The outcome of TSHoma from a tertiary care institute in India
Aditya DuttaNimisha JainAshutosh RaiRahul GuptaSivashanmugam DhandapaniAnil BhansaliBishan Das RadotraChirag AhujaPinaki Dutta
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Abstract:
Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is the rarest functioning pituitary adenoma.A retrospective analysis of eight patients of TSHomas to highlight the presentations, diagnostic challenges, and treatment outcomes.Median age at diagnosis was 42 years, median latency to diagnosis was 2.5 years, and thyrotoxic and compressive symptoms were the most common presenting symptoms. At presentation, three cases were plurihormonal, six cases were on medical treatment including thyroxine, and two cases were incidentally discovered. Imaging revealed macroadenoma in all cases. Seven cases underwent pituitary surgery, after which three achieved remission. Another case entered remission after adjunctive radiotherapy. Thyrotropin (TSH) immunostaining was demonstrated in six out of seven adenomas.TSHoma is a rare functioning pituitary tumor with both silent and symptomatic presentations. Diagnosis can be established with biochemical and imaging features, even without dynamic tests.Keywords:
Tertiary care
Presentation (obstetrics)
Immunostaining
Pituitary Tumors
下垂体腺腫の枠組みについて著者らは,1)GH-PRL-TSH細胞グループ,ACTH細胞グループ,ゴナドトロピン細胞グループに大別され,2)各グループの枠を超えた複数のホルモンが1つの腺腫に共存する可能性はきわめて低く,3)各グループにはホルモン過剰症状を呈する腺腫とそれを欠く腺腫とがある,と考えている.2004年秋に刊行される予定の新WHO分類はKovacsらの病理組織学的分類を基盤にしており,分類項目はGH producing adenoma, PRL producing adenoma, TSH producing adenoma, ACTH producing adenoma, gonadotroph adenoma, null cell adenoma, unusual plurihormonal adenoma に分けられている.GH producing adenomaはdensely granulated somatotroph adenoma, sparsely granulated somatotroph adenoma, mixed somatotroph-lactotroph adenoma, mammosomatotrophadenoma, acidophil stem cell adenoma の5型が細分され,後3者はGHとPRLをともに産生するタイプである.ACTH producing adenomaの亜型としてsilent ACTH producing adenoma とCrooke's cell adenoma が示され,前者をさらに電顕的にsubtype 1とsubtype 2 の2つのタイプに区別している.Gonadotroph adenoma はほとんどが臨床的に非機能性の腺腫であるが,下垂体腺腫手術例の約30%を占め,最近では最も頻度が高いタイプである.ナルセル腺腫は下垂体ホルモンあるいは転写因子がすべて陰性の腺腫と定義された.ナルセル腺腫の亜型としてoncocytomaが含まれている.unusual plurihormonal adenoma の1つとしてsilent subtype 3 adenoma があり,臨床的にはプロラクチノーマに類似し,GH, PRL,TSHがしばしば陽性である.下垂体癌は頭蓋外ないし髄膜へ転移播種した腫瘍と定義され,生命予後はきわめて不良である.転移病巣では多数の核分裂像,細胞異型,壊死巣などが認められるが,初日原発巣ではこれらの悪性所見に乏しい.転移の可能性を推測しようとする試みの1つとして,核分裂像とP53蛋白陽性細胞の存在.Ki-67標識率3%以上を指標にした「異型腺腫」が記載されている.
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Objective: Pituitary lesions cause morbidity and mortality in all age groups due to their hormonal hypersecretion, its mass effects, and post-surgery complications. The present study determined the frequency of functional and non-functional pituitary adenomas.
Materials & Methods: The study included patients (n = 114) presenting with functional and non-functional pituitary adenoma. Pituitary adenomas were diagnosed based on MRI brain with contrast and the size of the tumor was noted a tumor having a size of 10 mm or more was labeled as macro adenoma and a tumor having a size less than 10 mm was labeled as microadenoma. Pituitary adenomas were stratified among age, gender, duration of symptoms, types of adenomas, types of functional adenoma, and type of the tumor on a size basis.
Results: Most of the patients had TSH- secreting adenoma (21.9%). 52.6% were found with microadenoma and 47.4% had macro adenoma. Patients with functional adenoma were 30.7% and with non-functional adenoma 32.5% were male while patients with functional adenoma were 26.3% and with non-functional adenoma 10.5%were female (p = 0.018). Patients with functional adenoma (43.9%) and non-functional adenoma (8.8%) were found to have microadenoma, whereas patients with functional adenoma (13.2%) and non-functional adenoma (34.2%) were found to have macroadenoma (p = 0.000). Patients with functional adenoma having a duration of symptoms below 1 year were 11 (9.6%), 1 to 3 years were 25 (21.9%), 17 (14.9%) were 4 to 6 years, and 12 (10.5%) above 6 years duration of symptoms.
Conclusion: Patients with pituitary adenomas should be diagnosed early to receive successful therapy.
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The aim of this study was to detect the expression of cold-inducible RNA-binding protein in pituitary adenoma and to determine its effects on tumor recurrence.We collected a total of 60 post-op samples collected from pituitary adenoma patients (including 20 cases of invasive pituitary adenoma, 20 cases of non-invasive adenoma, and 20 cases of non-invasive recurrent adenoma) admitted in our hospital. Both protein and mRNA levels of CIRP in 3 types of pituitary adenoma samples were quantified by Western blotting and real-time PCR, respectively.Western blotting revealed significantly elevated CIRP expression levels in invasive pituitary adenoma compared to non-invasive tumors, with statistical significance (p<0.05). Recurrent pituitary adenoma expressed significantly higher CIRP levels compared to non-recurrent tumors (p<0.05). Real-time PCR for CIRP mRNA obtained consistent results: transcript levels were significantly higher in invasive pituitary adenoma compared to non-invasive adenoma (p<0.05); recurrent adenoma also had significantly higher CIRP mRNA levels compared to non-recurrent tumors (p<0.05). Among all 3 types of pituitary adenoma, recurrent tumors had the highest levels of CIRP mRNA and protein.The expression of CIRP in pituitary adenoma is closely related with tumor proliferation and invasion, and its significantly elevated expression level indicates post-op recurrence.
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Objective To assess the effect of endonasal transsphenoidal surgery for pituitary adenoma. Methods 20 patients underwent pituitary adenoma resection by endonasal transsphenoidal approach. There were 8 patients with micro adenoma(10 mm), 8 patients with little adenoma(10～20 mm), 3 patients with big adenoma(20～30 mm) and 1 patients with macro adenoma(30 mm). The pathologic diagnosis is PRL adenoma (9 cases), GH adenoma (6 cases) and ACTH adenoma (5 cases). Results All patients were followed up for 2 to 10 months without complication. The clinical symptoms improved postoperatively. Conclusion It is an effective, less trauma surgery for pituitary adenoma resection by endonasal transsphenoidal approach without or with less complications.
Transsphenoidal surgery
Endoscopic endonasal surgery
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Objective To study clinical,biological behavior,immunohistochemical and endocrinological characters of pituitary adenoma. Methods A total of 128 cases of pituitary adenoma were investigated clinically.PRL,GH,ACTH,TSH,LH and FSH were examined by ABC immunocytochemical method. Results All the cases of pituitary adenoma classified by immunohistochemistry were as follows:17.2% were nonhormonal adenoma,37.5% were monohormonal adenoma,including 7 cases of prolactin adenoma,12 cases of growth hormonal adenoma,14 cases of adrenocorticotropic hormonal adenoma,15 cases of other hormonal adenoma,25.0% were double hormonal adenoma and 20.3% were multiple hormone-expression adenoma including three kinds of hormones and more. Conclusion Immunohistochemical results are not always consistent with clinical manifestations.Other mechanism may participate into the hyperprolactinemia of non-prolactin-expression pituitary adenoma apart from compression effect of tumors.Based on the results of immunohistochemistry,it can conclude that pituitary adenoma is of diversity and complexity.
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Pituitary tumors constitute around 15-20% of intracranial tumors. The understanding of the molecular mechanisms of tumorigenesis and the functional regulation of pituitary adenoma has greatly advanced in the last decade. The current WHO classification scheme of pituitary tumors reflects this progress on tumor biology knowledge, and embraces the most widely utilized diagnostic methods of evaluation of these lesions. The present chapter highlights the different aspects of the tumor diagnosis and reviews the classification of pituitary tumors.
Pituitary Tumors
Classification scheme
Pituitary neoplasm
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Objectives: Invasiveness is the feature of malignant tumor,which some pituitary adenomas have.The DNA ploidy and the proliferation ability of invasive adenoma cells were studied. Methods: Pituitary adenoma cells were assayed by Flow Cytometer and Image Cytometer. Results: Invasiveness of pituitary adenoma correlated with the proportion of abnormal DNA ploidy cells. Conclusions: From the DNA ploidy of invasive pituitary adenoma,we could conclude that invasive pituitary adenoma developed malignantly.
Pituitary Tumors
Pituitary neoplasm
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Objective
To investigate the correlation between the uptake of 68Ga-DOTATATE in pituitary adenoma and clinical parameters such as hormonal hypersecretion, and to evaluate the curative effect with 68Ga-DOTATATE imaging after octreotide therapy in patients with growth hormone-secreting adenoma (GH adenoma).
Methods
A total of 34 patients (15 males, 19 females) with pituitary adenoma were recruited, including 5 adrenocorticotropic hormone-secreting adenoma (ACTH adenoma), 17 GH adenoma, and 12 non-functioning adenoma (NF adenoma). In the 17 patients with GH adenoma, there were 13 patients treated by octreotide intramuscular injection 3 times with a total dose of 60 mg for 3 months. The finial diagnosis was based on histology. 68Ga-DOTATATE imaging was performed, and SUVmean, tumor volume and density index (DI) were recorded in all patients. The DI was the ratio of tumor SUVmean to tumor volume. The effective therapy was defined as more than 50% of hormonal suppression or more than 20% of tumor shrinkage. Non-parametric Mann-Whitney u test was used.
Results
NF adenoma showed greater tumor volume than secretory adenoma, ((9.10±7.00) cm3vs (2.92±1.60) cm3,u=43.0, P<0.05), whereas DI of secretory adenoma was higher than that of NF adenoma (7.16±4.52 vs 1.08±1.40, u=48.5, P<0.05). Additionally, DI was significantly higher(3.55±0.91 vs 1.38±0.69, u=2.0, P<0.05) in patients (n=8) with effective treatment than that in patients without effective treatment (n=5).
Conclusion
68Ga-DOTATATE may be a useful probe for PET imaging in patients with pituitary adenoma, and may be valuable for predicting the therapeutic effect of somatostatin analog treatment.
Key words:
Pituitary neoplasms; Gallium radioisotopes; Tomography, emission-computed; Tomography, X-ray computed; DOTATATE
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Objective
To explore the pathogenesis of invasive pituitary adenomas, and to improve the effect of clinical treatment.
Methods
15 pairs of invasive pituitary adenoma tissues and noninvasive pituitary adenoma tissues were selected from 114 specimens collected and the Id1 gene expression and Id1 protein expression in invasive pituitary adenoma tissues and noninvasive pituitary adenoma tissues were tested by quantitative RT- PCR,Western blot and immunohistochemical methods; Then small interfering RNA(siRNA) was used to interfer Id1 gene expression in NQ - 04 cells.
Results
The Id1 gene expression in invasive pituitary adenoma tissues was significantly higher than that in noninvasive pituitary adenoma tissues(n= 15,t= 2.725,P= 0.013); The migration of pituitary adenoma cells interfered was significantly reduced.
Conclusion
The invasive pituitary adenoma tissues has high level of Id1 gene expression, which may be correlated with its invasion. And Id1 is expected to become a biological marker of diagnosis and determination in the prognosis of pituitary adenoma.
Key words:
Inhibitor of DNA binding 1(Id1)gene; Pituitary adenoma; Invasion
Pituitary neoplasm
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Objective To study the related factors of post-operative recurrence of nonfunctional pituitary adenoma.Methods The clinical data,therapeutic methods and following-up outcome of 113 patients of(nonfunctional) pituitary adenoma were recorded and statistically analyzed with logistic regression model.Results Recurrence after surgery was related to the invasion of adenomas,the resection range and the adjunct therapy after surgery.All these factors showed significant difference(P0.05).The recurrent risk of invasive adenoma was higher than that of non-invasive adenoma.The high risk of recurrence also presented in patients with non-total (resection) or patients without post-operative adjunct therapy.According to the standard(regression) coefficient,the factor of the adjunct therapy played the most important role in reducing the recurrence rate of nonfunctional(pituitary) adenoma.The factor of the total resection after surgery was secondary and the factor of the invasion of adenoma was least.Other factors such as age, sex and the size were unrelated to the recurrence of nonfunctional pituitary adenoma.Conclusion Many factors contribute to the post-operative recurrence of(nonfunctional) pituitary adenoma.Clinical surgeons should be acquainted with them correctly,so comprehensive therapy can be taken to reduce the recurrence of nonfunctional pituitary adenoma.
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