The Effects of Oral Furosemide on the Response of Urinary Excretion of Cyclic Adenosine Monophosphate and Phosphate to Parathyroid Extract in Normal Subjects

Abstract

We studied the effects of oral furosemide, 80 mg/day for 7 days, on the response of urinary excretion of phosphate and cyclic AMP to exogenous parathyroid extract (PTE) in 6 normal subjects. All 6 subjects had marked increases in urinary calcium and a significant increase in urinary cyclic AMP from the control to the furosemide periods: this suggests that furosemide-induced hypercalciuria produced elevated parathyroid activity. After treatment with furosemide, the response of urinary cyclic AMP and phosphate to PTE was blunted. During the subsequent calcium infusion (4 mg/kg), urinary cyclic AMP was suppressed to subnormal values, and the response to PTE returned to normal. The evidence suggests that furosemide may blunt the response to PTE, perhaps as a result of the elevated parathyroid activity produced by furosemide-induced hypercalciuria and lowering of plasma-ionized calcium. This blunting effect of furosemide on the response of urinary phosphate and cyclic AMP to PTE should be considered in the evaluation of parathyroid function in patients taking furosemide.

Risk factors for secondary hyperparathyroidism in a nursing home population

“…The PTH-elevating effect of frusemide might occur because of a deterioration in renal function. The lack of a difference in the calculated creatinine clearance rate between those treated and not treated with frusemide is consistent with acute and short-term studies of frusemide (Coe et al, 1973;Gabow et al, 1977;Hufnagle et al, 1982;Fujita et al, 1984Fujita et al, , 1985 but does not exclude an initial fall in creatinine clearance in those receiving the drug. The fall in the coefficient for frusemide when creatinine entered the regression equation (compare equations 1 and 2) is consistent with some contribution of the frusemide effect by creatinine, but both remain independent predictors.…”

“…The single most important predictor of PTH was the daily frusemide dose. The most likely mechanism for an effect of frusemide on PTH levels (Venkataraman et al, 1983;Fujita et al, 1984Fujita et al, , 1985Hermida et al, 1985) is that frusemide initially lowers the serum ionized calcium (Gabow et al, 1977;Hermida et al, 1985) through increased urinary calcium excretion (Tambyah & Lim 1969;Knapp & Heath 1969;Yu et al, 1981;Hufnagle et al, 1982;Venkataraman et al, 1983;Fujita et al, 1984;Ogawa et al, 1984;Hermida et al, 1985;Reichel et al, 1992) and/or an elevation in blood pH due to an associated chloruresis (Gabow et al, 1977;Hermida et al, 1985). PTH rises acutely in response to the fall in ionized calcium.…”

“…There was no difference in serum Pi nor UPi/UCr ratio according to frusemide treatment although under the non-fasting circumstances of data collection, these indices may reflect dietary phosphate. Change in Pi may be a reason for the frusemide induced elevation in PTH (Hermida et al, 1985) but evidence for this is scant with short-term studies reporting no or minimal changes in serum and urine Pi following frusemide administration (Steele, 1971;Coe et al, 1973;Gabow et al, 1977;Yu et al, 1981;Fujita et al, 1984Fujita et al, , 1985Ogawa et al, 1984). It remains possible that effects of frusemide on urine minerals were not detected in our study because urine collections were not fasting nor synchronized with medication.…”

Successful Reversal of Furosemide-Induced Secondary Hyperparathyroidism With Cinacalcet

“…3 -8 Coe et al 5 in 1973 demonstrated that adults treated with furosemide had elevated PTH similar to adults with persistent hypercalciuria. In 1985, Fujita et al 6 showed that adults treated for a week with oral furosemide had elevated urine calcium (effect on loop of Henle) and cyclic adenosine monophosphate excretion (effect of elevated PTH). More recently, cross-sectional analyses of large data sets from the United States, Brazil, and Australia have shown the loop diuretic to be associated with SHPT in adults with both normal and reduced renal function.…”

“…1,2 A less known complication of chronic treatment with furosemide is the development of secondary hyperparathyroidism (SHPT). 3 -6 The latter is attributed to the hypercalciuria, leading to the development of hypocalcemia, which stimulates parathyroid hormone (PTH) secretion, 6,7 but recent literature also suggests an additional, direct stimulating effect of furosemide on the parathyroid glands. 8 It is expected that discontinuation of the loop diuretic, at times combined with supplementation with calcium and active vitamin D metabolites, will reverse the SHPT.…”