予肾康2号中药灌胃,观察治疗前后肾康2号治疗组、激素对照组及正常组血清促肾上腺皮质激素(ACTH)、糖皮质激素水平和.肾上腺指数、肾上腺病理的差异.结果 在激素撤减后,治疗组、对照组大鼠血清ACTH、糖皮质激素和肾上腺指数与治疗前比较均有显著回升;治疗组血清ACTH、糖皮质激素和肾上腺指数回升速度快于对照组;治疗组肾上腺皮质束状带萎缩及细胞排列紊乱情况轻于对照组.结论 肾康2号中药有改善糖皮质激素引起的HPA轴抑制作用.     

Presence of immunoreactive beta-endorphin in normal human plasma: a concomitant release of beta-endorphin with adrenocorticotropin after metyrapone administration.

To elucidate whether or not beta-endorphin exists in plasma of normal subjects, plasma extracts obtained before and after metyrapone administration were subjected to gel exclusion chromatography, and fractions obtained were assayed by a sensitive radioimmunoassay for beta-endorphin. The basal plasma level of beta-endorphin was 5.8 +/- 1.1 pg/ml (mean +/- SE, n = 5), which rose significantly to the level of 48.9 +/- 3.8 pg/ml after a single oral dose (30 mg/kg of body wt) of metyrapone administration (P less than 0.001). Plasma ACTH levels also increased from the mean basal level of 73 +/- 4 pg/ml to 269 +/- 41 pg/ml after metyrapone administration. These results indicate that beta-endorphin, distinct from beta-lipotropin, exists in normal human plasma and that it is released from the pituitary concomitantly with ACTH.     

Nicotine, corticotropin, and smoking withdrawal symptoms: literature review and implications for successful control of nicotine addiction

The literature on corticotropin (ACTH) regulation of cortisol secretion, effects of nicotine on plasma cortisol and ACTH levels, and the cortisol response to smoking cessation is reviewed. A dose-dependent increase in plasma cortisol levels is found in habitual smokers after smoking two cigarettes. Nicotine mediates this response via a central mechanism to release cortisol from the adrenal cortex. The sites of action of nicotine appear to be in the hypothalamus or brain stem. Complete cessation of smoking is followed by a fall in plasma cortisol levels that is associated with the withdrawal of the nicotine stimulus. In addition, anxiety levels increase and plasma epinephrine levels decrease. Nicotine withdrawal symptoms confront smokers who want to quit. Many of the symptoms seem to be related to the body's response to changes in cortisol levels. As part of a comprehensive smoking cessation program, one or two intramuscular injections of ACTH gel have been shown to help smokers stop and continue to abstain from smoking.