SFEBES2009 Poster Presentations Pituitary (56 abstracts)
The acromegalic cardiovascular and respiratory outcomes with primary analogue therapy (A.C.R.O.P.A.T.) trial
A Webb 1 , E Gayton 1 , A Annamalai 1 , S Pilsworth 2 , S Wallace 3 , S Khan 5 , S O’Toole 1 , S Ariyaratnam 1 , K Maki-Petaja 2 , D Scoffings 4 , N Antoun 4 , I Wilkinson 2 , D Dutka 5 , J Shneerson 2 , H Simpson 1 & M Gurnell 1
1Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK; 2Respiratory Support and Sleep Centre, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, Cambridgeshire, UK; 3Department of Clinical Pharmacology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK; 4Department of Radiology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK; 5Department of Cardiovascular Medicine, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
Seventeen newly-diagnosed acromegalic patients (8 female, 9 male: mean age 55 year, range 26–73 year) were recruited to the A.C.R.O.P.A.T. trial. Patients were assessed prior to, and following, 6 months of treatment with Somatuline Autogel® (SA).
Growth hormone (GH) & insulin-like growth factor 1 (IGF1): Following treatment, GH and IGF1 levels fell significantly in all but one subject: median GH change −17.23 mU/l (interquartile range (IQR) −40.0 to −12.1, P=0.0024); median IGF1 change −49.9 nmol/l (IQR −90.4 to −27.2, P=0.0003). Ten patients achieved mean GH <5 mU/l, six of whom also fully normalised IGF1.
Pituitary MRI: Of 5/17 micro- and 12/17 macro-adenomas; tumour volumes were reduced by an average of 31% (median change −209.5 mm3, IQR −395.3 to −74.2, P=0.004).
Polysomnography: There was a statistically significant reduction in sleep latency (median change −10 mins, IQR −13.0 to 0.0, P=0.019). Unexpectedly, apnoea/hypopnoea index (AHI) and desaturation index (DI) showed variable responses: 9/17 and 8/17 subjects experienced improvements in AHI and DI respectively, but five exhibited a worsening of sleep disordered breathing despite improvements in GH/IGF1 levels. Further analysis revealed a positive correlation of body mass index and waist circumference with both AHI (P=0.02, P=0.03) and DI (P=0.005, P=0.002). Importantly, AHI and DI deteriorated only in subjects who gained weight.
Cardiovascular studies: Fourteen subjects had a reduction in blood pressure following treatment (median cohort change: systolic −4.0 mmHg, IQR −10 to −3, P=0.03; diastolic −4.0 mmHg, IQR −9 to 0, P=0.13). However, this did not always correlate with improvements in markers of arterial stiffness (pulse wave analysis), endothelial function (flow-mediated vasodilatation) or cardiac performance (tissue doppler echocardiography).
Conclusions: SA effectively lowers GH/IGF1 levels, promotes tumour shrinkage and reduces blood pressure when used as primary medical therapy in acromegaly. Interestingly, improvements in biochemical indices of disease activity are not necessarily paralleled by improvements in all biomarkers of respiratory and cardiovascular function.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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