In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5

Abstract

Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of pituitary adenomas. Medical therapy with somatostatin analogues (SSAs) effectively reduces TSH secretion in approximately 80% of patients and induces shrinkage in about 45% of tumors. According with previous data, resistance to SSA treatment might be due to heterogeneity in somatostatin receptors (SSTRs) expression. We report the case of TSHoma in a 41-year-old man treated with octreotide LAR that caused a dramatic decrease of TSH and thyroid hormones and tumor shrinkage already after 3 months of pre-surgical therapy. In search of potential molecular determinants of octreotide effectiveness, we measured, in primary cultures from this tumor, SSTR and dopamine D2 receptor (D2R) expression, and octreotide and/or cabergoline effects on TSH secretion and cell proliferation. SSTR5 and D2R expression was higher than SSTR2. Octreotide significantly inhibited TSH secretion more effectively than cabergoline (P<0.001), whereas the combined treatment was comparable with cabergoline alone. Similarly, octreotide resulted more effective than cabergoline on cell proliferation, while the combination did not show any additive or synergistic effects. In conclusion, the significant antisecretive and antiproliferative effect of octreotide in this patient might be related to the high expression of SSTR5, in the presence of SSTR2. After reviewing the literature, indeed, in line with previous observations, we hypothesize that SSTR5/SSTR2 ratio in TSHomas may represent a useful marker in predicting the outcome of therapy with SSAs. The role of D2R should be further explored considering that the presence of D2R can influence SSTRs functionality.

Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases

“…The efficacy of this treatment in the present series is similar to that in previous reports. 3,4,11,13,31,32 Preoperative octreotide administration led to FT4 normalization in 40 (83%) of 48 cases and tumor shrinkage in 24 (55%) of 44 cases in this study. These results are similar to those of Beck-Peccoz and Persani, who report that octreotide reduces TSH levels in more than 90% of cases, restores a euthyroid state in the majority of patients, and decreases tumor size as assessed by imaging in nearly half of patients.…”

“…4,32 Most TSH-secreting pituitary adenomas express a variable number of somatostatin receptors. Administering somatostatin analogs as a primary treatment or adjuvant to surgery is highly effective in reducing TSH secretion or shrinking these tumors, 3,4,11,13,31,32 although published reports are limited by small sample sizes. The purpose of the current study was to investigate the clinicopathological features and outcomes of surgical treatment in patients with TSH-secreting tumors treated at our center.…”

Short-term preoperative octreotide treatment for TSH-secreting pituitary adenoma

“…Similar to GH-producing adenomas, treatment with somatostatin analogues is effective for hormonal control and tumor shrinkage in TSHomas, since these tumors also express somatostatin receptors [8][9][10][11]. Short-and long-term octreotide treatment of patients with TSHoma had been reported to result in normalization of thyroid hormone levels in 72% and 95% of patients, respectively, with tumor shrinkage in 45-52% [2,4].…”

Thyroid storm induced by TSH-secreting pituitary adenoma: a case report

“…But, as TSHoma are more fibrotic and invasive than other pituitary adenomas [5], surgical remission is limited to 50-70% [5,11,16]. Somatostatin analogs (SSAs) including octreotide are commonly used as second-line treatment [15,17]. Somatostatin receptors are highly expressed on TSHomas [18].…”