Development of a cost-effective diagnostic algorithm incorporating transcription factor immunohistochemistry in the evaluation of pituitary tumours.

PURPOSE: To determine the utility of the 2022 WHO Classification of pituitary tumours in routine clinical practice and to develop an optimal diagnostic algorithm for evaluation of tumour type in a real-world setting. METHODS: Retrospective evaluation of pituitary tumour immunohistochemistry (IHC), operatively managed at St Vincent's Hospital Sydney, between 2019 and 2021. Routine IHC comprised evaluation of transcription factors [steroidogenic factor 1 (SF1), T-box transcription factor 19 (TPIT) and pituitary-specific positive transcription factor (PIT1)] and anterior pituitary hormones. Three tiered algorithms were tested, in which hormone IHC was performed selectively based on the initial transcription factor results. These were applied retrospectively and compared with current practice 'gold standard' comprising all transcription factor and hormone IHC. Diagnostic accuracy and cost were evaluated for each. RESULTS: There were 113 tumours included in the analysis. All three algorithms resulted in 100% concordance with the 'gold standard' in the characterisation of tumour lineage. While all three were associated with relative cost reduction, Algorithm #3, which omitted hormone IHC in the setting of positive SF1 or TPIT and performed IHC for growth hormone, prolactin and thyroid stimulating hormone only in the setting of PIT1 positivity, was the most cost-efficient. Additionally, there were 12/113 tumours with no distinct cell lineage. CONCLUSION: A diagnostic algorithm omitting hormone IHC except in cases of PIT1 positivity is an accurate and cost-effective approach to diagnose the type of pituitary tumour. A significant subgroup of pituitary tumours with no distinct cell lineage, frequently plurihormonal, remains difficult to classify with the new WHO criteria and requires further evaluation.

Exploring immunomodulation by endocrine changes in Lady Windermere syndrome.

Lung disease due to nontuberculous mycobacteria (NTM) occurs with disproportionate frequency in postmenopausal women with a unique phenotype and without clinically apparent predisposing factors. Dubbed 'Lady Windermere syndrome', the phenotype includes low body mass index (BMI), tall stature and higher than normal prevalence of scoliosis, pectus excavatum and mitral valve prolapse. Although the pathomechanism for susceptibility to NTM lung disease in these patients remains uncertain, it is likely to be multi-factorial. A role for the immunomodulatory consequences of oestrogen deficiency and altered adipokine production has been postulated. Altered levels of adipokines and dehydroepiandrosterone have been demonstrated in patients with NTM lung disease. Case reports of NTM lung disease in patients with hypopituitarism support the possibility that altered endocrine function influences disease susceptibility. This paper catalogues the evidence for immunomodulatory consequences of predicted endocrine changes in Lady Windermere syndrome, with emphasis on the immune response to NTM. Collectively, the data warrant further exploration of an endocrine link to disease susceptibility in Lady Windermere syndrome.

The cost-effectiveness of hospital-based telephone coaching for people with type 2 diabetes: a 10 year modelling analysis.

BACKGROUND: Type 2 diabetes (T2DM) is a burdensome condition for individuals to live with and an increasingly costly condition for health services to treat. Cost-effective treatment strategies are required to delay the onset and slow the progression of diabetes related complications. The Diabetes Telephone Coaching Study (DTCS) demonstrated that telephone coaching is an intervention that may improve the risk factor status and diabetes management practices of people with T2DM. Measuring the cost effectiveness of this intervention is important to inform funding decisions that may facilitate the translation of this research into clinical practice. The purpose of this study is to assess the cost-effectiveness of telephone coaching, compared to usual diabetes care, in participants with poorly controlled T2DM. METHODS: A cost utility analysis was undertaken using the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model to extrapolate outcomes collected at 6 months in the DTCS over a 10 year time horizon. The intervention's impact on life expectancy, quality-adjusted life expectancy (QALE) and costs was estimated. Costs were reported from a health system perspective. A 5 % discount rate was applied to all future costs and effects. One-way sensitivity analyses were conducted to reflect uncertainty surrounding key input parameters. RESULTS: The intervention dominated the control condition in the base-case analysis, contributing to cost savings of $3327 per participant, along with non-significant improvements in QALE (0.2 QALE) and life expectancy (0.3 years). CONCLUSIONS: The cost of delivering the telephone coaching intervention continuously, for 10 years, was fully recovered through cost savings and a trend towards net health benefits. Findings of cost savings and net health benefits are rare and should prove attractive to decision makers who will determine whether this intervention is implemented into clinical practice. TRIAL REGISTRATION: ACTRN12609000075280.

Effect of hospital-based telephone coaching on glycaemic control and adherence to management guidelines in type 2 diabetes, a randomised controlled trial.

BACKGROUND: Failure to achieve treatment targets is common among people with type 2 diabetes. Cost-effective treatments are required to delay the onset and slow the progression of diabetes-related complications. AIMS: This study aimed to measure the effect of a 6-month telephone coaching intervention on glycaemic control, risk factor status and adherence to diabetes management practices at the intervention's conclusion (6 months) and at 12 months. METHOD: This randomised controlled trial recruited 94 adults with type 2 diabetes and an HbA1C > 7% from the Diabetes Clinic of St Vincent's Hospital Melbourne. People who were non-English speaking, cognitively impaired, severely hearing impaired or without telephone access were excluded. Participants were randomised to receive usual care plus 6 months of telephone coaching focusing on achieving treatment targets and complication screening, or usual care only. The primary outcome was HbA1C at 6 months; secondary outcomes included other physiological and monitoring measures. RESULTS: Significant interaction effects were observed between group and time at 6 months, demonstrating improvement in HbA1C, fasting glucose, diastolic blood pressure and physical activity. The intervention's effect on these parameters was not sustained at 12 months. Intervention group participants also improved compliance with foot examinations and pneumococcal vaccination by 6 months and retinal screening by 12 months. CONCLUSIONS: Telephone coaching improved glycaemic control and adherence to complication screening in people with type 2 diabetes, for the duration of its delivery, but these effects were not maintained on withdrawal of the intervention. Strategies that assist patients to sustain these benefits are required.

Selective use of the insulin tolerance test to diagnose hypopituitarism.

The insulin tolerance test is considered the gold standard for assessing the hypothalamic-pituitary-adrenal and growth hormone (GH) axes, but its use varies considerably among different endocrine units. We recommend using the insulin tolerance test to assess the hypothalamic-pituitary-adrenal axis within 3 months of pituitary surgery, where adrenocorticotropic hormone 1-24 testing is equivocal, and to assess for GH deficiency where the patient is being considered for GH replacement therapy. We also discuss safety issues, how to ensure adequate hypoglycaemia and possible alternative tests, such as the overnight metyrapone test and glucagon test.

Skeletal muscle 11ßHSD1 activity of nondiabetic subjects is unaltered in central obesity-associated insulin resistance.

Local activation of glucocorticoids in insulin target tissues by the enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) has been implicated in the etiology of the metabolic syndrome. In obesity, adipose tissue 11ßHSD1 is upregulated, leading to the generation of higher tissue levels of cortisol, which may increase insulin resistance. However, skeletal muscle is the predominant site of insulin-mediated glucose disposal, which is known to be reduced in obesity. We aimed to determine if there is any relationship between skeletal muscle 11ßHSD1 and markers of central adiposity and insulin resistance in nondiabetic subjects. 20 nondiabetic volunteers (8 males and 12 females, mean age 55 ± 13 years, body mass index 21.5-47.6, mean 30.4 ± 1.6 kg/m (2)) underwent a single fasting blood sample followed by a muscle biopsy of vastus lateralis under local anesthetic. Fasting glucose, insulin and adiponectin were measured in serum. Skeletal muscle 11ßHSD1 oxoreductase activity was determined by measuring the conversion of radiolabelled (3)H-cortisone to cortisol by thin layer chromatography. When subjects were categorised according to abdominal obesity (waist circumference ≥ 102 cm in men, ≥ 88 cm in women), there was no difference between the groups in skeletal muscle 11ßHSD1 activity. There was no correlation between body mass index or waist circumference and 11ßHSD1 activity or between HOMA and 11ßHSD1 activity. Skeletal muscle 11ßHSD1 oxoreductase activity is not altered in nondiabetic subjects with central obesity-associated insulin resistance. It is therefore unlikely that the in vivo insulin resistance observed in skeletal muscle of centrally obese subjects is mediated by alterations in 11ßHSD1.

Acidosis in the hospital setting: is metformin a common precipitant?

BACKGROUND: Acidosis is commonly seen in the acute hospital setting, and carries a high mortality. Metformin has been associated with lactic acidosis, but it is unclear how frequently this is a cause of acidosis in hospitalized inpatients. The aim of this study is to explore the underlying comorbidities and acute precipitants of acidosis in the hospital setting, including the relationship between type 2 diabetes (T2DM) and metformin use. METHODS: Retrospective review. Cases of acidosis were identified using the hospital discharge code for acidosis for a 3-month period: October-December 2005. RESULTS: A total of 101 episodes of acidosis were identified: 29% had isolated respiratory acidosis, 31% had metabolic acidosis and 40% had a mixed respiratory and metabolic acidosis. There were 28 cases of confirmed lactic acidosis. Twenty-nine patients had T2DM, but only five of the subjects with T2DM had lactic acidosis; two were on metformin. The major risk factors for development of lactic acidosis were hepatic impairment (OR 33.8, P = 0.01), severe left ventricular dysfunction (OR 25.3, P = 0.074) and impaired renal function (OR 9.7, P = 0.09), but not metformin use. CONCLUSION: Most cases of metabolic and lactic acidosis in the hospital setting occur in patients not taking metformin. Hepatic, renal and cardiac dysfunction are more important predictors for the development of acidosis.

Review of intern preparedness and education experiences in General Medicine.

BACKGROUND: Few studies assess the transition from medical student to intern and there is limited understanding of what measures are required to assist intern development. The aim of the study was to assess interns' perception of their preparedness before commencing and on completion of their rotation in General Medicine, and their attitudes towards educational experiences at a tertiary metropolitan teaching hospital. METHODS: Self-assessed preparedness for the General Medical internship and educational experiences were evaluated using a quantitative 5-point scale (1 = low score and 5 = high score) and qualitatively through interview, on interns based at St Vincent's Hospital (Melbourne). Data were collected at the beginning and at the end of each 10-week rotation (n = 25). RESULTS: Before commencement of the rotation, the interns identified areas where they felt inadequately prepared, particularly resuscitation skills and medico-legal aspects. When resurveyed at the completion of their 10-week rotation, the interns felt they had been better prepared for their role than they initially perceived, both generally and in specific aspects. Nine out of 16 parameters showed a significant increase in preparedness score at week 10 compared to week 1. The educational experiences most valued were peer driven education sessions and informal registrar teaching. Formal consultant teaching and online learning were perceived as being the least useful. CONCLUSION: Interns at St Vincent's Hospital have been adequately prepared for their role in General Medicine, although many realize this only in retrospect. Deficiencies in educational opportunities for interns have been uncovered that emphasize areas of attention for medical educators.

Elevated basal adrenocorticotropin and evidence for increased central opioid tone in highly trained male athletes.

Basal cortisol and ACTH levels have previously been shown to be elevated in highly trained athletes, whereas the ACTH response to ovine CRH has been reported to be diminished compared to that in nonathletic controls. Naloxone, a nonselective opioid receptor antagonist, is known to stimulate ACTH and cortisol secretion. The mechanism of this response is thought to be via increased hypothalamic CRH secretion. The aim of this study was to examine basal and naloxone-stimulated levels of hypothalamic-pituitary-adrenal axis hormones in male athletes. Ten highly trained male athletes and 10 nonathletic controls took part in the study. Peripheral venous blood was sampled for cortisol, ACTH, CRH, and arginine vasopressin (AVP) for 2 h before the administration of 20 mg naloxone, i.v., and 15, 30, 45, 60, 90, and 120 min after naloxone treatment. Body mass index was significantly lower in the athletes (P < 0.001). Basal (prenaloxone) ACTH levels were higher in the athletes (P < 0.05), whereas levels of cortisol, CRH, and AVP were similar in both groups. After naloxone treatment, there was a significantly greater rise in ACTH in the athletes (P < 0.02). There was also a trend for the cortisol response to be greater, which was not statistically significant (P < 0.07). Although in both groups, peripheral CRH rose after naloxone treatment (P < 0.005), a rise of similar magnitude occurred over the 2-h period before naloxone (P < 0.0001). Plasma AVP did not change significantly after naloxone treatment. Neither the plasma cortisol level at baseline nor the body mass index correlated significantly with the ACTH or cortisol response to naloxone. The presence of an enhanced ACTH response to naloxone is evidence that central opioid tone may be increased in highly trained athletes. However, there is no associated suppression of the hypothalamic-pituitary-adrenal axis, and basal ACTH levels are raised, without any detectable change in peripheral plasma CRH or AVP. An additional factor (other than CRH) that stimulates ACTH secretion may be released after naloxone administration.

Activin effects on neoplastic proliferation of human pituitary tumors.

Factors underlying growth regulation in human pituitary tumors are largely unknown. Activin functions as an antiproliferative cytokine in a number of cell types and is endogenously expressed in normal and neoplastic human pituicytes. We investigated the effect of activin on proliferation in 16 clinically nonfunctioning pituitary adenomas in primary culture. Treatment for 24 h with activin (0-10 ng/mL) significantly inhibited cell proliferation in 5 tumors (P < 0.05), as determined by [3H]thymidine incorporation. In 9 tumors, we studied regulation of the cyclin-dependent kinase inhibitor p21WAF1/cip1 as a potential activin mediator. In tumors with activin-inhibited proliferation, p21WAF1/cip1 gene expression was up-regulated after 4 h in a dose-dependent manner (0-100 ng/mL). We also investigated tumor expression of follistatin messenger ribonucleic acid, an activin-binding protein with two isoforms of different potencies. In contrast to normal pituitary tissue, only four tumors expressed both follistatin isoforms, and three tumors expressed only the less potent form. Tumors in which activin induced antiproliferative responses showed diminished or no follistatin messenger ribonucleic acid expression compared to normal pituitary. These data indicate that activin has an antiproliferative effect in a subgroup of human pituitary tumors.

The utility of plasma CRH as a predictor of preterm delivery.

It has been suggested that CRH is a placental clock that controls the duration of pregnancy and that the timing of the rise in CRH may permit prediction of the onset of labor. We have performed a prospective longitudinal study, in 297 women, to examine the utility of a single second-trimester plasma CRH measurement to predict preterm delivery. Venous blood samples were taken at 4-weekly intervals, beginning at 16-20 wk gestation, until delivery for CRH and its binding protein. A time point at which a single plasma CRH test might give optimal data to predict preterm delivery was determined. Thirty-one subjects delivered prematurely (10.4%). Sampling for plasma CRH at 26 wk gestation seemed the optimal time point to maximize sensitivity and specificity of the test. The mean (+/- SD) plasma CRH in women at this gestation who eventually delivered after spontaneous labor within 1 wk of their due date (39-41 wk, n = 127) was 34.7 +/- 27.0 pM. A plasma CRH of more than 90 pM at 26 wk gestation had a sensitivity of 45% and a specificity of 94% for prediction of preterm delivery. The positive predictive value was 46.7%. Calculation of free CRH did not improve these figures. In conclusion, a single measurement of plasma CRH, toward the end of the second trimester, may identify a group at risk for preterm delivery, but over 50% of such deliveries will be unpredicted. These data do not support the routine clinical use of plasma CRH as a predictor of preterm labor.

Reduction in basal afternoon plasma ACTH during early treatment of depression with fluoxetine.

RATIONALE: Subjects with depression may exhibit activation of the hypothalamic-pituitary-adrenal (HPA) axis, but little is known about the response of basal hormone levels to antidepressant therapy. OBJECTIVES: To determine whether treatment of depression with standard antidepressant medications resulted in reductions in basal activity of afternoon cortisol, ACTH and AVP. A secondary aim was to examine whether there was any difference in hormonal response between an SSRI (fluoxetine) and a tricyclic antidepressant (nortriptyline). METHODS: Forty-three subjects with a DSM-IV diagnosis of depression (Hamilton score 18.9+/-0.6 at baseline) had five basal venous blood samples drawn at 15-min intervals between 1400 and 1500 hours for cortisol, ACTH and AVP, before and 6 weeks after randomisation to treatment with fluoxetine (n=27) or nortriptyline (n=16). RESULTS: Both medications resulted in a similar improvement in depression as determined by Hamilton score. In the group as a whole, ACTH levels showed a significant decrease over the 6 weeks (4.1+/-0.4 pmol/l at baseline versus 3.3+/-0.3 at 6 weeks, P<0.05), while cortisol and AVP levels were unchanged. Further analysis revealed that the fall in plasma ACTH occurred predominantly in the subgroup treated with fluoxetine (drug x time interaction by ANOVA, P=0.035). There was a significant relationship between cortisol and ACTH at baseline (r=0.48, P=0.002), that weakened considerably after treatment (r=0.22, P=0.16). The subgroup with baseline hypercortisolemia [mean cortisol >276 nmol/l (10 microg/dl), n=18] demonstrated a reduction in both cortisol and ACTH following treatment, but also showed a loss of the relationship between the two. CONCLUSIONS: It is postulated that the initial recovery of the HPA axis during the treatment of depression with fluoxetine is mediated via restoration of glucocorticoid negative feedback on ACTH levels.

Prolonged exercise increases peripheral plasma ACTH, CRH, and AVP in male athletes.

We wished to determine whether the increased ACTH during prolonged exercise was associated with changes in peripheral corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP). Six male triathletes were studied during exercise: 1 h at 70% maximal oxygen consumption, followed by progressively increasing work rates until exhaustion. Data obtained during the exercise session were compared with a nonexercise control session. Venous blood was sampled over a 2-h period for cortisol, ACTH, CRH, AVP, renin, glucose, and plasma osmolality. There were significant increases by ANOVA on log-transformed data in plasma cortisol (P = 0.002), ACTH (P < 0.001), CRH (P < 0.001), and AVP (P < 0.03) during exercise compared with the control day. A variable increase in AVP was observed after the period of high-intensity exercise. Plasma osmolality rose with exercise (P < 0.001) and was related to plasma AVP during submaximal exercise (P < 0.03) but not with the inclusion of data that followed the high-intensity exercise. This indicated an additional stimulus to the secretion of AVP. The mechanism by which ACTH secretion occurs during exercise involves both CRH and AVP. We hypothesize that high-intensity exercise favors AVP release and that prolonged duration favors CRH release.

The effect of glycerol and desmopressin on exercise performance and hydration in triathletes.

BACKGROUND: Hydration is an important determinant of athletic performance, and glycerol-containing solutions have been demonstrated to produce a state of hyperhydration. Secretions of arginine vasopressin (AVP) and/or other renal mechanisms may account for reduced urine output following glycerol ingestion. This study examined the effect of glycerol and the AVP analog desmopressin (DDAVP) on hydration and exercise performance in triathletes ingesting routine volumes of prerace fluids. METHODS: Eight male triathletes ages 19 to 43 participated. After determination of their VO(2peak), each athlete completed a strenuous exercise protocol three times involving 60 min of exercise at 70% VO(2peak) followed immediately by an incremental increase in workload every 2 min until exhaustion. RESULTS: Pretreatment with 1 gxkg(-1) glycerol or 20 microgram of DDAVP intranasally failed to produce hyperhydration or any enhancement of athletic performance. There was a significant difference in reduction in body mass between DDAVP and control (P < 0.05) but no change in sweat volume. No physiologically relevant differences in plasma sodium, renin, or hemoglobin were seen with either active agent. Plasma osmolality did have a different time course in response to exercise following glycerol (P < 0.03) owing to a smaller incremental increase. Urine osmolality was also raised at baseline following glycerol (P < 0.05). Responses to exercise of plasma AVP, cortisol, and indices of carbohydrate metabolism were similar, although AVP was elevated following DDAVP administration (P < 0.01) owing to assay cross-reactivity. CONCLUSION: Although maintaining adequate hydration remains important for the endurance athlete, the routine use of either glycerol of DDAVP before athletic training or competition in a thermoneutral environment does not seem to confer any advantage over conventional fluid replacement.

Anti-emetic doses of dexamethasone suppress cortisol response in laparoscopic cholecystectomy.

The efficacy of dexamethasone alone or in combination with a serotonergic antagonist to prevent nausea and vomiting in laparoscopic cholecystectomy is well established, but few data exist regarding its effects on perioperative cortisol and glucose levels. Fourteen non-diabetic subjects having elective laparoscopic choleycystectomy and standardised general anaesthesia were randomised to receive 8 mg of intravenous dexamethasone and tropisetron or tropisetron alone. Plasma cortisol and glucose were measured preinduction, at five and 24 hours postoperatively. There was no difference in plasma cortisol at five hours postoperatively in patients who received dexamethasone, but by 24 hours there was marked suppression compared to the control group (P < 0.005) to less than 5% of the preoperative value. There was a small but statistically significant elevation in blood glucose at 24 hours (P < 0.01) in the dexamethasone-treated group. In patients undergoing laparoscopic cholecystectomy, an anti-emetic dose of dexamethasone (8 mg) markedly suppresses plasma cortisol at 24 hours and causes a minor elevation in blood glucose.

Hyperprolactinaemia associated with a complex cystic pituitary mass: medical versus surgical therapy.

A 39-year-old woman presented with visual loss and hyperprolactinaemia. Magnetic resonance imaging showed an intrasellar and suprasellar mass with a large cystic component that was hyperintense on T2-weighted imaging. Prolactin levels were up to 5400 mIU/L. Following trans-sphenoidal surgery, histology showed -elements of both a Rathke's cleft cyst and prolactinoma. We suggest primary surgical management of large cystic pituitary lesions with associated hyperprolactinaemia, particularly when there is hyperintensity on T2-weighted imaging.

Outcome from surgical management of secretory pituitary adenomas in Christchurch, New Zealand.

BACKGROUND: Recent evidence has highlighted the importance of the neurosurgeon in the management of secretory pituitary tumours, but most reports are from major centres. AIMS: To audit the surgical outcome of patients with acromegaly and Cushing's disease treated in a small centre (Christchurch, New Zealand) by a dedicated neurosurgeon with an interest in pituitary disease, and follow-up through an outpatient Department of Endocrinology. METHODS: All cases of acromegaly and Cushing's disease admitted for surgery in Christchurch Hospital between 1984 and 2000 were audited. Data concerning preoperative findings, surgical remission rate, complications and follow-up were obtained from 44 patients (28 acromegaly, 16 Cushing's disease). RESULTS: Of the 28 acromegalic patients, 14 patients (50%) had a mean growth hormone level <2.5 micro g/L within the first postoperative week. Of the 15 Cushing's disease patients in whom the pituitary fossa was explored, 13 patients (87%) entered a postoperative remission, defined as an 08.00 h cortisol <200 nmol/L (normal range 250-800 nmol/L). No perioperative deaths occurred. Two of the 43 patients (4.7%) developed permanent diabetes insipidus, while eight of the 28 patients who were operated on for acromegaly (29%) eventually required some replacement treatment for hypopituitarism during follow-up (one presented with apoplexy and seven were treated with postoperative radiotherapy). CONCLUSION: In a small centre with a dedicated pituitary surgeon, operative remission rates approach those obtained in larger, more specialized centres. However, given New Zealand's small, but geographically spread population, consideration should be given to establishing one or two units for the surgical management of secretory pituitary adenomas.

Interleukin-1 potentiates basal and AVP-stimulated ACTH secretion in vitro--the role of CRH pre-incubation.

The acute-phase cytokine interleukin-1 (IL-1) is known to activate the hypothalamic pituitary adrenal axis, primarily via corticotropin releasing hormone (CRH). The aim of this study was to determine whether IL-1beta could directly stimulate ACTH secretion from perifused equine anterior pituitary cells, and whether CRH pre-incubation affected corticotroph responsiveness. Isolated equine anterior pituitary cells were pre-incubated with media containing 10 nM CRH or vehicle for 20 hours before being loaded onto columns and perifused with 0.02 nM CRH and 100 nM cortisol. Columns were given a 5-minute pulse of arginine vasopressin (AVP, 10 nM), perifused for 4 hours with 0 (control) or 1 nM IL-1beta, then given a further 5-minute pulse of AVP (10nM). ACTH was measured in 5 minute fractions. In the setting of CRH pre-incubation, cells perifused with IL-1beta for 4 hours showed increased basal ACTH secretion compared to control (114 +/- 6 pM vs. 86 +/- 4 pM [means +/- S.E.M.], p < 0.001) and a significantly greater ACTH response to the final AVP pulse (240 +/- 32% vs. 96 +/- 30%, p = 0.009, expressed as % of ACTH response to the initial AVP pulse). The potentiation of AVP-stimulated ACTH release by IL-1 was not observed in cells pre-incubated with vehicle alone. In conclusion, IL-1 increases ACTH release in equine corticotroph cells pre-incubated with CRH and potentiates responsivity to AVP.