Low Parathyroid Hormone Levels Research Articles

Inadequate PTH Response to Hypocalcemia in People Living with HIV.

Small experimental studies suggest that PTH-secretion following hypocalcemia might be blunted in people living with HIV. The aim of the study was to estimate the frequency of inadequately low concentrations of parathyroid hormone in the presence of hypocalcemia in people living with HIV. This was a retrospective study that was conducted among PLWH enrolled in the ongoing ArcHIV study between 2016 and 2017. PLWH with routine measurements for both calcium and parathyroid hormone levels were included in this analysis. The proportion of patients with a combination of low levels of both calcium and parathyroid hormone was the primary endpoint of this analysis. 496 PLWH were included (mean age 47.1 (± 10.2) years, 393 (79.2 %) men). In 14 (2.8 %) PLWH, low calcium levels with low levels of PTH were observed in the assessment conducted in both years. Undergoing a tenofovir disoproxil-containing treatment in both years was the only explanatory variable significantly associated with inadequately low levels of PTH in the presence of hypocalcemia in both years (OR 4.3 [CI95: 1.4; 16.0]). The combination of low levels of both calcium and PTH was found more frequent in our study sample when compared to what is expected from the general population. Interestingly, undergoing a tenofovir disoproxil-containing therapy was associated with this combination throughout both the years.

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

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

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.

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.

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.

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.

Which physical activity in patients affected by hypoparathyroidism? A review of the literature and practical recommendations.

Hypoparathyroidism (HypoP) is a rare endocrine condition characterized by hypocalcaemia and hyperphosphatemia, as a consequence of absent or improperly low parathyroid hormone (PTH) levels. Patients affected by HypoP have a clinical condition often characterized by paresthesias and muscle spasms, as well as long-term consequences as nephrolithiasis, extraskeletal calcification, and fractures. In the literature, likely due to these symptoms, few data exist regarding the appropriate physical activity (PA) in subjects suffering from HypoP. This review evaluates the literature on exercise-based approaches to the management of individuals affected by HypoP and evaluates: (1) the effects of physical exercise on muscle cramps and other clinical symptoms; (2) the effects of exercise on PTH and calcium level; (3) the most suitable clinical exercise testing; and (4) the most suitable exercise combination. A systematic search was conducted using the databases MEDLINE, Google Scholar using "hypoparathyroidism AND Physical Activity", "Training AND hypoparathyroidism", "Exercise AND muscle cramps", "Exercise AND Fatigue" as keywords. In addition, references list from the included articles were searched and cross-checked to identify any further potentially eligible studies. A total of 50 manuscripts were found among which 39 manuscripts were selected. A few clinical studies have been performed in HypoP patients to evaluate PA training protocols. Although further research is needed to draw solid conclusions regarding best PA protocols in subjects affected by HypoP, a PA protocol has been proposed within the manuscript to encourage patients to attempt exercise to improve their clinical conditions and their quality of life.

Bone Loss Correlated with Parathyroid Hormone Levels in Adult Celiac Patients.

BACKGROUND: Celiac disease (CD) is a gluten-sensitive enteropathy with intestinal and extra-intestinal presentations in genetically predisposed cases. Musculoskeletal problems are one of the most common extra-intestinal manifestations in adult patients with CD. In the present study, we evaluated parathyroid hormone (PTH) levels in men and premenopausal women with CD who had osteoporosis and osteopenia. METHODS: This was a cross-sectional study of 387adult patients with CD who were referred to the Mashhad Celiac Disease Center between 2014 and 2019. We excluded bone loss confounding factors, including cases with endocrine disorders, corticosteroid consumption, smoking, and age of more than 55 years. Factors such as intestinal pathology, bone mineral density (BMD), serum level of anti-tTG, serum vitamin D, and PTH levels were also assessed at the time of diagnosis. RESULTS: Femoral osteopenia was found in 140 (36.2%) patients, and osteoporosis was observed in 55 (14%) patients. Spinal osteopenia and osteoporosis were observed in 127 (33%) and 63 (16.4%) patients, respectively. High levels of PTH were detected in 72/193 (27.2%) of the patients with CD. There was a significant difference between PTH levels in patients with osteopenia, osteoporosis, and normal BMD (P=0.0001). CONCLUSION: This study showed a correlation between low BMD and PTH levels in patients with CD, which suggests autoimmune endocrine disorder as a cause of osteopenia and osteoporosis.

A novel GCM2 mutation identified in an infant with familial isolated hypoparathyroidism

Background: Isolated hypoparathyroidism comprises a set of heterogeneous inherited diseases associated with abnormal calcium metabolism exclusively due to parathyroid hormone (PTH) deficiency. Isolated hypoparathyroidism can be either sporadic or inherited. Genetic causes that impair the synthesis or secretion of PTH, such as calcium-sensing receptor and PTH defects, or defects in the development of the parathyroid gland [glial cell missing 2, (GCM2)], have been established as causes of familial isolated hypoparathyroidism. Transcription factor GCM2 is a crucial regulator of parathyroid gland homeostasis. Transmission of pathogenic variants encoding GCM2 occurs in an autosomal recessive or dominant manner. Case Presentation: Herein, we describe the case of a 12-year-old boy, born to consanguineous parents, who presented with abnormal movement during the first week of birth. Laboratory results revealed hypocalcemia, hyperphosphatemia, and low PTH levels. Genetic testing detected a novel homozygous variant in the GCM2 gene, c.391C&amp;gt;T (p.Arg131*). Although this variant has not been previously described, it is likely the pathogenic cause of this condition. Conclusion: To the best of authors&amp;apos; knowledge, this variant has not been listed in any database. Proper replacement therapy is likely to have good long-term outcomes for our patient.

Role of calcium metabolism in ADHD: The relationship between parathyroid hormone and ADHD symptom severity.

Background:Vitamin D has been found to be associated with the pathogenesis of attention deficit hyperactivity disorder (ADHD). However, the potential role of parathyroid hormone (PTH) is still unclear.Aim:We aimed to investigate the association between calcium metabolism and ADHD symptomatology.Methods:We included 106 participants aged between 7 and 13 years old (51 ADHD patients, mean age: 9.54 ± 1.77, 55 healthy controls mean age: 9.97 ± 0.94) to this study. K-SADS-PL and Conners’ Parent/Teacher Rating Scales, Stroop Test were performed. Blood samples to measure serum levels of Vitamin D, PTH, calcium (Ca), magnesium (Mg), phosphorus (P), and alkaline phosphatase (ALP) were collected in the spring (March–April–May) to prevent seasonal variability.Results:PTH, P, and ALP values were significantly lower and Vitamin D, Ca, and Mg values were significantly higher in the ADHD group (P < 0.05, for all). Both groups had Vitamin D deficiency. Control group has lower Vitamin D levels than the ADHD group (respectively; 17.66 ± 9.07, 21.99 ± 10.99, P < 0.05). There was a negative correlation between PTH and CTRS hyperactivity, CGI-RI and CGI-EL sub-scores, CGI-Total, DSM-IV-Inattention, DSM-IV Hyperactivity/Impulsivity, DSM-IV-Total scores (P < 0.05, for all).Conclusions:We found lower PTH levels in ADHD patients and a strong and negative correlation between PTH and symptom severity. Future studies are needed to clarify if these findings are due to the key role of PTH in ADHD pathology or PTH’s function in activating vitamin D.

Secondary Fahr’s disease: A differential to be considered in a COVID-19 pneumonia patient with neuropsychiatric presentations

Background, aim. Fahr’s disease is a rare neurodegenerative disease caused by intracranial classifications. This case report aims to accentuate the importance of considering rare disease like Fahr’s disease as the differential diagnosis of neuropsychiatric deficits, especially in patients with a history of thyroidectomy. Case presentation. A 50-year-old female who underwent thyroidectomy 5 years previously presented with incoherent speech, behavioral problems, and hand stiffness. On evaluation, several neurobehavioral deficits and carpopedal spasms were observed, along with low Mini-Mental State Examination (MMSE), Hachinski, Activities of Daily Living (ADL), and Instrumental Activities of Daily Living Scale (IADL) score of 22, 4, 13, and 12, respectively. Clinically significant laboratory abnormalities include low serum calcium of 4.7 mg/dl, low thyroid stimulating hormone (TSH) level of 0.113 mIU/l, and low parathyroid hormone (PTH) level of 1.2 pg/ml. In addition, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) test showed a positive result. Meanwhile, brain computerized tomography (CT)-scan results showed multiple bilateral calcifications in the basal ganglia, bilateral cortical-subcortical calcifications in the frontal lobe, and subcortical calcification in the left frontal lobe. Results. The patient was diagnosed with Fahr’s disease secondary to post-thyroidectomy hypoparathyroidism and coronavirus disease 2019 (COVID-19). The patient was treated with calcium lactate, levothyroxine, donepezil, favipiravir for COVID’s infection, vitamin B1, B6, and B12. Conclusions. Fahr’s disease should be considered in patients with neuropsychiatric deficits and spasm disorders, especially in patients with a history of thyroidectomy. Routine follow-up CT-scans after thyroidectomy are recommended.

Malnutrition-Inflammation Complex Syndrome: A Cause of Low Parathyroid Hormone in Patients With Chronic Kidney Disease

Secondary hyperparathyroidism is commonly seen in patients with chronic kidney disease (CKD) due to hypocalcemia, hyperphosphatemia and low vitamin D levels and is associated with high-turnover bone disease. In contrast, some patients with advanced CKD, including those requiring dialysis (end-stage renal disease [ESRD]), develop adynamic bone disease with features of low-turnover bone disease. Low serum parathyroid hormone (PTH) has been used as a biochemical marker of adynamic bone disease. Low PTH levels may not necessarily be due to adynamic bone disease but could be a manifestation of the malnutrition inflammation complex syndrome (MICS). The optimal management of hypoparathyroidism associated with MICS is not well known. Currently, there is insufficient evidence to suggest if there is any role in improving nutritional and inflammatory status among patients with CKD and MICS. Furthermore, it also remains unclear whether these changes will help address low PTH levels seen in these patients. We report three patients with advanced CKD who had very low PTH levels possibly attributed to MICS. In addition, we briefly discuss other characteristics and pathophysiology of MICS.

Childhood Hypercalciuric Hypercalcemia With Elevated Vitamin D and Suppressed Parathyroid Hormone: Long-Term Follow Up.

Purpose: Hypercalcemia with low parathyroid hormone (PTH) level, hypercalciuria, nephrocalcinosis, or nephrolithiasis, was recently reported as caused by mutations in CYP24A1 and SLC34A genes. These encode for vitamin D-24A-hydroxylase and for the renal phosphate transporters NaPiIIa and NaPiIIc, respectively. We aimed to describe the clinical course of these monogenic disorders in patients with and without found mutations during long-term follow-up.Methods: Ten patients with hypercalcemia, hypercalciuria, elevated 1,25-(OH)2D levels and suppressed PTH were followed in our center during 1998–2019. Relevant laboratory and imaging data and results of genetic evaluation were retrieved from medical files.Results: The median age at presentation was 9.5 months (range 1 month−11 years), six were males, and the median follow-up time was 3.8 (1.1–14) years. Mutations in CYP24A1 and SLC34A3 were identified in three and one patients, respectively. Five patients presented with nephrocalcinosis, three with nephrolithiasis, and two had normal renal ultrasound. High blood calcium and 1,25-(OH)2D levels at presentation decreased during follow-up [11.1 ± 1 vs. 9.9 ± 0.5 mg/dl (p = 0.012), and 307 ± 130 vs. 209 ± 65 pmol/l (p = 0.03), respectively]; this paralleled an increase in suppressed PTH levels (5.8 ± 0.9 vs. 11.8 ± 7.3 pg/ml, p = 0.2). Substantial improvements in hypercalciuria and renal sonography findings were not observed. Two patients had impaired renal function (eGFR 84–88 ml/min/1/73 m2) at the last follow up. Interventions included appropriate diet, citrate supplementation, and thiazides.Conclusion: Despite improvement in hypercalcemia and 1,25-(OH)2D levels, not all the patients showed improvements in hypercalciuria and nephrocalcinosis. Deterioration of renal function was also observed. Long-term follow up and intervention to prevent nephrocalcinosis and nephrolithiasis are recommended in these children.

Risk Factors for Low Levels of Parathyroid Hormone after Surgery for Thyroid Cancer: A Single Center Study

Background: Thyroidectomy is the definitive treatment for most patients with thyroid cancer. Hypoparathyroidism is the most frequent complication of thyroidectomy, and its pathogenesis is multifactorial. The aim of this study is to evaluate the patient- and surgical-related risk factors for hypoparathyroidism after surgery for thyroid cancer. Methods: In this retrospective study, patients referred to surgery for thyroid cancer from 2016 to 2019 were enrolled. Preoperative serum calcium and parathyroid hormone (PTH) and postoperative 24 h PTH and calcium levels were evaluated. Demographic data, type of surgery, incidence of hypoparathyroidism and hypocalcemia were recorded for all the patients. Patients were divided into two groups based on post-operative PTH levels (≤12 and >12 pg/mL). Results: A total of 189 patients were enrolled in this study. There were 146 women (87.3%) and 43 men (22.7%), with a mean age of 51.3 years. A total of 79 patients (41.7%) underwent a neck dissection. A total of 59 patients (31.1%) had a postoperative PTH level < 12 pg/mL. Female sex, neck dissection, the yield of lymph node dissection and incidental parathyroidectomy were significantly associated with postoperative hypoparathyroidism. Incidental parathyroidectomy was reported in 44 (23.2%) patients and was correlated with younger age (<40 years) and neck dissection. There was no difference in the rate of post-operative hypocalcemia between patients with incidental parathyroidectomy and those without. Conclusions: Young patients undergoing neck dissection and with incidental parathyroidectomy have the highest risk of postoperative hypoparathyroidism after surgery for thyroid cancer. However, a large proportion of patients without incidental parathyroidectomy may have temporary hypocalcemia, suggesting that impaired blood supply of parathyroid glands during their identification and dissection may play a relevant role.

Assessing Intraoperative Laser Speckle Contrast Imaging of Parathyroid Glands in Relation to Total Thyroidectomy Patient Outcomes.

Background: Accurate assessment of parathyroid gland vascularity is important during thyroidectomy to preserve the function of parathyroid glands and to prevent postoperative hypocalcemia. Laser speckle contrast imaging (LSCI) has been shown to be accurate in detecting differences in parathyroid vascularity. In this surgeon-blinded prognostic study, we evaluate the relationship between intraoperative LSCI measurements and postoperative outcomes of total thyroidectomy patients. Methods: Seventy-two thyroidectomy patients were included in this study. After thyroid resection, an LSCI device was used to image all parathyroid glands identified, and a speckle contrast value was calculated for each. An average value was calculated for each patient, and the data were grouped according to whether the patient had normal (16-77 pg/mL) or low levels of parathyroid hormone (PTH) measured on postoperative day 1 (POD1). The aim of this study was to establish a speckle contrast threshold for classifying a parathyroid gland as adequately perfused and to determine how many such glands are required for normal postoperative parathyroid function. Results: A speckle contrast limit of 0.186 separated the normoparathyroid and hypoparathyroid groups with 87.5% sensitivity and 84.4% specificity: 7 of 8 patients with low PTH on POD1 had an average parathyroid speckle contrast above this limit, while 54 of 64 patients with normal postoperative PTH had an average parathyroid speckle contrast below this limit. Taking this value as the threshold for adequate parathyroid perfusion, it was determined that only one vascularized gland was needed for normal postoperative parathyroid function: 64 of 69 patients (92.8%) with at least one vascularized gland (determined by LSCI) had normal postoperative PTH, while all 3 patients (100%) with no vascularized glands had low postoperative PTH. Overall, the rates of temporary and permanent hypoparathyroidism in this study were 8.3% and 1.4%, respectively. Conclusions: LSCI is a promising technique for assessing parathyroid gland vascularity. It has the potential to help reduce the incidence of hypocalcemia after thyroidectomy by providing surgeons with additional information during surgery to aid in the preservation of parathyroid function.

Quantitative Detection of Parathyroid Hormone Using Europium Complex Doped Silica Nanoparticles.

Parathyroid hormone (PTH) is a hormone that plays a critical role in bone remodeling because it regulates the calcium levels. Either higher or lower than normal range of PTH release can cause serious metabolic disorders such as hyperparathyroidism or hypoparathyroidism. Therefore, the demand of highly sensitive monitoring sensor of PTH is on the rise. However, due to its presence of small size and low concentration in serum, the monitoring of a small change of PTH level is extremely difficult. In this article, we suggested the fabrication of europium complex doped nanoparticles conjugated with PTH antibodies for the sensitive fluorescence monitoring of PTH. For the synthesis of europium complex, 4,4,4-trifluoro-1-(2-naphthyl)-1,3-butanedione (NTA) and trioctylphosphine oxide (TOPO) are used to encapsulate europium. The amphiphilic polymer, polyvinylpyrrolidone (PVP), was applied to hydrophobic europium complex, and then silica shell was synthesized on the complex. Using the europium complex doped silica nanoparticles, we could obtain approximately 4.24-fold enhanced fluorescence in low levels of PTH in PBS, when compared to the conventional enzyme-linked immunosorbent assay (ELISA). In addition, we could obtain the sensitive PTH immunoassay in PTH spiked serum with high selectivity.

Daily calcium profile in diagnosis of hypo- and hypercalcemia in patients with chronic hypoparathyroidism. clinical case series

Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia and hyperphosphatemia, due to absent or inappropriately low serum parathyroid hormone (PTH) levels. The chronic postoperative hypoparathyroidism accounts approximately 75% of patients; the genetic, autoimmune or idiopathic forms are significantly less common. Today, chronic hypoparathyroidism remains the last major endocrine deficiency, for which hormonal replacement therapy has not found widespread use. Achieving the target levels of phosphorus-calcium metabolism is an important factor of the disease control, required for the prevention of short- and long-term complications. The standard therapy with active metabolites/analogues of vitamin D (­alfacalcidol, calcitriol) and calcium supplements does not always allow to achieve the target treatment goals. Despite high doses of calcium and active vitamin D, some patients suffer from unstable calcium levels and associated symptoms.The measurement of serum calcium and phosphorus in the early morning hours remains the main laboratory tests for such patients, but in sometimes this diagnostic approach does not really reflect the true picture.The presented clinical cases describe the changes of both hyper- and hypocalcemia within one day in patients with chronic postsurgical hypoparathyroidism managed by standard therapy.

Суточный профиль как диагностический инструмент выявления гипо- и гиперкальциемии у пациентов с хроническим гипопаратиреозом. серия клинических случаев

Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia and hyperphosphatemia, due to absent or inappropriately low serum parathyroid hormone (PTH) levels. The chronic postoperative hypoparathyroidism accounts approximately 75% of patients; the genetic, autoimmune or idiopathic forms are significantly less common. Today, chronic hypoparathyroidism remains the last major endocrine deficiency, for which hormonal replacement therapy has not found widespread use. Achieving the target levels of phosphorus-calcium metabolism is an important factor of the disease control, required for the prevention of short- and long-term complications. The standard therapy with active metabolites/analogues of vitamin D (­alfacalcidol, calcitriol) and calcium supplements does not always allow to achieve the target treatment goals. Despite high doses of calcium and active vitamin D, some patients suffer from unstable calcium levels and associated symptoms. The measurement of serum calcium and phosphorus in the early morning hours remains the main laboratory tests for such patients, but in sometimes this diagnostic approach does not really reflect the true picture. The presented clinical cases describe the changes of both hyper- and hypocalcemia within one day in patients with chronic postsurgical hypoparathyroidism managed by standard therapy.

Extensive Intracranial Calcification in A Case of Hypoparathyroidism Which Presented With Generalized Tonic-clonic Seizure: A Case Report

Hypoparathyroidism is an endocrine disorder that can be congenital or acquired. Generally, hypoparathyroidism is characterized by hypocalcemia, hyperphosphatemia, and low or abnormal levels of Parathyroid Hormone (PTH). It can be asymptomatic or symptomatic. The symptoms include seizures, paresthesia, depression, psychosis, extrapyramidal manifestations, and increased intracranial pressure. In this case study, we reported a 40-yearold male patient who was admitted to the emergency department with generalized tonicclonic movements and urine incontinency. Laboratory investigations revealed hypocalcemia, hyperphosphatemia, and low parathyroid hormone levels and in paraclinical studies, including Electroencephalography (EEG) and brain CT-scan, despite normal EEG, extensive intracranial calcification involving the basal ganglia, thalamus, white matter of the cerebral hemispheres, and subcortical area of the frontal and parietal lobes were observed on CT-scan.

Hypoparathyroidism Associated with the DNA Variants in Non-Coding Sequence Region of Calcium-Sensing Receptor

A stable narrow range of extracellular calcium concentration in the blood is essential for life. The calcium-sensing receptor (CaSR), a member of the G protein-coupled receptors family, is required to adjust the set point of blood extracellular calcium concentration, thus regulate parathyroid hormone (PTH) secretion and renal calcium excretion. Loss or gain function of CaSR mutations may result in either hyper- or hypocalcaemia. The CaSR activating mutations increase its sensitivity to extracellular ionized calcium (Ca2+). As consequence, PTH synthesis and secretion are suppressed continuously at normal ionized calcium concentrations. Patients display hypocalcaemia, hyperphosphatemia and lower levels of PTH. Urinary calcium excretion is increased due to the decreased circulating inappropriately PTH level and the activation of the renal tubular CaSR. Therefore, CaSR becomes a good potential clinical therapeutic target for hypoparathyroidism treatment. In order to define new drugs and improve medical management of hypoparathyroidism patients, this study attempts to identify new CaSR variants and analyse in detail the functional change of these CaSR variants, thus better understand the molecular mechanism involved. The study is based on collected hypoparathyroidism patients in our clinical site. In the study we enrolled in 10 patients, obtained all their clinical results and DNA results from seven patients. Our results indicated that the effect of serum intact PTH level correlated to change of serum Ca2+ and phosphate level. The CaSR carrying newly identified DNA variants displayed strong phosphorylation of phospholipase C and mitogen-activated protein kinases. Although the size of clinical cases need to be accumulated, current cases have showed a tendency that the identified multiple DNA variants in CaSR gene revealed an effect on the diagnostic criterion of the hypocalcaemic syndrome. It is undeniable that our research has certain limitations. So far, we tested several DNA variants at the same time, further functional examination for individual DNA variant would largely help to be better understand the mechanisms of CaSR regulation on extracellular calcium concentration.