Parathyroid GlandsEdit

The parathyroid glands are a quartet of small, pea-sized organs tucked on the back side of the thyroid gland. Despite their modest size, they play a powerful role in maintaining calcium and phosphate balance in the body, which in turn influences bone health, nerve and muscle function, and cardiovascular stability. The activity of the parathyroid glands is governed by a tight feedback loop involving the calcium concentration in the blood, the parathyroid hormone (PTH) they secrete, vitamin D, and the kidneys. When this system works smoothly, calcium moves between bone, blood, and kidneys in a way that keeps essential processes—such as muscle contraction and nerve signaling—properly coordinated. When it does not, disorders of calcium metabolism arise and many body systems can be affected.

The glands are usually four in number, though anatomical variation is common. They derive from the pharyngeal pouch regions during development and typically sit on the posterior aspect of the thyroid gland, though they can be located in unusual places such as the mediastinum. Their blood supply generally comes from branches of the inferior thyroid arteries. Because of their proximity to the thyroid, thyroid surgery can affect them, sometimes with lasting consequences for calcium balance. Understanding their position and function is therefore central to both general endocrinology and head-and-neck surgery.

Anatomy and physiology

Anatomy

Location and number: Most people have four parathyroid glands, but there can be three or five, and they may be ectopic, appearing in places such as the upper chest or around the thymus. Knowledge of possible variations helps surgeons perform precise procedures when needed.
Vascular supply: The glands receive arterial blood primarily from branches of the inferior thyroid arteries, with venous drainage feeding back into nearby neck vessels.

Function and regulation

Hormone: The principal product is parathyroid hormone (PTH), which raises blood calcium levels and lowers blood phosphate. PTH acts on bone to stimulate release of calcium and phosphate, on the kidneys to boost calcium reabsorption and phosphate excretion, and on the gut indirectly by promoting formation of active vitamin D.
Calcium sensing: Parathyroid cells contain receptors that monitor circulating calcium. When calcium is low, PTH secretion rises; when calcium is high, PTH release falls.
Interactions with vitamin D and phosphate: Active vitamin D increases intestinal calcium absorption and supports bone remodeling; phosphate balance also intersects with PTH control, influencing how calcium is handled by the kidneys and bone.

Clinical significance

Hyperparathyroidism

Primary hyperparathyroidism: The most common disorder of the parathyroids, typically caused by a single gland adenoma but may involve gland hyperplasia or, rarely, carcinoma. Excess PTH leads to hypercalcemia, which can manifest as fatigue, weaknesses, kidney stones, bone pain, mood changes, and gastrointestinal symptoms. Many cases are discovered incidentally on routine blood tests showing elevated calcium.
Secondary hyperparathyroidism: A response to chronic hypocalcemia from other conditions, most notably chronic kidney disease, where reduced vitamin D activation and phosphate retention drive PTH upregulation. This is not a primary gland disorder but a compensatory process.
Tertiary hyperparathyroidism: Prolonged secondary hyperparathyroidism can lead to autonomous PTH secretion even after the initial stimulus (e.g., kidney failure) is corrected.

Hypoparathyroidism

Typically arises after neck surgery or radiation that damages or removes glands. It results in low PTH, hypocalcemia, and often neuromuscular irritability such as tingling, muscle cramps, or tetany. Management centers on calcium supplementation and active vitamin D to maintain normal calcium levels and prevent symptoms.

Other considerations

MEN syndromes: Inherited conditions such as MEN1 and MEN2 can include parathyroid involvement. Awareness of genetic context informs screening and management.
Bone health and cardiovascular implications: Chronic calcium imbalance can influence bone density and, in some circumstances, cardiovascular risk profiles.

Diagnosis and management

Diagnosis

Laboratory testing: Serum calcium and phosphate measurements, along with PTH levels, are the core tests. In primary hyperparathyroidism, calcium is elevated with inappropriately high or inappropriately normal PTH. In secondary hyperparathyroidism, PTH is elevated in the setting of low or normal calcium.
Localization and imaging: When surgical treatment is considered, imaging helps localize hyperactive glands. Techniques include high-resolution neck ultrasound and nuclear medicine scans such as sestamibi scans. In selected cases, computed tomography or magnetic resonance imaging may be used.

Treatment options

Observation: For some individuals with mild, asymptomatic hyperparathyroidism, careful monitoring of calcium levels, bone density, and kidney health can be appropriate, especially if surgical risk is high.
Surgical intervention: Parathyroidectomy is the definitive treatment for many forms of hyperparathyroidism and can be curative. Minimally invasive approaches, guided by preoperative localization, aim to remove the abnormal gland(s) with minimal disruption. Surgical decisions weigh symptom burden, calcium levels, bone health, kidney function, and patient preferences.
Medical therapy: In secondary hyperparathyroidism, management focuses on controlling phosphate, providing active vitamin D analogs, and addressing underlying kidney disease. Calcimimetic drugs (for example, cinacalcet) reduce PTH secretion and can be useful when surgery is not an option or is not immediately appropriate.
Postoperative care: After successful surgery, calcium can swing downward temporarily, risking hypocalcemia. Patients may require temporary calcium supplementation and monitoring for hungry bone syndrome during bone remineralization.

Controversies and debates

When to operate for asymptomatic disease: There is ongoing discussion about the timing of surgical intervention in people with hyperparathyroidism who do not have clear symptoms. Advocates for earlier surgery emphasize that normalization of calcium and PTH can protect bone density, reduce kidney stone risk, and improve quality of life. Critics argue that not all patients benefit equally, and surgery carries risks and costs; thus, a patient-centered approach with shared decision-making—including consideration of age, comorbidities, and preferences—remains important.
Role of imaging and localization: With advances in imaging, there is debate over the best sequence and combination of tests to localize adenomas or hyperactive tissue. Proponents of targeted, minimally invasive surgery favor precise localization to minimize tissue disruption, while others argue for broader surgical exploration in complex cases.
Medical management versus surgery in secondary hyperparathyroidism: In chronic kidney disease, the choice between aggressive medical therapy and surgical intervention is nuanced. While medical strategies aim to control PTH and mineral balance, some patients eventually require parathyroidectomy, and timing can influence outcomes such as bone turnover and vascular calcification. Critics of aggressive medical management contend that it may delay definitive treatment in patients who would ultimately benefit from gland removal.
Policy and access considerations: In broader health policy terms, debates around screening for calcium disorders, reimbursement for testing and surgery, and the allocation of limited healthcare resources often reflect differing views on the balance between early intervention, patient choice, and system-level efficiency. From a perspective that prioritizes stewardship of resources and patient autonomy, the focus is on evidence-based care that maximizes value and minimizes unnecessary intervention, while ensuring access for those who need it.