Excessive limb hypertrophy
Introduction
Introduction Excessive hypertrophy of the limbs: caused by excessive secretion of growth hormone (GH) in the pituitary gland. Adolescents develop giant disease due to patent forcing; after adolescence, osteophytes have merged to form acromegaly; a few puberty from onset to adulthood continue to develop acromegaly.
Cause
Cause
(1) Causes of the disease
The disease is caused by excessive secretion of growth hormone in the pituitary gland caused by pituitary tumors or other causes. GH secretion has a significant circadian rhythm, and the peak of adult secretion is mostly at night. GH mainly acts to promote the growth of bone tissue, muscle, connective tissue and viscera, promote DNA and RNA synthesis, fight insulin to promote sodium retention, and stimulate the body to secrete some peptides, such as growth mediators.
The effect of GH on glucose metabolism is insulin-like and anti-insulin-like. The former occurs earlier and the latter 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. It can increase the growth of cartilage through the influence of DNA and RNA protein synthesis. The growth factors include A, B and C, which can mediate the growth effect of GH on bone. . Interleukin A (SmA) stimulates collagen and non-collagen synthesis, and interleukin C (SmC) stimulates collagen synthesis in osteoblasts. BGP acts as a result of GH acting through SmA.
Too much GH can accelerate bone formation and maturation and promote bone growth. Bone remodeling increases and bone turnover is accelerated. Pituitary dwarfism causes bone growth and development to be stopped or delayed due to GH deficiency. In the human body, GH can increase intestinal calcium absorption, bone formation and bone mineralization, and increase bone mass. In vitro, it cannot directly stimulate bone matrix formation. Interleukin has a growth-promoting effect on various tissues, can mediate the effect of GH on bone growth, and promote growth of both bone and cartilage. GH can change the circadian rhythm of serum phosphorus, increase blood phosphorus, increase TRP, and change the maximum reabsorption/glomerular filtration rate (TMP/GFR) of renal phosphorus, further increasing blood phosphorus.
GH promotes an increase in TRP and inhibits PTH secretion, thereby lowering PTH levels and also increasing blood phosphorus. When the patient's diet has insufficient calcium, it may have a negative calcium balance, causing osteoporosis. After increasing the dietary calcium intake, it can be converted to a positive calcium balance. As the bone turnover increases, the GFR increases and the TRGa decreases, which promotes the increase of high urinary calcium and further increases bone lesions.
GH can stimulate subperiosteal bone formation, and the epithelial fibroblasts differentiate into primitive osteoblasts, promote new bone formation, and the original normal epithelial activity is activated again. The cartilage of the epiphyseal plate is active and promotes osteophytes. Cartilage hyperplasia.
GH can also promote the connective tissue changes in the joints, the joint capsules become thicker, the fat pad is fibrotic, and the fibrous tissue of the joints of bone and cartilage and periosteum proliferates. Osteoporosis in acromegaly is different from bone loss in other osteoporosis, but increases cortical bone formation with increased calcium conversion rate, increased bone mass, bone hyperplasia and osteoporosis, or local Such as saddle back bone absorption, saddle bottom bone absorption and other abnormalities.
(two) pathogenesis
Because the pituitary gland excessively secretes growth hormone, it can cause giant disease before the bones are closed in prepuberty, while adults with closed bones can cause enlargement of the hands, feet, soft tissues, internal organs and some flat bones. The clinical manifestation is Acromegaly.
Examine
an examination
The disease is less common, the general onset is slower, more common in young and middle-aged men, and the course of disease is longer, up to 30 years. The main clinical manifestations of acromegaly are related to the increase of GH, PRL, TSH, IGF-I and other hormones and their effects. It is related to the enlargement of the sella of the pituitary adenoma and the compression of adjacent tissues and the increase of intracranial pressure. It is also associated with organ hypertrophy and its functional variation. Early stage of the disease may have hypersecretory gland hyperfunction, and late stage may have endocrine dysfunction.
When the acromegaly is rough, the face is weak, the headache is weak, the sweat is sweaty, the back pain is increased, the hand and foot are widened, the cap number and the shoe size are increasing, and the symptoms and signs of diabetes and hyperthyroidism can also occur. Due to soft tissue hyperplasia, the skin is thick, the skin of the head pillow is often with sagging wrinkles, the subcutaneous connective tissue and deep fascia are thickened, the pores are enlarged, and the mucosa is thickened. The thickness of the normal human heel pad should be less than 23 mm, but this disease can be Increased to (26.5 ± 4.1) mm, lip thickening, ear and nose increased, tongue fat, throat thick, so often voice is low and blurred. Head bone changes, often the skull face widening and growth, the upper jaw, forehead, eyebrow arch, occipital trochanter, mandible and tibia protruding and enlarged, widened teeth, dentition, patient appearance is getting 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 deformity can be kyphosis or even pathological fracture due to osteoporosis. Because the optic nerve is affected by adenoma compression caused by blood circulation disorders, 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 mandibular protrusion, the teeth apart, the bite dislocation, the pillow The outskirts are protruding. The scalp is overgrown and sagging is a deep pleat, the eyelids are thick, the nose is enlarged and widened, and the lips are thick and thick. Due to tonsil, uvula, soft palate thickening and nasal soft tissue hyperplasia, patients may have low voice, nasal obstruction, olfactory sensation, often accompanied by obstructive sleep apnea syndrome. The thoracic sternum of the patient was prominent, the ribs were prolonged, the anterior and posterior diameters were enlarged, and the vertebral body was enlarged, and there were obvious posterior and light sidebend deformities. The pelvis is widened. The long bones of the limbs are thickened, the hands and feet are enlarged, the fingers and toes are thickened, and the feet are flat.
2. Glucose metabolism disorder
Because of the growth hormone antagonizing insulin, tissue sensitivity to insulin is reduced leading to disorders of glucose metabolism. About half of the patients have secondary diabetes or impaired glucose tolerance.
3. Hypertension
The incidence can be as high as 30% to 63%. Due to cardiac hypertrophy, increased myocardial weight, ventricular hypertrophy, development of heart failure, arrhythmia. The disease has an early onset of atherosclerosis and a high incidence.
4. Compression symptoms
Because the pituitary tumors compress the optic chiasm, swelling, vision loss, visual field reduction and even intracranial pressure near the sella. Fat, sleep disorders, diabetes insipidus, etc.
5. Musculoskeletal manifestations of blood vessels and other structures can cause headaches and papilledema. If the tumor oppresses the hypothalamus, there may be anorexia and obesity.
(1) Back and back pain: 50% of patients have this complaint, and there is a thoracic spine hunchback. This may be caused by the compression of nerve roots around the intervertebral foramen, or due to osteoporosis, the massive weight of the weight-bearing joints. Osteoporosis in acromegaly is not a direct effect of growth hormone, but is due to low levels of sex hormones in this disease. Due to the long-term over-stimulation of bone cells by growth hormone, fibroblasts and chondrocytes proliferate, early bone joint space increases, bone hyperplasia, and bone spurs occur. Osteoarthritis can occur in multiple places. Late calcareous calcium salts increased in the joint ligaments.
(2) Muscle: Due to the action of growth hormone, the muscle capacity of the patient increases, but the exercise tolerance decreases. Patients often complain of muscle weakness, and muscle pain is rare. 40% of patients may have obvious myopathy, manifested as proximal muscle atrophy, and EMG is similar to myopathy, but no irritation. Muscle enzymes are normal. Muscle biopsy showed various changes in type I muscle fiber proliferation, type II muscle fiber atrophy, 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 attack. The growth-promoting effect of growth hormone on cartilage can cause diffuse proliferation of cartilage, excessive growth of cartilage is prone to cracking, and ulcer bleeding can occur in the main weight-bearing femoral condyle. Late cartilage disappears, the joint cavity narrows or disappears, the joints are stiff and the movement is limited. These changes occur mostly in weight-bearing joints such as the spine, hip, knee, ankle, shoulder joints, etc.
(4) Nerves: The following two neuropathies can be seen in this disease:
1 compression neuropathy; due to excessive stimulation of growth hormone, ligaments, tendons and other soft tissues, connective tissue and bone hyperplasia can be oppressed? Nerve, median nerve, spinal horsetail and other clinical symptoms, such as finger palsy, lower limbs Symptoms such as numbness, urinary retention, and weakening or disappearance of deep sputum reflexes.
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.
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 the plasma GH concentration is increased above 10 ng/ml, and there may be findings such as elevated PRL, elevated blood glucose, elevated blood phosphorus, abnormal thyroid function and abnormal bone metabolism. Oral glucose tolerance test can show a high blood sugar curve, while not inhibiting plasma GH levels, GH more than 5ng / ml. In the TRH stimulation test, the plasma GH value is greater than 50% of the GH base value, and the GH value is more than 10 ng/ml. At the same time, SMc and IGF-work can be significantly increased.
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 density determination, as well as QCT determination of BMC content, etc., can be found abnormalities such as osteoporosis and / or bone hyperplasia. The QCT measurement reflects the credibility of the actual bone mineral content, CT value and bone calcium content are closely related, and the third lumbar vertebra is used as the measurement site. QCI can be used to determine the BMC of vertebrae in four aspects, namely:
1 Evaluation of the effects of various hormone levels on bone metabolism.
2 Evaluation and determination of bone loss associated with normal age.
3 Determine the fracture risk threshold and fracture threshold.
4 Evaluation of the impact of various drugs and exercise programs on BMC.
Diagnosis
Differential diagnosis
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. There are no abnormalities in the examination. The plasma GH level is not high, and the X-ray examination of the saddle does not expand. BMC is of normal level.
2. There is no testicular giant disease
The body is tall, the gonads are atrophy, the distance between the fingers exceeds the length of the body, the callus 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 that of giant disease and 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 were male youth, and the appearance was similar to acromegaly, but the endocrine students with no acromegaly showed metabolic disorders. The blood GH level is normal, the saddle does not enlarge, the skull is not large, and the bone changes are not obvious.
4. The lumbar spine, the sella and the hand and foot X-ray examination of this disease have special performance. The GH measurement indicates that GH is over-secreted too much, so it can be differentiated from ankylosing spondylitis. Late lesions are similar to osteoarthritis caused by other causes and are difficult to identify.
The disease is less common, the general onset is slower, more common in young and middle-aged men, and the course of disease is longer, up to 30 years. The main clinical manifestations of acromegaly are related to the increase of GH, PRL, TSH, IGF-I and other hormones and their effects. It is related to the enlargement of the sella of the pituitary adenoma and the compression of adjacent tissues and the increase of intracranial pressure. It is also associated with organ hypertrophy and its functional variation. Early stage of the disease may have hypersecretory gland hyperfunction, and late stage may have endocrine dysfunction.
When the acromegaly is rough, the face is weak, the headache is weak, the sweat is sweaty, the back pain is increased, the hand and foot are widened, the cap number and the shoe size are increasing, and the symptoms and signs of diabetes and hyperthyroidism can also occur. Due to soft tissue hyperplasia, the skin is thick, the skin of the head pillow is often with sagging wrinkles, the subcutaneous connective tissue and deep fascia are thickened, the pores are enlarged, and the mucosa is thickened. The thickness of the normal human heel pad should be less than 23 mm, but this disease can be Increased to (26.5 ± 4.1) mm, lip thickening, ear and nose increased, tongue fat, throat thick, so often voice is low and blurred. Head bone changes, often the skull face widening and growth, the upper jaw, forehead, eyebrow arch, occipital trochanter, mandible and tibia protruding and enlarged, widened teeth, dentition, patient appearance is getting 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 deformity can be kyphosis or even pathological fracture due to osteoporosis. Because the optic nerve is affected by adenoma compression caused by blood circulation disorders, it can cause optic atrophy, decreased vision, visual field defects, such as bilateral hemianopia.
