Hypoparathyroidism, referred to as parathyroidism, is a clinical syndrome in which parathyroid hormone (PTH) secretion is reduced and/or dysfunctional. The common ones in clinical practice are idiopathic hypoparathyroidism, secondary hypoparathyroidism, hypomagnesemic hypoparathyroidism and neonatal hypoparathyroidism, while other rare ones include pseudohypoparathyroidism, pseudo-pseudohypoparathyroidism and pseudo-idiopathic hypoparathyroidism. It is characterized by increased neuromuscular excitability, hypocalcemia, hyperphosphatemia and reduced or unmeasured serum PTH. This disorder can also be due to a defective response of target cells to PTH and is called pseudohypoparathyroidism.
I. Etiology of hypoparathyroidism
1. Insufficient PTH secretion
(1) Surgical hypoparathyroidism: Any neck surgery, including thyroid, parathyroid or malignant tumor resection in the neck, can cause postoperative hypoparathyroidism due to insufficient PTH production as a result of parathyroid gland removal, injury or impaired blood supply.
(2) Idiopathic parathyroidism: It can be classified as familial or sporadic according to the mode of onset, and there are early-onset and late-onset cases according to the age of onset, among which the sporadic late-onset cases are more common. The cause of glandular destruction is unclear. Most patients have only parathyroid atrophy, and a few patients have autoimmune polyglandular endocrinopathy. Most patients with early onset disease are familial and the mode of inheritance is not known, but most believe it is autosomal recessive.
(3) Functional parathyroidism: reversible reduction of PTH synthesis and/or release can occur.
(4) Other causes of PTH hyposecretion: metastatic parathyroid cancer can cause invasive destruction of the parathyroid glands, the most common primary tumor being breast cancer; pharmacologic hypoparathyroidism, such as oncologic chemotherapy; and congenital thymic dysplasia. The thymus and parathyroid glands are absent due to congenital dysgenesis of the III and IV gill sacs, and most die within 1 to 2 years of age due to severe hypocalcemia and/or infection; iron deposition disorders. If hemochromatosis and excessive blood transfusion can cause infiltrative destruction of the parathyroid glands in addition to gonadal and pancreatic β-cell insufficiency; hepatomegaly can also infiltrate the parathyroid glands and cause their hypofunction.
2.Non-biologically active PTH
3. PTH resistance – pseudohypoparathyroidism
II. Clinical manifestations of hypoparathyroidism
The symptoms of hypoparathyroidism depend on the degree and duration of hypocalcemia. However, the rate of serum decline also plays an important role.
1. Hypocalcemia
Numbness and tingling at the ends of the fingers or mouth, muscle spasms in the hands, feet and face, followed by hand and foot twitching (serum calcium is usually below 2 mmol/L) may occur. Typical manifestations are strong inward retraction of the thumbs bilaterally, flexion of the metacarpophalangeal joints, extension of the phalangeal shoulder joints, flexion of the wrist and elbow joints, forming an eagle’s claw, and sometimes tonic extension of both feet. The knee and hip joints are flexed. There may be pain during the attack, but the convulsions are aggravated because the patient is often unusually frightened due to the horrible shape; some patients, especially children, may have convulsions or epileptic-like generalized convulsions. If not accompanied by convulsions, it can often be misdiagnosed as a grand mal seizure. Hand-foot convulsions can also be accompanied by laryngeal spasms and wheezing due to hypoxia, which in turn can induce epileptiform grand mal seizures. Some patients with mild or prolonged disease do not necessarily present with hand-foot convulsions.
In addition to these manifestations, hypocalcemia can also cause the following manifestations. Cranial radiographs may reveal calcification of the basal meridians in most patients and may present with extrapyramidal neurological symptoms, including those typical of Parkinson’s disease. Correction of hypocalcemia may result in improvement of symptoms. A few patients may have increased intracranial pressure and optic papilloedema.
2. Chronic hypothyroidism
Patients may develop neurological symptoms, including irritability, agitation, depression or psychosis. Children often have mental retardation and dental development disorders.
3.Cataract
It is more common in this disease and can seriously affect vision. Correction of hypocalcemia can stop the development of cataracts. Long-term hypoparathyroidism makes the skin dry and flaky, the nails appear longitudinal agent ridge, the hair is coarse and dry, easy to fall off, and easy to get Candida infection. The above symptoms can also improve after the blood calcium is corrected. QT time prolongation can be found in ECG examination. After the serum calcium is corrected, the ECG changes also disappear.
Hypoparathyroidism examination
1.Laboratory tests
(1) Decrease in blood calcium and increase in blood phosphorus: PTH deficiency can weaken the role of osteoclasts and reduce bone calcium mobilization, coupled with a decrease in the production of 1,25-(OH)2D3 and a decrease in calcium reabsorption and phosphorus excretion by the renal tubules, so hypoparathyroidism has low blood calcium and high blood phosphorus, only a small number of oral acidophilus or dietary phosphorus deficiency can have normal blood phosphorus.
(2) Decreased urinary calcium and phosphorus: The decrease in urinary calcium due to parathyroidism is less severe than that of chondromalacia because the former is secondary to a decrease in blood calcium, whereas the latter is mostly due to an increase in blood PTH, which can promote calcium reabsorption by the renal tubules. Because PTH can inhibit phosphorus reabsorption by the renal tubules, urinary phosphorus reabsorption increases and phosphorus excretion decreases in PTH deficiency.
(3) Measurement of PTH in blood: Clinically, most of the hypoparathyroidism has lower than normal PTH in blood due to PTH deficiency, but some patients can also be in the normal range because hypocalcemia in non-parathyroidism has a strong stimulating effect on the parathyroid glands, and its low blood calcium is obviously negatively correlated with PTH in blood, so PTH in blood in hypocalcemia still indicates hypoparathyroidism even if it is in the normal range. However, when the parathyroid glands secrete biologically inactive PTH and in hypoparathyroidism due to resistance to PTH, there is a compensatory increase in PTH secretion, with an increase in iPTH measured in the former and an increase in biologically active PTH measured in the latter.
(4) Urinary cAMP: lowering urinary cAMP is a functional indicator of PTH; therefore, urinary cAMP in parathyroid patients is mostly lower than normal.
(5) Normal blood alkaline phosphatase: ALP is elevated in hyperparathyroid patients with skeletal changes in serum alkaline phosphatase. ALP is normal in patients with low parathyroidism.
2.Other auxiliary examinations
(1) Electrocardiogram: shows ST segment prolongation, Q-T interval prolongation and T wave changes.
(2) Imaging: About 20% of cranial X-ray shows calcification of the basal ganglia, and a few patients also have calcification of the pineal gland and choroid plexus; CT scan is more sensitive than X-ray, and can detect intracranial calcification foci earlier and more often.
Diagnosis of hypoparathyroidism
For the diagnosis of hypoparathyroidism, clinical vigilance should be raised. For those with a history of neck surgery, polyglandular endocrine insufficiency, chronic skin mucosal candidiasis, cataract, numbness and tightness of the fingers, and spontaneous and induced spasms of the facial muscles or hands and feet, blood calcium and blood phosphorus should be repeatedly measured. Those with typical hand and foot twitching, low blood calcium, high blood phosphorus, and reduced calcium and phosphorus in urine without renal insufficiency strongly suggest the diagnosis of hypoparathyroidism.
V. Treatment of hypoparathyroidism
1. Diet should be high in calcium and low in phosphorus, limiting the intake of milk and other dairy products, egg yolk, cauliflower and other high phosphorus foods. Try to avoid the application of drugs that can aggravate hypocalcemia, such as birth control pills, glucocorticoids, diazepam, phenytoin sodium, phenobarbital (sodium phenobarbital) and other preparations, and even if they are used, they should not be used for a long time.
2, the patient appears hypocalcemia, hand and foot convulsions must be treated with intravenous calcium injection. Do not use large doses of calcium, because hypercalcemia makes the heart extremely sensitive to cardiac glycosides and is prone to arrhythmia and even sudden death, so it is best to stop using cardiac glycosides.
3, patients with blood calcium as low as 2.0 mmol/L, but no hand and foot twitching or only mild neuromuscular symptoms, can only oral calcium or add vitamin D or its derivatives can be, without intravenous injection of calcium.
4. The patient’s blood calcium should be controlled at 2.13-2.25 mmol/L, and the daily calcium intake should be 3-6 g (1-2 g elemental calcium). Attention should be paid to the elemental calcium content of each calcium supplement when using calcium supplements.
5.To avoid vitamin D poisoning, a smaller dose of vitamin D should be used.
6. When using vitamin D and its derivatives, attention should be paid to the fact that their efficacy is influenced by various factors and should be noted in clinical prescription. The use of vitamin D or its derivatives in larger doses can easily cause hypercalcemia or even vitamin D toxicity. The effect of various vitamin D derivatives on calcium and phosphorus metabolism depends on intestinal absorption, renal excretion and bone resorption, so the blood calcium should be closely monitored during treatment and the dose should be adjusted in time.
7, patients such as after treatment, blood calcium has been elevated, but still have increased neurological stress, should take into account the possibility of hypomagnesemia, timely determination of blood magnesium. Do not only calcium or vitamin D and its derivatives to increase the amount.
8, postoperative if accompanied by hypothyroidism at the same time, should be supplemented with thyroid hormone. If accompanied by hypoadrenocorticism, should promptly supplement cortisol, but it should be noted that cortisol and vitamin D have obvious antagonistic effect, and can increase urinary calcium excretion, reduce intestinal calcium absorption, aggravate hypocalcemia, so if the use of cortisol need to adjust the dose of vitamin D and calcium.
9, aluminum hydroxide gel can bind with intestinal phosphate, while stimulating renal synthesis of 1,25-(OH)2D3, thus promoting intestinal calcium absorption; but long-term intake of aluminide can affect the absorption of phosphorus, interfere with phosphate metabolism; reduce adenosine triphosphate, affecting the activity of PTH; cause aluminum excess or chronic aluminum toxicity. Therefore, aluminum should be used with caution or not in patients with high doses of vitamin D application.