Parathyroid GlandEdit
The parathyroid glands are a small set of endocrine organs that play a central role in calcium and phosphate homeostasis. Most individuals have four glands, though the exact number can vary. Located on the posterior surface of the thyroid gland in the neck, these tiny structures synthesize and secrete parathyroid hormone (PTH), which acts at multiple sites to keep serum calcium within a narrow, life-sustaining range. The glands work in concert with the bones, kidneys, and intestine, and their function is tightly regulated by a calcium-sensing mechanism that responds to fluctuations in blood calcium levels.
Parathyroid hormone is the principal regulator of circulating calcium. It raises blood calcium by stimulating bone resorption, increasing renal calcium reabsorption, and enhancing intestinal calcium absorption indirectly through the activation of vitamin D. The antagonist axis of phosphate is also influenced, with PTH promoting phosphate excretion by the kidneys. The calcium-sensing receptor (CaSR) on parathyroid cells detects circulating calcium and provides negative feedback to suppress PTH release when calcium is high. This finely tuned system maintains calcium availability for critical physiological processes such as neuromuscular signaling, blood coagulation, and bone mineralization.
Anatomy and location
The parathyroid glands are typically four small glands positioned on the posterior aspect of the thyroid gland, usually near its upper and lower poles. Each gland is supplied by branches of the inferior and, less commonly, the superior thyroid arteries. Their intimate relationship with the thyroid gland means surgical approaches to the thyroid can sometimes involve the parathyroids, underscoring the importance of careful preservation during neck procedures. Ectopic parathyroid tissue can occasionally be found in the mediastinum or other neck regions, which has implications for diagnostic localization in cases of disease.
The glands derive from the pharyngeal pouch endoderm during development and migrate to their final position in the neck. Variations in anatomy—such as supernumerary glands or glands closely associated with the thyroid capsule—are clinically relevant, particularly when planning surgical intervention for disease.
Physiology and regulation
Parathyroid chief cells are the principal source of PTH. PTH exerts its effects through receptors on target tissues, including bone and kidney, and it modulates the activity of enzymes involved in vitamin D activation. In bone, PTH stimulates osteoclast-mediated resorption indirectly via osteoblast signaling, releasing calcium and phosphate into the bloodstream. In the kidney, PTH increases calcium reabsorption in the distal tubules and promotes the production of 1,25-dihydroxyvitamin D (the active form of vitamin D) by stimulating 1-alpha-hydroxylase in the proximal tubules. The active vitamin D then increases intestinal absorption of calcium and phosphate, contributing to calcium balance.
Regulation hinges on the CaSR on parathyroid cells. When serum calcium rises, CaSR activation inhibits PTH synthesis and secretion; when calcium falls, PTH release is stimulated. This feedback loop helps prevent dangerous swings in calcium concentration. Other factors that influence PTH secretion include magnesium status, phosphate levels, and, in certain pathological states, chronic kidney disease or vitamin D deficiency.
Disorders of the parathyroid glands
Primary hyperparathyroidism
Primary hyperparathyroidism arises from autonomous overproduction of PTH, most commonly due to a benign adenoma in a single gland, but it can also be caused by hyperplasia or, rarely, carcinoma. The resulting hypercalcemia can produce diverse symptoms, from subtle biochemical abnormalities to bone loss, kidney stones, fatigue, abdominal discomfort, neuropsychiatric changes, and peptic ulcer disease. Many patients are diagnosed through routine biochemical screening showing elevated calcium or in workups for kidney stones or osteoporosis. Diagnosis hinges on documenting elevated or inappropriately normal PTH in the setting of hypercalcemia, with imaging used to localize diseased tissue for potential surgical treatment.
Secondary and tertiary hyperparathyroidism
Secondary hyperparathyroidism occurs when prolonged hypocalcemia or other disturbances (often due to chronic kidney disease or vitamin D deficiency) stimulates continued PTH release. The glands may become hyperplastic over time, and PTH levels can remain elevated even after calcium balance is corrected. Tertiary hyperparathyroidism refers to autonomous, often lifelong, PTH overproduction that arises after longstanding secondary hyperparathyroidism, even in the absence of ongoing mineral imbalance. These conditions reflect adaptive changes in response to systemic illness and renal failure in particular.
Hypoparathyroidism
Hypoparathyroidism results from inadequate PTH production, typically after neck surgery or damage to the glands, though autoimmune or genetic causes exist. The hallmark is hypocalcemia, which can cause tingling, muscle cramps, tetany, seizures, and cardiac conduction abnormalities if severe. management focuses on calcium supplementation and active vitamin D to maintain serum calcium while monitoring for hypercalciuria and its risks.
Other parathyroid-related conditions
Less common scenarios include familial or genetic forms of hyperparathyroidism, multigland disease in MEN syndromes, and parathyroid carcinoma. These conditions require specialized diagnostic and therapeutic approaches, often in multidisciplinary settings.
Diagnosis
The diagnostic approach integrates biochemistry, imaging, and, when needed, genetic assessment. Initial testing typically measures total and ionized serum calcium, phosphate, PTH, magnesium, and renal function. In hypercalcemia, a non-suppressed or inappropriately normal PTH level suggests primary hyperparathyroidism, whereas suppressed PTH points toward non-parathyroid causes of hypercalcemia.
Localization imaging is frequently employed before surgical intervention. High-resolution neck ultrasound can identify enlarged glands and guide a targeted surgical approach. Nuclear medicine techniques, such as the technetium-99m sestamibi scan, help localize hyperactive parathyroid tissue and are especially useful when ultrasound findings are inconclusive or when minimally invasive surgery is planned. Additional imaging modalities, including CT or MRI, may be used in complex cases or ectopic disease. In some patients, selective venous sampling for PTH can assist localization when noninvasive imaging fails.
Genetic testing and family history assessments are relevant for hereditary forms of disease, especially in patients with MEN syndromes or a family pattern of parathyroid abnormalities.
Management
Surgical treatment
Surgery is the definitive treatment for primary hyperparathyroidism in most patients, particularly those with symptomatic disease or significant end-organ impact (e.g., osteoporosis, kidney stones, severe hypercalcemia). The standard operation is parathyroidectomy, which may be performed through a focused, minimally invasive approach when disease is localized preoperatively, or through a traditional bilateral exploration when anatomy is uncertain. Careful preservation of the recurrent laryngeal nerve and the remaining parathyroid tissue is essential to avoid complications such as voice change or postoperative hypocalcemia.
Nonoperative and medical management
For some patients with mild or asymptomatic primary hyperparathyroidism, watchful waiting with regular monitoring of calcium levels, bone density, and renal function may be appropriate. In secondary hyperparathyroidism, treatment focuses on correcting the underlying cause (e.g., optimization of phosphate control in chronic kidney disease, vitamin D supplementation). Hypoparathyroidism requires lifelong calcium and active vitamin D supplementation, with close monitoring to avoid hypercalciuria and related kidney issues.
Calcimimetics (for example, cinacalcet) can reduce PTH secretion and serum calcium in selected patients with hyperparathyroidism who are not surgical candidates or who have persistent hypercalcemia despite surgery. Vitamin D repletion and phosphate management are integral components of care across hyper- and hypoparathyroid states, tailored to individual patient needs.
History and research
The recognition of the parathyroid glands as distinct endocrine organs and the isolation of parathyroid hormone in the 20th century were pivotal moments in endocrinology. Ongoing research continues to refine diagnostic criteria, improve localization techniques for surgical planning, and optimize medical therapies for both hyper- and hypoparathyroid disorders. Investigations into the molecular regulation of CaSR signaling, bone–kidney–intestine axis interactions, and the systemic consequences of chronic mineral imbalance remain active areas of study.