High Parathyroid Hormone Levels Research Articles

#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.

#1235 Comparative effect on bone remodeling and inflammation biomarkers of citrate dialysate and bicarbonate dialysate in HDF-OL patients

Abstract Background and Aims Hemodialysis (HD) treatment increases the inflammatory state of chronic kidney disease (CKD), which is associated with dysregulation of mineral bone metabolism. Reduced inflammation and increased bone formation have been described in Hemodiafiltration (HDF) compared with conventional HD. On the other hand, HD and OL-HDF using citrate-enriched dialysate are known to be safe and anti-inflammatory. However, the effects of post-dilution OL-HDF with citrate dialysate compared to bicarbonate dialysate on biomarkers of bone formation and resorption have not been studied. We aimed to compare the effect of bone remodeling markers and inflammation of different dialysates (citrate vs bicarbonate) in post dilution OL- HDF treatment. Method A total of 33 patients on conventional HD with bicarbonate citrate were included. At month 1, 18 patients, who did not require individualized adjustment of the dialysate composition such as potassium, were changed to HD with citrate dialysate and 15 patients remained with bicarbonate dialysate. By the second month, however, all patients were on OL-HDF with no change in buffer dialysate. Pre-dialysis blood samples were taken in both treatment groups at baseline (prior to the initiation of citrate dialysate in 18 patients), and at the first, second and fifth months after the introduction of citrate. Measurements of mineral homeostasis (calcium, phosphate, magnesium, parathyroid hormone, intact parathyroid hormone), inflammation (interleukin-6, β2-microglobulin, C-reactive protein) and bone remodeling markers (carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX), as a biomarker of bone resorption and procollagen type 1 N-terminal pro-peptide (P1NP), as a biomarker of bone formation) were performed. All samples were collected before a mid-week dialysis session. Mineral homeostasis measurements were also performed before and after HD at the first and second month of the switch to citrate dialysate. Normally distributed data were presented as mean (standard deviation, SD) and median (interquartile range). Intra-subjects comparisons were analyzed using paired sample t-test or Wilcoxon signed-rank test. Comparisons between groups were analyzed using Mann-Whitney U test. Statistical analyses were performed using the SPSS (version 15.0, Chicago, IL, USA). p-value < 0.05. Results Overall, 75.7% (n = 25) of the subjects were male, the median age was 69 years (SD: 12) and 39.3% suffered diabetes (n = 13). Patients on citrate and bicarbonate dialysates were comparable for age, sex, comorbidities, months on dialysis and anemia control. Baseline mineral, bone remodeling and inflammation markers before HD, were also comparable in both groups. Only patients on bicarbonate dialysate had higher β2-microglobulin levels at baseline. Changes in serum levels of mineral, bone remodeling and inflammatory biomarkers at 5 months compared to baseline for both groups are shown in Table 1. After 5 months of follow-up, a 22% trend-reduction (p = 0.08) in P1NP as bone formation biomarker was observed in patients on citrate dialysate compared to those on bicarbonate dialysate. In addition, the fold change observed in CTX as parameter of bone resorption was attenuated in the citrate dialysate group (11% vs 116% in the bicarbonate dialysate group, p < 0.001). β2-microglobulin levels decreased significantly in both groups at 5 months but It is explained by the known effect of OL-HDF treatment on the inflammatory state of dialysis patients. Conclusion In patients on OL-HDF treatment the use of the citrate as dialysate may provide a benefit in bone remodeling by reducing bone resorption and trend to balance the bone formation/resorption. However, our results are in line with previous studies, where caution should be adopted in patients with very high parathyroid hormone levels, as this may be enhanced by reduced mineral turnover.

#3065 Factors associated with recurrence or persistently high parathormone levels after parathyroidectomy in patients with CKD

Abstract Factors associated with recurrence or persistently high parathormone levels after parathyroidectomy in patients with secondary hyperparathyroidism receiving renal replacement therapy Background and Aims Resistant hyperparathyroidism that indicates surgery usually occurs in patients with CKD who receive renal replacement therapy (RRT). This study aims to evaluate the factors associated with persistent or recurrent high levels of PTH after parathyroidectomy due to SHPT in patients receiving RRT. Method In this retrospective study, we included 66 adult patients (mean age: 46.86 ± 13.79) with parathyroidectomy for SHPT receiving renal replacement therapy. Clinicopathological features, laboratory parameters (preoperatively, at the first hour of surgery, at least every three months for at least two years after surgery), type of surgery and pathologic diagnosis were recorded from the medical records. Persistence was defined as failure to achieve a decrease in PTH level of more than fifty percent of preoperative PTH level. Recurrence was defined as elevated PTH levels after six months post-operation (>600 pg/mL). Results The demographics and clinical characteristics of the study population are described in Table 1. High PTH levels were observed in nineteen patients, while recurrence was observed in nine. Persistence was associated with lower preoperative ALP levels (455.27 ± 296.23, 619.72 ± 593.18, p = 0.017). Recurrence was associated with higher preoperative CRP levels (22.89 ± 6.82, 6.82 ± 5.35, p:0,046) and postoperative high phosphorus levels (4.93 ± 0.99, 4.16 ± 1.09, p = .049). Conclusion In our study persistence of high parathormone levels were more common in patients with lower preoperative ALP levels and recurrence was associated with higher preoperative CRP levels and postoperative inadequate phosphorus control. In conclusion, patients with lower ALP and higher CRP levels can be suitable for total parathyroidectomy, which is associated with a lower recurrence rate in SHPT. Also, postoperative phosphorus control can be a key point for preventing the patients' recurrence of high PTH level.

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.

Serum parathormone, vitamin D and cardiovascular risk factors and markers: A pilot study

Background and aimsVitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. The aim of this study is to evaluate the associations of serum vitamin D and parathormone (PTH) concentrations with blood pressure values and hypertension-mediated target organ damage (HMOD), including left ventricular (LV) hypertrophy and carotid plaque (CP). Methods and resultsWe enrolled consecutive patients admitted to the Hypertension Center of Federico II University Hospital in Naples, Italy. All patients underwent carotid doppler ultrasound and echocardiography, measurement of vitamin D and PTH levels and main clinical and laboratory parameters. A total of 126 patients (mean age 54 years, 68% males) were enrolled. Pearson's correlation analysis indicated that PTH levels directly correlated with age, diabetes, dyslipidemia, hypertension, fasting glucose, and LV mass, and inversely with glomerular filtration rate, LDL cholesterol, and vitamin D. Vitamin D levels correlated inversely with PTH, diabetes and CP. Multivariate regression models indicated that an increased LV mass was associated with the presence of obesity (β = 0.342; P = 0.001). Maximal intima-media thickness was significantly associated with an older age (β = 0.303; P = 0.033). Combined presence of low vitamin D/high PTH level was associated with more than 4-fold increased risk of having CP in both univariate (OR = 4.77, p = 0.0001) and multivariate regression analysis (OR = 4.52, p = 0.014). ConclusionIn a population at high cardiovascular risk, vitamin D and PTH levels were not directly associated with blood pressure values and HMOD. Secondary hyperparathyroidism due to vitamin D deficiency is associated with carotid atherosclerosis independently of other common cardiovascular risk factors.

The Molecular Mechanisms Underlying the Systemic Effects Mediated by Parathormone in the Context of Chronic Kidney Disease.

Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone-Vitamin D-Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated "trade-off hypothesis" reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient's prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin-Angiotensin-Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.

Biochemical characteristics and clinical manifestation of normocalcemic primary hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (nPHPT) is a condition characterized by persistently high levels of parathyroid hormone (PTH) and normal serum calcium levels in the absence of other causes for secondary hyperparathyroidism. The aim of the present study was to assess the clinical presentation and the biochemical characteristics in patients with nPHPT and to compare them with those in patients with hypercalcemic PHPT (hPHPT). The study included 316 patients (277 women and 39 men, average age 58.7 ± 12.1) diagnosed with PHPT. Total serum calcium, inorganic phosphates (PO4), PTH, urinary Ca (uCa), albumin, creatinine, 25(OH)D and bone markers (b-CTX and ALP) were examined in all of them. BMD of the lumbar spine (LS), distal third of the radius (DR), femoral neck (FN) and total proximal femur (TF) were measured by a dual-energy X-ray absorptiometry (DXA). The patients were divided into two groups according to albumin-corrected calcium (Ca) level - with hPHPT (Ca>2.62 mmol/L) and with nPHPT (Ca 2.12-2.62 mmol/l), without other causes for secondary hyperparathyroidism. The frequency of nPHPT was 15.2%. Normocalcemic patients had lower levels of PTH, higher PO4 and 25(OH)D, and smaller parathyroid adenomas. No significant difference in the frequency of osteoporosis, low-energy fractures, nephrolithiasis and gastrointestinal disorders was found between nPHPT and hPHPT. There was no difference in BMD between the two groups. The patients with nPHPT show a more favorable biochemical profile compared to those with hPHPT. Nevertheless, clinical manifestations and complications are similar, without a significant difference in the frequency of osteoporosis, nephrolithiasis, gastrointestinal disorders and low-energy fractures.

Is nociplastic pain, a new pain category, associated with biochemical, hematological, and inflammatory parameters?

Objective The aim of the study was to evaluate the relationship between biochemical, hematological, and inflammatory parameters and pain in patients with nociplastic pain. Methods In this cross-sectional study, a total of 8632 patients, aged between 20 and 65, were evaluated according to the nociplastic pain diagnosis criteria determined by IASP. Excluding individuals who did not meet the criteria for nociplastic pain, the study included a total of 660 participants. The biochemical, hematological, and inflammatory parameters of all individuals were examined. The pain levels of the patients were assessed using the Visual Analogue Scale (VAS). The patients were categorized based on nociplastic pain types and pain regions for evaluation. Results In this study, the female gender was more prevalent both in all nociplastic pain categories and in all pain region groups (p < 0.05). In the nociplastic pain categories, it was observed that vitamin D levels were lower in patients with chronic widespread pain, while ferritin and C-reactive protein levels were higher in patients with chronic primary musculoskeletal pain. Among patients with chronic widespread pain with low hemoglobin and/or ferritin levels, the Visual Analog Scale activity score was higher. For patients with chronic widespread pain and low vitamin D levels and/or high erythrocyte sedimentation rate levels, the Visual Analog Scale rest score was higher. In patients with fibromyalgia and high parathyroid hormone levels, the Visual Analog Scale activity score was higher. For patients with fibromyalgia and high Neutrophil/Lymphocyte ratio levels, the Visual Analog Scale rest score was higher. In patients with chronic primary musculoskeletal pain and high erythrocyte sedimentation rate and/or C-reactive protein levels, the Visual Analog Scale activity score was higher. While vitamin B12 levels were found to be lower in patients with widespread pain, no significant relationship was identified between electrolytes, other blood count results, and nociplastic pain. Conclusion In our study, it was observed that levels of vitamin D in individuals with nociplastic pain were low, while erythrocyte sedimentation rate, C-reactive protein, and Neutrophil/Lymphocyte ratio were high, and hemoglobin and ferritin levels were elevated. Furthermore, these findings were found to be associated with both the presence of pain and the severity of pain assessed using the visual analog scale.

O-05 A novel mutation of MEN1 gene in familial Multiple Endocrine Neoplasia Type 1 (MEN1): A report of two cases

Abstract Introduction Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare (1-9/100000) autosomal dominant disease. It is characterized by primary hyperparathyroidism (90%), enteropancreatic tumor (60-70%), non-functional adrenal adenomas (30%) and pituitary tumors (10-20%). Herein, we present two cases in the same family with MEN1 syndrome caused by a novel mutation. Clinical Case 1: 49-year-old male presented to our clinic with fasting hypoglycemia. Fasting serum glucose (FSG) was 51 mg/dl and serum cortisol was 18 ug/dl. During the hypoglycemia in prolonged fasting test, the serum levels of glucose, insulin and C-peptide were 37 mg/dl, 17.3 mu/l, 7.75 ng/ml respectively (Table 1). Abdominal MRI revealed mass lesions in the pancreas (Figure 1). Ultrasonography of the neck and MIBI scintigraphy performed because of the high levels of calcium and parathyroid hormone (PTH), were consistent with parathyroid adenoma (Table 2). Pituitary MRI showed a 12 mm macroadenoma. He underwent parathyroidectomy and distal pancreatectomy simultaneously. The resected specimens revealed a well-differentiated neuroendocrine tumor (NET) of the pancreas and parathyroid adenoma. The patient had no new hypoglycemic episodes after surgery and serum calcium remained within the normal range (Table 2). Central hypothyroidism and hypogonadotropic hypogonadism which was resulted from the pressure of the adenoma was managed medically. Genetic testing revealed a heterozygous mutation in NM_001370251.1:c.949del(HET). First degree relatives of the patient were screened for MEN. Clinical Case 2: The son of case 1, an 18-year-old male, presented with fasting hypoglycemia. He had a BMI of 37 kg/m2 and underwent gastric botox 3 months prior to his presentation. FPG was 52 mg/dl and serum cortisol was 20 ug/dl. Prolonged fasting test confirmed the diagnosis of insulinoma (Table 1). Abdominal MRI showed a pancreatic tail mass 37×22 mm in size. Gallium 68 PET/CT DOTATATE revealed increased uptake in multiple lesions in the pancreas. Ultrasonography and MIBI scintigraphy showed a parathyroid adenoma. A nonfunctional microadenoma was detected in pituitary MRI. The patient underwent distal pancreatectomy. Following pancreatectomy, right superior and left inferior parathyroidectomies were performed. Since his serum calcium levels started to increase in 48 hours after the operation, the patient has had second operation for left superior parathyroidectomy. After the operation, the serum calcium and parathyroid hormone levels were 9.2 mg/dl, 58 pg/ml respectively. Specimens revealed well-differentiated NET and atypical parathyroid adenoma. The patient was found to have the same genetic mutation with his father and during the follow up the serum glucose and calcium levels remained within the normal range (Table 2). Conclusion In the genetic examination the heterozygous mutation NM_001370251.1:c.949del(HET) in exon 7/11 of the MEN1 gene found in our patients represents a novel mutation.Figure 1.MRI showing pancreatic masses Table 1.Laboratory findings Table 2.Prolonged fasting test

The impact of accessibility to non-calcium-based phosphate binders and calcimimetics on mineral outcomes in patients receiving maintenance hemodialysis: A 10-year retrospective analysis of real-world data.

Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are usually required for optimum control of serum phosphate and parathyroid hormone (PTH) levels. The use of calcium-based phosphate binders (CBPBs) and active vitamin D is associated with an increase in serum calcium and worsening vascular calcification. To overcome these limitations, non-calcium-based phosphate binders (NCBPBs) and calcimimetics have been developed. However, the coverage for these new medications remains limited in several parts of the world due to the lack of patient-level outcome data and cost. The present study examined the differences in mineral outcomes between two main categories of healthcare programs that provided different coverage for medications used to control mineral and bone disorders (MBD). The Social Security/Universal Coverage (SS/UC) program covered only CBPBs and active vitamin D, whereas the Civil Servant/State Enterprise (CS/SE) program provided coverage of CBPBs, active vitamin D, NCBPBs, and calcimimetics. This 10-year retrospective cohort study examined the differences in mineral outcomes between two healthcare programs in maintenance hemodialysis patients. The differences in serum calcium, phosphate, and PTH levels, as well as the aortic arch calcification score, were analyzed according to dialysis vintage by linear mixed-effects regression analyses. The difference in the composite outcome of severe hyperparathyroidism and parathyroidectomy was analyzed by the Cox-proportional hazard regression model. 714 patients were included in the analyses (full cohort). Of these patients, 563 required at least one type of medication to control MBD (MBD medication subgroup). Serum calcium, phosphate, and the proportions of patients with hypercalcemia and hyperphosphatemia were substantially higher in the SS/UC group compared with the CS/SE group after appropriate adjustments for confounders in both the full cohort and the MBD medication subgroup. These findings were confirmed in propensity-score matched analyses. Higher parathyroid hormone levels and a higher rate of the composite endpoint of severe hyperparathyroidism and parathyroidectomy were also observed in the SS/UC group. A more rapid progression of aortic arch calcification was suggested in the SS/UC group, but between-group changes were not significant. Patients under the healthcare program that did not cover the use of NCBPBs and calcimimetics showed higher serum calcium and phosphate levels and a more rapid progression of hyperparathyroidism. The difference in the progression of vascular calcification could not be confirmed in the present study.

Associations of Changes in Bone Turnover Markers with Change in Bone Mineral Density in Kidney Transplant Patients.

Bone loss after kidney transplantation is highly variable. We investigated whether changes in bone turnover markers associate with bone loss during the first post-transplant year. Bone mineral density (BMD) was measured at 0 and 12 months, with biointact parathyroid hormone, bone-specific alkaline phosphatase (BALP), intact procollagen type I N -terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) measured at 0, 3, and 12 months post-transplant ( N =209). Paired transiliac bone biopsies were available in a subset ( n =49). Between-group differences were evaluated by Student's t test, Wilcoxon signed-rank test, or Pearson's chi-squared test. Changes in BMD varied from -22% to +17%/yr. Compared with patients with no change (±2.5%/yr), patients who gained BMD had higher levels of parathyroid hormone (236 versus 136 pg/ml), BALP (31.7 versus 18.8 μ g/L), and Intact PINP (121.9 versus 70.4 μ g/L) at time of transplantation; a greater decrease in BALP (-40% versus -21%) and Intact PINP (-43% versus -13%) by 3 months; and lower levels of Intact PINP (36.3 versus 60.0 μ g/L) at 12 months post-transplant. Patients who lost BMD had a less marked decrease, or even increase, in Intact PINP (+22% versus -13%) and TRAP5b (-27% versus -43%) at 3 months and higher Intact PINP (83.7 versus 60.0 μ g/L) and TRAP5b (3.89 versus 3.16 U/L) at 12 months compared with patients with no change. If none of the biomarkers decreased by the least significant change at 3 months, an almost two-fold (69% versus 36%) higher occurrence of bone loss was seen at 12 months post-transplant. Bone loss after kidney transplantation was highly variable. Resolution of high bone turnover, as reflected by decreasing bone turnover markers, associated with BMD gain, while increasing bone turnover markers associated with bone loss.

Parathyroid carcinoma case-report in a patient with multinodular goiter and chronic kidney disease: difficulties in diagnosis and treatment (observation from practice)

We would like to present a clinical case of severe primary hyperparathyroidism due to a parathyroid carcinoma of atypical location in a patient with chronic kidney disease of complex etiology and multinodular goiter. Patient S., 59 years old, was followed-up for a long time in tertiary referral hospitals for “chronic tubulointerstitial nephritis with nephrosclerosis”, secondary hyperparathyroidism due to chronic kidney disease (CKD) G3–4, osteoporosis, and a multinodular euthyroid colloid goiter. In July 2021 she was referred to the Endocrinology Research Centre in order to clarify the diagnosis because of the persistence of an extremely high level of parathyroid hormone (PTH) despite cinacalcet treatment. During examination, primary hyperparathyroidism, a left parathyroid gland lesion, multinodular goiter with subclinical thyrotoxicosis, and vitamin D deficiency were diagnosed. After the removal of the left parathyroid gland lesion (histologically confirmed parathyroid carcinoma) and a left-sided hemithyroidectomy, hypocalcemia («hungry bone syndrome») developed, but the level of parathyroid hormone remained elevated. After 3–18 months after surgery, no data for relapse of primary hyperparathyroidism was obtained. The persistent moderate increase in PTH was regarded as secondary hyperparathyroidism in CKD and hypocalcemia. Complex therapy of osteoporosis with the antiresorptive drug denosumab, vitamin D and its active metabolite, calcium preparations, and parathyroidectomy led to a significant increase in bone mineral density (BMD) and no repeated fractures 18 months after surgery.Conclusion. In patients with pre-dialysis CKD and high PTH levels, it is necessary to make a differential diagnosis between primary (PHPT) and secondary hyperparathyroidism (SHPT). Severe manifestations of primary hyperparathyroidism can be suspicious for parathyroid carcinoma.

Prevalence of pseudohypoparathyroidism and nonsurgical hypoparathyroidism in Japan in 2017: A nationwide survey.

Pseudohypoparathyroidism (PHP) and nonsurgical hypoparathyroidism (NS-HypoPT) are rare diseases with hypocalcemia, hyperphosphatemia, and high and low parathyroid hormone levels, respectively. In Japan, over 20 years have passed since the last survey on these diseases. We carried out a nationwide cross-sectional survey to estimate the prevalence of these diseases in 2018. We conducted a nationwide mail-based survey targeting hospitals in 2018. From a total of 13,156 departments throughout Japan, including internal medicine, pediatrics, neurology, and psychiatry, 3501 (27%) departments were selected using a stratified random sampling method. We asked each included department to report the number of patients with PHP and NS-HypoPT in 2017. The overall survey response rate was 52.0% (1807 departments). The estimated number of patients with PHP and NS-HypoPT was 1484 (95% confidence interval [CI], 1143-1825) and 2304 (95% CI, 1189-3419), respectively; the prevalence per 100,000 population was 1.2 and 1.8, respectively. In this study, we generated estimates of the national prevalence of PHP and NS-HypoPT in Japan during 2017, which were found to be higher than those previously reported.

Parathyroid adenoma in a 33 years female, manifesting as non-traumatic multiple bone fractures

A 33 years old female patient presented to OPD with chief complaints of prolonged fatigue, abnormal gait and difficulty in walking since 7 years. On further evaluation MRI pelvis revealed bilateral non-traumatic pelvic bone fractures, with high Serum parathyroid hormone level (1050 pcg/ml) and hypercalcemia. CECT Neck showed a well-defined soft tissue density lesion involving the posterior-inferior aspect of the right lobe of thyroid gland. Surgical resection was performed and histopathology revealed parathyroid adenoma. Clinical manifestations and PTH and calcium levels gradually decreased to normal after surgery. Patient’s symptoms gradually decreased over a period of 2 month after treatment of the underlying cause. In a young female presenting with bony pains and non-traumatic fractures, a differential diagnosis of parathyroid adenoma must be kept in mind.

Some genetic differences in patients with rheumatoid arthritis

ObjectiveVitamin D is important for bone and cartilage metabolism. Changes in vitamin D blood level may be related to pathological disorders such as rheumatoid arthritis (RA). The main aim of this study is to investigate the association between RA and the vitamin D receptor (VDR) genes FokI and TaqI polymorphisms. One hundred RA patients and fifty healthy matched controls were assessed for VDR FokI and TaqI genotyping. Intact parathyroid hormone (PTH) and calcium (Ca) levels were measured, categorized, and compared between the cases and control groups.ResultsWe found that the FokI genotype frequencies for the RA cases and control groups were FF:Ff:ff = 46%:52%:2% and 50%:50%:0%, respectively (P = 0.76). The TaqI genotype frequencies for the RA cases and control groups were TT:Tt:tt = 45%:44%:11% and 42%:42%:16%, respectively (P = 0.69). A statistically significant high serum PTH level was associated with the ff genotype (p = 0.03), and a significantly low serum Ca level was associated with the TT genotype (p = 0.003). In comparison with controls, no influence of VDR FokI and TaqI genotypes on RA susceptibility or risk was demonstrated.

Oral health, periodontal phenotype in patients with different mineral density (morphotypes) of bone tissue

Background. Studying the systemic influence of bone mineral density (BMD) and bone turnover on oral health and periodontal phenotype is relevant for predicting the course of periodontitis and making clinical decisions to achieve good treatment results. The purpose of the research is to study the oral health, periodontal phenotype, and bone metabolism depending on the BMD of the skeleton. Material and methods. One hundred and thirty-eight patients were examined and divided into three study groups depending on the BMD (Z-score): group І — increased BMD ­(Z-score &gt; +1 SD), group ІІ (Z-score from +1 to –1 SD), group ІІІ (Z-score &lt; –1 SD). The state of oral health, the severity and course of periodontal diseases, the peculiarities of bone metabolism according to biochemical markers of bone remodeling, and the BMD according to the results of dual-photon densitometry were determined. Results. Reduced bone turnover, resulting in decreased serum osteocalcin (18.96 ± 1.87 ng/ml in men and 19.11 ± 1.54 ng/ml in women), high level of parathyroid hormone was registered in patients with high BMD (group I). The oral health characteristics were identified, namely, the pathological tooth wear — abfraction (84.21 %) and attrition (76.31 %), the periodontal phenotype was characterized by a thick gingival biotype, mandibular exostoses, periodontitis and periodontitis were diagnosed. Increased bone turnover, active course of generalized periodontitis, thin gingival biotype, cervical caries and hyperesthesia of the dental hard tissues were registered in patients with low BMD (group III). Conclusion. The state of oral health, namely, the dental hard tissues, the periodontal phenotype has its own characteristics and are related to the morphotype of bone tissue — its BMD and bone metabolism. Such features must be taken into account when planning treatment measures for dental patients.

THU474 Primary Hyperaldosteronism As A Cause Of PTH Elevation After Parathyroid Surgery

Abstract Disclosure: W. Thi: None. A. Rao: None. Background: Primary hyperaldosteronism can cause hypercalciuria, parathyroid hormone (PTH) elevation due to secondary hyperparathyroidism, and reduce bone mineral density. Screening for primary hyperaldosteronism can be done with serum aldosterone-renin ratio (ARR). We report a case of recurrent hyperparathyroidism after parathyroid surgery. Workup identified primary hyperaldosteronism as the cause of recurrent hyperparathyroidism. Treatment with spironolactone normalized PTH levels. Case Presentation: A 59-year-old African-American female in the Columbia VA Health Care System presented with hypertension, hypokalemia, bone density loss, and elevated PTH with normal calcium, one year after resection of a right inferior parathyroid adenoma to treat primary hyperparathyroidism. The patient had uncontrolled hypertension with hypokalemia while on losartan and amlodipine. Serum calcium was 9.4mg/dl(8.4-10.2mg/dl), PTH 89.4 pg/ml(29.2-79.9pg/ml), albumin 3.8g/dl(3.5-5G/dl), vitamin D 34 ng/ml(&amp;gt;28.9ng/ml), aldosterone 9ng/dl(&amp;lt;/=28ng/dl), plasma renin activity 0.28ng/ml/h(0.25-5.82ng/ml/h), ARR 32. Treatment of the patient with potassium supplements corrected the hypokalemia to 3.7mmol/L (5-5.1mm/l), and ARR was 94 with aldosterone 17 ng/dl and PRA 0.18 ng/ml/h and 24-hour urine calcium 304mg/24h(35-250mg/24h). Based on the laboratory values, and the absence of adrenal nodules during a CT scan, a diagnosis of primary hyperaldosteronism due to idiopathic hyperplasia of the adrenal was made. Spironolactone was started and PTH levels dropped down to 64.8pg/ml and serum calcium remained normal 5 months after treatment was initiated. Discussion: Primary Hyperaldosteronism causes extravascular fluid volume expansion with a reduction in proximal tubular sodium and calcium reabsorption. Increased calcium and sodium delivery to distal segments of the nephron leads to sodium reabsorption by mineralocorticoids without reabsorbing calcium, resulting in hypocalcemia with concomitant secondary hyperparathyroidism. Bone loss results from direct mineralocorticoid receptor-mediated effects of aldosterone on osteoblasts and osteoclasts and indirectly from high PTH levels to promote bone resorption. Treatment of primary hyperaldosteronism can reverse bone loss and reduce fracture risk rate within 18-36 months. This case suggests that primary hyperaldosteronism be considered a cause of secondary hyperparathyroidism and successfully treated with mineralocorticoid receptor antagonists. Presentation: Thursday, June 15, 2023

Current and Emerging Markers and Tools Used in the Diagnosis and Management of Chronic Kidney Disease-Mineral and Bone Disorder in Non-Dialysis Adult Patients.

Chronic kidney disease (CKD) is a significant public health concern associated with significant morbidity and has become one of the foremost global causes of death in recent years. A frequent comorbidity of CKD is secondary hyperparathyroidism (SHPT), exemplified by high serum parathyroid hormone (PTH) levels. The mineral metabolism disturbances resulting from CKD and progression to SHPT are currently considered part of the definition of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, CKD-MBD does not only include abnormalities in laboratory-measured parameters; it is a complex condition characterized by dysregulation of bone turnover, mineralization, growth and strength, accompanied by vascular or another soft-tissue calcification. Together, this increases the risk of bone fractures, cardiovascular disease, and overall mortality in CKD-MBD patients. Monitoring serum markers is essential in diagnosing SHPT and CKD-MBD, and there are several recognized indicators for prognosis, optimal clinical management and treatment response in late-stage kidney disease patients receiving dialysis. However, far fewer markers have been established for patients with non-dialysis CKD. This review provides an overview of current and emerging markers and tools used in the diagnosis and management of CKD-MBD in non-dialysis adult patients.

Ultrasound-guided microwave ablation in the treatment of recurrent primary hyperparathyroidism in a patient with MEN1: a case report.

Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine syndrome caused by the mutation in the tumor suppressor gene MEN1. The recurrence rate of primary hyperparathyroidism (PHPT) in patients with MEN1 after parathyroidectomy remains high, and the management of recurrent hyperparathyroidism is still challenging. We reported a 44-year-old woman with MEN1 combined with PHPT who was diagnosed through genetic screening of the patient and her family members. After parathyroidectomy to remove one parathyroid gland, the patient suffered from persistent high levels of serum calcium and parathyroid hormone, which returned to normal at up to 8 months after ultrasound-guided microwave ablation (MWA) for bilateral parathyroid glands, suggesting an acceptable short-term prognosis. Ultrasound-guided MWA for parathyroid nodules may be an effective therapeutic strategy for recurrent PHPT in MEN1 patients.

Normocalcemic Primary Hyperparathyroidism. A Case Report and Literature Review

Normocalcemic primary hyperparathyroidism (PHP) has been proposed to be a new phenotype of the disease. It is characterized by persistently high levels of parathyroid hormone (PTH) and normal calcium levels. Since there are no known causes of secondary hyperparathyroidism or PTH elevation, the exact biological mechanism is not known. It could be the first stage of the disease or a unique situation marked by resistance of the kidneys and bones to the effects of PTH. This is a disease that is getting more and more common. It is often found when evaluating perimenopausal women with low bone mass or when evaluating or following up on patients with osteoporosis. Normocalcemic PHP has a diverse and varied phenotype that ranges from cases with no usual PHP symptoms to cases with symptoms and specific complications. The method to diagnosing secondary hyperparathyroidism should focus on ruling out all possible causes, especially vitamin D deficiency (25-OH vitamin D levels less than 30ng/mL) and kidney function impairment (glomerular filtration rate less than 60 mL/min, as measured by CKD- EPI). Not much is known about its past in the wild. Some people get hypercalcemia, but more than 75% of them don't. There don't seem to be any ways to predict who will get hypercalcemia, so measuring total and adjusted calcium levels once a year is recommended. Even though measuring ionic calcium is a part of what it means to have Normocalcemic PHP and is recommended by some writers during follow-up, there are a number of real problems with it that should be kept in mind.