Increased Parathyroid Hormone Levels Research Articles

Investigation of the function of the parathyroid glands during thyroid surgery.

Annotation The aim is to justify the need for a routine examination of the function of the parathyroid glands in all patients before thyroid surgery. Materials and methods The analysis of 249 patients who underwent thyroid surgery was carried out. All patients were divided into 2 groups. The main criterion for division is a routine assessment of the function of the parathyroid glands before thyroid surgery. In each group, we assessed the need for interventions on the parathyroid glands. Results In 3 patients of group I, in the period 3-5 months after thyroid surgery, an “unreasonable” increase in blood calcium levels was revealed. Upon further examination, laboratory and clinical signs of primary hyperaparthyroidism were revealed in them. These patients (2.1%) required surgery on the parathyroid gland. There were no such patients in the second group. According to the results of preoperative examination in group II, an increase in parathyroid hormone levels was detected in 32 (28%) patients. Parathyroid adenomas were confirmed in 9 (28%) of 32 patients with hyperparathyroidism. At the same time, according to ultrasound, adenomas were visualized only in 5 (56%). In retrospective analysis, all 9 patients showed signs of damage to target organs without pronounced clinical manifestations. All these 9 patients underwent simultaneous intervention on the thyroid and parathyroid glands. In this group of patients, the frequency of simultaneous operations was 8% (p 0.001). Conclusion Before performing surgery on the thyroid gland, it is advisable for all patients to conduct a routine examination of blood calcium and parathyroid hormone to determine the indications for surgery on the parathyroid gland. With this approach, laboratory and clinical signs of primary hyperparathyroidism can be detected in 8% of patients with thyroid pathology, which requires simultaneous operations. Key words: hyperparathyroidism; calcium; nephrolithiasis; parathyroid hormone; parathyroidectomy; thyroid gland. Conflict of interest: none.

Incorporation of Calcimimetics into ESRD Bundle: Changes in Etelcalcetide Utilization and PTH Control Following End of TDAPA Designation

Introduction: Calcimimetics, including intravenous etelcalcetide and oral cinacalcet, are often prescribed to hemodialysis patients to prevent complications of elevated parathyroid hormone (PTH) levels. In January 2021, US dialysis reimbursement policy switched from the transitional drug add-on payment adjustment (TDAPA) to an increased bundled payment, with $10.09 per session added for all hemodialysis patients to cover the expense for calcimimetics, whether or not patients are administered etelcalcetide. We leveraged this natural experiment to investigate the impact of this policy change. Methods: This analysis included 713 US in-center hemodialysis patients enrolled in the United States Dialysis Outcomes and Practice Patterns Study (US-DOPPS) who discontinued etelcalcetide during the TDAPA transition period (December 2020 – April 2021). Within a self-matched longitudinal design, within-patient changes in mean PTH, calcium, and phosphorus were assessed in the six months pre- vs. post- etelcalcetide discontinuation, using linear regression adjusted for potential confounders. Results: Etelcalcetide use in US-DOPPS decreased 58%, from 12% to 5% from July 2020 to July 2021; 73% of etelcalcetide discontinuers switched to cinacalcet within six months. Comparing the six months pre- vs. post- etelcalcetide discontinuation, mean PTH levels increased by 107 (95% CI: 80, 133) pg/mL, and the prevalence of PTH >600 pg/mL increased by 15% (95% CI: 11%, 19%), from 28% to 43% overall, and increased from 26% to 49% among Black patients. Mean serum calcium and phosphorus levels increased by 0.42 and 0.16 mg/dL, respectively. Conclusion: Etelcalcetide use decreased substantially after TDAPA ended in January 2021, with most patients switching to cinacalcet. The subsequent increase in PTH levels was swift and sustained, and especially pronounced among Black patients, raising concerns about disparities and potential downstream impact on clinical outcomes. Despite the spirit of the policy change, the flat per-treatment increased payment may have inadvertently created a financial incentive to restrict patient access to a more effective therapy, and potentially stifle drug innovation.

Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c

Pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter 2a and 2c are rare causes of phosphate wasting. Since data on presentation and outcomes are scarce, we collected clinical, biochemical and genetic data via an online questionnaire and the support of European professional organizations. One hundred thirteen patients (86% children) from 90 families and 17 countries with pathogenic or likely pathogenic variants in SLC34A1 or SLC34A3 and a median follow-up of three years were analyzed. Biallelic SLC34A1 variant carriers showed polyuria, failure to thrive, vomiting, constipation, hypercalcemia and nephrocalcinosis in infancy, while biallelic SLC34A3 carriers presented in childhood or even adulthood with rickets/osteomalacia and/or osteopenia/osteoporosis, hypophosphatemia and, less frequently, nephrocalcinosis, while the prevalences of kidney stones were comparable. Adult biallelic SLC34A3 carriers had a six-fold increase chronic kidney disease (CKD) prevalence compared to the general population. All biallelic variant carriers shared a common biochemical pattern including elevated 1,25(OH)2D and alkaline phosphatase levels, suppressed parathyroid hormone (PTH), and hypercalciuria. Heterozygous carriers showed similar but less pronounced phenotypes. In biallelic SLC34A1 carriers, an attenuation of clinical features was observed after infancy, independent of treatment. Phosphate treatment was given in 55% of patients, median duration two years, and resulted in significant reduction, although not normalization, of alkaline phosphatase and of hypercalciuria but an increase in PTH levels, while 1,25(OH)2D levels remained elevated. Thus, our study indicates that biallelic SLC34A1 and SLC34A3 carriers show distinct, albeit overlapping phenotypes, with the latter having an increased risk of CKD in adulthood. Phosphate treatment may promote kidney phosphate loss and enhance 1,25(OH)2D synthesis via increased PTH production.

Association between Chronic Kidney Disease-Mineral and Bone Disorder Biomarkers and Symptom Burden in Older Patients with Advanced Chronic Kidney Disease: Results from the EQUAL Study.

Patients with advanced chronic kidney disease (CKD) develop numerous symptoms, with a multifactorial origin. Evidence linking mineral disorders (CKD-MBD) and uremic symptoms is scant and mostly limited to dialysis patients. Here we aim to assess the association between CKD-MBD and symptom burden in non-dialysis CKD patients. We used data from the European Quality study, which includes patients aged ≥65 with eGFR ≤20 ml/min/1.73m2 from six European countries, followed up to five years. We used generalized linear mixed-effect models to determine the association between repeated measurements of parathyroid hormone (PTH), phosphate and calcium with the overall symptom number (0-33), the overall symptom severity (0-165), and the presence of 33 CKD-related symptoms. We also analyzed subgroups by sex, age, and diabetes mellitus, and assessed effect mediation and joint effects between mineral biomarkers. The 1396 patients included in the study had a mean of 13±6 symptoms at baseline, with a median overall severity score of 32 (IQR 19-50). The association between PTH levels and symptom burden appeared U-shaped with a lower symptom burden found for mild-to-moderately increased PTH levels. Phosphate and calcium were not independently associated with overall symptom burden. The highest symptom burden was found in patients with a combination of both severe hyperparathyroidism and severe hyperphosphatemia (+2.44 symptoms (0.50, 4.38), P=0.01). The association of both hypocalcemia and hyperphosphatemia with symptom burden seemed to differ by sex and age. In older patients with advanced CKD not on dialysis, mild-to-moderately increased PTH was associated with a lower symptom burden, although the effect size was relatively small (less than one symptom). Neither phosphate nor calcium were associated with the overall symptom burden, except for the combination of severe hyperphosphatemia and severe hyperparathyroidism which was associated with an increased number of symptoms.

A novel minimally invasive endoscopic approach of thyroid surgery-endoscopic thyroidectomy via sternocleidomastoid muscle posteroinferior approach.

Since the endoscopic thyroidectomy was firstly reported by Hüscher in 1997, there has been an ongoing debate regarding whether mainstream endoscopic thyroidectomy can be classified as minimally invasive surgery. In this study, we innovatively proposed the endoscopic thyroidectomy via sternocleidomastoid muscle posteroinferior approach (ETSPIA), a novel minimally invasive surgical technique, and compared its efficacy with the well-established transoral endoscopic thyroidectomy vestibular approach (TOETVA). We retrospectively analyzed 50 patients who underwent ETSPIA and 50 patients who underwent TOETVA at Beijing Tongren Hospital, comparing their clinical characteristics, operative duration, blood loss, postoperative alterations in parathyroid hormone (PTH) and serum calcium, recovery post-surgery, complications, and follow-up data. The ETSPIA group had a shorter operation time compared to the TOETVA group (243.40±58.67 vs. 278.08±78.50 min; P=0.01). The ETSPIA group also had less intraoperative blood loss than the TOETVA group (20.60±10.58 vs. 33.00±11.11 mL; P<0.001). More central lymph nodes were dissected in the ETSPIA group compared to the TOETVA group (5.90±4.72 vs. 3.36±2.80; P=0.002). However, the difference in the number of positive central lymph nodes dissected was not statistically significant (1.38±2.33 for ETSPIA vs. 0.94±1.39 for TOETVA; P=0.26). The ETSPIA group had a shorter length of stay (LOS) compared to the TOETVA group (6.82±2.02 vs. 8.26±2.72 days; P=0.003). The alteration in PTH levels 1 day after surgery was less pronounced in the ETSPIA group compared to the TOETVA group (-26.38%±18.43% vs. -35.75%±22.95%; P=0.04). At the 1-month postoperative mark, the ETSPIA group showed a marginal increase in PTH levels, whereas the TOETVA group exhibited a slight decrease (10.12%±35.43% vs. -11.53%±29.51%; P=0.03). Regarding the average percentage change in serum calcium level 1 day after surgery, the ETSPIA group showed a smaller change, though this difference was not statistically significant (-4.79%±5.47% vs. -5.66%±3.90%; P=0.40). Furthermore, the incidence of hoarseness attributable to transient recurrent laryngeal nerve (RLN) injury in postoperative patients was lower in the ETSPIA group compared to the TOETVA group, but this difference did not reach statistical significance (0% vs. 4%; P=0.15). Overall, compared to TOETVA, the ETSPIA is characterized by a shorter operative route, enhanced protection of the parathyroid glands, reduced trauma, and expedited postoperative recovery.

Changes in Serum Level of Vitamin D Four Years After Sleeve Gastrectomy in Patients with Morbid Obesity: A Single-Center Study

Background: Bariatric procedures are associated with various micronutrient and vitamin deficiencies, including vitamin D. Objectives: The aim of the study was to assess the effect of laparoscopic sleeve gastrectomy (LSG) on serum vitamin D levels in a 4-year follow-up of obese patients. Methods: All obese patients undergoing LSG at Modarres Hospital were included in this study. Patients were evaluated 4 years after surgery, and their serum levels of calcium, parathyroid hormone (PTH), and vitamin D were measured. Results: Analytical analysis demonstrated a statistically significant difference in vitamin D and calcium levels before and after LSG (P-value &lt; 0.001 for both). However, the change in PTH levels before and after LSG was not statistically significant. Additionally, the analysis showed no statistically significant relationship between vitamin D levels and PTH levels. Conclusions: The results of the present study showed that, four years after LSG, vitamin D and calcium levels significantly increased in patients with morbid obesity, although the observed increase in PTH levels was not statistically significant.

#191 An unusual cause of hypocalcemia in a young patient

Abstract Background and Aims A 33-year-old man visited the Nephrology Department outpatient clinic with abnormal laboratory findings: his serum calcium level was 5.9 mg/dL in a recent health examination. He denied any underlying disease and was on no medications. He complained of a tingling sensation in his hands and of eyelid twitching. On physical examination, he showed Chvostek's sign. His laboratory findings including serum calcium level are shown in Table 1. He did not have any morphological abnormalities, such as a round face, brachydactyly, or dental anomalies. Method Since he showed hypocalcemia, normal 25-hydroxyvitamin D, and elevated parathyroid hormone (PTH) levels, the presence of PTH resistance was presumed. Under strong suspicion of pseudohypoparathyroidism (PHP) in this patient, DNA sequence analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of GNAS and STX16, genetic regions that are often affected by mutations or imprinting changes in PHP, was performed. No pathogenic mutations in GNAS and STX16 were detected by sequencing. Results Results of MS-MLPA of the GNAS locus demonstrated abnormal methylation patterns in the patient after HhaI restriction enzyme treatment. The methylation ratio showed a gain of methylation in the NESP55 region and loss of methylation in the AS, XL, and A/B differentially methylated regions (DMRs) in the patient as compared to a healthy control (Fig. 1). The patient was diagnosed with PHP type 1B (PHP1B) due to the methylation abnormalities in multiple DMRs. His parents both showed normal serum calcium levels; thus, no further genetic testing was conducted. He is on outpatient follow-up with adequate calcium replacement and no specific symptoms. Conclusion PHP is a rare disorder of unknown prevalence. It is characterized by hypocalcemia, hyperphosphatemia, and increased PTH levels. PHP1B is a subtype of PHP characterized by isolated renal PTH resistance, usually without physical abnormalities such as Albright hereditary osteodystrophy or other endocrine abnormalities. PHP1B can be sporadic or familial. The genetic characteristics of most sporadic PHP1B remains unclear, but GNAS imprinting abnormalities and hypomethylation at the A/B DMRs have been reported. Symptoms of PHP1B usually begin in childhood due to low calcium levels and may include numbness, seizures, tetany, cataracts, and dental problems. However, as in our case, specific symptoms may not occur until adulthood. Therefore, when evaluating the cause of hypocalcemia, it is necessary to differentiate PHP1B, even in adults, and particularly in cases with hyperphosphatemia and high PTH levels.

When parathyroid adenoma meets osteopathia striata, rarest amalgam of bony dysplasia with brown tumors: a case report

BackgroundOsteopathia is a benign entity characterized by linear densities along the diaphysis and metaphysis of the longitudinal axes of the long bone. Parathyroid adenoma is a non-malignant parathyroid gland tumor characterized by increased parathormone levels, causing defecting calcium levels leading to multiple brown tumors, renal calculi, bone pains, polyuria, and arrhythmias in the patient. The coexistence of parathyroid adenoma with osteopathia striata has not been reported yet in the literature. To our knowledge, this is the first case of its kind.Case presentationAn 18-year-old male patient presented to our institution with the complaint of genu valgum deformity in his right knee and was admitted for corrective surgery. While undergoing a preoperative evaluation, we came across multiple focal, lytic lesions in his radiographs and an atypical finding of osteopathia striata in his long bones. Further examination led us to the findings of cranial sclerosis and acro-osteolysis of distal phalanges. The tumor, whose catalyst was unclear, directed us toward an ultrasonographic analysis of the patient’s neck, leading us to a solitary parathyroid adenoma.ConclusionsRadiological examinations played a very crucial role in the diagnosis of this condition. Though the reason behind osteopathia and the parathyroid lesion in this patient remains unknown, this presentation remains an exceptional and never-reported case of parathyroid adenoma and associated brown tumors in a patient with osteopathia striata.

Tertiary Hyperparathyroidism Presenting as Multifocal Brown Tumors: A Case Report

Brown Tumor (BT) of the bone is a rare manifestation of hyperparathyroidism (HPTH), an unusual reactive bone lesion attributed to disturbed bone remodeling, from long-standing increase in parathyroid hormone level (PTH). Historically, BTs were described with primary HPTH but due to early diagnosis of this entity, and improved survival in patients with end-stage renal disease (ESRD) especially those on renal replacement therapy (RRT), more cases of BT are now described in this population, and less in PHPTH. Thus, it is mostly the consequence of untreated secondary or tertiary HPTH whose major culprits are chronic kidney disease (CKD) and ESRD. The management of brown tumors related to chronic renal failure consists primarily of its prevention through the use of phosphate binders, vitamin D analogues, and calcimimetics with surgical parathyroidectomy reserved as the final resort in refractory cases. Herein, we present the case of a 24-year-old female patient with ESRD on intermittent hemodialysis (IHD) who developed recent onset facial tumefaction. Blood work revealed markedly elevated PTH at more than 5000 pg/ml, upper borderline hypercalcemia, and hyperphosphatemia. Further investigations with chest computed tomography (CT) and Technetium-99m (99mTc)- Sestamibi scan nuclear imaging showed multiple ribs lytic lesions as well as features of extensive BT and parathyroid adenomas. Thereafter, the patient was sent for parathyroidectomy after which the patient developed hungry bone syndrome.

Biochemical markers and FokI and TaqI vitamin D receptor genes polymorphism in rheumatoid arthritis

BackgroundPrevious studies have reported the role of genes in different metabolic processes in the human body, and any variation in gene polymorphisms could lead to disturbances in these processes and different diseases.ObjectiveThis study aimed to compare vitamin D receptor (VDR) FokI and TaqI genotypes in terms of parathyroid hormone (PTH) and some biomarkers of inflammation and susceptibility to rheumatoid arthritis (RA) disease.MethodsThis study included 100 patients with rheumatoid arthritis (RA). Genotyping was performed by polymerase chain reaction (PCR) and examined by specific restriction enzymes using restriction fragment length polymorphism (RFLP). Serum intact PTH, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibodies (ACCPs) levels were measured.ResultsAn increased PTH level (> 65 pg/ml) was found in 8% of patients. No significant differences among FokI and TaqI vitamin D receptor genes polymorphism regarding positive and negative RF or ACCPs were found. A significant difference was found among FokI (p = 0.009) and none in TaqI genotypes regarding intact parathyroid hormone level categories. No significant correlation was found between the serum intact PTH level and ESR or CRP levels (P = 0.13 and 0.28, respectively). The parathyroid hormone level was not a good predictor for RF or ACCPs (P = 0.5 and 0.06, respectively).ConclusionThe FokI gene may play a role in controlling PTH levels in patients with RA. There was no significant correlation found between the serum intact PTH level and RA severity according to ESR and CRP inflammatory biomarkers. There are no differences between VDR genes FokI and TaqI polymorphism in terms of RA susceptibility (for RF and ACCPs).

Brown Tumor with Multiple Lesions as a Manifestation of Tertiary Hyperparathyroidism: A Case Report and Literature Review

Brown tumor is an uncommon focal lytic bone lesion, which is considered as an end-stage lesion of abnormal bone metabolism, caused by long-standing increased parathyroid hormone levels. It is a rare manifestation of hyperparathyroidism that is classified into three types, of which tertiary is the rarest. It can be found in any part of the skeleton, and in some cases, occurs in multiple bones and can be easily misdiagnosed as a metastatic tumor. Therefore, although uncommon, it should be generally considered as a differential diagnosis with bone malignancy lesions, and particularly in patients with renal failure on long-term hemodialysis. In the present case report, a young patient with end stage renal disease presented with tertiary hyperparathyroidism revealed by multiple brown tumors of the pelvis and mandible. We recall through this observation the importance of clinical context, the complementary roles that different imaging modalities can play in different settings, and the relevance of measuring serum calcium and parathyroid hormone before the diagnosis of osteolytic bone lesions.

Brown tumor due to primary hyperparathyroidism in a familial case: a case report

BackgroundPrimary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor.Case presentationThe proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband’s daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient’s blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father’s first signs of brown tumor were in the right maxilla, while the daughter’s appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland.ConclusionWe report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.

Mechanistic impact of fibrosis by parathyroid hormone excess

Klotho is a protein that has been found to play a role in regulating parathyroid hormone (PTH) levels. The literature suggests an intricate relationship between Klotho and PTH. Klotho acts as a co-receptor for fibroblast growth factor 23 (FGF23), a hormone that helps regulate phosphate and vitamin D metabolism. Klotho deficiency has been associated with increased PTH levels and secondary hyperparathyroidism. Several studies have investigated the relationship between Klotho and PTH levels. Some studies have shown that Klotho levels are inversely correlated with PTH levels, suggesting that higher Klotho levels may lead to lower PTH levels. Other studies have found that Klotho deficiency can contribute to PTH resistance, leading to persistent hyperparathyroidism. Additionally, the Klotho-PTH axis holds promise as a potential target for therapeutic interventions in calcium and phosphate disorders.

Longitudinal trends in serum calcium, parathormone and bone mineral density in breast cancer survivors on aromatase inhibitor therapy: A single institutional cohort study.

e12531 Background: Aromatase inhibitors (AIs), when used as adjuvant treatment of hormone receptor positive breast cancer, have been associated with bone density loss. However, any impact on PTH and by extension calcium (Ca) homeostasis is yet to be elucidated as no study till date has investigated longitudinal trends in parathyroid hormone (PTH) while on AI therapy. We explored these to determine if long term AI therapy was associated with hyperparathyroidism. Methods: This is a retrospective study of female breast cancer patients at the Cleveland Clinic Foundation started on AIs (anastrozole, letrozole and exemestane) from January 2015 to April 2022. Included patients had both baseline and subsequent data (after starting AI therapy), on serum Ca, PTH and lumbar spine T-scores (LsTs). These values were compared using paired t-test. Results: We identified n=9657 patients on AI therapy and included n=249 with pre and post AI PTH values. Among these, n= 209 received anastrozole, n=34 received letrozole and n=6 received exemestane. Cohort median age was 68 (IQR 62-72) years and median duration of AI therapy was 3 years. While we observed a significant positive correlation between change in Ca and change in PTH (p=0.02), the differences between baseline and treatment median serum Ca and PTH were not statistically significant. There was no significant association between changes in either serum Ca or PTH and change in LsTs (p-value: 0.69 and p-value: 0.05 respectively). Notably, 4% patients had elevated PTH and Ca after AI therapy was initiated among whom n=4 had markedly elevated PTH with low urinary Ca. Three of these four patients also had a diagnosis of chronic kidney disease (CKD) with normal vitamin D levels. Two patients with elevated PTH were on biotin supplements. There was an overall downtrend in LsTs (p-value: 0.0039) with no significant difference between the three AIs (p-value 0.0613). However, in comparison to other AIs, letrozole had the least depreciation in LsTs. Conclusions: Our findings do not suggest any correlation between AI therapy and hyperparathyroidism among breast cancer survivors. No significant increase in PTH levels occurred during AI therapy and majority of patients with clinically significant PTH elevation also had CKD, which may have contributed also to elevation of PTH level and low urinary calcium excretion.[Table: see text]

Hypercalcemia in Chronic Myeloid Leukemia: An Unusual Presentation

AbstractHypercalcemia in CML is an unusual paraneoplastic syndrome and is associated with worse prognosis and reduced survival. It usually seen in blast crisis or accelerated phase but can also indicate bony infiltration by cancer cells. Multiple mechanisms can be involved in a patient. We present a case of hypercalcemia in CML in chronic phase without bony infiltration or increased parathormone levels. Increased calcium levels may also be first indication of tyrosine kinase inhibitor resistance. Patient was managed symptomatically with subsequent change of the drug for managing CML. He is currently stable at six months follow-up. Therefore, careful evaluation of the cause of hypercalcemia is necessary for appropriate management.

Comparison between the effects of older versus newer generations of antiepileptic drugs on bone metabolism in adult Iraqi patients: an observational study

Background: Metabolic bone disorder is a significant endocrine system disorder that encompasses any disorder that alters the natural skeleton's mineralization process. Epilepsy is a prevalent central nervous system disorder that can cause biochemical abnormalities involving bone metabolism in the epileptic patients. The present study aimed to investigate the effects of chronic use of older compared to the newer generations of antiepileptic drugs on bone metabolism-related biomarkers. Methods: The study included fifty-one epileptic outpatients who attended the Consultation Clinic of Baghdad Teaching Hospital at the Medical City Complex from October/2021 to December/2021. The selected patients were on antiepileptic drugs for more than 2 years, hence were grouped according to their antiepileptic therapy into: Group-1: 24 epileptic patients on old antiepileptic drugs (Carbamazepine or Valproate). Group-2: 27 epileptic patients on new antiepileptic drugs (Levetiracetam), compared with Group-3: 28 healthy control subjects. Serum was obtained from their blood specimens to measure: calcium and inorganic phosphate by colorimetric assays, parathyroid hormone, and level of bone alkaline phosphatase activity. Results: Data analysis revealed that the median value of serum parathyroid hormone levels was significantly elevated in the epileptic patients' groups compared to the healthy control group. However, group-2 (new generation antiepileptic drugs) presented higher values. Whereas serum calcium and inorganic phosphate levels showed non-significant variation for all the studied groups. Furthermore, serum bone alkaline phosphatase activity exhibited significantly higher values in the patients compared to the healthy subjects group, with more significant elevation among those on old generation antiepileptic drugs (Carbamazepine or Valproate). Conclusion: Epileptic individuals who had been on AEDs for more than two years had increased parathyroid hormone levels, which were boosted by the newer antiepileptic drug Levetiracetam. Furthermore, BAP serum levels were considerably greater in epileptic patients than in healthy control participants, with larger values generated by older antiepileptic medications.

The Effects of 12-Weeks Whey Protein Supplements on Markers of Bone Turnover in Adults With Abdominal Obesity - A Post Hoc Analysis.

BackgroundWhile osteoporosis is characterized by skeletal fragility due to increased bone turnover and low bone mineral density (BMD), subjects with abdominal obesity and type-2 diabetes have increased risk of bone fractures despite low bone turnover and increased BMD. Diets with increased protein content are reported to increase bone turnover in healthy adults and may be a point of interest in preserving bone strength in subjects with abdominal obesity and/or type-2 diabetes.MethodsWe examined the effect of 12-weeks dietary intervention on bone turnover in 64 adults with abdominal obesity using data from the MERITS trial. The trial was a randomized, controlled, double blinded study in which participants were allocated to receive either 60 g/d of whey protein hydrolysate or maltodextrin in combination with either high (30 g/d) or low dietary fiber intake (10 g/d). Primarily, we assessed changes in plasma markers of bone turnover Procollagen type 1 N-terminal propeptide (p1NP), C-terminal telopeptide type-1 collagen (CTX), and parathyroid hormone (PTH) within the four intervention groups. In addition, we measured u-calcium and u-carbamide excretion, 25(OH)D, and BMD by whole body DXA scans. Finally, we compared changes in insulin resistance (Homeostasis-model assessment of insulin resistance, HOMA-IR) with changes in bone turnover markers.The trial was registered at www.clinicaltrials.gov as NCT02931630.ResultsSixty-four subjects were included in the study. We did not find any effect of twelve weeks of high protein or high fiber intake on plasma levels of P1NP or CTX. There was a nonsignificant positive association between protein intake and PTH levels (p=0.06). U-calcium and u-carbamide increased in both protein groups. There was a positive association between change in HOMA-IR and PTH (p=0.042), while changes in P1NP and CTX did not associate to changes in HOMA-IR.ConclusionTwelve weeks of increased whey protein intake in subjects with abdominal obesity did not affect markers of bone turnover significantly, although tended to increase PTH levels. Dietary fiber intake did not affect bone turnover. We report a positive association between change in HOMA-IR and PTH supporting a hypothesis of insulin resistance as a potential key factor in the expanding field of bone fragility in T2D subjects.

Native thiol decreases in patients with asymptomatic primary hyperparathyroidism, especially in the presence of surgery indication.

Oxidative stress increases in many systemic and endocrine diseases. The effect of increased parathyroid hormone levels (PTH) and the effects of this hormone on oxidative stress in patients with primary hyperparathyroidism (pHPT) is unknown. We aimed to investigate the change of Thiol-disulfide (SH-SS), one of the oxidative stress parameters, in patients diagnosed with pHPT and the usability of this parameter in patients with pHPT. Forty-six patients who recently diagnosed with asymptomatic pHPT and 40 healthy controls were included in this prospective study. In addition to routine examinations for pHPT, serum SH-SS measurements were recorded. The pHPT patients included in the study were divided into two groups as patients with and without surgical treatment indication. It was observed that the pHPT group had lower total SH and native SH values and higher SS values compared to the control group (P<0.05 for each). Native SH values were found to be lower in pHPT patients who were indicated for surgical treatment compared to those who did not (P<0.05). An independent relationship was found between Native SH and serum calcium, urine calcium and T scores in DEXA level in asymptomatic pHPT patients with surgical treatment indication (P<0.05). In our study, native SH level decreases in patients with pHPT, especially in patients with surgical treatment indication for pHPT. The decrease in SH levels, which is a natural antioxidant that protects the body against oxidative stress, and the increase in SS levels in pHPT patients may be another metabolic effect of this disease. Native SH may be helpful in determining the indication for surgical treatment in asymptomatic pHPT patients.

Type 2 Diabetes Mellitus and Bariatric Surgery: Impact on Parathyroid Hormone, Calcium, and Vitamin D Levels

Background: Type 2 diabetes mellitus (DM2) has a deleterious impact on bone metabolism. There is a lack of studies evaluating the role of diabetic status on levels of calcium (Ca), parathyroid hormone (PTH), and 25-hydroxyvitamin D (VitD). after bariatric surgery (BS). Methods: Retrospective study of patients with obesity submitted to BS in comparison to patients with and without DM before and 36 months after BS. A multiple linear regression was used, adjusted to consider the outcome of the variation of the levels of Ca, PTH, and Vit D with surgery, according to diabetic status. Results: We evaluated 827 patients (36.6% with DM2) submitted to Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or gastric banding (GB). Diabetic patients submitted to RYGB had greater PTH levels 36 months after and those submitted to SG and GB had higher total Ca plasmatic levels 36 months after surgery. Diabetic patients presented an increase of PTH levels 36 months after RYGB, opposite to nondiabetic ones. Diabetic patients had significantly higher levels of Ca before and at every time point studied after surgery. Conclusion: Type 2 diabetes status is related with a significative increase of PTH during the first 36 months after BS. This increase was not mirrored by significant variations of levels of Ca or Vit D.

Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels.

Calciotropic hormones, parathyroid hormone (PTH) and calcitonin are involved in the regulation of bone mineral metabolism and maintenance of calcium and phosphate homeostasis in the body. Therefore, an understanding of environmental and genetic factors influencing PTH and calcitonin levels is crucial. Genetic factors are estimated to account for 60% of variations in PTH levels, while the genetic background of interindividual calcitonin variations has not yet been studied. In this review, we analyzed the literature discussing the influence of environmental factors (lifestyle factors and pollutants) on PTH and calcitonin levels. Among lifestyle factors, smoking, body mass index (BMI), diet, alcohol, and exercise were analyzed; among pollutants, heavy metals and chemicals were analyzed. Lifestyle factors that showed the clearest association with PTH levels were smoking, BMI, exercise, and micronutrients taken from the diet (vitamin D and calcium). Smoking, vitamin D, and calcium intake led to a decrease in PTH levels, while higher BMI and exercise led to an increase in PTH levels. In terms of pollutants, exposure to cadmium led to a decrease in PTH levels, while exposure to lead increased PTH levels. Several studies have investigated the effect of chemicals on PTH levels in humans. Compared to PTH studies, a smaller number of studies analyzed the influence of environmental factors on calcitonin levels, which gives great variability in results. Only a few studies have analyzed the influence of pollutants on calcitonin levels in humans. The lifestyle factor with the clearest relationship with calcitonin was smoking (smokers had increased calcitonin levels). Given the importance of PTH and calcitonin in maintaining calcium and phosphate homeostasis and bone mineral metabolism, additional studies on the influence of environmental factors that could affect PTH and calcitonin levels are crucial.