Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones

M J Veysey, L A Thomas, A I Mallet, P J Jenkins, G M Besser, J A Wass, G M Murphy, R H Dowling, M J Veysey, L A Thomas, A I Mallet, P J Jenkins, G M Besser, J A Wass, G M Murphy, R H Dowling

Abstract

Background: Treatment of acromegaly with octreotide increases the proportion of deoxycholic acid in, and the cholesterol saturation of, bile and induces the formation of gallstones. Prolongation of intestinal transit has been proposed as the mechanism for the increase in the proportion of deoxycholic acid in bile.

Aims: To study the effects of octreotide on intestinal transit in acromegalic patients during octreotide treatment, and to examine the relation between intestinal transit and bile acid composition in fasting serum.

Methods: Mouth to caecum and large bowel transit times, and the proportion of deoxycholic acid in fasting serum were measured in non-acromegalic controls, acromegalic patients untreated with octreotide, acromegalics on long term octreotide, and patients with simple constipation. Intestinal transit and the proportion of deoxycholic acid were compared in acromegalic patients before and during octreotide.

Results: Acromegalics untreated with octreotide had longer mouth to caecum and large bowel transit times than controls. Intestinal transit was further prolonged by chronic octreotide treatment. There were significant linear relations between large bowel transit time and the proportion of deoxycholic acid in the total, conjugated, and unconjugated fractions of fasting serum.

Conclusions: These data support the hypothesis that, by prolonging large bowel transit, octreotide increases the proportion of deoxycholic acid in fasting serum (and, by implication, in bile) and thereby the risk of gallstone formation.

Figures

Figure 1
Figure 1
Group data for MCTT in non-acromegalic control subjects, acromegalic patients untreated with octreotide (OT), acromegalic patients on long term octreotide treatment (LTOT), and patients with simple constipation.
Figure 2
Figure 2
Group data for LBTT in non-acromegalic control subjects, acromegalic patients untreated with octreotide (OT), acromegalic patients on long term octreotide treatment (LTOT), and patients with simple constipation.
Figure 3
Figure 3
Group data for the proportion of deoxycholic acid (DCA), expressed as a percentage of the total serum bile acids, in non-acromegalic control subjects, acromegalic patients untreated with octreotide (OT), acromegalic patients on long term octreotide treatment (LTOT), and patients with simple constipation.
Figure 4
Figure 4
Relation between LBTT and the proportion of deoxycholic acid (DCA), expressed as a percentage of the total serum bile acids.

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