THE SHORT AND LONG-TERM EFFECTS OF OCTREOTIDE ON CALCIUM HOMEOSTASIS IN PATIENTS WITH ACROMEGALY

OBJECTIVE The somatostatin analogue octreotide (Sandastatin, Sandoz) is effective in reducing growth hormone levels in patients with acromegaly. Early and transient gastrointestinal side-effects are frequent. The aim was to evaluate whether gastrointestinal side-effects during the initial phase of octreotide treatment affect calcium homeostasis, and whether effects on calcium homeostasis are seen during long-term treatment with octreotide in patients with optimal effect on GH and subjectively normal gastrointestinal function. DESIGN We first studied short-term treatment with octreotide during 14 days. From day 15 of the study medication was withdrawn, and on day 20 follow-up measurements were made. We then observed the effects of long-term treatment with octreotide. Mean duration of treatment until the day of blood sampling was 32 months (range 9-48 months). PATIENTS Sixteen patients with acromegaly were studied, ten in the short-term study and ten in the long-term study; four were included in both. MEASUREMENTS Serum levels of calcium, phosphate, PTH, alkaline phosphatase, 1,25(OH)2 Vit D, vitamin D-binding protein and sex hormone-binding globulin (SHBG) were measured before treatment (day 0) and on days 4, 6, 8,14 and 20 during the short-term study and, except SHBG, before treatment and during therapy in the long-term study. RESULTS During the short-term treatment mean (+/- SEM) serum calcium decreased significantly (on days 6 and 8, 2.21+/-0.08 and 2.15+/-0.09 mmol/l, respectively vs basal level, 2.38+/-0.08 mmol/l), whereas significant increments were seen in mean serum PTH (on day 14, 36+/-4 vs basal, 24+/-3 ng/l; ng/l divided-by 9.425=pmol/l), mean serum 1,25(OH)2 Vit D (on day 8, 112+/-7 vs basal 96+/-8 pmol/l), and 'free 1.25(OH)2 Vit D-index', i.e. molar ratio of 1,25(OH)2 Vit D and vitamin D-binding protein (on days 8 and 14, 1.72+/-0.09 x 10(-5) and 1.66+/-0.11 x 10(-5), respectively vs basal, 1.33+/-0.09 x 10(-5)). The changes were within the normal range. No changes were seen in serum phosphate, alkaline phosphatase, or vitamin D-binding protein. During the long-term study mean serum calcium and phosphate decreased significantly, 2.32+/-0.04 vs basal 2.42+/-0.04 mmol/l and 1.24+/-0.07 vs basal 1.40+/-0.09 mmol/l, respectively, whereas mean serum PTH increased significantly, 40+/-8 vs basal 21+/-5 ng/l. The changes were within the normal range. No changes were seen in serum alkaline phosphatase, 1,25(OH)2 Vit D, free 1,25(OH)2 Vit D-index, or vitamin D-binding protein. CONCLUSION Altered calcium homeostasis during octreotide treatment in acromegaly is not only initial and temporary, but can also be seen after several years of treatment. The clinical relevance of these long-standing effects needs to be further investigated.