Acromegaly
Introduction
Introduction to acromegaly Acromegaly is mainly caused by pituitary GH tumor or pituitary GH cell hyperplasia and excessive secretion of growth hormone (GH). Prolonged excessive secretion of GH causes giant disease before the closure of the epiphysis, and causes acromegaly after closure of the epiphysis. Limb finger hypertrophy is insidious and slow progress. It is characterized by hypertrophy of bone, soft tissue and internal organs. It is characterized by facial changes, hypertrophy of the toes at the ends of the hands, thick skin, enlarged internal organs, and bone and joint lesions. basic knowledge The proportion of illness: 0.0003% Susceptible people: no specific population Mode of infection: non-infectious Complications: diabetes, hypertension, arrhythmia, sleep disorders, diabetes insipidus, osteoporosis, optic atrophy
Cause
Cause of acromegaly
Pituitary tumors (55%):
The disease is caused by excessive secretion of growth hormone in the pituitary gland caused by pituitary tumors. The GH secretion has obvious circadian rhythm. The peak of adult secretion is mostly at night. The main role of GH is to promote the growth and promotion of bone tissue, muscle, connective tissue and viscera. DNA, RNA synthesis, anti-insulin promotes sodium retention, and can stimulate the body to secrete some peptides, such as growth mediators. GH has a dual role of insulin-like and anti-insulin-like effects on glucose metabolism. The former occurs earlier and later. It occurs later; GH also has a direct effect on islet B cells. About one-fourth of patients can have diabetes at the same time. Somatomedin (SM) is derived from the liver, and can affect the synthesis of DNA and RNA proteins. Increased cartilage growth, growth factors A, B and C, can mediate the growth effect of GH on bone, and growth hormone A (SmA) can stimulate collagen and non-collagen synthesis, interleukin C (SmC) It stimulates collagen synthesis in osteoblasts, and BGP acts as a result of GH acting through SmA.
Hyperplasia of pituitary GH cells (35%):
Hyperplasia of pituitary GH cells leads to a strong secretion of growth hormone (GH), and excessive GH can accelerate bone formation and maturation and promote bone growth. Can also cause acromegaly.
Prevention
Acromegaly prevention
Primary prevention
Giant disease and acromegaly are still more common in pituitary tumors. They not only affect bones, but also affect various organs in the body. Late complications are serious and serious. The focus of prevention of this disease is early It is found that, in suspicious patients with significant growth and increase in growth, blood GH concentration should be detected regularly and early, and the skull or saddle X-ray or pituitary CT examination should be performed to diagnose early.
2. Secondary prevention
(1) Early treatment: especially for pituitary ablation in the early stage before the disease or the main organs are not affected. Especially the microsurgery is the first choice. The success rate is high. About 80% of the patients have normal GH secretion after surgery. In particular, if the tumor is less than 2 cm, if the tumor is more than 2 cm in diameter, 60% to 70% of the postoperative GH will return to normal.
(2) Radiation therapy: The radiotherapy of pituitary tumors is 4500-5000 rad1, and the effective rate is 60%-80%. However, the GH level recovers slowly. It takes several years to be obvious. Radiotherapy also affects the function of pituitary. Recently, the pituitary gland is used. Adenoma is a fast-acting heavy particle radiotherapy, which is effective after 2 years of treatment, and the incidence of pituitary hypofunction is about 40%.
(3) Medical treatment: drug treatment is often used as an auxiliary treatment for surgery or radiotherapy. Commonly used drugs are:
1 bromocriptine: for dopamine synergist, the treatment effect is better, has the effect of inhibiting growth hormone, the general dosage is 2.5 ~ 7.5mg / d, taken in divided doses, with increasing dose method, side effects have nausea, vomiting, low Blood pressure and lower limb paralysis.
2 cyproheptadine: serotonin antagonist, also inhibits the secretion of growth hormone, the dosage is 8 ~ 24mg / d.
3 octreotide Sandostatin: is a somatostatin agonist, the therapeutic dose is 300 ~ 1500g / d, divided into 3 subcutaneous injections.
3. Three levels of prevention
When patients undergo early surgery or supplemented with radiotherapy, GH secretion often returns to normal without posterior symptoms, but there are still many patients who still have recurrence after treatment of this disease, and often have multiple organ lesions and even exhaustion, and more There is hypopituitarism, therefore, regular observation after surgery or radiotherapy, regular GH, plasma phosphorus, blood glucose and pituitary hormone testing, have found pituitary dysfunction, in addition to hormone replacement, increase nutrition, increase Protein and multivitamin intake should also be alert to the occurrence of crisis.
Complication
Acromegaly complications Complications, diabetes, hypertension, arrhythmia, sleep disorders, diabetes insipidus, osteoporosis, optic atrophy
1. Can be complicated by secondary diabetes or impaired glucose tolerance, high blood pressure, cardiac hypertrophy, ventricular hypertrophy, development of heart failure, arrhythmia.
2. Pituitary tumor compression optic chiasm near the sella, swollen, vision loss, visual field reduction or even increased intracranial pressure, fat, sleep disorders, diabetes insipidus.
3. Osteoporosis can be complicated by kyphosis, or pathological fracture. Because the optic nerve is affected by adenoma compression caused by blood circulation disorder, it can be complicated by optic atrophy, visual loss, visual field defect, such as bilateral hemianopia, etc. arthritis.
Symptom
Symptoms of acromegaly common symptoms fatigue endocrine function hyperthyroidism hypertrophy mandibular protrusion
The disease is rare, generally mild onset, green, middle-aged men more common, longer course, up to 30 years, the main clinical manifestations of acromegaly and GH, PRL, TSH, IGF-I and other hormone secretion Increased and its role, and pituitary adenoma occupying lesions of the saddle enlargement is affected by erosion, adjacent tissue compression and increased intracranial pressure, but also associated with organ hypertrophy and its functional variation, early stage of the disease may have endocrine gland hyperfunction In the late stage, endocrine dysfunction can occur.
Abdominal hypertrophy, rough face, headache, fatigue, sweating, back pain, increased hand and foot, cap number and shoe size increase, symptoms and signs of diabetes and hyperthyroidism, due to soft tissue hyperplasia, thick skin, The skin of the head pillow has many sagging wrinkles, the subcutaneous connective tissue and deep fascia thicken, the pores increase, the mucosa is thickened, the thickness of the normal human heel pad should be less than 23mm, and the disease can be increased to (26.5±4.1). Mm, lip thickening, enlarged ear and nose, thick tongue, thick throat, so often low voice and blurred, head bone changes, often increased skull face widening, upper jaw, forehead, eyebrow arch, occipital trochanter The mandible and humerus protrude and enlarge, the teeth are widened, the dentition is thin, the patient's appearance becomes ugly year by year, the patient grows faster than normal, the height grows rapidly, the hand and foot are hypertrophied, the spine bone is widened, and the bone is accompanied by bone. Loose bone can be deformed into kyphosis, or even pathological fracture. Because the optic nerve is affected by adenoma compression caused by blood circulation disorder, it can cause optic atrophy, decreased vision, visual field defects, such as bilateral hemianopia.
1. Special appearance
Due to the growth-promoting effect of growth hormone on bone, skin and soft tissue, patients with this disease may have a special face: the upper eyelid, the tibia, the mandible, the eyebrow arch, the jaw protruding, the teeth apart, the bite dislocation, the pillow The scalp is overextended, the scalp is overgrown and the sag is sag-like, the eyelid is thick, the nose is enlarged and widened, and the lip is thick and thick. Due to the tonsils, uvula, soft palate thickening and nasal soft tissue hyperplasia, the patient may have sound. Low, nasal obstruction, olfactory sensation, often accompanied by obstructive sleep apnea syndrome, patients with thoracic sternum protruding, rib extension, anterior and posterior diameter increase in barrel chest, vertebral body enlargement, obvious posterior curvature and light lateral deformity The pelvis is widened, the long bones of the extremities are thickened, the hands and feet are enlarged, the fingers and toes are thickened, and the feet are flat. The size of the shoes and gloves of the patients is increasing. Because of the hypertrophy of the sweat glands, the patients often sweat more, and the hair follicles can be hairy due to the expansion of the female hair.
2. Glucose metabolism disorder
Because growth hormone antagonizes insulin, the sensitivity of the tissue to insulin is reduced, leading to disorder of glucose metabolism. About half of the patients have secondary diabetes or impaired glucose tolerance.
3. Hypertension
The incidence rate can be as high as 30% to 63%. Due to cardiac hypertrophy, myocardial weight increase, ventricular hypertrophy, heart failure and arrhythmia can develop, the atherosclerosis occurs early and the incidence is high.
4. Compression symptoms
Because pituitary tumors oppress the optic chiasm near the sella, swollen, vision loss, visual field reduction or even increased intracranial pressure, fat, sleep disorders, diabetes insipidus.
5. Musculoskeletal
Blood vessels and other structures can cause headaches, papilledema, such as tumor compression of the hypothalamus, and there may be anorexia and obesity.
(1) Back and back pain: 50% of patients have this complaint, and there is a thoracic spinal hunchback, which may be caused by bone hyperplasia surrounding the intervertebral foramen, or due to osteoporosis, large Weight is caused by compression of the weight-bearing joints. Osteoporosis of acromegaly is not a direct effect of growth hormone, but is caused by low levels of sex hormones in this disease. Due to long-term over-stimulation of bone cells, fibroblasts and Chondrocyte proliferation, early bone and joint space enlargement, bone hyperplasia, bone spurs occur, osteoarthritis can occur in multiple places, and late calcareous calcium salt deposits in the intra-articular ligament.
(2) Muscle: Due to the action of growth hormone, the muscle capacity of patients with this disease increases, but the exercise endurance decreases. Patients often complain of muscle weakness, muscle pain is rare, 40% of patients may have obvious myopathy, and the performance is proximal. Muscle atrophy is weak, EMG performance is similar to myopathy, but no irritation, normal muscle enzymes, muscle biopsy can be seen in type I muscle fiber hyperplasia, type II muscle fiber atrophy and other changes, but no inflammation and destruction.
(3) Joint: ligament relaxation due to proliferation of fibroblasts around the joint, thickening of the burs, calcium deposition around the joint ligament, calcification of the joint capsule causing disorder of the internal structure of the joint, tearing of the meniscus, and pseudo-gout-like joint pain Onset, the effect of growth hormone on cartilage growth can cause diffuse proliferation of cartilage, excessive growth of cartilage is prone to cracking, ulcer bleeding can occur in the main weight-bearing femoral condyle, late cartilage disappears, joint cavity narrows or disappears, joint stiffness, movement Limited, these changes occur mostly in weight-bearing joints such as the spine, hips, knees, ankles, shoulder joints, etc.
(4) Nerves: The following two neuropathies can be seen in this disease:
1 oppressive neuropathy; due to excessive stimulation of growth hormone, ligaments, tendons and other soft tissues, connective tissue and bone hyperplasia can compress the phrenic nerve, median nerve, spinal horseshoe and other clinical symptoms, such as finger palsy, lower limbs Numbness, urinary retention, deep sputum reflexes or disappearance,
2 ischemic neuropathy: mainly secondary to intraneural and perineural tissue hyperplasia.
(5) Skin: Due to the growth-promoting effect of growth hormone on collagen tissue, the typical performance is an increase in the thickness of the heel fat.
Examine
Acromegaly examination
Laboratory inspection
When you are sick, you often have skeletal systems and a variety of mineral metabolism disorders.
1. Plasma: The GH measurement is often higher than 10 g/L, and the diurnal rule disappears.
2. PRL measurement: There may be an increase, often higher than 25 g / L.
3. Growth mediator (SMc) assay: can be significantly elevated, can be >200ng / ml.
4. Blood IGF-I measurement: there may be a significant increase.
5.T3, T4 determination: can increase, T3>3.4nmol/L, T4>161nmol/L, FT3>10pmol/L, FT4>31.0pmol/L, PSH is generally less than 10U/ml, and TSH increased pituitary tumor Very rare.
6. Oral Glucose Tolerance Test (OGTT): Both blood glucose and GH are elevated, and are not inhibited to 5 g/L or less, showing an autocrine state.
7. Other tests
(1) After stimulation with insulin, arginine and glucagon, plasma GH is significantly increased. If blood glucose drops below 2.8 mmol/L (50 mg/dl) after insulin injection, GH rises to 5-10 g/ L is a positive reaction, indicating that the pituitary GH reserve function is normal, such as >10g / L or more indicates pituitary GH adenoma.
(2) Blood calcium is generally normal, blood phosphorus is elevated, and blood magnesium is lowered.
(3) Blood AKP is lowered.
(4) There was no significant variation in blood PTH and CT.
(5) BGP is rising.
(6) urinary calcium, urinary phosphorus, urinary magnesium, urine HOP and urine sugar can be raised.
Serum GH, BGP, AKP, phosphorus, and urinary calcium, HOP values were different in active acromegaly and stable patients.
Film degree exam
1.X-ray film inspection
It can be seen that the sella of the acromegaly is enlarged, the lesions are caused by saddle circumference and erosion, and the bones of the saddle back bone, the saddle bone or the junction often have bone resorption. Some authors observed the anteroposterior diameter of 937 normal people. It is 7 ~ 16mm (average 11.7mm), deep diameter 7 ~ 14mm (average 9.5mm), the abdomen of patients with acromegaly can be greater than 25mm, so often accompanied by headaches and vision loss and other compression symptoms, skeletal system X-ray examination Can be found in the skull, humerus, occipital bulge enlargement thickening, mandibular enlargement of the protrusion, dentition sparse, increased phalanx and toe bone, combined with soft tissue hypertrophy, increased foot and foot, spinal bone, soft tissue hyperplasia, Periosteal calcification forms bone hyperplasia, but osteoporosis and joint disease often occur.
(1) Hand phase: the distal end of the finger is widened and has a plexiform shape; the proximal phalanx is thickened due to the formation of new bone.
(2) Lateral phase of lumbar vertebrae: increased intervertebral space, new bone formation on the anterior surface of the vertebral body, fan-shaped lordosis at the posterior margin, calcification of the intervertebral ligament, degeneration of the late intervertebral disc, and narrowing.
(3) The foot side phase: the heel fat pad is thickened. When the male and female fat pads are larger than 23mm and 21.5mm respectively, the disease should be highly suspected. For example, if the fat is more than 25mm and 23mm respectively, the disease can be diagnosed.
(4) X-phase of the lateral side of the skull: The volume of the sella can be increased.
2. Bone density examination
Bone mineral density can be lower than normal or higher than normal. Among the 40 cases reported by the author, 5 cases were lower than normal, 8 cases were higher than normal, and the remaining 12 cases were basically normal.
3.CT scan
CT scan of the brain can detect large adenomas and microadenomas of the pituitary, and visceral enlargement and other lesions can be found.
4. MRI examination
It can be used to evaluate the volume and shape of the pituitary, contours, etc., high-resolution images, similar to CT scans in the diagnosis of microadenomas and pituitary tumors.
5. Determination of bone mineral content
There are many quantitative methods for measuring BMC. Among them, radiography, optical density method, single photon absorption method can only measure the amount of cortical bone of surrounding bone. The method of measuring BMC of trunk bone can be determined by quantitative CT method, QCT method, two-photon. Absorption method (DPA), neutron activation analysis (NAA) and Compton scattering method, etc. QCT method is a non-invasive measurement method, which has been widely used, followed by single photon and two-photon method, which has been carried out in China, and the most widely used. The application is generally an X-ray examination, which is inexpensive and can also detect the lesion of the patient.
Diagnosis
Diagnosis and diagnosis of acromegaly
diagnosis
Typical cases of acromegaly can be diagnosed by symptoms and signs, but when the early stage of the disease is not typical, the clinical manifestations are not prominent, and biochemical examination and radiological examination are needed to confirm the diagnosis.
1. Special appearance
It is a typical acromegaly, with large hands and feet, enlarged head, thickened lips, low tone, and mandibular protrusion and dentition sparse.
2. Endocrinology and biochemical examination
It can be found that plasma GH concentration is increased above 10 ng/ml, and there may be elevated PRL, elevated blood glucose, elevated blood phosphorus, abnormal thyroid function and abnormal bone metabolism indicators. The oral glucose tolerance test may show hyperglycemia. The curve can not inhibit the plasma GH level, the GH is more than 5ng/ml. In the TRH stimulation test, the plasma GH value is greater than 50% of the GH basic value, and the GH value is more than 10ng/ml, while the SMc and IGF-work can be Significantly elevated.
3. X-ray and CT scan
It can be found that the sella is enlarged, the saddle area is occupying the lesion, the saddle circumference is compressed, the hand and foot are enlarged and widened, and the X-ray specific manifestations of the skull, long bone and spine bone can assist in diagnosis.
4. Special examination of bone
Such as single photon or two-photon bone mineral density measurement, as well as QCT determination of BMC content, etc., can be found abnormalities such as osteoporosis and / or bone hyperplasia, QCT measurements reflect the credibility of the actual bone mineral content, CT value It is closely related to the bone calcium content, and the third lumbar vertebra is used as the measurement site. The QCI can be used to determine the BMC of the vertebrae in four aspects, namely:
1 evaluate the effects of various hormone levels on bone metabolism;
2 evaluation to determine the loss of normal age-related bone;
3 determine the fracture risk threshold and fracture threshold;
4 Evaluation of the impact of various drugs and exercise programs on BMC.
Differential diagnosis
1. Acromegaly: The disease is familial or constitutional. It has a change in appearance from a young age, a tall body, and its appearance resembles acromegaly, but to a lesser extent. No abnormalities are found in the examination, and plasma GH levels are not high. X-ray examination of the saddle does not expand, BMC is normal.
2. There is no testicular giant disease: tall, gonad atrophy, the distance between the fingers exceeds the length of the body, the epiphysis is closed late, the bone age is delayed, the X-ray film shows that the saddle is not large, and the bone structure is smaller than the giant disease and the acromegaly. Gonadal function disappeared, sex hormone levels were mutated, GH levels were not high, and other biochemical tests and laboratory tests such as acromegaly were found.
3. Hand and foot skin skeletal hypertrophy: Most of the patients are male youth, the shape is similar to acromegaly, but the endocrine students with acromegaly have metabolic disorders, blood GH levels are normal, the saddle does not enlarge, the skull is not large, bones The change is not obvious.
4. The lumbar vertebrae, the sella and the hand and foot X-ray examination of the disease have special performance. The GH measurement indicates that the GH is over-secreted too much, so it can be differentiated from ankylosing spondylitis. The advanced lesions are caused by other causes. The inflammation is similar and the identification is difficult.
