Rise In ACTH Levels Research Articles

Feeding and Manual Brushing Influence the Release of Oxytocin, ACTH and Cortisol Differently During Milking in Dairy Cows.

AimThis study aimed to examine the effects of feeding or abdominal brushing on the release of the hormones oxytocin, ACTH and cortisol during milking in dairy cows.MethodsTwelve cows in early lactation were used (2 × 2 factorial experimental design), testing the effects of two types of sensory stimulation during milking over a 3 day period; feeding concentrate or manual abdominal brushing (1 stroke/s). Blood samples for hormone analyses were collected at time at −15, −1, 0 (onset of cluster), every min for 8 min, at 10, 12, 14, 16, 30, and 60 min. Hormone levels were assayed and AUC was calculated.ResultsMilking was associated with an immediate and significant rise of oxytocin. When milking was combined with feeding, significantly higher levels of oxytocin were observed at 2 and 4 mins (p < 0.05). No effect of brushing on oxytocin levels was observed. Milking alone was associated with a significant rise of ACTH levels. Feeding in connection with milking reduced the immediate rise of ACTH levels (p < 0.05) and AUC (p < 0.02), whereas no effects of brushing were found. Milking caused a progressive rise of cortisol levels. Concomitant feeding did not influence cortisol levels, whereas brushing significantly decreased cortisol levels at 1, 5 and 14 mins after onset of milking (p < 0.05).ConclusionFeeding increases oxytocin release in response to milking and decreases ACTH levels. Abdominal brushing did not influence these variables, but decreased cortisol levels. These data demonstrate that activation of afferent vagal nerve fibres and of cutaneous sensory nerves originating from the abdominal skin in front of the udder influence milking related hormone release differently.

Co Existence of a Corticotroph Adenoma and a Multifunctional Pituitary Cyst

The co-existence of a corticotroph adenoma and a pituitary cyst is very unusual. We present the case of a 50-year-old female who presented with a Cushingoid phenotype, severe hypokalaemia, hyperglycaemia and hypertension. Urinary free cortisol was markedly elevated at 50 fold. ACTH levels were elevated at 121.4 pg/ml. She failed both the low and high dose dexamethasone suppression tests. The CRF test did not show a satisfactory rise in ACTH levels but the Inferior petrosal sinus sampling revealed a central to peripheral ACTH gradient highly suggestive of Pituitary dependant Cushing’s. MRI pituitary revealed a large cystic lesion with a small solid component. Computed Tomography (CT) of thorax abdomen and pelvis was normal. A trans-sphenoidal hypophysectomy was performed, during which a fine needle aspiration of the intra-cystic fluid was obtained. This showed markedly elevated pituitary hormone levels of ACTH (1399pg/ml), prolactin (353,084mIU/L), TSH (217IU/L) FSH (205mIU/ml) and GH (519 ng/ml) consistent with a multifunctional pituitary cyst. Neuropathology of the solid component confirmed a corticotroph adenoma. Post-operative am cortisol levels were persistently suppressed to less than 50 nmol/l with marked improvement in clinical features. This case highlights the challenges in the work up of Cushing’s syndrome and the limitations of diagnostic tests. The coexistence of a corticotroph adenoma and a multifunctional pituitary cyst is very unusual and to our knowledge has not been reported before.

Visual vignette- Nelson’s syndrome: a giant pituitary

Nelson’s syndrome is an infrequent pituitary mass with an incidence of 8–43% in adults and 25–66% in children that develops following total bilateral adrenalectomy (TBA) for the treatment of Cushing’s disease. It is one of the most challenging of all endocrine conditions. The frequent aggressiveness of the underlying ACTH-secreting pituitary adenoma (corticotrophinoma) necessitates regular biochemical and radiological screening. Current evidence favours a lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in the year post TBA as factors that may predict the occurrence of Nelson’s syndrome. Though, computerized tomography (CT)/magnetic resonance imaging (MRI) have led to the early diagnosis and improvement in management. Nelson’s related tumours are sometimes detected late, through clinical manifestations of invasion and compression of the surrounding structures. With this perspective in mind, we describe a 22 year old gentleman 10 years after TBA who presented with right sided hemiparesis due to a corticotroph adenoma.

Nelson’s syndrome: a giant pituitary

Nelson’s syndrome is a pituitary mass that develops following total bilateral adrenalectomy (TBA) for the treatment of Cushing’s disease. It is one of the most challenging of all endocrine conditions. The frequent aggressiveness of the underlying ACTH-secreting pituitary adenoma (corticotrophinoma) necessitates regular biochemical and radiological screening. Failure to administer prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels during the first year following TBA are the main factors that may predict the occurrence of Nelson’s syndrome. Though, computerized tomography (CT) and magnetic resonance imaging (MRI) have led to the early diagnosis and improvement in management, these tumours are sometimes detected late, through clinical manifestations of invasion and compression of the surrounding structures. With this perspective in mind, we describe a 22-year-old gentleman who presented 10 years after TBA with right sided hemiparesis caused by a corticotroph adenoma.

Cortisol and ACTH responses to severe asphyxia in preterm fetal sheep

It has been hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis is immature in the preterm fetus and that this compromises their ability to adapt to hypoxic stress; however, there are few direct data. We therefore examined the effects of asphyxia on HPA responses in chronically instrumented preterm fetal sheep (104 days of gestation; term is 147 days), allocated to a sham control group (n = 7) or 25 min of complete umbilical cord occlusion (n = 8), followed by recovery for 72 h. During umbilical cord occlusion there was a rapid rise in ACTH levels (230.4 +/- 63.5 versus 14.1 +/- 1.8 ng ml(-1) in sham controls, 16-fold) and cortisol levels (7.4 +/- 4.9 versus 0.2 +/- 0.1 ng ml(-1), 31-fold), with further increases after release of cord occlusion. ACTH levels were normalized by 24 h, while plasma cortisol levels returned to sham control values 72 h after asphyxia. Fetal arterial blood pressure was elevated in the first 36 h, with a marked increase in femoral vascular resistance, and correlated positively with cortisol levels after asphyxia (P = 0.05). In conclusion, the preterm fetus shows a brisk, substantial HPA response to severe hypoxia.

Evidence for intraadrenal feed back regulation of steroidogenesis

Adrenal steroidogenesis is under control of pituitary ACTH secretion which may rapidly increase steroid production. Accordingly, inhibition of steroidogenesis by adrenostatic compounds leads to a compensatory rise in ACTH levels. We investigated whether also ACTH-independent intraadrenal compensatory mechanisms exist.

Hypothalamo-Pituitary-Adrenocortical Axis Function and Hedonic Behavior in Adult Male and Female Rats Prenatally Stressed by Maternal Food Restriction

Neuroendocrine activation during stress is affected by many factors contributing to the variability of the stress response. The present study was aimed at evaluating long-term changes in hypothalamo-pituitary-adrenocortical (HPA) axis function and in hedonic behavior in adult offspring prenatally stressed by maternal food restriction, with attention on possible gender differences. Adult offspring were blood sampled via a tail artery cannula. Prenatally stressed females had significantly higher adrenal weights compared to males. Plasma ACTH levels, which rose in response to acute stress induced by handling, were significantly higher in females compared to those in males. A similar pattern was found in plasma corticosterone. The rise in ACTH levels was more pronounced in prenatally stressed rats though the rise in corticosterone failed to be modified. Corticotropin releasing hormone (CRH) and proopiomelanocortin mRNA levels in the hypothalamic paraventricular nucleus and anterior pituitary, respectively, were found to be unchanged. The present experiments failed to reveal a decrease in hedonic behavior in prenatally stressed rats. In contrast, in male offspring a tendency to a higher sucrose preference was observed. These data together with observed changes in hormone and CRH mRNA levels indicate that the gestational stress used did not result in a depression-like state in adult offspring.

Leptin in pituitary adenomas--a novel paracrine regulatory system.

A growing number of physiological and pathophysiological processes have been shown to be influenced by leptin apart from its first recognised role as a modulator of hypothalamic appetite and weight control centers. We investigated the presence and pattern of distribution of leptin mRNA and the mRNA of the long isoform of the leptin receptor in the normal pituitary and in different types of pituitary adenomas. We also studied leptin secretion from human pituitary tumors in culture, and the in vitro pituitary hormone release following stimulation with human leptin. Leptin mRNA expression was detected at a low level of expression in 50% of tumors but in none of the normal pituitaries. By immunohistochemistry, leptin was present in occasional scattered cells in the normal pituitary and in pituitary tumors. The leptin receptor long isoform was detected in the majority (65%) of pituitary tumors and in all normal pituitaries. It did not segregate with any particular tumor type, and varying levels of expression were detected between the tissues studied. 34% of pituitary adenomas showed leptin release into the incubation media during in vitro culture. Leptin mRNA, the mRNA of the long isoform of the receptor, or in vitro leptin release, did not correlate with tumor type or with any of the other pituitary hormones released. In vitro leptin stimulation of pituitary tumors caused stimulation of FSH and a-subunit secretion from a non-functioning adenoma and TSH secretion from a somatotroph adenoma. As the co-localisation of ACTH and leptin in corticotroph cells was previously suggested, we investigated whether in vivo ACTH release is accompanied by a simultaneous plasma leptin level rise (i) in peripheral plasma samples after food intake-induced ACTH rise in healthy obese and nonobese individuals and (ii) in petrosal sinus samples after CRH injection in Cushing's disease patients. Our data suggest that a rise in ACTH levels is not accompanied by detectable rise in leptin levels in peripheral and in petrosal sinus blood samples. In summary, leptin is synthesized and stored within the pituitary and may modulate other pituitary hormone secretion, although probably it does not contribute to plasma leptin level changes. Pituitary leptin may therefore be a novel paracrine regulator of pituitary function.

The Pituitary-Adrenocortical System of Neonatal Rats Is Responsive to Stress throughout Development in a Time-Dependent and Stressor-Specific Fashion*

The responsiveness of the neonatal hypothalamus-pituitary-adrenal (HPA) axis to stress has been thought to be impaired or diminished during the first 2 weeks of life. Although we previously found full responsiveness of the hypothalamus-pituitary unit to adrenalectomy in young rats [days (d) 5-10], we failed to measure a significant increase in ACTH 10 min after ether administration until d14 of age. These studies were, therefore, designed to test the functional activation of the HPA axis after a single or repeated exposures to stress. Both qualitative (time-course, stressor-specific, circadian) and quantitative changes in the ACTH and corticosterone (B) responses to various stressors were tested during the first 10 days of life. Exposure to 3 min of ether vapor increased ACTH and B secretion (P less than 0.05-0.01) in 1-, 5-, and 10-d-old rats, with an increasing amplitude of both ACTH and B responses as a function of age. Peak secretion of ACTH occurred 5 min after the onset of stress (122 +/- 3.8 to 359 +/- 54 pg/ml on d1-10), while the time of maximal B increased as a function of age. Other stressors, such as maternal separation (12 h), cold (4 C; 60 min), or histamine injection (4 mg/kg BW, ip), provoked significant and stressor-specific ACTH and B responses in 10-d old rats. Histamine administration increased ACTH secretion above that of vehicle-injected rats, with a peak of secretion 15 min after drug injection (272 +/- 29 vs. 127 +/- 8 pg/ml; P less than 0.01). Histamine-induced B secretion peaked at 60 min (3.7 +/- 0.5 micrograms/dl). In contrast to early responses observed after ether, separation, or histamine stress, cold stress in 10-d-old pups caused a large ACTH and B release 4 h after the onset of cold compared to that in maternally deprived pups [ACTH: cold, 457 +/- 61 pg/ml; separated, 150 +/- 14 (P less than 0.01); B: cold, 3.3 +/- 0.4 micrograms/dl; separated, 1.8 +/- 0.2 (P less than 0.05)]. We did not detect morning-evening (AM-PM) differences in either the pattern or the magnitude of the ACTH or B response to maternal separation or cold stress. Suppression of cold-induced ACTH release by B injection (1 mg/kg BW) 2 h before stress was observed until 4 h after stress in the AM and PM, whereas when given after cold, B was less effective in the PM than in the AM at preventing the rise in ACTH levels observed at 4 h.(ABSTRACT TRUNCATED AT 400 WORDS)

The scopolamine model of dementia: determination of central cholinomimetic effects of physostigmine on cognition and biochemical markers in man

Administration of the muscarinic antagonist scopolamine has been proposed as a pharmacological model for Alzheimer's disease. We have attempted to characterize the cognitive deficits produced by the administration of scopolamine (0.2 and 0.4 mg intra muscularly) to normal volunteers. We have also demonstrated reversal of these deficits by the cholinesterase inhibitor physostigmine (1.2 mg intramuscularly). Physostigmine also elevated subjects' plasma ACTH levels, a marker of central cholinergic activity. In the cognitive study, we found that scopolamine impaired subjects' performance on verbal learning, spatial learning and choice reaction time. These changes were associated with subjective sedation as measured by analogue rating scales. Physostigmine attenuated the impairment in verbal learning and reduced subjective sedation. In the biochemical study we examined the effects of the same drug regimes on plasma ACTH levels. Physostigmine administered with a peripherally active cholinergic antagonist (glycopyrrolate 0.2 mg intramuscularly) produced a rise in ACTH level which reached a peak 30 min after drug administration. Such a rise was not apparent when the physostigmine was coadministered with scopolamine. These results suggest that cognitive and neuroendocrine indices of central cholinergic activity such as these may be useful in determining the effectiveness of potential new therapeutic agents for Alzheimer's disease.

Some Functional Aspects of Canine Corticotrophs

To examine the regulation and functional significance of canine pituitary pars intermedia corticotrophs, ACTH and cortisol responses to CRF were studied in healthy dogs before and after treatment with dexamethasone. In addition the effects of the dopamine agonist bromocriptine and the dopamine antagonist pimozide were investigated. In the latter two instances prolactin concentrations were also measured. Finally the pituitaries were studied immunocytochemically for ACTH and alpha-MSH. No response of ACTH or cortisol to bromocriptine was observed. Pimozide caused a slight rise in ACTH levels in some dogs. However, prolactin levels significantly decreased with bromocriptine and increased with pimozide. Injection of synthetic ovine CRF to dogs was followed by sharp increases in ACTH and cortisol values. These responses were obliterated by prior treatment with dexamethasone. In 1 of 4 dogs given dexamethasone before euthanasia, there were few pars distalis cells with ACTH(1-24) immunopositivity, although persistence of ACTH(1-24) reaction was noted within cells of the pars intermedia. The results indicate that none of the CRF-induced ACTH secretion in dogs is derived from pars intermedia corticotrophs. Dosages of bromocriptine and pimozide that clearly alter prolactin secretion do not consistently affect ACTH levels.

Mechanism of adrenal suppression by high-dose medroxyprogesterone acetate in breast cancer patients.

To investigate the mechanism of adrenal suppression by high-dose MPA, we performed direct and indirect stimulation tests in postmenopausal women with disseminated breast cancer who were receiving MPA and in a postmenopausal breast cancer control group. A partial adrenal insufficiency was found during Synacthen stimulation, confirmed by a slight increase of 11-desoxycortisol after metyrapone, despite a sufficient rise in ACTH levels. Peak levels of androstenedione and 17-OH progesterone after Synacthen correlated with those after metyrapone. Peak cortisol levels after Synacthen also correlated with the sum of cortisol and 11-desoxycortisol values after metyrapone, indicating the presence of a maximum adrenal response and a sufficient rise of endogenous ACTH after metyrapone. As the peak levels of cortisol and androstenedione were highly correlated with baseline values, a short Synacthen stimulation test may give a good indication as to whether adrenal suppression by MPA is adequate. The adrenal androgen androstenedione is the precursor of the main postmenopausal oestrogen, oestrone. In this way, adrenal suppression may constitute an important therapeutic effect of high-dose MPA.

Effect of hydrocortisone on ACTH, growth hormone, insulin and glucose in the blood of bilaterally adrenalectomized patients.

This study is aimed at elucidating the mechanism of paradoxical rise in plasma ACTH levels in response to glucocorticoids, observed by several authors in bilaterally adrenalectomized patients with Cushing's disease. Six control subjects and fourteen patients bilaterally adrenalectomized for Cushing's disease were given a dose of 200 mg hydrocortisone sodium succinate by 3-5 mm i.v. injection. Plasma ACTH (in 6 patients), serum cortisol, growth hormone (GH) and insulin and blood glucose levels were estimated at 0, 30, 60, 90, and 120 minutes. The administration of hydrocortisone significantly suppressed plasma ACTH levels only at 60 min. In one case a slight rise in ACTH level during the test was observed. A significant fall in blood glucose levels was found only in the adrenalectomized patients. No significant changes in serum insulin and GH levels were noted. The possible mechanisms are discussed, especially the potential role of transient glucose deficiency in the pathophysiology of plasma ACTH increase in response to hydrocortisone in the bilaterally adrenalectomized patients.

Twenty-two children with Cushing's disease were submitted to sequential plasma ACTH assays

Most patients were sampled before and after the injection of Lysine-Vasopressin (LVP), 10 IU / 1.73m2. Non treated patients had basal ACTH values within the normal range (< 100 pg/ml). After treatment, in spite of the wide dispersion of the natural course of the disease, the rises in ACTH levels were as follow: ACTH values remained-moderately elvated (<200μg/ml and 300pg/ml respectively before and after LVP )in patients treated with o-p'DDD ( 2-9g/day ) associated ( 3 patients) or not (8 patients) with pituitary cobalt therapy. A relapse was observed in 5 patients of the later group. After bilateral adrenalectomy ( 14 patients ) ACTH rose until much higher values. In this last group were observed 7 out of the 8 cases of confirmed ( 5 ) or suspected ( 3 ) Nelson's syndroms. ACTH values of those patients were as high as 6,000 pg/ml and 25,000'pg/ml respectivly before and after LVP. Important rise in ACTH levels at sequential determinations is thus a strorg argument for the detection of pituirary tumors and appear to be very useful for managenent of treatment and follow-up.

Paradoxical ACTH Response to Glucocorticoids in Cushing's Disease

To define further the defect in the steroid feedback mechanism in Cushing's disease, we studied the acute effects of intravenous administration of glucorticoids on plasma ACTH levels in seven patients with this disease after total adrenalectomy. In seven other patients with hypoadrenocorticism ACTH was readily suppressed; a significant decrease (72.5+/-5 per cent, mean +/- S.E.M., P less than 0.002) occurred within 15 minutes of the start of an infusion of 50 mg per hour of cortisol. In contrast, in the seven adrenalectomized patients with Cushing's disease, cortisol induced a transient paradoxical rise in ACTH levels, with a maximum at 15 minutes (347+/-99 per cent,, P less than 0.05). A similar ACTH response was observed with dexamethasone. Cushing's disease is characterized by a paradoxical transient rise in ACTH after glucocorticoid administration. This effect was more pronounced in adrenalectomized than in nonadrenalectomized patients.

The Interrelationship of Sodium Balance, Plasma Renin Activity and ACTH in Congenital Adrenal Hyperplasias

Metabolic studies in seven children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency revealed that all subjects displayed abnormalities in sodium balance which ranged from borderline depletion in the simple virilizers detectableonly by high levels of plasma renin activity to overt salt-loss and hypovolemia in the salt-losers. These abnormalities suggested that aldosterone biosynthesis was relatively impaired in all subjects, but more in the saltlosers. Sodium depletion, while on constant glucocorticoid replacement therapy, induced marked elevations of plasma renin activity which was associated with a hypersecretion of ACTH, with levels often over 1000 pg/ml. However, individuals whose hypothalamic-pituitary axis was completely suppressed with dexamethasone did not show a rise in ACTH levels. The degree of ACTH stimulation was significantly correlated with the levels of plasma renin activity (r = 0.811, P < 0.001) and was proportional to the degree of sodium loss, thus representin...