ABSTRACT
<p><b>BACKGROUND</b>Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin (SST) analogs work by interacting with somatostatin receptors (SSTRs). This study aimed to evaluate short-term preoperative octreotide (OCT) use in TSHoma patients and to investigate SSTR2 and SSTR5 expression and observe structural changes in tumor tissue.</p><p><b>METHODS</b>We reviewed records and samples from eight TSHoma patients treated between July 2012 and July 2015. We tested immunohistochemically for SSTR2/5 expression and examined TSHoma cells for morphological changes. Signed rank sum test was used to compare the efficacy of short-term preoperative OCT treatment.</p><p><b>RESULTS</b>OCT treatment (median time: 7.9 days, range: 3-16 days; median total dose: 1.8 mg, range: 0.9-4.2 mg) led to significant decrease in all patients' thyroid hormone levels (FT3 [nmol/L]: 8.33 [7.02, 12.29] to 4.67 [3.52, 5.37] [P = 0.008]; FT4 [pmol/L]: 25.36 [21.34, 28.99] to 16.66 [14.88, 21.49] [P = 0.016]; and TSH [μU/ml]: 5.80 [4.37, 6.78] to 0.57 [0.19, 1.24] [P = 0.008]). All the eight tumor specimens expressed high SSTR2 protein levels; 5/8 expressed high SSTR5, but 3/8 that expressed low SSTR5 presented a significantly higher TSH suppression rate (P = 0.036). Electron microscopy showed subcellular level impairments, including clumped nuclear chromatin and reduced cytoplasmic volume. Golgi complexes were observed in the OCT-treated TSHoma specimens.</p><p><b>CONCLUSIONS</b>OCT can control hormone levels and damage the ultrastructure of tumor cells and organelles. Short-term response to OCT may be related to SSTR5 expression. Preoperative SST analog treatment for TSHoma could be considered as a combination therapy.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Immunohistochemistry , Microscopy, Electron , Octreotide , Therapeutic Uses , Pituitary Neoplasms , Drug Therapy , Metabolism , Receptors, Somatostatin , Metabolism , Thyrotropin , Bodily SecretionsABSTRACT
<p><b>BACKGROUND</b>Little information about the current management of patients with thyroid-stimulating hormone (TSH)-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure.</p><p><b>METHODS</b>Fifteen patients with TSH-secreting pituitary adenomas (8 men and 7 women), who previously underwent incomplete surgical resection and/or adjuvant radiotherapy (n = 12) and failure of octreotide treatment (n = 15), followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables.</p><p><b>RESULTS</b>After two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine (FT4) ((16.02 ± 1.72) pmol/L) and free triiodothyronine (FT3) ((2.87 ± 0.43) pmol/L) levels of 15 patients significantly decreased compared with those after octreotide-treatment (FT4, (35.36 ± 7.42) pmol/L, P < 0.001; FT3, (17.85 ± 7.22) pmol/L, P < 0.001). Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment ((0.72 ± 0.21) mU/L) and were significantly lower than the pretreatment value ((5.27 ± 1.04) mU/L, P < 0.001), post-surgery value ((3.37 ± 0.31) mU/L, P < 0.001) and post-octreotide-treatment value ((4.52 ± 0.41) mU/L, P < 0.001). In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis.</p><p><b>CONCLUSION</b>The long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.</p>