Hypoparathyroidism In Children Research Articles

Influencing Factors of Hypoparathyroidism After Thyroidectomy in Children.

Objective: Hypoparathyroidism (HP) is the most common complication after total thyroidectomy. The purpose of this study was to summarize the recovery of HP in children after total thyroidectomy for thyroid cancer and to explore the related influencing factors. Methods: HP was identified in children who underwent total thyroidectomy for thyroid cancer between 2016 and 2020. Clinical characteristics, tumor stage, intraoperative parathyroid identification, and protection, lymph node metastasis, etc, were retrospectively analyzed. All patients were followed up for more than 1 year, and the recovery time of the parathyroid gland was recorded. The independent risk factors for HP recovery were determined by multivariate regression analysis. Results: In 121 cases of total thyroidectomy for thyroid cancer, 34 cases (28.1%) of HP occurred after surgery. The average age was 10.34 ± 3.01. Twenty-five cases of pattern of parathyroid hormone (PTH; 73.5%) recovered within half a year after surgery, 2 cases (5.9%) recovered after 1 year, and 2 cases (5.9%) were still not recovered after 2 years of follow-up. Univariate analysis suggested that PTH ≤ 1 on the first day after surgery and bilateral VI region lymph node metastasis were risk factors affecting the recovery of HP (P < .05). Multivariate regression analysis showed that PTH≤1 on the first day after surgery was an independent risk factor for HP recovery (OR = 0.092, 95% CI: 0.009-0.966, P = .047). Conclusion: Bilateral central lymph node metastasis and PTH ≤ 1 on the first day after surgery were the risk factors for HP recovery. In addition, HP may still recover more than 6 months after surgery, so the timing of diagnosis of permanent HP still needed to be discussed.

Clinical and genetic characteristics of hypoparathyroidism in children: a multicenter experience in China.

This study was aimed to analyze the clinical and genetic characteristics of hypoparathyroidism in children. We performed a retrospective analysis of 74 patients diagnosed with pediatric hypoparathyroidism from 2014 to 2023, recruited in five medical centers across China. Data of basic information and clinical tests were extracted from patients' records. Whole-exome sequencing (WES), multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray analysis (CMA) were utilized to identify the genetic causes. The results indicated a median onset age of 6.07 ± 4.82 years and a median diagnosis age of 6.91 ± 4.88 years. Of the 46 patients who underwent genetic tests, 35 were found to carry pathogenic variants related to hypoparathyroidism. Specifically, 19 cases (19/46, 41.30%) had 22q11.2 microdeletion, while other variations included AIRE (8/46, 17.39%), GATA3 (3/46, 6.52%), CaSR (2/46, 4.34%), and the rest 3 patients with mutations of TBCE, PTH and mitochondrial gene deletion respectively. Convulsions were the most common initial presentation, observed in 43 cases. The non-DGS group exhibited the lowest serum PTH levels compared to DiGeorge syndrome and gene-negative group. Among the 66 patients who underwent cranial CT or MR, 26 (26/66, 39.99%) presented with intracranial calcification. We reported the largest cohort of childhood hypoparathyroidism with genetic diagnoses, reinforcing the view that genetic disorders account for the majority of pediatric hypoparathyroidism, with the 22q11.2 microdeletion being the most prevalent. Identifying the genetic causes of hypoparathyroidism is crucial for predicting patient outcomes, managing comorbidities, and, importantly, informing decisions regarding the potential use of emerging recombinant human PTH therapy.

Hypoparathyroidism in children and adolescents.

Hypoparathyroidism is characterized by insufficient parathyroid hormone (PTH) release from the parathyroid glands to maintain serum calcium level within normal limits and unresponsiveness of target tissues despite normal serum PTH level. Hypoparathyroidism is defined as low or inappropriately normal serum PTH level. In this narrative review, we discuss the etiology of hypoparathyroidism in children.

Frequency of Hypoparathyroidism in Children Presenting with Beta-Thalassemia Major in Tertiary Care Center

Objective: Aim of our study is to determine the prevalence of hypoparathyroidism in children presenting with beta-thalassemia major in tertiary care center. Study Design: Cross-sectional study Place and Duration: The study was conducted at Thalassemia Center Divisional Headquarter Hospital Mirpur Azad Kashmir during the period from February 2021 to July 2021. Methods: There were eighty eight children with both genders had beta-thalassemia were presented in this study. Age of the patients was between 5-14 years. We have obtained formal permission from the authorities to collect full demographics, including age, sex, body mass index, chelation and transfusion therapy, calcium consumption, the age of beginning of HPT, any symptoms of hypocalcemia. Blood samples were taken for measurement of serum calcium and phosphorus. Prevalence of hypoparathyroidism was calculated among all the cases. SPSS 25.0 version was used to analyze all data. Results: Majority of the patients were males 48 (60%) and 32 (40%) females in this study. Mean body mass index was 7.12±3.13 kg/m2. Mean age of the patients was 8.12±6.35 years. 45(56.3%) were on combination therapy and chelation therapy was in 35 (43.7%). Mean serum calcium level was 6.17±3.55 mg/dl and phosphorus level was 4.15±9.97 mg/dl. We found frequency of HPT among 18 (22.5%) cases.5.45±7.17 years was the mean age of beginning HPT. Patients had HPT were mostly on single chelation therapy using deferiprone (DFP).There was high prevalence of hypocalcemia found in 43 (53.8%) cases. Among 43 cases of hypocalcemia, 24 (55.8%) patients were asymptomatic and 20 (44.2%) were symptomatic in which paresthesias &amp; numbness was the most common complication. Conclusion: We found in this study that the frequency of hypoparathyroidism was a common complication in patients with beta-thalassemia. Frequency of hypocalcemia was high among patients with most prevalent asymptomatic cases. Paresthesias &amp; numbness was the most common complication among symptomatic hypocalcemia. Keywords: Beta-thalassemia, Hypoparathyroidism, Complications, Hypocalcemia

To determine the prevelence of hypoparathyroidism in children with thalassemia major and its corelation to serum ferritin

To determine the prevelence of hypoparathyroidism in children with thalassemia major and its corelation to serum ferritin

Clinical and genetic characteristics of primary hypoparathyroidism in children

Objective: To analyze the clinical and genetic characteristics of primary hypoparathyroidism in children. Methods: The clinical data including age, symptoms, laboratory examination and cranial CT of 13 children with primary hypoparathyroidism diagnosed in the Capital Institute of Pediatrics from May 2017 to December 2019 were collected and analyzed retrospectively. These children and their parents also had gene detected by whole exome sequencing and (or) copy number variation sequencing. Results: Among the 13 patients, 7 were male and 6 female. The onset age was 3 years (1 day-12 years) old. The time from onset to confirmed diagnosis was 2 months (2 days-10 years). The clinical manifestations included convulsion (9 cases), tetany (2 cases), muscle pain (1 case), mental retardation (5 cases), deafness (1 case), and initially misdiagnosed epilepsy (5 cases). The lab examination showed average blood calcium level of (1.7±0.3) mmol/L, blood phosphorus of (2.8±0.4) mmol/L, and parathyroid hormone of 8.2 (3.9-28.7)ng/L. Head CT found 7 cases of ectopic calcification. Among the 7 cases who had genetic abnormalities according to the gene detection, 5 had heterozygous deletion of 22q11.2 region, and only one of whom was diagnosed with typical DiGeorge syndrome. As for the rest 2 cases, one had autosomal dominant hypocalcemia caused by novel heterozygous variation of CaSR gene c.2495T>G (p.F832C), and the other was hypoparathyroidism-deafness-renal dysplasia syndrome caused by GATA3 c.708dupC (p.S237Qfs*66) novel heterozygous variation. Conclusions: Primary hypoparathyroidism in children is mainly characterized by hypocalcemia and usually accompanied with diverse symptoms which may indicate genetic disorders. The detection of large fragment deletion should be considered to exclude 22q11.2 deletion syndrome.

MON-092 Clinical Characteristics and Management of Thyroid Cancer in Pediatrics: Results from the Mexican Population Registry Between 2010-2019

METHODSStudy: Analytical and retrospectivePatients files diagnosed with Thyroid Cancer treated during January 2010 to May 2019, who underwent surgical intervention and histopathological study were reviewed. Chi Square test were used as statistical analysis. A level of significance p <0.001 was established. INTRODUCTION: Cancer thyroid in pediatrics is characterized by advanced presentation, coupled with frequent lymph nodal metastases and often pulmonary metastases. There are few reports on the rate of cancer and hypoparathyroidism in children. OBJECTIVE: Describe of pediatric thyroid cancer with particular emphasis on the clinical characteristics, risk factors associated and with treatment outcomesRESULTS43 patients were included in the study 69.8% were female. Average age of 12 years (range 5 to 17 years). Association of cancer and thyroiditis 25% and Cancer with Graves Disease 2.3%.Histopathological diagnoses of thyroid cancer: 86% papillary, 2.3% follicular, 11.6% medullary, 69.8% patients presented with metastases, most often lymph node (46.5%), pulmonary (2.3%) and pulmonary plus lymph node (23.3%), 11.6% patients do not present metastasis and 16.3% without data.Surgical interventions: only thyroidectomy 16.3%, Hemitiroidectomy 4.7%, total thyroidectomy with lymph node emptying 74% and modified radical neck dissection 5%.In 16% of the patients, second surgery was required after the histopathological report. Post-surgical hypoparathyroidism was recorded in 27 patients (62%): transitory in 11 (25%) and 16 (37%) permanent.Biochemical variables: (N /%/ Hypoparathyroidism /NO hypoparathyroidism) of 18 patients with post-surgical PTH <10 pg/ml (18/42%/17/1) 17 of them presented post-surgical hypoparathyroidism (P <0.001), PTH >10 pg/ml (13/30%/9/4), and without post-surgical measurement of PTH (12/28% / 6/6). Post-surgical ionized calcium <4mg/dl in 29 patients of which 22 had hypoparathyroidism (P <0.001) (29 / 67.4% / 22/7), with calcium >4 mg/dL (14 / 32.6% / 9/5). 21 patients with seric calcium <8mg/dl 20 with hypoparathyroidism. (21/48%/ 20/1) (P <0.001). Seric calcium >8 (16/37%/9/7) without measurement data. Serial calcium in 6 patients (6/15% / 3/3). Postoperative positive thyroglobulin parameter was presented as an risk factor for complication and metastases OR 1.42 (1-1.6)Regarding iodine treatment, 29 patients received an average dose of 200 (range 100- 720 milicuries mCi).CONCLUSIONSPapillary cancer is the most common type in pediatric patients, evidence of metastases find in 69.8% most frequent lymph node, postoperative thyroglobulin OR 1.42. They should always be considered in the management of these patients. As a post-surgical complication, there is an increased risk to present hypoparathyroidism when PTH less < 10 pg / ml, post-surgical ionized calcium < 4 mg/dl and serum calcium <8 mg/dl.

Postoperative Hypoparathyroidism After Total Thyroidectomy in Children

BackgroundPostoperative hypocalcemia because of hypoparathyroidism is the most common complication of total thyroidectomy in children. We hypothesized that most children with postoperative hypocalcemia would be eucalcemic by 12 mo and sought to define risk factors for permanent hypoparathyroidism. MethodsWe retrospectively reviewed children who underwent total thyroidectomy at a single children's hospital from 2012 to 2019. Patients with prior neck surgery were excluded. Indication for operation, final pathologic diagnosis, and postoperative serum calcium up to 12 mo were recorded. Permanent hypoparathyroidism was defined as supplemental calcium requirement beyond 1 y postoperatively. ResultsSixty-eight patients underwent total thyroidectomy. Graves’ disease was the most common benign indication for surgery (38 patients). Twenty-six patients (38%) had cancer on final pathology. Central lymph node dissection (CLND) was performed in 12 cancer patients. Twenty-eight patients (41%) had postoperative hypocalcemia. Eight patients (12%) had hypocalcemia at 6 mo. Risk factors for hypoparathyroidism at 6 mo were a cancer diagnosis (odds ratio [OR] 6.7; P = 0.02), CLND (OR 12.6; P < 0.01), and parathyroid tissue in the surgical specimen on pathologic analysis (OR 19.5; P < 0.01). Only two patients (3%) developed permanent hypoparathyroidism, both of whom had thyroidectomy for cancer and underwent CLND. ConclusionsChildren with thyroid cancer are at high risk for postoperative hypocalcemia after total thyroidectomy. The risk is further increased by CLND, which should be performed selectively. A majority of patients with hypoparathyroidism at 6 mo postoperatively regain normal parathyroid function by 1 y. Permanent hypoparathyroidism in children after total thyroidectomy at a pediatric endocrine surgery center is rare.

Recombinant parathyroid hormone for hypoparathyroidism in children: a narrative review.

The conventional management of hypoparathyroidism in children involves the use of calcium and vitamin D analogs. This therapy effec-tively increases the serum calcium levels but worsens hypercalciuria and its consequences such as nephrocalcinosis and renal insuffi-ciency. Although replacement with the missing parathyroid hormone (PTH) is ideal and available for more than 2 decades, the reported concerns of osteosarcoma prohibited its use in children with open epiphyses. Nevertheless, the data accumulated over the past several years suggests that the fears of bone malignancies were probably overstated. With an aim to review the available data on recombinant PTH (rhPTH) use, we performed a literature search using international databases and identified 15 studies involving approximately 70 children with hypoparathyroidism due to various etiologies who received rhPTH1-34 for durations between 1 day and 13.5 years. All the studies appear to indicate that rhPTH1-34 therapy is an effective short and long-term strategy for treatment of hypoparathyroidism with better metabolic control, lesser effects on renal function and improved quality of life as compared to conventional therapy. A more significant conclusion is the safety of long-term use of rhPTH1-34 with no observed adverse skeletal effects so far. However, all studies mention the importance of a continued surveillance for adverse effects in the treated patients. This narrative review discusses the experi-ence of rhPTH1-34 use exclusively in children.

The Management of Permanent Primary Hypoparathyroidism in Children and Adolescents: A Complex Task.

Management of hypoparathyroidism (hypoPT), depends on the etiology and the severity of hypocalcemia. Treatment goals include control of hypocalcemic symptoms preserving serum calcium in the low-normal range and phosphate in the high normal range. While correction of serum calcium to low-normal range does not fully correct mineral and bone metabolism it may be associated with increased risk of complications such as nephrolithiasis, nephrocalcinosis and soft tissue calcifications. Therefore, it is imperative to find out ways to individualize treatment of patients with hypoPT to achieve the best prognosis while minimizing complications. Replacement therapy with recombinant human PTH (rhPTH) was recently tested for optimizing treatment of hypoPT in a small number of patients. For children and adolescents, further studies are needed to evaluate the long-term effects and safety of rhPTH. In this short review we summarize current knowledge on the management of hypoPT and debate our gaps on the long-term management of children and adolescents with hypoPT.

Permanent Hypoparathyroidism After Total Thyroidectomy in Children: Results from a National Registry

IntroductionHypoparathyroidism is the most common complication following thyroidectomy. There are few population-based reports on the rate of hypoparathyroidism in children. The incidence of medical treatment of permanent hypoparathyroidism in children is reported using a national registry.MethodsThe study population included patients below 18 years of age undergoing total thyroidectomy reported to the Scandinavian Quality Registry for Thyroid, Parathyroid and Adrenal Surgery 2004–2014. Patients with previous thyroid or parathyroid surgery or treatment with vitamin D before surgery were excluded from analysis. Permanent postoperative hypoparathyroidism was defined as treatment with vitamin D for more than 6 months after thyroidectomy. Risk factors for permanent hypoparathyroidism were calculated with uni- and multivariable logistic regression. Using data from the Swedish Inpatient Registry, rates of readmissions and annual number of days in hospital after total thyroidectomy were compared between patients with and without permanent hypoparathyroidism.ResultsSome 274 children (215 girls and 59 boys) underwent total thyroidectomy. The median age was 14 (range 0–17) years. Indications for surgery were Graves’ disease (214, 78.1%), other benign disease (27, 9.9%) and thyroid cancer (33, 12%). Median follow-up was 4.8 years. Twenty (7.3%) children developed permanent hypoparathyroidism. No statistically significant risk factors for permanent hypoparathyroidism were identified. Rates of readmission and annual number of days in hospital after discharge were similar in patients with and without permanent hypoparathyroidism.ConclusionsThe rate of permanent hypoparathyroidism following total thyroidectomy in children was high and is a cause of concern.

Hypoparathyroidism in children with β-thalassemia major and its relation to iron chelation therapy

Hypoparathyroidism in children with β-thalassemia major and its relation to iron chelation therapy

Epileptic seizure, as the first symptom of hypoparathyroidism in children, does not require antiepileptic drugs

ObjectivePatients with hypoparathyroidism exhibit metabolic disorders (hypocalcemia) and brain structural abnormalities (brain calcifications). Currently, studies have determined whether antiepileptic drug (AED) treatment is required for epileptic seizures in children with hypoparathyroidism.MethodThis study aims to evaluate the data of two medical centers in Beijing based on the diagnosis of epileptic seizures as the first symptom of hypoparathyroidism in children.ResultA total of 42 patients were included and assigned into AED and non-AED treatment groups in a 1:2 matched case–control study. Results show that the seizure outcome after 1 year of AED treatment is not significantly different from that of the control. In the subgroup analysis of patients with subcortical calcifications, the seizure outcome is still not significantly different from that of the control.ConclusionThus, AED treatment cannot improve the seizure outcomes in children with parathyroid disorder, even in such cases as suspected structural seizure caused by subcortical calcifications. Clinicians must take adequate considerations on the use of AEDs in these patients. Epileptic seizures, as the first symptom of hypoparathyroidism in children, do not require epilepsy drugs.

Hypoparathyroidism in Children

Hypoparathyroidism in Children

Long-Term Results of Continuous Subcutaneous Recombinant PTH (1-34) Infusion in Children with Refractory Hypoparathyroidism

Hypoparathyroidism in children is most often due to mutations in genes involved in parathyroid development and calcium homeostasis signaling. Some rare cases result from autoimmune attack on the parathyroid glands as a part of the type 1 polyglandular failure syndrome (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy). The majority of cases of pediatric hypoparathyroidism are well controlled under conventional treatment with calcium and vitamin D analogs. However, this treatment may be difficult to manage, especially in two situations: 1) in the context of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and 2) activating mutations in the calcium-sensing receptor. We successfully treated three patients with hypoparathyroidism with continuous subcutaneous administration of rhPTH(1-34) (recombinant human PTH(1-34)), two of which were refractory to conventional therapy.

Prevalence of Hypoparathyroidism in Children and Young Adults with Thalassemia Major.

Endocrinopathies are frequently reported in children with thalassemia major. Affected children at our center are transfused regularly to maintain hemoglobin of at least 8–9 gm/dl. Most subjects are chelated with Desferrioxamine or Deferiprone or a combination of the two drugs, although a majority of children have poor compliance and are poorly chelated. Hypoparathyroidism usually occurs in thalassemia major due to excess iron deposition in the parathyroid glands. All patients suffering from thalassemia major are screened routinely at our clinic for their bone metabolism. The fasting serum calcium, phosphorus, intact parathormone and alkaline phosphatase levels are checked annually to screen for hypoparathyroidism and Vitamin D deficiency. A diagnosis of hypoparathyroidism is made if the serum calcium is low, phosphorus is high, alkaline phosphatase level is normal and serum parathormone level (intact) is low normal. Mean S. ferritin levels of all the subjects were calculated by averaging the ferritin values over the last 5 years. We analyzed the screening results for hypoparathyroidism in 110 subjects with Thalassemia Major between the ages of 10–25 years. Of these 110 subjects 19 (17.3%) were found to be suffering from hypoparathyroidism and 91 patients had a normal screen. Mean S. ferritin level was 5997ng/ml in the affected subjects (ranging from 2900 to 10,904 ng/ml), compared with the mean S. ferritin level of 3793ng/ml in the unaffected subjects, which was clinically significant, showing a direct correlation between the poor chelation and development of hypoparathyroidism. Only 2 subjects from our affected group had an average ferritin of 2000–3000 ng/ml, although they also had other endocrine disorders such as short stature and hypothyroidism. Of the affected subjects, 9 were males and 10 were females (M: F = 1.1:1). The reported male: female ratio for hypoparathyroidism in thalassemics is 3:1. Age of onset of hypoparathyroidism ranged from 10.9 years to 23 years with mean age of onset being 16 years. The youngest subject (10.9 years) had an average ferritin of 2908 ng/ml. All the affected subjects above 15 years of age had hypogonadism, 7 of the 19 affected subjects (36.84%) had diabetes, 4 (21%) of them had an abnormal glucose tolerance test, and 5 (26.3%) had hypothyroidism. The incidence of hypoparathyroidism reported in our group of patients is higher compared to those reported from other continents (3.6–4.5%) probably due to poor chelation., both males and females are equally affected and the age of onset is earlier compared to reports from other countries.. This suggests that high ferritin levels due to poor chelation is a major factor in the development of hypoparathyroidism and most subjects who develop it, have multiple endocrine disorders.

Latent Hypoparathyroidism in Children With Conotruncal Cardiac Defects

DiGeorge anomaly is characterized by hypoplasia or atresia of the thymus and parathyroid glands resulting in T cell-mediated deficiency, hypocalcemic hypoparathyroidism, and conotruncal cardiac defects. It usually is associated with deletions of chromosomal region 22q11. We hypothesized that the stimulated (secretory reserve) but not the constitutive secretion of parathyroid hormone would be reduced in normocalcemic children with conotruncal cardiac defects but no overt immune deficiency and would be related to the presence of a deletion in the DiGeorge chromosomal region of 22q11. Blood-ionized calcium and serum-intact parathyroid hormone were measured at baseline and seven more times during hypocalcemia induced during cardiopulmonary bypass in 22 patients and 10 control subjects with an atrial septal defect. Chromosomal deletions were detected by fluorescent in situ hybridization and DNA dosage analysis. There were no differences in basal calcium and parathyroid hormone levels between patients and control subjects. All had increased parathyroid hormone in response to hypocalcemia; despite lower calcium levels, parathyroid hormone levels were lower in patients. The parathyroid hormone secretory reserve in 14 of 22 patients was reduced compared with control subjects; 4 of the 14 had deletions. A significant number of children with conotruncal cardiac defects have normocalcemia and a normal constitutive level of parathyroid hormone but deficient parathyroid hormone secretory reserve; about 30% also have 22q11 deletions. Such children may be at risk for the later development of hypocalcemic hypoparathyroidism.

Unmasking of latent hypoparathyroidism in a child with partial DiGeorge syndrome by ethylenediaminetetraacetic acid infusion

DiGeorge syndrome is a rare congenital anomaly with a wide range of clinical manifestations. This syndrome is usually associated with hypocalcaemia resulting from primary hypoparathyroidism. We report here a case of an 8-year-old boy with partial DiGeorge syndrome who presented initially with neonatal hypocalcaemia, but was subsequently normocalcaemic. Latent hypoparathyroidism was unmasked by a diagnostic EDTA infusion resulting in hypocalcaemia without a parathyroid hormone response. We propose that EDTA infusions can be useful in the diagnosis of latent hypoparathyroidism in children.

1,25-Dihydroxycholecalciferol: its use in the long-term management of idiopathic hypoparathyroidism in children.

The production of 1,25-dihydroxycholecalciferol, 1,25(OH)2D3, is reduced in the absence of parathyroid hormone (PTH), because conversion of 25-hydroxycholecalciferol (25-OHD3) to 1,25(OH)2D3 is primarily under PTH control. By managing idiopathic hypoparathyroidism (IHP) in children with very small doses of 1,25(OH)2D3, 0.40-0.50 µg/day, given orally, the intestinal absorption of calcium (Ca) can be increased to normal and thereby restore and maintain normal serum levels of Ca. Three children with previously untreated, undiagnosed and isolated IHP have been managed in this manner for 2650 treatment days. Two 4-year-old children achieved and maintained normal serum levels of Ca after 1-4 days on 0.03 µg/kg/day of 1,25(OH)2D3. While the hormone was continued, each child was placed on a low Ca diet: the total serum Ca fell by 0.80 to 1.0 mg/dl within 2 days. During 2300 treatment days, both children have remained normocalcemic on a regular diet. The third child, who required phenobarbital throughout treatment...