Low Parathyroid Hormone Research Articles

Relationship between serum parathyroid hormone levels and abdominal aortic calcification in patients starting hemodialysis who have never taken calcium tablets, calcitriol, or vitamin D analogs

Background Vascular calcification (VC) and secondary hyperparathyroidism (SHPT) are important causes of the high incidence of cardiovascular events in chronic kidney disease (CKD) patients. The relationship between parathyroid hormone (PTH) and VC is very complex. The aim of this study was to determine the correlation between PTH levels and abdominal aortic calcification (AAC) in patients starting hemodialysis who had not received calcium tablets, calcium-containing phosphorus binders, calcitriol, or vitamin D analogs. Methods Seventy-one patients were included. Latero-lateral X-ray lumbar radiography, serum intact PTH (iPTH) levels, and predialysis biochemical parameters were obtained. The degree of AAC was evaluated according to the methods described previously by Kauppila et al. Results We found that there was a strong negative correlation between serum PTH and AAC (Spearman’s rho −0.76, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that low serum PTH level could predict the presence and extent of AAC (area under the curve values were 0.9013 [p < 0.0001] and 0.780 [p = 0.0041], respectively). Conclusions Our results indicate that serum PTH level is significantly negatively correlated with AAC within a certain concentration range in patients starting hemodialysis who had not received calcium tablets, calcium-containing phosphorus binders, calcitriol, or vitamin D analogs.

Vitamin D Deficiency and Risk Factors Related to Acute Psychiatric Relapses in Patients with Severe Mental Disorders: A Preliminary Study.

Previous studies have indicated that vitamin (Vit) D deficiency is frequent in psychiatric patients, regardless of diagnostic category. We aimed to assess whether acute psychiatric relapses in inpatients was associated with Vit D deficiency compared to stabilized outpatients. The cohort (152 total patients, 75 males and 77 females) had a mean age of 47.3 ± 14.4 years at admission and was grouped according to psychiatric diagnosis. Psychopathological symptom severity was assessed by the Brief Psychiatric Rating Scale (BPRS), a multidimensional symptom inventory. Total calcium serum levels were measured using standard laboratory methods, while plasma levels of 25-OH-Vit D and parathyroid hormone (PTH) were measured by automated chemiluminescence immunoassays. The psychiatric inpatient subgroup showed a significant difference in serum levels of 25-OH-Vit D and PTH (p < 0.001). Correlation analysis between serum levels of 25-OH-Vit D and BPRS total and subitem scores indicated a significantly negative relationship. In addition, linear regression analysis evidenced that the inpatient condition might predict low PTH and 25-OH-Vit D serum levels. Hospitalized psychiatric patients are at increased risk for Vit D deficiency regardless of their diagnostic categories. The mechanism underlying the association between acute psychiatric relapses and Vit D deficiency remains unclear. Therefore, screening for Vit D deficiency should pertain to the health assessment of patients with major psychiatric disorders.

Effect of radioiodine therapy under thyroid hormone withdrawal on health-related quality of life in patients with differentiated thyroid cancer.

To investigate the effect of radioactive iodine therapy under thyroid hormone withdrawal in differentiated thyroid cancer patients on health-related quality of life. Patients who were diagnosed with differentiated thyroid cancer after thyroidectomy were involved in this study. All of them were managed with thyroid hormone withdrawal. Health-related quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and its thyroid cancer module at three different time points. Changes in health-related quality of life were evaluated by Wilcoxon and Kruskal-Wallis tests. Univariable logistic regression analysis was used to determine social-demographic and clinical factors associated with worse health-related quality of life. A total of 99 differentiated thyroid cancer patients were involved in this study. Changes in health-related quality of life at different time points showed that 1month post-radioactive iodine treatment, an improvement in nausea and vomiting, insomnia and appetite loss was observed. Impairments of global health, role, cognitive and social function and problems of discomfort in the head and neck, voice concerns, dry mouth, fatigue, pain, dyspnea, thyroid fatigue, fear, tingling or numbness, joint pain and shoulder function increased after radioactive iodine treatment. Univariable logistic regression analysis demonstrated potential factors associated with worse health-related quality of life. Thyroid stimulating hormone and parathyroid hormone levels were more sensible to changes in functional domain. Patients aged ≥55-year-old, with annual income under ¥50 000, low parathyroid hormone and pT4 tumour stage experienced higher changes in symptom scales after radioactive iodine treatment. After radioactive iodine treatment, differentiated thyroid cancer patients experienced negative health-related quality of life, and most of these impairments might not recover in the short term. Thyroid stimulating hormone and parathyroid hormone levels, annual income and pT tumours stage were independent risk factors for decreased health-related quality of life.

Autosomal dominant hypocalcemia with a novel CASR mutation: a case study and literature review.

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare inherited disorder characterized by hypocalcemia with low parathyroid hormone (PTH) levels and high urinary calcium. Its clinical presentation varies from mild asymptomatic to severe hypocalcemia. It is caused by gain-of-function mutations in the calcium-sensing receptor gene (CASR) which affect PTH secretion from the parathyroid gland and calcium resorption in the kidney. Here, we describe a case who presented with symptoms of recurrent seizure caused by hypocalcemia with a novel CASR variant. We comprehensively analyzed the phenotypic features of this presentation and reviewed the current literature to better understand clinical manifestations and the genetic spectrum.

Selective vitamin D receptor activator Paricalcitol and its potential benefits in hemodialysis patients with secondary hyperparathyroidism

Currently, the incidence and prevalence of chronic kidney disease (CKD) are increasing annually worldwide, and clinical data show that CKD patients commonly experience relative vitamin D insufficiency or deficiency. Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients. SHPT is an adaptive and in many cases ultimately maladaptive process that develops in response to declining kidney function, impaired phosphate excretion, failure to bioactivate vitamin D and hypocalcemia. SHPT is characterized by persistently elevated levels of parathyroid hormone (PTH) and complicated by important disturbances in mineral metabolism. Maintaining the level of vitamin D and parathyroid hormone concentrations in the target range reduce its associated complications (e.g., fractures, chronic kidney disease and cardiovascular calcification). Effective therapeutic interventions are highly desirable if the morbidity and mortality associated with uncontrolled SHPT are to be reduced. Major renal guidelines recommend use of vitamin D for secondary hyperparathyroidism in chronic kidney disease. However, because of the difficulties associated with lowering PTH while simultaneously controlling serum levels of calcium and phosphorous, traditional therapies for managing SHPT have several limitations. Selective vitamin D receptor activator paricalcitol mainly targets vitamin D receptors (VDR) in the parathyroid glands, has less effect on VDR in the intestine and other tissues, inhibits PTH strongly, triggers less hypercalcemia, and has less effect on intestinal absorption of calcium, phosphorus and bone metabolism and significantly lowers renin levels, albuminuria and blood pressure, which is supported by the results of most studies conducted over these decades. The article is devoted to the problem of treatment of patients with SHPT inpatient with renal replacement therapy with program hemodialysis.

Effects of Low-Flux and High-Flux Dialysis Membranes on Erythropoietin Responsiveness in Hemodialysis Patients.

Background Chronic kidney disease (CKD) is often accompanied by anemia. High-flux membranes contribute to a reasonable removal of uremic toxins which cause anemia in CKD. Inadequate data have described the efficiency of high-flux dialysis in promoting erythropoietin responsiveness in CKD patients in the Middle East. This study was conducted to compare the efficiency of maintaining high-flux hemodialysis versus low-flux dialysis for ≥1 year in promoting erythropoietin responsiveness and to show the factors associated with erythropoietin hyporesponsiveness in Arab chronic hemodialysis patients. Methods It was a retrospective cohort study that involved 110 subjects who were categorized into group 1 (50 patients receiving low-flux dialysis) and group 2 (60 patients receiving high-flux dialysis). History taking, examination, and laboratory investigations were conducted for all patients every 3 months from January 2021 to January 2022. Results Group 2 had significantly higher weight and body mass index than group 1 but lower cholesterol and intact parathyroid hormone levels than group 1. Erythropoietin resistance index levels did not differ between the two groups upon repeated measures over a 1-year follow-up. Significant risk factors for erythropoietin hyporesponsiveness on multivariate analysis were lower weight (Odds ratio (OR): 0.966; 95% Confidence interval (CI): 0.94–0.992; p=0.011), longer hemodialysis vintage (OR: 1.172; 95% CI: 1.036–1.325; p=0.012), lower hemoglobin levels (OR: 0.531; 95% CI: 0.362–0.779; p=0.001), and higher neutrophil-to-lymphocyte ratio (OR: 2.436; 95% CI: 1.321–4.493; p=0.004). Conclusion High-flux dialysis was not superior to low-flux dialysis in improving erythropoietin responsiveness.

Low Parathyroid Hormone in the Setting of Normal Calcium-The Importance of the Clinical-Laboratory Interface in Clinical Practice.

Low Parathyroid Hormone in the Setting of Normal Calcium-The Importance of the Clinical-Laboratory Interface in Clinical Practice.

Correlation of Serum Parathyroid Hormone and Calcium Level among Pre- and Post-menopausal Women

Background: Postmenopausal women are prone to osteoporosis due to estrogen deficiency.&#x0D; Objective: The purpose of the present study was to assess the correlation between serum parathyroid hormone level and serum calcium level among pre- and post-menopausal women.&#x0D; Methodology: This cross-sectional study was conducted in the Department of Physiology at Dhaka Medical College, Dhaka, Bangladesh during the period of January 2012 to December 2012. Women were selected from different areas of Dhaka city. Among them, postmenopausal women with age ranging from 50 to 60 years were taken as group A and apparently healthy premenopausal women with age ranging from 20 to 30 years were included as group B for comparison. Serum calcium and parathyroid hormone levels were estimated to assess the hormonal status in both groups.&#x0D; Results: A total number of seventy (70) postmenopausal women with age ranging from 50 to 60 years and duration of menopause was more than one year. Thirty (30) apparently healthy premenopausal women with age ranging from 20 to 30 years with regular menstrual cycle. Correlation between parathyroid hormone with serum calcium was analyzed. In group A, serum parathyroid hormone showed negative correlation with serum Calcium (r= -0.161, p= 0.184) which was statistically non-significant relationship. In group B, serum parathyroid showed positive correlation with serum calcium (r=+0.232, p=0.218) which was statistically non-significant relationship.&#x0D; Conclusion: In conclusion serum calcium is lower and serum parathyroid hormone is higher in postmenopausal women.&#x0D; Journal of Current and Advance Medical Research, January 2022;9(1):16-20

A prospective cohort study of renal function and bone turnover in adults with hepatitis B virus (HBV)-HIV co-infection with high prevalence of tenofovir-based antiretroviral therapy use.

Tenofovir disoproxil fumarate (TDF) is a common component of antiretroviral therapy in hepatitis B virus (HBV)-HIV co-infected adults but few studies have evaluated worsening renal function and bone turnover, known effects of TDF. Adults from eight North American sites were enrolled in this cohort study. Research assessments were conducted at entry and every 24 weeks for ≤192 weeks. Bone markers were tested at baseline, week 96 and week 192 from stored serum. We evaluated changes in markers of renal function and bone turnover over time and potential contributing factors. A total of 115 patients were prospectively followed; median age 49 years, 91% male and 52% non-Hispanic Black. Duration of HIV was 20.5 years. TDF use ranged from 80% to 92% throughout follow-up. Estimated glomerular filtration rate (eGFR) (ml/min/1.73m2 ) decreased from 87.1 to 79.9 over 192 weeks (p < 0.001); however, the prevalence of eGFR <60 ml/min/1.73m2 did not appear to differ over time (always <16%; p=0.43). From baseline to week 192, procollagen type I N-terminal propeptide (P1NP) (146.7 to 130.5ng/ml; p=0.001), osteocalcin (14.4 to 10.2ng/ml; p < 0.001) and C-terminal telopeptides of type I collagen (CTX-1) (373 to 273 pg/ml; p < 0.001) decreased. Younger age, male sex and overweight/obesity versus normal weight predicted a decrease in eGRF. Black race, healthy weight versus underweight, advanced fibrosis, undetectable HBV DNA, and lower parathyroid hormone level predicted worsening bone turnover. In this HBV-HIV cohort with high prevalence of TDF use, several biomarkers of renal function and bone turnover indicated worsening status over approximately 4 years, highlighting the importance of clinical awareness in co-infected adults.

Low Parathyroid Hormone Versus Secondary Hyperparathyroidism and Survival in Patients Undergoing Hemodialysis: A Propensity-Matched Analysis.

IntroductionLow serum parathyroid hormone (PTH) and secondary hyperparathyroidism (SHPT) are very common in patients undergoing hemodialysis. However, it remains unclear which of these has a lower mortality.ObjectiveIn this study, we compared outcomes between hemodialysis patients with low PTH and those with SHPT.MethodsThis was a multi-center, retrospective, matched cohort study. Median intact PTH (iPTH) was used as the cutoff for allocating participants to low PTH (iPTH<100 pg/mL) and SHPT groups (iPTH ≥600 pg/mL). Sex, diabetes, age, and dialysis vintage were matched between the groups. The primary outcome was all-cause death at 72 months.ResultsThe study cohort comprised 2282 patients (1166 in each study group). Prior to matching, the primary outcome occurred in 429/1166 patients (36.79%) in the low PTH group and in 284/1116 (25.45%) in the SHPT group. There were no significant differences in all-cause death between the groups according to multivariable Cox regression (P=0.423). The hazard ratio for low PTH versus SHPT was 1.08 (95% confidence interval, 0.90–1.30). Propensity matching created 619 pairs of patients. Baseline characteristics, including age, sex, diabetes, and dialysis vintage were comparable between the groups. The primary outcome occurred in 195/619 patients (31.50%) in the low PTH group and in 193/619 (31.18%) in the SHPT group. There were no significant differences in all-cause death between the groups according to multivariable Cox regression (P=0.43). The adjusted hazard ratio for low PTH versus SHPT was 1.10 (95% confidence interval, 0.87–1.39).ConclusionsHemodialysis patients with low PTH have similar all-cause death rates to the rates for those with SHPT.

Abstract #1182865: Hypocalcemia Induced by Both Hypomagnesemia and Vitamin D Deficiency in a Woman with Covert Alcohol Use Disorder

Calcium homeostasis depends on multiple factors including absorption, renal function, parathyroid hormone (PTH), vitamin D, phosphate and magnesium. Hypocalcemia may be classified as PTH dependent or independent. Hypocalcemia with low PTH is seen when parathyroid glands are compromised, most commonly due to surgery, but also due to autoimmune, congenital and genetic conditions. Hypocalcemia with high PTH is seen in vitamin D deficiency, chronic kidney disease (CKD), and several other conditions.

Abstract #1174395: Calcium Balance in Rhabdomyolysis and Acute Kidney Injury. A biphasic disease

Calcium homeostasis is closely regulated mainly by the parathyroid hormone (PTH) and to a lesser degree by the activated form of vitamin D. Primary hyperparathyroidism and underlying malignancy are the two most common causes of hypercalcemia. Few cases of rebound hypercalcemia have been reported in the recovery period of rhabdomyolysis-induced acute kidney injury (AKI) despite the relatively high incidence from up to one third of cases. Here we report a case of severe and symptomatic hypercalcemia in the recovery period of rhabdomyolysis and AKI with low PTH, PTH-related peptide (PTHrP) and 1,25-dihydroxycholecalciferol levels, and normal 25-hydroxycholecalciferol.

Abstract #1161627: Hypoparathyroidism Manifesting a Decade After Thyroidectomy

Postoperative hypocalcemia usually occurs in the first days after surgery and can be the result of dynamic changes in electrolytes after interventions. When accompanied by a low parathyroid hormone (PTH) level, it is considered hypoparathyroidism. 41-year-old female with history of hypertension and multinodular goiter status post total thyroidectomy (16 years prior) presented with full body and jaw stiffness of 1-hour duration. She reported perioral tingling for the last 5 years and bilateral forearm tingling in the past week. She recalled taking calcium supplements for a brief period after surgery and then again 5 years after surgery. She had not taken any supplements for the last 9 years. Examination shows no neck masses or lymphadenopathy, no limb deformities, and positive Chvostek sign. Laboratory showed serum calcium of 5.1mg/dL (8.9-10.7), ionized calcium 0.92mmol/L (1.16-1.32), albumin 3.7g/dL (3.7-4.9), phosphorus 6.0mg/dL (2.5-4.6), magnesium 1.2mg/dL (1.8-2.8), intact PTH 15.9pg/mL (8.7-77.1), and 25-OH vitamin D of 6.5ng/mL (30.0-100.0). Pathology report confirmed removal of only 1 parathyroid gland. She was started on intravenous calcium gluconate; followed by calcium carbonate, calcitriol, magnesium, and ergocalciferol. Two months after, while taking only calcium carbonate, she showed persistent hypocalcemia with serum calcium of 7.4mg/dL, PTH of 14pg/mL. Calcium decreased to 5.9mg/dL when supplements were stopped; increased to 9.5mg/dL after resuming calcium carbonate and calcitriol. The literature describes an incidence of 0% to 6% of permanent hypoparathyroidism following complete thyroid resection. The fragile nature of the parathyroid glands leaves them susceptible to injuries after manipulation. The short half-life of the PTH allows for prompt clinical manifestations of hypocalcemia after thyroidectomy. Rarely, the manifestations can take several years to present, which is known as “late-onset” or “delayed” hypoparathyroidism. It has been hypothesized that this phenomenon is the result of progressive atrophy of the parathyroid glands; others suggest that scar tissue in the glands leads to hypo-vascularization and slowly progressive ischemia. There are 5 case reports of delayed presentation of post-surgical hypoparathyroidism described in the literature. Four out of five cases were reported in women; three of these cases underwent thyroidectomy for thyroid cancer and two of them for multinodular goiter. Most of the cases presented 12-14 years after surgery; symptoms range from muscle cramps and paresthesia to seizures. Our patient may have had parathyroid insufficiency since her thyroidectomy with intermittent manifestations of hypocalcemia with unclear triggers. It is possible this admission was exacerbated by severely low vitamin D levels. She requires long term treatment for hypocalcemia now as parathyroid glands have completely failed. This case also illustrates that patients with permanent hypoparathyroidism should be followed on a yearly basis to ensure medication adherence and they should be warned about ominous manifestations of hypocalcemia in the long term.

Neonate with Respiratory Distress, Bilateral Microtia, Hypocalcemia, and Lymphopenia.

Neonate with Respiratory Distress, Bilateral Microtia, Hypocalcemia, and Lymphopenia.

Differential parathyroid and kidney Ca2+-sensing receptor activation in autosomal dominant hypocalcemia 1.

SummaryBackgroundParathyroid Ca2+-sensing receptor (CaSR) activation inhibits parathyroid hormone (PTH) release, while activation of renal CaSRs attenuates Ca2+ transport and increases expression of the pore-blocking claudin-14. Patients with autosomal dominant hypocalcemia 1 (ADH1), due to activating CASR mutations, exhibit hypocalcemia but not always hypercalciuria (elevated Ca2+ in urine). The latter promotes nephrocalcinosis and renal insufficiency. Although CaSRs throughout the body including the kidney harbor activating CASR mutations, it is not understood why only some ADH1 patients display hypercalciuria.MethodsActivation of the CaSR was studied in mouse models and a ADH1 patient. In vitro CaSR activation was studied in HEK293 cells.FindingsCldn14 showed blood Ca2+ concentration-dependent regulation, which was absent in mice with kidney-specific Casr deletion, indicating Cldn14 is a suitable marker for chronic CaSR activation in the kidney. Mice with a gain-of-function mutation in the Casr (Nuf) were hypocalcemic with low plasma PTH levels. However, renal CaSRs were not activated at baseline but only after normalizing blood Ca2+ levels. Similarly, significant hypercalciuria was not observed in a ADH1 patient until blood Ca2+ was normalized. In vitro experiments indicate that increased CaSR expression in the parathyroid relative to the kidney could contribute to tissue-specific CaSR activation thresholds.InterpretationOur findings suggest that parathyroid CaSR overactivity can reduce plasma Ca2+ to levels insufficient to activate renal CaSRs, even when an activating mutation is present. These findings identify a conceptually new mechanism of CaSR-dependent Ca2+ balance regulation that aid in explaining the spectrum of hypercalciuria in ADH1 patients.FundingErasmus+ 2018/E+/4458087, the Canadian Institutes for Health research, the Novo Nordisk Foundation, the Beckett Foundation, the Carlsberg Foundation and Independent Research Fund Denmark.

Comparative Effectiveness of Dialysis Modality on Laboratory Parameters of Mineral Metabolism

Introduction: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are prevalent in patients undergoing maintenance dialysis. Yet, there are limited and mixed evidence on the effects of different dialysis modalities involving longer treatment times or higher frequencies on CKD-MBD markers. Methods: This cohort study used data from 132,523 incident dialysis patients treated with any of the following modalities: conventional thrice-weekly in-center hemodialysis, nocturnal in-center hemodialysis (NICHD), home hemodialysis (HHD), or peritoneal dialysis (PD) from 2007 to 2011. We used marginal structural models fitted with inverse probability weights to adjust for fixed and time-varying confounding and informative censoring. We estimated the average effects of treatments with different dialysis modalities on time-varying serum concentrations of CKD-MBD markers: albumin-corrected calcium, phosphate, parathyroid hormone (PTH), and alkaline phosphatase (ALP) using pooled linear regression. Results: Most of the cohort were exclusively treated with conventional in-center hemodialysis, while few were ever treated with NICHD or HHD. At the baseline, PD patients had the lowest mean and median values of PTH, while NICHD patients had the highest median values. During follow-up, compared to hemodialysis patients, patients treated with NICHD had lower mean serum PTH (19.8 pg/mL [95% confidence interval: 2.8, 36.8] lower), whereas PD and HHD patients had higher mean PTH (39.7 pg/mL [31.6, 47.8] and 51.2 pg/mL [33.0, 69.3] higher, respectively). Compared to hemodialysis patients, phosphate levels were lower for patients treated with NICHD (0.44 mg/dL [0.37, 0.52] lower), PD (0.15 mg/dL [0.12, 0.19] lower), or HHD (0.33 mg/dL [0.27, 0.40] lower). There were no clinically meaningful associations between dialysis modalities and concentrations of calcium or ALP. Conclusion: In incident dialysis patients, compared to treatment with conventional in-center hemodialysis, treatments with other dialysis modalities with longer treatment times or higher frequency were associated with different patterns of serum phosphate and PTH. Given the recent growth in the use of dialysis modalities other than hemodialysis, the associations between the treatment and the CKD-MBD markers warrant additional study.

Parathyroidectomy versus cinacalcet in the treatment of tertiary hyperparathyroidism after kidney transplantation: a retrospective study.

BackgroundHyperparathyroidism is common in patients with chronic kidney disease with reduced renal function and has been observed after kidney transplantation. The optimal treatment for cases in which hyperparathyroidism persists after kidney transplantation has not been determined.MethodsThis retrospective study included 83 patients with tertiary hyperparathyroidism who underwent kidney transplantation between 2000 and 2018 at a single tertiary center in Korea. Sixty-four patients underwent parathyroidectomy and 19 patients were treated with cinacalcet following renal transplantation. Biochemical parameters and clinical outcomes were compared between the two groups.ResultsSerum calcium and parathyroid hormone (PTH) levels improved in both the parathyroidectomy and cinacalcet groups. One year after treatment, parathyroidectomy resulted in a lower mean serum calcium level than cinacalcet (9.7 ± 0.7 mg/dL vs. 10.5 ± 0.7 mg/dL, p = 0.001). Regarding serum PTH, the parathyroidectomy group showed a significantly lower PTH level than the cinacalcet group at 6 months (129.1 ± 80.3 pg/mL vs. 219.2 ± 92.5 pg/mL, p = 0.002) and 1 year (118.8 ± 75.5 pg/mL vs. 250.6 ± 94.5 pg/mL, p < 0.001). There was no statistically significant difference in the incidence of kidney transplant rejection, graft failure, cardiovascular events, fracture risk, or bone mineral density changes between the two groups.ConclusionParathyroidectomy appears to reduce PTH and calcium levels effectively in tertiary hyperparathyroidism. However, creatinine level and allograft rejection should be monitored closely.

Low serum parathyroid hormone, inflammation, and malnutrition in prevalent hemodialysis patients

Therapeutic Apheresis and DialysisEarly View LETTER TO THE EDITOR Low serum parathyroid hormone, inflammation, and malnutrition in prevalent hemodialysis patients Marisa Andreia de Oliveira Roldão, Corresponding Author Marisa Andreia de Oliveira Roldão marisa.roldao@chmt.min-saude.ptI orcid.org/0000-0002-0448-0203 Department of Nephrology, Centro Hospitalar do Médio Tejo, Torres Novas, Portugal Correspondence Marisa Andreia de Oliveira Roldão, Department of Nephrology, Centro Hospitalar do Médio Tejo, Av. Xanana Gusmão 45, Torres Novas 2350-754, Portugal. Email: marisa.roldao@chmt.min-saude.ptISearch for more papers by this authorRachele Escoli, Rachele Escoli orcid.org/0000-0002-2962-0794 Department of Nephrology, Centro Hospitalar do Médio Tejo, Torres Novas, PortugalSearch for more papers by this authorAna Vila Lobos, Ana Vila Lobos Department of Nephrology, Centro Hospitalar do Médio Tejo, Torres Novas, PortugalSearch for more papers by this author Marisa Andreia de Oliveira Roldão, Corresponding Author Marisa Andreia de Oliveira Roldão marisa.roldao@chmt.min-saude.ptI orcid.org/0000-0002-0448-0203 Department of Nephrology, Centro Hospitalar do Médio Tejo, Torres Novas, Portugal Correspondence Marisa Andreia de Oliveira Roldão, Department of Nephrology, Centro Hospitalar do Médio Tejo, Av. Xanana Gusmão 45, Torres Novas 2350-754, Portugal. Email: marisa.roldao@chmt.min-saude.ptISearch for more papers by this authorRachele Escoli, Rachele Escoli orcid.org/0000-0002-2962-0794 Department of Nephrology, Centro Hospitalar do Médio Tejo, Torres Novas, PortugalSearch for more papers by this authorAna Vila Lobos, Ana Vila Lobos Department of Nephrology, Centro Hospitalar do Médio Tejo, Torres Novas, PortugalSearch for more papers by this author First published: 04 February 2022 https://doi.org/10.1111/1744-9987.13810Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

Novel PTH Gene Mutations Causing Isolated Hypoparathyroidism.

Parathyroid hormone (PTH) gene mutations represent a rare cause of familial isolated hypoparathyroidism (FIH). These defects can cause hypoparathyroidism with increased or decreased serum levels of PTH through 1) impaired PTH synthesis; 2) induction of parathyroid cell apoptosis; or 3) secretion of bioinactive PTH molecules. Eight pathogenic mutations of this gene have been described previously. Through describing 2 novel mutations of the PTH gene, we aim to extend the molecular basis for FIH and further refine the proposed mechanisms by which PTH mutations cause hypoparathyroidism. Proband case reports were compiled with extended family analysis. The probands in both kindreds presented before age 10 days with hypocalcemia and elevated phosphate levels. Proband A had low PTH levels, whereas these levels were elevated in Proband B. Proband B was initially diagnosed with pseudohypoparathyroidism. Methylation analysis was performed of CpG dinucleotides within 3 GNAS differentially methylated regions; whole-genome sequencing; and PTH infusion with analysis of nephrogenous 3',5'-cyclic adenosine 5'-monophosphate. Proband A had a novel heterozygous sequence change in exon 2 of the PTH gene, c.46_47delinsAA (p.Ala16Lys), and proband B had a novel homozygous nucleotide transition in PTH exon 3 (c.128G > A; p.G43E) that led to replacement of glycine by glutamic acid at position 12 of PTH 1-84. PTH 1-34 infusion demonstrated that renal responsiveness to PTH was intact and not antagonized by circulating bioinactive PTH. PTH gene mutations are uncommon causes of hypoparathyroidism, but can be misdiagnosed as disorders of gland development or receptor function if PTH levels are decreased or elevated, respectively. Genetic testing should be considered early in the diagnostic approach to these presentations.

Phosphorus-Calcium and Bone Metabolism in Children with Dystrophic Epidermolysis Bullosa: Cross-Sectional Study

Background. Dystrophic epidermolysis bullosa (EB) is a rare skin disease, and secondary osteoporosis is one of its complications. The bone remodeling condition in this pathology has not been studied enough. Objective. The aim of the study is to study the characteristics of phosphorus-calcium and bone metabolism in children with dystrophic EB.Methods. The study included children with dystrophic EB aged from 3 to 18 years undergoing inpatient treatment. The ratio of children with phosphorus-calcium metabolism disorders was determined: reduced concentration of total calcium &lt; 2.2 mmol/l, and phosphorus &lt; 1.25 mmol/l. Additionally, deviations from reference values for 25(OH)D, parathormone, osteocalcin, C-terminal telopeptide of type 1 collagen (CTX-I) concentrations and alkaline phosphatase activity were established.Results. Hypocalcemia was revealed in 16 patients (41%) and hypophosphatemia — in 3 (8%) patients out of 39 children with EB (22 girls, median age 77 (46; 136) months). Vitamin D level was lower than optimal (&lt; 30 ng/ml) in 20 (77%) children with EB, while lower osteocalcin concentration — in 26 (67%), and lower CTX-I concentration — in all patients. At the same time, the median CTX-I concentration (1.32 ng/ml) more than doubled the upper values of the reference range for this indicator (&lt; 0.573 and &lt; 0.584 ng/ml for girls and boys, respectively). The low parathormone concentration was revealed in 1 (3%) patient. The alkaline phosphatase activity was within the reference range in all cases.Conclusion. Disorders of phosphoruscalcium (mainly calcium) metabolism are present in large number of children with dystrophic EB. Therewith, most patients have shown vitamin D deficiency, as well as signs of bone resorption dominance (high CTX-I concentration) over bone development (low osteocalcin concentration). In general, all revealed changes in the biochemical indicators of bone remodeling indicate the development of secondary osteoporosis in most children with EB.