Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor 5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma)

Abstract

BackgroundThyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin analogs have proved to be effective for inhibiting pituitary hormones secretion, working via interactions with somatostatin receptors (SSTRs). Moreover, antiproliferative activity of somatostatin analog is now demonstrated in several studies. In the present study, we determined the relative predominance of SSTR2 and SSTR5 subtypes among the different types of adenomas, especially TSHoma, and investigated the relationship between efficacy of short-term octreotide (OCT) treatment and SSTR expression.Material/MethodsSerum hormone determinations and histological findings in resected tissue resulted in 5 diagnoses: 16 TSHomas, 8 acromegaly, 3 prolactinomas, 3 corticotropinomas, 4 clinically nonfunctioning adenomas (NFPAs), and 4 normal pituitary specimens. IHC was performed on formalin-fixed and paraffin-embedded tissue in tissue microarrays.ResultsIHC of SSTR subtypes in the different cohorts showed SSTR2 staining intensity scores higher than SSTR5 in TSHoma, acromegaly and prolactinoma, whereas the expression of SSTR5 was stronger than SSTR2 in corticotropinoma and NFPA. SSTR2 and SSTR5 expressions were significantly higher in TSHoma than in other pituitary adenomas. OCT treatment for a median of 8.4 days (range: 3–18 days) and with a total median dose of 1.9 mg (range: 0.9–4.2 mg) showed a significant decrease of thyroid hormone levels (TSH [μIU/ml] in all patients. Patients with low SSTR5 expression presented a significantly higher TSH suppression rate (P values <0.05).ConclusionsThe present data confirm that somatostatin analogs should be considered as a medical alternative to surgical treatment, especially in patients with TSHoma, and short-term response to OCT therapy may be related to the expression of SSTR5.

The effect of preoperative short-term octreotide treatment to surgery in thyrotropin-secreting pituitary adenomas: a retrospective cohort study

“…SSAs were originally used to control high level of GH in acromegaly patients. SSAs stimulate p27 expression and inhibit the MAPK pathway in pituitary tumors by binding to SSRT2 and SSRT5 [ 17 – 19 ].Studies have found that SSTR2 and SSTR5 also express in TSHoma cells, suggesting that SSAs can be used to treat TSHoma [ 8 , 9 ]. The secretion of TSH is mediated through the interactions between SSAs and SSRT2, whereas the reduction in tumor size is influenced mainly by the interactions between SSAs and SSRT5 [ 20 , 21 ].…”

A case of TSHoma mimicing Graves 'disease and makes GH cosecrete

“…In this test, the TRH stimulation test and TSH-oma are applied when the differential diagnosis of thyroid hormone resistance is not made. In this test, the absence of suppression in TSH is interpreted in favor of TSHoma, and the presence of TSH suppression in favor of thyroid hormone resistance [22]. In addition, TSH suppression can be measured using somatostatin analogues.…”

“…Surgery is the gold standard treatment for TSHoma. Post-surgical remission rate is between 35-58% [1,22,24]. Preoperative medical treatment can be initiated in patients to increase remission after surgery.…”

Case Report and Literature Review: Ectopic Thyrotropin-Secreting Pituitary Adenoma in the Suprasellar Region

“…The somatostatin suppression test contributes to the diagnosis and differential diagnosis of TSH-oma. Because the somatostatin receptor is expressed on the surface of TSH-oma cells ( 22 ), the secretion of TSH could be inhibited after somatostatin analog injection in patients with TSH-oma. The TSH suppression rate was calculated by the proportion of the largest decrease in the initial TSH level.…”