Three large, functioning cystic parathyroid adenomas

ObjectiveTo report a very rare case of 3 large, functioning cystic parathyroid adenomas causing primary hyperparathyroidism.MethodsWe present the history, clinical findings, laboratory test results, radiologic findings, endocrine workup results, intraoperative surgical challenges, and surgical pathology report of the study patient. We review the literature and discuss the importance of intraoperative parathyroid hormone (PTH) measurement in such cases.ResultsA 79-year-old woman presented with primary hyperparathyroidism and elevated levels of calcium and PTH. Localization studies confirmed the presence of a large right upper parathyroid adenoma. On exploration, a very large cystic parathyroid gland was identified at that location. Because intraoperative PTH levels remained elevated, further exploration was pursued, which revealed 2 more large cystic glands on the left side that were resected. This resulted in an adequate but slow PTH drop. The right lower gland appeared normal. On follow-up 4 days and 6 weeks after surgery, the calcium and PTH levels had normalized.ConclusionThis case highlights the aspects of intraoperative PTH use and underscores the need to exclude multigland disease even in the setting of a very large parathyroid cyst with concordant localization studies. (Endocr Pract. 2012;18:e14-e16)     

Suppressibility of Parathyroid Hormone in Primary Hyperparathyroidism

ObjectiveTo describe an unusual case of pathologically confirmed primary hyperparathyroidism in a patient presenting with severe hypercalcemia and an undetectable parathyroid hormone (PTH) level.MethodsWe present a detailed case report and outline the serial laboratory findings. In addition, the possible causes of low serum PTH levels in the setting of primary hyperparathyroidism are discussed.ResultsA 16-year-old female patient presented with severe epigastric pain, found to be attributable to acute pancreatitis. At hospital admission, her serum calcium concentration was high (14.0 mg/dL); the patient also had a normal serum phosphorus level of 3.6 mg/dL and an undetectable PTH level (< 0.2 pmol/L). An evaluation for non-PTH-mediated causes of hypercalcemia revealed a partially suppressed thyroid-stimulating hormone concentration and a below normal 1,25-dihydroxyvitamin D level, consistent with her suppressed PTH. One week after the patient was dismissed from the hospital, repeated laboratory studies showed a serum calcium value of 11.1 mg/dL, a serum phosphorus level of 2.8 mg/dL, and an elevated PTH concentration of 11.0 pmol/L, consistent with primary hyperparathyroidism. A repeated 1,25-dihy-droxyvitamin D measurement was elevated. A parathyroid scan showed a parathyroid adenoma in the left lower neck area, and she subsequently underwent successful surgical resection of a pathologically confirmed parathyroid adenoma.ConclusionThis case demonstrates that the serum PTH level can be suppressed in patients with primary hyperparathyroidism. Moreover, it emphasizes the need for careful evaluation of the clinical context in which the PTH measurement is determined. Consideration should be given to repeating measurement of PTH and serum calcium levels when the initial laboratory evaluation of hypercalcemia is unclear because dynamic changes in calcium metabolism may occur in the presence of secondary contributing factors. (Endocr Pract. 2007;13:785-789)     

Identifying Parathyroid Hormone Disorders and their Phenotypes through a Bone Health Screening Panel: It's not Simple Vitamin D Deficiency!

Objectives: To determine the utility of bone health screening panels in identifying disorders of parathyroid gland secretions.Methods: A retrospective analysis of biochemical parameters in a bone health screening panel (BHSP) was conducted. Low and high cutoffs were applied to determine hypofunctioning and hyperfunctioning conditions related to parathyroid hormone. Clinical phenotypes of parathyroid gland abnormalities were determined using a combination of levels of calcium, 25-hydroxyvitamin D, and intact parathyroid hormone (iPTH). A PTH nomogram was applied to calculate the maximum expected PTH for existing levels of 25-hydroxyvitamin D. Medical records of patients were reviewed for clinical validation of biochemical findings.Results: Sixty-eight percent of subjects showed abnormal PTH secretion. Primary hyper- and hypoparathyroidism were detected in 1% (n = 5) and 0.4% (n = 2) of subjects, respectively. Normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high-normal PTH were identified in 8.5% (n = 37) and 2% (n = 10) of subjects, respectively. All subjects with primary and normocalcemic hyperparathyroidism had higher measured PTH than calculated maximum PTH using the PTH nomogram. Secondary hyperparathyroidism and functional hypoparathyroidism were present in 18% (n = 88) and 39% (n = 194) of subjects, respectively. High prevalence of bone pains, renal stones, and low bone mineral density were identified in patients with abnormal PTH secretion.Conclusion: Panel testing is useful in early diagnosis of metabolic bone disorders related to PTH. A BHSP helps identify normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high PTH.Abbreviations:25OHD = 25-hydroxyvitamin DAKUH = Aga Khan University HospitalBHSP = bone health screening paneliPTH = intact parathyroid hormonemaxPTH = maximum parathyroid hormoneMBD = metabolic bone diseaseNCHPT = normocalcemic hyperparathyroidismPHPT = primary hyperparathyroidismPTH = parathyroid hormoneSHPT = secondary hyperparathyroidismVDD = vitamin D deficiency     

Does Baseline PTH Influence Recovery of Bone Mineral Density,Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism

Objective: This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery.Methods: This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery.Results: Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638 ± 0.093 versus 0.698 ± 0.041 g/cm²; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH.Conclusion: The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score     

Alendronate increases bone mineral density in patients with symptomatic primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is often associated with low bone mineral density (BMD). An open-labeled, prospective trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with advanced PHPT. All patients had symptomatic PHPT and met surgical guidelines however refused surgery. Nineteen patients was treated with alendronate for 2 years. The primary outcome index, BMD, was measured at the lumbar spine (LS) and femoral neck (FN) every 6 months by dual-energy x-ray absorptiometry. Serum calcium, phosphorous and PTH, and urinary calcium excretion were monitored every 3 months. Treatment with alendronate over 2 years was associated with a significant (5.3+/-0.4%; p<0.01) increase in LS BMD in comparison with baseline. FN BMD increased significantly at 24 months with alendronate by 2.5%+/-0.7 (p<0.01) from baseline. Serum calcium, phosphorus and PTH, and urine calcium excretion did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS and FN at 24 months from baseline values with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in symptomatic PHPT among those with low BMD, who are candidates for surgery but either decline or for whom surgery is contraindicated.     

Falsely Low Parathyroid Hormone Secondary to Biotin Interference: A Case Series

ObjectiveTo present a case series on biotin interference in parathyroid hormone (PTH) level measurement.MethodsWe review the presentation and management of patients at our institution evaluated for unexpectedly low PTH levels while taking biotin supplements in the setting of high or normal serum calcium.ResultsTwo patients presented with surprising low parathyroid levels—one during preoperative evaluation for hyperparathyroidism and another during postoperative follow-up after subtotal parathyroidectomy. The patients were found to be taking 1,500 mcg and 5,000 mcg of biotin per day, respectively. The role of biotin interference was confirmed in one of the patients when she was retested off biotin, and PTH levels responded appropriately. Biotin supplements remain as unbound molecules in the serum, thus interfering with PTH enzyme-linked immunosorbent assay (ELISA) results and falsely depressing the PTH level.ConclusionBiotin supplement use has expanded over the years, ranging from medically endorsed therapies to home remedies. Review of the 2 ELISA systems used at our institution demonstrates that free biotin mimics the biotinylated antibody used in the detection process. Screening for biotin use prior to PTH measurement and automatic biotin levels for clinically aberrant PTH levels provide the clinician with a true PTH level-lowering the disease burden of untreated hyperparathyroidism while avoiding unnecessary work-ups for other processes. (Endocr Pract. 2013;19:451-455)     

Primary Hyperparathyroidism: Comparing Between Solid and Cystic Adenomas and the Efficacy of Ultrasound and Single-Photon Emission Computed Tomography in their Diagnosis

Objective: Primary hyperparathyroidism (PHPT) is a disorder that results from abnormal functioning of the parathyroid glands. The purpose of this study was to compare cystic and solid adenomas by analyzing different variables associated with PHPT and parathyroid adenomas (age, calcium, phosphorus, and parathyroid hormone &lsqb;PTH] levels, adenoma volume) while comparing the efficacy of ultrasound and single-photon emission computed tomography in differentiating between both types of adenoma.Methods: From 152 patients diagnosed with PHPT between January 2013 and 2014, only 109 patients who had positive ultrasonographic findings for single parathyroid adenoma were included in the study.Results: A total of 26 patients had cystic adenomas and 83 patients had solid adenomas. Sestamibi (MIBI) was negative in 50% of the cystic adenoma group and 27.7% of the solid adenoma group, with an overall technetium-MIBI efficacy of 67%. Age, phosphorus level, and adenoma volume were significantly higher in patients with cystic adenomas (P = .001, P = .02, and P = .02, respectively), whereas calcium and PTH levels were significantly higher in patients with solid adenomas (P = .02, P = .038, respectively). MIBI had a significant correlation with PTH levels (P = .031) and adenoma volume (P = .05) only in patients with solid adenomas. No significant correlation was found between sex and type of parathyroid adenoma.Conclusion: The current study is the first to compare age, PTH levels, and adenoma volume between cystic and solid adenoma patients, providing more information for the poorly understood pathology of cystic adenomas. Our findings showed that age and calcium and PTH levels are significantly higher in patients with solid adenomas, whereas adenoma volume and phosphorus levels are significantly higher in patients with cystic adenomas.Abbreviations: BMD = bone mineral density GFR = glomerular filtration rate iPTH = intact parathyroid hormone MIBI = sestamibi PHPT = primary hyperparathyroidism PTH = parathyroid hormone SPECT = single-photon emission computed tomography Tc = technetium US = ultrasound     

Celiac Disease Manifesting as Isolated Hypocalcemia

ObjectiveTo describe a patient who presented with hypocalcemia and hypocalciuria as the initial manifestations of celiac disease, despite a normal vitamin D status.MethodsWe review the diagnostic evaluation, treatment, and biochemical and bone mineral density responses of a patient with asymptomatic celiac disease, which was initially suggested because of a low serum calcium level that became attributable to isolated malabsorption of calcium.ResultsA 36-year-old woman presented with hypocalcemia in the presence of normal serum 25- hydroxyvitamin D and high serum 1,25-dihydroxyvitamin D levels. She had hypocalciuria and secondary hyperparathyroidism that were refractory to pharmacologic calcium and cholecalciferol supplementation. Fecal calcium excretion indicated malabsorption of calcium, and biopsy of the small intestine demonstrated pathologic changes characteristic of celiac disease. Bone mineral density, determined by dual-energy x-ray absorptiometry, was in the osteopenic range at the femoral neck. The initiation of a gluten-free diet resulted in correction of all biochemical abnormalities and a substantial increase in bone mineral density.ConclusionPrimary intestinal malabsorption of calcium without concomitant vitamin D deficiency is possible in celiac disease because of the preferential involvement of the proximal small intestine early in the disease process. Our patient had hypocalcemia caused by celiac disease and values for serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D that were normal and elevated, respectively. Correction was demonstrated after dietary gluten withdrawal. (Endocr Pract. 2004;10:203-207)     

Optimization of Minimally Invasive Radio-Guided Parathyroidectomy: The Importance of Neck Ultrasonography and Intraoperative Parathyroid Hormone Assay

ObjectiveTo determine whether close collaboration between a neck ultrasound–certified endocrinologist and a skilled endocrine surgeon can optimize minimally invasive radio-guided parathyroidectomy (MIRP) surgical outcomes.MethodsOutcome data were collected on patients with primary hyperparathyroidism whom we intended to treat with MIRP at the induction of anesthesia between October 1, 2005, and December 31, 2007. Patients underwent preoperative gamma camera sestamibi scanning (GCSS), intraoperative gamma probe sestamibi scanning (IOSS), and preoperative neck ultrasonography. Intraoperative parathyroid hormone (PTH) monitoring was performed. Postoperative surgical success was defined as a serum calcium concentration between 8.0 and 10.4 mg/dL within 4 weeks of surgery.ResultsDuring the study period, MIRP was planned for 46 patients. Of the 46 patients, 39 had preoperative neck ultrasonography; 7 underwent evaluation by an endocrinologist or internist who was not ultrasound certified and they therefore did not undergo preoperative ultrasonography. IOSS correctly identified 1 adenomatous gland in 38 of 46 patients (83%), while GCSS correctly localized 1 adenomatous gland in 30 of 46 patients (65%). In 11 GCSS–negative patients, IOSS identified the abnormal gland in 7 (64%), while ultrasonography identified the abnormal gland in 8 (73%). The surgical approach was converted to traditional parathyroidectomy in 3 patients. Every patient exhibited at least a 51% drop in intraoperative PTH levels with resection of the final adenoma; average decrement for the entire group was 79 ± 8% from the highest baseline level. Forty-five patients (98%) demonstrated sustained normalization of serum calcium within several days of surgery.ConclusionA collaborative endocrinology and surgical endocrine oncology practice arrangement, emphasizing careful preoperative physician-supervised neck ultrasonography and the use of intraoperative PTH measurement, optimizes MIRP outcomes. (Endocr Pract. 2008;14: 856-862)     

Abnormalities of Vitamin D and Calcium Metabolism after Surgical Treatment of Morbid Obesity: A Study of 136 Patients

ObjectiveTo assess the effect of bariatric surgical treatment of morbid obesity on bone mineral metabolism.MethodsWe analyzed pertinent vitamin D and calcium metabolic variables in 136 patients who had undergone a malabsorptive bariatric operation. Measurements of bone mineral density (BMD), serum 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D [1,25-(OH)₂D], parathyroid hormone (PTH), calcium, phosphorus, and alkaline phosphatase were performed. Statistical analyses assessed correlations among various factors.ResultsThe mean age (± SD) of the study group was 48.34 ± 10.28 years. Their mean weight loss was 114.55 ± 45.66 lb, and the mean duration since the bariatric surgical procedure was 54.02 ± 51.88 months. Seventeen patients (12.5%) had a T-score of -2.5 or less, and 54 patients (39.7%) had a T-score between –1.0 and –2.5. Of 119 patients in whom serum 25-OHD was measured, 40 (34%) had severe hypovitaminosis D (25-OHD < 8 ng/mL), and 50 patients (42%) had low hypovitaminosis D (serum 25-OHD 8 to 20 ng/mL). The magnitude of weight loss correlated negatively with serum 25-OHD, calcium, phosphorus, and calcium × phosphorus product values and positively with serum alkaline phosphatase level. Serum 25-OHD and calcium concentrations correlated positively with the BMD. PTH, serum 1,25-(OH)₂D, and alkaline phosphatase concentrations correlated negatively with the BMD, a reflection of the presence of secondary hyperparathyroidism, an accelerated conversion of 25-OHD to 1,25-(OH)₂D by the elevated PTH levels, and increased osteoblastic activity. The mean daily vitamin D supplementation was 6,472 ± 9,736 IU.ConclusionHypovitaminosis D and subsequent bone loss are common in patients who have undergone a bariatric surgical procedure for morbid obesity. These patients require rigorous vitamin D supplementation. (Endocr Pract. 2007;13:131-136)     

Trabecular Bone Score in Patients with Normocalcemic Hyperparathyroidism

Objective: The effects of normocalcemic hyperparathyroidism (NHPT) on bone remain unclear. The objective of this study was to evaluate differences in the trabecular bone score (TBS) of NHPT patients and asymptomatic hypercalcemic hyperparathyroidism (HHPT) patients.Methods: We performed a prospective study that enrolled consecutive patients with asymptomatic hyperparathyroidism (NHPT and HHPT) with a follow-up ≥1 year at the University Hospital of Valladolid, Spain. Metabolic phosphocalcium plasma and urine parameters were evaluated in ≥2 determinations during follow-up to classify patients as NHPT patients or asymptomatic HHPT patients. A control group was enrolled during the same period. TBS and bone mineral density (BMD) were evaluated.Results: Thirty-nine patients with asymptomatic HPT (24 with NHPT and 15 with HHPT) and 24 controls were recruited. NHPT patients and HHPT patients had a similar mean age, vitamin D level, TBS, and areal BMD (all sites). Compared to controls, symptomatic HPT patients had significantly higher parathyroid hormone (PTH) and calcium levels and significantly lower TBS and areal BMD at all sites (all P<.05). A significant negative relationship between TBS and PTH was found in asymptomatic HPT patients (r = -0.320, P = .043), which remained significant after adjustment for age, sex, and body mass index.Conclusion: There was no difference in the TBS between NHPT and HHPT patients. However, there was a reduction in the TBS of patients with asymptomatic HPT that was related to PTH levels but had no repercussion on bone mass. Higher levels of PTH seem to be responsible for this alteration in microarchitecture texture.Abbreviations:aBMD = areal bone mineral densityBMD = bone mineral densityBMI = body mass indexDXA = dual-energy X-ray absorptiometryHHPT = hypercalcemic hyperparathyroidismHPT = hyperparathyroidismHR-MRI = high-resolution magnetic resonanceHR-pQcT = high-resolution peripheral quantitative computed tomographyNHPT = normocalcemic hyper-parathyroidismPTH = parathyroid hormoneTBS = trabecular bone score25vitD = 25-hydroxyvitamin D     

Significance of Elevated Parathyroid Hormone After Parathyroidectomy

ObjectiveTo review the prevalence of parathyroid hormone elevation after parathyroidectomy for primary hyperparathyroidism and to discuss possible mechanisms.MethodsA Medline search of the English-language literature published between 1990 and 2009 was performed using the search terms “elevated PTH after parathyroidectomy.” All of the identified articles reported either prospective or retrospective studies without control groups. Studies that included patients with secondary or tertiary hyperparathyroidism were not reviewed.ResultsWithin 1 week to 5 years after parathyroidectomy, 9% to 62% of patients with a normal serum calcium concentration are reported to have an elevated parathyroid hormone concentration. No evidence suggests that postoperative normocalcemic parathyroid hormone elevation is an indication of surgical failure and recurrent hypercalcemia. Preoperative findings in patients with postoperative parathyroid hormone elevation include lower vitamin D concentration, higher concentrations of bone turnover markers, and higher parathyroid hormone concentration. Potential mechanisms for parathyroid hormone elevation in the setting of normocalcemia include vitamin D deficiency, hungry bone syndrome, and parathyroid hormone resistance. Study findings suggest a possible benefit of postoperative calcium and vitamin D supplementation, but no randomized trials have been done.ConclusionElevation of parathyroid hormone commonly occurs after parathyroidectomy for primary hyperparathyroidism, although the underlying mechanism remains unclear. (Endocr Pract. 2010;16:112-117)     

Preoperative Calcium and Parathyroid Hormone Values Are Poor Predictors of Gland Volume and Multigland Disease in Primary Hyperparathyroidism: A Review of 2000 Consecutive Patients

ObjectiveCalcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland size, with higher values predicting single-gland disease. In this modern series, these preoperative values were correlated with operative findings to determine their utility in predicting the gland involvement at parathyroid exploration.MethodsTwo thousand consecutive patients who underwent initial surgery for sporadic primary hyperparathyroidism from 2000 to 2014 were reviewed. All patients underwent a 4-gland exploration. Relationships between preoperative calcium and PTH values with the total gland volume of each patient were examined and stratified using the number of involved glands: single adenoma (SA), double adenoma (DA), and hyperplasia (H).ResultsThere were 1274 (64%) SA, 359 (18%) DA, and 367 (18%) H cases. There was a poor correlation between preoperative calcium and PTH values (R = 0.37) and both poorly correlated with the total gland volume (R < 0.40). Similarly, subgroup analysis using the number of involved glands showed poor correlation. The mean total gland volume was similar among all subgroups (SA = 1.28 cm³, DA = 1.43 cm³, and H = 1.27 cm³; P = .52), implying that individual glands were smaller in multigland disease. SA was found in 271 (53%) of patients with calcium levels of ≤10.5 mg/dL and 122 (78%) with levels of ≥12 mg/dL (P < .001).ConclusionThis is the largest series correlating preoperative calcium and PTH values with operative findings of gland size and number of diseased glands. Although a lower calcium value predicts somewhat more multigland disease, the overall poor correlation should make the parathyroid surgeon aware that gland size and multigland disease cannot be predicted by preoperative laboratory testing.     

Calcium-Creatinine Clearance Ratio is not Helpful in Differentiating Primary Hyperparathyroidism from Familial Hypercalcemic Hypocalciuria: A Study of 1,000 Patients

Objective: With increasing recognition of more subtle presentations of primary hyperparathyroidism (pHPT), laboratory values are frequently seen in a range that would be expected for patients who have familial hypercalcemic hypocalciuria (FHH). Calcium-creatinine clearance ratio (CCCR) has been advocated as a diagnostic tool to differentiate between these two disorders. However, it is limited by an indeterminate range (0.01 to 0.02). The aim of this study was to assess the relevance of CCCR in a modern series of patients with surgically managed pHPT.Methods: We performed a retrospective cohort study of 1,000 patients who underwent parathyroid surgery for pHPT over 11 years. CCCR was evaluated by degree of biochemical derangement, single versus multiple gland disease, and interfering medications.Results: Patient demographics and resected histopathology were typical for a current series of patients with pHPT. In retrospect, none of the patients were suspected to have FHH postoperatively. CCCR was <0.01 for 19.0%, between 0.01 and 0.02 for 43.7%, and >0.02 in 37.3%. Distribution of CCCR for patients free from interfering medications and different histologic subtypes were the same. One-third of the cohort had mild calcium elevations, more typical for FHH. Of these, almost two-thirds had a CCCR in a range suspect for FHH (<0.02).Conclusion: To our knowledge, this is the largest series to evaluate the validity of CCCR for patients with surgically confirmed pHPT. The utility of CCCR in screening for FHH is limited, as 63% of modern patients with confirmed pHPT have low values.Abbreviations: CaSR = calcium sensing receptor; CCCR = calcium-creatinine clearance ratio; CeE = calcium excretion; FHH = familial hypercalcemic hypocalciuria; pHPT = primary hyperparathyroidism; PTH = parathyroid hormone     

Associations of Serum Ionized Calcium,Phosphate, and Pth Levels with Parathyroid Scan in Primary Hyperparathyroidism

Objective: To evaluate the relationship between various biochemical parameters in patients with primary hyperparathyroidism (PHPT) with positive and negative technetium-99 sestamibi (Tc) parathyroid scans performed with single-photon emission computed tomography/computed tomography (SPECT/CT).Methods: This retrospective analysis was used to develop a logistic probability model. It included 218 patients with PHPT. The main outcome measures were serum total calcium, ionized calcium, intact parathyroid hormone (PTH), albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-h urinary calcium levels, and parathyroid adenoma weight.Results: Individually, using cut-off levels of 6.0 mg/dL for ionized calcium, 3.0 mg/dL for phosphate, and 90 pg/mL for intact PTH, we found that 91.3% (P = .005), 70.7% (P = .004) and 87.90% (P = .023) of the patients had a positive Tc scan with their corresponding strengths of associations in the parentheses. Similar significant associations were sustained in multivariate setting for serum ionized calcium (P = .015), phosphate (P = .016), and intact PTH (P = .028). A logistic probability model was designed to predict the probability of being positive for Tc scan given a set of covariates.Conclusion: There are significant associations between the levels of serum ionized calcium, phosphate, intact PTH, and Tc scan positivity. Further studies with larger patient populations are needed.Abbreviations: BMI = body mass index; CT = computed tomography; CV = coefficient variation; DXA = dual-energy x-ray absorptiometry; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PPV = positive predictive value; PTH = parathyroid hormone; SPECT = single-photon emission computed tomography; Tc = technetium-99 sestamibi     

Utility of Ultrasound-Guided Fine-Needle Aspiration of Parathyroid Adenomas for Localization Before Minimally Invasive Parathyroidectomy

ObjectiveTo determine the sensitivity and specificity of ultrasound (US)-guided fine-needle aspiration (FNA) and measurement of parathyroid hormone (PTH) in the aspirate (FNA/PTH) as a preoperative localization procedure.MethodsThe study group consisted of 34 consecutive patients with primary hyperparathyroidism. The FNA/PTH estimations in these patients were compared with those from 13 proven thyroid nodules. All patients underwent US study of the neck, which suggested the presence of a solitary adenoma in 30 patients and of hyperplasia in 2; no adenoma or hyperplasia could be visualized in 2 patients. Thirty-two patients underwent FNA/PTH, which yielded a mean PTH level of 22,060.0 ± 6,653.0 pg/mL. This result was significantly different (P < 0.001) from the mean PTH level in 13 thyroid nodules (9.0 ± 1.0 pg/mL).ResultsOn the basis of the FNA/PTH results, 28 patients with suspected adenomas underwent minimally invasive parathyroidectomy (MIP), and 2 patients are awaiting a surgical procedure. Of these 28 patients, 27 had more than a 50% decline in intraoperative PTH level after removal of the suspected adenoma, confirming surgical success. In 1 patient, multigland hyperplasia was discovered during the operation. The 2 study subjects with US findings of suspected hyperplasia underwent 4-gland surgical procedures. All patients treated surgically continued to have normal serum calcium levels 6 to 18 months post-operatively.ConclusionPrimary hyperparathyroidism is caused most commonly by a solitary adenoma and less commonly by multigland hyperplasia of the parathyroid glands. Surgical resection is the only curative therapy. MIP has become a frequently used strategy, but there are limitations to current preoperative localization techniques. We conclude that US-guided FNA is a useful technique that facilitates MIP, with a high degree of specificity (95%) and sensitivity (91%). (Endocr Pract. 2007;13:333-337)     

Safety of Vitamin D Replacement in Patients with Primary Hyperparathyroidism and Concomitant Vitamin D Deficiency

ObjectiveTo evaluate the safety of vitamin D replacement in patients with vitamin D deficiency and primary hyperparathyroidism.MethodsRetrospective chart review of 35 patients from our endocrine clinic, age 22 to 89 years, diagnosed with primary hyperparathyroidism and vitamin D deficiency, and treated with either 1,000 to 2,000 international units (IU) of vitamin D daily or 50,000 IU of vitamin D weekly for 5 months. Data were collected before and after treatment on serum calcium, 25-hydroxyvitamin D (25-OH D), intact parathyroid hormone (iPTH), phosphorus, alkaline phosphatase, nephrolithiasis, fractures, and osteoporosis.Results25-OH D increased significantly, from a baseline of 14.65 ± 6.57 ng/mL to 42.17 ± 12.98 ng/ mL after weekly treatment with 50,000 IU of vitamin D (P<.0001), and from 22.42 ± 5.47 ng/mL to 33.33 ± 6.39 ng/mL following daily treatment with 1,000 to 2,000 IU of vitamin D (P<.0001). Pre- and posttreatment unadjusted serum calcium remained stable in the high-dose group (10.80 ± 0.43 mg/dL vs. 10.72 ± 0.67 mg/dL; P = .47), but decreased slightly in the low-dose group (10.76 ± 0.58 mg/dL vs. 10.11 ± 0.54 mg/dL; P = .0007). After adjusting for age, sex, vitamin D, and PTH levels, the small calcium difference in the low-dose group became statistically insignificant. Treatment with either high or low doses of vitamin D did not significantly change iPTH levels. Creatinine remained stable in all patients, and no new cases of nephrolithiasis were reported.ConclusionReplacing vitamin D in mild primary hyperparathyroidism is safe, effective, and does not increase calcium to dangerous levels. (Endocr Pract. 2013;19:420-425)     

Increased Serum Calcium is not Common in Hospitalized Patients with Primary Hyperparathyroidism: A Retrospective,Observational Study

Objective: Serum calcium levels often decrease during acute illness in patients with an intact calcium-regulating system. However, the dynamics of serum calcium levels in hospitalized patients with primary hyperparathyroidism (PHPT) have not yet been described.Methods: Clinical and laboratory data were retrospectively retrieved from the electronic medical records of patients with PHPT before, during, and after hospitalization for various reasons (excluding parathyroid surgery).Results: There were 99 nonselected patients with asymptomatic, hypercalcemic PHPT, hospitalized for various reasons; 42% were admitted for apparent infectious or septic conditions, and 58% were admitted for noninfectious conditions. Total serum calcium increased >0.5 mg/dL in 7.4% of the patients: 10.9% and 2.5% of the patients with noninfectious and infectious conditions, respectively. In 65.7% of the patients, the mean total serum calcium (TsCa), but not albumin-corrected calcium (corrCa), decreased significantly during hospitalization, down to below the upper limit of the reference range. Although prehospitalization TsCa and corrCa were similar in patients with infectious and noninfectious conditions, during hospitalization, TsCa was lower in patients with infectious conditions (P = .02). Both TsCa and albumin returned to prehospitalization levels after recovery.Conclusion: TsCa increases in a minority of hospitalized PHPT patients. In the majority of hospitalized patients with PHPT, TsCa, but not corrCa, decreases to within the normal reference range, more so in patients with infectious conditions, obscuring the major characteristic of PHPT. Therefore, it is prudent to follow calcium and corrCa during hospitalization in patients with PHPT.Abbreviations: corrCa = albumin-corrected serum calcium; IQR = interquartile range; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TsCa = total serum calcium     

Association of Plasma Parathyroid Hormone with Metabolic Syndrome and Risk for Cardiovascular Disease

ObjectiveTo review the current literature investigating the association of plasma parathyroid hormone (PTH) with the prevalence of metabolic syndrome and the risk for cardiovascular disease (CVD).MethodsWe conducted a search of PubMed and Medline database using the terms hyperparathyroidism, metabolic syndrome, hypertension, hyperlipidemia, hyper-glycemia, and CVD. We reviewed relevant studies from 2004 to 2012.ResultsThe current literature assessing the association of plasma PTH levels with metabolic syndrome and CVD is inconsistent; however, positive associations among hyperparathyroidism, metabolic syndrome, and CVD were found in a majority of the studies. The differences in the study populations may partly explain the mixed results.ConclusionIn the general population, a high serum PTH level predisposes patients to CVD mortality. Further research is needed to determine the role of PTH in the etiology of metabolic syndrome and CVD. (Endocr Pract. 2013;19:712-717)     

Parathyroid Hormone,Cognitive Function and Dementia: A Systematic Review

BackgroundMetabolic factors are increasingly recognized to play an important role in the pathogenesis of Alzheimer’s disease and dementia. Abnormal parathyroid hormone (PTH) levels play a role in neuronal calcium dysregulation, hypoperfusion and disrupted neuronal signaling. Some studies support a significant link between PTH levels and dementia whereas others do not.MethodsWe conducted a systematic review through January 2014 to evaluate the association between PTH and parathyroid conditions, cognitive function and dementia. Eleven electronic databases and citation indexes were searched including Medline, Embase and the Cochrane Library. Hand searches of selected journals, reference lists of primary studies and reviews were also conducted along with websites of key organizations. Two reviewers independently screened titles and abstracts of identified studies. Data extraction and study quality were performed by one and checked by a second reviewer using predefined criteria. A narrative synthesis was performed due to the heterogeneity of included studies.ResultsThe twenty-seven studies identified were of low and moderate quality, and challenging to synthesize due to inadequate reporting. Findings from six observational studies were mixed but suggest a link between higher serum PTH levels and increased odds of poor cognition or dementia. Two case-control studies of hypoparathyroidism provide limited evidence for a link with poorer cognitive function. Thirteen pre-post surgery studies for primary hyperparathyroidism show mixed evidence for improvements in memory though limited agreement in other cognitive domains. There was some degree of cognitive impairment and improvement postoperatively in observational studies of secondary hyperparathyroidism but no evident pattern of associations with specific cognitive domains.ConclusionsMixed evidence offers weak support for a link between PTH, cognition and dementia due to the paucity of high quality research in this area.