Evaluation of the treatment of thyrotropin-secreting pituitary adenomas with a slow release formulation of the somatostatin analog lanreotide

Somatostatin analogs have been shown to be effective for the treatment of T SH-secreting pituitary adenomas. However, their use in this indication is l imited by the fact that available analogs require several daily sc injectio ns. The present study was performed to evaluate the effects of a slow relea se formulation of the somatostatin analog lanreotide (SR-L) on both hormone secretion and tumor size and to assess the tolerance in a series of thyrot ropinomas treated for 6 months. Eighteen patients with hyperthyroidism rela ted to a TSH-secreting pituitary adenoma, evidenced by pituitary magnetic r esonance imaging, were studied. After a basal assessment, each patient rece ived 30 mg SR-L, im, every 14 days for 1 month. Then, according to the free T-3 (fT(3)) plasma level measured, 9 of 18 patients were injected twice mo nthly, and 7 of 18 patients received SR-L every 10 days for 5 additional mo nths. One patient was dismissed from the study in month 1 of the study for side-effects and another in month 3 for noncompliance to the protocol. Clin ical and biological evaluations (plasma TSH, free alpha-subunit, fT(4), fT( 3), and lanreotide levels) were performed before and in months 1, 3, and 6 of treatment. Pituitary magnetic resonance imaging and gallbladder ultrason ography were performed both at entry and at the end of the study. Clinical signs of hyperthyroidism improved within 1 month in all 16 evaluable patien ts. Mean (+/- SEM) plasma lanreotide levels reached 1.11 +/- 0.43 and 1.69 +/- 0.65 ng/mL in month 3 using 2 and 3 injections/month, respectively, the n remained stable until the end of the study. During therapy, the plasma TS H level decreased from 2.72 +/- 0.32 to 1.89 +/- 0.27 mU/L (P < 0.01), with parallel significant changes in free ar-subunit. During the same period, p lasma fT(4) and fT(3) levels decreased from 37.9 +/- 2.9 to 19.7 +/- 2.5 pm ol/L (P < 0.01) and from 14.6 +/- 1.1 to 8.3 +/- 0.8 pmol/L (P < 0.01), res pectively. No statistically significant change in mean adenoma size was obs erved after 6 months of treatment. Side-effects, including pain at the inje ction point, abdominal cramps, and diarrhea, were mild and transient and di d not lead to intenuption of the treatment. No gallstones occurred during t he study. SR-L appears to be able to suppress clinical signs of hyperthyroi dism in our series of patients with TSH-secreting pituitary adenomas. The a nalog also reduces plasma TSH and thyroid hormone levels, which were normal ized in 13 of 16 cases. The effect was maintained throughout the treatment using 2 or 3 SR-L injections: monthly without any problem of tolerance. We conclude that SR-L is a safe and effective treatment of thyrotropinomas and avoids the drawbacks of the modes of administration of other somatostatin analogs, given three times daily.