Secondary Hyperparathyroidism Research Articles

Secondary hyperparathyroidism: Update

Secondary hyperparathyroidism is a clinical condition characterized by an increase in the synthesis and secretion of parathyroid hormone (PTH). Its presentation will be conditioned by the development of stimuli such as hyperphosphatemia, hypocalcemia, vitamin D deficiency, and PTH resistance. The most common cause of secondary hyperparathyroidism is chronic kidney disease, a pathological condition in which all the afore mentioned stimuli converge. Secondary hyperparathyroidism is evidenced by an increase in the size of the parathyroid glands, favored by cellular hyperplasia and hypertrophy. At the bone level, there will be an increase in the quantity and activity of osteoblasts and osteoclasts, leading to bone with unusual structural characteristics. Symptoms related to the disease include itching, bone pain, concentration alteration, and depression. In the long term, patients have a higher risk of cardiovascular mortality. Therapeutic options include calcimimetics, phosphate binders, vitamin D supplements, and surgery.

Biological profile of secondary hyperparathyroidism in chronic renal failure patients

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease, especially in hemodialysis patients. It is characterized by overproduction of parathyroid hormone in response to chronic deterioration of renal function. The aim of this retrospective study was to determine the average time to develop secondary hyperparathyroidism, analyze the initial phosphocalcic profiles, and evaluate the evolution of these profiles in hemodialysis patients, following the recommendations of the KDOQI 2003 and KDIGO 2009 groups. The study included 134 hemodialysis patients from two private dialysis centers. Data were collected from patients' medical records and analyzed using SPSS software. The results showed that the average time to develop secondary hyperparathyroidism was 3.15 years according to KDOQI recommendations and 4.64 years according to KDIGO recommendations based on parathyroid hormone levels. The initial assessment revealed an imbalance in phosphocalcic metabolism in approximately 20.1% to 22.5% of patients, a proportion that increased to 27.5% during follow-up, according to both sets of recommendations. In conclusion, secondary hyperparathyroidism is an inevitable complication of chronic kidney disease, affecting the vital and functional prognosis of hemodialysis patients. Diagnosis primarily relies on parathyroid hormone levels, associated with phosphocalcemia, vitamin D, and PAL analyses. Treatment aims mainly to maintain blood levels of calcium, phosphorus, and vitamin D within recommended limits and to reduce parathyroid response to phosphocalcic disturbances.

Anesthetic management of a high-risk patient with complex medical conditions: A case report of multimodal analgesia and regional nerve blocks in urgent transfemoral amputation

This case article presents the anesthetic management of a patient with complex medical conditions and surgical requirements. The patient had secondary hyperparathyroidism due to chronic renal failure, resulting in hypocalcemia. The patient required a transfemoral amputation due to progressive bacterial infection and global foot gangrene. The urgency of the operation prevented preoperative preparation and necessitated careful consideration of the patient's cardiovascular and respiratory challenges. Due to the patient's facial deformity and limited neck mobility, general anesthesia was not feasible. Instead, a multimodal analgesia approach was adopted, utilizing regional nerve blocks targeting various nerves involved in lower limb innervation. This approach, combined with sedation, provided effective surgical anesthesia.

Pharmaceutical Management of Secondary Hyperparathyroidism and the Role of Surgery: A 5-Year Retrospective Study

Background and Objectives: Secondary hyperparathyroidism (SHPT) poses a common condition among patients with chronic kidney disease (CKD) due to the chronic stimulation of the parathyroid glands as a result of persistently low calcium levels. As a first option for medical treatment, vitamin D receptor analogs (VDRAs) and calcimimetic agents are generally used. Apart from cinacalcet, which is orally taken, in recent years, another calcimimetic agent, etelcalcetide, is being administered intravenously during dialysis. Materials and Methods: In a 5-year retrospective study between 2018 and 2023, 52 patients undergoing dialysis were studied. The aim of this study is to highlight the possible effects and/or benefits that intravenously administered calcimimetic agents have on CKD patients. A total of 34 patients (65.4%) received cinacalcet and etelcalcetide while parathormone (PTH) and calcium serum levels were monitored on a monthly basis. Results: A total of 29 out of 33 patients (87.9%) that received treatment with etelcalcetide showed a significant decrease in PTH levels, which rose up to 57% compared to the initial values. None of the included patients needed to undergo parathyroidectomy (PTx) due to either extremely high and persistent PTH levels or severe side effects of the medications. It is generally strongly advised that parathyroidectomies should be performed by an expert surgical team. In recent years, a significant decrease in parathyroidectomies has been recorded globally, a fact that is mainly linked to the constantly wider use of new calcimimetic agents. This decrease in parathyroidectomies has resulted in an important decrease in complications occurring in cervical surgeries (e.g., perioperative hemorrhage and nerve damage). Conslusions: Despite the fact that these surgical complications cannot be easily compared to the pharmaceutical side effects, the recorded decrease in parathyroidectomies is considered to be notable, especially in cases of relapse where a difficult reoperation would be considered based on previously published guidelines.

Persistent changes in calcium-regulating hormones and bone turnover markers in living kidney donors more than 20 years after donation

Abstract In a previous study, we observed decreased 1,25-dihydroxyvitamin D levels, secondary hyperparathyroidism, and increased bone turnover markers in living kidney donors (LKDs) at 3 months and 36 months after kidney donation. In our recent survey-based study, we found no increased risk of fractures of all types but observed significantly more vertebral fractures in LKDs compared to matched controls. To elucidate the long-term effects of kidney donation on bone health, we recruited 139 LKDs and 139 age and sex matched controls from the survey-based participants for further mechanistic analyses. Specifically, we assessed whether LKDs had persistent abnormalities in calcium and phosphorus-regulating hormones and related factors, in bone formation and resorption markers, and in density and microstructure of bone compared with controls. We measured serum markers, bone mineral density (BMD), bone microstructure and strength (via high-resolution peripheral quantitative computed tomography and micro-finite element analysis [HRpQCT]), and advanced glycation end-products (AGEs) in donors and controls. LKDs had decreased 1,25-dihydroxyvitamin D concentrations (donors mean 33.89 pg/mL vs. controls 38.79 pg/mL, percent difference = -12.6%; P < 0.001), increases in both parathyroid hormone (PTH when corrected for ionized calcium; donors mean 52.98 pg/mL vs. controls 46.89 pg/mL,% difference 13%; P = 0.03) and ionized calcium levels (donors mean 5.13 mg/dL vs. controls 5.04 mg/dL; P < 0.001) and increases in several bone resorption and formation markers versus controls. LKDs and controls had similar measures of BMD; however, HRpQCT suggested that LKDs have a statistically insignificant tendency towards thinner cortical bone and lower failure loads as measured by micro-finite element analysis. Our findings suggest that changes in the hormonal mileu after kidney donation and the long-term cumulative effects of these changes on bone health persist for decades after kidney donation and may explain later-life increased rates of vertebral fractures.

Secular trends in the incidence and treatment patterns of primary hyperparathyroidism in Korea: a Nationwide cohort study

Abstract Data on epidemiology and secular trend in primary hyperparathyroidism (PHPT) in adults is relatively limited in Asian countries. This study aims to provide an overview of the secular trends in incidence, clinical characteristics, and treatment patterns of PHPT in South Korea. We used Korea’s National Health Insurance Claim database (2005–2020) to identify newly diagnosed PHPT cases. Individuals with age below 19, fewer than two E21.0 diagnoses, fewer than two parathyroid hormone measurements, secondary hyperparathyroidism, undergoing dialysis or kidney transplantation within a year of diagnosis, parathyroidectomy (PTX) within a year prior to the diagnosis code, and diagnosis of multiple endocrine neoplasm or parathyroid carcinoma were excluded from the analysis. A total of 6837 patients with PHPT (PTX, n = 2989; non-surgery, n = 3848) were compared to 1:10 age- and sex-matched controls (n = 68 370). The mean age of patients with PHPT was 56.0 years, with 77.4% being women. The annual incidence of PHPT increased from 0.23/100000 persons in 2005 to 1.75 in 2020, with higher rate in women than in men. Compared to 2005-2010 (n = 675), the number of newly diagnosed PHPT cases increased up to 3.1-fold (n = 2119) in 2011-2015 and 6.0-fold (n = 4043) in 2016-2020 periods. Among all patients with PHPT, 43.7% of patients underwent PTX, with decrement of proportion of bilateral surgery among PTX group across time (11.9% in 2005-2010 to 8.9% in 2016-2020, p for trend 0.033). Among all patients with PHPT, non-surgery group increased from 41.6% in 2005-2010 to 58.0% in 2016-2020 (p for trend <0.001). Patients with PHPT had higher odds of osteoporosis (odds ratio [OR] 7.03), renal stones (OR 10.55), chronic kidney diseases (OR 7.42), and cardiovascular, metabolic, and neurological conditions after adjustment for comorbidity index. In summary, the incidence of PHPT increased from 2005 to 2020 with predominance of non-surgical treatment, which calls for research focus on improving non-surgical management.

Pretransplant Parathyroidectomy in Patients with Severe Secondary Hyperparathyroidism and Long-Term Effectiveness After Kidney Transplantation.

Kidney transplantation (KT) is the best option for patients with end-stage renal disease, but recipients still have legacy bone mineral disease from the pretransplant period, especially patients with severe secondary hyperparathyroidism (sHPT). Patients who had severe sHPT and underwent KT were analyzed retrospectively. Two groups were identified (patients with severe sHPT who had parathyroidectomy or calcimimetic before KT). Bone mineral density (BMD) was measured in the first year and last follow-up at the femoral neck, total hip, and lumbar spine using the dual-energy X-ray absorptiometry (DXA). Persistent hyperparathyroidism (perHPT) incidence was significantly higher in the calcimimetic group (75% vs. 40%, p=0.007). In patients with parathyroidectomy, BMDs were higher at femoral neck (0.818±0.114 vs. 0.744±0.134, p=0.04) and lumbar spine (1.005±0.170 vs. 0.897±0.151, p=0.01) at the first assessment. The BMD comparison between patients treated with parathyroidectomy and calcimimetic found a significant difference only in the femoral neck at second evaluation (0.835±0.118 vs. 0.758±0.129; p=0.03). In multivariate, linear regression revealed a positive association between the last BMD of the femoral neck with body mass index (CC: 0.297, 95% CI, 0.002-0.017) and parathyroidectomy (CC: 0.319, 95% CI, 0.021-0.156). Parathyroidectomy is associated with a significantly better femoral neck BMD and a lower incidence of perHPT in patients with severe sHPT.

A Mandibular Brown Tumor: A Pediatric Case Report and Summary of Adolescence Cases

Mandibular brown tumors are often radiographically and histologically indistinguishable from cherubism, aneurysmal bone cyst, giant cell granuloma, and odontogenic fibroma. Laboratory findings of hyperparathyroidism (HPT) aid in directing therapy. We present a case of a 14-year-old male with a brown tumor of the mandible associated with secondary HPT due to vitamin D deficiency. Core biopsy exhibited a proliferation of plump spindle cells and osteoclast-like giant cells within variably fibrous stroma. Parathyroid hormone (PTH) levels were elevated to 288 pg/mL (normal 8.5-77.1 pg/mL) and vitamin D was low at a level of 6.9 ng/mL (normal > 20.0 ng/mL). Six months after the introduction of weekly vitamin D supplementation, PTH and vitamin D levels improved but remained abnormal with PTH of 86.8 pg/mL and vitamin D of 9.3 ng/mL. Alongside an improvement in laboratory indices, the tumor character stabilized and became less clinically friable; however, the burden remained unchanged. At 9 months, the patient underwent surgical debulking of the tumor with local soft tissue coverage. A review of pediatric literature was performed, among which 16 patients were identified. Most children who developed brown tumors were found to have secondary HPT and ultimately 44% underwent some degree of surgical debridement of the mass.

Secondary hyperparathyroidism after total en bloc gastrectomy due to Non-Hodgkin's lymphoma

Secondary hyperparathyroidism after total en bloc gastrectomy due to Non-Hodgkin's lymphoma

Management of maxillary osteitis fibrosa cystica in a patient with secondary hyperparathyroidism: a report of a case

Management of maxillary osteitis fibrosa cystica in a patient with secondary hyperparathyroidism: a report of a case

Predictive factors of early postoperative hypocalcemia in patients with secondary hyperparathyroidism undergoing parathyroidectomy

Predictive factors of early postoperative hypocalcemia in patients with secondary hyperparathyroidism undergoing parathyroidectomy

Multiscale effects of the calcimimetic drug, etelcalcetide on bone health of rats with secondary hyperparathyroidism induced by chronic kidney disease

Chronic kidney disease-induced secondary hyperparathyroidism (CKD-SHPT) heightens fracture risk through impaired mineral homeostasis and elevated levels of uremic toxins (UTs), which in turn enhance bone remodeling. Etelcalcetide (Etel), a calcium-sensing receptor (CaSR) agonist, suppresses parathyroid hormone (PTH) in hyperparathyroidism to reduce excessive bone resorption, leading to increased bone mass. However, Etel's effect on bone quality, chemical composition, and strength is not well understood. To address these gaps, we established a CKD-SHPT rat model and administered Etel at a human equivalent dose concurrently with disease induction. The effects on bone and mineral homeostasis were compared with a CKD-SHPT (vehicle-treated group) and a control group (rats without SHPT). Compared with vehicle-treated CKD-SHPT rats, Etel treatment improved renal function, reduced circulating UT levels, improved mineral homeostasis parameters, decreased PTH levels and prevented mineralization defect. The upregulation of mineralization-promoting genes by Etel in CKD-SHPT rats might explain its ability to prevent mineralization defects. Etel preserved both trabecular and cortical bones with attendant suppression of osteoclast function besides increasing mineralization. Etel maintained the number of viable osteocytes to the control level, which could also contribute to its beneficial effects on bone. CKD-SHPT rats displayed increased carbonate substitution of matrix and mineral, and decreased crystallinity, mineral-to-matrix ratio, and collagen maturity, and these changes were mitigated by Etel. Further, Etel treatment prevented CKD-SHPT-induced deterioration in bone strength and mechanical behavior. Based on these findings, we conclude that in CKD-SHPT rats, Etel has multiscale beneficial effects in a bone that involve remodeling suppression, mineralization gene upregulation, and preservation of osteocytes.

Effect of paricalcitol on biochemical markers of secondary hyperparathyroidism in hemodialysis patients

Effect of paricalcitol on biochemical markers of secondary hyperparathyroidism in hemodialysis patients

Brown Tumor From Secondary Hyperparathyroidism Mimicking Metastatic Renal Cell Carcinoma in a Patient With End-Stage Renal Disease

Brown Tumor From Secondary Hyperparathyroidism Mimicking Metastatic Renal Cell Carcinoma in a Patient With End-Stage Renal Disease

Serum 25(OH)D Levels and Mitral Valve Calcification in Patients with Severe Rheumatic Mitral Stenosis

Background: Rheumatic heart disease (RHD) imposes a significant burden on patients and the health system, especially in the developing countries. Recently, the role of vitamin D deficiency in increasing the severity of valve involvement and calcification in patients with RHD has been suggested. However, its role in the severe stenosis of the mitral valve is unknown. The aim of this study was to determine the relationship between serum levels of 25(OH)D and mitral involvement severity scores in patients with severe mitral stenosis (MS). Materials and Methods: In this cross-sectional study conducted in Shahid Madani Heart Center, Tabriz, Iran, 104 patients with severe rheumatic MS were reviewed, in the absence of other underlying diseases. Trans-esophageal Echocardiography was performed for all patients, and mitral valve Wilkins score and mitral valve area were calculated. Blood samples were taken from patients and levels of 25(OH)D, total calcium, phosphorus, and i-PTH were measured. Results: Eighty eight cases were female and 16 were male. Eighty-one patients had mild to moderate mitral calcification and in 23 patients with mitral valve was severely calcified. Furthermore, 54 were vitamin D deficient, while 35 had insufficient vitamin D levels, and only 15 had normal blood levels of vitamin D. In addition high serum iPTH levels were present in 83 patients (80%). The levels of 25(OH)D, calcium, phosphorous, and iPTH with total Wilkins score, calcification score and mitral valve area were not significantly correlated (p>0.05 for all above). Conclusions: Although no correlation was found between the severity of mitral valve involvement, and vitamin D and iPTH levels, vitamin D deficiency and secondary hyperparathyroidism tend to be common among patients with severe rheumatic MS, which may play a role in the progression of the disease.

Benign paroxysmal positional vertigo: case developed with hyperparathyreoidism and vitamin D deficiency

The most common cause of spinning vertigo is benign paroxysmal positional vertigo (BPPV). Most cases are related to idiopathic BPPV, which pathogenesis is still not fully understood. In this manuscript the clinical case of recurrent benign paroxysmal positional vertigo is depicted. BPPV in this case was occurred primary in menopausal period. A clinical feature of this case is its combination not only with vitamin D deficiency and postmenopausal osteopenia (confirmed according to osteodensitometry), but also with secondary hyperparathyroidism, laboratory confirmed. The literature has accumulated data to link the development and recurrence of BPPV with vitamin D deficiency and osteoporosis, but few comprehensive studies of all crucial indicators of calcium-phosphorus metabolism in these patients have been published. Meanwhile, according to the author, a comprehensive endocrinological study of calcium-phosphorus metabolism in a patient with newly diagnosed BPPV can help optimize therapy for this category of patients.

The value of ultrasound in combination with 99mTc-MIBI imaging department of ultrasound medicine, for the diagnosis of ectopic parathyroid glands in the thyroid gland in patients with secondary hyperparathyroidism.

To investigate the value of preoperative ultrasound combined with 99mTc-MIBI imaging for the diagnosis of ectopic intrathyroid parathyroid gland (ETPG) in patients with secondary hyperparathyroidism (SHPT). One hundred and eleven patients with SHPT who underwent total parathyroidectomy plus forearm transplantation from January 2015 to January 2022 in the Third Hospital of Hebei Medical University were selected. All patients underwent routine preoperative ultrasonography and 99mTc-MIBI imaging, and with pathological diagnosis as the gold standard, the clinical data of ETPG patients were selected, including clinical manifestations, laboratory tests, preoperative ultrasonography and 99mTc-MIBI imaging for localization and diagnosis, intraoperative exploration and postoperative pathology, and postoperative follow-up. To analyze the ultrasound manifestations of preoperative parathyroid hyperplasia and the results of 99mTc-MIBI imaging in patients with ETPG. Among 111 patients with SHPT, there were 5 patients with ETPG, 1 male and 4 females with a mean age of (45.00 ± 5.05) years, and 6 ectopic parathyroid glands were located in the thyroid gland. The incidence of ETPG was 4.5% (5/111), 4 were detected by ultrasound, 2 were not detected with a diagnostic accuracy of 66.7% (4/6), 3 were positive for 99mTc-MIBI imaging, 3 were negative with a diagnostic accuracy of 50.0% (3/6). Among them, one was not detected by ultrasound, but was positive for 99mTc-MIBI imaging, 2 with negative 99mTc-MIBI imaging, but all were detected by ultrasound, and one with negative 99mTc-MIBI imaging was detected by ultrasound but misdiagnosed as a thyroid nodule. A total of 5 ETPGs were detected by ultrasound combined with 99mTc-MIBI imaging, with a diagnostic accuracy of 83.3% (5/6). Patients' postoperative serum calcium and serum parathyroid hormone (PTH) levels were normalized or significantly decreased from preoperative levels. Ultrasound combined with 99mTc-MIBI imaging can achieve higher accuracy than either examination alone in the preoperative localization and diagnosis of ETPG in SHPT patients.

Extended-Release Calcifediol: A Data Journey From Phase 3 Studies to Real-world Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism.

Early secondary hyperparathyroidism (SHPT) diagnosis and treatment are crucial to delay the progression of SHPT and related complications, in particular, cardiovascular events and bone fractures. Extended-release calcifediol (ERC) has been developed for the treatment of SHPT in patients with stage 3/4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). This review compares baseline characteristics and treatment responses of SHPT patients receiving ERC in Phase 3 studies with those treated with ERC in a real-world study. Mean ± standard deviation baseline parathyroid hormone (PTH) levels were 147 ± 56 pg/mL and 148 ± 64 pg/mL in the Phase 3 ERC cohorts, and 181 ± 98 pg/mL in the real-world study. Other baseline laboratory parameters were consistent between the clinical and real-world studies. ERC treatment increased 25-hydroxyvitamin D [25(OH)D] and significantly reduced PTH levels, regardless of baseline CKD stage, in all studies. In the pooled Phase 3 per-protocol populations, 74% of the ERC cohort were up-titrated to 60 μg/day after 12 weeks at 30 μg/day, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% PTH reduction. Despite a much lower rate of uptitration in the real-world study, 70% of patients achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH. These data establish a 'continuum' of clinical and real-world evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage, baseline PTH levels, and ERC dose. This evidence supports early treatment initiation with ERC, following diagnosis of SHPT, VDI, and stage 3 CKD, to delay SHPT progression.

Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease.

Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD. Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness. Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.

The molecular mechanisms of peptidyl-prolyl cis/trans isomerase Pin1 and its relevance to kidney disease.

Pin1 is a member of the peptidyl-prolyl cis/trans isomerase subfamily and is widely expressed in various cell types and tissues. Alterations in Pin1 expression levels play pivotal roles in both physiological processes and multiple pathological conditions, especially in the onset and progression of kidney diseases. Herein, we present an overview of the role of Pin1 in the regulation of fibrosis, oxidative stress, and autophagy. It plays a significant role in various kidney diseases including Renal I/R injury, chronic kidney disease with secondary hyperparathyroidism, diabetic nephropathy, renal fibrosis, and renal cell carcinoma. The representative therapeutic agent Juglone has emerged as a potential treatment for inhibiting Pin1 activity and mitigating kidney disease. Understanding the role of Pin1 in kidney diseases is expected to provide new insights into innovative therapeutic interventions and strategies. Consequently, this review delves into the molecular mechanisms of Pin1 and its relevance in kidney disease, paving the way for novel therapeutic approaches.