pseudohypoparathyroidism
Introduction
Introduction to pseudohypoparathyroidism Pseudo-hypoparathyroidism (pseudo-hypoparathyroidism) is a hereditary disease with symptoms and signs of hypoparathyroidism. It was first reported by Albright in 1942, so it is also called Albright hereditary bone dystrophy; The main symptoms are target organ (bone and kidney) desensitization to parathyroid hormone, parathyroid hyperplasia, increased parathyroid hormone in the blood, and clinical manifestations of hypoparathyroidism; typical cases also have unique bone and development defect. basic knowledge The proportion of illness: 0.001% Susceptible people: no specific population Mode of infection: non-infectious Complications: anemia, hypothyroidism, adrenal insufficiency, diabetes, epilepsy
Cause
Cause of pseudohypoparathyroidism
First, the cause of the disease
Pseudohypoparathyroidism is a hereditary disease, but the genetic pattern of the disease is unclear and may be diverse; in some families, its genetic pattern is X-linked dominant inheritance; in others, it may be chromosome-displayed. Due to sexual mutation, its performance varies, and the cause is related to genetic factors.
1, secondary is more common, the most common cause of parathyroidectomy or injury caused by thyroid surgery, such as most or all of the gland is removed, often permanent hypoparathyroidism, accounting for about the thyroid gland 1% to 1.7% of the operation, excessive thyroid hyperplasia can cause the disease, as for thyroid inflammation, hyperthyroidism after receiving radioactive iodine or due to malignant tumor invasion of the parathyroid gland see.
2, idiopathic less common, is an autoimmune disease, can be combined with thyroid and adrenal insufficiency, diabetes, such as multiple endocrine gland hypofunction; some patients can still detect anti-gastric cells, thyroid Autoantibodies to the paragonads, adrenal cortex and thyroid gland.
Second, the pathogenesis
Mainly due to the target organ (kidney, bone) of parathyroid hormone (PTH), especially the proximal renal tubular epithelial cell receptor can not accept or accept can not activate adenylate cyclase, leading to cAMP production disorders; The situation is that despite the formation of cAMP, PTH can not react or the peripheral organs are resistant to PTH, causing increased secretion of PTH, showing osteodystrophy syndrome, and the cause is related to genetic defects.
Prevention
Pseudohypoparathyroidism prevention
First, prevention: Because of the hereditary diseases, there is no effective way to prevent the occurrence of this disease, but the diagnosis of patients should be given active treatment, mainly to prevent complications.
For the thyroid surgery, the parathyroid gland is removed or damaged by mistake. If most or all of the glands are removed and permanent hypoparathyroidism occurs, the doctor's technical level and responsibility are emphasized.
Second, care
1, serious hypocalcemia care
Emphasis on multi-person collaboration, when patients have convulsions, they should be placed supine immediately, head to one side, quickly open mouth or tongue tongs to prevent tongue bites and tongue fall, and timely suck, oxygen, keep the airway open, Establish venous access, ECG monitoring, patrol once every 15 minutes, accompanied by family members, closely monitor the patient's heart rate, blood pressure, consciousness, mental state changes, timely and accurate record 24h access, timely and correct collection of blood samples, roots The condition needs to adjust the infusion speed, ensure that the intravenous infusion is smooth and no liquid extravasation, all kinds of operation actions should be light, avoiding all kinds of bad stimulation and causing emotional excitement of the patient, pay attention to keep warm, mild hypocalcemia: follow the doctor to push 10% calcium gluconate 10ml, pay attention to the slow rate of push to prevent heart suppression, the drug quickly enters the center to relieve limb twitching, according to the situation can be repeated every 4 ~ 6h, moderate to severe hypocalcemia patients give 10% calcium gluconate 20ml intravenous injection At the same time, muscle or intravenous injection of diazepam 5 ~ 10mg, the majority of patients treated by the above treatment can effectively control, for difficult to control or short-term Frequent seizures can be given 10% calcium gluconate 10 ~ 20ml slow intravenous infusion, control of acute symptoms and prevention of repeated effects, and safe, will not significantly inhibit the heart, in addition, with magnesium reduction can give 25% Intravenous infusion of 10-20 ml of magnesium sulfate can increase the sensitivity of PTH to target organs and improve symptoms of hypocalcemia.
2, non-acute episodes of care
Inform patients and their families that the disease is a genetic defect disease, and there is no specific treatment, early detection, early treatment, prevention of irreversible pathological damage and progression of the disease, life-long calcium and vitamin D supplementation is effective in preventing acute attacks and preventing further development of the disease Method, you must pay attention during treatment:
(1) Prevention of vitamin D deficiency, hypocalcemia, can not prevent acute attacks or prevent the progression of the disease.
(2) Prevention of hypercalcemia and urinary stones caused by vitamin poisoning.
(3) Blood calcium control is appropriate at the normal limit, which can prevent vitamin D deficiency and low blood calcium.
(4) In the first 3 months of starting treatment, check blood calcium, blood phosphorus once a week, then review every 3 to 6 months thereafter, and adjust the dosage according to the level of calcium and phosphorus. Eat high-phosphorus foods on the diet. Such as: milk, meat, soy products, eat more foods rich in high calcium and low phosphorus.
3. Strengthen memory training
To prevent further decline of memory function, nursing staff should consciously train patients' memory. Daily memory training should be simple to complex, step by step, such as: repeated training of patients on the ward environment, surrounding people, item placement, living facilities positioning and recent The events that occur are memorized. You can also use the playing cards to train the patients, arrange them from small to large or provide simple pictures, let the patients classify the color items, and train the patient's analysis, judgment, reasoning and calculation ability to let the patients Do some simple operations, such as: washing dishes, sweeping the floor, establishing new conditioning in the patient's brain through daily training, gradually self-care, encouraging patients to learn new things, and cultivating a variety of hobbies to activate brain cells. Prevent brain function decline. In short, individualized nursing strategies should be developed and implemented to help patients recover as soon as possible.
4, psychological care
When the disease occurs, the situation is dangerous, there is a danger of death, patients and their families have obvious fear and anxiety, and the mood is highly nervous. The medical staff should take the initiative to contact the patient, explain the characteristics of the disease to the family, and let the patient know that the nurse is not Will discriminate, ridicule him, respect his privacy, avoid patients being stimulated, prevent convulsions and aggravate the condition, explain the disease to the patients and their families to understand the disease is not terrible, through medication, actively cooperate with treatment and care The condition can be controlled and the quality of life is improved.
5, discharge guidance and follow-up
Explain to the patients and their families about the disease-related knowledge of pseudohypoparathyroidism, to understand the importance of regular outpatient follow-up, and to adhere to the regular hospital review. Blood calcium should be taken regularly to prevent convulsions caused by hypocalcemia, so as not to aggravate mental retardation. Provide health care brochures to patients and their families, receive standardized treatment and care, encourage patients to build confidence in the fight against disease, and take calcium preparations for life.
Complication
Pseudohypoparathyroidism complications Complications anemia hypothyroidism adrenal insufficiency diabetes epilepsy
In idiopathic hypoparathyroidism, prone to anemia, Candida albicans infection, etc., can also be accompanied by Schmidt syndrome, hypothyroidism with adrenal insufficiency or (and) diabetes, mainly Dysplasia, mental retardation, hand and foot snoring, epilepsy and basal ganglia calcification, ectopic calcification.
Symptom
Symptoms of pseudohypoparathyroidism Common symptoms Osteoporosis convulsions Vitamin D deficiency Smooth muscle spasm tachycardia Hair loss Shedding bone pain Reversing neuromuscular symptoms
Mainly due to long-term hypocalcemia with paroxysmal aggravation caused by the following symptoms:
(A) neuromuscular symptoms due to increased neuromuscular stress, mild symptoms only paresthesia, limbs tingling, numbness, hand and foot spasm, easy to be ignored or misdiagnosed, when blood calcium is reduced to a certain level (80mg / L or less) often occurs in the hand and foot sputum, bilateral symmetrical wrist and palm knuckle flexion, the interphalangeal joint is straight, the thumb is adducted, forming an eagle claw shape; at this time the feet often have a straight stretch, knee joint And hip flexion; severe cases of systemic skeletal muscle and smooth muscle spasm, can occur throat and bronchospasm, asphyxia and other dangers; myocardial fatigue in time for tachycardia, ECG shows QT prolongation, mainly ST segment extension, with abnormal T wave; There are hiccups in the diaphragmatic tendon; children are more convulsed, mostly systemic, like unexplained epileptic seizures without coma, incontinence and other manifestations, the above symptoms can be induced by infection, overwork and mood, women in It is more prone to attack before and after menstruation, blood calcium is about 70 ~ 80mg / L, clinically there is no obvious nickname for recessive snoring, if the induction of serum free calcium or neuromuscular stress can occur, the next The column test can make the recessive person show his condition:
1, facial nerve slamming test (Chvostek sign) with the finger to hit the front of the nerve surface of the ear, can cause the same side of the mouth or nose twitching, the same side of the muscles also have convulsions.
2. The beam arm compression test (Trousseau sign) wraps the sphygmomanometer rubber bag around the upper arm, and inflates the bag to maintain blood pressure between diastolic blood pressure and systolic blood pressure, reducing or stopping the upper arm venous return for 3 minutes, which can cause partial arm twitch.
(B) mental symptoms often accompanied by anxiety, anxiety, depression, hallucinations, dysregulation, memory loss and other symptoms, but in addition to convulsions, there is little loss of consciousness, mental symptoms may be related to brain basal dysfunction.
(3) ectodermal tissue vegetative degeneration and abnormal calcification group such as hypoparathyroidism is too long, often found rough skin, pigmentation, hair loss, finger (toe) nails soft and atrophy, and even shedding; intraocular lens Cataract can occur, the disease starts in childhood, tooth calcification is incomplete, tooth enamel development disorder, yellow spots, horizontal stripes, small holes and other lesions, children with more mental decline, EEG often have abnormal performance, epilepsy can occur Wave (unlike unexplained epilepsy, after the calcium supplementation, the epileptic wave can disappear): The cerebral ganglion calcification can be seen on the skull X-ray film, the bone is also denser than normal, and sometimes the cerebellum can also be calcified.
Examine
Examination of pseudohypoparathyroidism
1. Urine examination: urinary calcium and urinary phosphorus are reduced. When the blood calcium concentration is lower than 70 mg/L, the urinary calcium concentration is significantly reduced or disappeared, and the qualitative test of ammonium oxalate solution is negative.
2, blood biochemical examination: the blood biochemical performance of this disease is similar to true hypoparathyroidism, serum calcium is often reduced to below 80mg / L, can be as low as 40mg / L, mainly the reduction of calcium ion concentration, blood calcium If the temperature is too low, the plasma protein should be measured at the same time to eliminate the total amount of calcium caused by the low protein concentration. The increase of serum inorganic phosphorus in adult patients is usually around 60mg/L. In younger patients, the concentration is higher, serum alkaline phosphatase is often Normal or slightly lower, serum immunoreactive parathyroid hormone (iPTH) levels may be reduced or increased in different types.
(1) Low blood calcium and high blood phosphorus.
(2) The blood parathyroid hormone (PTH) is normal or increased. After injection of PTH 200U, the urinary cAMP and phosphorus do not increase, which may prove that the renal tubule is resistant to PTH.
(3) Blood alkaline phosphatase is normal.
X-ray bone examination revealed early skeletal line fusion and thickening of the cranial parietal bone.
Diagnosis
Diagnosis and diagnosis of pseudohypoparathyroidism
diagnosis
After thyroid surgery, the diagnosis is easy, and the idiopathic and symptomatic hidden stalks are easy to be ignored. It is not uncommon to think that neurosis or epilepsy is not common, but if you can perform multiple tests of blood and urine, most of them can The timely detection of hypocalcemia of blood calcium, the above induced test can help diagnosis, the main diagnostic basis is:
1 no thyroid surgery or anterior cervical radiation therapy and other medical history;
2 chronic seizures;
3 blood calcium is too low, blood phosphorus is too high;
Except 4 other causes of low calcium in the plasma, such as renal insufficiency, fatty sputum, chronic diarrhea, vitamin D deficiency and alkalosis;
5 serum iPTH is significantly lower than normal or absent;
The 6Ellsworth-Howard test has a phosphorus rejection reaction;
7 no body deformity, such as short stature, short toe and deformity of the toes or cartilage development disorders.
Idiopathic hypoparathyroidism is still necessary and pseudo idiopathic hypoparathyroidism, pseudohypoparathyroidism type I and type II, pseudohypoparathyroidism, etc. It must be distinguished from other causes of hand, foot and sputum. Spasmophilie constitutionnelle id-iopathique is a chronic constitutional neuromuscular overstress condition with insomnia, ant itching and pain. The symptoms of dysfunction, and typical hand and foot sputum, plasma calcium, magnesium concentrations are normal, but the red blood cell magnesium content is reduced, although this disease is rare, it also needs to be differentiated from idiopathic hypoparathyroidism.
1, AHO malformation: typical performance is short stature, round face, short neck, shield chest, unilateral or bilateral short fingers, toe deformity, more common in the 4th, 5 metacarpal or humerus, short and wide thumb, said For Murder's thumb, short limbs, curved humerus, knee varus or valgus, early healing of the epiphysis, late teething, poor tooth quality, easy to fall off, wide eye distance, small eyeball, a few with macular degeneration or optic atrophy, often Inferior intelligence, taste and smell, etc., there may be a variety of endocrine hormone non-response syndrome, in addition to pseudohypothyroidism may also occur hypothyroidism, adrenal insufficiency, hypogonadism and diabetes insipidus.
2, parathyroidism performance: PHP's parathyroidism is similar to other causes of hypoparathyroidism, there are hypocalcemia, hyperphosphatemia, the difference is that blood PTH is increased, most patients with hypocalcemia, lighter, There may be Chvostek sign and Trousseau sign positive, a small number of patients with obvious hypocalcemia, symptoms such as hand and foot spasm, soft tissue calcification such as intracranial calcification, cataract, skin calcification, etc., more common than other parathyroidism, skin calcification can form blue Hard nodules, called osteoma cutis.
According to the target cells, the non-reaction to PTH occurs before or after cAMP production, and is divided into PHPI type (Ia type, Ib type, Ic type) and type II. PHPI type and type II are different depending on the target organ to PTH reaction. It can be divided into kidney and bone resistance type, kidney resistance bone reaction type and kidney reaction bone resistance type.
(1) PHP-I type:
Type 1PHP-Ia: is the type originally described by Albright, which is a defect in the target cell membrane receptor-adenylate cyclase system, does not react to PTH, the receptor cannot bind to PTH or can bind but does not produce cAMP, the lack of cAMP PTH can not exert the physiological effects of hormones, urine cAMP is reduced or even not detected, and urine cAMP and urinary phosphorus are not increased after injection of active PTH.
2PHP-Ib type: Some type I patients have no AHO malformation, hormone resistance is limited to FTH target organs, G8 activity is normal, this type may be caused by defects of PTH receptor, but the molecular mechanism of PTH receptor activity decline is still Unclear, more manifested as kidney resistance to bone reaction subtypes.
3PHP-Ic type: a small number of type I patients are accompanied by a variety of other hormones that do not respond, there is AHO malformation, the cause of cAMP not produced is not clear, and may be related to some other membrane cell receptor-adenylate cyclase system The composition of the component is abnormal, such as the catalytic unit, and may be a functional defect of G8 or Gi, but the current method cannot be identified by such a defect.
(2) PHP-II type: PTH can normally bind to target cell membrane receptors to produce cAMP, but defects in procedures after intracellular cAMP, including insufficient intracellular calcium concentration or protein kinase activation disorder, cAMP can not further physiological Effect, urinary cAMP increased, urinary phosphorus decreased, urine cAMP continued to increase after injection of active PTH, but urinary phosphorus did not increase.
(3) Clinical subtypes:
1 Kidney and bone resistance: The most common clinical, bone and kidney have no response to PTH, manifested as hypocalcemia and hyperphosphatemia, elevated blood PTH, decreased urinary calcium and phosphorus.
2 Kidney resistance bone reaction type: also known as PHP parathyroidism type, due to the kidney resistance to PTH, causing secondary hyperparathyroidism, and bone tissue response to PTH is normal, excessive PTH can promote bone resorption, accelerate bone turnover Clinically visible bone pain, pathological fractures, etc. X-ray showed general osteoporosis, subperiosteal bone resorption and fibrous cystic osteitis and other bone lesions such as parathyroidism, blood PTH, blood alkaline phosphatase and Urinary hydroxyproline increased, urinary calcium and phosphorus decreased.
3 renal reaction bone resistance type: this type is rare, the bone lacks response to PTH, bone calcium release is reduced, hypocalcemia and secondary hyperparathyroidism occur, the kidney responds normally to PIH, and the urinary phosphorus discharge increases, resulting in low Phosphemia, elevated blood PTH, normal blood alkaline phosphatase and urinary hydroxyproline, decreased urinary calcium and increased urinary phosphorus, X-ray showed normal or increased bone density.
According to the patient's clinical manifestations (especially the special posture) and laboratory test results, it is not difficult to diagnose the condition of PTH without reaction.
1. Incidence status: Family history with developmental defects, more common in children under 10 years old, more common in women, but male symptoms are heavier.
2. Symptoms: There are symptoms similar to hypoparathyroidism, but serum parathyroid hormone does not decrease.
(1) Chronic episodes, athletes with episodes may have epileptic seizures and tendons, throat, and paresthesia.
(2) abnormal posture: rough and short body, round face, short finger (toe), metacarpophalangeal deformity, strabismus.
(3) Developmental disorders: often have mental retardation, late teething, tooth dysplasia or enamel damage.
The epiphyseal line fuses too early, the cranial parietal bone thickens, subcutaneous or deep tissue calcification, basal ganglia calcification, cataract.
(4) a small number of low metabolic rate, impaired glucose tolerance, gonadal dysplasia (Turner syndrome).
Laboratory tests have reduced urinary calcium and urinary phosphorus, low blood calcium, high blood phosphorus, normal or elevated blood PTH, and normal blood alkaline phosphatase.
Differential diagnosis
Classification and identification of hypoparathyroidism and pathological major defects in physical abnormalities * Hypocalcemia and hyperphosphorus Gs protein subunits lack exogenous PTH reactivity.
Increased urinary phosphorus and increased urine cAMP
iPTH reduced hypoparathyroidism
First, surgery, radionuclide, tumor and other parathyroid damage and destruction - +-++.
Second, DiGeorge sign parathyroid embryo developmental disorders - +-++.
Third, speciality
1, familial (sexual chain recessive, autosomal recessive and dominant, may be autoimmune) parathyroid atrophy - + - ++.
2, sporadic (autoimmune) as above - +-++.
Fourth, the blood calcium is too high, the birth of the newborn mother PTH secretion is temporarily suppressed -+-++.
iPTH normal hypoparathyroidism, pseudo-pseudohypoparathyroidism hereditary body abnormalities, biochemical normal +-+++.
iPTH increased hypoparathyroidism.
(1) Pseudohypoparathyroidism Type Ia target tissue (bone and kidney) cell receptors do not respond to PTH +++--.
(2) pseudohypoparathyroidism type Ib ± + ---.
(3) Pseudohypoparathyroidism type II target cells do not respond to cAMP ++ - Ca2+ after ++.
1, secondary is more common, the most common cause of parathyroidectomy or injury caused by thyroid surgery, such as most or all of the gland is removed, often permanent hypoparathyroidism, accounting for about the thyroid gland 1% to 1.7% of the operation, excessive thyroid hyperplasia can cause the disease, as for thyroid inflammation, hyperthyroidism after receiving radioactive iodine or due to malignant tumor invasion of the parathyroid gland see.
2, idiopathic is less common, is an autoimmune disease, idiopathic hypoparathyroidism is heavier, ectopic calcification is rare, no abnormal body shape and short finger (toe) deformity, blood PTH is reduced, different The treatment of PTH is effective in the treatment of the disease, that is, the urinary cAMP is significantly increased, the urinary phosphorus excretion can be increased by 5 to 6 times than before the injection, while the pseudohypoparathyroidism is only 2 times more, and the thyroid can be combined at the same time. And adrenal cortical hypofunction, diabetes, such as multiple endocrine gland hypofunction; some patients can detect autoantibodies against gastric parietal cells, parathyroid glands, adrenal cortex and thyroid.
3, pseudo-pseudohypoparathyroidism: the disease is actually an incomplete type of pseudohypoparathyroidism, may be due to abnormal or dysfunction of cAMP-dependent protein kinase in proximal renal tubular epithelial cells It may also be related to heredity. Most of the symptoms appear in adulthood. The clinical manifestations are similar to those of pseudohypoparathyroidism. There are also abnormalities in body posture, but no convulsions, laboratory tests, normal blood calcium and phosphorus, and normal serum PTH. The PTH test was normal and the results of these laboratory tests were different from those of pseudohypoparathyroidism.
