I. Preface
Acromegaly (hereinafter referred to as acromegaly) is a chronic progressive endocrine disease with insidious onset, which may be several years or even 10 years old at the time of consultation. The main cause of acromegaly is the excessive production of growth hormone (GH) in the body, and more than 95% of patients with acromegaly are caused by GH-secreting pituitary adenomas. Long-term overproduction of GH can lead to excessive hyperplasia of soft tissues, bone and cartilage throughout the body, causing facial changes, hypertrophy of hands and feet, thick skin, enlarged internal organs, bone and joint lesions, and sleep apnea syndrome.
In addition, the incidence of pituitary tumor compression symptoms, diabetes, hypertension, cardiovascular and cerebrovascular diseases, respiratory diseases, and malignant tumors such as colon cancer will also increase accordingly. These metabolic disorders and complications seriously affect patients’ health and quality of life, resulting in shorter life expectancy. Clinical delays in diagnosis and treatment can significantly increase the incidence of these complications.
The Guidelines for the Diagnosis and Treatment of Acromegaly in China (2013 Edition) (hereinafter referred to as the Guidelines 2013 Edition) aim to summarize and learn from the existing experience in the diagnosis and treatment of acromegaly in China, combine the latest evidence-based evidence from home and abroad, improve the understanding of acromegaly, and advocate a standardized management model of diagnosis and treatment.
Diagnosis
The diagnosis of limbomegaly is usually made after collecting relevant clinical information, and is finally clarified by the determination of serum GH and insulin-like growth factor (IGF)-1, imaging examination and examination of related complications. Very few patients with large limbs are caused by single gene defects, such as multiple endocrine adenoma (MEN) type 1, McCune-Albfight syndrome and Carney syndrome, and further screening and diagnosis of related co-morbidities are required.
2, clinical manifestations: the limb has characteristic appearance, such as ugly face, large nose and thick lips, enlarged hands and feet, thickened skin, excessive sweating and sebaceous gland secretion, with the prolongation of the disease, there are longer head shape, protruding eyebrow arch, long oblique forehead, protruding jaw, sparse teeth and backbite, enlarged posterior occipital ridge, forehead and scalp folds, barrel-shaped chest and hunchback.
Other clinical manifestations are.
(1) Headache, visual dysfunction, increased intracranial pressure, hypopituitarism and pituitary stroke due to pituitary adenoma compression and invasion of surrounding tissues;
(2) Insulin resistance, hypoglycemic tolerance, diabetes mellitus and its acute or chronic complications;
(3) Cardiovascular system involvement: hypertension, myocardial hypertrophy, cardiac enlargement, arrhythmia, cardiac decompensation, atherosclerosis, coronary artery disease, cerebral infarction and cerebral hemorrhage;
(4) Respiratory system involvement: tongue hypertrophy, low voice, ventilation disorders, wheezing, snoring and sleep apnea, respiratory tract infections;
(5) Bone and joint involvement: synovial tissue and articular cartilage hyperplasia, hypertrophic osteoarthropathy, impaired function of hip and knee joints;
(6) Amenorrhea, lactation, infertility in women and sexual dysfunction in men;
(7) The incidence of colon polyps, colon cancer, thyroid cancer, and lung cancer may be increased.
The possibility of limbomegaly needs to be considered and screened when patients do not have obvious characteristic manifestations of limbomegaly but present with 2 or more of the following symptoms, including: new onset diabetes mellitus, multiple joint pains, new or uncontrollable hypertension, heart disease such as ventricular hypertrophy or systolic and diastolic dysfunction, fatigue, headache, carpal tunnel syndrome, sleep apnea syndrome, excessive sweating, decreased vision, colon polyps, and progressive Progressive jaw protrusion.
3. Laboratory tests.
(1) Measurement of serum GH levels: serum GH levels are continuously elevated in patients with active limbomegaly and are not suppressed by hyperglycemia. Therefore, the diagnosis of limbomegaly should not only depend on the fasting or random GH level, but also on whether the serum GH level is suppressed to normal after loading with glucose.
A fasting or random serum GH level <2.5 μg/L can be judged as normal GH; if it is ≥2.5 μg/L an oral glucose tolerance test (OGTT) is required to determine the diagnosis. The OGTT is usually performed with 75 g of oral glucose, and blood is taken at 0, 30, 60, 90 and 120 min to determine blood glucose and GH levels, and if the GH trough level in the OGTT test is <1 μg/L, it is judged to be normally suppressed. Patients with diagnosed diabetes can replace OGTT with 75g bun meal. it is recommended to use GH test with sensitivity ≤0.05μg/L.
(2) Measurement of serum IGF-1 level: GH action is mainly mediated by IGF-1 to complete, and the correlation between serum IGF-1 level and the disease activity of patients with limb big is closer than that of serum GH. Serum IGF-1 levels are elevated in patients with active limbomegaly. Since the normal range of IGF-1 levels is significantly correlated with age and gender, the results of the assay should be compared with the age- and gender-matched normal range of values (normal mean ± 2 standard deviations). When the patient’s serum IGF-1 level is higher than the normal value range matched with gender and age, it is judged as elevated serum IGF-1 level.
4, imaging: cranial MRI and CT scan can understand the size of pituitary GH adenoma and the relationship between adenoma and adjacent tissues, MRI is better than CT. high resolution thin fractionation, enhancement scan and dynamic enhancement MRI scan can improve the detection rate of pituitary microadenoma. For large adenomas, these techniques can be used to understand whether the adenoma has aggressive growth and whether it is compressing and involving the optic crossing (paracentral or subsaddle).
5. Evaluation of other pituitary functions: Blood prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) levels and their corresponding target gland functions should be measured. If the patient has significant polyuria, irritable thirst, and excessive drinking, posterior pituitary function should be evaluated.
6.Visual acuity and visual field examination: observe the visual field changes before treatment, and also as one of the evaluation indicators of treatment effect.
7, the diagnosis of limb large complications: after the qualitative diagnosis of limb large patients should be blood pressure, blood lipids, electrocardiogram, cardiac ultrasound, respiratory sleep function testing; according to clinical manifestations can choose thyroid ultrasound, colonoscopy and other tests. According to the patient’s clinical manifestations, laboratory tests and imaging examinations, the diagnosis of limb enlargement should be made through comprehensive analysis, and a clear judgment should be made on the patient’s disease activity, acute and chronic complications of each system and the control of disease activity after treatment.
III. Treatment
1.Treatment goals of limb big
There are five treatment goals as follows.
(1) To control serum GH level to random GH <2.5μg/L and OGTT GH trough value <1μg/L;
(2) To bring serum IGF-1 levels down to within the age- and sex-appropriate normal range;
(3) Eliminate or shrink pituitary tumors and prevent their recurrence;
(4) To eliminate or reduce clinical symptoms and comorbidities, especially cardiovascular, respiratory and metabolic, and to effectively monitor comorbidities;
(5) Preserve pituitary endocrine function as much as possible, and patients with existing hypopituitarism should do the corresponding target gland hormone replacement therapy.
Random GH values <2.5 μg/L and OGTF GH trough values <1 μg/L after limbic major treatment; the patient survival rate is similar to that of the normal population. Surgery, radiotherapy and pharmacotherapy are all options to achieve the above treatment goals. However, to maximize the efficacy and preserve pituitary function at the same time, each of these 3 treatment methods has its own advantages and disadvantages; therefore, an individualized treatment plan should be designed for each patient.