Persistently elevated parathyroid hormone levels after parathyroid surgery

BACKGROUND: Persistent elevation of serum parathyroid hormone (PTH), despite normocalcemia, occurs in 8% to 40% of patients after parathyroidectomy. Explanations have included hypocalcemia owing to vitamin D deficiency or bone remineralization, and persistent hyperparathyroidism. METHODS: A retrospective chart review of 816 consecutive patients who underwent surgery for primary hyperparathyroidism was conducted. RESULTS: One hundred fourteen patients (15%) had persistently elevated PTH levels (PPTH). Patients with PPTH had higher preoperative PTH levels than those with normal PTH levels postoperatively. They also had lower postoperative Ca(++) and vitamin D levels. Multiple gland enlargement was identified in fewer patients with PPTH than in those with normal postoperative PTH levels. In patients with PPTH and a postoperative Ca(++) less than 9.6 mg/dL (group I), there was a greater decrease in IOPTH, a higher initial postoperative PTH level, and a lower postoperative vitamin D level than in PPTH patients whose postoperative Ca(++) was > or =9.6 mg/dL (group II). Postoperative Ca(++) and vitamin D levels were also lower in patients whose PPTH did not ultimately resolve. Three patients in group II had recurrent disease. CONCLUSIONS: Persistent elevation of postoperative serum PTH levels in normocalcemic patients is associated with mild hypocalcemia, probably owing to vitamin D deficiency. In some patients it may also be indicative of mild persistent hyperparathyroidism.     

Primärer Hyperparathyreoidismus

Introduction

Normocalcemic hyperparathyrinemia, i.e. elevated parathyroid hormone (PTH) levels after parathyroidectomy in patients with primary hyperparathyroidism (pHPT) may occur in the course of postoperative recovery without the development of persistence or relapse.

Materials, methods and results

Intraoperative and long-term (7 year) postoperative PTH and calcium levels after curative parathyroidectomy are demonstrated on the basis of a case report of a 62-year-old female patient with severe pHPT and pronounced osseous and renal manifestations. The intraoperative PTH gradient displayed a decrease from 1072 pg/ml to 13 pg/ml (normal range 11–67 pg/ml) followed by an increase of up to 287pg/ml. The hyperparathyoid values decline to subnormal levels on administration of calcium and vitamin D and increase again after tapering these medications. The inverse calcium/PTH correlation in the course of the 7-year observation period suggests an intact feed-back mechanism. Preoperative PTH screening was performed in 316 consecutive normocalcemic thyroid patients to evaluate the rate of incidental hyperparathyroidism in patients with normal serum calcium levels. Of these patients 31 (9.8%) with normocalcemia (average 2.28 mmol/l, normal range 2.1–2.7 mmol/l) exhibited increased PTH levels averaging 84.2 pg/ml. A parathyroid adenoma was found intraoperatively as the cause for normocalcemic pHPT in only 1 of these 31 patients.

Discussion and conclusions

A review of the literature revealed that late postoperative elevated parathyroid hormone levels after successful pHPT surgery occur in 21.5%. Multiple causes are discussed, e.g. reactive hyperparathyroidism in cases of relative hypocalcemia, hungry bone syndrome, vitamin D deficiency, renal dysfunction and ethnic or lifestyle differences. In mild cases of postoperative hyperparathyrinemia observation of the patient may be sufficient. In cases of reactive hyperparathyroidism due to hypocalcemia, administration of calcium is indicated, in symptomatic patients, additional administration of vitamin D or calcitriol is necessary. Vitamin D deficiency per se needs adequate substitution. In cases of ongoing hyperparathyrinemia an interdisciplinary diagnostic and therapeutic approach is required.     

The role of parathyroid hormone measurements after surgery for primary hyperparathyroidism

BACKGROUND: During parathyroidectomy for primary hyperparathyroidism (pHPT), intraoperative parathyroid hormone (IOPTH) levels are used to confirm removal of all hyperfunctioning parathyroid tissue. The phenomenon of elevated parathyroid hormone (PTH) levels with normocalcemia after curative parathyroidectomy, seen in up to 40% of patients, continues to be an unexpected and unexplained finding. We therefore investigated whether postoperative PTH levels are as reliable as IOPTH levels in predicting cure after surgery for pHPT. METHODS: We reviewed our prospective database of consecutive patients undergoing surgery for pHPT between December 1999 and November 2004. Curative parathyroidectomy was defined as normocalcemia 6 months or longer postoperatively. RESULTS: A total of 328 patients who underwent 330 operations for pHPT had IOPTH measurements and serum follow-up calcium levels at 6 months or longer. Surgery was curative in 315 (95.5%) operations. IOPTH levels correctly predicted operative success in 98.2% (positive predictive value [PPV]. Postoperatively, the PPV of a normal PTH level at 1 week, 3 months, and 6 months was 97.1%, 97.3%, and 96.5%, respectively. Of all patients with an elevated postoperative PTH level at 1 week, 3 months, or 6 months, only 13.7%, 14.3%, and 14%, respectively, were not cured. CONCLUSIONS: Normal postoperative PTH levels reliably predict operative success. However, they do not improve upon results predicted by IOPTH levels. Elevated postoperative PTH levels do not predict operative failure in most patients. We propose that PTH measurements after surgery for pHPT may be misleading, costly, and not indicated in normocalcemic patients.     

Reelevation of parathyroid hormone level after parathyroidectomy in patients with primary hyperparathyroidism: importance of decreased renal parathyroid hormone sensitivity

BACKGROUND: We hypothesized that impaired peripheral sensitivity to parathyroid hormone (PTH) may play a role in reelevation of PTH after successful operation for primary hyperparathyroidism (pHPT). METHODS: Factors affecting reelevation of PTH were determined in 90 patients who underwent parathyroidectomy for pHPT. PTH/nephrogenous cyclic adenosine monophosphate ratio, as an index of renal resistance to PTH, was examined in relation to factors shown to influence reelevation of PTH. RESULTS: Serum PTH levels were elevated above the upper limit of normal in 23 patients (26%) at 1 week and in 39 patients (43%) at 1 month after parathyroidectomy. These 39 normocalcemic patients with elevated serum PTH at 1 month after parathyroidectomy had a higher preoperative serum level of PTH and lower serum phosphate and 25-hydroxyvitamin D (25OHD) concentrations than those with normal PTH (n = 59). Elevated PTH and low 25OHD were shown by multivariate analysis to be significant predictors of reelevation of PTH. Renal resistance to PTH was higher in patients with vitamin D deficiency or renal insufficiency than in patients with normal serum vitamin D concentrations or normal renal function, and it increased according to increases in levels of PTH. CONCLUSIONS: The mechanism of PTH reelevation in patients with pHPT after successful parathyroidectomy appears to be renal resistance to PTH.     

Measurement of intraoperative parathyroid hormone predicts long-term operative success

HYPOTHESIS: A decrease in the intraoperative parathyroid hormone (PTH) level predicts long-term operative success. DESIGN: A case series of consecutive patients undergoing parathyroidectomy with intraoperative PTH measurement. SETTING: A university hospital. PATIENTS AND INTERVENTION: One hundred two patients with sporadic primary hyperparathyroidism underwent parathyroidectomy according to the principles of unilateral exploration with intraoperative PTH measurement. MAIN OUTCOME MEASURES: Longitudinal effects on levels of serum calcium and PTH. RESULTS: In 94 of 98 patients who underwent primary exploration because of a solitary adenoma, intraoperative PTH decreased at least 60% 15 minutes after gland excision. The 4 cases in which PTH fell to less than 60% were classified as false negatives. Patients examined for multiglandular disease (n = 4) were correctly predicted not to have an adenoma. Twenty-two patients (22%) were unavailable for 5-year follow-up. These patients were followed up for 2 months to 48 months (median, 24 months), and none developed recurrent primary hyperparathyroidism. Of the remaining 80 patients (78%), all but 1 patient had normal or slightly decreased serum calcium levels (mean +/- SD, 9.24 +/- 0.4 mg/dL [2.31 +/- 0.10 mmol/L]) at 5-year follow-up. One patient with hypercalcemia (10.6 mg/dL [2.65 mmol/L]) was interpreted to have developed renal failure with secondary hyperparathyroidism. Thirty-four patients had elevated serum PTH levels at least once during the postoperative study period, with normal or slightly decreased calcium concentrations. The prediction of late postoperative normocalcemia by means of intraoperative PTH measurement had an overall accuracy of 95%. CONCLUSIONS: The measurement of intraoperative PTH during surgery for primary hyperparathyroidism accurately differentiates between single- and multiple-gland disease and ensures good long-term results.     

Surgical management of secondary hyperparathyroidism

Most patients with renal failure maintained on chronic dialysis have elevated parathyroid hormone (PTH) levels and PTH-mediated bone disease (secondary hyperparathyroidism [sHPT]). Elevated PTH production in this setting represents a progressive, exaggerated physiologic response to hypocalcemia by the parathyroid glands, and generalized growth of the parathyroids is an adaptive response to chronic stimulation. Effective medical strategies to reduce PTH secretion and PTH-mediated bone turnover in sHPT (eg, controlling hyperphosphatemia, normalizing serum calcium, and administering vitamin D analogs) has decreased the need for parathyroidectomy in recent years. However, failure of medical therapy because of inadequate treatment, persistent hyperphosphatemia, or acquired parathyroid neoplasia still leads to recommendations for parathyroidectomy in select patients. Furthermore, increased awareness of potential long-term, irreversible cardiovascular effects of uncorrected hyperparathyroidism has led some to advocate parathyroidectomy earlier in the course of this disease. This monograph will review parathyroidectomy for secondary and tertiary hyperparathyroidism.     

Factores de riesgo de persistencia en pacientes con tratamiento quirúrgico de hiperparatiroidismo primario

IntroductionPrimary hyperparathyroidism is the third most common endocrine disease. The aim of our study was to determine long-term outcomes and risk factors for persistence in patients undergoing parathyroidectomy for primary hyperparathyroidism.MethodsRetrospective study including patients undergoing parathyroidectomy between 2009- 2019. Cure was defined as reestablishment of normal calcium homeostasis lasting a minimum of 6 months. Persistence was defined by ongoing hypercalcemia more than 6 months after surgery. Recurrent PHTP was defined by recurrence of hypercalcemia after a normocalcemic interval at more than 6 months after surgery. A more detailed analysis was performed on patients with normocalcemia and persistently elevated PTH levels after surgery. Variables independently related to persistence were analyzed by multivariate analysis.ResultsWe included 212 patients. Mean age was 59 years and 83% were women. Cure was observed in 204 patients (96.2%), persistence in 8 (3.8%) and recurrence in 3 (1.4%). Four patients (1.9%) presented normocalcemia and persistently elevated PTH after surgery. All presented parathyroid pathology (2 adenomas and 2 hyperplasia). In follow-up we observed that adenoma subgroup presented one patient with CKD and one with vitamin D deficiency while in the hyperplasia subgroup two patients presented CKD. Persistence was independently associated with hyperplasia (Odds ratio=12.6, IC95%=1.28-124, p=0.030) and normal parathyroid tissue (Odds ratio=188, IC95%=9.33-379, p=0.001) on histopathological report.ConclusiónPrimary hyperparathyroidism is a safe procedure in terms of morbidity and long-term outcomes. Hyperplasia and normal parathyroid tissue on histopathological report are risk factors for persistence. An interdisciplinary diagnostic and therapeutic approach is required to prevent persistence.     

Parathormone response to thyroid surgery

BACKGROUND: Confident determination of adequate residual parathyroid function early after thyroid surgery could facilitate the discharge of patients soon after their operation without the need for subsequent serum calcium monitoring and/or calcium and vitamin D supplementation. METHODS: Thirty-one patients who underwent 33 thyroid operations (22 unilateral lobectomies and 11 bilateral thyroid resections) were prospectively studied. Parathormone (PTH) levels were measured intraoperatively, and serum calcium was monitored before and after surgery to determine PTH and calcium homeostatic response to thyroid surgery. RESULTS: A significant decrease in circulating PTH occurred during 27 procedures, most markedly after specimen mobilization. Intraoperative PTH and postoperative calcium levels were lowest in those who underwent bilateral operations. Patients who underwent unilateral procedures experienced significant decreases in PTH but not postoperative calcium levels. A PTH level >50% of baseline predicted normocalcemia by postoperative day 3. However, PTH level did not accurately triage other patients' risk for postoperative hypocalcemia. CONCLUSIONS: A decrease in PTH levels intraoperatively is a common event during both unilateral and bilateral thyroid operations. Although normal PTH levels at the end of surgery ensure normocalcemia after surgery, patients with low final PTH measurements may not develop significant hypocalcemia after surgery.     

Oral vitamin D supplementation reduces the incidence of eucalcemic PTH elevation after surgery for primary hyperparathyroidism

BACKGROUND: As many as 43% of patients will have normocalcemic intact parathyroid hormone (PTH) elevation after undergoing curative parathyroidectomy for primary hyperparathyroidism. This phenomenon may be due in part to an absolute or relative deficiency of vitamin D, which is under-recognized in patients with primary hyperparathyroidism. METHODS: From September 1, 2004, to September 30, 2005, 86 consecutive patients underwent parathyroidectomy for primary sporadic hyperparathyroidism (psHPT). The patients were segregated into 2 groups based on postoperative management. Group 1 was composed of 26 patients who received routine oral calcitriol and calcium carbonate postoperatively. The 60 patients in the second group (group 2) received calcium carbonate postoperatively at the discretion of the primary surgeon. RESULTS: A total of 85 patients (99%) achieved postoperative cure with sustained reduction in serum calcium. Within 30 days postoperatively, mean serum PTH levels normalized in both groups (41 +/- 31 vs 39 +/- 31 pg/ml; P = .91). However, at 1 to 3 months postoperatively, mean serum calcium levels remained similar (9.5 +/- 0.7 vs 9.3 +/- 0.5 mg/dl; P = .39) whereas mean serum PTH levels in groups 1 and 2 were 43 +/- 25 pg/ml and 67 +/- 45 pg/ml (P = .02), respectively. At 4 to 6 months postoperatively, mean PTH was again higher in group 2 (36 +/- 22 vs 67 +/- 35; P = .03), whereas mean serum calcium levels were normal (9.2 +/- 0.8 vs 9.6 +/- 0.4 mg/dl; P = .18). The incidence of postoperative normocalcemic PTH elevation was significantly higher in group 2 at 1 to 3 months (14% vs 39%; P = .04) and at 7 to 12 months (22% vs 83%; P = .04). CONCLUSIONS: Vitamin D supplementation following parathyroidectomy for primary hyperparathyroidism reduces the incidence of postoperative eucalcemic PTH elevation.     

Elevated serum parathormone level after "concise parathyroidectomy" for primary sporadic hyperparathyroidism

BACKGROUND: Cure after parathyroid exploration is traditionally assessed by serum calcium concentration 6 months postoperatively. Postoperative normocalcemic elevation of serum parathormone (PTH) level has been described but is of unclear significance. METHODS: In a 6-year prospective study of outcomes in 380 patients undergoing initial parathyroidectomy for primary sporadic hyperparathyroidism, we measured intact serum PTH and calcium levels at more than 5 months. Those with normocalcemic high PTH levels were begun on oral calcium + vitamin supplements and monitored. RESULTS: At more than 5 months postoperatively, normocalcemic elevation in serum PTH level occurred in 28% of patients, was more common after resection of double adenomas (P =.01), and predated the onset of recurrent hypercalcemia in 3 of 3 patients with unrecognized multiglandular disease. Although delayed treatment with calcium and vitamin supplements produced no clear benefit, patients who took such supplements from the date of surgery were much less likely to have an elevated serum PTH level more than 5 months later (P =.0005). CONCLUSIONS: After successful parathyroid surgery, compensatory normocalcemic elevation in serum PTH level is frequent and may arise from dietary deficiency. Monitored supplemental intake of calcium and vitamin D appears to prevent or to normalize the condition in most patients. Patients with normocalcemic elevation in serum PTH level should receive evaluation for dietary deficiencies as well as follow-up for possible residual disease.     

Successful use of cinacalcet HCl in a patient with end-stage renal failure and refractory secondary hyperparathyroidism due to parathyromatosis

We present the case of a 65-year-old male on long-term dialysis for end-stage renal failure, who developed persistent secondary hyperparathyroidism after subtotal parathyroidectomy, which proved refractory to treatment. Parathyromatosis, a rare cause of recurrent hyperparathyroidism, which may develop when tissue seeded into the neck during subtotal or total parathyroidectomy becomes hyperfunctioning [Maxwell and Winearls 1997], was diagnosed. The patient had excessively high levels of circulating parathyroid hormone (PTH), elevated serum calcium and deteriorating cardiovascular status. Repeated surgery and treatment with high-dose vitamin D failed to provide a sustained decrease in serum PTH levels. Administration of cinacalcet HCl, a second generation calcimimetic, at doses of 30 - 180 mg/day provided a gradual and sustained suppression of PTH (> 1,700 - 344 ng/l) without increasing the calcium-phosphate product.     

Postoperative Elevated Serum Levels of Intact Parathyroid Hormone after Surgery for Parathyroid Adenoma: Sign of Bone Remineralization and Decreased Calcium Absorption

Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT) despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical variables known to reflect PTH activity, and bone mineral content (BMC). In addition, an oral calcium loading test was performed 8 weeks after the operation. All patients had low or normal serum calcium levels during follow-up. Eight weeks after operation six patients (35%) had an increased serum PTH level. These patients (group I) preoperatively had higher serum levels of PTH and alkaline phosphatase than patients with normal PTH levels (group II). They also had lower BMC and larger parathyroid adenomas. They did not differ in renal function. At 8 weeks after operation group I showed higher mean serum levels of osteocalcin and propeptide of type I procollagen but lower urinary calcium excretion. In contrast to patients in group II, they also showed a lower calciuric response and a trend to a lower calcemic response during the oral calcium load. The two groups showed similar parathyroid sensitivity for calcium. Patients in group I demonstrated a significant increase in BMC the first year after the operation. Increased serum PTH 8 weeks after surgery for sporadic parathyroid adenoma was not due to persistent pHPT or impaired renal function. Instead, the results imply there is diminished calcium absorption and increased bone turnover with cortical bone remineralization.     

Long-term effects of parathyroid operation on serum calcium and parathyroid hormone values in sporadic primary hyperparathyroidism.

BACKGROUND. This study investigates 410 persons (median age, 67 years) who underwent parathyroid operation for sporadic primary hyperparathyroidism 6 to 32 years (mean, 14.2 years) before 1991. METHODS. Patient records and operative specimens were scrutinized, the patients answered a questionnaire, and fasting serum samples were analyzed for calcium, albumin, creatinine, and intact parathyroid hormone (PTH) values. RESULTS. After primary parathyroid operations were performed with a conservative surgical approach, persistent and recurrent hypercalcemia were noticed in 3.7% and 1.7% of patients, respectively, whereas 4.7% of patients required vitamin D substitution or had essentially mild hypocalcemia. The PTH values were generally increased in patients with postoperative hyperparathyroidism, low in those with vitamin D substitution, and normal to elevated in the patients with hypocalcemia and in those with postoperative normocalcemia. The mean serum creatinine concentration was just below the upper reference range and correlated strongly with serum PTH value. No significant differences in serum PTH values were present between the normocalcemic patients and matched control patients after operation (n = 107), but the patients who underwent operation exhibited greater variation in the PTH concentration. CONCLUSIONS. The results substantiate the efficacy of parathyroid operation in sporadic primary hyperparathyroidism. Biochemical derangements compatible with secondary hyperparathyroidism may evolve during long-term follow-up and contribute to decreases in serum calcium values and increases in serum PTH values of these patients.     

Parathyroidectomy for tertiary hyperparathyroidism associated with X-linked dominant hypophosphatemic rickets

BACKGROUND: X-linked dominant hypophosphatemic rickets (XLHR) is a hereditary metabolic bone syndrome that is only beginning to be understood and is rarely associated with progression to irreversible tertiary hyperparathyroidism. We report our surgical experience with 6 patients with XLHR who underwent parathyroidectomy for associated autonomous parathyroid hyperfunction. HYPOTHESIS: Parathyroidectomy can successfully treat tertiary hyperparathyroidism in the setting of XLHR, although an understanding of expected operative findings and postoperative complications is essential. DESIGN: The study group comprised 6 patients with XLHR identified from our endocrine surgery database. Presentation, surgical procedure, parathyroid pathologic findings, and subsequent outcome are outlined. RESULTS: There were 4 women and 2 men. All were exposed to long-term vitamin D and phosphate supplementation therapy. All had persistently elevated preoperative levels of parathyroid hormone and serum calcium. The patients were treated as follows: 3 had total parathyroidectomy, 2 had 3 parathyroid glands identified and resected, and 1 had 2 abnormal parathyroid glands resected with 2 normal-appearing parathyroid glands left in situ. One patient subsequently required completion parathyroidectomy for recurrent disease. Pathologic examination results revealed hyperplasia of all resected parathyroid glands in 4 of 6 patients. One patient had a single adenoma with 3-gland hyperplasia, and 1 patient had a double adenoma. The principal complication of this procedure was profound symptomatic hypocalcemia requiring intravenous calcium infusion. Hungry bone syndrome was also observed in most subjects. Long-term, all patients achieved normocalcemia. CONCLUSION: Tertiary hyperparathyroidism is a rare but recognized complication of XLHR. Parathyroidectomy effectively treats this complication caused by autonomous parathyroid hyperfunction, but profound postoperative hypocalcemia necessitates careful management.     

Long-Term Changes in Parathyroid Function After Subtotal Thyroidectomy for Graves’ Disease

BACKGROUND: Transient hypocalcemia is one of the postoperative complications of thyroidectomy for Graves' disease, and perioperative parathyroid hormone (PTH) assays are used to predict postoperative hypocalcemia. We evaluated long-term changes in parathyroid function after surgery for Graves' disease. METHODS: Serum PTH values were measured in Graves' patients with postoperative hypocalcemia, and those patients were followed postoperatively. RESULTS: Subtotal thyroidectomy was performed in 275 patients with Graves' disease. Their serum calcium levels were measured on postoperative day (POD) 1, and patients with transient postoperative hypocalcemia were treated with calcium and vitamin D supplementation and followed up. The amount of calcium and vitamin D supplementation was adjusted to keep the patient's serum calcium level within the normal range. Measurement of their serum intact PTH value on POD 1 revealed normal value in 18 patients, a below normal level in 22, and an above normal level in the other 2. During the follow-up period, the serum iPTH values remained normal in 12 patients, recovered to the normal level in 21 patients, and rose above the normal range in 9 patients. The serum iPTH values of all patients eventually reached the normal range during the follow-up period. A marked difference in preoperative serum alkaline phosphatase concentration was observed between the high-iPTH patients and the normocalcemic patients. CONCLUSIONS: The phenomenon of an elevated serum PTH level after surgery for Graves' disease was observed in 21% of the patients with postoperative hypocalcemia despite the achievement of normal serum calcium levels by calcium and vitamin D supplementation.     

Markers of Bone and Calcium Metabolism Following Gastric Bypass and Laparoscopic Adjustable Gastric Banding

BACKGROUND: Several studies have suggested that morbid obesity is associated with vitamin D deficiency and elevated parathyroid hormone (PTH). Studies have also suggested that there is an increase in vitamin D deficiency, bone resorption, and elevated PTH after gastric bypass surgery. Few studies have evaluated markers of bone and calcium metabolism after laparoscopic adjustable gastric banding or compared these results to those after gastric bypass. METHODS: Data on all patients undergoing primary gastric bypass (GBP; n = 979) and laparoscopic adjustable gastric banding (LAGB; n = 269) procedures at a tertiary-referral center from June 1996 through March 2005 were reviewed from a prospective database. Only patients with 25OH vitamin D levels available were included in this study (n = 534; GBP = 403, LAGB = 131). All patients were advised to take at least 1,200 mg calcium and 800-1,200 IU of vitamin D daily before and subsequent to their operation. Markers for bone metabolism [25OH Vitamin D, corrected serum calcium, alkaline phosphatase (AP), and PTH] were evaluated preoperatively and 3, 6, 12, and 24 months postoperatively. An analysis of variance and chi-square were performed to determine differences between the operative groups. Linear regression analysis was performed to evaluate the relationship between preoperative body mass index (BMI) and 25OH vitamin D and PTH levels and between percent excess weight loss and 25OH vitamin D and PTH after surgery. RESULTS: Sixty-four percent of all patients presented with vitamin D deficiency (<20 ng/ml) and 14% presented with elevated PTH preoperatively. Mean 25OH vitamin D levels and AP levels increased significantly after GBP surgery (vitamin D, 17 to 25 ng/ml 12 months post-op; AP, 80 to 90 IU/L 24 months post-op). Corrected calcium levels remained within normal limits and showed no change over time after both procedures. AP levels significantly increased from 76 IU/l preoperatively to 82 IU/l 6 months after LAGB surgery and then decreased to 59 IU/l 24 months after LAGB surgery. Linear regression analysis of preoperative vitamin D, PTH, and BMI values showed a significant positive relationship between initial BMI and PTH (r = 0.29) and a significant negative relationship between vitamin D and initial BMI (r = -0.19). A significant positive linear relationship between vitamin D and percent excess weight loss was evident 12 and 24 months after GBP surgery (r = 0.39 and 0.57, respectively). A negative relationship was evident between PTH and vitamin D 6 months after GBP surgery (r = -0.35) and 12 months after LAGB surgery (r = -0.61). CONCLUSIONS: These findings suggest that morbid obesity is associated with vitamin D deficiency, and elevated PTH and with adequate supplementation, GBP, and particularly LAGB, patients can improve their bone metabolism abnormalities related to obesity. Furthermore, adequate supplementation for GBP patients may attenuate the increased risk for bone loss associated with malabsorption from the bypass.     

The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism.

BACKGROUND: Treatment of persistent hyperparathyroidism in renal transplant patients resistant to calcium and vitamin D sterols is limited and often requires parathyroidectomy. Given the potential hazards linked to surgery, an alternative approach to manage excess parathyroid hormone (PTH) secretion is needed. Calcimimetics inhibit PTH secretion by modulating the calcium-sensing receptor in the parathyroid. Lowering of the serum calcium concentration with the calcimimetic cinacalcet has previously been demonstrated in patients with primary hyperparathyroidism or with secondary hyperparathyroidism on dialysis. Here we present the first clinical observations of a calcimimetic in patients with persistent hyperparathyroidism. METHODS: A 30 mg dose of cinacalcet was prescribed once daily for 3 months to seven female and seven male stable renal transplant patients, aged 23-65 years, 7 months to 14 years after transplantation, with a serum creatinine ranging from 89 to 229 micromol/l and persistent hyperparathyroidism. Concomitant medication included cyclosporin and low-dose prednisone in all patients. RESULTS: On cinacalcet, serum calcium decreased and normalized in all but two patients (baseline 2.72+/-0.03 mmol/l; 1 month 2.42+/-0.04 mmol/l, P<0.001), whereas serum PTH and phosphate levels did not change significantly. A slight reduction in renal function, as assessed by serum creatinine concentration, was observed at months 2 and 3 (P<0.05). An immunoglobulin-deficient patient developed colitis after 1 week of treatment and cinacalcet was withdrawn. No patient stopped cinacalcet because of other presumed side effects. CONCLUSION: Calcimimetics are a promising therapy in renal transplant patients with persistent hyperparathyroidism. Prospective controlled studies must now be designed focusing on functionally relevant musculo-skeletal end-points and allowing the exclusion of negative effects on long-term renal and general outcome of such patients.     

Surgical management of parathyroid disease

Primary hyperparathyroidism is a common endocrine disorder caused by excessive PTH production by one or more parathyroid glands. The diagnosis is via biochemistry and surgery is the only definitive treatment. All patients may be considered for surgery, particularly those under 50 years of age, symptomatic disease or evidence of end-organ damage. Imaging studies are often used to plan surgical strategy. The majority of patients with primary hyperparathyroidism have single gland disease. Positive imaging studies allow patients to undergo targeted surgery. Patients with negative imaging should be offered a traditional four-gland bilateral neck exploration. Secondary hyperparathyroidism is most commonly caused by vitamin D deficiency and renal failure. Medical management is the first-line treatment, followed by parathyroidectomy in selected cases with renal disease and extremely high PTH levels. Tertiary hyperparathyroidism is seen in patients with continued autonomous function of the parathyroid glands after removal of the underlying stimulus. It is commonly seen in renal transplant patients and parathyroidectomy has a role.     

Postoperative tetany in Graves disease: important role of vitamin D metabolites

OBJECTIVE: To test the authors' hypothesis of the causal mechanism(s) of postoperative tetany in patients with Graves disease. SUMMARY BACKGROUND DATA: Previous studies by the authors suggested that postoperative tetany in patients with Graves disease occurs during the period of bone restoration and resulted from continuation of a calcium flux into bone concomitant with transient hypoparathyroidism induced by surgery. PATIENTS AND METHODS: A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and bone metabolic markers in 109 consecutive patients with Graves disease who underwent subtotal thyroidectomy. RESULTS: Preoperative serum iPTH levels negatively correlated with ionized calcium levels and positively correlated with 1,25(OH)2D or 1,25(OH)2D/25OHD. After the operation, there was a significant decline in levels of ionized calcium, magnesium, and iPTH. Serum iPTH was not detected in 15 patients after surgery. Four of these 15 patients, and 1 patient whose iPTH level was below normal, developed tetany. Preoperative serum ionized calcium levels were significantly lower, and iPTH levels were higher, in the 5 patients with tetany than in the 11 patients who did not develop tetany despite undetectable iPTH levels. The tetany group had significantly lower serum 25OHD levels and higher 1,25(OH)2D levels, and had increased 1,25(OH)2D/25OHD as an index of the renal 25OHD-1-hydroxylase activity than those in the nontetany group. These results suggest that patients with a high serum level of iPTH as a result of low serum calcium levels (secondary hyperparathyroidism) are susceptible to tetany under conditions of hypoparathyroid function after surgery. CONCLUSIONS: Postoperative tetany occurs in patients with secondary hyperparathyroidism caused by a relative deficiency in calcium and vitamin D because of their increased demand for bone restoration after preoperative medical therapy concomitant with transient hypoparathyroidism after surgery. Calcium and vitamin D supplements may be recommended before and/or after surgery for patients in whom postoperative tetany is expected to develop.     

Genetic hypercalcemia

A genetic disorder should be suspected in patients with hypercalcemia, notably those who are young; have family members with hypercalcemia; or have had a tumor of the endocrine pancreas, thyroid, pituitary, adrenal gland, or jaw bone. All forms of hypercalcemia should be interpreted according to the serum level of parathyroid hormone (PTH). Genetic forms are thus classified as related or unrelated to a parathyroid gland disorder. When the PTH level is elevated or is not depressed despite the hypercalcemia, findings that suggest family history of hypercalcemia due to a genetic cause include syndromic manifestations in the patient or family members, parathyroid cancer (either suspected before surgery or confirmed during parathyroidectomy), multiple or recurrent parathyroid tumors, a family history of primary hyperparathyroidism, and the onset of primary hyperthyroidism before 50 years of age. In patients with moderate hypercalcemia, a normal PTH level, and relative hypocalciuria, the first hypothesis is a mutation in the calcium-sensing receptor gene, which is often difficult to distinguish from primary hyperparathyroidism, particularly when there is no known family history of hyperparathyroidism, as is often the case. A low PTH level suggests non-parathyroid hypercalcemia due to a genetic defect in patients with no evidence of other conditions associated with hypercalcemia and low PTH levels and in those whose calcitriol levels are elevated or normal (instead of depressed as expected when PTH is elevated). Patients with hypercalciuria but no evidence of conditions such as granulomatous diseases should be evaluated for increased vitamin D sensitivity due to a CYP 4A1 mutation. Other very rare causes include hypophosphatasia due to ALPL mutations, which is characterized by a low alkaline phosphatase level; and renal phosphate wasting due to an NPT2A mutation, in which serum phosphate levels are low. A thorough analysis of the clinical and laboratory data can point toward a genetic disorder in patients with hypercalcemia. The diagnosis is then confirmed by obtaining genetic tests tailored to the clinical and laboratory test abnormalities. The current development of diagnostic genetic testing is shedding new light on the phenotypes, thereby improving their management.