Hypoparathyroidism

It has been estimated that 115,000 patients in the United States have hypoparathyroidism of any cause.

It most commonly occurs as a complication of anterior neck surgery (78%).

The overall incidence of hypo parathyroidism after anterior neck surgery is approximately 8%, with 75% of cases resolving within six months and the remaining 25% resulting in permanent hypoparathyroidism.

Post surgical hypo parathroidism is much less common when surgery is performed by experience next surgeons: at high-volume centers hypoparathyroidism develops in less than 2% of patients.

Higher rates of postsurgical hypothyroidism occur with: extensive neck dissection, bilateral neck surgery, repeat neck surgery, history of Graves’ disease, inability to visualize the parathyroid glands during surgery, calcium with less than 7.5 mg/dL, and postoperative bleeding resulting in additional surgery.

Seen more commonly in older adult women, who are more likely than others to undergo thyroid surgery.

Genetic and nonsurgical acquired causes, including autoimmune causes.

The incidence of chromosome 22q11.2 deletion syndrome is 1 case per 3000 live births, and hypoparathyroidism of varying severity is present in approximately half the affected persons.

Autoimmune polyendocrinopathy candidiasis with ectodermal dystrophy is considered in patients with hypoparathyroidism who have chronic candidiasis or other autoimmune disorders.

Cutaneous manifestations include xerotic skin, skin pigmentation, and changes in the hair and nails. 

Often a parent or older sibling is identified as having hypoparathyroidism after the diagnosis is made in a child.

PTH is critical for maintaining the level of circulating calcium within a narrow normal range through its actions on bone, kidney, and intestine.

Because of PTH-mediated bone resorption, patients have low bone turnover, so bone mass increases.

Bone turnover is low in patients with hypoparathyroidism.

Bone turnover is stimulated by intermittent subcutaneous PTH.

With PTH therapy bone turnover is often elevated above the normal range several years into treatment.

PTH therapy has anabolic effects on trabecular bone and catabolic effects on cortical bone.

PTH increases cancellous bone volume, trabecular number, and cortical porosity.

The fracture risk may be increased.

PTH is critical for maintaining the level of circulating calcium within a narrow normal range through its actions on bone, kidney, and intestine.

The discontinuation of PTH therapy should be done gradually, to prevent severe hypocalcemia as the bone returns to a low-turnover state.

The frequent monitoring of blood calcium, phosphate, magnesium, creatinine levels and of urinary calcium excretion is essential to avoid overtreatment or undertreatment of hypoparathyroidism.

Hypoparathyroidism is suspected in patients with a low ionized or albumin-corrected blood calcium level, hyperphosphatemia, and an intact PTH level that is low or that is inappropriately in the normal range.

Blood calcium levels are targeted at or slightly below the lower limit of the normal range to avoid the neuromuscular symptoms of hypocalcemia, and to avoid hypercalciuria.

The differential diagnosis of hypoparathyroidism is subdivided into disorders of parathyroid gland formation, parathyroid hormone secretion, and parathyroid gland destruction.

PTH secretion is regulated primarily by the calcium-sensing receptor (CaSR) found on parathyroid chief cells.

The CaSR is inactive and PTH synthesis and secretion are increased when calcium levels are low.

PTH then regulates calcium and phosphate levels by actions on the bone, kidney, and, indirectly, intestine

Symptoms, if present, include paresthesias muscle cramps, seizures and laryngospasm.

Most patients with hypoparathyroidism have neuromuscular signs and symptoms of hypocalcemia, ranging from mild paresthesias, muscle cramps and prolongation of the correct QT interval to severe, life-threatening manifestations such as arrhythmias, laryngeal spasm, and seizures.

The emergency management of hypocalcemia-induced tetany and seizures is 10% calcium gluconate infused over a period of 10 to 15 minutes, often followed by a continuous infusion to prevent recurrent hypocalcemia while oral therapy is being initiated.

Calcium carbonate, which is 40% by weight elemental calcium, is given orally, is utilized.

An acidic environment is required for effective absorption of calcium carbonate.

Therefore calcium citrate, that does not require a low gastric pH, is recommended for persons taking acid-blocking therapy.

PTH is needed for activation of renal 25-hydroxyvitamin D 1α-hydroxylase, vitamin D analogues that have already undergone 1α-hydroxylation, calcitriol and alfacalcidol, are generally preferred.

During calcium gluconate infusions cardiac monitoring is recommended because of its arrhythmogenic effects.

The process is associated with a reduced quality of life, fatigue, lack of focus, depression, and other neuropsychiatric difficulties.

Rarely, hypoparathyroidism can develop years after surgery.

Most patients have neuromuscular signs and symptoms of hypocalcemia, ranging from mild paresthesias, muscle cramps, and prolongation of the corrected QT (QTc) interval to severe, life-threatening manifestations such as arrhythmias, laryngospasm, and seizures.

In some patients, the hypocalcemia may be asymptomatic.

It is often associated with basal ganglia calcification, cataracts, and neuropsychiatric symptoms.

Cataracts may be seen with long-standing nonsurgical hypoparathyroidism, and there may be dental abnormalities, including enamel hypoplasia and hypodontia.

There may be an increased risk of infection and cardiovascular disease.

Basal ganglia calcification occurs in more than 50% of patients with hypoparathyroidism and is thought to be mediated, in part, by chronic hyperphosphatemia.

Reduces intestinal calcium absorption and an inability to reabsorb calcium from the distal renal tubule.

As a result of low circulating PTH levels which causes low circulating 1,25(OH)2D concentrations resulting in decreased intestinal calcium absorption.

Causes include idiopathic or autoimmune, as part of polyglandular failure, associated with Grave’s disease. Hashimoto’s thyroiditis, Addison’s disease, diabetes, vitiligo, mucocutaneous candida and as a result of surgical treatment for thyroid, parathyroid and laryngeal diseases.

Most cases secondary to surgical and autoimmune reasons.

The overall incidence of hypoparathyroidism after anterior neck surgery is approximately 8%, with 75% of cases resolving within 6 months and the remaining 25% resulting in permanent hypoparathyroidism.

Possibilities of permanent postsurgical hypoparathyroidism include: extensive neck dissection, bilateral exploration of the neck, repeat neck surgery, history of Graves’ disease, an inability to visualize the parathyroid glands during surgery, and calcium level of less than 7.5 mg per deciliter 24 hours after surgery.

At high-volume centers, hypoparathyroidism develops in less than 2% of patients undergoing thyroid surgery.

Approximately 78% of cases result as a complication of anterior neck surgery. is therefore seen more frequently in older adult women, who are more likely than others in the general population to undergo thyroid surgery.

Less common causes include isolated parathyroid failure, DiGeorge syndrome, calcium receptor gene mutation, parathyroid hormone gene mutation, glial cell missing B gene, infiltration with metastatic cancer, Wilson’s disease, hemochromatosis or sarcoidosis.

Diagnosis made by establishing a low ionized serum calcium with an inappropriately low parathyroid hormone level.

Serum phosphorus concentration usually high normal or elevated while plasma 1,25(OH)2D concentrations are decreased.

Treatment includes use of parathyroid hormone, increasing intestinal calcium absorption via the use of large doses of calcium in conjunction with vitamin D2, or large doses of Vitamin D, 1,25(OH)2D.

Hypoparathyroidism is conventionally treated with high-dose vitamin D and calcium supplements.

Vitamin D analogues that have already undergone one alpha-hydroxylation are generally preferred (calcitriol) as these have relatively short half-life compared with other vitamin D analogues thud decreasing the risk of prolonged hypercalcemia, if vitamin D intoxication occurs.

Hypercalciuria is a possible complication of vitamin D therapy.

Treatment seeks to maintain the blood calcium level near the low end of the normal range while preventing symptoms of hypocalcemia, with oral calcium and active vitamin D supplementation but may involve treatment with subcutaneous parathyroid hormone therapy.

Renal insufficiency is increased in patients with hypoparathyroidism.

Recombinant human PTH has been approved for the treatment of hypoparathyroidism

Hypocalcemia can be adequately managed in most patients by means of once-daily or twice-daily subcutaneous injections of teriparatide.

The use of PTH also reduces blood phosphate levels, which may be important in preventing ectopic calcifications.

Despite a decrease in urinary calcium excretion and an increase in the estimated glomerular filtration rate, PTH therapy induces hypocitraturia, which is an established risk factor for renal calcification.

PTH therapy has inconsistent effects on hypercalciuria,.

Treatment may be complicated by hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal insufficiency, thus emphasizing the need for careful monitoring and improved therapies.

Goal of treatment is to induce intestinal calcium absorption to overwhelm the kidney to excrete it, with the possibility of causing hypercalcemia with nephrocalcinosis and nephrolithiasis.

Parathyroid hormone controls hypocalcemia in patients with hypoparathyroidism, a rare disease that affects approximately 60,000 people in the United States.

Increases serum calcium levels and reduce the need for large doses of calcium and active vitamin D.

In most cases, hypoparathyroidism occurs as a result of surgical removal of the parathyroid glands.

Hypoparathyroidism associated with numbness, tingling, muscle twitching, spasms or cramps, abnormal heart rhythm, and seizures as a consequence of low blood calcium levels.

Hypoparathyroidism associated with long-term complications such as kidney damage, kidney stones, development of cataracts and calcification of soft tissues.

Periodic renal imaging is used to evaluate for nephrocalcinosis and nephrolithiasis, and in patients with long-standing hypoparathyroidism regular ophthalmologic and dental examinations should be done.

Patients with  non-surgical hypo parathyroidism may have dental abnormalities in, including enamel hypoplasia and hypodontia.

Many patients have reduce quality of life, with fatigue, and brain fog, depression, and other neuropsychiatric issues.

Thiazide diuretics combined with a low-salt diet, which decrease urinary calcium excretion is considered as adjuvant therapy in patients treated for hypoparathyroidism.

An alternative for patients whose calcium levels cannot be controlled on calcium supplementation and active forms of vitamin D.

Is a hormonal injection administered once daily, helps to regulate the body’s calcium levels.

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Recombinant human PTH is approved for the treatment of hypo parathyroidism and its use can adequately manage hypocalcemia most patients by once daily or twice daily subcutaneous injection of teriparatide or intact PTH.

A consequence of PTH therapy includes in nephrocalcinosis or nephrolithiasis.

PTH has anabolic effects on trabecular bone and effects on catabolic effects on cortical bone with increased bone turnover.

Frequent monitoring of blood calcium, phosphate, magnesium, and creatinine and of urinary calcium excretion is essential to provide therapy that is appropriate.