Hyper- or hypoparathyroidism

Clinical information

Parathyroid hormone (PTH) is produced and secreted by the parathyroid glands, which are small pea-sized glands located behind the thyroid gland. It is secreted as an 84-amino acid molecule, which is cleaved into carboxyl-terminal, amino-terminal and mid-molecule fragments. Only those portions of the molecule that carry the amino terminus are biologically active. The active forms have a half-live of approximately 5 minutes whereas the inactive PTH-C fragments, with half-lives of 24 to 36 hours, make up over 90 % of the total circulating PTH and are primarily cleared by the kidneys. As a result, in patients with renal failure, PTH-C fragments can accumulate to high levels.

The function of parathyroid hormone is to maintain serum calcium levels within circulation. In hypo-calcaemic states, PTH production is increased, which stimulates renal resorption of calcium, increases calcium absorption from the intestines and stimulates bone resorption to increase release of calcium from bone. This action is controlled by a negative feedback mechanism to decrease PTH production as serum calcium levels increase.

Hyperparathyroidism occurs when the parathyroid glands release high levels of PTH into the bloodstream. There are 2 main types of hyperparathyroidism (HPT) – primary and secondary.

Primary HPT is the most common form and occurs as a result of a disorder of the parathyroid gland(s) causing incompletely regulated, excessive excretion of PTH resulting in high levels of circulating calcium. The most common cause of primary HPT is the presence of a non-cancerous adenoma in a gland, which accounts for around 84 % of cases. Other causes of primary HPT include hyperplasia of two or more parathyroid glands (15 % of cases) and, rarely, a cancerous tumour (1 %).

Secondary HPT is characterised by appropriately elevated PTH levels in response to conditions causing low calcium levels. Such conditions include vitamin D deficiency, due to the reduced ability of the body to absorb calcium, chronic kidney failure – the kidneys are responsible for conversion of 25 hydroxyvitamin D into the active form – and malabsorption of calcium.

In some cases of prolonged secondary HPT, the parathyroid glands may continue to produce elevated PTH levels even after the underlying cause of hypocalcaemia has been resolved. This is referred to as tertiary HPT and typically occurs in individuals with chronic kidney disease, usually following a kidney transplant.

Hypoparathyroidism is a very rare condition in which the parathyroid glands do not produce sufficient levels of PTH or the secreted PTH lacks biological activity. This leads to abnormally low calcium levels and hyperphosphataemia. The most common cause of hypoparathyroidism is damage to or removal of the parathyroid glands during (neck) surgery.

Diagnostics

Mild forms of HPT are typically asymptomatic and identified as part of blood tests requested for other reasons. In more severe forms, typical signs and symptoms of HPT include kidney stones, bone or joint pain, fragile bones and fatigue.

Hyperparathyroidism is usually diagnosed with routine blood tests measuring the levels of parathyroid hormone (PTH), calcium and other related minerals such as phosphorus. Additional tests and scans may include a 24-hour urine analysis to determine the level of calcium excretion, as well as bone density assessments.