Hyperparathyroidism is typically recognized by elevated parathyroid hormone (PTH) and high calcium levels. However, some individuals can have hyperparathyroidism even with PTH levels within the normal laboratory range. This presents a diagnostic challenge, as it deviates from the expected biochemical markers.
The Parathyroid Glands and Calcium Balance
The parathyroid glands are typically four small glands located in the neck behind the thyroid. Their primary role is to produce parathyroid hormone (PTH), crucial for maintaining precise calcium levels in the bloodstream. Calcium is necessary for proper nerve and muscle function, and strong bones.
The body regulates calcium through a feedback loop involving PTH. When blood calcium levels decrease, the parathyroid glands release more PTH. Conversely, if calcium levels become too high, PTH production is suppressed. PTH acts on several organs to raise calcium: it prompts bones to release stored calcium, signals the kidneys to reabsorb calcium, and activates Vitamin D, which helps the intestines absorb more calcium from food.
When PTH is Normal: Understanding Normohormonal Hyperparathyroidism
Normohormonal hyperparathyroidism (NHPT) is a distinct form of primary hyperparathyroidism where PTH levels are within the normal range, yet blood calcium levels are consistently or intermittently elevated. This occurs because one or more parathyroid glands are overactive, operating autonomously despite normal PTH readings. The PTH level, while numerically “normal,” is inappropriately normal given the elevated calcium, indicating a loss of proper regulation.
The glands’ “set point” for sensing calcium may be altered, causing them to secrete PTH even when calcium is high, or they may exhibit subtle overactivity. Some cases involve specific types of adenomas or glandular hyperplasia that produce PTH amounts just enough to maintain hypercalcemia without a significant rise in the hormone itself. NHPT differs from classic primary hyperparathyroidism, where both calcium and PTH levels are high, and from secondary hyperparathyroidism, which arises as a response to consistently low calcium, often due to kidney disease or severe vitamin D deficiency.
Recognizing and Diagnosing Normohormonal Hyperparathyroidism
Recognizing NHPT often begins when individuals experience symptoms associated with high calcium, such as fatigue, bone or joint pain, kidney stones, increased urination, or cognitive issues. A single normal PTH result is insufficient to rule out the condition, especially if hypercalcemia is present. Diagnosis requires careful evaluation, including repeated measurements of blood calcium (total and ionized) to confirm persistent elevation.
Other blood tests include vitamin D levels and kidney function tests, as deficiencies or impairments can influence calcium and PTH readings and must be ruled out. NHPT is diagnosed when there is persistently elevated calcium with consistently normal PTH, after excluding other potential causes of hypercalcemia. Imaging studies, such as ultrasound or Sestamibi scans, help locate an overactive gland once the biochemical diagnosis is suspected, but are not initial diagnostic tools for NHPT itself.
Management and Outlook
Managing NHPT involves careful consideration of symptoms, hypercalcemia severity, and associated complications. For individuals without significant symptoms or progressive complications, active surveillance (watchful waiting) may be an initial approach. This involves regular monitoring of blood calcium and PTH levels, bone density scans to detect bone loss, and kidney imaging to check for stone formation.
Surgical removal of the overactive parathyroid gland(s), known as parathyroidectomy, is the definitive treatment, particularly for symptomatic patients or those developing complications like osteoporosis or kidney stones. This procedure aims to remove the source of the inappropriate PTH secretion and restore normal calcium balance. For those not candidates for surgery or preferring alternatives, medical management with medications like calcimimetics or bisphosphonates can lower calcium levels or protect bone density, though these do not cure the underlying problem. Ongoing monitoring and follow-up with an endocrinologist are important for all individuals with NHPT to manage the condition and prevent long-term health issues.