Hyperparathyroidism

Hyperparathyroidism is a condition in which the parathyroid glands produce too much parathyroid hormone (PTH). There are four tiny parathyroid glands, usually located behind the thyroid gland in the neck. PTH plays a crucial role in regulating calcium, phosphorus, and vitamin D levels in the blood and bones. When too much PTH is produced, it leads to elevated calcium levels (hypercalcemia) and lowered phosphorus levels. This imbalance can cause a variety of health problems, affecting bones, kidneys, and other organ systems. Hyperparathyroidism is most commonly caused by a benign growth (adenoma) on one of the parathyroid glands.

Causes:

Hyperparathyroidism is primarily categorized into primary, secondary, and tertiary forms, each with distinct underlying causes.

• Primary Hyperparathyroidism:
  • This is the most common cause of hypercalcemia.
  • Usually caused by a single benign tumor (adenoma) on one of the parathyroid glands (85-90% of cases).
  • Less commonly, it can be due to enlargement of two or more parathyroid glands (hyperplasia).
  • Rarely, it can be caused by parathyroid cancer.
  • Genetic syndromes, such as Multiple Endocrine Neoplasia (MEN) types 1 or 2, can also lead to primary hyperparathyroidism.
• Secondary Hyperparathyroidism:
  • Occurs when another condition causes the body to produce too much PTH, typically in response to low calcium levels.
  • Severe Vitamin D Deficiency: Vitamin D is necessary for calcium absorption, so a deficiency can lead to chronically low calcium, stimulating PTH production.
  • Chronic Kidney Failure: The most common cause. Damaged kidneys cannot convert vitamin D to its active form, and they also retain phosphorus, both of which lead to low blood calcium, triggering the parathyroid glands to overwork.
  • Severe Calcium Deficiency: Chronically low dietary calcium intake.
• Tertiary Hyperparathyroidism:
  • Develops after prolonged secondary hyperparathyroidism.
  • In this form, the parathyroid glands, after years of overstimulation (e.g., due to chronic kidney disease), become abnormally enlarged and produce excessive PTH independently of blood calcium levels, even if calcium levels are normalized.

Symptoms:

Many people with hyperparathyroidism, especially in its early stages, have no symptoms (asymptomatic). When symptoms do appear, they are often related to high calcium levels in the blood and can be vague or affect multiple systems.

• Bone and Joint Symptoms:
  • Osteoporosis (thinning of bones) and increased risk of fractures.
  • Bone pain and tenderness.
  • Joint pain.
• Kidney-Related Symptoms:
  • Kidney stones (nephrolithiasis) due to excess calcium in urine.
  • Frequent urination (polyuria).
  • Excessive thirst (polydipsia).
  • Kidney damage or failure over time.
• Digestive Symptoms:
  • Abdominal pain.
  • Nausea and vomiting.
  • Constipation.
  • Loss of appetite.
• Neurological and Psychological Symptoms:
  • Fatigue and weakness.
  • Depression and anxiety.
  • Memory problems or confusion.
  • Difficulty concentrating.
  • Headaches.
• General Symptoms:
  • Muscle weakness.
  • Heart palpitations or arrhythmias (due to calcium’s effect on heart function).
  • High blood pressure.

Diagnosis:

Diagnosis of hyperparathyroidism primarily relies on blood tests to measure calcium and PTH levels, along with other tests to assess complications and locate affected glands.

• Blood Tests:
  • Calcium Levels: Elevated blood calcium (hypercalcemia) is a key indicator.
  • Parathyroid Hormone (PTH) Levels: High PTH levels confirm that the parathyroid glands are overactive. The combination of high calcium and high PTH is characteristic of primary hyperparathyroidism.
  • Vitamin D Levels: To check for vitamin D deficiency, which can cause secondary hyperparathyroidism.
  • Phosphorus Levels: Often low in primary hyperparathyroidism.
  • Kidney Function Tests: (Creatinine, GFR) to assess kidney health and rule out kidney disease as a cause of secondary hyperparathyroidism.
• Urine Tests:
  • 24-hour Urine Calcium: Measures calcium excretion in urine, which can help differentiate causes of high calcium.
• Bone Mineral Density Test (DEXA scan): To assess for bone loss (osteoporosis) caused by prolonged PTH excess.
• Imaging Tests (to locate the affected gland(s) before surgery):
  • Sestamibi Scan: A nuclear medicine scan that uses a radioactive tracer taken up by overactive parathyroid glands.
  • Ultrasound of the Neck: To visualize the parathyroid glands.
  • CT Scan or MRI: May be used in more complex cases, especially if initial imaging is inconclusive.

Treatment:

Treatment for hyperparathyroidism varies depending on the type, severity of symptoms, and the presence of complications. Surgery is the most common treatment for primary hyperparathyroidism.

• For Primary Hyperparathyroidism:
  • Surgery (Parathyroidectomy): The definitive treatment. The surgeon removes the overactive parathyroid gland(s). This is highly effective in curing the condition.
  • Observation (Watchful Waiting): For asymptomatic patients with mild elevation of calcium and no complications, regular monitoring of blood calcium, kidney function, and bone density may be an option.
  • Medications:
    • Cinacalcet (Sensipar): A calcimimetic drug that mimics calcium, tricking the parathyroid glands into releasing less PTH. Used for patients who cannot undergo surgery or for severe hypercalcemia.
    • Bisphosphonates: (e.g., alendronate) Can help strengthen bones and reduce calcium levels.
    • Hormone Replacement Therapy (HRT): For postmenopausal women, can help maintain bone density but does not address the underlying parathyroid issue.
• For Secondary Hyperparathyroidism:
  • Treat the Underlying Cause:
    • Vitamin D Supplementation: To correct vitamin D deficiency.
    • Calcium Supplements: If due to dietary calcium deficiency.
    • Phosphate Binders: For chronic kidney disease patients to reduce phosphorus levels.
    • Calcimimetics: (e.g., cinacalcet) To reduce PTH levels in chronic kidney disease.
    • Active Vitamin D Analogs: (e.g., paricalcitol, doxercalciferol) To help manage calcium and PTH in kidney disease.
• For Tertiary Hyperparathyroidism:
  • Surgery (Parathyroidectomy): Often necessary, as the glands have become autonomous. Usually, 3.5 of the 4 glands are removed, or sometimes all four with reimplantation of a small piece of parathyroid tissue elsewhere.

Long-term follow-up is important for all forms of hyperparathyroidism to ensure proper calcium balance and monitor for any recurrence or complications.