The Frequency and Mechanisms of Urolithiasis in Acromegaly

Abstract

It is generally accepted that acromegaly is often associated with hypercalciuria, but there are few reports on the frequency and the mechanisms of urolithiasis. Recently we consecutively experienced 2 cases of acromegaly with urolithiasis, and these experiences made us investigate the association between urolithiasis and acromegaly. Among 18 acromegalies from 1977 to March 1990 (10 males, 8 females, 24-64 years old), 13 cases (72%) fulfilled the criteria of hypercalciuria (urinary calcium (u-Ca) greater than or equal to 200 mg/day or u-Ca/urinary creatinine (u-Ca/u-Cr) greater than or equal to 0.15), and 7 cases (39%) suffered from urolithiasis that was diagnosed by KUB (4 cases) or X-ray computed tomography (CT) (3 cases). Especially in the last 2 years, 5 out of 7 cases (71%) were complicated with urolithiasis and all 7 cases were associated with hypercalciuria. These results suggest that hypercalciuria and urolithiasis are both much more frequent than previously reported. In 6 cases who were treated by pituitary adenomectomy from 1988-1989 (4 males, 2 females, 24-59 years old), we examined Ca metabolism before and after operation. Before operation, the levels of serum growth hormone (GH), u-Ca (mg/day), u-Ca/u-Cr (in all cases) and plasma somatomedin-C (Sm-C) (in 4 cases) were increased above the normal range. To determine the etiology of hypercalciuria, we performed the oral Ca load test under restriction of Ca (400 mg/day) and P (650 mg/day) intake. The results suggested that the hypercalciuria might be mainly due to the increased absorption of Ca from the intestine (so-called "Absorptive hypercalciuria"). However, the levels of serum vitamin D (Vit. D) metabolites were all within the normal range before operation. After operation, GH and u-Ca/u-Cr (in 5 cases) and u-Ca (mg/day) (in all cases) decreased significantly compared with before operation, and the levels of Sm-C (in all cases), serum 25-(OH)D3, 1 alpha, 25-(OH)2D3 (in 4 cases) and 24,25-(OH)2D3 (in 3 cases) were also reduced after operation. Surprisingly, u-Ca and u-Ca/u-Cr normalized only in 4 cases who showed a reduction in 1 alpha, 25-(OH)2D3 levels after operation, although there were no correlations between u-Ca (mg/day) or u-Ca/u-Cr and 1 alpha, 25-(OH)2D3. Significant correlations were found between u-Ca (mg/day) or u-Ca/u-Cr and Sm-C. The parathyroid function evaluated by the rapid Ca infusion test or nephrogenous cyclic adenosine monophosphate (NcAMP) was normal before and after operation.(ABSTRACT TRUNCATED AT 400 WORDS)

Recurrent Kidney Stone Episodes Leading to a Diagnosis of Occult Acromegaly

“…The mechanism in which acromegaly underlies kidney stone formation involves intestinal hyperabsorption of calcium via the increased promotion of vitamin D activation in the kidneys by excess growth hormone (GH). 1 , 4 Increased serum calcium is then excreted into the urine and binds with oxalate to form calcium oxalate stones. 1 , 3 Although previous reports have elucidated the causative factors of the relationship between a pituitary tumor secreting excess GH and chronic development of primarily calcium oxalate stones in the urinary tract, these reports have not delineated the process by which accurate and timely diagnosis is reached.…”

“… 1 , 4 Increased serum calcium is then excreted into the urine and binds with oxalate to form calcium oxalate stones. 1 , 3 Although previous reports have elucidated the causative factors of the relationship between a pituitary tumor secreting excess GH and chronic development of primarily calcium oxalate stones in the urinary tract, these reports have not delineated the process by which accurate and timely diagnosis is reached. The patient was refractory to both medical and surgical therapy for his kidney stones over 2 decades of his life.…”

“…The association between acromegaly and nephrolithiasis has been previously described. 1 , 2 , 3 , 4 Although the mechanism has been well studied, clinically suspecting patients with recurrent nephrolithiasis who could have acromegaly and referring them for accurate diagnosis and treatment has not been promulgated in urological literature. This is the first case to be reported in the United States of a Caucasian elderly man found to have acromegaly secondary to a pituitary adenoma, explaining his long-standing history of stones.…”

Vanishing hypercalciuric kidney stones after treating underlying acromegaly

“…Although several studies have been published on this subject, the exact mechanism is not yet clear. Moreover, nephrolithiasis with calcium-containing stones occurs more frequently in patients with acromegaly, presumably as a consequence of this hypercalciuria (2) (4) (5) (6) (7).…”