nonPTHmediated

NonPTHmediated, often written non-PTH-mediated, is an adjective used in physiology and medicine to describe processes, signaling pathways, or disease states that occur independently of parathyroid hormone (PTH). It is used to distinguish mechanisms and etiologies that do not rely on PTH action from those that do.

In calcium and phosphate homeostasis, PTH raises serum calcium and lowers serum phosphate by acting on bone and kidney and by promoting the activation of vitamin D. Non-PTH-mediated pathways include vitamin D–driven intestinal calcium absorption, fibroblast growth factor 23 (FGF23)–regulated phosphate handling, calcitonin effects, and other hormonal or cellular mechanisms that influence calcium or phosphate without PTH signaling.

Clinically, the term is often used in the context of hypercalcemia or hypophosphatemia to indicate PTH-independent etiologies. Non-PTH-mediated hypercalcemia refers to conditions in which PTH is suppressed or normal and elevated calcium results from alternative drivers, such as malignancy with secretion of PTH-related protein (PTHrP), vitamin D intoxication or granulomatous disease, excessive calcium or vitamin D intake, or certain medications. Conversely, non-PTH-mediated bone loss or mineral disturbances may arise from hormonal or metabolic factors outside PTH control.

Diagnosis typically starts with measuring serum PTH to classify the abnormality as PTH-mediated or non-PTH-mediated, followed by targeted tests for PTHrP, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and other relevant factors.

See also: parathyroid hormone, hypercalcemia, vitamin D, PTHrP.