Long-term Treatment of Acromegaly with Lanreotide: Evidence of Increased Serum Parathormone Concentration

Abstract

Abstract. The somatostatin analogue lanreotide is effective in reducing growth hormone levels in patients with acromegaly. Acromegaly is characterized by calcium homeostasis alterations. The aim of our study was to evaluate the effects of lanreotide on bone turnover markers in a group of acromegalic patients and to verify a possible increase of intact parathormone (iPTH) levels in a transient or persistent way. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before treatment and on months 3 and 24. In short-term treatment (3 months), lanreotide significantly decreased GH, IGF-I, serum calcium, osteocalcin and alkaline phosphatase levels, but increased iPTH level (49 ± 16.7 vs pre-treatment 28.3 ± 7.6 ng/L, p<0.001). During long-term study (24 months) GH and IGF-I were significantly still low; serum calcium and alkaline phosphatase levels returned to pre-treatment levels. iPTH level was significantly still higher compared with pre-treatment (46.4 ± 9.2 vs 28.3 ± 7.6 ng/L, p<0.05). No changes were seen in serum albumin, creatinine and vitamin D during short and long term treatment. The changes of most bone markers during lanreotide treatment can be explained by the decrease of GH and IGF-I. The increase of iPTH concentration suggests that lanreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the lanreotide could contribute to this "secondary" hyperparathyroidism. The clinical relevance of these long-standing effects needs to be further investigated.

Calcium and Bone Turnover Markers in Acromegaly: A Prospective, Controlled Study

“…Even in normocalcemic acromegaly patients, we identified changes of calciumphosphate balance after treatment of acromegaly: a decrease in mean serum and urine calcium, along with a decrease in phosphorus levels. This is consistent with previous studies that indicated a decrease in serum calcium level at 3 to 4 weeks after pituitary surgery (8) and 3 to 4 months after treatment with somatostatin analogs (7,10). The role of 1,25(OH) 2 D in calcium perturbations in acromegaly has been attributed to the activation of renal 1-a-hydroxylase by GH (25) or PRL (26).…”

“…Treatment of acromegaly with surgery (2) or a GH receptor antagonist (8) resulted in a reduction of mean 1,25(OH) 2 D levels, whereas GH supplementation in GH-deficient adults had the opposite effect (27). On the other hand, a reduction of mean 1,25(OH) 2 D levels has not been found in longitudinal studies where patients were treated with somatostatin analogs (10,11 (5). The patient population enrolled in prior studies was heterogeneous with regards to the duration and biochemical severity of acromegaly, while assays for IGF-1 and 1,25(OH) 2 D have also evolved.…”

“…Studies in patients treated for acromegaly have reported that posttreatment mean parathyroid hormone (PTH) levels were unchanged (2) or higher compared with baseline (7,8). Similarly, mean 1,25(OH) 2 D levels decreased after treatment of acromegaly in some studies (2,8,9) and remained unchanged in others (10,11). A confounding factor may be coexisting hyperprolactinemia, as one report indicated patients with prolactinomas had higher 1,25(OH) 2 D levels than controls (12).…”

“…Interestingly, the risk remains high for a few years after biochemical remission, suggesting a long-lasting effect of acromegaly on bone quality (19). Bone formation and resorption are high in patients with active acromegaly (13) and decrease after medical treatment of acromegaly (7,8,10). The mechanism by which GH excess induces bone resorption is unknown.…”

Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess

“…Mean 25OH-D3 levels did not change during short and long-term SA therapy, suggesting that long-term SA therapy does not affect serum vitamin D [59]. Similar data were found by Cappelli et al, who demonstrated that 24 months of treatment with lanreotide in 35 patients with acromegaly did not associate with significant changes in 1,25(OH)2-D3 levels [68]. Conversely, only during the short-term treatment (8 and 14 days) with octreotide, was a rise shown in mean serum 1,25(OH)2-D3, with no changes in VDBP [69].…”