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The Journal of Clinical Pediatric... May 2024Patients being reported for vitamin D deficiency (VDD) are increasing, particularly among the children and adolescents. This study aims to manifest the clinical and...
Patients being reported for vitamin D deficiency (VDD) are increasing, particularly among the children and adolescents. This study aims to manifest the clinical and dental evaluations of a child with VDD, referred to the dental office. A 10-year-old British Asian boy was referred to the paediatric specialist dentistry clinic by the general dentist for dental management. The medical history depicted that the patient was diagnosed with VDD, secondary hyperparathyroidism and delayed growth. Moreover, his mother had the VDD during pregnancy. The patient was breast fed and had rickets in infancy. He was prescribed vitamin D supplements at the age of 16 months. He had received multiple dental treatments under local anaesthesia but with limited cooperation. Clinical examination revealed that the patient had chronological enamel hypoplasia shown as bands at the occlusal third on specific teeth. Suboptimal hygiene with general plaque induced gingivitis, dental caries in permanent and primary teeth, and delayed the teeth eruption. Preventions included appropriate oral hygiene and dietary advice, fluoride varnish application and fissure sealant placement. The treatments included anterior direct composite restoration, posterior composite restoration, stainless steel crowns and extractions. Thorough medical history is essential to understand the underlying causes of dental defects. Early dental intervention can restore the patient appearance and function and prevent further dental damage.
Topics: Humans; Male; Dental Enamel Hypoplasia; Child; Vitamin D Deficiency; Hyperparathyroidism, Secondary; Dental Caries; Pit and Fissure Sealants; Growth Disorders; Crowns; Rickets; Gingivitis; Pregnancy; Dental Restoration, Permanent; Female; Tooth Extraction
PubMed: 38755997
DOI: 10.22514/jocpd.2024.072 -
American Journal of Surgery Aug 2024Veterans with primary hyperparathyroidism are under diagnosed and undertreated. We report the results of a pilot study to address this problem.
BACKGROUND
Veterans with primary hyperparathyroidism are under diagnosed and undertreated. We report the results of a pilot study to address this problem.
METHODS
We implemented a stakeholder-driven, multi-component intervention to increase rates of diagnosis and treatment for primary hyperparathyroidism at a single VA hospital. Intervention effects were evaluated using an interrupted time series analysis.
RESULTS
The mean age of Veterans affected by the intervention was 67 years (SD 12.1) and 84 % were men. Compared to the pre-intervention period, the intervention doubled the proportion of Veterans who were appropriately evaluated for hyperparathyroidism (absolute difference 25 %, 95 % CI 11 %-38 %, p < 0.001) and increased referrals for treatment by 27 % (95 % CI 7 %-47 %, p < 0.012).
CONCLUSION
Our pilot study suggests it is feasible to address the underdiagnosis and undertreatment of primary hyperparathyroidism among Veterans.
Topics: Humans; Hyperparathyroidism, Primary; Male; Female; Aged; Pilot Projects; Middle Aged; Parathyroidectomy; Hospitals, Veterans; Veterans; United States; Interrupted Time Series Analysis; Referral and Consultation
PubMed: 38755025
DOI: 10.1016/j.amjsurg.2024.04.029 -
Endocrine-related Cancer Jul 2024The age-specific development of the three constituent components of multiple endocrine neoplasia type 2 (MEN 2) is incompletely characterized for many of the >30...
The age-specific development of the three constituent components of multiple endocrine neoplasia type 2 (MEN 2) is incompletely characterized for many of the >30 causative rearranged during transfection (RET) mutations, which this genetic association study aimed to specify. Included in the study were 683 carriers of heterogeneous RET germline mutations: 53 carriers with 1 highest-risk mutation (codon 918); 240 carriers with 8 different high-risk mutations (codon 634); 176 carriers with 16 different intermediate-risk mutations (codon 609, 611, 618, 620, or 630); and 214 carriers with 6 different low-risk mutations (codon 768, 790, 804, or 891).There was a strong genotype-specific development of MEN 2 constituent components, with distinct age gradients from C cell disease to node negative medullary thyroid cancer (MTC), from node negative to node positive MTC, from node positive MTC to pheochromocytoma, and from pheochromocytoma to primary hyperparathyroidism. Primary hyperparathyroidism was not observed among the 53 MEN 2B patients who carried highest-risk mutations (age range: 0.5-50 years), of whom no more than 12 (23%) and 3 (6%) carriers were older than age 30 years and 35 years, respectively. The age-specific development of MTC differed significantly between the four RET risk categories, whereas the age-specific development of pheochromocytoma differed significantly only between the two strongest RET risk categories. No significant differences were noted in the development of primary hyperparathyroidism. These findings delineate age-specific disease manifestation corridors for the three constituent components of MEN 2 by RET genotype. These corridors are useful for initial risk assessment and organ-specific surveillance of newly identified RET carriers going forward.
Topics: Humans; Proto-Oncogene Proteins c-ret; Middle Aged; Adult; Multiple Endocrine Neoplasia Type 2a; Adolescent; Male; Female; Thyroid Neoplasms; Young Adult; Pheochromocytoma; Child; Aged; Child, Preschool; Adrenal Gland Neoplasms; Genotype; Infant; Germ-Line Mutation; Carcinoma, Neuroendocrine; Heterozygote; Hyperparathyroidism, Primary; Multiple Endocrine Neoplasia Type 2b; Aged, 80 and over
PubMed: 38753300
DOI: 10.1530/ERC-24-0038 -
Pediatric Nephrology (Berlin, Germany) May 2024Infantile hypercalcemia (IH) is a rare genetic disorder characterized by hypercalcemia, hypercalciuria, low parathyroid hormone, and nephrocalcinosis during the first...
Infantile hypercalcemia (IH) is a rare genetic disorder characterized by hypercalcemia, hypercalciuria, low parathyroid hormone, and nephrocalcinosis during the first months of life. Biallelic variants in the genes CYP24A1 and SCL34A1 cause IH1 and 2, respectively. We present the case of a newborn with an antenatal diagnosis of IH2 due to the identification of echogenic, yet normal-sized kidneys at 23 weeks gestation. Trio whole-exome sequencing initially identified only a heterozygous pathogenic variant in SLC34A1. Re-analysis of the exome data because of the clinical suspicion of IH2 revealed a 21-basepair deletion in trans that had initially been filtered out because of its high allele frequency. The diagnosis of IH2 enabled postnatal screening for hypercalcemia, present already at week 1, resulting in early treatment with phosphate supplementation and vitamin D avoidance. In the subsequent course, biochemical parameters were normalized, and the patient showed no obvious clinical complications of IH2, apart from the nephrocalcinosis.
PubMed: 38753084
DOI: 10.1007/s00467-024-06403-8 -
Endocrinology and Metabolism (Seoul,... Jun 2024Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder.... (Review)
Review
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.
Topics: Humans; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Parathyroid Hormone; Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary; Animals
PubMed: 38752265
DOI: 10.3803/EnM.2024.1978 -
Transplant International : Official... 2024Tertiary hyperparathyroidism (THPT) is characterized by elevated parathyroid hormone and serum calcium levels after kidney transplantation (KTx). To ascertain whether...
Pre-Transplant Calcimimetic Use and Dose Information Improves the Accuracy of Prediction of Tertiary Hyperparathyroidism after Kidney Transplantation: A Retrospective Cohort Study.
Tertiary hyperparathyroidism (THPT) is characterized by elevated parathyroid hormone and serum calcium levels after kidney transplantation (KTx). To ascertain whether pre-transplant calcimimetic use and dose information would improve THPT prediction accuracy, this retrospective cohort study evaluated patients who underwent KTx between 2010 and 2022. The primary outcome was the development of clinically relevant THPT. Logistic regression analysis was used to evaluate pre-transplant calcimimetic use as a determinant of THPT development. Participants were categorized into four groups according to calcimimetic dose, developing two THPT prediction models (with or without calcimimetic information). Continuous net reclassification improvement (CNRI) and integrated discrimination improvement (IDI) were calculated to assess ability to reclassify the degree of THPT risk by adding pre-transplant calcimimetic information. Of the 554 patients, 87 (15.7%) developed THPT, whereas 139 (25.1%) received pre-transplant calcimimetic treatment. Multivariate logistic regression analysis revealed that pre-transplant calcimimetic use was significantly associated with THPT development. Pre-transplant calcimimetic information significantly improved the predicted probability accuracy of THPT (CNRI and IDI were 0.91 [ < 0.001], and 0.09 [ < 0.001], respectively). The THPT prediction model including pre-transplant calcimimetic information as a predictive factor can contribute to the prevention and early treatment of THPT in the era of calcimimetics.
Topics: Humans; Kidney Transplantation; Retrospective Studies; Male; Female; Middle Aged; Calcimimetic Agents; Adult; Calcium; Hyperparathyroidism; Parathyroid Hormone; Logistic Models
PubMed: 38751772
DOI: 10.3389/ti.2024.12704 -
Biochemical and Biophysical Research... Aug 2024The T-BOX transcription factor TBX1 is essential for the development of the pharyngeal apparatus and it is haploinsufficient in DiGeorge syndrome (DGS), a developmental...
The T-BOX transcription factor TBX1 is essential for the development of the pharyngeal apparatus and it is haploinsufficient in DiGeorge syndrome (DGS), a developmental anomaly associated with congenital heart disease and other abnormalities. The murine model recapitulates the heart phenotype and showed collagen accumulation. We first used a cellular model to study gene expression during cardiogenic differentiation of WT and Tbx1 mouse embryonic stem cells. Then we used a mouse model of DGS to test whether interfering with collagen accumulation using an inhibitor of lysyl hydroxylase would modify the cardiac phenotype of the mutant. We found that loss of Tbx1 in a precardiac differentiation model was associated with up regulation of a subset of ECM-related genes, including several collagen genes. In the in vivo model, early prenatal treatment with Minoxidil, a lysyl hydroxylase inhibitor, ameliorated the cardiac outflow tract septation phenotype in Tbx1 mutant fetuses, but it had no effect on septation in WT fetuses. We conclude that TBX1 suppresses a defined subset of ECM-related genes. This function is critical for OFT septation because the inhibition of collagen cross-linking in the mutant reduces significantly the penetrance of septation defects.
Topics: Animals; DiGeorge Syndrome; Mice; T-Box Domain Proteins; Minoxidil; Disease Models, Animal; Collagen; Cell Differentiation
PubMed: 38749189
DOI: 10.1016/j.bbrc.2024.150104 -
JAMA Network Open May 2024Hypoparathyroidism following thyroid surgery is a serious complication that occurs frequently when surgery is performed by low-volume thyroid surgeons without experience...
IMPORTANCE
Hypoparathyroidism following thyroid surgery is a serious complication that occurs frequently when surgery is performed by low-volume thyroid surgeons without experience in parathyroid surgery.
OBJECTIVE
To evaluate the occurrence of hypoparathyroidism following total thyroidectomy after the introduction of autofluorescence in low-volume, nonparathyroid institutions.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, multicenter cohort study, with a follow-up period of up to 1 year, was conducted in Denmark at 2 low-volume nonparathyroid institutions between January 2021 and November 2023. All adult patients referred for total thyroidectomy were assessed for eligibility (n = 90). Only patients with no history of thyroid surgery were considered (n = 89). Patients who only underwent lobectomy (n = 6) or declined to participate (n = 5) were excluded. All included patients completed follow-up. The prospective cohort was compared with a historical cohort of successive patients undergoing primary total thyroidectomy from 2016 to 2020 (before autofluorescence was available).
INTERVENTION
Included patients underwent autofluorescence-guided total thyroidectomy.
MAIN OUTCOMES AND MEASURES
Rate of hypoparathyroidism. Immediate hypoparathyroidism was defined as the need for active vitamin D postoperatively, whereas permanent hypoparathyroidism was considered when there still was a need for active vitamin D 1 year after surgery.
RESULTS
Seventy-eight patients underwent autofluorescence-guided surgery (mean [SD] age, 55.6 [13.1] years; 67 [86%] female) and were compared with 89 patients in the historical cohort (mean [SD] age, 49.7 [12.8] years; 78 [88%] female). The rate of immediate hypoparathyroidism decreased from 37% (95% CI, 27%-48%) to 19% (95% CI, 11%-30%) after the introduction of autofluorescence (P = .02). Permanent hypoparathyroidism rates decreased from 32% (95% CI, 22%-42%) to 6% (95% CI, 2%-14%) (P < .001), reaching 0% at the end of the study. More parathyroid glands were identified with autofluorescence (75% [95% CI, 70%-80%] vs 61% [95% CI, 56%-66%]) (P < .001) and less parathyroid glands were inadvertently excised (4% [95% CI, 1%-11%] vs 21% [95% CI, 13%-31%]) (P = .001).
CONCLUSIONS AND RELEVANCE
In this cohort study of autofluorescence-guided thyroid surgery in low-volume, nonparathyroid institutions, the use of autofluorescence was associated with a significant decrease in both immediate and permanent hypoparathyroidism. When autofluorescence was used, hypoparathyroidism rates were comparable with those of high-volume surgeons who also perform parathyroid surgery.
Topics: Humans; Thyroidectomy; Hypoparathyroidism; Female; Male; Middle Aged; Prospective Studies; Postoperative Complications; Adult; Denmark; Optical Imaging; Aged; Surgery, Computer-Assisted
PubMed: 38748422
DOI: 10.1001/jamanetworkopen.2024.11384 -
BJS Open May 2024Multicentre studies have previously reported on national outcomes of surgery for primary hyperparathyroidism, but not investigated whether management and outcome are... (Observational Study)
Observational Study
BACKGROUND
Multicentre studies have previously reported on national outcomes of surgery for primary hyperparathyroidism, but not investigated whether management and outcome are uniform among countries. This study investigated whether there are differences among European countries in operative management and outcome of surgery for primary hyperparathyroidism.
METHODS
Using data from Eurocrine®, a pan-European registry for endocrine surgeries, a retrospective observational cross-sectional multicentre study with 99 participating centres in 14 European countries was performed. Data on age, sex, calcium levels, operative strategy, conversion rate and rate of failed exploration were analysed for patients who underwent initial surgery for sporadic primary hyperparathyroidism. Primary outcome measures were intention to perform limited parathyroidectomy and the rate of hypercalcaemia at first follow-up.
RESULTS
A total of 9548 patients were registered between 2015 and 2020. There were 7642 (80%, range 74.5-93.2%) females. There was intention to perform limited parathyroidectomy in 7320 of 9548 (76.7%) operations, ranging from 498 of 1007 (49.5%) to 40 of 41 (97.6%) among countries. Hypercalcaemia at first follow-up (median time to follow-up 15 days) was found in 416 of 9548 (4.4%) operations, ranging from 0 of 119 (0%) to 3 of 38 (7.9%) among countries.
CONCLUSION
This study demonstrated large differences in the intention to perform limited parathyroidectomy for primary hyperparathyroidism among European countries, as well as differences in the rate of postoperative hypercalcaemia. Future studies are needed to evaluate the impact of these different healthcare practices on patient outcomes.
Topics: Humans; Hyperparathyroidism, Primary; Female; Male; Parathyroidectomy; Europe; Retrospective Studies; Middle Aged; Cross-Sectional Studies; Hypercalcemia; Aged; Adult; Treatment Outcome; Registries
PubMed: 38747104
DOI: 10.1093/bjsopen/zrae037 -
JBMR Plus Mar 2024Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing... (Clinical Trial)
Clinical Trial
UNLABELLED
Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX. Patients received only 2 doses of rhPTH(1-84) in PARALLAX and were considered treatment-naive at the start of the current study. rhPTH(1-84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 yr; 81.8% were women, and 90.9% were White. By the end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-h urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402-855 mg/d and 0.8-0.2 μg/d, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2-5 fold from baseline to EOT. The HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1-84) once daily for 1 yr improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings.
CLINICAL TRIAL IDENTIFIER
NCT03364738.
PubMed: 38741607
DOI: 10.1093/jbmrpl/ziad010