Low Parathyroid Hormone Research Articles

Graded Replacement of Carbohydrate-Rich Breakfast Products with Dairy Products: Effects on Postprandial Aminoacidemia, Glycemic Control, Bone Metabolism, and Satiety

BackgroundPostprandial metabolic responses following dairy consumption have mostly been studied using stand-alone dairy products or milk-derived nutrients. ObjectiveAssessing the impact of ingesting dairy products as part of a common breakfast on postprandial aminoacidemia, glycemic control, markers of bone metabolism, and satiety. MethodsIn this randomized, crossover study, 20 healthy young males and females consumed on 3 separate occasions an iso-energetic breakfast containing no dairy (NO-D), 1 dairy (ONE-D), or 2 dairy (TWO-D) products. Postprandial concentrations of amino acids, glucose, insulin, glucagon-like peptide-1 (GLP-1), calcium, parathyroid hormone (PTH), and markers of bone formation (P1NP) and resorption (CTX-I) were measured before and up to 300 min after initiating the breakfast, along with VAS-scales to assess satiety. ResultsPlasma essential and branched-chained amino acids availability (expressed as total area under the curve (tAUC)) increased in a dose-dependent manner (P<0.05 for all comparisons). Plasma glucose tAUCs were lower in ONE-D and TWO-D compared with NO-D (P<0.05 for both comparisons). Plasma GLP-1 tAUC increased in a dose-dependent manner (P<0.05 for all comparisons), whereas no differences were observed in plasma insulin tAUC between conditions (P>0.05 for all comparisons). Serum calcium tAUCs were higher in ONE-D and TWO-D compared with NO-D (P<0.05 for both comparisons), along with lower PTH tAUCs in ONE-D and TWO-D compared with NO-D (P=0.001 for both comparisons). In accordance, serum CTX-I concentrations were lower in the late postprandial period in ONE-D and TWO-D compared with NO-D (P<0.01 for both comparisons). No differences were observed in P1NP tAUCs between conditions (P>0.05). The tAUC for satiety was higher in TWO-D compared with NO-D and ONE-D (P<0.05 for both comparisons). ConclusionsIso-energetic replacement of a carbohydrate-rich breakfast component with one serving of dairy improves postprandial amino acid availability, glycemic control, and bone metabolism. Adding a second serving of dairy in lieu of carbohydrates augments postprandial amino acid and GLP-1 concentrations while further promoting satiety.This study was registered at https://doi.org/10.1186/ISRCTN13531586 with Clinical Trial Registry number ISRCTN13531586.

Treatment of Hypercalcemic Hyperparathyroidism After Kidney Transplantation Is Associated With Improved Allograft Survival.

Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival. We identified 280 KT recipients (2015-2019) with elevated post-KT adjusted serum calcium and parathyroid hormone (PTH). KT recipients were characterized by treatment: cinacalcet, parathyroidectomy, or no treatment. Time-varying Cox regression with delayed entry at the time of first elevated post-KT calcium was conducted, and death-censored and all-cause allograft failure were compared by treatment groups. Of the 280 recipients with tHPT, 49 underwent PTx, and 98 received cinacalcet. The median time from KT to first elevated calcium was 1 month (IQR: 0-4). The median time from first elevated calcium to receiving cinacalcet and parathyroidectomy was 0(IQR: 0-3) and 13(IQR: 8-23) months, respectively. KT recipients with no treatment had shorter dialysis vintage (P = .017) and lower PTH at KT (P = .002), later onset of hypercalcemia post-KT (P < .001). Treatment with PTx (adjusted hazard ratio (aHR) = 0.18, 95%CI 0.04-0.76, P = .02) or cinacalcet (aHR = 0.14, 95%CI 0.004-0.47, P = .002) was associated with lower risk of death-censored allograft failure. Moreover, receipt of PTx (aHR = 0.28, 95%CI 0.12-0.66, P < .001) or cinacalcet (aHR = 0.38, 95%CI 0.22-0.66, P < .001) was associated with lower risk of all-cause allograft failure. This study demonstrates that treatment of hypercalcemic tertiary HPT post-KT is associated with improved allograft survival. Although these findings are not specific to hypercalcemia of malignancy, they do demonstrate the negative impact of hypercalcemic tertiary HPT on kidney function. Hypercalcemic HPT should be screened and aggressively treated post-KT.

Validating the risk of hypoparathyroidism after total thyroidectomy in a population-based cohort: plea for improved follow-up.

A previous nationwide study from Sweden showed that the rate of permanent hypoparathyroidism is high and under-rated in the Swedish Quality Register. This retrospective population-based study aimed to validate the rate and diagnosis of permanent hypoparathyroidism found in the previous study. A secondary aim was to assess the relationship between the rate of low parathyroid hormone (PTH) levels within 24 h after surgery and the rate of permanent hypoparathyroidism. All patients who underwent total thyroidectomy from 2005 to 2015 in a region of Sweden were included. Data were retrieved from local health records, the National Patient Registry, the Swedish Prescribed Drug Registry, and the Swedish Quality Register. A strict definition of permanent hypoparathyroidism was used, including biochemical data and attempts to stop the treatment. A total of 1636 patients were included. Altogether, 143 patients (8.7 per cent) developed permanent hypoparathyroidism. Of these, 102 (6.2 per cent) had definitive permanent hypoparathyroidism, whereas 41 (2.5 per cent) had possible permanent hypoparathyroidism, because attempts to stop the treatment were lacking (28) or patients were lost to follow-up (13). The agreement between the Swedish Quality Register and the chart review was 29.3 per cent. A proportion of 23.2 per cent with a PTH level below the reference value corresponded to a 6.7 per cent rate of permanent hypoparathyroidism. The risk of permanent hypoparathyroidism after total thyroidectomy is high. Some patients are overtreated because attempts to stop the treatment are lacking. Quality registers might underestimate the risk of permanent hypoparathyroidism. Approximately one-quarter of all patients with low PTH levels immediately after surgery developed permanent hypoparathyroidism.

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.

FGFR Inhibitors in Cholangiocarcinoma and Urothelial Bladder Cancer Resulting in Hyperphosphatemia, Low Parathormone, and High Calcitriol: The Side Effects of FGF23 Blockade

FGFR Inhibitors in Cholangiocarcinoma and Urothelial Bladder Cancer Resulting in Hyperphosphatemia, Low Parathormone, and High Calcitriol: The Side Effects of FGF23 Blockade

Lower Parathyroid Hormone Levels Are Associated with Lower Risk of Fractures in Japanese Hemodialysis Patients: A Nationwide Cohort Study

Lower Parathyroid Hormone Levels Are Associated with Lower Risk of Fractures in Japanese Hemodialysis Patients: A Nationwide Cohort Study

The Effect of Variation in Dietary Cation-Anion Difference on Calcium Status, Blood Metabolites and Rumen Activity during the Transition Period of Holstein Dairy Cows

A negative dietary cation-anion difference (DCAD) induces a compensated metabolic acidosis, stimulating calcium (Ca) absorption and mobilization before calving, thereby decreasing clinical and subclinical hypocalcemia postpartum. The study was designed to determine the effects of varying pre- and postpartum DCAD diets on serum total calcium, ionized calcium, blood and ruminal fluid metabolites, and milk production in prepartum and postpartum Holstein cows. Fifty-four multiparous dry Holstein cows n= 54, were enrolled in a completely randomized block experimental design at 29 days prior to expected parturition through 86 days in milk. A 3 x 2 factorial arrangement of treatments was utilized. Three DCAD levels were fed precalving (0, -120 and -200 mEq/kg DM), n=18 cows per treatment and two DCAD levels were fed post calving (+200 and +400 mEq/kg DM), n=27 cows per treatment. Prepartum urine pH was lower for cows fed -200 DCAD compared with those fed -120 or 0 DCAD. Postpartum urine pH was higher for cows fed +400 mEq/kg compared to cows fed +200 mEq/kg DCAD. Prepartum serum total calcium, ionized calcium, and hydroxyproline was highest for cows fed -200 DCAD compared to those fed -120 and 0 DCAD. Parathyroid hormone was highest for cows fed 0 DCAD compared to those fed -120 and -200 DCAD. Prepartum dry matter intake (DMI) was lower for -200 and -120 DCAD compared with 0 DCAD. Postpartum DMI was not different among treatments. Pre- and postpartum DCAD treatments did not affect total milk yield or milk fat, percentage of milk protein not affected by different pre-and postpartum DCAD levels. Prepartum anionic diets lowered urine pH and parathyroid hormone and raised serum hydroxyproline, resulting in improved Ca availability after parturition. Postpartum blood metabolites were unaffected in cows given positive DCAD (+200 and +400 mEq/kg DM). Calves born to cows fed low DCAD had no change in calf bieth weight. Colostrum amount and IgG concentrations were unaffected by treatments. No effects of pre-or postpartum DCAD treatments were observed for milk yield and fat-corrected milk. Feeding prepartum an acidogenic diet improved postpartum Ca status in multiparous Holstein cows.

Estimation of serum levels of Parathyroid hormone, Vitamin D, Calcium and Phosphorus to study their association with age, gender, disease duration, and severity of chronic plaque psoriasis: Results of a case control study

: Psoriasis is a chronic inflammatory disease characterized by rapid turnover of epidermal keratinocytes; presenting clinically as erythema, induration, and scaling Parathyroid hormone (PTH) is secreted by parathyroid glands and its elevated levels may be seen in psoriasis and several other disorders of keratinization. PTH/PTH-related peptide receptors are present in dermal fibroblasts &amp; regulate proliferation and maturation of fibroblasts and keratinocytes. Release of PTH is under the feedback regulation of serum Ca2+, Vit.D and PO: To assess the Parathyroid hormone levels in patients of Psoriasis along with Vitamin D, Serum Calcium and Serum Phosphorus levels.: Out of the 50 cases aged between 18 and 91 years majority of patients i.e 22 (44%) were in the age group of 18-40 years followed by 20 (40%) patients in 41-60 years age group. Eight (16%) patients were above &amp;#62;60 years. 32 (64%) patients who had psoriasis for less than ≤60 months while 18 (36%) patients had psoriasis for more than &amp;#62;60 months Serum PTH (normal 10–65pg/ml), Vitamin D(normal 20-50(ng/ml), calcium (normal 9-11mg/dl and phosphorus (normal 2.5-4.5mg/dl) levels were measured after overnight fasting. : A total of 50 psoriasis patients along with 50 non-psoriatic age and sex matched controls were recruited for the study. There were 28 males and 22 females in the patient group aged between 18 and 91 years (mean±SD 43.52±16.23 years). The mean age of controls was 47.12±16.29 years with 19(38%) subjects in 18-40 years age group and 21(42%) in 41-60 years age group. Amongst the cases, there were 10(20%) patients who had abnormal PTH levels (six had elevated levels of PTH and four patients with low PTH levels) while 40(80%) had normal levels (mean±SD 47.97±25.46 pg/ml). : The interpretation of our observation remains complex and any conclusion for the significance of these biochemical abnormalities remain conjectural. Moreover, association of psoriasis with abnormal biochemical parameters remains debatable in view of limited number of studies whether abnormal biochemical parameters can serve as markers of severity and their correction can lead to improvement in the disease needs confirmation with more well designed experimental and prospective clinical studies.

OR23-03 Sustained Normalization Of Mineral Homeostasis In Autosomal Dominant Hypocalcemia Type 1: Results From A Phase 2 Study Over 18 Months Of Encaleret (CLTX-305) Treatment (NCT04581629)

Abstract Disclosure: R.I. Gafni: Advisory Board Member; Self; Ascendis Pharma, Hypoparathyroidism Association. Grant Recipient; Self; Calcilytix Therapeutics. I.R. Hartley: Grant Recipient; Self; Calcilytix Therapeutics. K.L. Roszko: Grant Recipient; Self; Calcilytix Therapeutics. E.F. Nemeth: Consulting Fee; Self; Calcilytix Therapeutics. K.A. Pozo: Grant Recipient; Self; Calcilytix Therapeutics. A. Mathew: Employee; Self; Calcilytix Therapeutics. M. Roberts: Employee; Self; Calcilytix Therapeutics. S.H. Adler: Employee; Self; Calcilytix Therapeutics. M.T. Collins: Grant Recipient; Self; Calcilytix Therapeutics. Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR) variants, is characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. Conventional therapy (calcium and active vitamin D) worsens hypercalciuria, which may result in renal complications. Calcilytics that act as negative allosteric modulators of the calcium-sensing receptor (CaSR), like encaleret, decrease the sensitivity of hyperactive receptors to extracellular calcium and normalize biochemical abnormalities in ADH1 rodent models. This Phase 2b open-label study of the oral investigational calcilytic encaleret was comprised of 3 periods followed by a long-term extension (LTE). Conventional therapy was discontinued prior to encaleret initiation. Periods 1&amp;2 included dose-finding and safety/tolerability evaluation. Period 3 (P3) optimized dosing and assessed safety and efficacy over 24 outpatient weeks; participants were then allowed to continue in the LTE. Thirteen adults with ADH1 were enrolled and encaleret was individually titrated to normalize albumin-corrected calcium (cCa) and minimize hypercalciuria. Encaleret was well-tolerated with no serious adverse events reported. There were no treatment discontinuations or withdrawals prior to the LTE; one participant withdrew during the LTE for family planning. The mean±SD encaleret sulfate dose at the end of P3, Week 24 (P3W24) was 86±70mg BID, remaining stable at LTE Month 12 (LTEM12) (n=11) (71±62mg BID). Mean±SD values taken 4-hours post-dose for P3W24 and LTEM12 compared to baseline (BL) are presented. PTH levels were low at BL (6.3±7.8 pg/mL [nl 10-65]), normal at P3W24 (35.3±10.2), and remained consistent through LTEM12 (36.9±15.2 [p&amp;lt;0.01]). Similarly, hypocalcemia at BL (cCa=7.1±0.4 mg/dL [nl 8.4-10.2]) was normal at P3W24 (9.2±0.5); eucalcemia was maintained through LTEM12 (9.2±0.4 [p&amp;lt;0.01]). BL hypercalciuria (395±216 mg/d [nl &amp;lt;250-300]) decreased to 202±83 at P3W24 and normalization was sustained through LTEM12 (177±94 [p&amp;lt;0.05]). BL blood phosphate (4.5±1.1 mg/dL [nl 2.3-4.7]) decreased by P3W24 (3.4±0.4) and was maintained at LTEM12 (3.4±0.5 [p&amp;lt;0.01]). Blood magnesium increased (BL 1.7±0.2 mg/dL [nl 1.6-2.6]); P3W24 2.0±0.2; LTEM12 2.1±0.2 [p&amp;lt;0.01]). Bone turnover markers increased from BL (n=7) (CTX=253±111 pg/mL; P1NP=34±10 mcg/L) by P3W24 (n=13) (CTX=744±565; P1NP=104±87) and remained elevated at LTEM12 (CTX=988±652; P1NP=83±49 [p&amp;lt;0.01]. This study represents a molecularly targeted, precision medicine approach to the treatment of ADH1. The consistent and sustained results from over 18 months of outpatient encaleret treatment are clinically meaningful and support Phase 3 evaluation of the efficacy and safety of encaleret as the first potential treatment indicated for ADH1. Presentation: Saturday, June 17, 2023

THU406 24-hydroxylase Deficiency, A Rare Cause Of Hypercalcemia

Abstract Disclosure: J. Hodge: None. M. Gortakowski: None. N. Barua: None. Background: 24-hydroxylase is encoded by CYP24A1 and functions to convert 1,25 dihydroxyvitamin D and 25-hydroxyvitamin D to their inactive metabolites[1]. 24-hydroxylase deficiency due to CYP24A1 variants is rare and clinical presentation is characterized by hypercalcemia, nephrolithiasis and nephrocalcinosis. Treatment may include thiazide diuretics, sodium cellulose phosphate and ketoconazole.[1] We present a case of hypercalcemia due to 24-hydroxylase deficiency. Clinical Case: A 56-year-old male with chronic kidney disease initially presented with hypercalcemia at age 48 to another institution. He was initially diagnosed with primary hyperparathyroidism in the setting of an inappropriately normal parathyroid hormone (PTH) with hypercalcemia. He subsequently had one parathyroid gland removed a year after diagnosis, then another two years later due to continued hypercalcemia. However, he continued to have persistent hypercalcemia, 10.9-12.7 mg/dL but now in the setting of low PTH. In addition, his 1,25 dihydroxyvitamin D was high normal and 25-hydroxyvitamin D was high off exogenous vitamin D supplementation, which raised the suspicion for 24-hydroxylase deficiency. He presented to our institution eight years later. Initial evaluation revealed, calcium 12.4 (8.6-10.5 mg/dL), phosphorous 2.9 (2.5-4.5 mg/dL), normal albumin, PTH 13 (15-65 pg/mL), 1,25 dihydroxyvitamin D 87.2 (19-79.3 pg/mL) and 25-hydroxyvitamin D 38.3 (20-50 ng/mL), 24hr urine calcium 0.23 (0.05-0.30 g/24hr), fractional excretion calcium 0.02. His 25-hydroxyvitamin D:24,25 dihydroxy vitamin D ratio was unable to be calculated, since 24,25 dihydroxy vitamin D was below the limit of quantification. He also had evidence of nephrocalcinosis on renal ultrasound. Evaluation of other causes of non-PTH mediated hypercalcemia included normal angio converting enzyme, PTHrP level, vitamin A level, SPEP and UPEP. Chest X-ray did not demonstrate any evidence of granulomatous disease. He has been managed conservatively for suspected 24-hydroxylase deficiency. He has been advised to limit calcium and vitamin D intake, as well as sun exposure, with close monitoring of his calcium levels. His calcium levels have ranged from 10.7-12.4 mg/dL and he has had one hospitalization in the setting of heart failure where his calcium levels improved with furosemide to 8.7-9.9 mg/dL. Conclusion: In patients with persistent non-PTH dependent hypercalcemia, 24-hydroxylase deficiency should be a differential diagnosis when other common causes are excluded.

Assessment of thyroid and parathyroid function in patients treated for laryngeal carcinoma

Background The close proximity of both thyroid and parathyroid glands to the larynx puts them at high risk to develop hypofunction from the treatment of cancer larynx. Aim Thyroid and parathyroid function evaluation after treatment modalities of cancer larynx. Patients and methods Thyroid and parathyroid function was evaluated in 60 patients treated from laryngeal carcinoma. Patients were classified into three groups based on treatment type. Group 1 included patients with primary radiotherapy while group 2 included patients with total laryngectomy and group 3 involved patients with combined total laryngectomy and postoperative radiotherapy. Laboratory assessment of thyroid function included thyroid-stimulating hormone (TSH), free T4, while parathyroid function included corrected serum calcium and parathormone levels. The association of gland hypofunction was studied against tumor and treatment characteristics. Results Among the 60 patients; group 1 included 27 patients, group 2 included 21 patients, and group 3 included 12 patients. Twenty-five (41.7%) patients showed high TSH level and low FT4 level indicating clinical hypothyroidism while 12 (20%) patients showed high TSH level with normal FT4 level indicating subclinical hypothyroidism. Twenty-three (38.3%) patients showed normal levels of both TSH and FT4 being euthyroid. Concerning parathyroid function; 19 (31.7%) showed hypoparathyroidism diagnosed by low corrected serum calcium level and confirmed by low parathyroid hormone level. Conclusion The study detects the occurrence of hypothyroidism with or without hypoparathyroidism after treatment modalities of cancer larynx emphasizing the need of high clinical suspicion and routine evaluation for early detection of any post treatment thyroid or parathyroid gland hypofunction.

Clinical heterogeneity and therapeutic options foridiopathic infantile hypercalcemia caused byCYP24A1 pathogenic variant.

Infantile hypercalcemia-1(HCINF1) is a rare disease caused by pathogenic variants in the CYP24A1 gene, resulting in the inability to metabolize active vitamin D. This leads to hypercalcemia and severe complications. On December 8th, 2022, a systematic literature search was conducted in PubMed, Wanfang, and CNKI usingthe keywords "hypercalcemia" and "CYP24A1". Data extraction included patient demographics, clinical presentation, treatment medications, and outcomes. The findings were synthesized to identify common patterns and variations among cases and to assess the efficacy of different therapies in reducing serum calcium. Our findings revealed two distinct peaks in the incidence of HCINF1 caused by CYP24A1 pathogenic variant. Kidney stones or renal calcifications were the most common clinical manifestations of the disease, followed by polyuria and developmental delay. Laboratory investigations showed hypercalcemia, elevated vitamin D levels, hypercalciuria, and low parathyroid hormone. Genetic analysis remains the only reliable diagnostic tool. Although there is no definitive cure for HCINF1, multiple drugs, including bisphosphonates, calcitonin, and rifampicin, have been used to control its symptoms. Blocking the production and intake of vitamin D is the preferred treatment option. Our review highlights the basic clinical and biochemical features of HCINF1 and suggests that targeted diagnostic and therapeutic strategies are needed to address the clinical heterogeneity of the disease. The insights gained from this study may facilitate the development of innovative treatments for HCINF1.

Impact of autofluorescence for detection of parathyroid glands during thyroidectomy on postoperative parathyroid hormone levels: parallel multicentre randomized clinical trial.

Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy. This parallel multicentre RCT investigated the use of Fluobeam® LX to visualize the parathyroid glands by autofluorescence during total thyroidectomy compared with no use. There was no restriction on the indication for surgery. Patients were randomized 1 : 1 and were blinded to the group allocation. The hypothesis was that autofluorescence enables identification and protection of the parathyroid glands during thyroidectomy. The primary endpoint was the rate of low parathyroid hormone (PTH) levels the day after surgery. Some 535 patients were randomized, and 486 patients received an intervention according to the study protocol, 246 in the Fluobeam® LX group and 240 in the control group. Some 64 patients (26.0 per cent) in the Fluobeam® LX group and 77 (32.1 per cent) in the control group had low levels of PTH after thyroidectomy (P = 0.141; relative risk (RR) 0.81, 95 per cent c.i. 0.61 to 1.07). Subanalysis of 174 patients undergoing central lymph node clearance showed that 15 of 82 (18 per cent) in the Fluobeam® LX group and 31 of 92 (33 per cent) in the control group had low levels of PTH on postoperative day 1 (P = 0.021; RR 0.54, 0.31 to 0.93). More parathyroid glands were identified during operation in patients who had surgery with Fluobeam® LX, and fewer parathyroid glands in the surgical specimen on definitive histopathology. No specific harm related to the use of Fluobeam® LX was reported. The use of autofluorescence during thyroidectomy did not reduce the rate of low PTH levels on postoperative day 1 in the whole group of patients. It did, however, reduce the rate in a subgroup of patients. Registration number: NCT04509011 (http://www.clinicaltrials.gov).

Misdiagnosis of chronic kidney disease and parathyroid hormone testing during the past 16 years

Chronic kidney disease (CKD) is a prevalent pathological condition worldwide. Parathyroid hormone (PTH) is an important index related to bone metabolism in CKD patients and has not received enough attention. This study was performed to investigate the incidence and diagnostic rate of CKDin hospital as well as PTH testing and treatment for secondary hyperparathyroidism (SHPT) in patients with stage 3 to 5 CKD. The data of patients who visited Zhejiang Provincial People's Hospital from February 2006 to April 2022 were retrieved from the hospital database. All data were divided into three subgroups using PTH testing and SHPT treatment as major comparative indicators for analysis. The data were then analyzed for overall PTH testing, CKD incidence, and diagnostic rate. Among 5,301,391 patients, the incidence of CKD was 13.14%. The missed diagnosis rate for CKD was 65.76%. The total PTH testing rate was 1.22%, of which 15.37% of PTH testing was performed in patients with stage 3 to 5 CKD. The overall diagnosis rate of SHPT in patients with stage 3 to 5 CKD was 31.0%. The prophylactic medication rate was 7.4%, and the rate of post-diagnostic drug therapy was 22.2% in patients who underwent SHPT treatment. The high misdiagnosis rate and low PTH testing rate of CKD requires prompt attention from clinicians. SHPT treatment should be considered especially in patients with stage 3 to 5 CKD.

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.

Diagnostic Value of Four-Dimensional Dynamic Computed Tomography for Primary Hyperparathyroidism in Patients with Low Baseline Parathyroid Hormone Levels.

Low baseline levels of parathyroid hormone (PTH) are associated with a higher rate of multiglandular disease, lower localization rates of preoperative imaging modalities, and a higher rate of unsuccessful minimally invasive parathyroidectomies. The objective of this study is to assess the diagnostic value of four-dimensional dynamic computed tomography (4D-CT) in localizing primary hyperparathyroidism (pHPT) in patients with low baseline PTH levels, compared to patients with high baseline PTH levels. Patients with pHPT who received a 4D-CT scan as part of their standard diagnostic evaluation were divided into two groups based on the following criteria: (1) preoperative PTH levels less than 100 pg/mL and (2) patients with preoperative PTH levels greater than 100 pg/mL. All patients underwent parathyroidectomy based on 4D-CT findings, with intraoperative parathyroid hormone monitoring. The lesion-based sensitivity of 4D-CT was 88% in patients with low baseline PTH levels and 94.7% in patients with high baseline PTH levels (p = 0.33). However, the success rate of image-guided resection based on 4D-CT findings was 71.4% in the low baseline PTH group compared to 90.6% in the high baseline PTH group (p = 0.06). Our study demonstrated that 4D-CT has a high lesion-based sensitivity in patients with pHPT and low baseline PTH levels but led to a relatively low rate of successful image-guided resection in patients with low baseline PTH levels. Therefore, it is important to exercise increased caution during 4D-CT-guided surgical exploration of patients with low baseline PTH levels to ensure successful surgical resection of all parathyroid lesions.

Improvement of hypertension control and left-ventricular function after cure of primary hyperparathyroidism.

Cardiovascular mortality is significantly higher in patients with primary hyperparathyroidism (PHPT) compared to the general population. The role of the renin-angiotensin-aldosterone system (RAAS) as a mediator of cardiovascular pathology in PHPT is unclear, as is the question whether successful parathyroidectomy (PTX) mitigates hypertension (HT), and left-ventricular (LV) dysfunction. In 45 consecutive, hypercalcemic PHPT patients (91% female, 20 normotensive, mean age 54.6 ± 14.6), laboratory examinations, and 24h ambulatory blood pressure monitoring (ABPM) were performed before, one and six months after successful PTX, while transthoracic echocardiography (TTE) pre- and six months post-PTX. Both in patients with normotension (NT) and HT, lower calcemia and parathyroid hormone (PTH) as well as higher phosphatemia were observed on follow-up, while B-type natriuretic peptide, aldosterone, plasma renin activity, and aldosterone-to-renin ratios were comparable. Six months post-PTX, only in patients with HT, median 24-hour SBP/DBP decreased by 12/6 mmHg, daytime SBP by 10, and nighttime DBP by 5 mmHg. Improvement in BP was observed in approximately 78% of patients with HT. Six months post-PTX, TTE revealed: 1) decrease in median LV mass index (by 2 g/m2) and end-diastolic dimension (by 3mm) among patients with HT; 2) normalization of global longitudinal strain in 22% of patients (comparable between those with NT and HT); 3) a mean 12.7% reduction in left-atrium volume index among patients with HT, which underlay normalization of indeterminate diastolic function in 3 out of 6 patients with HT, who exhibited it at baseline (dysfunction persisted in 2). PTX was shown to significantly reduce BP, LV hypertrophy and diastolic dysfunction parameters in PHPT patients with HT, and improve systolic function in all PHPT patients.

Early postoperative PTH level following total thyroidectomy as a predictor of hypocalcemia: a single center-based study in Bangladesh

Background: Assessment of parathyroid hormone (PTH) following thyroid surgery assists in the prediction of hypocalcemia and permits early intervention and therapy with oral calcium and/or vitamin D supplements.&#x0D; Methods: This retrospective analysis comprised 141 individuals who had undergone a total or completion thyroidectomy over the previous four years. The blood PTH level was measured 3 hours after surgery to determine its change and to predict hypocalcemia.&#x0D; Results: Patients were predominately female (75.2%), and the mean age was 48.73 ± 13.44 years. The main surgical procedure was total thyroidectomy (80.14%), and the main cause for surgery was a multinodular goiter (34.04%). A comparable number of patients with each type of thyroid disease (multinodular goiter, papillary thyroid cancer, thyroiditis, Graves’ disease or toxic multinodular goiter were enrolled. Three hours after surgery 93 patients (65.95%) had serum PTH levels of &gt;10 pg/ml (mean 28.06) and 90 patients (68.38%) had normal serum calcium (mean 8.66). Most of these 93 patients (65.95%) didn't require postoperative supplementation, whereas 48 patients (34.05 %) with serum PTH levels less than 10 pg/ml required some form of supplementation; 39 (27.65 %) required both oral calcium and vitamin D supplements, and 9 (6.4 %) required only oral vitamin D supplementation. There was a significant correlation between the 3-h postoperative PTH level and hypocalcemia (P-value 0.000). The type of pathology had no significant association with low serum PTH level after surgery (P-value 0.166).&#x0D; Conclusion: Asymptotic individuals with PTH levels less than 10 pg/ml, who are regarded as being in the high-risk category, can start taking calcium and/or vitamin D supplements early if their PTH levels are measured at 3 hours following complete thyroidectomy. To predict hypocalcemia, more research is required to compare the outcome of early serum PTH level with the day one serum PTH level following complete thyroidectomy.&#x0D; Central Medical College Journal Vol 6 No 2 Jauly 2022 Page: 82-89

DISCORDANT CALCIUM AND PARATHYROID HORMONE WITH PRESUMED EPILEPTIC SEIZURES

Epileptic seizures are a neurological condition characterized by abnormal electrical activity in the brain, leading to involuntary and unpredictable movements, changes in consciousness, and other symptoms. The study's main objective is to find the discordant calcium and parathyroid hormone with presumed epileptic seizures. This study aims to investigate the association between discordant calcium and parathyroid hormone (PTH) levels and presumed epileptic seizures in a cohort of 200 patients. The study was conducted between June 2022 and December 2022. The study was conducted in collaboration with the neurology department. Patients admitted to the hospital with presumed epileptic seizures were included in the study. This study found that out % of the 200 patients who met the inclusion criteria, 65% had discordant calcium and PTH levels. Among these patients, 80% had low calcium and high PTH levels, while 20% had high calcium and low PTH levels. The logistic regression analysis showed a significant association between discordant calcium and PTH levels and presumed epileptic seizures (p&lt;0.05). In conclusion, the results of this study suggest that abnormalities in calcium and parathyroid hormone (PTH) levels are not a major contributor to the development of epileptic seizures in most patients. While patients with hypocalcemia appeared to have a higher risk of seizures than those with normal calcium levels, most patients with hypocalcemia did not experience seizures.

#3154 MALIGNANT HYPERCALCEMIA IN A CASE OF SMALL BOWEL GASTROINTESTINAL STROMAL TUMOUR

Abstract Background and Aims Malignant hypercalcemia is the most common cause of hypercalcemia, occurring in 30% of cancer patients and rendering a poor prognosis. Most cases have a humoral cause, the majority mediated by parathyroid hormone related peptide (PTHrP), rarely by 1,25-dihydroxyvitamin D3 (1,25(OH)2D) and very rarely by parathyroid hormone (PTH) ectopic production; other cases are due to local osteolysis. In the literature, there are only 5 reported cases of hypercalcemia associated to gastrointestinal stromal tumour (GIST), only 2 of them due to 1,25(OH)2D overproduction. Method Case report. Results Sixty-two years-old male with small bowel GIST diagnosed in 2014, subjected to enterectomy and on tyrosine kinase inhibitor (TKI) since 2017. TKI was changed from imatinib to sunitinib 25mg since August 2020 to the present date due to disease progression with liver metastasis. In March 2022, a PET scan showed no bone or soft tissue metastasis and there was a finding of right ureteral lithiasis with asymptomatic mild pyelocaliceal dilation. The patient had also subclinical hypothyroidism and several episodes of acute kidney injury (AKI) associated with hypercalcemia and hyperphosphatemia managed in outpatient clinic. He did not take any other medication besides the TKI. In April 2022, symptoms of disequilibrium, confusion, asthenia, and anorexia drove the patient to the Oncology Department. At physical examination the patient had an ECOG 3, was disoriented, cachectic and dehydrated, with no other noticeable findings. Blood lab tests showed a serum creatinine (sCr) of 2,86 mg/dL (baseline 1,10 mg/dL, estimated glomerular filtration rate of 72 mL/min/1,73 m2), a corrected serum total calcium (sCa) of 16,6 mg/dL and a normal serum phosphate of 4,0 mg/dL. The patient was admitted in the oncology ward with the collaboration of the nephrology department and was started on fluid therapy with 3000–4000cc NaCl 0,9%/day for a target urinary output of 75–200 mL/h. Hypercalcemia work-up showed low PTH of 8,8 pg/dL (reference range: 12–65 pg/dL). Measurement of PTHrP and 1,25(OH)2D were requested but took longer. After 3 days, despite the improvement of both sCr (2,23 mg/dL) and sCa (13,6 mg/dL), zoledronic acid was started. Results revealed an increased 1,25(OH)2D of 309 pg/dL (reference range: 10,9-79,3 pg/dL) and negative PTHrP. At the 6th day, a clear improvement of analytical (sCr 1,60 mg/dL; sCa 11,9 mg/dL) and clinical status, so the patient was discharged. The diagnosis was GIST 1,25(OH)2D overproduction causing malignant hypercalcemia and prednisolone on 20mg id was started. In June 2022, the patient had tumour progression, presenting lethargic, disoriented, and dehydrated; blood lab results showed AKI (sCr 1,97 mg/dL) and worsening hypercalcemia (sCa 14,7 mg/dL). He was admitted for fluid therapy and bisphosphonates but, even though there was a recovery of the hypercalcemia and renal function, the patient's clinical status got worse and he had a fatal outcome in the following days. Conclusion Malignant hypercalcemia caused by GIST 1,25(OH)2D overproduction is a rare condition. The work-up of an oncological patient with ureteral lithiasis and recurrent hypercalcemia should prompt us to a more in-depth investigation.