Cervical sympathectomy affects adrenocorticotropic hormone and thyroid-stimulating hormone in rats

To examine the effects of bilateral cervical sympathectomy on the secretion of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), and prolactin (PRL), 18 male rats were divided into three groups: control (Cont), sham operation (Sham), and bilateral cervical sympathectomy (Symp). All rats were kept under a normal circadian rhythm for 2 weeks. Subsequently, blood was collected and plasma ACTH as well as serum TSH, GH, and PRL levels were measured. The difference in ACTH levels between the Cont and Sham groups was not significant, but ACTH levels in the Symp group were significantly higher than those in the other groups. The difference in TSH levels between the Cont and Sham groups was also not significant, but TSH levels in the Symp group were significantly lower than those in the Cont group. There were no statistically significant differences in GH and PRL levels among these groups. The present results suggest that cervical sympathectomy in the rat increases ACTH secretion and decreases TSH secretion in the pituitary. These effects seem to be due to a mildly increased secretion of melatonin in the pineal body that probably in turn increases corticotropin-releasing factor (CRF) secretion and decreases thyrotropin-releasing hormone (TRH) secretion in the hypothalamus. Extrapolation of these findings to humans suggests that longterm and repeated stellate ganglion block would affect the pituitary secretions of ACTH and TSH.     

Neuroendocrine stress response in gynecological laparoscopy: TIVA with propofol versus sevoflurane anesthesia

Study ObjectiveTo compare intraoperative and postoperative neuroendocrine stress responses during total intravenous anesthesia (TIVA) using propofol and remifentanil versus sevoflurane anesthesia, during laparoscopic surgery.DesignProspective, randomized study.SettingTertiary-care university hospital.Patients46 ASA physical status I patients undergoing laparoscopic surgery for benign ovarian cysts.InterventionPatients were randomly allocated to two groups to receive either TIVA (Group A = 23) or sevoflurane anesthesia (Group B = 23).MeasurementsPerioperative plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), prolactin (PRL), and thyroid hormones (TSH, FT₃, FT₄) were measured. Blood samples were collected preoperatively, 30 minutes after the beginning of surgery, after extubation, and two and 4 hours after the end of surgery (times 0, 1, 2, 3, and 4).Main ResultsIn Group A, perioperative levels of NE, E, ACTH, cortisol, and GH compared with preoperative values significantly decreased; in Group B they increased (Groups A vs. B: time 1, P < 0.001 for all markers; time 2, P < 0.001 for E, ACTH, cortisol, and GH; time 3, P < 0.01 for cortisol, NE, and E, and P < 0.05 for ACTH and GH). Perioperative PRL levels were significantly enhanced in both groups versus preoperative values. In both groups, TSH levels increased while FT₃ levels decreased significantly relative to basal values. In both groups, perioperative FT₄ levels significantly increased compared with preoperative values.ConclusionsTIVA inhibited the ACTH-cortisol axis and reduced NE, E, and GH levels, but it enhanced PRL and had a weak effect on thyroid hormone concentrations as compared to sevoflurane anesthesia.     

Pituitary functions in the acute phase of traumatic brain injury: are they related to severity of the injury or mortality?

Primary objective: There are only limited data regarding pituitary functions in the acute phase of traumatic brain injury (TBI) and previous studies have been conducted in only small cohorts of subjects. Therefore we have investigated the pituitary functions in the early acute phase, within 24 hours of trauma, in 104 patients with TBI. Additionally, the relationships between basal pituitary hormones, severity of the trauma and mortality due to trauma were also investigated.

Methods and procedures: One hundred and four TBI patients were included in the study consecutively. All patients underwent basal hormonal evaluation within the first 24 hours of admission. Twenty of 104 patients died during the acute phase.

Main outcomes: Prolactin levels were negatively correlated with the Glasgow coma scale (GCS), cortisol levels were positively correlated with the GCS and cortisol levels were positively correlated with ACTH levels. Additionally there was a significant positive correlation between the total testosterone levels and the GCS in males. Logistic regression analysis revealed that mortality after TBI was unrelated to basal pituitary hormone levels. However age and GCS were significantly related to the mortality. The percentages of pituitary hormone deficiencies were as follows: 3.8% had TSH deficiency, 40.0% had gonadotrophin deficiency, 8.8% had ACTH deficiency and 20.0% had GH deficiency.

Conclusions: Present data clearly demonstrate that pituitary function is disturbed in TBI and the most frequently deficient pituitary hormones were gonadotrophins in the early acute phase of TBI. Basal hormone levels including cortisol, prolactin and total testosterone were related to the severity of the trauma. However there was no relation between basal hormones and mortality due to TBI. Age and GCS were significantly related to mortality.     

Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling

Introduction In anorexia nervosa (AN) patients osteoporosis occurs within a framework of multiple hormonal abnormalities as a result of bone turnover uncoupling, with decreased bone formation and increased bone resorption. The aim of study was to evaluate the hormonal and nutritional relationships with both of these bone remodeling compartments and their eventual modifications with age. Patients and measurements In a cohort of 115 AN patients (mean BMI:14.6 kg/m2) that included 60 mature adolescents (age: 15.5–20 years) and 55 adult women (age: 20–37 years) and in 28 age-matched controls (12 mature adolescents and 16 adults) we assessed: bone markers [serum osteocalcin, skeletal alkaline phosphatase (sALP), C-telopeptide of type I collagen (sCTX) and tartrate-resistant acid phosphatase type 5b (TRAP 5b)], nutritional markers [ body mass index (BMI, fat and lean mass), hormones (free tri-iodothyronine (T3), free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 β estradiol, free testosterone index (FTI), dehydroepiandrosterone (DHEAS), insulin-like growth factor 1 (IGF-1), growth hormone (GH) and cortisol], plasma methoxyamines (metanephrine and normetanephrine) and calcium metabolism parameters [parathyroid hormone (PTH), Ca, vitamin D₃]. Results Osteocalcin reached similar low levels in both AN age subgroups. sCTX levels were found to be elevated in all AN subjects and higher in mature adolescents than in adult AN (11,567±895 vs. 8976±805 pmol/l, p<0.05). sALP was significantly lower only in mature adolescent AN patients, while there were no significant differences in the levels of TRAP 5b between AN patients and age-matched control groups. Osteocalcin correlated with sCTX in the control subjects (r=0.65) but not in the AN patients, suggesting the independent regulation of these markers in AN patients. Osteocalcin levels strongly correlated with freeT3, IGF-I, 17 β estradiol and cortisol, while sCTX correlated with IGF-I, GH and cortisol in both age subgroups of the AN patients. Other hormones or nutritional parameters displayed age-related correlations with bone markers, leading to different stepwise regression models for each age interval. In mature adolescent AN patients, up to 54% of the osteocalcin variance was due to BMI, cortisol and 17 β estradiol, while 54% of the sCTX variance was determined by GH. In adult subjects, freeT3 and IGF-I accounted for 64% of osteocalcin variance, while 65% of the sCTX variance was due to GH, FTI and methoxyamines. Conclusions We suggest a more complex mechanism of AN bone uncoupling that includes not only “classical” influence elements like cortisol, IGF-I, GH or 17 β estradiol but also freeT3, catecholamines and a “direct” hormone-independent impact of denutrition. Continuous changes of these influences with age should be considered within the therapeutic approach to AN bone loss.     

A background infusion of morphine does not enhance postoperative analgesia after cardiac surgery

PURPOSE: To compare the effects of patient-controlled analgesia (PCA), with or without a background infusion of morphine on postoperative pain relief and stress response after cardiac anesthesia. METHODS: With University Ethics approval, 35 consenting adults undergoing elective open-heart surgery were randomly assigned preoperatively in a double-blind fashion to receive either morphine PCA alone (Group I, n = 15) or morphine PCA plus a continuous basal infusion (Group II, n = 14) for 44 hr postoperatively. Pain scores with visual analogue scale (VAS) at rest, deep inspiration and with cough, sedation scores, stress hormone levels [cortisol, adrenocorticotropin (ACTH) and growth hormone (GH)] and morphine consumption were assessed, and serum morphine levels were measured at four, 20, 28 and 44 hr after surgery. Adverse effects including nausea, vomiting, constipation, urinary retention and pruritus were noted. Total blood, fluid requirements, drainage and urinary output were recorded. RESULTS: Postoperative morphine consumption at 44 hr was less in Group I (29.43 +/- 12.57 mg) than in Group II (50.14 +/- 16.44 mg), P = 0.0006. There was no significant difference between groups in VAS scores, GH levels, blood levels of morphine and adverse effects. While VAS scores, ACTH and GH levels decreased significantly in both groups, plasma cortisol levels increased significantly in Group I only at four hours. In Group II, ACTH and cortisol were higher at four and 44 hr respectively. CONCLUSION: PCA with morphine effectively controlled postoperative pain after cardiac surgery. The addition of a background infusion of morphine did not enhance analgesia and increased morphine consumption.     

Physiology of the pituitary, thyroid and adrenal glands

The pituitary gland is made of clusters of cells producing specific hormones that control growth (growth hormones, GH), thyroid function (TH), adrenal function (ACTH), gonadal function (FSH and LH). In addition, the neurons that join the posterior pituitary (neurohypophysis) secrete vasopressin - the antidiuretic hormone involved in maintaining water balance.The negative feedback loop is the basic mechanism to control the regulation of all endocrine glands. Hypothalamic peptides - releasing hormones (e.g. TRH, CRH) reach the hypophysis via the portal venous system and induce the secretion of specific stimulating hormones (e.g. TSH, ACTH) that drive the end-target endocrine cells to secrete hormones (e.g. thyroid hormones - T3 and T4 or adrenal hormones - cortisol, DHEAS). The plasma levels of these circulating hormones inhibit the pituitary (short feedback) or the hypothalamus (long feedback) and limit the further release of releasing- and stimulating- hormones.The effects of circulating hormones on different tissues are mediated via specific receptors on the cell membrane (e.g. vasopressin receptors), in the cytoplasm (steroid receptor for cortisol) or in the nucleus (e.g. thyroid hormone receptors). Understanding the physiological effects of peripheral hormones helps understanding the mechanisms by which clinical signs and symptoms developed in diseases characterised by excessive hormone secretion (e.g. thyrotoxicosis, Cushing syndrome, phaeochromocytomas) or lack of hormone secretion (e.g. diabetes insipidus).     

Combined acromegaly and subclinical Cushing disease related to high-molecular-weight adrenocorticotropic hormone

A 36-year-old man with a 1-year history of diabetes mellitus was referred to the authors' hospital for further endocrinological evaluation of acromegaly. On physical examination, typical acromegalic features but no typical cushingoid features were observed. The clinical diagnosis of growth hormone (GH)-producing pituitary adenoma was confirmed by MR imaging findings, nonsuppression of serum GH levels during a 75-g oral glucose tolerance test (trough GH 6.33 ng/ml), and elevated serum insulin-like growth factor-I levels (1361.3 ng/ml). Moreover, autonomic adrenocorticotropic hormone (ACTH) secretion was suspected, based on inadequate suppression of ACTH or cortisol levels by an 0.5-mg overnight dexamethasone suppression test. Analysis of the patient's plasma by using the gel filtration method revealed the presence of a high-molecular-weight (HMW) form of ACTH known to exhibit low biological activity. Transsphenoidal adenomectomy was performed for the pituitary tumor. Immunohistochemical investigation of the resected specimen showed strong and diffuse immunoreactivity to GH and focal immunoreactivity to ACTH. Although there have been a few cases of pituitary adenoma that produced GH and ACTH concomitantly, this is the first report of the detection of HMW ACTH in patients with GH- and ACTH-producing adenomas. Furthermore, the previous cases also did not exhibit typical cushingoid features. It is suggested that the secretion of ACTH in patients with concurrent GH- and ACTH-secreting adenomas might consist of the HMW form and that the HMW ACTH is consequently associated with a subclinical Cushing state.     

Sevoflurane improves the neuroendocrine stress response during laparoscopic pelvic surgery

PURPOSE: Stress response to surgery is modulated by several factors, including magnitude of the injury, type of procedure (e.g., laparoscopy vs laparotomy) and type of anesthesia. Our purpose was to compare intra- and postoperative hormonal changes during isoflurane vs sevoflurane anesthesia, in a clinical model of well defined operative stress (laparoscopic pelvic surgery). METHOD: In this prospective randomized clinical study, 20 women requiring laparoscopic pelvic surgery for benign ovarian cysts received either a standard isoflurane plus fentanyl (Group A) or sevoflurane plus fentanyl anesthesia (Group B). Blood samples were collected preoperatively, 30 min after the beginning of surgery, at the end of surgery after extubation, and two and four hours after the end of surgery. Intra- and postoperative plasma levels of norepinephrine, epinephrine, adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH) and prolactin (PRL) were measured. RESULTS: Catecholamine levels and postoperative pain were similar in both groups. Nonetheless, in comparison to Group A, Group B showed a significant decrease of ACTH, cortisol and GH levels (A vs B at the end of surgery: ACTH 160 +/- 45 vs 100 +/- 40 pg.mL(-1); cortisol 45 +/- 8 vs 23 +/- 7 microg.dL(-1); GH 3 +/- 2 vs 0.8 +/- 0.4 ng.mL(-1); P < 0.001 for all), but enhanced PRL levels (A vs B, at 30 min after the beginning of surgery: 139 +/- 54 vs 185 +/- 22 ng.mL(-1); at the end of surgery: 100 +/- 27 vs 141 +/- 45 ng.mL(-1); P < 0.001 for both). CONCLUSIONS: In the clinical setting of low stress laparoscopic surgery, the type of volatile anesthetic significantly affected the stress response; the changes associated with sevoflurane suggested a more favourable metabolic and immune response compared to isoflurane.     

Multiple Pituitary Hormone Gradients from Cavernous Sinus Sampling in Patients with Cushing's Disease

Summary  Objective. Cavernous sinus sampling in patients with adrenocorticotropic-hormone (ACTH) secreting pituitary adenomas has been used to identify directly ACTH hypersecretion from the pituitary and to predict the lateralization of a microadenoma. In our previous series, cavernous sinus sampling provided a sufficient central/peripheral (c/p) ratio of ACTH and the correct laterality of the pituitary lesion in all microadenomas situated in the lateral wing. To clarify the diagnostic value of other anterior pituitary hormones in relation to ACTH gradients, we evaluated multiple pituitary hormone gradients between a cavernous sinus and a peripheral vein and between both cavernous sinuses in patients with Cushing's disease.  Methods. Cavernous sinus sampling was done in 11 patients with clinical and biochemical features of ACTH-dependent Cushing's syndrome. In 9, pituitary adenoma was detected during transsphenoidal surgery and histologically confirmed, while 2 others were suspected of having ectopic lesions. Serum ACTH, prolactin (PRL), thyroid stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) from catheters in both cavernous sinuses and from a peripheral vein were measured. The c/p ratios of each hormone and the intercavernous gradients were evaluated.  Results. The c/p ratio of ACTH indicated the presense of pituitary lesions in all 9 patients with ACTH-secreting microadenomas. In addition, the intercavernous gradients of ACTH indicated the correct localization of microadenomas in all 6 patients with lateralized lesions. As for other hormones, the c/p ratios of GH, PRL, TSH and LH were significantly high in number 7, 6, 6 and 3 patients, respectively. In contrast, the significant step up of FSH was observed only in one patient. The intercavernous gradients of GH and PRL were significantly high in number 5 and 4 patients, respectively.  Conclusions. The intercavernous gradients of GH and PRL tend to indicate the lateralization of a microadenoma. The measurement of GH and PRL during cavernous sinus sampling may provide additional information, in the lateralization of ACTH-secreting microadenomas.     

Plasma osteocalcin values and related hormonal parameters in patients subjected to a variety of prostate anticancer agents

Summary Circulating osteocalcin (OC) and cortisol levels were measured in blood samples from 93 patients with dissaminated prostate cancer. Among these subjects 79 had not responsed to therapy, while 14 had responded to a variety of anticancer treatment strategies (orchiectomy, cyproterone acetate (CPA), flutamide, Buserelin, diethylstilbestrol (DES), Estracyt, and polyestradiol phosphate). The control group consisted of 19 patients with benign prostatic hypertrophy. In the majority of these patients blood adrenocorticotropic hormone (ACTH), estradiol human growth hormone (hGH), and thyroid stimulating hormone (TSH) levels were also assessed. In nonresponders to therapy with DES and Estracyt subnormal circulating OC levels were measured, while normal OC values were found in nonresponders to other treatment strategies. In patient given Estracyt highly elevated estradiol levels were recorded. Subnormal and/or low-normal estradiol concentrations were found in patients subjected to CPA and DES. Elevated blood cortisol levels were assessed in subjects treated with DES and Estracyt while at the same time either subnormal and low-normal plasma ACTH concentrations were measured in these same patients. Accordingly, the decline observed in OC concentration seems to be a consequence of the well-established inhibitory effect of glucorticoids on osteoblast activity. The decline in blood cortisol levels obtained after administration of dexamethasone in patients given DES and Estracyt may be attributed both to possible changes in catabolic pathways and to the contribution of the negative neuroendocrinological feedback.     

Altered hormonal activity in severely ill patients after injury or sepsis

We studied the hormonal millieu and possibility of altered thyroid function in 25 patients in a surgical intensive care unit (ICU) who had severe life-threatening illnesses. Sixteen patients had septic complications and nine patients had multiple-system injuries. On admission to the ICU, serial measurements were begun of thyroxine (T4), triiodothyronine (T3), T4-binding globulin, thyrotropin (thyroid-stimulating hormone [TSH]), corticotropin (adrenocorticotropic hormone [ACTH]), cortisol, prolactin, human growth hormone, catecholamine, insulin and glucose, lactate, retinol-binding protein, prealbumin, and transferrin levels. All patients initially had low normal levels of T4 (4.5 +/- 2 micrograms/dL) and T3 (55 +/- 26 ng/dL), with normal TSH levels (2.3 +/- 2.3 microU/mL) (the "low T3 syndrome"). The 11 surviving patients had their levels increase to normal before leaving the ICU (T4, 7.0 +/- 2.1 micrograms/dL; T3, 110 +/- 48 ng/dL; and TSH, no change). The 14 patients who died showed further decreases before death (T4, 2.6 +/- 2.1 micrograms/dL; T3, 30.6 +/- 23.5 ng/dL; and TSH, 0.9 +/- 0.7 microU/mL). The corticotropin, cortisol, prolactin, and growth hormone levels were normal throughout the study. Catecholamine levels were high initially and decreased in surviving patients. Epinephrine levels increased greatly in nonsurvivors before death, and the norepinephrine-epinephrine ratio decreased from 5.7:1 to 2:1. After protirelin (thyroid-releasing hormone [TRH]) stimulation, the TSH level increased either minimally or not at all in six patients who eventually died. This indicates hypothalamic-pituitary dysregulation or suppression, and altered release and/or peripheral metabolism of T4. Whether this represents a deficiency of thyroid hormone for cell and organ function remains to be established.     

Study on testicular tissue in animals with congenital hormone deficiency

Of 3 kinds of animals with congenital hormone deficiency, i.e., mouse with Snell pituitary dwarfism (dw) in which hypoplasia of the pituitary anterior lobe is seen from embryonal stage and which almost lacks in growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH); mouse with little dwarfism lacking only in GH (lit); and mouse with congenital primary hypothyroidism in which the thyroidal gland shows hypoplasia, thyroxine (T4) in blood is not measurable and, conversely, TSH level is abnormally high (hyt), the males of dw/dw and hyt/hyt have been proved to be infertile, but it is little known about lit/lit. After performing early recovery experiment by administering GH + T4 to dw/dw, GH to lit/lit and T4 to hyt/hyt from birth, the testicles of 40-day-old mice were investigated morphologically in the normal control group, non-treated group and treated group in order to clarify the relation between hormones and the sperm-generating potency. The total number of sperm-generating cells, which consist of spermatogonia, spermatocytes, spermatids and sperms, showed remarkable decreases, compared with each control group, and the decrease in total cell number was improved favorably by treatment with hormone. In comparison with the control groups, significant decreases were showed in the spermatid number for the dw/dw group, sperm number for the lit/lit group, and spermatid and sperm numbers for the hyt/hyt group. These results indicate that GH and T4 have a potential effect on sperm-generating function.     

The effect of clonidine pretreatment on the perioperative proinflammatory cytokines, cortisol, and ACTH responses in patients undergoing total abdominal hysterectomy

We investigated the hypothesis that oral clonidine premedication would decrease the release of proinflammatory cytokines interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha, and stress hormones cortisol and adrenocorticotropic hormone (ACTH), in patients who underwent total abdominal hysterectomy. Twenty patients were randomly assigned to one of two groups: the control group received no premedication, whereas the treatment group received clonidine 0.15 mg oral dose 90 min before surgery. Venous blood samples were obtained at preinduction time and immediately, 1, and 3 h after the start of surgery. IL-6 increased significantly at 3 h, and cortisol and ACTH at 1 and 3 h after the start of surgery compared with the baseline values within both groups. IL-1beta levels decreased at all times compared with the baseline value in the control group. In the comparison study between the control group and the clonidine group, there was a significant decrease in IL-6 level 3 h after the start of surgery and IL-1beta at preinduction time in the clonidine group, whereas there were no changes in tumor necrosis factor-alpha, cortisol, and ACTH levels. These results show that clonidine modulates the IL-6 response related to surgical stress. Implications: We assessed the effect of the alpha(2)-adrenoreceptor agonist clonidine on the immunoendocrine activity during the perioperative period. Clonidine 0.15 mg given as oral premedication resulted in the reduced Interleukin-6 production in response to total abdominal hysterectomy.     

Influence of long term erythropoietin therapy on the hypothalamic-pituitary-thyroid axis in patients undergoing capd

OBJECTIVE: Treatment of anemia with recombinant human erythropoietin (rHuEpo) in hemodialysis patients has been associated with improvement of several abnormalities in hypothalamic-pituitary function. The aim of the present study is to investigate the effects of long term erythropoietin therapy on the hypothalamic-pituitary-thyroid hormone axis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Single center, prospective study. PATIENTS AND METHODS: Ten patients who were clinically stable and had been on CAPD were evaluated. Eleven age and sex matched healthy volunteers were chosen as controls. All of the patients were clinically euthyroid. All patients were on CAPD therapy and none of them had received rHuEpo treatment previously. In all patients after basal estimations of free T3, free T4, TSH, GH and prolactin levels, a bolus of 400 microg TRH was administered intravenously. Levels of TSH, GH and prolactin were measured in blood samples collected every 30 min of the 3 h test period. After the treatment with rHuEpo, TRH test with the same protocol was repeated. RESULTS: Before the improvement in serum hemoglobin levels with rHuEpo treatment, the patients on CAPD showed abnormal hypothalamic-pituitary-thyroidal functions, including delayed and prolonged TSH (NS), paradoxically elevated GH (p < 0.001) and increased and prolonged prolactin (p = 0.001) responses to TRH. After improvement of anemia with rHuEpo no significant difference was found between the patients and control groups for baseline TSH levels. In the patients peak TSH level and AUC of TSH secretion were significantly reduced after the treatment (p < 0.05 for both). Furthermore the improvement in anemia did not eliminate the paradoxic GH and prolonged prolactin responses to TRH administration. CONCLUSION: Some hypothalamic-pituitary-thyroid function abnormalities including delayed and blunted TSH, increased and prolonged prolactin and paradoxical GH responses to TRH administration were observed in uremic patients treated with CAPD and the improvement in anemia with rHuEpo seems to cause slight changes on the hypothalamic-pituitary-thyroid axis and peripheral thyroid hormones.     

Immunoreactive ACTH, beta-endorphin, and cortisol levels in plasma following spinal manipulative therapy

This study examines the possibility of a humorally mediated analgesic response to spinal manipulative therapy by determination of plasma levels of beta-endorphin, adrenocorticotropic hormone (ACTH), and cortisol before and after intervention. Forty male subjects (20 symptomatic, 20 asymptomatic) were allocated into four equal groups. Two treatment groups were given spinal manipulative therapy, and two groups underwent a sham procedure. Blood samples were taken via indwelling butterfly needles pre- and postintervention in all four groups, and levels of immunoreactive ACTH, immunoreactive beta-endorphin, and cortisol determined by radioimmunoassay. No differences in ACTH or beta-endorphin were found between sham and treated groups, or between pre- and postintervention in any group; cortisol levels fell over the course of the study in all groups. The findings thus appear to exclude a humoral role for beta-endorphin in mediating the analgesic response to spinal manipulative therapy; in addition, they suggest that such therapy is not a stressor that activates the hypothalamo-pituitary-adrenal axis.     

Dehydroepiandrosterone sulfate and growth axis hormones in patients after surgery

We selected 38 patients scheduled for cholecystectomy and studied their serum concentrations of dehydroepiandrosterone (DHEA) and growth axis hormones [growth hormone/insulin-like growth factor-1 (GH/IGF-1)]. We aimed to determine whether alterations in these concentrations resulted from surgical stress or, on the contrary, preceded surgery and were themselves a cause of chronic diseases that reduce life expectancy. We measured the serum concentrations of DHEA sulfate (DHEA-S), ACTH, cortisol, human GH (hGH), IGF-1, and IGF-1 binding protein-3 (IGFBP-3) preoperatively and then 2 and 7 days after surgery; we also compared the preoperative findings with those of a healthy control group. The results were analyzed by gender because DHEA and GH/IGF-1 are known to present sexual dimorphism. There were no significant differences between the preoperative and control results for any of the parameters studied. We found a significant reduction in the concentrations of DHEA-S and IGF-1 on days 2 and 7 after surgery versus the preoperative values. We conclude that the decrease in DHEA-S in patients after surgery is a result of surgical trauma and does not precede surgical stress. The decrease in hormone levels observed in patients with chronic disease may therefore be a result, not a cause, of disease, as some have claimed. Further studies with a later endpoint would be of interest to assess any subsequent return of DHEA-S levels to baseline measurements.     

Effect of an exercise and dietary intervention on serum biomarkers in overweight and obese adults with osteoarthritis of the knee

OBJECTIVE: To determine the effects of exercise and weight loss interventions on serum levels of four biomarkers and to examine if changes in biomarker levels correlate with clinical outcome measures in obese and overweight adults with knee osteoarthritis (OA). METHODS: Serum was obtained at baseline, 6 and 18 months from 193 participants in Arthritis, Diet and Activity Promotion Trial. This was a single-blind 18-month trial with subjects randomized to four groups: healthy-lifestyle (HL), diet (D), exercise (E) and diet plus exercise (D+E). Serum levels of cartilage oligomeric matrix protein (COMP), hyaluronan (HA), antigenic keratan sulfate (AgKS), and transforming growth factor-beta1 (TGF-beta1) were measured by enzyme linked immunosorbent assay. RESULTS: At baseline there were no significant differences in biomarker levels between intervention groups. When results for all the intervention groups were combined, the levels of HA were found to be negatively correlated with medial joint space width and positively correlated with Kellgren-Lawrence scores (K-L scores) while TGF-beta1 levels negatively correlated with K-L scores. When biomarker levels measured at 6 and 18 months were adjusted for baseline values, age, gender, and body mass index, weak but significant differences between intervention groups were present for mean levels of COMP and TGF-beta1. Furthermore, AgKS levels averaged over all groups tended to decrease over time. There were no significant associations of baseline biomarkers and the follow-up outcomes. Weak associations were noted between change in the biomarkers at 18 months and change in outcome measures that included change in weight with AgKS and COMP and change in Western Ontario and McMaster Universities Osteoarthritis Index pain with AgKS. CONCLUSION: Overall, the E and D interventions did not show a consistent effect on levels of potential OA biomarkers. The four biomarkers showed differences in correlations with outcome measures suggesting that they may measure different aspects of disease activity in OA. The strongest correlations were between serum HA and radiographic measures of OA at baseline.     

43例垂体瘤术后成人生长激素水平调查

[摘要]目的了解垂体瘤患者在接受治疗后生长激素的储备功能及生长激素缺乏与多种垂体激素缺乏之间的关系。方法以2008年5月至2013年7月间,以在河北省沧州市中心医院接受治疗的43位垂体瘤患者作为调查对象,进行胰岛素低血糖兴奋试验（11Tr）,分析生长激素（GH）、促性腺激素（Gn）、促甲状腺激素（TSH）、精氨酸加压素（AVP）和促肾上腺皮质激素（ACTH）的分泌功能。结果共入组43例垂体瘤患者,男性29例,女性14例,中位年龄为48岁。其中仅5例Irrr实验兴奋后GH分泌正常,余38例均患严重的生长激素缺乏症,且表现出一种或一种以上的垂体激素缺乏症状。结论垂体瘤术后,生长激素缺乏症的发生率很高;患有一种或一种以上垂体激素缺乏的患者都会伴有生长激素缺乏症。     

Sex hormone modulation of serum TSH levels

This study was undertaken to determine the effects of estrogen and testosterone on baseline and thyrotropin-releasing hormone (TRH)-stimulated serum thyroid-stimulating hormone (TSH) levels in rats. Seven groups of 20 rats each were studied: intact males (group I), intact females (group II), castrated males (group III), castrated females (group IV), castrated males with testosterone replacement (group V), castrated females with testosterone supplement (group VI), and intact females with testosterone supplement (group VII). Two weeks after initiation of these hormone treatments, blood samples for TSH levels were obtained before and 10 minutes after TRH injection. Testosterone levels were also determined to verify hormone release. The results of these studies indicated that (1) testosterone has a primary, stimulatory role in the control of TSH concentration in that it causes elevation of both baseline and TRH-stimulated TSH levels, (2) endogenous estrogens have no such direct effect on TSH levels, and (3) in the presence of testosterone, endogenous estrogens partially inhibit the TSH-elevating effect of the androgen. As TSH stimulation is considered requisite for thyroid carcinogenesis, the different effects of testosterone and estrogen on TSH levels, demonstrated in this study, may in part explain differences in incidence and prognosis of thyroid carcinoma observed between the sexes in both rats and human beings.     

Ghrelin is not necessary for adequate hormonal counterregulation of insulin-induced hypoglycemia

Ghrelin is a novel enteric hormone that stimulates growth hormone (GH), ACTH, and epinephrine; augments plasma glucose; and increases food intake by inducing the feeling of hunger. These characteristics make ghrelin a potential counterregulatory hormone. At present, it is not known whether ghrelin increases in response to insulin-induced hypoglycemia. To answer this question, we compared plasma ghrelin concentrations after a short-term insulin infusion that was allowed or not (euglycemic clamp) to cause hypoglycemia (2.7 +/- 0.2 mmol/l at 30 min) in five healthy volunteers. In both studies, plasma ghrelin concentrations decreased (P < 0.01) after insulin infusion (hypoglycemia by 14%, euglycemia by 22%), reached a nadir at 30 min, and returned to baseline at 60 min, without differences between the hypoglycemia and the euglycemia studies. Glucagon, cortisol, and GH increased in response to hypoglycemia despite the decreased ghrelin. There was a strong correlation (R(2) = 0.91, P < 0.002) between the insulin sensitivity of the subjects and the percentage suppression of ghrelin from baseline. These data demonstrate that ghrelin is not required for the hormonal defenses against insulin-induced hypoglycemia and that insulin can suppress ghrelin levels in healthy humans. These results raise the possibility that postprandial hyperinsulinemia is responsible for the reduction of plasma ghrelin that occurs during meal intake.