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PubMed1984

Successful localisation of parathyroid adenomata by thallium-201 and technetium-99m subtraction scintigraphy: description of an improved technique.

An improved method for parathyroid scanning using thallium-201 and technetium-99m subtraction imaging is described. The technique successfully localised ten of eleven parathyroid adenomas confirmed at neck exploration. Two false-positive studies were encountered in patients with no adenoma at operation, probably due to thyroid nodules. The technique was less successful in identifying diffusely hyperplastic parathyroid glands and was negative in a single patient with recurrent, functional parathyroid carcinoma.

Adenoma↗

PubMed1992

[Diagnosis and treatment of primary hyperparathyroidism].

Primary hyperparathyroidism is nowadays not uncommon in Japan. The incidence is considered to be one in every 2,500 to 5,000 persons. Many advances have occurred in diagnosis, localization study, and treatment of the disease. Surgery remains the treatment of choice for patients with primary hyperparathyroidism. Notwithstanding, there are still controversies concerning the management of primary hyperparathyroidism. One of the current disputable points is whether the use of localization study in patients who are undergoing and initial operation is justified or not. Another is whether unilateral exploration is justified or not. The basic reasons for these persistent controversies is the lack of consensus about incidence of multiglandular hyperplasia or double adenomas. Our observation implies that the incidence of hyperplasia or double adenomas among all the patients with primary hyperparathyroidism in Japan is lower than that in western countries. Since diagnostic accuracy of noninvasive localization studies has recently improved, it seems reasonable to adopt unilateral neck exploration in our country. It is also characteristic in Japan that the incidence of parathyroid carcinoma is relatively high (6%) compared with that reported in many other countries.

Adenoma↗

PubMed2005

Minimally invasive surgery for treatment of hyperparathyroidism.

BACKGROUND: Minimal invasive surgery for parathyroidectomy has been introduced in the treatment of hyperparathyroidism. OBJECTIVE: To evaluate the contribution of the sestamibi-SPECT (MIBI) localization, cervical ultrasonography, and intraoperative rapid turbo intact parathormone assay in minimal invasive parathyroidectomy. METHODS: Between August 1999 and March 2004, 146 consecutive hyperthyroid patients were treated using the MIBI and ultrasound for preoperative localization and iPTH measurements for intraoperative assessment. RESULTS: Parathyroid adenoma was detected in 106 patients, primary hyperplasia in 16, secondary hyperplasia in 16, tertiary hyperplasia in 5, and parathyroid carcinoma in 1 patient. Minimal invasive exploration of the neck was performed in 84 of the 106 patients (79.2%) with an adenoma, and in 17 of them this procedure was performed under local cervical block anesthesia in awake patients. Adenoma was correctly diagnosed by MIBI scan in 74% of the patients, and by ultrasound in 61%. The addition of ultrasonography to MIBI increased the accuracy of adenoma detection to 83%. In 2 of the 146 patients (1.4%) iPTH could not be significantly reduced during the initial surgical procedure. Minimal invasive surgery with minimal morbidity, and avoiding bilateral neck exploration, was achieved in 79.2% of patients with a primary solitary adenoma. CONCLUSIONS: Preoperative localizationof the parathyroid gland by MIBI and ultrasound together with intraoperative iPTH measurements resulted in an overall cure rate of 98.6% for the entire series, The addition of ultrasound to the MIBI scan increased the accuracy of adenoma detection.

Adenoma↗

PubMed1977

Secretory and ultrastructural responses of hyperfunctioning human parathyroid tissues to varying calcium concentration and vinblastine.

Parathyroid hormone (PTH) secretion from abnormal hyperfunctioning human parathyroid tissues was studied in vitro to determine whether abnormal tissues were responsive to changes in calcium concentration and what role their subcellular organelles played in secretion. Hyperfunctioning tissues from one patient with secondary parathyroid hyperplasia, four patients with parathyroid adenomas, and one patient with parathyroid carcinoma were incubated in media containing low calcium (0.75 mM), normal calcium (1.5 mM), high calcium (3.0 mM), or vinblastine (0.01 mM), a microtubular disrupter. Also, in order to correlate ultrastructural responses with PTH secretion, after incubation tissues of one adenoma were objectively quantitated by stereologic techniques. Low calcium consistently stimulated mean PTH secretion from hyperplastic and adenomatous tissue, but only during the 1st hour of secretion. Low calcium inconsistently stimulated carcinomatous tissue. High calcium suppressed mean PTH release from all tissues. Vinblastine did not consistently inhibit secretion from adenomatous or hyperplastic tissue. Ultrastructural analysis of adenomatous tissue showed a sparsity of granules (0.87 per cent of cellular volume) compared to previously studied bovine tissues. Low calcium significantly increased the volume fraction of pinocytotic vesicles to 300 per cent (p less than 0.01) and reduced the surface area of straight (inactive) membrane to 60 per cent (p less than 0.01) of the normal calcium control. Secretion granules, when present, were adjacent to submembrane vesicles. The number and structure of microtubules were not changed by low or high calcium or vinblastine. Our findings indicate that parathyroid adenomas and hyperplastic tissues can respond acutely to low calcium stimulation and high calcium suppression. However, the acute response to low calcium stimulation may not be sustained in some cases because of limited storage of hormone. The increase in pinocytosis in low calcium-stimulated tissue suggests a coupling of exocytosis with membrane endocytosis, possibly related to membrane recycling. Our findings with vinblastine suggest that microtubular integrity is not a prerequisite for basal PTH secretion in adenomatous tissue.

Adenoma↗

PubMed1990

[Carcinoma of the parathyroid glands. Apropos of a case associated with thyroid struma].

The paper reports a case of carcinoma of the parathyroid associated with thyroid struma and underlines the difficulties of intraoperative diagnosis and the surgical approach which should be adopted on the basis of this finding. Often the diagnosis of the malignant nature of the neoplasia is based on the possible appearance of local or distant recurrence rather than histological examination.

Adenoma↗

PubMed1993

In situ correlation of synthesis and storage of parathormone in parathyroid gland disease.

The distribution and expression of parathyroid hormone (PTH) were investigated in normal and abnormal parathyroid tissue. PTH was detected using a monoclonal antibody with specificity for the 44-68 region of the PTH molecule. Prominent reactivity for PTH was seen in normal parathyroid with a granular pattern of staining. Active parathyroid tissue (adenoma and hyperplasia) showed much less reactivity for PTH, although there was prominent reactivity in the normal tissue around adenomas. Comparison of expression of PTH with that of parathormone mRNA showed a reciprocal pattern in normal tissue and, to a less marked extent, in abnormal tissue. Parathyroid carcinoma in particular had coinciding areas of PTH and PTH mRNA expression. Oxyphil cells had little or no PTH expression, except in the associated 'colloid' in some cases. The findings indicate an inverse relationship between storage and cellular synthesis of PTH, this being more marked in physiological than in pathological conditions of the parathyroid.

Adenoma↗

PubMed2005

Cinacalcet HCl: a novel therapeutic for hyperparathyroidism.

Hyperparathyroidism (HPT) is a significant clinical concern for patients with a variety of diseases, notably the secondary HPT associated with chronic kidney disease requiring dialysis. Secondary HPT is associated with elevated para-thyroid hormone (PTH) levels, decreased levels of 1,25 dihydroxyvitamin D, and disordered mineral levels (usually high calcium and phosphorus). If not controlled, secondary HPT can result in bone disease, vascular calcification, and ultimately, patient mortality. Established, conventional therapies, such as 1,25dihydroxyvitamin D analogues (vitamin D analogues) and phosphate binders, have proven to be inadequate in enabling patients to meet the National Kidney Foundation's-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) treatment goals for PTH, calcium and phosphorus levels. A novel therapeutic, cinacalcet HCl (formerly AMG 073; Sensipar in the US and Mimpara in Europe; Amgen, Inc.), binds directly to the calcium-sensing receptor (CaR) on the cells of the parathyroid gland, increasing the receptor's sensitivity to calcium and reducing PTH, serum calcium and phosphorus levels. Treatment with cinacalcet in clinical trials has safely and effectively improved achievement of the NKF-K/DOQI goals. Cinacalcet has also reduced serum calcium levels in patients with primary HPT, including parathyroid carcinoma, in the clinical trial setting. Evidence suggesting the utility of cinacalcet in these diseases and the potential for additional therapeutic applications will be discussed.

Calcitriol↗

PubMed2005

Radioguided surgery of primary hyperparathyroidism using the low-dose 99mTc-sestamibi protocol: multiinstitutional experience from the Italian Study Group on Radioguided Surgery and Immunoscintigraphy (GISCRIS).

UNLABELLED: This study evaluated the accuracy of (99m)Tc-sestamibi scintigraphy and neck ultrasonography in patients with primary hyperparathyroidism (PHPT) and the role of intraoperative hand-held gamma-probes in minimally invasive radioguided surgery (MIRS) of patients with a high likelihood of a solitary parathyroid adenoma (PA). The study was undertaken under the aegis of the Italian Study Group on Radioguided Surgery and Immunoscintigraphy (GISCRIS). METHODS: Clinical records were reviewed for 384 consecutive PHPT patients undergoing radioguided surgery using a low dose of (99m)Tc-sestamibi. Selection of patients for MIRS instead of traditional bilateral neck exploration was based on preoperative imaging indicating a solitary PA. (99m)Tc-Sestamibi (37-110 MBq, or 1-3 mCi) was injected in the operating theater 10-30 min before the start of the intervention. Either 11-mm collimated (309 patients) or 14-mm collimated (75 patients) gamma-probes were used. Intraoperative quick parathyroid hormone (IQPTH) assay was used on 308 patients (80.2%). RESULTS: MIRS was successfully performed on 268 (96.8%) of 277 patients. Conversion to bilateral neck exploration was necessary in 9 patients (3.3%) because of either persistently high IQPTH levels after removal of the preoperatively visualized PA (4 patients), intraoperative frozen-section diagnosis of parathyroid carcinoma (2 patients), or hard-to-remove PA (3 patients). MIRS, which was performed under locoregional anesthesia in 72 patients, required a mean operating time of 37 min and a mean hospital stay of 1.2 d. MIRS was successfully performed also on 32 (78.0%) of 41 patients who had previously undergone thyroid or parathyroid surgery. No major surgical complications were observed in the MIRS group, and there were only 24 cases (11%) of transient postoperative hypocalcemia. The probe was of little help in patients with concomitant (99m)Tc-sestamibi-avid thyroid nodules and not helpful at all in patients with negative scan findings preoperatively. IQPTH measurement helped to disclose some cases of multigland parathyroid disease. CONCLUSION: (99m)Tc-Sestamibi scintigraphy, especially if combined with neck ultrasonography, is highly accurate in selecting PHPT candidates for MIRS. The low-dose (99m)Tc-sestamibi protocol (which entails a low-to-negligible radiation exposure to the surgical team) is safe and effective for MIRS. MIRS plays a limited role in patients with concomitant (99m)Tc-sestamibi-avid thyroid nodules and should be discouraged in patients with negative (99m)Tc-sestamibi finding preoperatively. IQPTH can be recommended during MIRS to facilitate intraoperative identification of previously undiagnosed multigland parathyroid disease.

Adult↗

PubMed2003

[Radio-guided surgery in primary hyperparathyroidism: clinical indications and technical procedure].

AIM: The purpose of the present study was to assess the utility of the intraoperative gamma probe technique in a group of 128 patients suffering from primary hyperparathyroidism (PH). METHODS: In view of surgery, these patients were homogeneously subjected to a diagnostic protocol comprising double tracer scintigraphy ((99mTc)-Pertecnetate/(99mTc)-MIBI) and neck echotomography, carried out in a single session. They were then all operated on by the same surgical team. RESULTS: In 97 patients with scintigraphic and echographic evidence of single parathyroid enlargement and normal thyroid gland, mini-invasive radio-guided surgery (MRS) was planned. In 94 of these 97 patients (96%) MRS was carried out successfully by removal of a single parathyroid adenoma (PA) through a small cutaneous incision of 2-2.5 cm; in the remaining 3/97 patients (3.1%), it proved necessary to convert to bilateral surgical exploration of the neck following intraoperative diagnosis of a parathyroid carcinoma in 2 cases and of multiglandular pathology (MGP) suggested by the persistence of elevated values of intraoperative parathormone (PTH) in 1 case. It should be pointed out that the use of IGP enabled us to carry out limited surgical exploration in 18 of 23 patients who had previously undergone operation on the thyroid and/or parathyroids. In a second group of 31 patients with presumed preoperative diagnosis of MGP (5 cases) or nodular goitre concomitant with PH (26 cases), IGP was used in the course of standard bilateral surgical exploration of the neck and enabled us to locate: an ectopic parathyroid gland in the thymus in 1 case of MGP, a PA in the deep levels of the neck in 2 cases with goitre and an ectopic PA at the bifurcation of the carotid in 1 other case with goitre. It should however be specified that in certain other patients with goitre it proved difficult intraoperatively to distinguish thyroid nodes from a PA adhering to the thyroid. CONCLUSIONS: On the basis of the data to emerge from the present study we can conclude that: 1) in patients with PH presenting a scintigraphic and echographic picture indicating single PA and normal thyroid with high probability, the IGP technique proves effective in carrying out an MRS; 2) 37 MBq of (99mTc)-MIBI are an adequate dose for the correct performance of MRS; 3) a rapid intraoperative dose of PTH is to be recommended so as to confirm complete removal of the hyperfunctioning parathyroid tissue; 4) MRS may be employed successfully also in those patients previously subjected to thyroid or parathyroid surgery for the purpose of limiting the surgical trauma connected to reintervention and, therefore, to reducing the risk of complications; 5) IGP would not appear to be recommendable in patients with PH and concomitant goitre, with the possible exception of ectopic PA.

Adenoma↗

PubMed2002

Targeted parathyroidectomy in the era of intraoperative parathormone monitoring.

A combination of preoperative localization and intraoperative parathormone (PTH) monitoring permits targeted parathyroidectomy. Multiple approaches have been developed, ranging from unilateral neck exploration (UE) to radio-guided parathyroidectomy (RP) to endoscopic parathyroidectomy (EP). The purpose of this study was to evaluate the efficacy of these approaches in the management of primary hyperparathyroidism. From June 1998 to November 2000 a total of 110 targeted parathyroid operations were performed at a university medical center. All patients underwent technetium-99m-sestamibi scanning, ultrasonography, or both prior to surgery. Intraoperative PTH monitoring was utilized in all cases. Thirty-seven patients underwent UE, 59 underwent RP, and 14 underwent EP. Follow-up ranged from 1 to 24 months. All patients were cured following parathyroidectomy as predicted by a more than 50% reduction of the intraoperative PTH level following removal of all hypersecreting glands. Altogether, 103 patients had a solitary adenoma (95%), and 1 patient had a parathyroid carcinoma. Six patients (5%) had multigland disease, including four cases of hyperplasia and two patients with a double adenoma. Eighty-three patients (75%) were discharged the day of surgery. The use of preoperative localization and intraoperative PTH monitoring permits a targeted approach to the treatment of primary hyperparathyroidism. Endocrine surgeons should be facile in all minimally invasive parathyroid techniques to individualize the operative approach.

Adult↗

PubMed1999

Preservation of the recurrent laryngeal nerves in thyroid and parathyroid reoperations.

BACKGROUND: The recurrent laryngeal nerve (RLN) is vulnerable to injury in thyroid and parathyroid reoperations because of the presence of scar tissue and displacement of the nerve from its normal position. METHODS: Since 1993, we have performed 132 reoperations for recurrence of thyroid or parathyroid carcinoma (102 cases), persistent hyperparathyroidism (21 cases), and recurrent goiter (9 cases). One or both RLNs were identified in all cases (208 nerves). Exposure of the nerve was accomplished by a lateral approach (159 nerves), a low anterior approach (41 nerves), or the identification of the nerve between the larynx and the upper pole of the thyroid, in parathyroid reoperations (8 nerves). Dissection was then done while the nerve was kept in view at all times. RESULTS: Preoperatively, unilateral vocal cord paralysis was noted in 6 patients. Resection of a functioning RLN encased with a tumor was intentionally carried out in 5 patients. The RLNs were identified and preserved in all other cases. Among these 121 patients, transient hoarseness lasting up to a month occurred in 12 patients. CONCLUSIONS: Careful identification and exposure of the RLN through a previously undissected area can be done safely in thyroid and parathyroid reoperations and resulted in no permanent recurrent nerve injuries in our experience.

Follow-Up Studies↗

PubMed2006

Sonography of the abnormal parathyroid gland.

In 80% to 90% of patients with primary hyperparathyroidism, a single parathyroid adenoma will be identified as the culprit, whereas the remaining 10% to 20% are caused by multiple adenomas, parathyroid hyperplasia, and rarely, parathyroid carcinoma. At the 2002 National Institute of Health consensus meeting, minimally invasive parathyroidectomy was endorsed as a promising and attractive alternative to total parathyroidectomy. Therefore, preoperative localization of the adenoma is critical in the clinical evaluation of the patient before surgical resection. Although adenomas less than 1 cm may be difficult to visualize sonographically, knowledge of typical imaging characteristics of parathyroid adenomas and use of special sonographic techniques will facilitate identification in most patients. Typical imaging characteristics of parathyroid adenomas include homogeneously hypoechoic echotexture on gray scale with an enlarged feeding artery and peripheral arc of vascularity seen on color and power Doppler. Proper neck extension, unilateral graded compression techniques, and patient swallowing will improve visualization of adenomas.

Humans↗

PubMed2000

Papillary thyroid carcinoma associated with parathyroid adenoma detected by pertechnetate-MIBI subtraction scintigraphy.

Two cases of papillary thyroid carcinoma coexisting with a parathyroid adenoma are reported. A double-tracer pertechnetate-MIBI subtraction scan combined with neck ultrasound correctly visualized the site of the parathyroid adenoma despite the presence of thyroid nodule(s) located in the opposite thyroid lobe in one case and in both thyroid lobes in the other case. In both patients, the papillary thyroid carcinoma was cold with Tc-99m pertechnetate and hot with MIBI. Total thyroidectomy and parathyroidectomy of a solitary parathyroid adenoma were performed in both patients. Pertechnetate-MIBI subtraction scanning associated with neck ultrasound appears to be a useful imaging technique to detect parathyroid adenoma before operation in patients with concomitant thyroid nodular disease. A MIBI-hot and Tc-99m pertechnetate-cold thyroid nodule can indicate the possible presence of a malignant lesion.

Adenoma↗

PubMed2004

Unusual functioning endocrine tumors.

Endocrine surgeons should maintain a high index of suspicion when patients are diagnosed with clinical signs or symptoms of parathyroid carcinoma. Although rare, the best chance for cure of these patients is at the time of the initial operation. Surgical resection of recurrent disease can provide effective palliation and can sometimes be assisted using gamma-probe directed dissection of sestamibi-labeled tumor tissue. Treatment of hyperparathyroidism in the setting of multiple endocrine neoplasia type 1 (MEN-1), particularly in the reoperative setting, can be aided by using the rapid intraoperative parathyroid hormone assay to judge the adequacy of parathyroid debulking. In addition, in selected cases, the gamma probe can assist in identifying the location of ectopic or autografted sestamibi-labeled parathyroid tissue. Patients with incidental adrenal masses rarely require fine needle aspiration to exclude metastatic cancer. Fine needle aspiration, if performed, should never precede hormone evaluation to exclude pheochromocytoma. Patients who are diagnosed with incidental adrenal masses in the setting of a prior or concurrent cancer diagnosis are equally likely to have a primary adrenal mass as they would be to have metastatic cancer in the adrenal gland. Pheochromocytomas occasionally develop in patients with MEN-1. In suspicious cases, molecular identification of an MEN-1 mutation can be used to confirm the diagnosis. Preoperative hormone evaluation of a patient with an adrenal incidentaloma should include evaluation for subclinical Cushing's syndrome through an overnight 1-mg dexamethasone suppression test. Identification of this condition allows for safe peri- and postoperative steroid hormone replacement, with very slow withdrawal of exogenous steroids to allow the opposite adrenal gland to recover and avoid postoperative Addisonian crisis. Paragangliomas are more commonly multifocal and malignant compared to pheochromocytomas. Evaluation of patients with paragangliomas should include radiographic staging for multifocality and metastatic disease, and postoperative hormone and radiographic follow-up evaluation should be performed. Consideration should be given to genetic testing for von Hippel-Lindau and succinate dehydrogenase mutations. Surgical treatment of rare functioning pancreatic and duodenal endocrine tumors, such as metastatic sporadic insulinoma and MEN-1-associated gastrinoma, can provide effective palliation. Surgical treatment should be integrated into a comprehensive treatment scheme that recognizes the natural history of the disease and incorporates appropriate adjunctive therapies and follow-up strategies.

Adrenal Gland Neoplasms↗

PubMed2002

99mTc-tetrofosmin or 99mTc-sestamibi for double-phase parathyroid scintigraphy?

Several years ago technetium-99m tetrofosmin was reported to localise parathyroid adenomas. The aim of this study was to compare the sensitivity of this radiopharmaceutical with that of (99m)Tc-sestamibi using a double-phase parathyroid scintigraphy protocol. Scans of 12 patients were evaluated visually and lesion to thyroid ratios were calculated. Nine of the patients were subsequently operated on; a total of eight parathyroid adenomas or hyperplastic glands were histologically confirmed in seven of the patients, while in one patient a parathyroid carcinoma was histologically proven. All of these patients had positive (99m)Tc-sestamibi scintigrams, whereas only two (99m)Tc-tetrofosmin scintigrams were positive. With (99m)Tc-sestamibi there was a significant increase in the lesion to thyroid ratio from 10 min to 90 min and 150 min p.i. which was not seen on scintigraphy with (99m)Tc-tetrofosmin. This makes (99m)Tc-tetrofosmin less suitable for double-phase parathyroid scintigraphy.

Adenoma↗

PubMed1993

Cervical exploration for primary hyperparathyroidism.

The classical presentation of primary hyperparathyroidism, "moans, bones, groans," is no longer commonly seen since the diagnosis of hypercalcemia is now made much earlier with the routine use of the SMA 12. In the past 8 1/2 years, 85 patients underwent cervical exploration in our institution for primary hyperparathyroidism. There were 34 male and 51 female patients, ranging in age from 18-84 years. The specific symptoms included hypertension in 40 patients, generalized weakness in 25, renal stones in 14, psychiatric problems in 2, and bone changes on X-ray in 4. Forty-one patients were totally asymptomatic. The diagnosis was made mainly on the basis of history, serum calcium and phosphorous levels, parathormone assay, and 24-hour urinary calcium studies. Preoperative localization studies were performed in 38 patients. Thallium technetium subtraction scans, when positive, were very helpful. The surgical approach involved stepwise exploration of both sides of the neck with identification of all four parathyroid glands. In patients with uniglandular pathology (87%), the adenoma was removed with biopsy of at least one normal gland. In multiglandular disease, the abnormal glands were removed. Frozen section was routinely performed to confirm the presence of parathyroid tissue and no attempt was made to pathologically distinguish adenoma from hyperplasia. Two patients had parathyroid carcinoma. In three patients, serum calcium levels did not fall, resulting in an operative success rate of 96%. One patient treated by subtotal parathyroidectomy developed permanent hypoparathyroidism and one other patient developed temporary hypocalcemia. Only a single patient developed vocal cord palsy. Early exploration in patients with primary hyperparathyroidism is indicated. The basic diagnostic workup is sufficient for initial exploration. It is important to distinguish uniglandular from multiglandular pathology after careful bilateral exploration and identification of all four parathyroid glands.

Adenoma↗

PubMedDate not supplied

Hyperparathyroidism after radiation of the head and neck: a case report and review of the literature.

A 66-year-old woman presented with hypercalcemia and a past history of external radiation to the neck. Hyperparathyroidism in this patient was caused by a parathyroid adenoma. The literature associating hyerparathyroidism with prior radiation of the head and neck was reviewed and analyzed. Current evidence supports a relationship between external radiation of the head or neck and the development of hyperparathyroidism as a late complication. Analysis of data available suggests that radiation-association hyperparathyroidsim develops after an average latent period of 38 years. Parathyroid adenoma occurred more often than did hyperplasia. Parathyroid carcinoma has not been reported in irradiated patients with hyperparathyroidsim. Neither age at radiation exposure, age at diagnosis of hyperparathyroidsim, nor interval between exposure and diagnosis was associated with a specific histologic diagnosis (adenoma or hyperplasis).

Adenoma↗

PubMed2005

Cinacalcet hydrochloride.

Oral cinacalcet hydrochloride (HCl) [Sensipar, Mimpara] is the first in a new class of therapeutic agents, the calcimimetics, and has a novel mechanism of action. It directly modulates the principal regulator of parathyroid hormone (PTH) secretion, namely the calcium-sensing receptor (CaR) on the chief cells in the parathyroid gland. Cinacalcet HCl reduces circulating PTH levels by increasing the sensitivity of the CaR to extracellular calcium. In three pivotal phase III, 26-week, randomised, double-blind, multicentre trials in chronic kidney disease (CKD) patients (n = 1136) on dialysis with uncontrolled secondary hyperparathyroidism (HPT), a significantly higher proportion of oral cinacalcet HCl 30-180 mg/day than placebo recipients achieved a reduction in intact PTH levels to < or =250 pg/mL. Cinacalcet HCl treatment also simultaneously lowered serum calcium and phosphorus, and calcium-phosphorous product levels. Notably, cinacalcet HCl proved effective in a broad range of CKD patients on dialysis with uncontrolled secondary HPT, regardless of disease severity, duration of dialysis treatment, dialysis modality, race, age, gender, or concurrent phosphate binder or vitamin D sterol use. Cinacalcet HCl (60-360 mg/day) also reduced elevated serum calcium levels by > or =1 mg/dL in 15 of 21 (71%) patients with parathyroid carcinoma in an open-label, multicentre, dose-titration trial. Cinacalcet HCl was generally well tolerated in clinical trials. Most treatment-emergent adverse events were mild to moderate in severity.

Animals↗