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Endocrinology and Metabolism (Seoul,... Jun 2024Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder.... (Review)
Review
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.
Topics: Humans; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Parathyroid Hormone; Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary; Animals
PubMed: 38752265
DOI: 10.3803/EnM.2024.1978 -
Prostate International Sep 2020The present study investigated the association of serum parathyroid hormone (PTH), vitamin D, and calcium levels with prostate cancer (CaP).
BACKGROUND
The present study investigated the association of serum parathyroid hormone (PTH), vitamin D, and calcium levels with prostate cancer (CaP).
METHODS
The study population consisted of an experimental group [459 patients including 216 patients with CaP and 243 patients with benign prostate hyperplasia (BPH)] and a prostatectomy group (47 patients who underwent radical prostatectomy). Patients with serum creatinine levels >1.4 mg/dl, parathyroid disease, and/or PTH levels <10 pg/ml were excluded. Patients with CaP and patients with BPH were compared, and the correlation between serum parameters and clinical data was determined. Preoperative and postoperative PTH levels were compared in the prostatectomy group.
RESULTS
Mean PTH levels were 41.67 ± 28.82 and 27.06 ± 17.32 pg/ml in the CaP and BPH groups, respectively ( < 0.001). When patients were divided into two groups as per prostate-specific antigen levels (≤20 or >20 ng/ml), Gleason score (≤7 or ≥8), and stage (≤T3 or ≥ T4), there was no significant difference in PTH levels between the two groups. Mean postoperative PTH levels (26.93 ± 13.58 pg/ml) were significantly lower than preoperative PTH levels (36.71 ± 21.04 pg/ml) in the same patients who underwent radical prostatectomy.
CONCLUSION
Serum PTH levels were higher in patients with CaP than in patients with BPH and decreased significantly after radical prostatectomy. The present results suggest an association between serum PTH and CaP. Further large cohort studies are necessary to validate the present data.
PubMed: 33102392
DOI: 10.1016/j.prnil.2020.02.002 -
Journal of Clinical Medicine Jul 2023(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary...
(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary hyperparathyroidism (PHPT). The purpose of this study was to compare classical and functional/secreting cystic parathyroid lesions and identify risk factors for severe hypercalcemia; (2) Methods: A total of 17 patients with PHPT and parathyroid cysts (study group) were compared with the group of 100 patients with hyperparathyroidism caused by adenoma or hyperplasia (control group). In both groups the majority were women (88% vs. 12%, with gender ratio 7, 3:1). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium and phosphate serum and urine concentrations and calcidiol serum levels were assessed; (3) Results: Patients with parathyroid cyst had statistically higher PTH and calcium serum concentration, higher calciuria and lower serum phosphate concentration. There were no statistically significant differences in the concentration of creatine in serum and urine and tubular reabsorption of phosphorus (TRP); (4) Conclusions: Due to higher PTH and calcium levels, cystic parathyroid adenomas could be one of the rare risk factors for severe hypercalcemia and hypercalcemic crisis which can be life threatening.
PubMed: 37568342
DOI: 10.3390/jcm12154939 -
Nephrology (Carlton, Vic.) Feb 2021The present study aimed to investigate the value of calcium-mediated parathyroid hormone (PTH) suppression test in evaluating the autonomic secretory function of...
AIM
The present study aimed to investigate the value of calcium-mediated parathyroid hormone (PTH) suppression test in evaluating the autonomic secretory function of parathyroid, and the management of uraemic secondary hyperparathyroidism (SHPT).
METHODS
Calcium-mediated PTH suppression test was performed in dialysis with SHPT, who were candidates for parathyroidectomy from June 2017 to December 2019 in our hospital. The PTH inhibition rate (PTH-IR) was calculated, and the correlation between PTH-IR and clinical indicators was explored.
RESULTS
Fifty-one subjects were included. PTH-IR was negatively correlated with baseline PTH (r = -0.35, P = .012), it was also correlated with dialysis years, coronary artery calcification score (CACS) and parathyroid mass (r = -0.397, P = .004; r = -0.327, P = .028; r = -0.363, P = .015), which were not found for baseline PTH. Forty-four patients underwent surgical treatment. According to the histological results, 26 patients presented with parathyroid non-nodular hyperplasia, and 18 patients presented with parathyroid nodular hyperplasia. The mass of parathyroid of patients with nodular hyperplasia was higher than that of patients with non-nodular hyperplasia (ρ = 0.01). The difference of the PTH-IR was not found between the two groups (ρ = 0.296). During the test, the highest serum calcium was 2.9 ± 0.4 mmol/L, which dropped to normal at the end of the test.
CONCLUSION
Parathyroid hormone inhibition rate might be a useful indicator in evaluating the autonomic secretory function of parathyroid and the progression of SHPT on top of intact PTH. Calcium-mediated PTH suppression test was safe in uraemic SHPT patients, but need to monitor for transient hypercalcaemia.
Topics: Adult; Autonomic Nervous System; Biomarkers; Calcium Gluconate; Female; Humans; Hyperparathyroidism, Secondary; Infusions, Intravenous; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Predictive Value of Tests; Renal Dialysis; Renal Insufficiency, Chronic; Uremia
PubMed: 33058364
DOI: 10.1111/nep.13807 -
Cirugia Espanola Sep 2022Primary 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...
INTRODUCTION
Primary 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.
METHODS
Retrospective 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.
RESULTS
We 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.
CONCLUSION
Primary 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.
Topics: Adenoma; Calcium; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Hyperplasia; Male; Middle Aged; Parathyroid Hormone; Parathyroid Neoplasms; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors
PubMed: 35504549
DOI: 10.1016/j.cireng.2022.04.008 -
Seminars in Dialysis Sep 2019Secondary hyperparathyroidism, characterized by increased PTH synthesis and secretion, is often seen in advanced stages of chronic kidney disease. Excessive... (Review)
Review
Secondary hyperparathyroidism, characterized by increased PTH synthesis and secretion, is often seen in advanced stages of chronic kidney disease. Excessive proliferation of parathyroid cells leads to the development of diffuse hyperplasia that subsequently progresses to nodular histology. Refractory hyperparathyroidism occurs when parathyroid glands fail to respond to medical therapy. Parathyroidectomy (PTX), surgical resection of parathyroid glands, is usually performed in cases of persistent serum levels of PTH above 1000 pg/mL associated with hypercalcemia or when hyperparathyroidism is refractory to conservative therapy. Parathyroidectomy can be carried out using different procedures: subtotal PTX or total PTX with or without parathyroid autotransplantation. Parathyroid surgery may have undesirable consequences due to PTH oversuppression, such as the development of adynamic bone disease; hungry bone syndrome is quite common after this surgery. However, PTX improves survival and parameters of mineral metabolism. Parathyroidectomy needs to be considered in those patients with severe hyperparathyroidism with a poor response to pharmacological treatment and with distinct undesirable effects of PTH on bone and mineral metabolism parameters.
Topics: Biomarkers; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Parathyroidectomy; Renal Dialysis
PubMed: 30656752
DOI: 10.1111/sdi.12772 -
Renal Failure Dec 2023The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one...
BACKGROUND
The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one year after kidney transplantation (KT) and identify the influencing factors of MBD.
METHODS
A total of 95 KTRs in our center were enrolled. The changes in bone mineral density (BMD) and bone metabolism biochemical markers, including serum calcium (Ca), phosphorus(P), 25-hydroxyvitamin D(25(OH)vitD), intact parathyroid hormone (iPTH), bone alkaline phosphatase, osteocalcin (OC), type I collagen N-terminal peptide and type I collagen C-terminal peptide (CTx), over one year after KT were assessed. The possible influencing factors of BMD were analyzed. The relationships between bone metabolism biochemical markers were evaluated. The indicators between groups with or without iPTH normalization were also compared.
RESULTS
MBD after KT was manifested as an increased prevalence of hypophosphatemia and bone loss, persistent 25(OH)vitD deficiency, and partially decreased PTH and bone turnover markers (BTMs). Femoral neck BMD was positively correlated with body mass index (BMI) and postoperative 25(OH)vitD, and negatively correlated with postoperative PTH. Lumbar spine BMD was positively correlated with BMI and preoperative TG, and negatively correlated with preoperative OC and CTx. BMD loss was positively associated with glucocorticoid accumulation. Preoperative and postoperative iPTH was negatively correlated with postoperative serum P and 25(OH)vitD, and positively correlated with postoperative Ca and BTMs. The recipients without iPTH normalization, who accounted for 41.0% of all KTRs, presented with higher Ca, lower P, higher BTMs, advanced age, and a higher prevalence of preoperative parathyroid hyperplasia.
CONCLUSIONS
MBD persisted after KT, showing a close relationship with hyperparathyroidism, high bone turnover, and glucocorticoid accumulation.
Topics: Humans; Biomarkers; Bone Density; Bone Remodeling; Cohort Studies; Collagen Type I; Glucocorticoids; Kidney Transplantation; Parathyroid Hormone; Peptides; Hyperparathyroidism; Chronic Kidney Disease-Mineral and Bone Disorder; Osteoporosis
PubMed: 37183797
DOI: 10.1080/0886022X.2023.2210231 -
Acromegaly and non-parathyroid hormone-dependent hypercalcemia: a case report and literature review.BMC Endocrine Disorders May 2021Hypercalcemia associated with acromegaly is mostly parathyroid hormone (PTH)-dependent, being caused by parathyroid hyperplasia or adenoma, which are common in... (Review)
Review
BACKGROUND
Hypercalcemia associated with acromegaly is mostly parathyroid hormone (PTH)-dependent, being caused by parathyroid hyperplasia or adenoma, which are common in individuals with multiple endocrine adenomatosis-1 (MEN-1). The rare occurrence of non-PTH-dependent hypercalcemia associated with acromegaly is attributable to complex factors involving increased intestinal calcium absorption, enhanced bone calcium release, and reduced urinary calcium elimination. Although patients with acromegaly often have mild hyperphosphatemia and hypercalciuria, clinically significant hypercalcemia is extremely rare.
CASE PRESENTATION
Here we present a case of non-PTH-dependent hypercalcemia associated with a growth hormone- (GH) and prolactin- (PRL) co-secreting pituitary macroadenoma. A 37-year-old Chinese man presented with a 6-year history of increasing ring and shoe sizes and was referred to the West China Hospital of Sichuan University for treatment of acromegaly. Pituitary magnetic resonance imaging (MRI) showed a 2.0 × 1.7 × 1.9 cm macroadenoma. Laboratory examinations revealed high serum concentrations of GH and PRL with mild hypercalcemia, hyperphosphatemia, hypercalciuria, inhibited PTH concentration, and increased bone turnover markers. Administration of cabergoline together with somatostatin resulted in sharp decreases in his GH, PRL, and serum and urinary calcium concentrations. These values were further reduced 5 months later and his PTH and bone turnover markers gradually returned to within the normal range.
CONCLUSIONS
Mild hyperphosphatemia and hypercalciuria are common in individuals with acromegaly and deserve attention because they may contribute to osteoporosis and urolithiasis. However, overt hypercalcemia is rare in such individuals. It is usually attributable to a coexisting parathyroid hyperplasia or adenoma, rarely being non-PTH-dependent. In such cases, the hypercalcemia is attributable to excessive PRL and hypogonadism and reverses with remission of acromegaly.
Topics: Acromegaly; Adenoma; Adult; China; Growth Hormone-Secreting Pituitary Adenoma; Humans; Hypercalcemia; Male; Parathyroid Hormone; Pituitary Neoplasms; Prolactinoma
PubMed: 33933067
DOI: 10.1186/s12902-021-00756-z -
Endocrine Practice : Official Journal... Jan 2022Calcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland...
Preoperative Calcium and Parathyroid Hormone Values Are Poor Predictors of Gland Volume and Multigland Disease in Primary Hyperparathyroidism: A Review of 2000 Consecutive Patients.
OBJECTIVE
Calcium 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.
METHODS
Two 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).
RESULTS
There 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 cm, DA = 1.43 cm, and H = 1.27 cm; 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).
CONCLUSION
This 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.
Topics: Calcium; Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Retrospective Studies
PubMed: 34403781
DOI: 10.1016/j.eprac.2021.08.003 -
International Journal of Endocrinology 2021Parathyroid carcinoma (PC) is the rarest endocrine cancer and an infrequent cause of primary hyperparathyroidism (PHPT), responsible for less than 1% of cases. Due to...
BACKGROUND
Parathyroid carcinoma (PC) is the rarest endocrine cancer and an infrequent cause of primary hyperparathyroidism (PHPT), responsible for less than 1% of cases. Due to its rarity, treatment is challenging.
METHODS
A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. We identified and individually described the patients affected with PC. Then, we split all patients treated for PHPT into four groups based on the cause: PC, adenoma, atypical adenoma, and hyperplasia. Patients' demographics, preoperative evaluation results, intraoperative findings, and outcomes for the PC group were compared with groups of PHPT due to benign causes.
RESULTS
Eight cases of PC were identified, five males and three females. Seven cases presented with symptoms of hypercalcemia and one with a neck mass. Five underwent en bloc resections and three local excisions. Histopathological features showed capsular invasion in four patients, capsular and soft tissue invasion in three patients, and vascular invasion in one case. No patients had distant metastasis. One patient was classed as high risk based on the Schulte classification system. All patients treated for PC were alive and disease-free at a mean follow-up of 38.4 months. When compared with other PHPT patients, PC patients were more frequently male and had higher preoperative blood calcium and PTH and lower phosphate levels, larger and heavier parathyroids excised, lower postoperative calcium, and a higher rate of postoperative hypoparathyroidism.
CONCLUSION
Our study highlights some aspects valuable to suspect PC and differentiate PHPT-PC from benign causes of PHPT preoperatively. Preoperative suspicion of malignancy is essential to guarantee the best course of treatment for patients. Although limited for size and follow-up, the excellent outcome of our series seems to support the value of both surgery extension and risk class according to the Schulte classification as possible prognostic factors for recurrence.
PubMed: 34659402
DOI: 10.1155/2021/5397941