| Growth hormone-type pituitary adenoma is a common functional tumor in pituitary adenoma.It originates from anterior pituitary lobe.It accounts for 20%-30%of pituitary adenoma.Besides the symptoms of tumor compression such as headache,vomiting,blurred vision and visual field defect,it also cause endocrine and metabolic disorders due to long-term excessive secretion of growth hormone(GH)and insulin-like growth factor(IGF-1),which usually occur after puberty,with soft tissue,bone,visceral hypertrophy as the main characteristics.Cardiac disease is common in patients with GH adenoma.GH adenoma with cardiomyopathy is a special type of cardiomyopathy in patients with acromegaly.Long-term excessive secretion of GH,IGF-1 can lead to cardiac hypertrophy,cardiac enlargement,arrhythmia,cardiac dysfunction and other cardiac structural and functional abnormalities,which may seriously affecting health and quality of life of patients,and even causing death.Therefore,the first part of this paper aims to explore its clinical efficacy through clinical case retrospective analysis.Although pituitary adenomas originate from the anterior pituitary lobe,all subtypes have their own characteristics,the clinical manifestations vary greatly,ranging from acromegaly,gigantism or Cusing's disease,to amenorrhea,lactation or sexual dysfunction.There are similarities as well as differences,specific pathogenesis of various types still remain uncertain.Growth hormone-type pituitary adenoma has a hidden pathogenesis and may cause great harm.the specific mechanism of the occurrence and development of growth hormone adenoma is still unclear.Present research mainly focus on the signal pathway of external environment promoting tumor cell growth.Notch signaling pathway is a highly conserved signaling pathway that mediates cell-to-cell signaling.The precise regulation of cell proliferation,differentiation,phagocytosis and apoptosis through Notch signaling pathway is crucial to the normal development of most organs and tissues.Nowadays,Notch 1,Notch 3 and Hesl are the most important and key signaling molecules in Notch signaling pathway.The expression and significance of receptor Notchl,Notch3 and downstream target gene Hes1 in growth hormone pituitary adenoma are not much studied.Therefore,the related basic and clinical research will be carried out.Part one Clinical treatment efficacy of GH pituitary adenoma complicated with cardiomyopathyobjectivewe retrospectively analyzed the clinical features,endocrinological level and imaging features of GH pituitary adenoma with cardiomyopathy,and the treatment and clinical efficacy were discussed.Method86 patients with growth hormone pituitary adenoma complicated with cardiomyopathy who underwent surgery from January 2010 to December 2017 in the Department of Neurosurgery,First Affiliated Hospital of Suzhou University and Anqing Affiliated Hospital of Anhui Medical University were analyzed.Pituitary hormone,brain magnetic resonance imaging,biochemical assessment of cardiac function and echocardiography were performed before and after operation.The serum levels of growth hormone,insulin-like growth factor-1,left ventricular inner diameter of end-diastolic(LVIDd),interventricular septal thickness(IVST),left ventricular posterior wall thickness(LVPWT),left ventricular ejection fraction(EF),mitral valve flow spectrum(E/A ratio)before and after operation were measured noninvasively.Results were compared.Results1.Of the 86 cases,there were 23 cases of micro adenoma,27 cases of large adenoma,and 36 cases of giant adenoma.There were 28 cases of invasive adenoma and 58 cases of noninvasive adenoma.Total resection was performed in 51 cases,subtotal resection in 25 cases,partial resection in 8 cases and partial resection in 2 cases.2.The clinical symptoms of most cases were improved after operation.The long-term follow-up cure rate was 39.17%,and the remission rate was 77.29%.The levels of pituitary hormones were significantly decreased.Serum level of mean GH(31.23±3.29)ng/ml,mean IGF-1(782.6±38.7)ng/ml before operation,and mean GH(12.07±1.25)ng/mland mean IGF-1(126.8±17.5)ng/ml after operation,both were significantly different before and after operation(P<0.01).3.Cardiac function improved significantly after operation.The serum levels of atrial natriuretic peptide B and troponin were significantly lower than those before operation.The mean levels of BNP(376.3±18.1)pg/ml,Tn(38.7±5.2)pg/mlbefore operation,BNP(86.2±7.5))pg/ml and Tn(7.31±1.8)pg/ml)after operation both were significantly different before and after operation(P<0.05).At the same time,echocardiography showed that the values of LVIDd,IVST,LVPWT,EF and E/A were significantly improved compared with those before operation(P<0.05).conclusion1.Patients with growth hormone pituitary adenoma with cardiomyopathy can achieve satisfactory results through operation.2.Surgery can excise the tumor,control the hormone level,and improve the cardiac structure and function.Part two Expression and significance of Notchl and Notch3 protein in GH adenomaobjectiveThe expression levels of Notch 1,Notch 3 protein and mRNA in growth hormone pituitary adenoma were detected by immunohistochemistry,Western Blot and Real Time PCR,with the aim to explore whether Notch signaling pathway is involved in the pathogenesis of growth hormone pituitary adenoma.Method38 clinical specimens of somatotrophic pituitary adenomas were collected,21 nonfunctional pituitary adenomas and 25 prolactin pituitary adenomas were also collected.The expression levels of Notchl,Notch3 protein and mRNA in the control group were detected by immunohistochemistry,Western Blot and Real Time PCR.results1.Immunohistochemistry showed that Notch1 and Notch3 proteins were expressed in various types of pituitary adenomas to varying degrees.Notchl and Notch3 proteins were strongly positive in somatotrophic pituitary adenomas,but slightly expressed in nonfunctional pituitary adenomas and prolactin pituitary adenomas.2.The expression of Notchl,Notch3 protein and mRNA was the highest in the growth hormone pituitary adenoma group with Western Blot?Real Time PCR,but the expression was low in PRL adenoma and NPA adenoma,the difference was statistically significant(P<0.05).conclusion1.Notchl and Notch3 were expressed differently in different types of pituitary adenomas,the expression in growth hormone type pituitary adenomas was the highest.2.Notchl and Notch3,as important components of Notch signaling pathway,play an important role in the occurrence and development of growth hormone-type pituitary adenoma.Part three Expression and significance of Notch signal target gene Hesl in growth hormone adenomaobjectiveTo further confirm the role of Notch signaling pathway in growth hormone pituitary adenoma,the transcriptional mRNA and protein expression levels of Notch 1 and Notch 3 target genes Hes1 in growth hormone pituitary adenoma were detected.MethodWestern Blot and Real Time PCR were used to detect the expression of Hes1 transcription protein and mRNA in growth hormone pituitary adenoma tissues,and the expression levels of Hes1 in nonfunctional adenoma and prolactinoma tissues were compared.Results1.With Western Blot method,the relative expression of Hes1 protein was(1.025±0.121)in growth hormone adenoma,(0.426+0.018)in non-functional adenoma group and(0.512+0.033)in prolactinoma group.The differenct was significant with the highest in growth hormone adenoma and the lowest in non-functional adenoma group(P<0.05).2.With Real-time PCR method,expression of Hes1 gene transcription mRNA in GH adenomas was(0.736±0.032),(0.428±0.045)in prolactinomas and(0.352±0.028)in non-functional adenomas,the difference was statistically significant(P<0.05).conclusions1.The expression of Hesl gene transcription was the highest in GH adenoma.Notchl and Notch3 could promote Hes1 gene transcription after activation.2.Hesl gene plays an important role in the growth hormone pituitary adenoma,regulating the occurrence and development of the tumor,it is a promising molecular target for the treatment of growth hormone pituitary adenoma. |
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