Normocalcemic Hyperparathyroidism Research Articles

Clinical Expression of Calcium Sensing Receptor Polymorphism (A986S) in Normocalcemic and Asymptomatic Hyperparathyroidism.

Normocalcemic and asymptomatic hyperparathyroidism diagnosis are becoming more common. However, their pathophysiology is incompletely known. The aim of the present study was to evaluate the clinical effect of calcium-sensing receptor polymorphism (A986S) in normocalcemic and asymtomatic HPT. Prospective study conducted with 61 consecutive normocalcemic and asymptomatic HPT patients was followed up during a minimum period of 1 year. Secondary causes of hyperparathyroidism were ruled out. Calcium and phosphorus metabolism parameters were evaluated in at least 2 determinations during follow-up to classify as normocalcemic or asymptomatic hyperparathyroidism. Bone mineral density and A986S polymorphism genotype were also analyzed. Thiry-eight patients (62.3%) had the genotype A986A, and 23 (36.7%) patients had A986S (20 patients, 32.8%) or S986S (3 patients, 4.9%). Age, sex, and genotype distributions were comparable in both normocalcemic and asymptomatic hyperparathyroidism. In normocalcemic patients, S allele genotype was associated to statistically significant higher level of intact PTH: 92.0 (SD 18.5) vs. 110.6 (SD 24.4) pg/ml, p<0.05; and remained significant after adjustment by multiple linear regression. In asymptomatic hyperparathyroidism, A986A genotype resulted in a statistically significant higher level of intact PTH, alkaline phosphatase and procollagen amino-terminal propeptide; but only serum calcium remained as an independent predictor of serum intact PTH levels after a multiple linear regression. Bone mineral densitometry between genotypes did not show statistically significant differences. A986S polymorphism of CaSR is an independent predictor of PTH level in normocalcemic hyperparathyroidism patients, but not in asymptomatic hyperparathyroidism. More studies are needed to evaluate the effect of other polymorphisms in normocalcemic and asymptomatic hyperparathyroidism.

Routine parathyroid hormone testing as part of the secondary osteoporosis screen in an ortho-geriatric population

ObjectivesTo determine the prevalence of routine parathyroid hormone (PTH) testing as part of the secondary osteoporosis screen in an inpatient ortho-geriatric population, and the incidence of diagnosing primary hyperparathyroidism (PHPT). DesignRetrospective Audit of the Ortho-geriatric database from January 2010 to March 2014. SettingA single-centre study at a tertiary referral and teaching hospital in metropolitan Victoria, Australia. ParticipantsAll patients with fragility fracture recorded in the Ortho-geriatric database from January 2010 to March 2014. ResultsOne thousand two hundred and sixty-one patients were included in this study. All but seventeen patients in the study were 65 years old and above. Eighty-five percent were ≥75 years old, of which about half of the population were ≥85 years old. The overall male to female ratio was about 1 to 3. 81.4% (1026/1261) of patients had PTH tested. Of this population who were tested, 0.8% (8/1026) had a new diagnosis of PHPT and two patients underwent parathyroidectomy. A total of 87.3% (891/1021) of patients had PTH levels tested despite having normal serum calcium levels. ConclusionWe found that excessive PTH testing was prevalent in a single hospital in metropolitan Victoria. We propose that PTH levels not be done routinely as part of the secondary osteoporosis screen, particularly in ortho-geriatric patients with normal serum calcium levels, as it is unlikely to change management. We acknowledge normocalcemic hyperparathyroidism as a separate entity with risk of progression to PHPT, however the clinical significance of this entity remains unclear.

High offset point for normocalcaemic secondary hyperparathyroidism due to vitamin D deficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Use of cinacalcet in nephrolithiasis associated with normocalcemic or hypercalcemic primary hyperparathyroidism: results of a prospective randomized pilot study.

To evaluate, by means of a prospective randomized study, the efficacy of cinacalcet in the forms of nephrolithiasis associated with primary hyperparathyroidism in both the hypercalcemic and normocalcemic variant. Ten patients suffering from active nephrolithiasis associated with primary hyperparathyroidism (4 hypercalcemics and 6 normocalcemics), equally divided between males and females, were randomly but not blindly addressed to treatment with potassium citrate and allopurinol, or to the same therapeutic regimen in combination with cinacalcet. The dosage of cinacalcet was optimized for each patient in order to obtain a reduction of parathyroid hormone (PTH) within normal limits while enabling the maintenance of adequate calcemic values. All study participants were given the same diet based on a reduction in sodium intake, oxalate-rich foods and animal protein with standardized intake of calcium and an increase in hydration. After a follow up period of 10 months , cinacalcet was associated to standard therapy and diet in patients who were not taken it, conversely cinacalcet was withdrawn in the remaining patients who remained on standard therapeutic regimen and diet. Follow up was continued for a second period of observation of the same duration of the first. At the end of the period of treatment with cinacalcet, for both variants of hyperparathyroidism, a statistically significant reduction in the overall number and in the diameter of renal stones was found. This prospective randomized study shows the effectiveness of cinacalcet used in combination with a diet with normalized calcium intake, in reducing the number and size of urinary stones in hypercalemic and normocalcemic forms of primary hyperparathyroidism.

Normocalcemic Hyperparathyroidism and Insulin Resistance

To determine whether insulin resistance (IR) accompanies normocalcemic primary hyperparathyroidism (NCPHP). Twenty-five patients with NCPHP and 25 age-, sex-, and body mass index (BMI)-matched controls were included the study. Patients were diagnosed NCPHP if their serum calcium (Ca) concentrations and ionized serum Ca levels were in the normal range but parathyroid hormone (PTH) levels were inappropriately and persistently high. Subjects with 25-hydroxyvitamin D (25[OH]D) levels ≥20 ng/dL were included in the study. The upper limit of PTH was calculated using a nomogram for each subject. Patients and controls underwent a standard 75-gram oral glucose tolerance test (OGTT). IR was assessed by the homeostasis model assessment (HOMA-IR) and insulin sensitivity index (ISogtt). There were no differences between the demographic features of patients with NCPHP and the control group. IR frequency was not different between groups (P = .14). HOMA-IR was higher and ISogtt was lower in patients with NCPHP than the control group, but the differences were not significant (P = .17 and P = .22, respectively). We did not find any correlation between PTH and glucose metabolism markers (HOMA-IR, ISogtt, glycated hemoglobin [HbA1c], and BMI) in either of the groups. The results of this study indicate that IR is not more common in patients with NCPHP, and PTH is not related to ISogtt or HOMA-IR.

ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА НОРМОКАЛЬЦИЕМИЧЕСКОГО ВАРИАНТА ГИПЕРПАРАТИРЕОЗА

Objective: to describe a case of normocalcemic hyperparathyroidism. Materials and methods. A female patient aged 51 years sought medical advice for complaints of spinal column and bone pains, periodic dizziness, and hand numbness. The patient underwent clinical and biochemical blood tests, determination of the blood levels of calcium, phosphorus, parathyroid hormone, concentrations of total vitamin D, calciuria, electrocardiography, thyroid ultrasonography, and neck computed tomography. Results. Based on her complaints, examination evidence, evaluation of the clinical presentations of the disease, and objective and instrumental examination findings, the patient was diagnosed with left parathyroid adenoma and primary hyperparathyroidism; stage II hypertensive disease, grade I, a moderate risk; retinal angiopathy of both eyes; stage I dyscirculatory encephalopathy with liquor and venous dyscirculation and moderate vestibular ataxia; urolithiasis; kidney stones; and spondylosis mainly involving the lumbar spine. The diagnostic determinants for verifying the diagnosis were the results of neck computed tomography, namely: the signs of space-occupying lesion in the projection of the left parathyroid gland; the blood level of parathyroid hormone 118.6 pg/ml (normal value (N) 9.5–75.0 pg/ml); total vitamin D 21.64 nmol/l (N 75–250 nmol/l); and calcium 2.48 mmol/l (N 2.15–2.50 mmol/l). The history of urolithiasis, repeated lithotripsy, as well as spondylosis with lumboischalgia was an absolute indication for surgical treatment. Conclusion. The practical interest in this case is due to the complexity of diagnosing normocalcemic hyperparathyroidism after vitamin D deficiency. The early stages of primary hyperparathyroidism are asymptomatic and frequently give rise to irreversible renal complications, causing renal failure and, as a consequence, disability. This clinical case demonstrates the importance of routinely determining vitamin D concentrations, which in turn triggers parathyroid adenomas.

Normocalcemic hyperparathyroidism: A new clinical type of primary hyperparathyroidism

Normocalcemic hyperparathyroidism: A new clinical type of primary hyperparathyroidism Primary hyperparathyroidism is the third most common endocrine disorder and the most common cause of hypercalcemia in the outpatient setting. After the introduction of automated serum calcium measurements in the 1970s, its prevalence increased significantly. In addition, the clinical phenotype had shifted from a symptomatic disorder to a less symptomatic or even asymptomatic state. This clinical profile has been called asymptomatic primary hyperparathyroidism. A newer presentation of primary hyperparathyroidism has been described over the past decade, in which parathyroid hormone is elevated but total and ionized serum calcium concentrations are consistently normal, in the absence of secondary causes for elevated parathyroid hormone concentration. This new condition has been called normocalcemic primary hyperparathyroidism. This review presents the current data in relation to this newly described type of primary hyperparathyroidism.

Effects of alendronate and vitamin D in patients with normocalcemic primary hyperparathyroidism.

No data on the pharmacological treatment of normocalcemic hyperparathyroidism (NPHPT) are available. We treated 30 NPHPT postmenopausal women with alendronate/cholecalciferol (treated group) or vitamin D alone (control group). Over 1 year, bone mineral density (BMD) increased significantly in treated group, but not in control group. Both treatments did not affect serum or urinary calcium. Normocalcemic primary hyperparathyroidism (NPHPT) is defined by normal serum calcium and consistently elevated PTH levels after ruling out the causes of secondary hyperparathyroidism. It is likely that subjects with NPHPT may develop kidney and bone disease. As no data on the pharmacological treatment of NPHPT are available, we aimed to investigate the effects of alendronate and cholecalciferol on both BMD and bone biochemical markers in postmenopausal women with NPHPT. Safety of vitamin D was evaluated as secondary endpoint. The study was a prospective open label randomized trial comparing 15 postmenopausal women with NPHPT (PMW-NPHPT), treated with oral alendronate plus cholecalciferol (treated group) and 15 PMW-NPHPT treated only with cholecalciferol (control group). Blood samples were obtained at baseline and after 3, 6, and 12 months. Bone turnover markers (BTM) were measured at baseline, 3, and 6 months, respectively. BMD was assessed at baseline and after 12 months. After 1 year of treatment, BMD increased significantly at the lumbar, femoral neck, and hip level in the treated group, but not in the control group (p = 0.001). No differences were found between or within groups in serum calcium, PTH, and urinary calcium levels. BTM significantly decreased in the treated group but not in the control group, at 3 and 6 months (p < 0.001), respectively. No cases of hypercalcemia or hypercalciuria were detected during the study. The results of this study indicate that alendronate/cholecalciferol increases BMD in postmenopausal women with NPHPT. Alendronate/cholecalciferol or vitamin D alone does not affect serum or urinary calcium.

Impact of vitamin D replacement in patients with normocalcaemic and hypercalcaemic primary hyperparathyroidism and coexisting vitamin D deficiency.

Vitamin D deficiency is increasingly recognized in patients with primary hyperparathyroidism but some clinicians are reluctant to replace vitamin D due to concerns with aggravating hypercalcaemia. We investigated the impact of vitamin D repletion in asymptomatic patients with normocalcaemic and hypercalcaemic primary hyperparathyroidism. This is a retrospective analysis of 111 patients with elevated parathyroid hormone concentrations (>6.4 pmol/L) referred to our endocrine clinic between January and December 2012; we identified 39 patients with primary hyperparathyroidism and vitamin D deficiency, i.e. 25 hydroxy vitamin D <20 µg/L. Patients were categorized into normocalcaemic (n = 23) and hypercalcaemic (n = 16) groups and the impact on biochemical parameters was recorded after at least six months treatment with either 1600 or 3200 units daily of cholecalciferol. Both normocalcaemic and hypercalcaemic groups showed a rise in 25 hydroxy vitamin D concentrations after replacement (p <0.0001). Parathyroid hormone concentrations fell in the normocalcaemic group (p = 0.08) but individually, five patients showed a rise (8-38% of baseline). In the hypercalcaemic group, parathyroid hormone remained static but the adjusted calcium concentration fell significantly (p = 0.006) except in two patients who showed mild rises (3 and 6%, respectively). There was no deterioration in renal function or calcium-related adverse events in any of the groups. Our study supports the safety of vitamin D replacement in patients with mild asymptomatic primary hyperparathyroidism and coexistent vitamin D deficiency. Repletion does not aggravate hypercalcaemia and may limit disease progression. Patients with normocalcaemic primary hyperparathyroidism need further characterization from longitudinal studies.

Characteristics of hyperparathyroid states in the Canadian multicentre osteoporosis study (CaMos) and relationship to skeletal markers.

PTH is an essential regulator of mineral metabolism; PTH hypersecretion may result in hyperparathyroidism including normocalcaemic, primary and secondary hyperparathyroidism. To examine the characteristics of participants with hyperparathyroid states and the relationship to bone mineral density (BMD). A cross-sectional study of 1872 community-dwelling men and women aged 35+ years (mostly Caucasian) with available serum PTH from Year 10 Canadian Multicentre Osteoporosis Study follow-up (2005-07). PTH was determined using a second-generation chemiluminescence immunoassay. L1-L4, femoral neck and total hip BMD. We established a PTH reference range (2·7-10·2 pmol/l) based on healthy participants (i.e. normal serum calcium, serum 25-hydroxyvitamin D, kidney function and body mass index, who were nonusers of antiresorptives, glucocorticoids and diuretics and not diagnosed with diabetes or thyroid disease). Participants with PTH levels in the upper reference range (5·6-10·2 pmol/l), representing a prevalence of 10·7%, had lower femoral neck and total hip BMD, by 0·030 g/cm(2) [95% confidence interval: 0·009; 0·051] and 0·025 g/cm(2) (0·001; 0·049), respectively, than those with levels 2·7-5·6 pmol/l. Participants with normocalcaemic and secondary hyperparathyroidism also had lower total hip BMD than those with levels 2·7-5·6 pmol/l, and CaMos prevalences of normocalcaemic, primary and secondary hyperparathyroidism were 3·3%, 1·4% and 5·2%, respectively. We found reduced BMD in participants with accepted hyperparathyroid states but also a notable proportion of other participants that might benefit from having lower PTH levels.

Primary Hyperparathyroidism: An Analysis of Failure of Parathyroidectomy

Dear Editor, We read the article by Bagul et al. [1] with interest and would like to congratulate the authors for highlighting an untold story. Series on primary hyperparathyroidism are available from almost all centers, but the authors have done a commendable job by highlighting this issue. However, there are certain observations in the article that need further clarification and comment. The collection of data seems to be heterogeneous, with large differences observed between center 1 and center 2. At center 1, four surgeons operated on 318 patients (mean 79.5 patients per surgeon), whereas at center 2, one surgeon operated on 223 patients (mean 223 patients per surgeon). Hence, there is a large difference between the expertise of surgeons at both centers. Surgeons at center 2 had operated on 2.8 times the cases per surgeon as compared with surgeons at center 1. Did this really have any influence on the study? The data also suggest, similarly, that there were more failures in center 1. Another difference between both centers is the difference in imaging policies: 79 % or more patients at center 1 received at least one imaging compared with 43–44 % of patients at center 2, making the study population inhomogeneous between the two centers. This was found to be highly significant and also caused skewing of data. It also resulted in more targeted approaches at center 1. Was it necessary to include data from both centers? It seems it has caused heterogeneity in the results. What are authors’ views regarding this? The authors defined success of surgery as normalization of serum calcium levels after surgery. However, they did not mention how many patients suffered from normocalcemic hyperparathyroidism before surgery [2]. How did they define successful surgery in these normocalcemic patients? The authors described that 40 % of failures were due to large adenomas. What was their definition of large adenoma and what was their policy if they found a large adenoma? Overall, how many large adenomas were present in the study population and what was the failure rate among this subgroup? In patients 16, 17, 18, 19, and 24, who had large adenomas, it seems that the imaging findings before surgery were misinterpreted and inadequate surgery performed in the first instance only. In patient number 6, whose disease was localized in the mediastinum, sternotomy should have been planned in the first instance when the authors were not sure of the nature of the excised lesion [3]. In patients 7 and 8, bilateral neck exploration was negative in the first surgery and curative in the second without differences in imaging before the first and second surgery. Similarly, in patients 13 and 15, what were the reasons for the inadequate first surgery? Were these possibly attributable to surgeon’s experience? What did the authors infer for this difference? One comment we would like to make is that the patients’ safety and curative intent is more important than the cost factor. We agree cost is an important factor, but considering the possibility of failure simply to cut costs seems inappropriate. R. Agrawal (&) Department of General Surgery, Aarupadai Veedu Medical College, Kirumampakkam, Puducherry 607402, India e-mail: drriteshagrawal@rediffmail.com

Normocalcemic hyperparathyroidism: preoperatively a disease, postoperatively cured?

BackgroundUp to 44% of primary hyperparathyroidism patients have elevated parathyroid hormone (ePTH) with normal calcium postparathyroidectomy (PTx). The question is whether the surgical approach affects the incidence of this phenomenon. MethodsPatients with hyperparathyroidism and presumed single-gland disease on preoperative imaging who underwent PTx between 1994 and 2008 were identified and contacted for long-term follow-up. PTx was either a focused approach (minimally invasive approach [MIP]) or a bilateral neck exploration (BNE). ResultsIn total, 171 patients had PTH measured postoperatively (95 MIP and 76 BNE); 30 of 171 (17%) had ePTH with normal calcium (MIP 21 [22%] and BNE 9 [12%], P = .08). This occurred within 2 years in 48% and 67% and after 2 years in 52% and 33%, MIP vs BNE, respectively. Four patients recurred, 2 MIP and 2 BNE. ConclusionsThere is a trend toward a higher incidence of ePTH in patients having undergone an MIP. The etiology of ePTH is multifactorial but may represent an early recurrence.

Cinacalcet in the management of normocalcaemic secondary hyperparathyroidism after kidney transplantation: one-year follow-up multicentre study

The effect of cinacalcet in patients with persistent secondary hyperparathyroidism (SHPT) after kidney transplantation (RT) has mainly been reported in patients with secondary hypercalcaemia. Our objective was to assess the long-term effect of cinacalcet on patients with a RT and normocalcaemic SHPT. A one-year multicentre, observational, retrospective study that included kidney recipients with SHPT (intact parathyroid hormone [iPTH] >120 pg/ml) and calcium levels within the normal range (8.4-10.2 mg/dl). Patients began treatment with cinacalcet in clinical practice. 32 patients with a mean age (standard deviation [SD]) of 54 (11) years, 56% male, were included in the study. Treatment with cinacalcet began a median of 16 months after RT (median dose of 30 mg/day). Levels of iPTH decreased from a median (P25, P75) of 364 (220, 531) pg/ml at the start of the study to 187 (98, 320) after 6 months (48.6% reduction, P=.001) and to 145 (91, 195) after 12 months (60.2% reduction, P=.001), without there being changes in calcium and phosphorus levels (P=.214 and P=.216, respectively). No changes were observed in kidney function or anti-calcineuric drug levels. 3.1% of patients discontinued cinacalcet due to intolerance and 6.2% due to a lack of efficacy. In patients with normocalcaemic SHPT after RT, cinacalcet improves the control of serum PTH values without causing changes to calcaemia, phosphataemia or kidney function. Cinacalcet showed good tolerability.

Case Report: Normocalcemic Hyperparathyroidism

A case of normocalcemic hyperparathyroidism is diagnosed basing on the clinical manifestations & laborotary investigation supported by finding of unilateral parathyroid adenoma on imaging studies and the patient was referred for surgical exploration for the parathyroid adenoma.

Normocalcemic Hyperparathyroidism and Hypoparathyroidism in Two Community-Based Nonreferral Populations

Normocalcemic primary hyperparathyroidism is typically identified after referral to a specialty clinic. At diagnosis, patients demonstrate features seen in hypercalcemic primary hyperparathyroidism. Normocalcemic hypoparathyroidism has been discovered after hypocalcemia unmasked after bisphosphonate administration. We hypothesized that screening unselected, nonreferral populations, such as The Osteoporotic Fractures in Men (MrOS) study and Dallas Heart Study (DHS), would identify asymptomatic subjects with normocalcemic hyperparathyroidism and hypoparathyroidism. Normocalcemic hyperparathyroidism was defined as serum PTH greater than the upper reference range with normal albumin-adjusted serum calcium, excluding common secondary causes (renal failure [estimated glomerular filtration rate <60 mL/min], 25-hydroxyvitamin D <20 ng/mL, and thiazide use), and normocalcemic hypoparathyroidism as PTH below the reference range with normocalcemia. Cross-sectional data were obtained from MrOS, and longitudinal data (baseline and 8 years) from DHS. In 2364 men from MrOS, we identified 9 with normocalcemic hyperparathyroidism (prevalence 0.4%) and 26 with normocalcemic hypoparathyroidism (1.1%). In 3450 men and women from DHS, we identified 108 with normocalcemic hyperparathyroidism (3.1%) and 68 with normocalcemic hypoparathyroidism (1.9%). Of the 108 normocalcemic hyperparathyroid subjects, 64 had follow-up data. Hypercalcemic primary hyperparathyroidism developed in 1 subject whereas 13 (0.6% of the follow-up cohort) showed persistently elevated PTH levels with normocalcemia. Of the 26 normocalcemic hypoparathyroid subjects with follow-up data, none developed overt hypoparathyroidism and 2 (0.09%) had persistent evidence of normocalcemic hypoparathyroidism. This study documents normocalcemic primary hyperparathyroidism and hypoparathyroidism identified among community-dwelling individuals. Larger studies are needed to determine the true prevalence and natural history of these parathyroid disorders.

Normocalcemic Hyperparathyroidism and Treatment Resistant Depression

In years past, primary hyperparathyroidism (pHPT) would often present itself as a problem related to bone disease or to kidney stones. Today, most patients with pHPT are so-called asymptomatic and discovered incidentally because of elevated levels of serum calcium and parathyroid hormone (PTH). Patients suffering from asymptomatic hyperparathyroidism may display a range of neuropsychiatric symptoms, including depression, anxiety, behavioral disturbances and psychosis, and reduced neurocognitive function. Table 1 shows typical signs and symptoms of pHPT, a condition that is more common in the elderly and in women. A prevalence of 21/ 1000 has been found in women aged 55-75 years (Table 1). The diagnosis of pHPT may easily be missed if not suspected by the clinician and if the appropriate biochemical tests are not performed. A high level of albumin-corrected calcium is often the sign that leads to further investigation. Other relevant biochemical tests are ionized calcium, urinary calcium excretion, phosphate, PTH, vitamin D, and creatinine. Patients with pHPT will usually, but not always, have an increased serum calcium level as well as an increased level of PTH. The level of vitamin D may be normal, but patients with pHPT more often have a vitamin D deficiency than matched controls. Figure 1 presents a flow chart that outlines a biochemical examination procedure for patients with treatment-resistant depression, in order to detect whether a patient suffers from HPT. We present a patient with pHPT and treatment-resistant depression, where the level of calcium was in the normal range. His symptoms disappeared after surgery. Our discussion of the case is placed in the context of recent literature on the topic of pHPT and neuropsychiatric symptoms.

Normocalcemic primary hyperparathyroidism in a patient with severe osteoporosis receiving teriparatide

We describe here the case of an elderly female with severe osteoporosis, who presented with a worsening backache, following teriparatide treatment. She was subsequently diagnosed to have normocalcemic primary hyperparathyroidism. Before prescribing teriparatide, an appropriate endocrine evaluation must be undertaken by all healthcare physicians (serum intact parathyroid hormone (iPTH) level), despite having a normal serum calcium. Normocalcemic hyperparathyroidism should be considered as an important alternate cause for osteoporosis.

What Is Hypercalcemia? The Importance of Fasting Samples

The differentiation between primary or tertiary (both hypercalcemic) and secondary (normocalcemic) hyperparathyroidism requires the identification of hypercalcemia. Calcium in the blood exists as bound, complexed and ionized fractions. Calcium sensors on parathyroid cells interact only with the ionized fraction (about 50% of the total calcium concentration). Many formulas using albumin, total protein or phosphate to correct or adjust total calcium to reflect the level of ionized calcium may be accurate only within a limited range. In addition, they can introduce errors based on inaccuracies in the measurement of these other metabolites. Clinical conditions, mainly those illnesses affecting acid-base balance, can alter the proportions of bound and free calcium. How and when the blood samples are drawn can alter the level of total calcium. Prolonged standing or prolonged venous stasis causes hemoconcentration, increasing the bound fraction. Preceding exercise can also affect blood calcium levels. Ingestion of calcium supplements or calcium-containing nutrients can cause transient elevations in blood calcium levels lasting several hours, leading to unnecessary further testing. Fasting total calcium levels may be sufficient for monitoring progress. However, for diagnostic purposes, fasting ionized calcium levels should be used. Therefore, for an isolated high total calcium level, we recommend obtaining a repeat fasting total and ionized calcium measurement before further investigations. Hypercalcemia may be diagnosed if there are persistent or frequent total or, preferably, ionized calcium levels >3 SD above the mean of the normal range or if there are progressively rising levels.

Further Insights into the Pathogenesis of Primary Hyperparathyroidism: A Nested Case-Control Study

The pathogenesis of primary hyperparathyroidism (PHPT) is largely unknown. The objective of the study was to ascertain the plasma levels of calcium, PTH, and 25-hydroxyvitamin D (25OHD) as measured prior to a clinical diagnosis of PHPT. Within three population-based cohorts, we identified participants diagnosed with PHPT after their inclusion. Cases (n = 117) were compared with age, gender, and season-matched controls (n = 233). Time from inclusion until a diagnosis of PHPT was median 5.6 yr. Parathyroidectomy was performed in 97%. At the cohort inclusion, undiagnosed PHPT was present in 63% of the cases. Among those without PHPT at inclusion (n = 43), 55% had normocalcemic hyperparathyroidism (vs. 21% in the matched controls, P < 0.01), and 31% had normoparathyroid hypercalcemia. Overall, 25OHD levels were lower in the cases. Compared with their matched controls, 25OHD levels were lower in normocalcemic hyperparathyroidism but not in normoparathyroid hypercalcemia. An adenoma was removed from 78% of the cases with normocalcemic hyperparathyroidism, whereas 39% of the cases with normoparathyroid hypercalcemia had parathyroid hyperplasia (P = 0.02). Overlap performance showed a positive predictive value for later PHPT of 95% for plasma calcium levels greater than 2.52 mmol/liter. Excluding cases with vitamin D insufficiency, the positive predictive value for later PHPT was 83% for PTH levels greater than 5.0 pmol/liter. Years prior to a clinical diagnosis of PHPT, calcium homeostasis shows signs of perturbations. Latent PHPT may be characterized by either normocalcemic hyperparathyroidism or normoparathyroid hypercalcemia. Such patients should be offered long-term follow-up to ascertain whether their biochemical profile represents an early state of PHPT.

Hiperparatiroidismo primario e hipoparatiroidismos

The most common clinical presentation of primary hyperparathyroidism (HPP) is asymptomatic hypercalcemia. Measurement of serum intact paratohormone (iPTH) is necessary to diagnose primary hyperparathyroidism (HPP), in patients with vitamin D in the normal range. HPP Surgery criteria includes serum calcium concentration >1.0 mg/dL above the upper limit of normal, creatinine clearance < 60mL/min, T score < -2.5 at any level and age less than 50 years. Normocalcemic hyperparathyroidism is a new variant of hyperparathyroidism, which must be confirmed at least two times. It must be diagnosed by exclusion of other causes of secondary hyperparathyroidism. Natural history of asymptomatic and normocalcemic HPP notes that it usually does not evolve to hypercalcemia.Hypoparathyroidism presents hypocalcemia and low level of PTH. The condition can be inherited, but it is usually encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes. The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results. The treatment of hypoparathyroidism consists ofcalcium replacement and vitamin D..