Endocrine Abstracts (2004) 7 P163

Primary therapy with somatostatin analogues in acromegaly does not restore orderly GH secretion

C Parkinson1, K Darzy2, SR Peacey3, MO Thorner4, JD Veldhuis5, PJ Trainer2 & SM Shalet2

1Diabetes and Endocrinology, Ipswich Hosptial, Ipswich, UK; 2Endocrinology, Christie Hospital, Manchester, UK; 3Endocrinology, Bradford Hospital, Bradford, UK; 4Medicine, University of Virginia Health Sciences Centre, Charlttesville, Virginia, USA; 5Endocrinology/Metabolism and Internal Medicine, Mayo Clinic Foundation, Rochester, Minnesota, USA.

Tumoural GH secretion in acromegaly is characterised by increased non-pulsatile (basal) release, pulse amplitude and pulse frequency. We have studied the effect of primary therapy with Sandostatin LAR on GH pulsatility in 9 patients with acromegaly who achieved disease control (mean serum GH<2ug/L) on therapy (7 males; median (range) age 67 (43-75). Data obtained were compared with 16 healthy subjects (10 males, age 50 (30-75)). Spontaneous 24-h GH secretion (20 minute sampling) was measured using an ultrasensitive GH assay (lower limit of detection 0.002 ug/L). Analysis of secretion and regularity used multiparameter deconvolution and approximate entropy (ApEn) respectively.

Mean GH and serum IGF-I were not significantly different between controls and patients receiving LAR (GH (mean±SD) 0.76±0.86 vs. 0.98±0.56 ug/l, P=0.5; IGF-I 166±64 vs. 127±29, P=0.2). Despite this, LAR patients had elevated ApEn (median (range) 1.14 (0.86-1.15) vs. 0.568 (0.27-1.2); P=0.0024), increased basal secretion (0.014 (0.003-0.065) vs. 0.0015 (0.001-0.02) ug/min; P=0.0014), increased burst number ((mean±SD) 15.7±4.30 vs. 12.6±2.6; P=0.037) and increased burst amplitude (0.58 (0.02-21.6) vs. 0.05 (0.001-0.24); P=0.0161). No difference in inter-pulse interval or burst mass was observed.

In summary, despite similar mean GH and IGF-I levels patients receiving LAR as primary therapy for acromegaly have disordered GH release as suggested by elevated ApEn levels. Continued tumoral GH release is implied by overall pattern irregularity (increased ApEn), increased burst frequency, increased burst amplitude and non-suppressible basal secretion that is approximately ten fold higher than control levels.

In conclusion, epidemiologically 'safe' serum GH levels during primary somatostatin analogue therapy in acromegaly are not associated with restoration of orderly GH secretion despite similar GH and IGF-I levels between LAR treated subjects and controls.

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