Overview
Growth Hormone (GH) is essential for maintaining fat, muscle, bone, and energy balance. Adult Growth Hormone Deficiency (GHD) affects about 0.3% of adults. GHD, common post-pituitary tumor surgery or radiotherapy, disrupts lipid metabolism, increasing triglycerides and low-density lipoprotein cholesterol while decreasing high-density lipoprotein cholesterol. This is especially severe in GH adenoma patients, whose lipid metabolism issues worsen post-surgery, increasing the risk of atherosclerosis. Fat accumulates in the liver first, making liver fat content a key early indicator of metabolic disorders, which can lead to diabetes and atherosclerosis. Early intervention is crucial as liver fat deposition in Nonalcoholic Fatty Liver Disease (NAFLD) is reversible.
Recombinant human growth hormone can treat GHD-related lipid metabolism disorders, but research on its effects on liver fat in post-surgery GH adenoma patients is limited. We plan to treat these patients with 1 mg/week of recombinant human growth hormone for 24 weeks, aiming to normalize their insulin-like growth factor-1 levels. Liver fat content changes will be measured using proton magnetic resonance spectroscopy (1H MRS) and Fibroscan. We will also evaluate changes in weight, BMI, waist circumference, fasting blood glucose, blood lipids, and other metabolic factors to assess treatment efficacy and safety.
Zhongshan Hospital, affiliated with Fudan University, performs over 300 pituitary tumor surgeries annually, including 100 GH adenoma cases. The hospital has extensive experience and can enroll 40 patients. The Endocrinology Department excels in evaluating lipid metabolism disorders in NAFLD using non-invasive methods. As a major hospital in Shanghai, it has ample patients to meet study requirements. We have established detailed exit criteria and rescue plans to address potential adverse events during the study.
Description
Growth Hormone (GH) is an important hormone secreted by the pituitary gland and is essential for maintaining normal fat, muscle, bone content and energy balance in the body. The prevalence of adult Growth Hormone Deficiency (GHD) is approximately 0.3% in adults. When human growth hormone is deficient, lipid metabolism is most prone to disorder. The study found that the blood triglyceride and low density lipoprotein cholesterol levels increased in GHD patients, and the blood high density lipoprotein cholesterol levels decreased. GHD is most common in patients with pituitary tumor after surgery or radiotherapy, especially in patients with GH adenoma after surgery. The lipid metabolism disorder is the most serious among all GHD patients, because the excessive growth hormone before surgery has caused the patients to be in a state of severe lipid metabolism disorder, and after the patients are directly converted to a state of growth hormone deficiency after surgery, the lipid metabolism disorder is the most serious. The disorder of lipid metabolism will progress from the poor to the worse side, and long-term follow-up shows that it is more likely to develop secondary atherosclerotic diseases after surgery. Current studies have shown that when abnormal lipid metabolism occurs in GHD patients, fat will first accumulate in the liver. Therefore, compared with changes in blood lipid metabolism indexes and body components, changes in liver fat content can detect abnormal lipid metabolism in patients earlier. Liver fat deposition, as the initiating factor of systemic metabolic disorders, is involved in the occurrence and development of diabetes and atherosclerotic diseases. Currently, it is considered that the fat deposition in Nonalcoholic Fatty Liver Disease (NAFLD) is reversible. Therefore, it is particularly urgent to conduct very early intervention for GHD patients with pituitary GH adenoma after operation to block the occurrence of subsequent metabolic adverse events.
It has been reported that recombinant human growth hormone can be used in the treatment of abnormal lipid metabolism due to GHD, but at present, there is a lack of relevant studies on recombinant human growth hormone in the treatment of abnormal lipid metabolism in patients with pituitary GH adenoma after surgery, especially the study on the change of liver fat content. We intend to apply recombinant human growth hormone dose of 1mg/W(6IU is 1mg) to GH adenoma patients with GHD and NAFLD after GH adenoma surgery, so as to increase the insulin like growth factor-1 of patients to the median of normal level of peers, and the treatment time is 24 weeks. After treatment, the changes of liver fat content at baseline and 24 weeks after intervention were measured by proton magnetic resonance spectroscopy (1H MRS) and Fibroscan liver hardness. The changes of metabolic parameters (body weight, body mass index (BM), waist circumference, fasting blood glucose, blood lipids, high iron content and other metabolic related inflammatory factors) before and after recombinant human growth hormone treatment were evaluated. In order to evaluate the efficacy and safety of recombinant human growth hormone in the treatment of GHD-induced NAFLD patients with abnormal lipid metabolism after GH adenoma surgery, and propose a suitable treatment method for people with abnormal lipid metabolism due to GHD after GH adenoma surgery, providing a direct basis for establishing a standardized clinical treatment path in the next step.
The Department of Neurosurgery of Zhongshan Hospital Affiliated to Fudan University carries out more than 300 cases of various types of pituitary tumors every year, including more than 100 cases of pituitary GH adenoma. It has developed a multidisciplinary joint clinic for pituitary tumors earlier in China, and has rich experience in the diagnosis and treatment of pituitary tumors. It can meet the needs of 40 enrolled cases. The Department of Endocrinology has been committed to the evaluation of lipid metabolism disorders in nonalcoholic fatty liver for a long time. At present, ultrasound and imaging are proficient in the non-invasive methods of determining liver fat such as MRS Liver hardness test. Our hospital is a large Class III hospital in Shanghai, with a wealth of pituitary tumor patients, which can meet the enrollment requirements of subjects, and the endocrinology department can complete the assessment of lipid metabolism disorder. We jointly developed detailed exit criteria and rescue plans. The adverse events that may occur during the study were defined and treated in detail.
Eligibility
Inclusion Criteria:
- Have fully understood the informed consent and signed the informed consent;
- Age: 18-60 years old;
- Patients diagnosed with adult growth hormone deficiency (AGHD) (GH stimulation test: GH peak ≤5ug/l or organic hypothalamic-pituitary disease ≥3 pituitary hormone deficiency with IGF-1 < -2SD)
- Patients with pituitary growth hormone adenoma proved pathologically after surgery
- Anterior pituitary hormone supplementation (except growth hormone)
- The liver fat content was more than 11% after six months to two years of operation by proton magnetic resonance spectroscopy (1H MRS).
- Those who have not taken lipid-regulating drugs (statins, Bates);
- Blood pressure <150/95mmHg, did not take any antihypertensive drugs;
Exclusion Criteria:
- Have any of the following liver disease history: chronic hepatitis, cirrhosis, liver cancer, autoimmune liver disease, alcoholic liver disease, hereditary liver disease
- Significant abnormal liver function: ALT or AST≥ 2 times the upper limit of normal; HBsAg (+), and/or HCV-Ab (+);
- Patients with serum creatinine value ≥1.5mg/dL (133umol/L);
- Patients with severe heart disease (patients with a history of myocardial infarction and heart failure and/or severe arrhythmia);
- Patients with severe infection, other operations within 6 months, or severe trauma;
- Alcohol consumption (alcohol): male ≥140g/week; Female ≥70g/week;
- Poorly controlled diabetic patients: HbA1c >9.5% within three months; Or use hypoglycemic drugs that may affect liver histopathology, including pioglitazone, GLP-1, and DP-4 inhibitors;
- Patients with allergy or intolerance to the same drug used in the trial;
- In the next 1 year, there are pregnancy plans or breastfeeding patients or patients with mental disorders;
- Patients who have participated in other clinical trials within 24 weeks.