A state of excess parathyroid hormone and hypercalcemia, often with skeletal and renal complications.

Primary hyperparathyroidism results from a hyperfunction of the parathyroid glands.

There is oversecretion of PTH due to adenoma, hyperplasia or, rarely, carcinoma of the parathyroid glands.

Primary hyperparathyroidism is diagnosed in about 100,000 Americans per year.

Vast majority of patients are asymptomatic at diagnosis.

Familial hypocalciuric hypercalcemia (FHH) is a very rare condition, affecting only about 1 in 78,000 individuals.

An autosomal dominant disease, it is due to mutations in the calcium-sensing receptor gene.

Surgery for an individual with FHH is not indicated, as the hypercalcemia would persist.

In a minority of cases this occurs as part of a multiple endocrine neoplasia (MEN) syndrome, either type 1 (caused by a mutation in the gene MEN1) or type 2a (caused by a mutation in the gene RET).

Parathyroid hormone increases serum calcium by stimulating the release of calcium from bone matrix, increases calcium and decreases phosphate reabsorption by the kidney, indirectly increases calcium absorption from the small intestine by stimulating renal production of 1,25-dihydroxyvitamin D.

Excess parathyroid hormone leads to hypercalcemia in the absence of significant renal dysfunction resulting in: stones, bones, abdominal groans, and psychiatric moans, rreferring  to renal stones, bone related complications, gastrointestinal symptoms, and the effects on the CNS.

Serum phosphorus levels are commonly low due to the phosphaturic effect of the parathyroid hormone on the kidney.

Moderate anemia may be seen with hyperparathyroidism, and is of unknown etiology.

PTH targets osteoblasts and induces the osteoclastogenic cytokine RANKL (receptor activator of nuclear factor kB ligand).

Usually caused by a solitary parathyroid adenoma and the treatment of choice is parathyroidectomy.

Less commonly cause by multiple parathyroid glands, and these cases may be familial.

Sporadic cases related to abnormal tissue in the parathyroid gland.

Prevalence varies by age and sex with women being more commonly affected.

Peak incidence between 50 and 60 years of age.

Annual incidence among individuals less than 40 years is less than 100,000 thousand.

Approximately 80-85% of patients with primary disease have a benign parathyroid adenoma.

Hereditary forms, including familial hyperparathyroidism, multiple endocrine neoplasia syndrome, hyperparathyroidism jaw tumor syndrome account for approximately 10% of case of primary disease.

Cancers of the parathyroid are rare accounting for approximately 1% of case of primary hyperparathyroidism/.

The most common cause of hypercalcemia in nonhospitalized patients, affecting about 1% of the adult population.

More common in women and affects nearly 1 in 700 patients.

2 forms of primary hyperparathyroidism: asymptomatic and symptomatic.

Asymptomatic forms account for 75-80% of cases and have calcium levels that are no higher than 1 mg/dL higher than the normal range of 8.9 to 10.1 mg/dL.

Measurement of serum calcium is indicated to identify patients with primary hyperparathyroidism.

Symptomatic disease has no specific clinical presentation

Patients with symptomatic disease usually have a serum calcium level higher than 12 mg/dL and nearly all have symptoms over the level of 14 mg/dL.

Associated with increased prevalence of hypertension, diabetes, dyslipidemia and cardiac abnormalities.

Prevalence increases with age in both sexes.

Initial parathyroidectomy results in resolution of biochemical and metabolic abnormalities greater than 95% of patients when performed by experienced surgeons.

Reoperation success rate 85-95%.

Selective venous sampling for intact parathyroid hormone is clinically useful in patients with persistent or recurrent hyperparathyroidism, when noninvasive localization studies do not locate abnormal parathyroid glands.

Most patients have vague symptomotology presenting with psychiatric problems, a general feeling of illness, with nausea, epigastric pain weight loss, polyuria, and polydipsia without apparent organic cause.

Today the majority of patients are elderly women.

With progression of the disease diffuse osteopenia, bone pain, and pathological fractures occur.

Multifocal subperiosteal resorption is considered pathognomonic of primary hyperparathyroidism.

Earliest bone changes occur in the hands, particularly the phalanges and terminal tufts.

Histologically long-standing disease is associated with tunneling resorption and peritrabecular fibrosis.

With severe disease lytic lesions with cyst formation, known as osteitis fibrosa cystica and frequently with prominent multinucleated giant cells grossly appearing as brown tumors.

Mutations that have been linked to parathyroid neoplasia include mutations in the genes HRPT2, and CASR.

Patients with bipolar disorder who are receiving long-term lithium treatment are at increased risk for hyperparathyroidism.

Elevated calcium levels are found in 15% to 20% of patients who have been taking lithium long-term, but only a few of these patients have significantly elevated levels of parathyroid hormone and clinical symptoms of hyperparathyroidism.

Secondary hyperparathyroidism is due to secretion of parathyroid hormone by the parathyroid glands in response to hypocalcemia.

The most common causes of secondary hyperparathyroidsm are vitamin D deficiency and chronic renal failure.

Lack of vitamin D leads to reduced calcium absorption by the intestine leading to hypocalcemia and increased parathyroid hormone secretion.

In chronic renal insufficiency the failure to convert vitamin D to its active form in the kidney results in secondary hyperparathyroidism.

Tertiary hyperparathyroidism is seen in patients with long-term secondary hyperparathyroidism which eventually leads to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels.

Tertiary hyperparathyroidism is most often seen in patients with chronic renal failure and is an autonomous activity.

In primary hyperparathyroidism about 50% of patients have no symptoms and the problem is found as an incidental finding, while other patients may have only non-specific symptoms.

Symptoms directly due to hypercalcaemia are relatively rare.

Symptons are more common in patients with malignant hypercalcemia..

Manifestations of hypercalcemia include: weakness, fatigue, depression, bone pain, myalgias, anorexia, nausea, vomiting, constipation, polyuria, polydipsia, cognitive impairment, kidney stones and osteoporosis.

Parathyroid adenomas are very rarely clinically detected.

In primary hyperparathyroidism, parathyroid hormone (PTH) levels are elevated or normal in the presence of elevated calcium.

PTH levels may vary over time and must be retested several times to see the pattern.

In cases of primary hyperparathyroidism or tertiary hyperparathyroidism elevated PTH leads to increased serum calcium levels due to: increased bone resorption, reduced renal clearance of calcium and increased intestinal calcium absorption.

In primary hyperparathyroidism, serum phosphate levels are abnormally low in about 50% of cases, as a result of decreased renal tubular phosphate reabsorption.

With secondary hyperparathyroidism, in which serum phosphate levels are generally elevated because of renal disease.

Alkaline phosphatase levels are usually elevated.

The gold standard of diagnosis is the parathyroid immunoassay.

A high PTH level with a high serum calcium suggests primary hyperparathyroidism.

A high PTH level with a low or normal serum calcium suggests secondary hyperparathyroidsm..

Tertiary hyperparathyroidism has a high PTH and a high serum calcium.

Tertiary hyperparathyroidism is differentiated from primary hyperparathyroidism by a history of chronic kidney failure and secondary hyperparathyroidism.

A sestamibi scan is used to locate ectopic parathyroid adenomas, most commonly found in the anterior mediastianum.

Treatment depends on the type of hyperparathyroidism encountered: with symptomatic primary hyperparathyroidism, benefits from surgery are derived by removing the parathyroid adenoma, and in patients with secondary hyperparathyroidism treatment is directed at the underlying cause, usually vitamin D deficiency or chronic renal failure.

The biochemical findings of classic primary hyperparathyroidism consists of both elevated calcium and parathyroid hormone levels.

The standard of care is parathyroidectomy unless prevented by the presence of medical comorbidities.

A subset of patients have been identified with a biochemically mild form of the HPT with either an elevated calcium or parathyroid hormone level.

In patients with mild hyperparathyroidsm who have overt symptoms, are improved after parathyroidectomy.

In addition there is also a group of patients with biochemically mild disease who progress to classic HPT over time.

With successful treatment PTH levels should naturally return to normal levels unless PTH secretion has become autonomous as in tertiary hyperparathyroidism.

Evaluation for hyperparathryroidism includes measuring calcium level, bone density, vitamin D level, and phosphorus


A calcimimetic therapy is a considered therapy for some patients with severe hypercalcemia and primary hyperparathyroidism who are unable to undergo parathyroidectomy and for secondary hyperparathyroidism on dialysis.

Calciminetics control PTH release from parathyroid glands without increasing calcium and phosphorus levels.

The most common side effects of calcimimetics are mild or moderate nausea and vomiting.

Parathyroidectomy improves physical and cognitive performance.

Secondary hyperparathyroidism associated with an increase in osteoclast number and is frequently reported to be related to bone and joint pain.

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