Evaluation of relationship between biochemical parameters and osteoporosis in patients with β-thalassemia major

Background: Osteoporosis is one of the late complications of β-Thalassemia major. The pathogenesis of osteoporosis depends on different factors. Ineffectiveness of hematopoiesis is the major factor, and the other factors are defected by hormonal functions or biochemical parameters. Osteoclasts hyperactivity in thalassemia increases the serum receptor activator of nuclear factor Kappa B ligand (RANKL), which plays a crucial role in bone development. This study aimed to evaluate the biochemical and hormonal parameters in patients with β-thalassemia major and their association with osteoporosis. Materials and Methods: In this case-control study, 52 patients with β-thalassemia major and 23 with thalassemia minor as controls were enrolled. The patients’ Bone Mineral Density (BMD) was measured using the Dual Energy X-ray absorptiometry (DEXA) method, and 6 mL peripheral blood of the patients and controls was obtained to detect hormonal and biochemical parameters. Data were analyzed using ANOVA, Spearman correlation coefficient, and T-test. Results: The mean of BMD in patients was 0.59±0.01 and 0.69±0.11 in femur and vertebrae, respectively. The biochemical parameters in the (patients/ controls) including calcium and alkaline phosphatase (ALK) were 9.1/ 10.2 mg/dL and 171.1/310 IU, respectively indicating a significant decrease (P< 0.05) compared to the controls. On the contrary, the mean levels of Ferritin and Zinc were 1914.18 µg/L and 113.92 mg/mL, respectively which were significantly increased (P= 0.015 and P=0.045, respectively). There was a negative correlation between the femurs BMD of patients with the RANKL level (r= - 0.8, p = 0.034) and the vertebrae BMD of patients with a Parathormone (PTH) level (r= - 0.8, P = 0.028). Conclusion: The study results indicated that the hyperactivity of RANKL and PTH in thalassemia patients might cause osteoporosis; therefore, detecting biomarkers mentioned above could be useful to diagnose osteoporosis.

The Study of the Association of Serum Parathyroid Hormone Level with Obesity in Patients Admitted to a Tertiary Care Center in Basrah

<b><i>Background:</i></b> Parathyroid hormone (PTH) has been reported to have a positive correlation with insulin resistance and the development of the metabolic syndrome. This study aims to evaluate if there is an association between obesity and serum PTH levels. <b><i>Methods:</i></b> This case-control study was conducted at the Faiha Specialized Diabetes Endocrine and Metabolism Center in Basrah (Southern Iraq) from September 2018 to July 2019. A total of 230 patients were recruited for this study (103 male and 127 female), divided into 2 groups according to the BMI: &#x3c;30 kg/m² were considered as the control group (83 persons) and ≥30 kg/m² were considered as obese persons (147 persons). The study groups were also subdivided into 3 groups according to the serum level of PTH: &#x3c;40 pg/mL, 40–65 pg/mL, and &#x3e;65 pg/mL. <b><i>Results:</i></b> The mean age of the obese and control groups was 44.39 ± 10.64 and 30.12 ± 8.95 years, respectively. About 46.25% of obese were men and 53.75% were women, while 42% of the control group were men and 58% were women. Serum PTH level was significantly higher (<i>p</i> &#x3c; 0.001) among obese persons with a mean level of 53.21 ± 19.58 pg/mL for obese and 37.63 ± 21.8 pg/mL for control. Vitamin D deficiency was seen in 84.4% of the obese group while in 71.1% of the control group (<i>p</i> value 0.04). Females turned to have higher PTH levels than males in both the obese and the control group (<i>p</i> value &#x3c;0.001). However, age and the presence of diabetes mellitus were not associated with higher PTH levels (<i>p</i> value 0.155 and 0.6, respectively). <b><i>Conclusion:</i></b> Obesity was associated with a higher serum PTH level related to the severity of vitamin D deficiency.

Brown Tumors of the Mandible Revealing Hyperparathyroidism: About Two Cases

The diagnosis of osteolytic lesions of the jaws can be challenging. Case Reports: Two cases of brown tumor of hyperparathyroidism were reported. A 76- year-old female patient presented with indolent swelling of her right lower jaw measuring approximately 5 cm /6 cm. The panoramic radiograph showed a well-defined osteolytic radiolucency involving the entire mandibular symphysis. Blood investigations revealed High level of parathyroid Hormone (PTH): 102pg/ml. The diagnosis of a brown tumor of hyperparathyroidism was suspected. A parathyroid technetium scintiscan revealed abnormally high uptake at the lower pole of the thyroid lobe interpreted as hyperplasia of right inferior parathyroid gland with possible brown tumor of the mandible. Second case: A 36- year-old female patient presented for the replacement of her missing teeth. Her medical history revealed chronic renal failure and a recent surgical excision of an Osteitis fibrosa cystica of her fifth left proximal phalange. Panoramic radiograph showed multiple well defined osteolytic lesions of the mandible. The diagnosis of a brown tumor of the mandible secondary to hyperparathyroidism was suspected. Laboratory investigations showed increased PTH level, serum hypocalcemia and hyperphosphatemia and vitamin D deficiency. The patient was referred to the department of endocrinology for further investigation and the correction of PTH level. At Six months follow up all the lesions disappeared on radiological control. Discussion: Brown tumor of hyperparathyroidism is a metabolic disorder causing bone resorption that can affect the jaw bones. Clinical symptoms depend on the size and the location of the lesion. Radiographically, it appears as radiolucent unique or multiple well-defined intra-osseous radiolucency. Biological examination is the key to the diagnosis and it is marked by high level of parathyroid hormone (PTH). Key words: Jaw, Tumors, Osteitis Fibrosa Cystica, Hyperparathyroidism, Diagnosis.

A case of a hemodialysis patient with secondary hyperparathyroidism who was resistant to etelcalcetide treatment but not to cinacalcet hydrochloride

Although both cinacalcet and etelcalcetide are calcimimetics that directly inhibit parathyroid hormone (PTH) secretion by activating the calcium (Ca)-sensing receptor (CaSR), their binding sites are different. We report a first case of a hemodialysis (HD) patient with secondary hyperparathyroidism (SHPT), in whom cinacalcet, but not etelcalcetide, could reduce serum intact PTH (i-PTH) levels. A HD patient received total parathyroidectomy (PTx) with auto-transplantation 16 years earlier. Due to SHPT relapse, cinacalcet was started at 7 years after PTx. His i-PTH levels had been controlled with both 75–100 mg of cinacalcet and 4.5 μg/week of calcitriol for a year before switching from cinacalcet to etelcalcetide. At 1 month following the switch, his serum i-PTH level increased to 716 pg/mL. The dose of etelcalcetide was gradually increased and finally reached the maximal dose of 45 mg/week. Because even the maximal dose of etelcalcetide for > 4 months did not reduce his serum i-PTH levels to < 700 pg/mL, etelcalcetide was switched to 50 mg/day of cinacalcet, which reduced the levels to 208 pg/mL at 2 months after the switch. Genomic sequencing test using whole blood revealed no mutation in the portion including Cys 482 of CaSR gene. The patient was resistant to etelcalcetide treatment but not to cinacalcet, suggesting the possibility that the enlarged parathyroid gland has some change in the portion including Cys 482 in the CaSR gene. Therefore, considering the possibility of etelcalcetide resistance during SHPT treatment should be kept in mind.

The Association between Parathyroid Hormone (PTH) Level and Hemoglobin and Hematocrit Level in Chronic Kidney Disease (CKD) Patients with Regular Hemodialysis

Introduction: Chronic Kidney Disease (CKD) is a pathophysiological process with various etiology that causes a progressive decline in kidney function and ends in kidney failure. [1] CKD is a health problem that occurs in the community and has covered globally. The 2010 Global Burden of Disease stated that CKD was the 27th leading cause of death in the world in 1990. This has increased to 18th in 2010. Parathyroid hormone is a potential factor in the incidence of anemia in CKD patients. In CKD patients, there is an increase in levels of parathyroid hormone which is a uremic toxin that inhibits erythropoietin by increasing fibrosis in the bone marrow (myelofibrosis). The role of PTH in cases of renal anemia has been extensively investigated by various clinical observational studies. This study aimed to determine the association between parathyroid hormone (PTH) levels and hemoglobin and hematocrit levels in chronic kidney disease (CKD) patients with regular hemodialysis in Haji Adam Malik Central General Hospital. Methods: This is an analytical study with a cross-sectional design. A total of 45 study subjects met the inclusion criteria and exclusion criteria, underwent history taking, physical examination, anthropometry, and laboratory examination to measure parathyroid hormone, hemoglobin, hematocrit, and albumin levels. Data analysis was performed using SPSS. Results: The measured PTH level had a minimum value of 113 pg/ml and a maximum of 595 pg/ml with an average of 431.4. The minimum hemoglobin value is 6.3 g/dl and a maximum of 11.5 g/dl with an average of 7.9, while for the hematocrit the minimum value is 19% and the maximum is 35% and the average is 24.7. The Mann-Whitney U test showed that there is a significant relationship between PTH levels and hemoglobin, indicated by a significant p value of 0.001 (p value < 0.05). A significant relationship was also found between PTH levels and hematocrit (p value = 0.039). Conclusion: Parathyroid hormone has a statistically significant relationship with haemoglobin and haematocrit levels in CKD patients with regular hemodialysis. Keywords: Chronic kidney disease; haemoglobin; haematocrit; parathyroid hormone; anemia; hemodialysis.

Serum Level of Parathyroid Hormone, Alkaline Phosphatase, Calcium and Ionized Calcium After Forearm Fractures

Background During the last two decades, our understanding of fracture healing has evolved rapidly. Bone is one of the few body tissues that can heal without forming a fibrous scar and, as such, the process of fracture healing recapitulates bone development and may be considered a form of tissue regeneration. The complex cell and tissue proliferation and differentiation processes involved in fracture healing are regulated by growth factors, inflammatory cytokines, antioxidants, hormones, amino acids, and other nutrients. Objective: To identify changes in serum level of calcium, ionized calcium, alkaline phosphatase and parathyroid hormone according to mode of trauma (low and high energy) in forearm fractures and their role in fracture healing. Patients and Methods 50 Patients with forearm fracture were prospectively recruited from the Accident and Emergency Department of Trauma Surgery, El Zaitoun specialized hospital within 48 hours of sustaining the fracture. Patients included in the study were asked to avoid calcium supplementation during fracture healing. Results Mean PTH was elevated in both groups at Day 1 with low energy group was insignificantly higher than high energy group, whereas after 8 weeks mean PTH level decreased in both groups but in low energy group mean PTH level was significantly higher than high energy group. Mean ALP level increased in both groups at Day 1 whereas in low energy group it was insignificantly higher than that of high energy group, After 8 weeks mean ALP level insignificantly decreased to normal level in both groups. Mean serum calcium level was below normal level in both groups where it was insignificantly higher in high energy group than that of low energy group which increased after 8 weeks in both groups but remained elevated in high energy than low energy group. Mean serum ionized calcium level was below normal level at Day 1 in both groups whereas it was insignificantly higher in high energy group than low energy group which after 8 weeks increased in both groups but remained elevated in high energy group than low energy group. Conclusion Serial monitoring of these physiological markers reflect the actual status of bone resorption, and bone formation respectively over a short period. Thus, they can be used as an adjunct to clinical and radiological evidence of fracture healing.

ONCOCYTIC INTRATHYROID PARATHYROID ADENOMA MASQUERADING AS HURTHLE CELL NEOPLASM: FINE NEEDLE ASPIRATION CYTOLOGY OF TWO CASES

Ectopic parathyroid adenomas in thyroid tissue are uncommon (0.7 - 6%), and their oncocytic variants are exceedingly rare. We report two cases of intrathyroid parathyroid adenoma which were diagnosed as Hurthle cell adenoma on cytology. Case 1 is a 49-year-old female with a 2.4 cm hypoechoic nodule in the left lateral neck. Electrochemiluminescent immunoassay of the aspirate revealed PTH level of 422 pg/ml, conrming the presence of hyperfunctional parathyroid tissue. Subsequent resection of the left thyroid lobe revealed an enlarged intrathyroidal parathyroid. Case 2 is a 58-year-old female with a 2.1 cm hypoechoic nodule in the posterior-mid left thyroid lobe. Strong overexpression of parathyroid hormone and Chromogranin A genes and low expression of thyrocyte-related genes suggested parathyroid origin of the cells sampled. MEN1 mutation and multiple copy number alterations indicated the neoplastic nature of the nodule. Parathyroid oxyphil cells and oncocytic thyrocytes share cytomorphological ndings and distinguishing them by cytology alone is challenging, especially when the targeted lesion is intrathyroidal. Distinguishing intrathyroid oncocytic parathyroid adenoma from oncocytic thyroid follicular lesions has signicant clinical implications as Bethesda-IV category lesions have 20%–30% risk of malignancy. While stippled chromatin or intracytoplasmic fat vacuoles may be suggestive of parathyroid origin, these are not specic. Classifying the origin of a nodule as parathyroid vs thyroid rests upon the detection of PTH in aspirate material by ECL, immunocytochemistry or next-generation sequencing. In parathyroid aspirates, PTH level 100 pg/mL is suggestive of the presence of PTH-secre ≥ ting tissue at the site biopsied or along the needle track.

Effect of Pretransplant Use of Calcimimetic on Parathyroid Function after Renal Transplantation

Objective. Persistence of hyperparathyroidism (HPT) after renal transplantation leads to undesirable outcomes such as increase in cardiovascular events, graft dysfunction, and increased mortality. Options for therapy include medical management with calcimimetic or operative management. The present study was undertaken to evaluate the natural history of HPT after renal transplantation and to determine risk factors for persistent HPT in the era of calcimimetic. Design. The study is a retrospective review of data from 74 consecutive patients who underwent renal transplantation at our institution from April 2011 to November 2019. Methods. The natural history of HPT after renal transplantation and associations between intact parathyroid hormone (PTH) level after transplantation and clinical variables such as age, sex, duration of pretransplant dialysis, and use of calcimimetic before transplantation were evaluated. Results. Intact PTH decreased after renal transplantation in most of the patients without receiving parathyroidectomy. Known risk factors of persistent HPT did not associate with intact PTH level after renal transplantation in patients who had been receiving calcimimetic before transplantation. Conclusion. In conclusion, we have found that HPT after renal transplantation could be managed successfully by medical treatments. When predicting the prognosis of HPT after transplantation, pretransplant use of calcimimetic should be taken into consideration.

The impact of CASR A990G polymorphism in response to cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism

The objective of this study was to determine the impact of calcium sensing receptor (CASR) A990G genetic polymorphism on parathyroid hormone (PTH) lowering response to cinacalcet treatment when controlling for significant influencing clinical factors. This retrospective study was conducted on 135 Thai hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). CASR A990G genotypes were determined. The patients were identified as either G carriers (heterozygous or homozygous CASR 990G allele carriers) or noncarriers (homozygous CASR 990A carriers). Tested covariates were baseline PTH level (bPTH), baseline serum phosphate (bPhos), baseline serum calcium (bCa), baseline calcitriol equivalent dose (bCtriol), baseline ergocalciferol dose (bErgo), and age. The ANCOVA showed that intact PTH levels after 12 weeks of cinacalcet treatment (PTHw12) was significantly lower among G carriers compared with noncarriers after controlling for bPTH, bPhos, bCtriol, and bErgo (F(1, 127) = 15.472, p < 0.001), with the adjusted mean difference of 253.7 pg/mL. The logistic regression analysis revealed that the odds of a G carrier achieving 30% PTH reduction after 12-week cinacalcet treatment were 3.968 times greater than the odds for a noncarrier after adjusting for bPhos, bCtriol, and age. In conclusion, the CASR A990G polymorphism significantly influences cinacalcet response in HD patients with SHPT.

Diagnostic performance of the calcium/phosphate ratio for primary hyperparathyroidism in southwest China

Background: The diagnosis of primary hyperparathyroidism (PHPT) remains a challenge because of increased asymptomatic PHPT or patients with normocalcaemic PHPT (NPHPT). In addition, some primary hospitals in China have no equipment to measure PTH levels. Therefore, an additional, simple, and inexpensive laboratory biochemical marker is urgently needed. The calcium/phosphate (Ca/P) ratio and chloride/phosphate (Cl/P) ratio have been proposed as suitable tools to diagnose PHPT in Europe; however, the Ca/P ratio has never been tested in China. We aimed to conduct a confirmatory study to explore the diagnostic performance of the Ca/P ratio for PHPT in China. Methods: From January 2015 to December 2020, a total of 155 patients who underwent parathyroidectomy (143 PHPT patients and 12 NPHPT patients) and 153 controls were enrolled in this single-center, retrospective study. Serum calcium, phosphate, parathyroid hormone, 25-OH vitamin D, chloride, ALT, AST, eGFR, and creatinine levels were recorded for all the study participants. Pairwise comparisons were made between groups, and the diagnostic performance of the Ca/P ratio was determined using receiver operating characteristic (ROC) analysis. Results: Patients with PHPT had a higher Ca/P ratio than controls (P < 0.001). A Ca/P ratio above 2.94 with a sensitivity of 95.5% and specificity of 98.7% can distinguish PHPT patients from healthy individuals. This index was positively correlated with the PTH level (r = 0.875, P < 0.001). Conclusion: The Ca/P ratio is an ideal and inexpensive indicator for diagnosing PHPT in China when using a cutoff value of 2.94.