these tumors may cause hyperthyroidism through inappropriate secretion of tsh , which can also lead to perioperative thyroid storm . thus , thyroid hormone ( th ) levels need to be preoperatively controlled for these patients . the first - line therapy for tshoma is neurosurgery , yet surgical cure rates vary reportedly around only 5060% . tshomas are often invasive and fibrous which hamper complete removal ; somatostatin ( sst ) analogs are therefore primarily used in palliative care or for patients who were not cured by surgery . the role of somatostatin receptors ( sstrs ) as therapeutic targets in pituitary adenomas sst analogs are reportedly effective in hormonal control of tshomas and growth hormones ( gh)-secreting adenomas . sstr have five subtypes ( sstr15 )  mostly sstr2 and sstr5  those are widely expressed in both normal and neoplastic human pituitary cells . understanding of the highly variable expression of sstr subtypes in pituitary adenomas has risen sharply in recent years . interactions between ligands and receptors serve as the molecular basis of drug - targeting therapy . therefore , the expression profile of sstr subtypes in pituitary adenomas would be helpful to know . octreotide ( oct ) , a clinically available sstr2-preferring analog , normalizes hormone levels for approximately 90% of tshoma patients , yet its preoperative use is rarely reported . in our center , patients with tshoma are started on short - term preoperative sst analog to restore euthyroidism before transsphenoidal surgery as a definitive therapy . to probe into the underlying mechanisms of oct in tshoma treatment , we assessed the outcomes of short - term preoperative oct treatment for patients with tshoma and investigated sstr2 and sstr5 expression by immunohistochemistry ( ihc ) in tumor specimens , as well as their subcellular characteristics at electron microscopy , aiming at providing evidence for tshoma medical therapy . we included eight patients ( six men and two women ) who were diagnosed with tshoma in the department of endocrinology , beijing tiantan hospital , between july 2012 and july 2015 , based on their combinations of typical signs and symptoms of hyperthyroidism and/or intracranial compression ( e.g. , visual loss , headache , nasal obstruction , and hypopituitarism ) ; unsuppressed tsh levels with elevated th levels ; evidence of a pituitary tumor by imaging ; and confirmation by pathological diagnosis . all participants gave written informed consent and the study was approved by the institutional ethical review board of beijing tiantan hospital ( no . sanger sequencing was used to search for point mutations and deletions in the thyroid hormone receptor ( tr )  gene , but no definite pathogenic mutations were found . medical records of all the patients were thoroughly reviewed in terms of their sexes , ages at diagnosis , pathological diagnoses , tumor sizes , and dates of their last follow - ups . oct used in this investigation was obtained from novartis pharmaceuticals corporation ( east hanover , nj , usa ) . each patient received an initial dose of 100 g , injected subcutaneously at 8:00 a.m. if the patient showed no obvious side effects ( such as nausea , vomiting , stomach ache , and diarrhea ) , dosages were increased to 100 g 2 or 3 times / day . serum tsh , free triiodothyronine ( ft3 ) , free thyroxin ( ft4 ) , total triiodothyronine ( tt3 ) , and total thyroxin ( tt4 ) concentrations were measured by chemiluminescent enzyme assays using commercially available kits . the following formula was used to determine tsh suppression rate : tsh suppression rate ( % ) = ( before treatment  after treatment)/before treatment  100% . serial 4-m - thick sections were cut from formalin - fixed and paraffin - embedded pituitary adenoma tissues and used for histological diagnosis and ihc staining for sstr2 and sstr5 . for adenoma classification , specimens were subjected to routine ihc staining with monoclonal antibodies against tsh , adrenocorticotropic hormone , growth hormone , luteinizing hormone , follicle - stimulating hormone , and prolactin . fixed in formalin , the slides were prepared in unstained 3-m sections and 48 dot cores ( diameter : 2.0 mm ) matrix chip template . ihc staining was performed using a leica bond - iii , automatic ihc and ish stainer ( leica biosystems , nussloch , germany ) , which was a fully automated , continuous - access ihc slide - staining system . the primary sstr2 antibody was ab13120 ( 1:100 ) , and the primary sstr5 antibody was ab13121 ( 1:100 ; abcam , cambridge , uk ) . sections were assessed independently by two experienced pathologists who were blinded to both clinical and pathological data . scoring of each section was determined by consensus , by the immunoreactive score ( irs ) method , which entailed multiplying staining intensity ( 0 = no staining , 1 = weak staining , 2 = moderate staining , and 3 = strong staining ) by percentage of positively stained cells ( 0 = 0% , 1 = 133% , 2 = 3466% , and 3 = > 66% ) , for irs scores ranging from 0 ( no staining ) to 9 ( maximum staining ) , irs scores of 04 were considered low expression and 59 were high expression . specimens from all the eight patients were examined by an electron microscope . for electron microscopy , 1-mm - thick sections were double fixed by 2.5% glutaraldehyde ( by volume ) and 2% formaldehyde solution for 2 h at 4c , and then washed three times with phosphate - buffered saline ( pbs ) . samples were then fixed in 1% osmium tetroxide , washed with pbs , dehydrated in an ethanol gradient , and embedded , using fresh embed-812 , in labeled embedding molds and polymerized . section blocks were conformed and cut into 60-nm sections , stained in uranyl acetate and lead citrate , and their specific ultrastructure features were observed under a hitachi h-7650 ( 120 kv ) transmission electron microscope . as controls , we randomly selected eight sets of electron microscopy data from patients who received surgical treatment instead of oct therapy . sas 9.4 ( sas institute , inc , north carolina , usa ) was used to analyze the data , and the statistical description of variables was shown as median ( interquartile range ) . signed rank sum test was used to compare the efficacy of short - term preoperative oct treatment . wilcoxon rank - sum test was used to investigate tsh suppression rate and sstr5 expression . we included eight patients ( six men and two women ) who were diagnosed with tshoma in the department of endocrinology , beijing tiantan hospital , between july 2012 and july 2015 , based on their combinations of typical signs and symptoms of hyperthyroidism and/or intracranial compression ( e.g. , visual loss , headache , nasal obstruction , and hypopituitarism ) ; unsuppressed tsh levels with elevated th levels ; evidence of a pituitary tumor by imaging ; and confirmation by pathological diagnosis . all participants gave written informed consent and the study was approved by the institutional ethical review board of beijing tiantan hospital ( no . sanger sequencing was used to search for point mutations and deletions in the thyroid hormone receptor ( tr )  gene , but no definite pathogenic mutations were found . medical records of all the patients were thoroughly reviewed in terms of their sexes , ages at diagnosis , pathological diagnoses , tumor sizes , and dates of their last follow - ups . oct used in this investigation was obtained from novartis pharmaceuticals corporation ( east hanover , nj , usa ) . each patient received an initial dose of 100 g , injected subcutaneously at 8:00 a.m. if the patient showed no obvious side effects ( such as nausea , vomiting , stomach ache , and diarrhea ) , dosages were increased to 100 g 2 or 3 times / day . serum tsh , free triiodothyronine ( ft3 ) , free thyroxin ( ft4 ) , total triiodothyronine ( tt3 ) , and total thyroxin ( tt4 ) concentrations were measured by chemiluminescent enzyme assays using commercially available kits . the following formula was used to determine tsh suppression rate : tsh suppression rate ( % ) = ( before treatment  after treatment)/before treatment  100% . serial 4-m - thick sections were cut from formalin - fixed and paraffin - embedded pituitary adenoma tissues and used for histological diagnosis and ihc staining for sstr2 and sstr5 . for adenoma classification , specimens were subjected to routine ihc staining with monoclonal antibodies against tsh , adrenocorticotropic hormone , growth hormone , luteinizing hormone , follicle - stimulating hormone , and prolactin . fixed in formalin , the slides were prepared in unstained 3-m sections and 48 dot cores ( diameter : 2.0 mm ) matrix chip template . ihc staining was performed using a leica bond - iii , automatic ihc and ish stainer ( leica biosystems , nussloch , germany ) , which was a fully automated , continuous - access ihc slide - staining system . the primary sstr2 antibody was ab13120 ( 1:100 ) , and the primary sstr5 antibody was ab13121 ( 1:100 ; abcam , cambridge , uk ) . sections were assessed independently by two experienced pathologists who were blinded to both clinical and pathological data . scoring of each section was determined by consensus , by the immunoreactive score ( irs ) method , which entailed multiplying staining intensity ( 0 = no staining , 1 = weak staining , 2 = moderate staining , and 3 = strong staining ) by percentage of positively stained cells ( 0 = 0% , 1 = 133% , 2 = 3466% , and 3 = > 66% ) , for irs scores ranging from 0 ( no staining ) to 9 ( maximum staining ) , irs scores of 04 were considered low expression and specimens from all the eight patients were examined by an electron microscope . for electron microscopy , 1-mm - thick sections were double fixed by 2.5% glutaraldehyde ( by volume ) and 2% formaldehyde solution for 2 h at 4c , and then washed three times with phosphate - buffered saline ( pbs ) . samples were then fixed in 1% osmium tetroxide , washed with pbs , dehydrated in an ethanol gradient , and embedded , using fresh embed-812 , in labeled embedding molds and polymerized . section blocks were conformed and cut into 60-nm sections , stained in uranyl acetate and lead citrate , and their specific ultrastructure features were observed under a hitachi h-7650 ( 120 kv ) transmission electron microscope . as controls , we randomly selected eight sets of electron microscopy data from patients who received surgical treatment instead of oct therapy . , north carolina , usa ) was used to analyze the data , and the statistical description of variables was shown as median ( interquartile range ) . signed rank sum test was used to compare the efficacy of short - term preoperative oct treatment . wilcoxon rank - sum test was used to investigate tsh suppression rate and sstr5 expression . the study included eight patients ( 6 men and 2 women ) with tshoma whose average age was 39.8 years ( range : 2552 years ) . their average duration of symptoms was 2.6 years ( range : 2 months7 years ) . magnetic resonance imaging showed one patient with microadenoma and seven with macroadenoma [ table 1 ] . all the eight patients had unsuppressed tsh levels with elevated th levels ; neuroimaging revealed pituitary lesions . clinical characteristics of eight patients with tshomas sstr : somatostatin receptor ; irs : immunoreactive score ; tsh : thyroid - stimulating hormone ; ft3 : free triiodothyronine ; ft4 : free thyroxin ; gd : graves disease ; ht : hashimoto s thyroiditis ; tshoma : thyrotropin - secreting pituitary adenoma . all the patients showed various thyrotoxicosis symptoms with goiters , including palpitations , excessive sweating , fatigue , and weight loss ; five also exhibited symptoms of intracranial compression , including paroxysmal headache and blurry vision . patient 3 had been misdiagnosed with graves disease and treated with antithyroid drugs ( thiamazole ) irregularly for 2 years . patient 4 had been misdiagnosed with hashimoto 's thyroiditis for 3.5 years , but had received no treatment before his tshoma diagnosis . patient 8 presented with high levels of tsh receptor antibodies and antithyroid peroxidase antibodies associated with hyperthyroxinemia and  unexpectedly  normal tsh values . short - term preoperative oct administration was highly effective in normalizing excessive hormone concentrations , with tolerable side effects . after oct treatments for a median of 7.9 days ( range : 316 days ) and with a total median dose of 1.8 mg ( range : 0.94.2 mg ) , all patients presented significant decreased tsh and th levels ( ft3 [ nmol / l ] : 8.33 [ 7.02 , 12.29 ] to 4.67 [ 3.52 , 5.37 ] [ p = 0.000 ] ; ft4 [ pmol / l ] : 25.36 [ 21.34 , 28.99 ] to 16.66 [ 14.88 , 21.49 ] [ p = 0.016 ] ; and tsh [ u / ml ] : 5.80 [ 4.37 , 6.78 ] to 0.57 [ 0.19 , 1.24 ] [ p = 0.008 ] ) [ table 2 ] . reference ranges are tsh : 0.354.94 u / ml ; ft3 : 2.635.7 nmol / l ; and ft4 : 9.0019.04 pmol / l . comparison of thyroid function before and after short - term octreotide treatment ( n = 8) data were shown as median ( interquartile range ) . tt3 : total triiodothyronine ; tt4 : total thyroxin ; ft3 : free triiodothyronine ; ft4 : free thyroxin ; tsh : thyroid - stimulating hormone . safety of treatment with sst analogs was proven ; no patients discontinued treatment due to unbearable side effects although patient 4 suffered diarrhea for 2 days , for which his oct dose was reduced to 100 g one time / day for 11 days . patients histology examinations showed positive staining for tsh , thus confirming the diagnoses of tshoma [ figure 1 ] . the ihc staining for sstr2 and sstr5 was positive in the cytoplasm , and notably , greater for sstr2 than sstr5 in tshoma . all patients showed high sstr2 immunoreactivity ( irs 9 ) , yet with heterogeneous and less intense staining for sstr5 ( sstr5 irs : 5/8 high and 3/8 low ) . due to small sample size , we saw no significant relationships between the tsh suppression rate and patients age , sex , tumor size , or treatment dosage ; however , tsh suppression rate and sstr5 expression were significantly related [ p = 0.036 , table 3 ] . relationship between thyroid - stimulating hormone suppression rate and sstr5 expression ( n = 8) * low expression : 04 ; high expression : 59 . tsh suppression rate ( % ) = ( before treatment  after treatment)/before treatment  100% . analyzed with two independent sample wilcoxon rank sum test , patients with low sstr5 expression presented a significantly higher tsh suppression rate ( p = 0.036 ) . ultrastructurally , well - differentiated adenomatous thyrotrophs resemble normal ones , whereas poorly differentiated adenomas were composed of elongated angular cells with irregular nuclei , poorly developed rough endoplasmic reticulum , long cytoplasmic processes , and sparse small secretory granules ( 50200 nm ) that mostly line up along the cell membrane [ figure 2 ] . compared with the normal specimens , those from patients treated with oct showed changes ( to varying degrees ) in such tumor subcellular structure as mitochondrial swelling , dilatation of endoplasmic reticulum , vacuole formation , membrane dissolution and fracture , blurring of nucleus and organelle , cell disintegration , and thickened vascular basal lamina . characteristic apoptotic morphological changes were seen in tshoma cells after treatment with oct under transmission microscope . various types of damages were found at organelles and subcellular level , and decreased secretion activity in oct - treated tumor cells , which contribute to tumor shrinkage due to long - term actions of oct . ( b ) arrow points to untreated adenoma cells  mostly round ; exteriors are dotted evenly with black tsh secretion granules along the cell membranes . ( c ) arrow points to actively growing pituitary adenoma cell with an irregular shape , mild dysplasia , and deep staining ; its nucleus is larger than those seen in normal cells . ( d ) arrow points to mitochondria with varying degrees of swelling , transparent mitochondrial matrix , missing granules , disorderly arrangement , and fractured cristae . ( e ) electron microscope shows cell membrane missing and fractured , as well as local defect and blurred structure of cell organelles and nuclei . g ) arrow points to elongated rough endoplasmic reticulum , which may lead to vacuole denaturalization if extended significantly . tshoma : thyrotropin - secreting pituitary adenoma ; oct : octreotide ; tsh : thyrotropin . the study included eight patients ( 6 men and 2 women ) with tshoma whose average age was 39.8 years ( range : 2552 years ) . their average duration of symptoms was 2.6 years ( range : 2 months7 years ) . magnetic resonance imaging showed one patient with microadenoma and seven with macroadenoma [ table 1 ] . all the eight patients had unsuppressed tsh levels with elevated th levels ; neuroimaging revealed pituitary lesions . clinical characteristics of eight patients with tshomas sstr : somatostatin receptor ; irs : immunoreactive score ; tsh : thyroid - stimulating hormone ; ft3 : free triiodothyronine ; ft4 : free thyroxin ; gd : graves disease ; ht : hashimoto s thyroiditis ; tshoma : thyrotropin - secreting pituitary adenoma . all the patients showed various thyrotoxicosis symptoms with goiters , including palpitations , excessive sweating , fatigue , and weight loss ; five also exhibited symptoms of intracranial compression , including paroxysmal headache and blurry vision . patient 3 had been misdiagnosed with graves disease and treated with antithyroid drugs ( thiamazole ) irregularly for 2 years . patient 4 had been misdiagnosed with hashimoto 's thyroiditis for 3.5 years , but had received no treatment before his tshoma diagnosis . patient 8 presented with high levels of tsh receptor antibodies and antithyroid peroxidase antibodies associated with hyperthyroxinemia and  unexpectedly  normal tsh values . short - term preoperative oct administration was highly effective in normalizing excessive hormone concentrations , with tolerable side effects . after oct treatments for a median of 7.9 days ( range : 316 days ) and with a total median dose of 1.8 mg ( range : 0.94.2 mg ) , all patients presented significant decreased tsh and th levels ( ft3 [ nmol / l ] : 8.33 [ 7.02 , 12.29 ] to 4.67 [ 3.52 , 5.37 ] [ p = 0.000 ] ; ft4 [ pmol / l ] : 25.36 [ 21.34 , 28.99 ] to 16.66 [ 14.88 , 21.49 ] [ p = 0.016 ] ; and tsh [ u / ml ] : 5.80 [ 4.37 , 6.78 ] to 0.57 [ 0.19 , 1.24 ] [ p = 0.008 ] ) [ table 2 ] . reference ranges are tsh : 0.354.94 u / ml ; ft3 : 2.635.7 nmol / l ; and ft4 : 9.0019.04 pmol / l . comparison of thyroid function before and after short - term octreotide treatment ( n = 8) data were shown as median ( interquartile range ) . tt3 : total triiodothyronine ; tt4 : total thyroxin ; ft3 : free triiodothyronine ; ft4 : free thyroxin ; tsh : thyroid - stimulating hormone . safety of treatment with sst analogs was proven ; no patients discontinued treatment due to unbearable side effects although patient 4 suffered diarrhea for 2 days , for which his oct dose was reduced to 100 g one time / day for 11 days . patients histology examinations showed positive staining for tsh , thus confirming the diagnoses of tshoma [ figure 1 ] . the ihc staining for sstr2 and sstr5 was positive in the cytoplasm , and notably , greater for sstr2 than sstr5 in tshoma . all patients showed high sstr2 immunoreactivity ( irs 9 ) , yet with heterogeneous and less intense staining for sstr5 ( sstr5 irs : 5/8 high and 3/8 low ) . due to small sample size , we saw no significant relationships between the tsh suppression rate and patients age , sex , tumor size , or treatment dosage ; however , tsh suppression rate and sstr5 expression were significantly related [ p = 0.036 , table 3 ] . relationship between thyroid - stimulating hormone suppression rate and sstr5 expression ( n = 8) * low expression : 04 ; high expression : 59 . tsh suppression rate ( % ) = ( before treatment  after treatment)/before treatment  100% . analyzed with two independent sample wilcoxon rank sum test , patients with low sstr5 expression presented a significantly higher tsh suppression rate ( p = 0.036 ) . ultrastructurally , well - differentiated adenomatous thyrotrophs resemble normal ones , whereas poorly differentiated adenomas were composed of elongated angular cells with irregular nuclei , poorly developed rough endoplasmic reticulum , long cytoplasmic processes , and sparse small secretory granules ( 50200 nm ) that mostly line up along the cell membrane [ figure 2 ] . compared with the normal specimens , those from patients treated with oct showed changes ( to varying degrees ) in such tumor subcellular structure as mitochondrial swelling , dilatation of endoplasmic reticulum , vacuole formation , membrane dissolution and fracture , blurring of nucleus and organelle , cell disintegration , and thickened vascular basal lamina . characteristic apoptotic morphological changes were seen in tshoma cells after treatment with oct under transmission microscope . various types of damages were found at organelles and subcellular level , and decreased secretion activity in oct - treated tumor cells , which contribute to tumor shrinkage due to long - term actions of oct . ( b ) arrow points to untreated adenoma cells  mostly round ; exteriors are dotted evenly with black tsh secretion granules along the cell membranes . ( c ) arrow points to actively growing pituitary adenoma cell with an irregular shape , mild dysplasia , and deep staining ; its nucleus is larger than those seen in normal cells . ( d ) arrow points to mitochondria with varying degrees of swelling , transparent mitochondrial matrix , missing granules , disorderly arrangement , and fractured cristae . ( e ) electron microscope shows cell membrane missing and fractured , as well as local defect and blurred structure of cell organelles and nuclei . ( g ) arrow points to elongated rough endoplasmic reticulum , which may lead to vacuole denaturalization if extended significantly . tshoma : thyrotropin - secreting pituitary adenoma ; oct : octreotide ; tsh : thyrotropin . tshoma is a rare lesion of the endocrine system , which favors no particular age group and neither sex . tshoma and primary hyperthyroidism share some symptoms of thyrotoxicosis and diffuse enlargement of the thyroid gland . tsh secretion is autonomous and refractory to negative feedback by ths ( inappropriate tsh secretion ) . tsh itself can hyperstimulate the thyroid gland and lead to hypersecretion of t4 and t3 . the differential diagnosis of inappropriate tsh secretion includes nonthyroidal illness , medications , assay interference due to heterophilic antibodies , th resistance , and tshoma . the syndrome of pituitary resistance to thyroid hormone ( prth ) is characterized by tissue hyposensitivity to elevated levels of ft3 and ft4 in association with unsuppressed serum tsh ( signs and symptoms are subjective ) . differentiating between these forms of prth and tshomas may be difficult . as mutations in the tr gene are responsible for prth , we excluded prth by sanger sequencing . normal or elevated tsh levels with elevated ft3 and ft4 concentrations in these hyperthyroid patients provided a clue to tshoma , and the confirmed diagnoses were based on ihc results . approximately , 30% of the patients with tshoma are misdiagnosed with primary hyperthyroidism and might undergo such thyroid ablative treatment as antithyroid medication , thyroidectomy , or radioactive iodine thyroid ablation before their pituitary lesion is found . in our study , another was misdiagnosed with graves disease and treated with antithyroid drugs that worsened his thyroid functions . most patients present with mild signs of thyrotoxicosis and possible neurological features , due to pituitary mass ; they often have thyroid nodule disease . tshomas may be associated with thyroid diseases , and in diagnosing tshoma , the possibility of thyroid disease should be investigated and followed up . nmol / l ( normal range [ nr ] : 1.182.23 nmol / l ) , total thyroxine of 54.22 nmol / l ( nr : 57.92154.44 nmol / l ) , and tsh of 0.263 mu / ml ( nr : 0.474.64 mu / ml ) . central hypothyroidism was diagnosed , and postoperative hypothyroidism replacement therapy with levothyroxine 50 g once daily was begun postoperatively . tshomas are often diagnosed as macroadenomas and as plurihormonal ; they are clinically heterogeneous and difficult to treat . medically , sst analogs can control hormone hypersecretion for 90% of patients ; long - time therapy should cause significant tumor shrinkage for about 45% of patients . reportedly , tshomas that express sstrs support the use of oct for tsh - dependent hyperthyroidism . characteristic sstr expression patterns in pituitary adenomas are species- , tissue- , and subtype - specific . an sstr5 mutation in tumor tissue was reported in one acromegalic patient who was resistant to sst analog treatment , which implies a role for sstr5 in predicting response . sstr5 expression on the top of sstr2 reportedly may account for long - term suppression of hormone hypersecretion and tumor growth . additional studies with a larger number of cases are necessary to establish the exact role of sstr5 in oct therapy for tshoma . in general , sstr2 was expressed at higher levels than sstr5 in tshomas . use of sstr2- and sstr5-preferring oct and lanreotide may be a useful treatment for tshoma . all patients were significantly improved by oct treatment in our study , implying that oct can both help restore euthyroidism preoperatively and decrease the risk of perioperative thyroid storm , for better surgical outcomes . the oct test before surgery can also predict whether oct therapy would be effective if surgery alone is not curative . current studies on the effects of bromocriptine have shown shrunken cytoplasm and greater karyoplasmic ratios . changes confirmed with ultrastructural analyses included nuclear chromatin aggregation and margination , marked reduction of rough endoplasmic reticulum and golgi complexes , vascular degenerations , and necrosis and autolysis of tumor cells with dark cells and/or naked nuclear cells . electron microscopy used to elucidate the mechanism of oct in treating tshomas showed that specimens from patients who received short - term oct treatment presented ultrastructural changes at the organelle and subcellular levels that were not seen in tshomas patients who did not receive oct treatment . our main finding was that short - term preoperative oct use achieved the desired clinical outcome and biochemical euthyroidism . all these facts indicate that oct acts directly on tumor cell sstrs , causing damage to tumor cells and organelles to varying degrees , which is consistent with the existing studies . the first - generation sst analogs may serve as a medical alternative to surgical treatment , especially for patients in whom surgery is contraindicated or who present with invasive macroadenomas that render complete surgical resection difficult . the most obvious limitations of this study were the small size of our cohort , its single - institution design , and the patients rather short follow - up . optimally , a larger series with long - term follow - up is needed to determine outcomes and remission rates for oct - treated tshomas . safety and ethical concerns require that surgery should be performed only on the premise of hyperthyroidism control . after studies in the same patients and case - control study may be biased , and can also mask cause - and - effect relationships or , alternatively , suggest correlations where none exist . finally , apoptosis and necrosis measured by electron microscopy reflect only qualitative instead of quantitative analysis levels . resolving these limitations is the objective of our ongoing studies . in conclusion , oct works on pituitary adenoma cells by binding to sstr2 and sstr5 . its short - term use as part of preoperative preparation for patients with tshomas can effectively control central hyperthyroidism , increase surgical safety , and present favorable long - term effects on proliferation , apoptosis , and tumor growth . we suggest that patients with tshoma can be managed with a combination of oct therapy and subsequent surgery , and recommend immunohistochemical staining to detect sstr subtypes in all surgical specimens . this study was supported by grants from the special research fund for public welfare industry heath ( no . 201402008 ) , and the national high technology research and development program of china (  863  program ; no . this study was supported by grants from the special research fund for public welfare industry heath ( no . 201402008 ) , and the national high technology research and development program of china (  863  program ; no .
background : 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.methods: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.results:oct treatment ( median time : 7.9 days , range : 316 days ; median total dose : 1.8 mg , range : 0.94.2 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 [ u / 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.conclusions: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 .