What Is Pseudohypoparathyroidism?

Pseudohypoparathyroidism is a genetic disease with the symptoms and characteristic signs of hypoparathyroidism. Defects in any link from the glands to the target tissue cells can cause hypoparathyroidism, which is a rare familial disease. The patient's parathyroid hormone-PTH receptor does not respond completely or completely to PTH The patient's clinical manifestations were hypocalcemic convulsions, laboratory abnormalities were hypocalcemia with hyperphosphatemia, and elevated blood PTH.

Basic Information

English name: pseudohypoparathyroidism
Visiting department: Endocrinology

Common causes: PTH receptor mutation
Common symptoms: Limbs tingling, tingling, hand and foot spasms, stiffness, anxiety, anxiety, depression, hallucinations, disorientation, memory loss, etc.

Causes of Pseudohypoparathyroidism

Pseudoparathyroidism is due to a mutation in the PTH receptor, which reduces or does not respond to PTH, which can manifest a defect in the Gsa gene on the cell membrane surface, or the adenylate cyclase-cAMP system does not respond to PTH, or the target cell does not respond to cAMP These factors make the clinical manifestations of parathyroidism, but biochemically determined PTH is elevated. A few patients can be resistant to multiple hormones at the same time, such as hypothyroidism and adrenocortical function, diabetes, such as multiple endocrine gland function; Some patients can still detect autoantibodies against gastric parietal cells, parathyroid glands, adrenal cortex and thyroid.

Clinical manifestations of pseudohypoparathyroidism

Symptoms are mainly caused by chronic hypocalcemia with paroxysmal exacerbations that cause the following symptoms:

Neuromuscular symptoms

Caused by increased neuromuscular stress. Mild symptoms include only paresthesia, tingling in the extremities, numbness, and stiffness in the hands and feet, which are easily overlooked or misdiagnosed. When blood calcium is reduced to a certain level (below 80mg / L), tremor convulsions often occur, showing bilateral symmetrical wrist and palm knuckle flexion, interphalangeal joints straightened, thumbs adducted, forming eagle claws; at this time Feet often show ankylosis, knee and hip extensions; severe cases of systemic skeletal and smooth muscle spasms, which can cause life-threatening crises such as throat and bronchospasm; Hiccups; children with more convulsions are mostly systemic, like unexplained epilepsy without coma and incontinence. All of the above symptoms can be caused by infection, overwork and mood. Women are more prone to seizures before and after menstruation. The blood calcium is about 70 80mg / L. There is no obvious twitch in the clinic. It is called recessive twitch disease. It can occur when the serum free calcium is reduced or the neuromuscular stress is increased. The following tests can make the recessive show its condition. :

(1) Facial nerve tapping test (Chvostek sign) A finger bounce on the outer skin of the nerves in front of the ear can cause ipsilateral mouth corners or nasal convulsions. In severe cases, there is also convulsions in the muscles on the ipsilateral side.

(2) Beam arm compression test (Trousseau sign) Wrap the sphygmomanometer rubber bag around the upper arm, inflate the bag to maintain the blood pressure above the systolic pressure, and stop the upper arm vein reflux for 2 to 3 minutes, which can cause local arm convulsions, Similar to a "midwife hand" (thumb adduction).

Mental symptoms

It is often accompanied by symptoms of restlessness, anxiety, depression, hallucinations, disorientation, memory loss, etc., but there is very little loss of consciousness except during convulsions. Mental symptoms may be related to dysfunction of the basal nucleus of the brain.

3. Ectoderm nutritional degeneration and abnormal calcification group

Rough skin, pigmentation, and hair loss are often found. Fingers (toenails) are brittle and atrophied, and even fall off; cataracts can occur in the lens of the eye. The disease starts in childhood, with inadequate tooth calcification, impaired tooth enamel development, and yellow spots, horizontal stripes, small holes and other lesions. Children with mental retardation.

4. Characteristic signs

Typical patients often have congenital developmental defects, including short stature, fat body, round face, short neck, short fourth metacarpal and / or metatarsal bone.

Examination of pseudoparathyroidism

Blood test

Serum calcium is often reduced below 80mg / L, and in severe cases it can be as low as 40mg / L, mainly due to the decrease in calcium ion concentration. Those with hypocalcemia should measure plasma protein at the same time to exclude the decrease of total calcium caused by low plasma protein concentration. The increase of serum inorganic phosphorus in adult patients is usually around 60mg / L, and the concentration is higher in young patients. Serum alkaline phosphatase is usually normal or slightly lower. Serum immune-active parathyroid hormone (iPTH) levels can be reduced or increased in different types.

2. Urine test

When the blood calcium concentration was lower than 70mg / L, the urine calcium concentration was significantly reduced or disappeared, and the qualitative test of the ammonium oxalate solution showed a negative reaction.

3. Biochemical examination

Hypocalcemia, hyperphosphatemia, high PTH, normal alkaline phosphatase

4.X-ray inspection

Normal bone mineral density, abnormal calcification of the basal ganglia, or multiple ectopic calcifications.

5. Posture deformity

Such as short stature, short neck, short metamorphosis of the fourth metacarpal and / or phalanges, or cartilage development disorders.

6. Identification with false hypoparathyroidism

The clinical and biochemical and skeletal features of pseudoparathyroidism are normal, but there are specific signs of pseudoparathyroidism.

Complications of pseudoparathyroidism

Due to hypocalcemia and hyperphosphatemia, ectopic calcification is prone to occur in the body. The most common sites are calcification of the basal ganglia of the brain and calcification of the lens (cataract). Renal calcification occurs in some patients. In severe cases, renal dysfunction occurs.

Treatment of pseudohypoparathyroidism

1. Seizure management

Immediately intravenously inject 10% calcium gluconate 10ml 1 to 3 times daily as appropriate, supplemented with a sedative such as phenobarbital sodium or phenytoin sodium intramuscularly as necessary. Supplement calcium and active vitamin D (1,25 (OH) 2D3-Rogai). If there is no active vitamin D preparation, a large dose of vitamin D preparation can be used instead. Most patients need 10,000 to 30,000 units of vitamin D per day, and some even need 100,000 to 200,000 units per day or more. When supplementing large doses of vitamin D preparations, pay attention to avoid excessive urinary calcium and control urinary calcium within 40mg / kg per day. The purpose of calcium supplements and vitamin D preparations is to relieve hypocalcemic convulsions. Generally, the clinical symptoms disappear. Do not increase the blood calcium to normal value, otherwise hyperphosphatemia may easily cause ectopic calcification.

2. Intermittent treatment

The purpose is to alleviate the symptoms of hypocalcemia and prevent convulsions and ectopic calcification.

(1) It is advisable to enter a diet high in calcium and low in phosphorus, and not in foods such as dairy products, egg yolk, and cauliflower (more phosphorus).

(2) Oral vitamin D2 (calciferol) or D3, which promotes the absorption of calcium from the intestinal tract, 50,000 to 200,000 units per day. Because the relative activity of 1a-hydroxylase in renal tubules of patients is weakened, if the effect of D2 or D3 is not good, 1,25- (OH) 2D3 can be given, the initial dose is 0.5 g, and then it is increased by 0.25 g every 1 to 2 days to low Calcium symptoms disappear, the daily dose can reach 2.0 g. The daily dose of 1a (OH) D3 is about 2.0-4.0 g.

(3) If the effect of vitamin D is unsatisfactory, try dihydrostelogen (AT-10) or active vitamin D-1a (OH) D3. (AT-10) 0.5 3.0ml per day (containing 1.25mg per ml), its effect is between parathyroid hormone and vitamin D, and the effect starts faster than vitamin D, and the effect of promoting phosphorus excretion is less than vitamin D. Vitamin D, AT-10 and 1,25- (OH) 2D3 excess can cause hypercalcemia, which can damage the kidneys after a long time, and can cause ectopic calcification due to increased calcium and phosphorus concentrations, so it should be used during the medication Observe the changes in urine calcium and blood calcium, adjust the dose, and maintain the blood calcium at the lower limit of normal value or slightly lower than the normal value.

(4) Calcium salts can be taken orally as calcium carbonate, 2 to 4 grams per day, often used together with vitamin D and other drugs.

(5) 50mg of chlorthalidone daily and low-salt diet to maintain normal blood calcium.

(6) Magnesium. Although a few patients have been treated with the above-mentioned treatments, although the blood calcium has been raised to normal, twitch disease is still suspected and may be accompanied by hypomagnesemia. Magnesium should be used, such as magnesium sulfate 50% 10 Add 20ml to 500 1000ml, intravenous drip in 5% dextrose saline, or intramuscular injection with 50% solution, the dosage depends on the low level of blood magnesium. Follow up during the treatment to avoid excessive magnesium.