Thyroid-Releasing Hormone (TRH) is Not Increased
Among the options listed—parathyroid hormone, serum calcium, calcitonin, and thyroid-releasing hormone—thyroid-releasing hormone (TRH) is the one that is NOT increased in primary hyperparathyroidism, which is the clinical context where the other three parameters are characteristically elevated.
Understanding Primary Hyperparathyroidism
Primary hyperparathyroidism is characterized by a specific hormonal pattern that helps distinguish it from other calcium disorders:
What IS Increased in Primary Hyperparathyroidism
- Parathyroid hormone (PTH) is inappropriately elevated or remains in the normal range despite hypercalcemia, representing autonomous PTH secretion from parathyroid adenoma or hyperplasia 1
- Serum calcium is elevated due to excessive bone resorption, increased renal calcium reabsorption, and enhanced intestinal calcium absorption via increased 1,25-dihydroxyvitamin D production 2, 1
- Calcitonin increases in response to hypercalcemia through feedback mechanisms, as calcitonin secretion is directly stimulated by increases in serum calcium concentration 3, 4
What is NOT Increased
- Thyroid-releasing hormone (TRH) has no direct role in calcium homeostasis and is not part of the pathophysiology of hyperparathyroidism 2
- TRH is a hypothalamic hormone that regulates thyroid-stimulating hormone (TSH) secretion from the pituitary, which in turn controls thyroid hormone production
- The thyroid axis (TRH-TSH-thyroid hormones) operates independently of the calcium regulatory system involving PTH, calcitonin, and vitamin D 5
The Calcium Regulatory System
The three primary hormones that maintain calcium homeostasis are 5:
- PTH - the principal calcium-regulating hormone secreted when calcium-sensing receptors detect hypocalcemia 1, 5
- Calcitriol (1,25-dihydroxyvitamin D) - raises serum calcium primarily by stimulating intestinal calcium absorption 1, 5
- FGF23 - mainly controls phosphate homeostasis and indirectly influences calcium balance 5
Calcitonin acts as a protective hormone against hypercalcemia but is not considered one of the three main regulatory hormones 4. However, it does increase in response to elevated calcium levels 3, 6, 7.
Clinical Diagnostic Approach
When evaluating suspected primary hyperparathyroidism 2:
- Screen with serum calcium - hypercalcemia is the initial finding
- Confirm with serum PTH - inappropriately elevated or normal PTH in the setting of hypercalcemia establishes the diagnosis
- TRH measurement has no role in the diagnostic workup of calcium disorders
Important Caveat
PTH measurement can vary by up to 47% between different assay generations, requiring use of assay-specific reference values and trend monitoring within the same laboratory 1. Additionally, vitamin D deficiency must be excluded before diagnosing primary hyperparathyroidism, as PTH reference values are 20% lower in vitamin D-replete individuals 1.