Nephrogenous cyclic adenosine monophosphate as a parathyroid function test.

Area of Science:

• Endocrinology
• Nephrology
• Clinical Chemistry

Background:

• Primary hyperparathyroidism (1° HPT) is characterized by elevated parathyroid hormone (PTH) levels.
• Assessing cyclic AMP (cAMP) excretion is crucial for understanding PTH activity and diagnosing related disorders.
• Previous methods for measuring total cAMP excretion (UcAMP) faced interpretive challenges, particularly in patients with renal impairment.

Purpose of the Study:

• To prospectively measure nephrogenous cyclic AMP (NcAMP), UcAMP, and plasma immunoreactive parathyroid hormone (iPTH) in control subjects and patients with 1° HPT and chronic hypoparathyroidism.
• To develop and validate a novel parametric expression for UcAMP that accounts for renal function, improving diagnostic utility.
• To evaluate the diagnostic performance of NcAMP and the new UcAMP expression in identifying hyperparathyroidism, including in subgroups with varying degrees of renal insufficiency.

Main Methods:

• Prospective measurement of NcAMP, UcAMP, and plasma iPTH in 55 controls, 57 patients with 1° HPT, and 10 with hypoparathyroidism.
• Analysis of NcAMP and plasma iPTH levels using established immunoassay techniques.
• Development and application of a new parametric expression for UcAMP, normalizing excretion to glomerular filtration rate (GFR), to overcome limitations of previous methods (e.g., normalization to creatinine excretion).

Main Results:

• Elevated NcAMP was observed in 91% of patients with 1° HPT, including those with mild or intermittent hypercalcemia and varying degrees of renal insufficiency.
• Plasma iPTH was elevated in 73% of patients with 1° HPT.
• The novel UcAMP expression, normalized to GFR, demonstrated elevated values in 89% of 1° HPT patients, outperforming normalization to creatinine excretion (81% elevated) and absolute excretion rates, especially in patients with renal impairment.

Conclusions:

• NcAMP measurements are highly sensitive for detecting hyperparathyroidism.
• A novel parametric expression for UcAMP, normalized to GFR, significantly enhances the diagnostic accuracy of cAMP excretion measurements in hyperparathyroidism, even in the presence of renal insufficiency.
• The validated measurements and expressions provide reliable tools for assessing cAMP metabolism and diagnosing parathyroid disorders.