A Study Examining the Peri- and Post-operative Dynamics of the GH-IGF-1 Axis in Subjects With Acromegaly During the First Year After Surgical Resection
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Correlation of normalization of Growth hormone postoperatively with 1 year remission rates
研究概览
简要总结
Acromegaly is a rare disorder characterized by excessive production of growth hormone most often by a pituitary adenoma. A pituitary adenoma is a tumor, almost always benign or non-cancerous, that grows on the pituitary, a small gland located at the base of the brain. Treatment of acromegaly usually involves surgery, medication, or radiation, but can involve a combination of these three treatments.
Subjects for this study will be recruited if they are:
- Adults, male or female, between the ages of 18-90.
- Have been diagnosed with acromegaly, based on elevated levels of growth hormone, IGF-I (a hormone made in response to growth hormone), and a pituitary adenoma visualized on an MRI.
- Patients would have already agreed to have their acromegaly treated with surgery prior to study entry.
Subjects will have measurements of growth hormone using an oral glucose tolerance test (OGTT), IGF-I, free IGF-I and levels of IGF binding proteins at four time points after their pituitary surgery: Day 1, Day 42 (6 weeks), Day 84 (12 weeks), and day 365 (1 year). Subjects will also have an MRI of the pituitary done at 12 weeks and 1 year. OGTT and IGF-I are routinely measured to assess whether or not a person is cured of their acromegaly. An MRI of the pituitary is routinely done at 12 weeks and 1 year after surgery to assess the results of surgery. Free IGF-I and IGF binding proteins are not routinely measured after surgery, but are being done to see if they relate more strongly to disease activity than IGF-I and growth hormone.
OGTT and the IGF-I binding proteins are not routinely measured on the day after surgery, but are being done to examine the predictive ability of these tests at a very early time after surgery. Data obtained from these tests will be compared to the data gathered at the 1 year time point.
IGF-I and growth hormone will be measured by a commercial clinical lab, Quest Diagnostics, for clinical decision-making at the time of service. IGF-I and growth hormone will also be measured using other methods to attempt to investigate the variability of these hormones when different assays are used.
详细描述
Acromegaly Overview
Acromegaly is a rare, insidious disorder characterized by excessive secretion of growth hormone (GH) almost always from a pituitary adenoma. (Melmed NEJM 1990) Excess GH secretion in turn leads to increased levels of insulin-like growth factor-I (IGF-I), which is primarily responsible for the clinical manifestations of the disease. Features of acromegaly are numerous and include acral and soft tissue growth, arthropathy, excessive sweating, glucose intolerance, and carpal tunnel syndrome. Many patients have cardiomyopathy and hypertension and the diagnosis of acromegaly carries with it an excessive morbidity and mortality related to cardiovascular disease.
Therapy
The goals of therapy include management of the pituitary mass, control of symptoms of GH excess, improvement in long term morbidity and mortality associated with GH excess, and biochemical normalization of IGF-I and GH secretion without disruption of normal anterior pituitary function. Treatment for acromegaly has generally included one or a combination of three modalities, surgery, radiation and medication.
Classically, surgery has been the primary treatment modality with surgical cure being dependent upon pituitary tumor size and the surgical expertise of the surgeon. In experienced hands, transsphenoidal surgical resection of pituitary adenomas is a low risk procedure with few peri-operative or long term complications. Published cure rates for microadenomas and macroadenomas range from 39-91% and 12-71%, respectively. (Melmed S, Kleinberg DL, Williams Textbook of Endocrinology.) Subjects who are not controlled with surgery alone require additional therapy in the form of radiation or medication.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or Female age 18-90
- •Diagnosed with acromegaly from a pituitary adenoma visualized by MRI, and with elevated IGF-1 levels compared to age and gender matched control values and nadir GH response to OGTT>1mg/L
- •Having already agreed to undergo surgical resection of their pituitary adenoma prior to study entry
- •Must provide informed consent
排除标准
- •Inability to complete the protocol due to intercurrent medical or psychiatric illness
- •Pregnant or breastfeeding
- •Use of insulin
- •Use of estrogen, progesterone, testosterone or thyroid hormone will be allowed as long as the dose is stable during the study
结局指标
主要结局
Correlation of normalization of Growth hormone postoperatively with 1 year remission rates
时间窗: 1 year
The primary endpoint will be to assess if a higher proportion of subjects in group 2b (low normal IGF-1 and elevated GH) normalize their GH nadir responses to OGTT than subjects in group 2a (high normal IGF-1 and elevated GH) at either the three month time point or 12 month time point.
次要结局
- Predictor of remission(1 year)
- Assay variability of IGF-1 and GH(1 year)
研究者
Odelia Cooper
Associate Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism
Cedars-Sinai Medical Center