Overview.
Pseudohypoparathyroidism is a hereditary disease with symptoms and characteristic signs of hypoparathyroidism. It is a rare familial disease in which the parathyroid hormone-PTH receptor does not respond to PTH at all or not at all, and the patient presents clinically with hypocalcemic tics and laboratory abnormalities such as low calcium with high phosphorus and elevated PTH.
Etiology
Pseudoparathyroidism is due to mutations in the PTH receptor, reduced or no response to PTH, which may be manifested by defects in the Gsa gene on the surface of the cell membrane, or by a lack of response of the adenylate cyclase-cAMP system to PTH, or by a lack of response of the target cells to cAMP, which make the clinical manifestation of parathyroidism, but biochemical measurements of PTH are elevated. A small number of patients may be resistant to a variety of hormones at the same time, such as A few patients may be resistant to multiple hormones at the same time, such as hypothyroidism and adrenocorticism, diabetes mellitus, e.g., multiple endocrine hypoplasia; in some cases, autoantibodies against gastric lining cells, parathyroid, adrenal cortex, and thyroid may also be detected in the patient’s blood.
Symptoms
Symptoms are mainly due to chronic low blood calcium with paroxysmal exacerbation causing the following symptoms:
1. Neuromuscular symptoms
Due to increased neuromuscular stress. In mild cases, there are only sensory abnormalities, tingling and numbness of the limbs, spasticity and rigidity of the hands and feet, which can be easily overlooked or misdiagnosed. When the blood calcium is reduced to a certain level (below 80mg/L), tetany often occurs, with bilateral symmetrical flexion of the wrists and palmar phalangeal joints of the hands, straightening of the interphalangeal joints, inward retraction of the thumbs to form an eagle claw; at this time, the feet are often tonic extension, knee and hip extension; in severe cases, the whole body skeletal muscle and smooth muscle spasms, laryngeal and bronchospasm, asphyxiation, and other critical signs of life-threatening; cardiac involvement Tachycardia; diaphragmatic spasm with eructation; pediatric polyconvulsions are mostly generalized, like unexplained grand mal seizures without coma, incontinence and other manifestations. All of the above symptoms can be triggered by infection, overwork and emotional factors. Women are more likely to have seizures around the time of menstruation. If the blood calcium is around 70~80mg/L, there may be no obvious convulsions clinically, which is called cryptogenic convulsions. If it is induced by the decrease of serum free calcium or the increase of neuromuscular stress, it may have seizures, and the following tests can show the condition of cryptogenic people:
(1) Facial nerve percussion test (Chvostek’s sign) Snapping a finger against the skin in front of the nerve in front of the ear can cause twitching of the corner of the mouth or the nose on the same side, and in severe cases, twitching of the facial muscles on the same side.
(2) Bundle arm compression test (Trousseau’s sign): Wrap the rubber bag of sphygmomanometer around the upper arm, pump the bag to maintain the blood pressure above the systolic blood pressure, and stop the venous return of the upper arm for 2-3 minutes, which may cause localized twitching of the arm, similar to the “midwife’s hand” (inwardly retracting the thumb).
2. Mental symptoms
Seizures are often accompanied by restlessness, anxiety, depression, hallucinations, disorientation, memory loss, etc., but there is rarely a loss of consciousness except during convulsions. The psychiatric symptoms may be related to the dysfunction of the basal ganglia.
3. Ectodermal tissue trophic degeneration and abnormal calcification syndrome
Rough skin, hyperpigmentation, hair loss, brittle and soft atrophy of finger nails, or even loss of nails, and cataract may occur in the lens of the eye. If the disease starts in childhood, the teeth are not fully calcified, and the enamel development is impaired, showing yellow spots, transverse lines, small holes and other lesions. Children with mental retardation.
4. Characteristic signs
Typical patients often have congenital developmental defects, including short and stout stature, chubby body size, round face, short neck, short fourth metacarpal and/or metatarsal bones.
Examination
1. Blood tests
Serum calcium often decreases to less than 80mg/L, and in severe cases can be as low as 40mg/L, mainly due to the decrease in calcium ion concentration. If the blood calcium is too low, plasma protein should be measured at the same time, in order to exclude the decrease of total calcium caused by low plasma protein concentration. Rising serum inorganic phosphorus is often around 60 mg/L in adult patients, and higher concentrations are seen in juvenile patients. Serum alkaline phosphatase is often normal or slightly low. Serum immunoreactive parathyroid hormone (iPTH) levels may be decreased or increased in different types.
2. Urinalysis
When the blood calcium concentration is lower than 70 mg/L, the urinary calcium concentration decreases significantly or disappears, and the qualitative test of ammonium oxalate solution is negative.
3. Biochemical examination
Low blood calcium, high blood phosphorus, high PTH, alkaline phosphatase is normal.
4. X-ray examination
Bone density is normal, abnormal calcification of the basal ganglia of the brain, or multiple ectopic calcifications.
5. Physical deformity
such as short stature, short neck, short and deformed fourth metacarpal and/or phalanges, or chondrodysplasia.
6. Differentiation from pseudopseudoparathyroidism
Pseudopseudoparathyroidism is normal in clinical biochemical and skeletal manifestations, but there are specific signs of pseudopseudoparathyroidism.
Diagnosis
The disease is resistant to parathyroid hormone.
1. It has the clinical and laboratory features of hypoparathyroidism.
2. It is a dominantly inherited metabolic bone disease and may have a family history.
3. Physical deformities such as short stature and obesity, strabismus, short metacarpal (limb) bones (the 4th metacarpal bone is common), short fingers (toes), etc..
4. Mental retardation.
5. No increase in urinary phosphorus and cAMP excretion after parathyroid hormone injection.
Complications
Due to low blood calcium and high blood phosphorus, ectopic calcification can easily occur in the body, the most common sites are basal ganglia calcification of the cranium and lens calcification (cataract), and individual patients develop renal calcification, which can cause renal hypoplasia in severe cases.
Treatment
1. Treatment during convulsive seizure
Immediate intravenous injection of 10% calcium gluconate 10 ml 1 to 3 times a day as appropriate, supplemented with sedatives such as sodium phenobarbital or phenytoin sodium intramuscular injection if necessary. Also supplement with calcium and active vitamin D (1,25(OH)2D3-Roquefort). If active vitamin D preparations are not available, they can be replaced with high-dose vitamin D preparations, which require 10,000 to 30,000 units of vitamin D/day in most patients, and even more than 100,000 to 200,000 units/day in some cases. When supplementing with large doses of vitamin D preparations, care should be taken to avoid excessive urinary calcium and to control urinary calcium within 40 mg/kg per day. The purpose of calcium and vitamin D supplementation is to relieve low calcium convulsions, generally supplementation until the disappearance of clinical symptoms can be, never raise the blood calcium to the normal value, otherwise high blood phosphorus easily cause ectopic calcification.
2. Intermittent treatment
The purpose is to relieve the symptoms of hypocalcemia and prevent tetany and ectopic calcification.
(1) High-calcium, low-phosphorus diet is recommended, not more dairy products, egg yolks and cauliflower and other foods (containing more phosphorus).
(2) Oral vitamin D2 (osteopontanol) or D3, to promote calcium absorption from the intestine, 50,000 to 200,000 units per day. Due to the relative activity of renal tubular 1a-hydroxylase is weakened, so if the effect of D2 or D3 is not good, can be given 1,25-(OH)2D3, the initial dose of 0.5 μg, and then increase 0.25 μg every 1-2 days until the disappearance of symptoms of hypocalcemia, the daily dose can be up to 2.0 μg. 1a (OH) D3 daily dose of about 2.0 ~ 4.0 μg.
(3) If the effect of vitamin D is unsatisfactory, try dihydrotachysterol (AT-10) or active vitamin D-1a(OH)D3. (AT-10) 0.5-3.0 ml per day (1.25 mg per ml), its effect between parathyroid hormone and vitamin D, the onset of efficacy is faster than that of vitamin D, and its effect on phosphorus excretion is not as strong as that of vitamin D. Vitamin D, AT-10, and 1,25-(OH)D3 can also be used. Vitamin D, AT-10 and 1,25-(OH)2D3 excess can cause hypercalcemia, after a long time, injury to the kidneys, and can be due to the increase in calcium and phosphorus concentration, ectopic calcification occurs, so it is advisable to observe the changes in urinary and blood calcium during the use of medication, adjust the amount of medication, to maintain the blood calcium at the lower limit of the normal value or a little lower than the normal value.
(4) Calcium salts can be taken orally as calcium carbonate, 2 to 4 grams/day, often used together with vitamin D and other drugs.
(5) Chlorthalidone 50mg per day and low salt diet to maintain normal blood calcium.
(6) magnesium agent, a few patients after the above treatment, although the blood calcium has been raised to normal, but still have tetany should be suspected and may be accompanied by low blood magnesium, magnesium agent should be used, such as magnesium sulfate 50% 10 ~ 20 ml added to 500 ~ 1000 ml of 5% dextrose saline intravenous drip, or with 50% solution intramuscular injection, the dose depending on the degree of low blood magnesium, the treatment process must be followed up to avoid overdose of blood magnesium.
Questions you may be concerned about
What about pseudohypoparathyroidism?
Pseudohypoparathyroidism can be treated with general treatment and medications such as calcium and vitamin D. The following medications should be taken under a doctor’s supervision.
1. General treatment: A well-balanced diet should be adopted to ensure an appropriate amount of calcium in the daily diet, and to reduce the high phosphorus diet such as milk, cheese, eggs and so on.
2. Medication:
(1) Calcium: oral calcium gluconate, calcium carbonate, calcium lactate and other calcium supplements can raise blood calcium, which can help control the progression of the disease, often used together with vitamin D and other drugs.
(2) Vitamin D: oral vitamin D can promote calcium absorption from the intestine.
Patients should follow the doctor’s instructions and actively treat the disease to avoid adverse consequences.