Clinical Features And Postoperative Improvement Of The Systemic Complications In The Patients With Growth Hormone-Secreting Pituitary Adenomas:A Clinical Study

Background:The patients with growth hormone(GH)-secreting pituitary adenomas,or the acromegaly patients,are susceptible to systemic complications because of the chronic irritation of high levels of GH and insulin-like growth factor 1(IGF-1).The systemic complications contribute to a 2-fold mortality,reduced life expectation by 10 years and decreased quality of life in acromegaly patients.Till now,screening,diagnosis,treatment and follow up for these acromegaly-associated complications have not been widely adopted throughout our nation,and studies on their clinical features,postoperative reversibility and related factors are lacking.Purpose:This study aimed to analyze the preoperative clinical characteristics of the four major acromegaly-associated fatal systemic complications,including cardiovascular complications,respiratory complications,body composition and metabolism complications and skeletal complications,to re-evaluate these systemic complications at 3 months and 12 months after trans-sphenoidal surgery,and to explore the correlations between these complications and patients' clinical parameters including hormones.After achieving the above purposes,we hope to update our understanding on the nature and reversibility of these fatal complications,and provide research basis for improving the clinical prognosis for acromegaly patients.Methods:We firstly analyzed the preoperative landscape of patients' systemic complications using the retrospective method,and then launched a comprehensive study for the preoperative features and postoperative improvement of these complications using the prospective method.One-hundred-and-five indices of complications from 23 aspects of the 4 systems in acromegaly patients were involved.Multiple latest and gold-standard clinical tests were used to assess the complications.Echocardiography and cardiovascular magnetic resonance imaging were used to evaluate heart chamber diameters,ventricular volumes,myocardium thickness,myocardial fibrosis,and ventricular function.Overnight polysomnography,upper airway CT,upper airway MRI,pulmonary function test machine,and blood-gas analyzer were used to evaluate sleep apnea and hypopnea status,pharyngeal wall thickness,airway diameter and cross-section area,lung volume,pulmonary function,and blood gas condition.Body composition analyzer and metabolic analyzer were used to evaluate body compositions,total energy expenditure and basal metabolic rate.Dual-energy X-ray absorptiometry was used to evaluate bone mass density of multiple sites in the lumber spine and the hip.Age,sex,body mass index(BMI),disease duration,GH level,and IGF-1 level of patients were recorded.Correlations between these indices and the clinical features and postoperative changes of systemic complications in acromegaly patients were explored.Results:The results were divided and detailed into four parts below.1)Cadiovascular complications:(a)Diameters of atria and ventricles were extended,ventricular myocardium was thickened,diastolic function was decreased,systolic function was elevated,and great vessels were expanded.In male patients,the degrees of left ventricular(LV)hypertrophy,heart chambers enlargement and pulmonary artery expansion were greater than female patients;The frequencies of LV enlargement,LV systolic dysfunction,right ventricular(RV)enlargement,RV systolic dysfunction and myocardial fibrosis were 13%,6.5%,4.3%,2.2%and 12%,respectively.(b)Postoperatively,LV hypertrophy was reversed,left atrium structure was remodeled,and interventricular septum was initially thickened and then thinned.In male patients,degrees of cardiac changes were greater than female patients.(d)Advanced age and high BMI were two independent risk factors for myocardial hypertrophy and ventricular diastolic dysfunction.Long disease duration was the independent risk factor for great vessel expansion.The patients with normalized postoperative GH and IGF-1 levels had greater improvement of ventricular hypertrophy.2)Respiratory complications:(a)Pulmonary volume was increased,carbon dioxide partial pressure was elevated,while oxygen partial pressure was within the normal range,in acromegaly patients.The frequencies of obstructive sleep apnea hypopnea syndrome(OSAHS)and sleep hypoxia were 62.4%and 72.3%,respectively.The average times of apnea and hypopnea per hour of acromegaly patients during sleep were 17.(b)Postoperatively,the condition of pulmonary function and OSAHS in acromegaly patients did not change significantly.(c)Advanced age was the independent risk factor for OSAHS,and high BMI was the independent risk factor for sleep hypoxia.Small airway resistance was more obvious in elder acromegaly patients.Soft palate was thickened and the cross-section area of upper airway was reduced in acromegaly patients with OSAHS than those without.The thickness of soft palate and lateral pharyngeal wall was positively correlated with the severity of OSAHS,and the transverse diameter and cross-section area of upper airway were negatively correlated with the severity of OSAHS.IGF-1 level was positively correlated with the thickness of the posterior pharyngeal wall.3)Body composition and metabolic complications:(a)Adipose tissue,visceral fat index and tricep skinfold thickness were lower,protein,skeletal muscle,sclerotin,total body water,intracellular water and extracellular water were higher,and total energy expenditure and basal metabolic rate were greater,in acromegaly patients.(b)After surgery,tricep skinfold thickness was initially increased and then decreased,waistline was increased,and sclerotin,skeletal muscle,total body water and basal metabolism were decreased.(c)Changes in the body composition and metabolism differed between sexes and ages.4)Skeletal system complications:(a)Bone mass density was higher at the 1st lumber,the 2nd lumber,Ward triangle,femoral neck,femoral shaft,trochanter and total hip in acromegaly patients.(b)Z scores of the bone mass density at lumber spine was reduced to normal after surgery,but Z scores at total hip and femoral neck were increased.(c)Disease duration was negatively correlated with the Z score at lumbar spine,and IGF-1 burden was independently and negatively correlated with the Z score at lumbar spine in acromegaly patients.Conclusions:The systemic complications of acromegaly patients can be quantitatively and qualitatively assessed by multiple clinical methods.Male patients and female patients differ from each other in many parameters of the systemic complications.Along with the disease duration,systemic complications deteriorate gradually in acromegaly patients.However,this process can be stoped or be reversed after surgery,especially in patients with normalized GH and IGF-1.High BMI,high IGF-1 level,high IGF-1 burden,advanced age and long disease duration are risk factors for the worsening of complications.These factors need to be attached more importance.Encouraging the obese patients to lose weight,early recognision of the disease to lower patients' age at diagnosis and reduce their disease duration,and timely surgery to decrease hormone levels are acceptable and optimal measures to slow the worsening process of the systemic complications and improve them after surgery.This would in turm be beneficial to improve the quality of life and reduce the mortality of acromegaly patients in the long run.