Hyperparathyroidism: when the parathyroid glands secrete too much PTH hormone

Hyperparathyroidism is a condition in which one or more parathyroid glands produce an excessive amount of parathyroid hormone (PTH). The role of PTH is to regulate calcium, magnesium, and phosphorus levels in the blood and bones. Specifically, PTH activates the hydroxylation of vitamin D in the kidneys to generate its active form. This active vitamin promotes intestinal calcium absorption.

Additionally, PTH performs the following functions:

• In the bones: it activates osteoclast function, increasing bone resorption (loss) to raise plasma calcium levels
• In the kidneys: it stimulates renal calcium reabsorption while promoting phosphate excretion, leading to hyperphosphaturia and hypocalciuria
• In the intestines: it indirectly enhances calcium absorption by increasing the synthesis of 1,25-(OH)2-cholecalciferol (vitamin D3), which acts on the intestinal epithelium

Magnesium is a crucial regulator of PTH activity, while calcitriol or vitamin D3 inhibits PTH secretion. For instance, when blood calcium levels drop, PTH secretion increases to extract calcium from bones and digestion.

There are different types of hyperparathyroidism:

• Primary hyperparathyroidism: this occurs when the parathyroid glands produce excess PTH despite normal calcium levels in the blood. The causes, in order of frequency, are adenomas, hyperplasia, cancer, and polyglandular syndromes. Primary hyperparathyroidism is twice as common in women as in men, with postmenopausal women being at higher risk. It is also more prevalent in colder climates
• Secondary hyperparathyroidism: caused by low calcium or vitamin D levels in the blood (hypocalcemia) or indirectly by hyperphosphatemia (elevated phosphorus). This can result from diets low in calcium, intestinal malabsorption, or kidney failure, leading to increased PTH secretion to maintain calcium levels
• Tertiary hyperparathyroidism: occurs in patients with kidney failure when one or more parathyroid glands become autonomous (hyperplasia), causing hypercalcemia
• Ectopic hyperparathyroidism: caused by tumors in locations outside the parathyroid glands that secrete PTH, such as certain lung cancers
• Congenital hyperparathyroidism: often due to a response to maternal hypoparathyroidism

Symptoms can include:

• Bone tenderness or pain
• Depression and forgetfulness
• Fatigue, weakness, and malaise
• Fragile bones in the limbs and spine that fracture easily
• Increased urination and frequent urination
• Kidney stones
• Nausea and loss of appetite

There are numerous causes and risk factors for hyperparathyroidism, with benign tumors of unknown cause being the most common. Other risk factors include:

• Age: most common in people over 60 but can occur in younger adults. Rarely affects children
• Gender: women are more likely to be affected than men
• Radiation exposure: to the head and neck
• Genetic syndromes: such as multiple endocrine neoplasia type I (MEN I)
• Parathyroid cancer: a very rare cause of hyperparathyroidism

Medical conditions that lower blood calcium levels or increase phosphate levels, potentially leading to hyperparathyroidism, include:

• Conditions that hinder phosphate breakdown
• Kidney failure
• Dietary calcium deficiency (malnutrition)
• Excessive calcium loss in urine
• Vitamin D disorders (e.g., in children with poor diets or adults lacking sunlight exposure or post-bariatric surgery)
• Nutrient malabsorption

Tests to diagnose hyperparathyroidism include blood tests:

• Creatinine, urea, and blood urea nitrogen (BUN)
• PTH
• Calcium
• Alkaline phosphatase
• Magnesium
• Phosphorus
• Vitamin D
• 24-hour urine collection to assess calcium excretion levels

Other diagnostic tools include:

• Bone density testing
• Kidney ultrasound or CT scans to detect kidney stones or calcifications
• Kidney X-rays
• MRI
• Neck ultrasound
• Sestamibi scintigraphy to locate parathyroid adenomas

Treatment options for hyperparathyroidism or asymptomatic high calcium levels include:

• Increasing fluid intake to prevent kidney stones
• Regular exercise
• Avoiding thiazide diuretics
• Estrogen therapy for postmenopausal women
• Surgery to remove overactive glands

If symptoms are present or calcium levels are very high, surgery to remove the affected parathyroid gland(s) may be necessary.

For secondary hyperparathyroidism caused by another condition, treatments may include:

• Additional calcium and vitamin D
• Diet low in phosphate
• Cinacalcet (Sensipar) medication
• Dialysis or kidney transplantation
• Parathyroid surgery if PTH levels are uncontrollably high

Hyperparathyroidism cannot be fully prevented. However, risk reduction strategies include maintaining a varied and balanced diet, monitoring calcium and vitamin D levels, and staying hydrated.