Relationship between parathyroid gland size and responsiveness to maxacalcitol therapy in patients with secondary hyperparathyroidism

Okuno, Senji; Ishimura, Eiji; Kitatani, Kayoko; Chou, Hidenori; Nagasue, Kyoko; Maekawa, Kiyoshi; Izumotani, Tsuyoshi; Yamakawa, Tomoyuki; Imanishi, Yasuo; Shoji, Tetsuo; Inaba, Masaaki; Nishizawà, Yoshiki

doi:10.1093/ndt/gfg451

Cited by 56 publications

(53 citation statements)

References 21 publications

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“…It is well known that, in patients with SHPT, the presence of parathyroid enlargement is a major determinant of response to treatment with vitamin D sterols (11)(12)(13). This finding is attributed to the observation that most of the enlarged glands removed from severe SHPT patients exhibit a nodular pattern of hyperplasia and decreased VDR expression (6,9,10), which could render the parathyroid glands less responsive to the biologic actions of vitamin D. In contrast, the present study showed that treatment with cinacalcet, an allosteric activator of the CaSR, is effective in suppressing PTH secretion even in patients with enlarged glands, in which the expression of CaSR is likely to be markedly decreased (7)(8)(9).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the response to vitamin D sterols is substantially reduced once parathyroid hyperplasia has progressed to the advanced nodular form, presumably because of the reduced expression of calcium-sensing receptors (CaSR) and vitamin D receptors (VDR) (6 -10). Several clinical studies suggest that parathyroid gland volume in excess of 500 mm 3 , as evaluated by ultrasonography, appears to be a useful indicator of responsiveness to vitamin D therapy (11)(12)(13). This concept is supported by the observation that surgically removed parathyroid glands weighing Ͼ500 mg usually exhibit nodular formations (3).…”

mentioning

confidence: 97%

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Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

Komaba¹,

Nakanishi²,

Fujimori³

et al. 2010

Clinical Journal of the American Society of Nephrology

127

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Background and objectives: Cinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not been proven whether parathyroid gland size predicts response to therapy and whether cinacalcet is capable of inducing a reduction in parathyroid volume.Design, setting, participants, & measurements: This 52-week, multicenter, open-label study enrolled hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted between 25 and 100 mg to achieve intact PTH <180 pg/ml. Ultrasonography was performed to measure the parathyroid gland size at baseline, week 26, and week 52. Findings were also compared with those of historical controls.Results: Of the 81 subjects enrolled, 56 had parathyroid glands smaller than 500 mm 3 (group S) and 25 had at least one enlarged gland larger than 500 mm 3 (group L). Treatment with cinacalcet effectively decreased intact PTH by 55% from baseline in group S and by 58% in group L. A slightly greater proportion of patients in group S versus group L achieved an intact PTH <180 pg/ml (46 versus 32%) and a >30% reduction from baseline (88 versus 78%), but this was not statistically significant. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size, which was in sharp contrast to historical controls (n ‫؍‬ 87) where parathyroid gland volume progressively increased with traditional therapy alone.Conclusions: Cinacalcet effectively decreases serum PTH levels and concomitantly reduces parathyroid gland volume, even in patients with marked parathyroid hyperplasia.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

Komaba¹,

Nakanishi²,

Fujimori³

et al. 2010

Clinical Journal of the American Society of Nephrology

127

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“…Very high serum levels, as seen in this patient, could be a marker for the severity and controllability of hyperparathyroidism in these cases. Such a possibility needs to be examined in future clinical studies, especially in comparison with previously known markers, such as parathyroid size (42,45) and serum fibroblast growth factor 23 levels (46,47).…”

Section: Discussionmentioning

confidence: 99%

Overproduction and Secretion of a Novel Amino-Terminal Form of Parathyroid Hormone from a Severe Type of Parathyroid Hyperplasia in Uremia

Arakawa¹,

D'Amour²,

Rousseau³

et al. 2006

Clinical Journal of the American Society of Nephrology

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Measurement of bioactive parathyroid hormone (PTH) is essential for optimal management of bone abnormalities in dialysis patients. This can be accomplished by PTH measurements using third-generation PTH assays, which detect more or less of the first six amino acids of the PTH structure. Such assays do not detect non-(1-84) PTH fragments, such as human PTH (7-84), which are recognized by the second-generation PTH assays that use a detection antibody that recognizes an epitope within the 13-34 region of the PTH structure. Therefore, third-generation PTH results are expected to be lower than those that are obtained with second-generation PTH assays. Rare exceptions to this rule have been reported for patients with severe primary hyperparathyroidism or parathyroid cancer. Sera and gland extracts were analyzed from a dialysis patient with high bone turnover disease and with surprising higher PTH levels by a third-generation assay than by a second-generation assay. This finding normalized after the surgical removal of an enlarged gland with a single nodule, an advanced type of nodular hyperplasia. HPLC fractionation of sera and gland extracts revealed the overproduction and secretion of a PTH molecule with an intact amino-terminus structure distinct from (1-84) PTH. This form of PTH was readily detectable by third-generation PTH assays but was poorly reactive in second-generation PTH assays. Therefore, parathyroid glands with advanced uremic nodular hyperplasia may overproduce and secrete a novel, biologically active form of PTH with an intact 1-6 region but a presumably modified 12-18 region required for the detection in second-generation PTH assays.

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“…Thus, when the gland has a volume of more than 300 mm 3 or a largest diameter of more than 1 cm, it is likely that the gland represents nodular hyperplasia. In these patients, 2HPT may be refractory to medical treatment, and PTx should be required (22)(23)(24).…”

Section: Pathogenesis Histopathology and Pathophysiology Of 2hptmentioning

confidence: 99%

Surgical Treatment of Secondary Hyperparathyroidism due to Chronic Kidney Disease

Tominaga¹

2006

Upsala Journal of Medical Sciences

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Relationship between parathyroid gland size and responsiveness to maxacalcitol therapy in patients with secondary hyperparathyroidism

Cited by 56 publications

References 21 publications

Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

Overproduction and Secretion of a Novel Amino-Terminal Form of Parathyroid Hormone from a Severe Type of Parathyroid Hyperplasia in Uremia

Surgical Treatment of Secondary Hyperparathyroidism due to Chronic Kidney Disease

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