No treatment is generally required, as bone demineralisation and kidney stones are relatively uncommon in the condition.

Radiation exposure increases the risk of primary hyperparathyroidism. A number of genetic conditions including multiple endocrine neoplasia syndromes also increase the risk.

Most cases of FHH are associated with loss of function mutations in the calcium-sensing receptor (CaSR) gene, expressed in parathyroid and kidney tissue. These mutations decrease the receptor's sensitivity to calcium, resulting in reduced receptor stimulation at normal serum calcium levels. As a result, inhibition of parathyroid hormone release does not occur until higher serum calcium levels are attained, creating a new equilibrium. This is the opposite of what happens with the CaSR sensitizer, cinacalcet. Functionally, parathyroid hormone (PTH) increases calcium resorption from the bone and increases phosphate excretion from the kidney which increases serum calcium and decreases serum phosphate. Individuals with FHH, however, typically have normal PTH levels, as normal calcium homeostasis is maintained, albeit at a higher equilibrium set point. As a consequence, these individuals are not at increased risk of the complications of hyperparathyroidism.

Another form has been associated with chromosome 3q.

The incidence of primary hyperparathyroidism is approximately 1 per 1,000 people (0.1%), while there are 25-30 new cases per 100,000 people per year in the United States. The prevalence of primary hyperparathyroidism has been estimated to be 3 in 1000 in the general population and as high as 21 in 1000 in postmenopausal women. It is almost exactly three times as common in women as men.

Primary hyperparathyroidism is associated with increased all-cause mortality.

The most common cause of primary hyperparathyroidism is a sporadic, single parathyroid adenoma resulting from a clonal mutation (~97%). Less common are parathyroid hyperplasia (~2.5%), parathyroid carcinoma (malignant tumor), and adenomas in more than one gland (together ~0.5%).

Primary hyperparathyroidism is also a feature of several familial endocrine disorders: Multiple endocrine neoplasia type 1 and type 2A (MEN type 1 and MEN type 2A), and familial hyperparathyroidism.

Genetic associations include:

In all cases, the disease is idiopathic, but is thought to involve inactivation of tumor suppressor genes (Menin gene in MEN1), or involve gain of function mutations (RET proto-oncogene MEN 2a).

Recently, it was demonstrated that liquidators of the Chernobyl power plant are faced with a substantial risk of primary hyperparathyroidism, possibly caused by radioactive strontium isotopes.

Primary hyperparathyroidism can also result from pregnancy. It is apparently very rare, with only about 110 cases have so far been reported in world literature, but this is probably a considerable underestimate of its actual prevalence in pregnant women.

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. This disorder is most often seen in patients with chronic renal failure and is an autonomous activity.

Hypercalcemia is suspected to occur in approximately 1 in 500 adults in the general adult population. Like hypocalcemia, hypercalcemia can be non-severe and present with no symptoms, or it may be severe, with life-threatening symptoms. Hypercalcemia is most commonly caused by hyperparathyroidism and by malignancy, and less commonly by vitamin D intoxication, familial hypocalciuric hypercalcemia and by sarcoidosis. Hyperparathyroidism occurs most commonly in postmenopausal women. Hyperparathyroidism can be caused by a tumor, or adenoma, in the parathyroid gland or by increased levels of parathyroid hormone due to hypocalcemia. Approximately 10% of cancer sufferers experience hypercalcemia due to malignancy. Hypercalcemia occurs most commonly in breast cancer, lymphoma, prostate cancer, thyroid cancer, lung cancer, myeloma, and colon cancer. It may be caused by secretion of parathyroid hormone-related peptide by the tumor (which has the same action as parathyroid hormone), or may be a result of direct invasion of the bone, causing calcium release.

Symptoms of hypercalcemia include anorexia, nausea, vomiting, constipation, abdominal pain, lethargy, depression, confusion, polyuria, polydipsia and generalized aches and pains.

Hypocalcemia is common and can occur unnoticed with no symptoms or, in severe cases, can have dramatic symptoms and be life-threatening. Hypocalcemia can be parathyroid related or vitamin D related. Parathyroid related hypocalcemia includes post-surgical hypoparathyroidism, inherited hypoparathyroidism, pseudohypoparathyroidism, and pseudo-pseudohypoparathyroidism. Post-surgical hypoparathyroidism is the most common form, and can be temporary (due to suppression of tissue after removal of a malfunctioning gland) or permanent, if all parathyroid tissue has been removed. Inherited hypoparathyroidism is rare and is due to a mutation in the calcium sensing receptor. Pseudohypoparathyroidism is maternally inherited and is categorized by hypocalcemia and hyperphosphatemia. Finally, pseudo-pseudohypoparathyroidism is paternally inherited. Patients display normal parathyroid hormone action in the kidney, but exhibit altered parathyroid hormone action in the bone.

Vitamin D related hypocalcemia may be associated with a lack of vitamin D in the diet, a lack of sufficient UV exposure, or disturbances in renal function. Low vitamin D in the body can lead to a lack of calcium absorption and secondary hyperparathyroidism (hypocalcemia and raised parathyroid hormone). Symptoms of hypocalcemia include numbness in fingers and toes, muscle cramps, irritability, impaired mental capacity and muscle twitching.

Primary hyperparathyroidism and malignancy account for about 90% of cases of hypercalcaemia.

A hypercalcaemic crisis is an emergency situation with a severe hypercalcaemia, generally above approximately 14 mg/dL (or 3.5 mmol/l).

The main symptoms of a hypercalcaemic crisis are oliguria or anuria, as well as somnolence or coma. After recognition, primary hyperparathyroidism should be proved or excluded.

In extreme cases of primary hyperparathyroidism, removal of the parathyroid gland after surgical neck exploration is the only way to avoid death. The diagnostic program should be performed within hours, in parallel with measures to lower serum calcium. Treatment of choice for acutely lowering calcium is extensive hydration and calcitonin, as well as bisphosphonates (which have effect on calcium levels after one or two days).

Osteitis fibrosa cystica is the result of unchecked hyperparathyroidism, or the overactivity of the parathyroid glands, which results in an overproduction of parathyroid hormone (PTH). PTH causes the release of calcium from the bones into the blood, and the reabsorption of calcium in the kidney. Thus, excess PTH in hyperparathyroidism causes elevated blood calcium levels, or hypercalcemia.

There are four major causes of primary hyperparathyroidism that result in OFC:

- Parathyroid adenoma

The vast majority of cases of hyperparathyroidism are the result of the random formation of benign, but metabolically active, parathyroid adenoma swellings. These instances comprise approximately 80–85% of all documented cases of hyperparathyroidism.

- Hereditary factors

Approximately 1 in 10 documented cases of hyperparathyroidism are a result of hereditary factors. Disorders such as familial hyperparathyroidism, multiple endocrine neoplasia type 1 (MEN Type 1) and hyperparathyroidism-jaw tumor syndrome can, if left unchecked, result in OFC. MEN Type 1 is an autosomal dominant disorder and the most common hereditary form of hyperparathyroidism, affecting about 95% of genetic cases of OFC, and also tends to affect younger patients than other forms. Major mutations which can lead to hyperparathyroidism generally involve the parathyroid hormone receptor, G proteins, or adenylate cyclase. Certain genetic mutations have been linked to a higher rate of parathyroid carcinoma occurrence, specifically mutations to the gene HRPT2, which codes for the protein parafibromin.

- Parathyroid carcinoma

Parathyroid carcinoma (cancer of the parathyroid gland) is the rarest cause of OFC, accounting for about 0.5% of all cases of hyperparathyroidism. OFC onset by parathyroid carcinoma is difficult to diagnose.

- Renal complications

OFC is a common presentation of renal osteodystrophy, which is a term used to refer to the skeletal complications of end stage renal disease (ESRD). OFC occurs in approximately 50% of patients with ESRD. ESRD occurs when the kidneys fail to produce calcitriol, a form of Vitamin D, which assists in the absorption of calcium into the bones. When calcitriol levels decrease, parathyroid hormone levels increase, halting the storage of calcium, and instead triggering its removal from the bones. The concept of renal osteodystrophy is currently included into the broader term chronic kidney disease-mineral and bone disorder (CKD-MBD).

The condition is due to:

- Bilateral idiopathic (micronodular) adrenal hyperplasia (66%)

- Adrenal adenoma (Conn's syndrome) (33%)

- Primary (unilateral) adrenal hyperplasia—2% of cases

- Aldosterone-producing adrenocortical carcinoma—<1% of cases

- Familial Hyperaldosteronism (FH)

- Glucocorticoid-remediable aldosteronism (FH type I)—<1% of cases

- FH type II (APA or IHA)—<2% of cases

- Ectopic aldosterone-producing adenoma or carcinoma—< 0.1% of cases

Osteitis fibrosa cystica has long been a rare disease. Today, it appears in only 2% of individuals diagnosed with primary hyperparathyroidism, which accounts for 90% of instances of the disease. Primary hyperparathyroidism is three times as common in individuals with diabetes mellitus.

The hospitalization rate for hyperparathyroidism in the United States in 1999 was 8.0 out of 100,000. The disease has a definite tendency to affect younger individuals, typically appearing before the age of 40, with a study in 1922 reporting that 70% of cases display symptoms before the age of 20, and 85% before 35. Primary hyperparathyoidism, as well as OFC, is more common in Asiatic countries. Before treatment for hyperparathyroidism improved in the 1950s, half of those diagnosed with hyperparathyroidism saw it progress into OFC.

Rates of OFC increase alongside cases of unchecked primary hyperparathyroidism. In developing countries, such as India, rates of disease as well as case reports often mirror those published in past decades in the developed world.

The other 10% of cases are primarily caused by primary hyperplasia, or an increase of the number of cells. Parathyroid carcinoma accounts for less than 1% of all cases, occurring most frequently in individuals around 50 years of age (in stark contrast to OFC as a result of primary hyperparathyroidism) and showing no gender preference. Approximately 95% of hyperparatyhroidism caused by genetic factors is attributed to MEN type 1. This mutation also tends to affect younger individuals.

Hahner et al. investigated the frequency, causes and risk factors for adrenal crisis in patients with chronic adrenal insufficiency. Annane et al.'s landmark 2002 study found a very high rate of relative adrenal insufficiency among the enrolled patients with septic shock.

In one study, hypouricemia was found in 4.8% of hospitalized women and 6.5% of hospitalized men. (The definition was less than 0.14 mmol l-1 for women and less than 0.20 mmol l-1 in men.)

Adrenal crisis is triggered by physiological stress (such as trauma). Activities that have an elevated risk of trauma are best avoided. Treatment must be given within two hours of trauma and consequently it is advisable to carry injectable hydrocortisone in remote areas.

Primary hyperaldosteronism can be mimicked by Liddle syndrome, and by ingestion of licorice and other foods containing glycyrrhizin. In one case report, hypertension and quadriparesis resulted from intoxication with a non-alcoholic pastis (an anise-flavored aperitif containing glycyrrhizinic acid).

Medical conditions that can cause hypouricemia include:

- Fanconi syndrome

- Hyperthyroidism

- Multiple sclerosis

- Myeloma

- Nephritis

- Wilson's disease

Renal tuberculosis

And other causes of hypercalcemia (and thus hypercalciuria)

- Immobilization (leading to hypercalcemia and hypercalciuria)

- Milk-alkali syndrome

- Hypervitaminosis D

- Multiple myeloma

These conditions can cause nephrocalcinosis in association with hypercalciuria without hypercalcemia:

- Distal renal tubular acidosis

- Medullary sponge kidney

- Neonatal nephrocalcinosis and loop diuretics

- Inherited tubulopathies

- Chronic hypokalemia

- Beta thalassemia

There is no known treatment at present, although some investigators have tried to lessen the hypercalcemia with various forms of bisphosphonates.

The lack of vasopressin production usually results from some sort of damage to the pituitary gland. It may be caused due to damage to the brain caused by:

- Benign suprasellar tumors (20% of cases)

- Infections (encephalitis, tuberculosis etc.)

- Trauma (17% of cases) or neurosurgery (9% of cases)

- Non-infectious granuloma (sarcoidosis, Langerhans cell histiocytosis etc.)

- Leukaemia

- Autoimmune - associated with thyroiditis

- Other rare causes which include hemochromatosis and histiocytosis.

Vasopressin is released by the posterior pituitary, but unlike most other pituitary hormones, vasopressin is produced in the hypothalamus. Neurogenic diabetes insipidus can be a failure of production at the hypothalamus, or a failure of release at the pituitary.

In at least 25% of cases (the most commonly occurring classification), neurogenic diabetes insipidus is of unknown cause, meaning that the lack of vasopressin production arose from an unknown cause.

It is also due to damage of the hypothalamus, pituitary stalk, posterior pituitary, and can arise from head trauma.

Parathyroid adenoma can be associated with overexpression of the cyclin D1 gene.

Parathyroid cancer occurs in midlife at the same rate in men and women.

Conditions that appear to result in an increased risk of parathyroid cancer include multiple endocrine neoplasia type 1, autosomal dominant familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome (which also is hereditary). Parathyroid cancer has also been associated with external radiation exposure, but, most reports describe an association between radiation and the more common parathyroid adenoma.