Fredstorp L, Pernow Y, Werner S
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Clin Endocrinol (Oxf). 1993 Sep;39(3):331-6. doi: 10.1111/j.1365-2265.1993.tb02373.x.
The somatostatin analogue octreotide (Sandostatin, 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.
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 From day 15 of the study medication was withdrawn, and on day 20 follow-up measurements were made.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).
Sixteen patients with acromegaly were studied, ten in the short-term study and ten in the long-term study; four were included in both.
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.
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.
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.
生长抑素类似物奥曲肽（善得定，山德士公司）可有效降低肢端肥大症患者的生长激素水平。早期和短暂的胃肠道副作用很常见。本研究旨在评估奥曲肽治疗初始阶段的胃肠道副作用是否会影响钙稳态，以及在生长激素水平得到最佳控制且主观胃肠道功能正常的患者长期使用奥曲肽治疗期间，是否能观察到对钙稳态的影响。
我们首先研究了奥曲肽14天的短期治疗。从研究第15天起停用研究药物，并在第20天进行随访测量。然后我们观察了奥曲肽长期治疗的效果。至采血日的平均治疗时长为32个月（范围9 - 48个月）。
对16例肢端肥大症患者进行了研究，10例参与短期研究，10例参与长期研究；4例同时参与了两项研究。
在短期研究的治疗前（第0天）以及第4、6、8、14和20天，以及长期研究中除性激素结合球蛋白（SHBG）外的治疗前及治疗期间，测量血清钙、磷、甲状旁腺激素（PTH）、碱性磷酸酶、1,25(OH)₂维生素D、维生素D结合蛋白和性激素结合球蛋白（SHBG）水平。
短期治疗期间，血清钙均值（±标准误）显著下降（第6天和第8天分别为2.21±0.08和2.15±0.09 mmol/L，而基础水平为2.38±0.08 mmol/L），而血清PTH均值显著升高（第14天为36±4，基础值为24±3 ng/L；ng/L除以9.425 = pmol/L），血清1,25(OH)₂维生素D均值升高（第8天为112±7，基础值为96±8 pmol/L），以及“游离1,25(OH)₂维生素D指数”，即1,25(OH)₂维生素D与维生素D结合蛋白的摩尔比（第8天和第14天分别为1.72±0.09×10⁻⁵和1.66±0.11×10⁻⁵，基础值为1.33±0.09×10⁻⁵）。这些变化均在正常范围内。血清磷、碱性磷酸酶或维生素D结合蛋白未见变化。长期研究期间，血清钙和磷均值显著下降，分别为2.32±0.04 vs基础值2.42±0.04 mmol/L和1.24±0.07 vs基础值1.40±0.09 mmol/L，而血清PTH均值显著升高，为40±8 vs基础值21±5 ng/L。这些变化均在正常范围内。血清碱性磷酸酶、1,25(OH)₂维生素D、游离1,25(OH)₂维生素D指数或维生素D结合蛋白未见变化。
肢端肥大症患者在奥曲肽治疗期间钙稳态的改变不仅是初始和暂时的，而且在数年治疗后也可观察到。这些长期影响的临床相关性需要进一步研究。
