fibrous dysplasia polyostosis
Introduction
Introduction to multi-bone fiber dysplasia Polyostotic fibrosis dysplasia, also known as Albright syndrome or McCune-Albright syndrome (MAS). The disease was first described by McCune (1936) and Albright (1937). It is a bone growth and developmental disease. It is a disease with three major causes of bone damage, precocious puberty and skin pigmentation. A few patients also have other diseases. Abnormal endocrine function. basic knowledge The proportion of illness: 0.0025% Susceptible people: no special people Mode of infection: non-infectious Complications: acromegaly hyperprolactinemia
Cause
Cause of polyfibrosis dysplasia
(1) Causes of the disease
The etiology has not been fully elucidated, but there have been breakthroughs in recent years. Intrinsic patients have extensive mutations in the excitatory alpha subunit (Gs) gene of the avian nucleotide binding protein (G protein), which leads to pro-osteoblast proliferation and Bone fiber dysplasia, Gs mutations are mostly located in the gene-encoded RaolC or RaolH site.
(two) pathogenesis
Since 1994, the etiology of the disease has made a breakthrough. Malchoff and Shenker et al. first discovered the widespread presence of avian nucleotide-binding protein in the cells of patients with MAS by tissue and cell molecular biology. In the guanine nucleotide binding protein, G protein), the G protein (Gs) subunit gene is mutated (Gs is composed of , , 3 subunits), and when the function of Gs is impaired, intracellular cAMP accumulation Increased intracellular cAMP, the result is:
1 Stimulate those receptors that depend on cAMP (such as ACTH, TSH, FSH, LH receptors) to activate, so that the relevant hormones directly act on certain target organs, and the target cells function enhanced, for example, to increase the secretion of melanin by melanocytes Skin pigmentation.
2 The body is resistant to a variety of hormones, such as resistance to PTH leading to bone softening and rickets.
3 Activated Gs down-regulates osteocalcin levels, increases the proliferation of pre-osteoblasts, inhibits their differentiation, leads to bone fiber dysplasia, and forms a conformational deformity of bone tissue.
Recently, some scholars have used the specific allele primers, specific allelic nucleotide hybridization and DNA sequencing by reverse transcriptase polymerase chain reaction to detect that the mutation of the subunit of Gs is located in the R201C or R201H region of the gene encoding. The cause of the mutation is due to an increase in the activity of the GTPase, which impairs the activity of the mediated receptor.
Prevention
Multi-bone fiber dysplasia prevention
Clinically, bone damage, precocious puberty and skin pigmentation are the three major diseases of the disease. A small number of patients also have other abnormalities in endocrine function.
Complication
Bone fiber dysplasia complications Complications, acromegaly, hyperprolactinemia
Acromegaly and hyperprolactinemia: may occur in a small number of MAS patients, acromegaly patients in MAS are similar to those in patients with acromegaly caused by pituitary auxin, using TRH, GHRH, GH levels Increased by glucose inhibition, children's acromegaly promote bone growth, fibrous dysplasia of the skull surface is similar to acromegaly, because the MAS course is slowly gradual, so MAS cases should be regularly scanned for the skull, MAS extremity often It is associated with hyperprolactinemia, but may have hypogonadism and galactorrhea. The most common pathological reports are pituitary adenomas and nodular hyperplasia. Treatment includes surgery, radiotherapy, bromocriptine, long-term growth. Inhibitory analogs, if fibrosis occurs in the surgical operation of the base of the sphenus, radiation therapy has the risk of increasing the deterioration around the bone, and drug treatment can be considered.
Symptom
Symptoms of multi-bone fiber dysplasia Common symptoms Multiple nodules muscle fiber size unequal bone pain Goiter hypophosphatemia response slow cortical thinning jaundice
Bone damage
The bone lesions are mainly focal lesions. The focal lesions are composed of fibrous connective tissue and scattered immature interwoven bone fragments and cartilage tissue nodules. The bone lesions often swell to the cortical bone with the bone marrow cavity, resulting in thinning of the cortical bone. Some local lesions with multiple fibrous dysplasia may have liquefaction, cystic changes, ossification in hemorrhage and cartilage nodules, and focal defects, which may lead to lameness and even pathological fractures.
The above lesions can be involved in the whole body bone and bone. According to the nature of the lesion, it can be divided into single hair style and multiple hair style. The single hair is the most common femur, tibia and rib. The spine and pelvis are relatively rare, 30% involve the craniofacial bone, but mainly Involved in the upper mandible and the top of the skull, the skull base hyperplasia hardening the cranial nerve, leading to optic atrophy, hyperplasia of the facial bone, facial asymmetry, sinus occlusion, spine, pelvis and limb long bone damage leading to bone deformity and pathology Sexual fractures and bone pain, multiple cases involving the body side or side of the main, lower limbs, femur, humerus and pelvis are more common, less involved in the ribs and skull invasion, can involve the skull base.
2. Skin pigmentation
Skin pigmentation occurs on the same side of the bone lesions, with localized dark brown flat spots. Typical pigment spots are called Cafe-au-lait spots, which are irregular in shape and often distributed in small pieces; skin pigmentation is more common in the back. More common in the lips, neck, hips and thighs, etc., at birth, pigment spots can not be obvious, but with age or sun exposure, significantly increased, deeper, pigmentation shape and the number of bone lesions, such as The pigmentation edge is clear, generally only a single bone is involved; if the edge is unclear, it is a map-like shape, generally involving multiple sites of bone.
3. Precocious puberty
More common in women, precocious puberty before the age of 6 years, the average developmental age is 3 years old, there are reports of precocious puberty in the first month after birth, women's menstrual cramps are the primary symptoms of precocious puberty, occurring in mammary gland development Before, plasma estrogen levels fluctuated between normal or significantly elevated (>900pg/ml), often cyclical, and LH and FSH levels were suppressed in young women and did not respond to GnRH stimulation (except for adult patients). Girls' precocious puberty does not depend on gonadotropin. Female precocious puberty is consistent with bone age. The long-acting GnRH analogue cyproheptadine is not effective in treating prepubertal patients. The aromatase inhibitor testosterone is obvious to girls. Therapeutic effect.
The precocious puberty of the boy is much less than that of the girl. The testicular enlargement is symmetrical, followed by penis enlargement and pubic hair, which is equal to normal puberty. The histological examination of the testis confirms that the seminiferous tubules increase, with or without a small amount. Interstitial cells.
In girls and boys, when the bone age reaches pubertal age, gonadotropin secretion begins, and the response to GnRt becomes puberty, when gonadotropin-dependent precocious puberty overlaps with earlier non-gonadotropin-dependent precocious puberty. In men, menstruation has become more regular. In the adult stage, female patients have normal puberty and normal reproductive function.
4. Multiple endocrine abnormalities and other organ diseases
In addition to the two or one of the above three major signs, some patients also have endocrine or non-endocrine abnormalities.
(1) thyroid abnormalities: can occur at any age of MAS, even shortly after birth. The symptoms of hyperthyroidism and Graves disease in this disease are different, and the distribution is the same in men and women, and the goiter tends to multiple knots. Sections, nodules are often benign, showing increased radioactive iodine uptake. In most cases, nodules are often complicated by hyperthyroidism, but thyroid hormone is often measured at the upper limit. TRH stimulation test shows that TSH release is inhibited, and thyroid pathology shows no lymphocytes. Infiltration, no thyroid antibodies, these can be differentiated from clinical severe hyperthyroidism, if the hyperthyroidism is clinically obvious, anti-thyroid drugs, isotope or surgery can also be used.
(2) Cortisol: not common in hyperthyroidism and precocious puberty in MAS, children with hypercortisolism showed a decrease in growth rate, the age of MAS-induced hypercortisolism may be very early and the symptoms are severe, ACTH levels are higher Low, high-dose dexamethasone does not inhibit adrenal function.
(3) Hyperphosphatemia and hypophosphatemia rickets or osteomalacia can be combined with MAS: urinary cAMP increases in MAS patients, and is associated with increased filtration of glomerular cAMP. If urinary phosphorus reacts normally, urinary cAMP is input. The response of the source PTH is slow, with vitamin D treatment and oral phosphate, rickets and rickets can usually be corrected, but most are resistant to treatment.
(4) Others: Abnormal livers include severe neonatal jaundice, increased enzyme activity in the liver, and manifestations of cholestasis and bile duct abnormalities during liver biopsy. Heart abnormalities include cardiac enlargement, sustained tachycardia, and in young patients. Sudden death, atypical cardiomyocyte hypertrophy also shows histological abnormalities, restrictive lung disease, arteriovenous shunt or primary cardiac abnormalities and abnormal cardiac conduction are still unclear, other MAS-related abnormalities are not See the report.
Examine
Examination of polyfibrosis dysplasia
Biochemical or radioimmunoassay, its changes are related to endocrine abnormalities, such as hyperparathyroidism, elevated blood calcium, increased urinary phosphorus, decreased blood phosphorus, increased ALP, combined precocious puberty, serum estrogen, pregnancy or androgen levels Increased, combined with acromegaly and hyperprolactinemia can be measured by increased GH or PRL, etc., due to slow course of disease, individual disease can also be no biochemical abnormalities.
X-ray inspection
The bone tissue of MAS is replaced by abnormally hyperplastic fibrous tissue, which shows different degrees of bone swelling. The cortical bone is thin, but intact. The bone density can be reduced in uniformity, or it is ground glass, or see strips, spots. Dense shadow, domestic summary X line is divided into 4 types:
(1) cystic changes: divided into single capsule and polycystic, edge hardening, common strip bone and spotted dense shadow in the capsule, common in tubular bone and rib.
(2) Change of frosted glass: The cystic expansion of the medullary cavity is a frosted glassy density with stripe bone spots and spotted calcification.
(3) Loofah rib-like changes: The trabecular bone is thick and distorted, which is quite like a loofah-like rib. In severe cases, it is like a spider web, the long tubular bone is thick, and the bone-like lines are generally parallel to the longitudinal axis.
(4) worm-like changes: single or multiple osteolytic changes, sharp edges such as worm-like, can be similar to osteolytic metastatic destruction.
In addition, the spine and long bones are often associated with pathological fractures.
2. CT and MRI examination
Although the cost of CT examination is higher than that of X-ray photographs, its density is higher than that of X-ray. The cystic changes, destruction, calcification and ossification in the diseased bone are more sensitive and accurate than X-flat sheets. The CT cross-section overcomes the conventional X-ray film. The disadvantages of overlapping before and after can be used for the overlap of the skull, spine and pelvis. MRI is more sensitive to the pathological display of MAS than conventional X-ray or CT. It can show that most of it can not be displayed on X-ray or CT. Lesions (such as necrosis, liquefaction, hemorrhage), fibrous or fibrous bone-like tissue lesions showed low signal in both T1-weighted images and T2-weighted images. The poor backbone structure may have different pathological changes at different stages of the lesion, such as necrosis in the lesion. Liquefaction shows a low signal on the T1-weighted image and a high signal on the T2-weighted image.
If the necrotic tissue is combined with hemorrhage, the T1 weighted image shows a high signal, and the calcification in the lesion and the hardening of the periphery show a significant low signal on the T1-weighted image and the T2-weighted image.
In addition, the margins of a few lesions showed a thin band-like ring-high signal on T1 and T2-weighted images, and the pathological mechanism was unclear. Some lesions showed uneven medium-low signal on T1-weighted images, while on T2-weighted images. The "Loofah"-like fiber seen in the plain film has a poor structure, while the liquefied lesion has a medium-low signal on the T1 plus image and a uniform high signal on the T2-weighted image.
Diagnosis
Diagnosis and diagnosis of multi-bone fiber dysplasia
Diagnostic criteria
With the following item 1 or item 2, the diagnosis can be established. If item 3 is considered, the possibility of MAS diagnosis should be highly considered.
1. There are three major signs of bone damage, skin pigmentation and precocious puberty.
2. X-ray manifestations of poor bone fiber structure, skin Cafe-au-lait point, age below 30 years old, accompanied by endocrine or non-endocrine abnormalities.
3. Young patients with either or both of the first items plus endocrine or non-endocrine abnormalities.
Differential diagnosis
Mainly differentiated from osteoarthritis and neurofibromatosis (von Recklinghausen disease).
Deformable osteitis
MAS bone disease is atypically confused with osteoarthritis, but osteoarthritis is asexually precocious, and there is no pigmentation of Cafe-au-lait spots, and blood ALP is significantly elevated, which can be identified.
2. Neurofibromatosis
Involved in bones, often combined with skin coffee spots, without endocrine abnormalities, can be similar to MAS, neurofibromatosis has subcutaneous nodules or soft color block changes and multiple neurofibromatosis, also without precocious puberty.
