Many patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis explores the efficacy and safety of switching therapeutic arms in inadequately controlled patients during a 12-month crossover extension.

CONTEXT Acromegaly is associated with reduced life expectancy, which has been reported to be normalized if treatment is successful in controlling GH/IGF-I levels. OBJECTIVE Most previous studies have invariably used the last available GH/IGF-I, which may be biased as it only assesses exposure at a single point in time. We compared the last available GH/IGF-I analysis to a "time-dependent" and cumulative method, during follow-up to assess risk of mortality in the West Midlands Acromegaly study (n = 501). RESULTS Using the last available GH, there was a statistically significant increase in mortality comparing groups as low as GH ≤ 1 μg/L vs >1 μg/L (relative risks [RR] 1.8, P = .03). This was not the case when using the "time-dependent method," where only comparisons of GH values of GH ≤5 μg/L vs >5 μg/L were suggestive of being associated with an increased risk of mortality (RR = 1.5, P = .08). When the time-dependent GH method of analysis was used, the RR of mortality at each level was lower and the associated P value was less significant. Irrespective of using the last available or time-dependent method, when IGF-I was divided into levels according to quartile or arbitrary cutoffs, there was no significant increase in mortality with higher levels. CONCLUSIONS This study emphasizes the potential bias of using the latest available GH/IGF-I levels to predict mortality. Our study again highlights the limitations of IGF-I in predicting mortality.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Although there are international guidelines orienting physicians on how to manage patients with acromegaly, such guidelines should be adapted for use in distinct regions of the world. A panel of neuroendocrinologists convened in Mexico City in August of 2007 to discuss specific considerations in Latin America. Of major discussion was the laboratory evaluation of acromegaly, which requires the use of appropriate tests and the adoption of local institutional standards. As a general rule to ensure diagnosis, the patient's GH level during an oral glucose tolerance test and IGF-1 level should be evaluated. Furthermore, to guide treatment decisions, both GH and IGF-1 assessments are required. The treatment of patients with acromegaly in Latin America is influenced by local issues of cost, availability and expertise of pituitary neurosurgeons, which should dictate therapeutic choices. Such treatment has undergone profound changes because of the introduction of effective medical interventions that may be used after surgical debulking or as first-line medical therapy in selected cases. Surgical resection remains the mainstay of therapy for small pituitary adenomas (microadenomas), potentially resectable macroadenomas and invasive adenomas causing visual defects. Radiotherapy may be indicated in selected cases when no disease control is achieved despite optimal surgical debulking and medical therapy, when there is no access to somatostatin analogues, or when local issues of cost preclude other therapies. Since not all the diagnostic tools and treatment options are available in all Latin American countries, physicians need to adapt their clinical management decisions to the available local resources and therapeutic options.

AIChE JournalVolume 53, Issue 12 p. 3022-3028 Perspective Sustaining fossil fuel use in a carbon-constrained world by rapid commercialization of carbon capture and sequestration Michael C. Sheppard, Corresponding Author Michael C. Sheppard [email protected] Schlumberger Cambridge Research, High Cross, Madingley Road, Cambridge, U.K. CB3 0EL Michael C. Sheppard, Schlumberger Cambridge Research, High Cross, Madingley Road, Cambridge, U.K. CB3 0EL Robert H. Socolow, Mechanical and Aerospace Engineering, 139 Guyot Hall, Princeton University Princeton, NJ 08544Search for more papers by this authorRobert H. Socolow, Corresponding Author Robert H. Socolow [email protected] Mechanical and Aerospace Engineering, 139 Guyot Hall, Princeton University Princeton, NJ 08544 Michael C. Sheppard, Schlumberger Cambridge Research, High Cross, Madingley Road, Cambridge, U.K. CB3 0EL Robert H. Socolow, Mechanical and Aerospace Engineering, 139 Guyot Hall, Princeton University Princeton, NJ 08544Search for more papers by this author Michael C. Sheppard, Corresponding Author Michael C. Sheppard [email protected] Schlumberger Cambridge Research, High Cross, Madingley Road, Cambridge, U.K. CB3 0EL Michael C. Sheppard, Schlumberger Cambridge Research, High Cross, Madingley Road, Cambridge, U.K. CB3 0EL Robert H. Socolow, Mechanical and Aerospace Engineering, 139 Guyot Hall, Princeton University Princeton, NJ 08544Search for more papers by this authorRobert H. Socolow, Corresponding Author Robert H. Socolow [email protected] Mechanical and Aerospace Engineering, 139 Guyot Hall, Princeton University Princeton, NJ 08544 Michael C. Sheppard, Schlumberger Cambridge Research, High Cross, Madingley Road, Cambridge, U.K. CB3 0EL Robert H. Socolow, Mechanical and Aerospace Engineering, 139 Guyot Hall, Princeton University Princeton, NJ 08544Search for more papers by this author First published: 30 October 2007 https://doi.org/10.1002/aic.11356Citations: 16Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Literature Cited 1 Petit JR,Jouzel J,Barkov NI et al. Climate and atmospheric history of the past 420,000 years from the Vostok ice core, Antarctica. Nature. 1999; 399: 429–436. 2 Jouzel J,Masson-Delmotte V,Cattani O et al. 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Growth hormone (GH) measurement has been the cornerstone of the biochemical evaluation of GH excess and GH deficiency syndromes for over 30 years. In normal individuals GH secretion is pulsatile, diurnal and stimulated by a variety of factors, including exercise, stress and sleep, and thus a random GH measurement alone is not helpful in confirming the diagnosis of acromegaly or GH deficiency (GHD). In current clinical practice the diagnostic evaluation of acromegaly includes biochemical confirmation of GH hypersecretion, based on serum measurements of both GH and insulin-like growth factor-1 (IGF-1). Diagnosis of GHD is established by a provocative test of GH secretion. The measurement of GH has evolved from polyclonal radioimmunoassays (RIA) of limited sensitivity to contemporary two-site monoclonal antibody, nonisotopic assays with enhanced sensitivity, allowing accurate quantification of previously undetectable values, including nadir and glucose-suppressed GH levels. These assays are of value in diagnosis and monitoring following treatment of acromegaly because they allow better definition of the neurosecretory properties of GH particularly in characterizing the lower limit of spontaneous and suppressed GH secretion. They have permitted diagnosis of mild and subtle manifestations of acromegaly and improved critical evaluation of therapeutic outcomes. Discrepancies between GH results from different centres have, however, been a continuing problem and result from inaccurately assigned calibrator values, variable antibody recognition of GH isoforms, the lack of consensus for reporting GH (results in USA are quoted in μ g / l, whereas in UK and other countries in mU/l) and variability of unit conversion factors. 1,2 It is not possible to apply a simple conversion factor to compare GH levels measured by current assays with those obtained in the past by RIA or when converting μ g / l to mU/l. The statement published in this edition of Clinical Endocrinology is particularly welcome as a major step forward in standardizing GH measurements with consistency of reporting in mass units. The availability of the second International Standard for GH (World Health Organization (WHO) IS 98/574) provides the opportunity for adopting a single calibrant for GH immunoassays. An International Collaborative has recommended the reporting of GH concentrations in micrograms per litre ( μ g / l) of IS 98/574 3 (see Appendix 1); Clinical Endocrinology and the European Journal of Endocrinology starting from September 1, 2007 will publish papers on GH data only if expressed in mass units of IS 98/574. This change will result in more effective clinical decision-making in patients with GH-related disorders whose care is increasingly dependent on consensus guidelines employing mass units. 4,5

CONTEXT:Population-based screening has been advocated for subclinical thyroid dysfunction in the elderly because the disorder is perceived to be common, and health benefits may be accrued by detection and treatment.OBJECTIVE:The objective of the study was to determine the prevalence of subclinical thyroid dysfunction and unidentified overt thyroid dysfunction in an elderly population.DESIGN, SETTING, AND PARTICIPANTS:A cross-sectional survey of a community sample of participants aged 65 yr and older registered with 20 family practices in the United Kingdom.EXCLUSIONS:Exclusions included current therapy for thyroid disease, thyroid surgery, or treatment within 12 months.OUTCOME MEASURE:Tests of thyroid function (TSH concentration and free T4 concentration in all, with measurement of free T3 in those with low TSH) were conducted. EXPLANATORY VARIABLES: These included all current medical diagnoses and drug therapies, age, gender, and socioeconomic deprivation (Index of Multiple Deprivation, 2004).ANALYSIS:Standardized prevalence rates were analyzed. Logistic regression modeling was used to determine factors associated with the presence of subclinical thyroid dysfunction.RESULTS:A total of 5960 attended for screening. Using biochemical definitions, 94.2% [95% confidence interval (CI) 93.8-94.6%] were euthyroid. Unidentified overt hyper- and hypothyroidism were uncommon (0.3, 0.4%, respectively). Subclinical hyperthyroidism and hypothyroidism were identified with similar frequency (2.1%, 95% CI 1.8-2.3%; 2.9%, 95% CI 2.6-3.1%, respectively). Subclinical thyroid dysfunction was more common in females (P < 0.001) and with increasing age (P < 0.001). After allowing for comorbidities, concurrent drug therapies, age, and gender, an association between subclinical hyperthyroidism and a composite measure of socioeconomic deprivation remained.CONCLUSIONS:Undiagnosed overt thyroid dysfunction is uncommon. The prevalence of subclinical thyroid dysfunction is 5%. We have, for the first time, identified an independent association between the prevalence of subclinical thyroid dysfunction and deprivation that cannot be explained solely by the greater burden of chronic disease and/or consequent drug therapies in the deprived population.

Objectives This study sought to prospectively evaluate the prevalence of cardiovascular abnormalities in patients with overt hyperthyroidism before and after antithyroid therapy.Background Overt hyperthyroidism is associated with recognized cardiovascular effects believed to be reversed by antithyroid therapy; however, increasing data suggest significant long-term cardiovascular mortality.Methods A total of 393 (312 women, 81 men) consecutive unselected patients with overt hyperthyroidism were recruited and compared with 393 age- and gender-matched euthyroid control subjects. Hyperthyroid patients were reevaluated after antithyroid therapy. Findings in patients and matched control subjects were compared at presentation, after treatment when patients had subclinical hyperthyroidism biochemically, and when patients were rendered biochemically euthyroid. All had a structured cardiovascular history and examination, including measurements of blood pressure (BP) and pulse rate. All had resting 12-lead electrocardiogram and 24-h digital Holter monitoring of cardiac rhythm.Results A higher prevalence of cardiovascular symptoms and signs, as well as abnormal hemodynamic parameters, was noted among hyperthyroid patients at recruitment compared with control subjects. Cardiac dysrhythmias, especially supraventricular, were more prevalent among patients than among control subjects. Palpitation and dyspnea, postural decrease in systolic pressure, and atrial fibrillation (AF) remained more prevalent in treated hyperthyroid subjects with subclinical hyperthyroidism compared with control subjects, and remained more prevalent after restoration of euthyroidism. Predictors for successful reversion to sinus rhythm in those with AF associated with hyperthyroidism were lower BP measurements at recruitment and an initial hypothyroid state induced by antithyroid therapy. Mortality was higher in hyperthyroid subjects than in control subjects after a mean period of follow-up of 66.6 months.Conclusions Cardiovascular abnormalities are common in patients with overt hyperthyroidism at presentation, but some persist despite effective antithyroid therapy. (c) 2007 by the American College of Cardiology Foundation

Single-dose pharmacokinetic (PK) profiles and multiple-dose PK modeling were compared for long-acting octreotide (20 or 60 mg) and prolonged-release lanreotide (90 or 120 mg) over 91 days; steady-state profiles were simulated. All treatments were well tolerated. Octreotide 20-mg profile showed increased concentration on clay 1, lag from days 2 to 6, then prolonged plateau phase (days 11-41); 60-mg PK was dose proportionol. Lonreotide 90-mg profile showed C-max on day 1 then elimination (apparent t(1/2) 25.5 days); 120-mg profile was underproportional. Steady-state PK of octreotide 20 mg/28 d suggested a C-mean of 1216 pg/mL (range, 1065-1585) with low fluctuation index (43%). Steady-state PK of lanreotide 90 mgl 28 d suggested a C-mean of 4455 pglmL (range, 2499-9279) with high fluctuation index (152%). Long-acting octreotide had more predictable PK than prolonged-release lanreotide. Simulated steady-state profiles suggest long-acting octreotide could be optimized to meet individual patient needs. In contrast, proloned-release lanreotide requires exposure canstantly above the therapeutic target to enable monthly long-term therapy.

Thyroid enlargement is common, with a prevalence of 15%; post-mortem studies and high-resolution ultrasonography demonstrate single or multiple nodules in up to 50% of the population. In contrast, thyroid cancer comprises less than 0.5% of all new malignancies. Iodine deficiency is the most important environmental factor contributing to endemic and sporadic goitres. Exposure to ionizing radiation is an important risk factor for benign and malignant disease. No laboratory test specifically distinguishes benign from malignant goitre. Serum thyroglobulin concentrations are valuable in following patients treated for differentiated thyroid cancer. Most thyroid malignancies do not concentrate radioisotopes, but less than 20% of cold nodules are malignant. Malignancy is rare in hot nodules. Ultrasonography distinguishes solid from cystic lesions, but cannot specifically define benign or malignant disease. Fine-needle aspiration cytology has a diagnostic accuracy of up to 90%. Papillary carcinoma is the most common thyroid cancer (70–85%), and may be multifocal and spread to lymph nodes. Surgery is the primary treatment, but there is controversy about its extent and the role of radioiodine ablation. Mortality after 10 years is 5%. Follicular thyroid carcinoma is less common (about 10%) and usually occurs in older individuals. Distant metastases develop in 20% of patients. Optimal treatment is total thyroidectomy and radioiodine ablation; the prognosis is less favourable and 10-year mortality is 15%. Prognostic factors associated with poor survival in differentiated cancers include greater age, male gender, histological variants, large tumour size and extension, and distant metastases. Thyroxine suppressive therapy postoperatively improves recurrence rates and survival.

Growth hormone (GH) acts predominantly via insulin-like growth factor-I (IGF-I) expression. Acromegaly is associated with an increased mortality which can be reversed by optimal treatment. Somatostatin analogues are effective adjunctive therapies in patients treated with surgery and/or radiotherapy and result in tumour shrinkage in many patients. Pegvisomant is a GH analogue which inhibits functional dimerization of GH receptors, inhibits GH activity and normalizes IGF-I in over 90% of subjects. Adult GH deficiency is associated with changes in body composition, insulin status, lipid profile and Quality of Life measures. Hypopituitarism is associated with an increased mortality. Replacement with GH has clinically beneficial effects but there are no data on effects on mortality. Taller individuals are at a 20-60 percent increased risk of a range of cancers, an effect that may be mediated via IGFs. These observations suggest that there is an optimal level of circulating GH and IGF-I required to maintain normal health.

Accepted for publication 10 October 1995 Abstract Objectives-To define the effects of longterm thyroxine treatment upon heart rate, blood pressure, left ventricular systolic function, and left ventricular size, as well as indices ofautonomic function, and to compare findings with those in patients with thyrotoxicosis before and during treatment. Design-Cross sectional study of patients prescribed thyroxine long term (n = 11), patients with thyrotoxicosis studied at presentation (n = 23), compared with controls (n = 25); longitudinal study of patients with thyrotoxicosis studied at presentation and serially after beginning antithyroid drug treatment (n = 23). Methods-24 h ambulatory monitoring of pulse and blood pressure, echocardiography, forearm plethysmography, and autonomic function tests. Results-Long-term thyroxine treatment in doses that reduced serum thyrotrophin to below normal had no effect on blood pressure, heart rate, left ventricular systolic function or stroke volume index, but was associated with an 18-4% increase in left ventricular mass index (mean (SEM) 101'9 (3.09) g/m' v controls 86-1 (4.61), P < 0.01). Thyroxine treatment, like thyrotoxicosis, had no effect on tests of autonomic function. Untreated thyrotoxicosis resulted in pronounced changes in systolic and diastolic blood pressure and an increase in heart rate during waking and sleep. Patients with thyrotoxicosis at presentation had an increase in left ventricular systolic function (ejection fraction 70 5 (1P66)% v 65 4 (1.79), P < 0 01; fractional shortening 40 4 (1.54)% v 35 6 (1.46), P < 0.01), increased stroke volume index (45.9 (2.4) mu/m2 v 36-6 (1.7), P < 0.001), and