H L Simpson

Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom

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Publications (8)23.72 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Context:Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management.Objective:The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort.Study Design:This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy.Results:Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 μg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged.Conclusions:Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.
    The Journal of clinical endocrinology and metabolism 02/2013; · 6.50 Impact Factor
  • Endocrine 02/2012; 42(2):453-5. · 1.42 Impact Factor
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    ABSTRACT: Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.
    Pituitary 11/2011; 15(3):276-87. · 2.67 Impact Factor
  • QJM: monthly journal of the Association of Physicians 11/2011; · 2.36 Impact Factor
  • QJM: monthly journal of the Association of Physicians 09/2011; 104(9):807-8. · 2.36 Impact Factor
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    ABSTRACT: Several studies have suggested an increased prevalence of benign and malignant tumors in acromegaly, particularly colonic neoplasms. The gallbladder's epithelial similarity to the colon raises the possibility that gallbladder polyps (GBP) may occur more frequently in acromegaly. Thirty-one patients with newly diagnosed acromegaly (14 females, 17 males; mean age 54.7 yr, range 27-76 yr) were referred to our center between 2004 and 2008. All had pituitary adenomas and were treated with somatostatin analogs prior to transsphenoidal surgery. Biliary ultrasonography was performed at the time of referral. In a retrospective case-cohort study, we compared the prevalence of GBP in these scans with those of 13,234 consecutive patients (age range 20-80 yr) presenting at the hospital for abdominal/biliary ultrasound during the same time interval. Associations between GH and IGF-I levels and GBP in acromegaly were also examined. There was a higher prevalence of GBP in patients with acromegaly compared with controls (29.03 vs 4.62%, P = 0.000008); relative risk was 6.29 (95% confidence interval 3.61-10.96). Eight of nine patients with acromegaly and GBP were older than 50 yr of age. GH levels were higher in those with GBP (median 30.8 μg/liter, interquartile range 10.9-39.1) than those without (8.2 μg/liter, interquartile range 6.0-16.0), but IGF-I levels were comparable. This is the first study to demonstrate an increased prevalence of GBP in patients with newly diagnosed acromegaly. Further studies are required to determine whether these patients are at increased risk of developing gallbladder carcinoma and to define the role, if any, of biliary ultrasound surveillance.
    The Journal of clinical endocrinology and metabolism 05/2011; 96(7):E1120-5. · 6.50 Impact Factor
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    ABSTRACT: Antithyroglobulin antibodies are a prevalent cause of interference in serum thyroglobulin immunoassays. Current guidelines recommend that antithyroglobulin antibodies should be measured concurrently with thyroglobulin when monitoring thyroid cancer patients post-thyroidectomy. However, the concordance between different antithyroglobulin assays has been questioned despite the availability of an international thyroglobulin antibody Reference Preparation. Four antithyroglobulin assays currently in use in UK laboratories (Siemens Immulite(®), Brahms GmbH, PerkinElmer AutoDELFIA and Siemens ADVIA Centaur(®)) were compared in a cohort of 145 thyroid cancer patients. Using reference data provided by the kit manufacturer, concordance between the assays was 74%. Adjusting the cut-offs to maximize agreement increased concordance to 90%. Recovery of exogenous thyroglobulin using the Brahms Tg-plus immunoradiometric assay was neither a specific nor a sensitive test for the presence of a positive antibody result by any assay. Despite the availability of an international reference preparation, current antithyroglobulin assays show unacceptable variance.
    Annals of Clinical Biochemistry 04/2011; 48(Pt 4):367-9. · 1.92 Impact Factor
  • Regulatory Peptides - REGUL PEPTIDES. 01/2010; 164(1):13-13.