• Changes in arterial stiffness but not carotid intimal thickness in acromegaly.

      Paisley, Angela N; Banerjee, M; Rezai, M; Schofield, R E; Balakrishnannair, S; Herbert, A; Lawrance, Jeremy A L; Trainer, Peter J; Cruickshank, J K; Department of Endocrinology, The Christie National Health Service Foundation Trust, Manchester M20 4BX, United Kingdom. anpaisley@doctors.org.uk (2011-05)
      Acromegaly increases cardiovascular morbidity. We tested the hypothesis that increased arterial stiffness together with left ventricular hypertrophy may be a contributory factor.
    • Early diagnosis of acromegaly: computers vs clinicians.

      Miller, Ralph; Learned-Miller, Erik G; Trainer, Peter J; Paisley, Angela N; Blanz, Volker; Division of Endocrinology, Department of Medicine, University of Kentucky, Lexington, KY (2011-08)
      Background  Early diagnosis of a number of endocrine diseases is theoretically possible by the examination of facial photographs. One of these is acromegaly. If acromegaly were found, early in the course of the disease, morbidity would be lessened and cures more likely. Objectives, design, patients, measurements  Our objective was to develop a computer program which would separate 24 facial photographs, of patients with acromegaly, from those of 25 normal subjects. The key to doing this was to use a previously developed database that consisted of three-dimensional representations of 200 normal person's heads (SIGGRAPH '99 Conference Proceedings, 1999). We transformed our 49, two-dimensional photos into three-dimensional constructs and then, using the computer program, attempted to separate them into those with and without the features of acromegaly. We compared the accuracy of the computer to that of 10 generalist physicians. A second objective was to examine, by a subjective analysis, the features of acromegaly in the normal subjects of our photographic database. Results  The accuracy of the computer model was 86%; the average of the 10 physicians was 26%. The worst individual physician, 16%, the best, 90%. The faces of 200 normal subjects, the original faces in the database, could be divided into four groups, averaged by computer, from those with fewer to those with more features of acromegaly. Conclusions  The present computer model can sort photographs of patients with acromegaly from photographs of normal subjects and is much more accurate than the sorting by practicing generalists. Even normal subjects have some of the features of acromegaly. Screening with this approach can be improved with automation of the procedure, software development and the identification of target populations in which the prevalence of acromegaly may be increased over that in the general population.
    • Small vessel remodeling and impaired endothelial-dependent dilatation in subcutaneous resistance arteries from patients with acromegaly.

      Paisley, Angela N; Izzard, A S; Gemmell, I; Cruickshank, K; Trainer, Peter J; Heagerty, A M; Department of Endocrinology, Christie Hospital, Manchester, UK; Department of Cardiovascular Medicine, Manchester Royal Infirmary, Manchester, UK; National Primary Care Research and Development Centre, University of Manchester, UK. (2009-01-27)
      Context: Patients with acromegaly have increased morbidity and mortality, predominantly from cardiovascular disease. Hypertension and diabetes are more prevalent, both of which cause small vessel remodeling and endothelial dysfunction. Objective: To understand the structure and function of small arteries in acromegaly, subcutaneous blood vessels from gluteal fat biopsies were harvested from 18 patients with active disease (AD:56+/-15y, 14m), 23 in remission (CD:55+/-12y, 15m) and 20 healthy controls (55+/-11yrs, 10m) and examined in-vitro using pressure myography. Design: Contractile responses to cumulative noradrenaline concentrations were recorded followed by dose dependent dilator responses to acetylcholine. The acetylcholine protocol was repeated after incubation with a nitric oxide synthase inhibitor (L-NAME) and cyclooxygenase inhibitor (indomethacin). Following perfusion with Ca(2+)-free physiological saline solution, structural measurements were recorded at varying intraluminal pressures (3-180mmHg). Results: Wall thickness and wall:lumen ratio were increased in AD, reduced with treatment but remained greater in CD than controls. Wall cross-sectional area was increased in AD versus controls (P<0.001), decreased with treatment (AD vs CD: P<0.001) but remained higher than controls (CD vs controls: P=0.015). Growth index was increased in AD (20%) compared to controls (CD 9%). Contractility was similar in all groups. Endothelial-dependent dysfunction was evident in AD compared with CD (P<0.001) and controls (P<0.01). Dilation did not change following L-NAME but was impaired after indomethacin incubation. Conclusion: Active acromegaly is associated with hypertrophic remodeling of the vascular wall and embarrassed endothelial function due to reduced NO and EDHF bioavailability, both of which may contribute to the early mortality from cardiovascular disease.
    • A subnormal peak cortisol response to stimulation testing does not predict a subnormal cortisol production rate.

      Paisley, Angela N; Rowles, Susannah V; Brandon, D; Trainer, Peter J; Department of Endocrinology, Christie Hospital, Manchester M20 4BX, United Kingdom. (2009-05)
      INTRODUCTION: The decision to commence lifelong glucocorticoid replacement therapy is often based on a cortisol stimulation test. We investigated the relationship between the peak cortisol response to insulin-induced hypoglycemia and daily cortisol production rate (CPR) to ascertain whether provocative tests are accurate in indicating the need to initiate lifelong glucocorticoid replacement. PATIENTS AND METHODS: Ten patients (five male; mean age, 44 +/- 13 yr) with pituitary disease and with demonstrably suboptimal peak cortisol response (350-500 nmol/liter) to insulin-induced hypoglycemia, underwent CPR measurement by isotope dilution using gas chromatography-mass spectrometry and 24-h urinary free cortisol (UFC). RESULTS: The median baseline and peak cortisol attained with hypoglycemia were 284 (164-323) and 473.5 (366-494) nmol/liter, respectively. A strong positive correlation was seen between peak stimulated cortisol and CPR (adjusted for body surface area) (r = 0.75; P = 0.02), and in all patients CPR [4.6 (2.9-15.1) mg/d x m(2)] was within the reference range (2.1-12 mg/d x m(2)) or elevated (one patient). A wide range was found for 24-h UFC [116.5 (20.5-265.9) nmol/liter] in this group of patients, and this parameter lacked significant correlation with either serum cortisol concentration or CPR. CONCLUSION: This is the first study to demonstrate a significant correlation between CPR and peak cortisol values during hypoglycemic challenge. An inadequate cortisol response to hypoglycemia suggests the need for glucocorticoid cover at times of stress, but these data indicate that a suboptimal peak cortisol does not equate to a low CPR and should not be an automatic indication for lifelong glucocorticoid replacement therapy. UFC bears no relation to serum cortisol or CPR and is therefore unhelpful in assessment of such patients.