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Mean ( SEM) changes in bone mineral density at 3 sites in patients with primary hyperparathyroidism. Data shown are cumulative % changes from baseline at each site in subjects who did not undergo parathyroidectomy after 1-15 years of follow-up. *, P 0.05 as compared to baseline.
Source publication
At the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (PHPT) in May 2008, recent data on the disease were reviewed. We present the results of a literature review on issues arising from the clinical presentation and natural history of PHPT.
Questions were developed by the International Task Force on PHPT. A comprehensive li...
Context in source publication
Context 1
... resulted in early and persistent improve- ment in biochemical and densitometric parameters. After sur- gery, normalization of biochemical parameters, including serum calcium, PTH, vitamin D levels (25-hydroxy and 1,25-dihy- droxy), and 24-h urinary calcium levels, was observed. Even more impressive was the postsurgical improvement in BMD: at all sites (lumbar spine, femoral neck, and distal 1/3 radius), BMD increased and remained above the 10% line for 15 yr after surgery (76) (Fig. 1). The improvements were seen in those who met and did not meet surgical criteria at study entry, confirming the salutary effect of parathyroidectomy in this regard on all ...
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Primary hyperparathyroidism is an endocrine disorder with variable clinical expression, frequently presenting as asymptomatic hypercalcemia in Western countries but still predominantly as a symptomatic disease in developing countries. The objective of this retrospective study was to describe the diagnostic presentation profile, parathyroidectomy in...
Normocalcemic primary hyperparathyroidism (NHPT) was first described over 10 years ago, but uncertainties still remain about its definition, prevalence and rates of complications. As a result, consensus management guidelines for this condition have not yet been published. Several hypotheses have been proposed for the pathophysiology of NHPT, but it...
Context:
Several studies define optimal serum 25-hydroxyvitamin D (25-OHD) levels based on serum PTH level reaching an asymptote. However, results differ widely, ranging from 25-OHD levels of 12-44 ng/ml: many studies are constrained by small sample size.
Objective:
The objective of the study was to determine the relationship between serum PTH a...
Primary hyperparathyroidism is diagnosed by the presence of hypercalcemia, hypercalciuria and elevated serum levels of parathyroid hormone and is treated surgically by removal of the enlarged gland. Both ultrasound and 99m-Tc-MIBI scintigraphy are used to localize enlarged parathyroid glands. With sonography, enlarged parathyroid glands are hypoech...
Primary aldosteronism represents major cause of secondary hypertension, strongly associated with high cardiovascular morbidity and mortality. Aldosterone excess may influence mineral homeostasis, through higher urinary calcium excretion inducing secondary increase of parathyroid hormone. Recently, in a cohort of PA patients a significant increase o...
Citations
... The effect on morbidity and mortality including effect on behavioral, renal, gastrointestinal, cardiovascular systems needs to be established, if asymptomatic PHPT is to be treated as a separate entity. [7][8][9] In this study, we have attempted to differentiate between the characteristics of symptomatic and asymptomatic cases at the time of detection and see if there are significant differences in their clinical profile. ...
Introduction : Primary hyperparathyroidism (PHPT) is a common endocrine disease with a variable presentation. There is a recent increase in the number of asymptomatic cases due to the use of multichannel automated analyzers.
Aim : To analyze the changing trend of PHPT patients from South India.
Materials and methods : We collected the data on clinical presentation, biochemistry, radiological features, and operative findings of patients with PHPT treated in our hospital over a period of six years and looked at the differences between symptomatic and asymptomatic PHPT.
Results : Our study included 80 patients. A significant proportion (~41%; n=33) of the patients were asymptomatic. Fifty-seven percent of asymptomatic patients were females. Mean age at presentation of asymptomatic patients was 50.58 (±14.67) compared to 47.28 (±14.78) for the symptomatic group, which was not statistically significant ( p =0.34). The mean levels of serum calcium, phosphorous, 25(OH)D, iPTH, and 24-hour urinary calcium in symptomatic vs. asymptomatic patients were 12.47 (±2.26) mg/dl vs. 12.27 (±1.82) mg/dl ( p =0.70), 2.59 (±0.74) mg/dl vs. 2.38 (±0.77) mg/dl ( p =0.27), 12 (±1.2) ng/ml vs. 10.85 (±1) ng/ml ( p =0.78), 1212.5 pg/ml vs. 678.5 pg/ml ( p =0.31), and 292.6 mg/day vs. 262 mg/day ( p =0.64), respectively. When Ca and gland weight were compared with variations in the iPTH levels, there was a significant positive correlation with PTH >600 pg/ml ( p =0.001) with no between-group differences. The adenoma weight increased by 0.5291 mg for every unit increase in iPTH in the entire cohort, with no between-group differences ( p =0.52).
Conclusion : Asymptomatic hyperparathyroidism is increasingly being identified in clinical practice and constitutes a significant proportion of primary hyperparathyroidism. Though asymptomatic PHPT is expected to be milder, such a difference in presentation was not obvious in our study.
... within 6 months of treatment, although they were on appropriate calcium/cholecalciferol therapy. 6 Stages 4 and 5 CKD and male sex were associated with subsequent hypocalcemia. 6 In the FREEDOM trial, hypocalcemia was defined as an albumin-adjusted calcium level of less than 8.0 mg per deciliter (2.0 mmol/L) in fasting specimens drawn just before injection of the study drug. 2 There was no reported hypocalcemia in the denosumab arm compared to the placebo group 0.1% (3 cases). ...
... 6 Stages 4 and 5 CKD and male sex were associated with subsequent hypocalcemia. 6 In the FREEDOM trial, hypocalcemia was defined as an albumin-adjusted calcium level of less than 8.0 mg per deciliter (2.0 mmol/L) in fasting specimens drawn just before injection of the study drug. 2 There was no reported hypocalcemia in the denosumab arm compared to the placebo group 0.1% (3 cases). In AMG 162 Bone Loss Study Group, the mean albuminadjusted serum calcium levels in denosumab-treated subjects demonstrated early but small decreases from baseline compared to the placebo and alendronate groups. ...
Objective
The reported hypocalcemia in postmenopausal women with osteoporosis who received Denosumab was low (0.05%-1.7% to 7.4%). The major prediction factors were vitamin D and calcium levels and renal function. The objective is to evaluate the incidence of hypocalcemia in patients with osteoporosis, normal renal function, and vitamin D who received Denosumab.
Method
A retrospective analysis was conducted using the medical records (2022-2023). We looked for hypocalcemia (albumin-adjusted calcium lower than 2.2 mmol/L).
Results
Two hundred one postmenopausal women diagnosed with osteoporosis and received denosumab treatment were included. All patients received vitamin D3 capsules and calcium supplementation. The mean age of the patient was 75.7 ± 7.0 years (56-91 years). Hypocalcemia was observed in 46 (23%) patients following a subcutaneous dose of Denosumab 60 mg. Median calcium was 2.25 mmol/L (minimum: 0.890 mmol/L, maximum: 2.6 mmol/L). Fourteen (30.4%) patients had severe hypocalcemia (<1.8 mmol/L) and required parenteral correction. A comparison between hypocalcemia and patients with normal calcium indicated that the significant predictor of hypocalcemia was pretreatment parathyroid hormone levels (9.9 ± 11.8vs 7.6 ± 2.56 pmol/L, respectively; P < .005). The prognostic role of parathyroid hormone for the denosumab-associated hypocalcemia was assessed using ROC curve analysis. For the cut-off value of Parathyroid hormone = 6.8 pmol/L, giving serum parathyroid measurement an AUC of 0.668 (0.599-0.737) - P = .0007; sensitivity 85%; specificity 52%.
Conclusion
Hypocalcemia induced by the denosumab treatment is more prevalent than previously shown in patients with osteoporosis receiving adequate calcium and vitamin D supplements. An elevated parathyroid hormone predicts hypocalcemia related to denosumab therapy in patients with normal calcium and vitamin D levels.
... When these symptoms first appear, they might not be attributed to PHPT, but after surgery, there is frequently a noticeable improvement that betters the quality of life. 21,22 Our patient demonstrated a full spectrum of the disease and the typical symptoms of primary hyperparathyroidism, which is quite rare. ...
... Hyperparathyroidism is almost always to blame [9]. Hypercalciuria is usually present in kids with hematuria, back or stomach pain, and occasionally voiding symptoms. ...
... An international panel of experts recognized this phenotype of primary hyperparathyroidism HPT in which PTH levels are consistently elevated, but serum total and ionized calcium levels are normal. 5 The secondary causes for hyperparathyroidism should be excluded, e.g., chronic kidney disease, decreased calcium intake, malabsorption, Vitamin D deficiency, bariatric surgery, renal calcium loss, and certain medications (loop diuretics, bisphosphonates and denosumab). 5 Normal serum calcium with elevated Parathyroid Hormone (PTH) is normocalcemic Hyperparathyroidism (HPT). ...
... 5 The secondary causes for hyperparathyroidism should be excluded, e.g., chronic kidney disease, decreased calcium intake, malabsorption, Vitamin D deficiency, bariatric surgery, renal calcium loss, and certain medications (loop diuretics, bisphosphonates and denosumab). 5 Normal serum calcium with elevated Parathyroid Hormone (PTH) is normocalcemic Hyperparathyroidism (HPT). Autonomous secretion of PTH from the parathyroids can lead to normocalcemic Primary Hyperparathyroidism (PHP). ...
... In normocalcemic secondary Hyperparathyroidism (HPT), PTH secretion increases as a reflex to a low calcium stimulus. 5,6 The evaluation of patients who may receive denosumab is the same as recommended for all patients with osteoporosis, e.g., complete blood count, complete chemistry profile (including alkaline phosphatase), calcium, phosphorus, and 25-hydroxyvitamin D. 7 Physicians tend not to check the parathyroid hormone levels in patients with normal serum calcium levels. Therefore, correcting hypocalcemia and hypovitaminosis D before starting denosumab therapy is essential. ...
... Furthermore, patients with mild pHPT frequently experience neuropsychiatric symptoms and a diminished quality of life as compared to the general population [16,34]. These patients often present with nebulous symptoms such as mood changes, irritability, fatigue, and memory loss, the biochemical underpinnings of which remain elusive [42]. There are reports suggesting that the near-equivalent rates of fatigue (~60% of patients), nocturia (~40% of patients), and difficulty concentrating (~40% of patients) are similar between patients with calcium levels greater than as well as less than 11.2 mg/dL [43]. ...
Background:
Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2-1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT.
Study design:
This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, and Web of Science by two teams of investigators. Analysis was run using R packages.
Results:
A total of 12 publications including seven randomized control, two prospective, and three retrospective trials with a total of 1346 patients were included for analysis. The average follow-up for all patients was 41 ± 23.8 months. Demographics, pre-treatment calcium, PTH, and bone mineral density (BMD) were similar between the medical (N = 632) and surgical (N = 714) cohorts. Post-treatment calcium and PTH levels were significantly higher in the medical cohort (10.46 vs. 9.39, p < 0.01), (106.14 vs. 43.25, p = 0.001), respectively. Interestingly, the post-treatment PTH in the medical cohort increased when compared to pre-treatment (83.84 to 106.14). Patients in the medical cohort had lower BMD in lumbar (0.48 g/cm2; OR = 0.42, 95% CI = 0.21, 0.83), femoral (0.48; OR = 0.42, 95% CI = 0.29, 0.61), and hip (0.61; OR = 0.33, 95% CI = 0.13, 0.85). Incidences of fracture, nephrolithiasis, cardiovascular death, or overall mortality were not significantly different between the cohorts.
Conclusions:
The present study is the most comprehensive meta-analysis on mild pHPT to date. Our findings reflect that parathyroidectomy is the superior option in the treatment of mild pHPT patients as opposed to medical management.
... it is characterized by hypercalcemia with inappropriately high levels of serum parathyroid hormone (PTh), although occasionally serum PTh or calcium levels are within the reference range. 1,2 in case of phPT, hyperfunctioning parathyroid glands are mostly solitary lesions, while in 15-20% of pa-tients, there is hyperplasia of parathyroid glands or multiple adenomas (multiglandular disease, Mgd); parathyroid carcinoma is very rare. 3 Symptomatic patients usually undergo parathyroidectomy of the affected glands, the only curative therapy. ...
... Elevated PTH levels (hyperparathyroidism) lead to side effects like increased fracture risk, coronary microvascular dysfunc tion, arterial hypertension, and increased stiffness of the aorta. 19 Aldosterone excess leads to increased Ca 2+ and Mg 2+ excretion, secondary hyperparathyroidism, and bone resorption. Blocking the MR with spironolactone improved the electrolyte balance and increased bone density and strength. ...
The spironolactone derivative drospirenone is combined with ethinylestradiol or estetrol in combined oral contraceptives. Formulations with 17-β-estradiol are used to treat climacteric symptoms. A drospirenone-only formulation has been introduced for contraception. Here, the pharmacological properties of drospirenone, the impact of the different formulations on metabolic and laboratory parameters, and the resulting clinical implications are reviewed. Ethinylestradiol, an inhibitor of CYP metabolic enzymes, changes the pharmacokinetics of drospirenone, leading to a higher drospirenone exposure with ethinylestradiol/drospirenone compared to the drospirenone-only preparation. In addition, several metabolic alterations have been described. The impact of estetrol is less pronounced, and for 17-β-estradiol/drospirenone and drospirenone-only, decreased triglyceride and cholesterol levels were observed. Ethinylestradiol induces various pro-coagulatory factors, leading to hypercoagulability. The effect is significantly reduced with estetrol, and no influence was observed with the drospirenone-only preparation. The anti-mineralocorticoid activity of drospirenone seems to positively counteract the renin-angiotensin-aldosterone-system-activating action of ethinylestradiol. There is no influence on blood pressure with ethinylestradiol/drospirenone and estetrol/drospirenone formulations, while in clinical trials, a reduction has been observed with 17-β-estradiol/drospirenone and drospirenone-only. Anti-aldosterone activity via non-renal mineralocorticoid receptors is associated with cardiovascular health, while interactions with parathyroid hormone signaling impact bone structure and vascular calcification. Though the clinical relevance is unclear for drospirenone, data in this context are reviewed. To sum up, the advantages of drospirenone in hormonal contraception and treatment of menopausal symptoms have been demonstrated for all the formulations described here. Combination with estrogen confers benefits and risks, which must be considered.
... According to the guidelines issued by the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism, PTX has been recommended for those with osteoporosis (T-score ≤ −2.5 at the hip, spine, or one-third distal radial site), hypercalcemia (serum calcium > 0.25 mmol/L above normal), creatinine clearance below 60 mL/min, or age < 50 years (7). Besides restoring normocalcemia, PTX increases BMD and decreases fracture risk in patients with osteoporosis and osteopenia (8). However, up to 75-80% of PHPT patients are asymptomatic at the time of presentation (9), and not everyone fits the aforementioned criteria for surgery. ...
PurposePrimary hyperparathyroidism (PHPT) is characterized by increased bone remodeling and hypercalcemia. Parathyroidectomy (PTX), the current standard of care, is recommended in all symptomatic and some groups of asymptomatic patients. Anti-resorptive therapies (bisphosphonates and denosumab) have been used in patients where PTX is refused or contraindicated. In this meta-analysis, we investigated the effectiveness of anti-resorptives in preventing/treating PHPT-induced bone loss and mitigating hypercalcemia.Method
PubMed, Scopus, and Cochrane Library databases were searched for articles with keywords containing PHPT, bisphosphonates, and denosumab in various combinations. We extracted and tabulated areal BMD (aBMD), serum mineral, and bone turnover parameters from the qualified studies and used comprehensive meta-analysis software for analysis.ResultsOf the 1,914 articles screened, 13 were eligible for meta-analysis. In the pooled analysis, 12 months of anti-resoptives (bisphosphonates and denosumab) therapy significantly increased aBMD at the lumbar spine (Standard difference in means (SDM)=0.447, 95% CI=0.230 to 0.664, p=0.0001), femoral neck (SDM=0.270, 95% CI=0.049 to 0.491, p=0.017) and increased serum PTH (SDM=0.489, 95% CI=0.139 to 0.839, p=0.006), and decreased serum calcium (SDM=-0.545, 95% CI=-0.937 to -0.154, p=0.006) compared with baseline. 12 months of bisphosphonate use significantly increased aBMD only at the lumbar spine (SDM=0.330, 95% CI=0.088 to 0.571, p=0.007) with a significant increased in serum PTH levels (SDM=0.546, 95% CI= 0.162 to 0.930, p=0.005), and a decreased in serum calcium (SDM=-0.608, 95% CI=-1.048 to -0.169, p=0.007) and bone-turnover markers (BTMs) compared with baseline. Denosumab use for 12 months significantly increased aBMD at both the lumbar spine (SDM=0.828, 95% CI=0.378 to 1.278, p=0.0001) and femur neck (SDM=0.575, 95% CI=0.135 to 1.015, p=0.010) compared with baseline. Mean lumbar spine aBMD (SDM=0.350, 95% CI=0.041 to 0.659, p=0.027) and serum PTH (SDM=0.602, 95% CI= 0.145 to 1.059, p=0.010) were significantly increased after 12 months of alendronate use compared with placebo. When compared with baseline, alendronate significantly decreased BTMs after 12 months and increased aBMD without altering the PTH and calcium levels after 24 months.Conclusion
Anti-resorptives are effective in mitigating bone loss and hypercalcemia in PHPT while maintaining or increasing aBMD. PTX reversed all changes in PHPT and normalized PTH levels.
... It is often diagnosed with elevated levels of calcium, which is investigated for other reasons (1). In symptomatic patients, pathological fractures, kidney stones, abdominal pain, dyspepsia, psychiatric disorders are the most frequent cases of referral to the hospital (2). The annual incidence of PHPT is 21/100000 -51/100000 (3). ...
