COVID-19 infection with severe hypocalcaemia and superior mesenteric artery syndrome-a case report.

Background: Coronavirus disease 2019 (COVID-19) infection has been associated with various endocrinopathies. Few literatures have reported cases of transient hypoparathyroidism in acute COVID-19 infections, or even exacerbation of hypocalcaemia in previously known hypoparathyroidism patients. The mechanism of hypocalcaemia in COVID-19 infection remains unclear. Case Description: Our patient is a young gentleman who was incidentally diagnosed with superior mesenteric artery (SMA) syndrome and symptomatic primary hypoparathyroidism while presenting with an acute COVID-19 infection. He initially presented with high-grade fever, followed by multiple episodes of vomiting and abdominal pain and subsequently hypocalcaemic symptoms such as tonic-clonic seizures and carpopedal spasms. A computed tomographic scan of his abdomen revealed a SMA syndrome while his blood investigation showed a parathyroid hormone (PTH)-dependent hypocalcaemia. His SMA syndrome was a result of severe malnourishment and improved with refeeding, but his primary hypoparathyroidism persisted despite having recovered for 6 months from the initial COVID-19 infection. There was no evidence to suggest a congenital cause of hypoparathyroidism. Conclusions: To the best of our knowledge this is the first case report that describe this unique case of persistent primary hypoparathyroidism related to COVID-19 infection. Parathyroid gland involvement in a COVID-19 infection is rare but not impossible. Further studies are needed to determine the mechanism and extent of damage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the parathyroid glands.

Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial.

INTRODUCTION: Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitamin D and calcium) have an increased risk for renal dysfunction versus age- and sex-matched controls. Treatments that replace the physiologic effects of parathyroid hormone (PTH) while reducing the need for conventional therapy may help prevent a decline in renal function in this population. This post hoc analysis examined the impact of palopegteriparatide treatment on renal function in adults with chronic hypoparathyroidism. METHODS: PaTHway is a phase 3 trial of palopegteriparatide in adults with chronic hypoparathyroidism that included a randomized, double-blind, placebo-controlled 26-week period followed by an ongoing 156-week open-label extension (OLE) period. Changes in renal function over 52 weeks (26 weeks blinded + 26 weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60 mL/min/1.73 m2. RESULTS: At week 52, over 95% (78/82) of participants remained enrolled in the OLE and of those, 86% maintained normocalcemia and 95% achieved independence from conventional therapy (no active vitamin D and ≤ 600 mg/day of calcium), with none requiring active vitamin D. Treatment with palopegteriparatide over 52 weeks resulted in a mean (SD) increase in eGFR of 9.3 (11.7) mL/min/1.73 m2 from baseline (P < 0.0001) and 43% of participants had an increase ≥ 10 mL/min/1.73 m2. In participants with baseline eGFR < 60 mL/min/1.73 m2, 52 weeks of treatment with palopegteriparatide resulted in a mean (SD) increase of 11.5 (11.3) mL/min/1.73 m2 (P < 0.001). One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide. CONCLUSION: In this post hoc analysis of the PaTHway trial, palopegteriparatide treatment was associated with significantly improved eGFR at week 52 in addition to previously reported maintenance and normalization of serum and urine biochemistries. Further investigation of palopegteriparatide for the preservation of renal function in hypoparathyroidism is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT04701203.

Chronic hypoparathyroidism is caused by inadequate parathyroid hormone (PTH) levels. Hypoparathyroidism is managed with conventional therapy (active vitamin D and calcium), but over time the disease itself and conventional therapy can increase the risk of medical complications including kidney problems. This study looked at how a new treatment for chronic hypoparathyroidism, palopegteriparatide (approved in the European Union under the brand name YORVIPATH^®), affects kidney function in adults in the PaTHway clinical trial. Participants were randomly assigned to receive palopegteriparatide or a placebo injection once daily along with conventional therapy. For both groups, clinicians used a protocol to eliminate conventional therapy while maintaining normal blood calcium levels. After 26 weeks, participants on placebo switched to palopegteriparatide. Ninety-five percent of participants were still enrolled in the PaTHway trial after 52 weeks. Of those, 86% had normal blood calcium levels and 95% did not need conventional therapy (not taking vitamin D and not taking therapeutic doses of calcium [> 600 mg/day]). After 52 weeks of treatment with palopegteriparatide, significant improvements were seen in a measure of kidney function called estimated glomerular filtration rate (eGFR). Improvements in eGFR from the beginning of the trial to week 52 were considered clinically meaningful for over 57% of participants. In participants with impaired kidney function at the beginning of the trial, eGFR improvements were even greater, and 74% of participants had a clinically meaningful improvement. These results suggest that palopegteriparatide treatment may be beneficial for kidney function in adults with chronic hypoparathyroidism, especially those with impaired kidney function.

Feasibility and safety of modified en-bloc resection in endoscopic thyroid surgery via bilateral areolar approach - long-term institutional analysis ten years after surgery.

Purpose: This study aimed to introduce a new modified en-bloc resection method and evaluate its feasibility and safety in endoscopic thyroid surgery via bilateral areolar approach (BAA). Methods: Papillary thyroid carcinoma (PTC) patients who underwent lobectomy and ipsilateral central node dissection (CND) via the BAA approach were retrospectively reviewed. Their clinical characteristics and outcomes were evaluated, including operative duration, lymph node yield (LNY), surgical complications, recurrence rate, and metastasis rate, over a ten-year follow-up period. Simultaneous lobectomy and CND were performed in the modified en-bloc group, whereas lobectomy was performed first, followed by CND in the conventional group. Results: The study included 108 patients in the modified en-bloc group and 213 in the conventional group. There were no significant differences in gender, age, tumor locations, tumor dominant nodule size, or the incidence of concomitant Hashimoto thyroiditis when comparing clinicopathologic characteristics. The comparison of operative duration (P = 0.14), blood loss (P = 0.13), postoperative hospital stay (P = 0.58), incidence of transient vocal cord paralysis (P = 0.90) and hypocalcemia (P = 0.60) did not show any differences. The mean LNY achieved in the central compartment of the modified en-bloc group (7.5 ± 4.5) was significantly higher than that in the conventional group (5.6 ± 3.6). Two patients in the modified en-bloc group and two in the conventional group experienced metastasis after surgery during the ten-year follow-up (1.8% vs. 0.9%, P = 0.60). The learning curve analysis showed a significant decrease in operative duration after the 25-35th cases for modified en-bloc resection. Conclusions: The modified en-bloc resection method in endoscopic thyroid surgery via BAA is a technically feasible and safe procedure with excellent cosmetic outcomes for selective PTC patients.

Autosomal dominant hypercalciuric hypocalcaemia: the calcium-sensing receptor in renal calcium homeostasis and the impact of renal transplantation.

Calcium-sensing receptors (CaSRs) are G protein-coupled receptors that help maintain Ca2+ concentrations, modulating calciotropic hormone release (parathyroid hormone (PTH), calcitonin and 1,25-dihydroxyvitamin D) by direct actions in the kidneys, gastrointestinal tract and bone. Variability in population calcium levels has been attributed to single nucleotide polymorphisms in CaSR genes, and several conditions affecting calcium and phosphate homeostasis have been attributed to gain- or loss-of-function mutations. An example is autosomal dominant hypercalciuric hypocalcaemia, because of a missense mutation at codon 128 of chromosome 3, as reported in our specific case and her family. As a consequence of treating symptomatic hypocalcaemia as a child, this female subject slowly developed progressive end-stage kidney failure because of nephrocalcinosis and nephrolithiasis. After kidney transplantation, she remains asymptomatic, with decreased vitamin D and elemental calcium requirements, stable fluid and electrolyte homeostasis during intercurrent illnesses and has normalised urinary calcium and phosphate excretion, reducing the likelihood of hypercalciuria-induced graft impairment. We review the actions of the CaSR, its role in regulating renal Ca2+ homeostasis along with the impact of a proven gain-of-function mutation in the CaSR gene resulting in autosomal dominant hypercalciuric hypocalcaemia before and after kidney transplantation.

Economic burden of patients with post-surgical chronic and transient hypoparathyroidism in the United States examined using insurance claims data.

BACKGROUND: Hypoparathyroidism (HP) is a rare endocrine disease commonly caused by the removal or damage of parathyroid glands during surgery and resulting in transient (tHP) or chronic (cHP) disease. cHP is associated with multiple complications and comorbid conditions; however, the economic burden has not been well characterized. The objective of this study was to evaluate the healthcare resource utilization (HCRU) and costs associated with post-surgical cHP, using tHP as a reference. METHODS: This analysis of a US claims database included patients with both an insurance claim for HP and thyroid/neck surgery between October 2014 and December 2019. cHP was defined as an HP claim ≥ 6 months following surgery and tHP was defined as only one HP claim < 6 months following surgery. The cHP index date was the first HP diagnosis claim following their qualifying surgery claim, whereas the tHP index date was the last HP diagnosis claim following the qualifying surgery claim. Patients were continuously enrolled at least 1 year pre- and post-index. Patients' demographic and clinical characteristics, all-cause HCRU, and costs were descriptively analyzed. Total all-cause costs were calculated as the sum of payments for hospitalizations, emergency department, office/clinic visits, and pharmacy. RESULTS: A total of 1,406 cHP and 773 tHP patients met inclusion criteria. The average age (52.1 years cHP, 53.5 years tHP) and representation of females (83.2% cHP, 81.2% tHP) were similar for both groups. Neck dissection surgery was more prevalent in cHP patients (23.6%) than tHP patients (5.3%). During the 1-2 year follow-up period, cHP patients had a higher prevalence of inpatient admissions (17.4%), and emergency visits (26.0%) than the reference group -tHP patients (14.4% and 21.4% respectively). Among those with a hospitalization, the average number of hospitalizations was 1.5-fold higher for cHP patients. cHP patients also saw more specialists, including endocrinologists (28.7% cHP, 15.8% tHP), cardiologists (16.7% cHP, 9.7% tHP), and nephrologists (4.6% cHP, 3.3% tHP). CONCLUSION: This study demonstrates the increased healthcare burden of cHP on the healthcare system in contrast to patients with tHP. Effective treatment options are needed to minimize the additional resources utilized by patients whose HP becomes chronic.

Incidence of Post-Thyroidectomy Hypoparathyroidism and Associated Preoperative and Intraoperative Risk Factors.

INTRODUCTION: Thyroidectomy technique and extent are related to parathyroid injury and hypoparathyroidism. Total thyroidectomy is one of the most commonly performed endocrine surgeries, and the majority of patients recover completely without any complications. However, persistent hypoparathyroidism is the most prevalent long-term consequence following total thyroidectomy. While it is seldom deadly, it can cause severe morbidity for the patient and raise healthcare expenses. METHODS: This retrospective cohort study was conducted at King Abdulaziz Medical City, Jeddah, Saudi Arabia. We included all confirmed thyroid cancer cases that underwent thyroidectomy with or without neck dissection between July 2016 and August 2022. The data was collected from a chart review of the electronic medical record system (BEST-care), and a data collection sheet was utilized. SPSS version 26 was used to analyze the data. RESULTS: A total of 192 patients undergoing thyroid surgery were enrolled. One hundred forty-three (74.5%) were females and the mean age of participants was 45.29 ± 16.88 years. Most patients, 170 (88.5%), had a papillary histological type, and total thyroidectomy was performed in 150 (78.1%). A significant association was found between the type of surgery and postoperative hypoparathyroidism (p=<0.05*). In addition, hypocalcemia was seen in 147 (76.6%) of the patients. Postoperative hypoparathyroidism was significantly higher among patients who had asymptomatic postoperative hypocalcemia and those who received IV calcium gluconate (p=<0.05*). Moreover, postoperative hypocalcemia, hypomagnesemia, and hyperphosphatemia were significantly associated with postoperative hypoparathyroidism (p=<0.05*). CONCLUSION: The incidence of postoperative hypoparathyroidism is significantly higher among patients who underwent total thyroidectomy and had a normal level of preoperative parathyroid hormone (PTH) and magnesium (Mg) levels. Identifying these factors is a crucial step to minimize the occurrence of such complications.

Hypoparathyroidism: changes in brain structure, cognitive impairment, and reduced quality of life.

Hypoparathyroidism (HypoPT) is a disease with no/or inadequate production/secretion of parathyroid hormone (PTH) from the parathyroid glands. Low levels of PTH result in hypocalcemia, which is often treated with calcium supplementation and active vitamin-D analogs. However, increasing evidence suggests that HypoPT has a profound impact on several organ systems. Quality of life (QOL) is reduced in patients with HypoPT, partly due to symptoms related to the central nervous system-including subjective feelings of confusion, a reduced ability to focus and think clearly(i.e., "brain fog"). However, the extent to which these complex symptoms relate to quantifiable changes in patients' cognitive performance as determined by neuropsychological tests remains unclear. The brains of HypoPT patients may reveal tissue calcifications, but the extent to which long-term brain exposure to low PTH levels and/or changing calcium levels affects brain structure is unknown. In a cross-sectional study, we investigated PTH levels, QOL, cognitive impairment, and brain structure in well-treated post-surgical and non-surgical hypoparathyroid patients compared with healthy controls. QOL was quantified by the SF36v2, WHO-5 wellbeing Index, and two disease-specific questionnaires-the HPQ28 and Hypoparathyroidism Symptom Diary. Cognitive functions were tested using comprehensive neuropsychological. Brain structure was quantified by morphological analyses of MRI images. We found reduced QOL and cognitive functioning in terms of processing speed, executive functions, visual memory, and auditory memory in HypoPT. Furthermore, HypoPT revealed a reduced volume of the hippocampus-and the size of the thalamus in postsurgical patients was associated with the disease duration. Importantly, patients reporting severe brain fog had a smaller hippocampus than those with less brainfog. HypoPT is associated with quantifiable cognitive deficits and changes in brain structure that align with patient symptoms. Our exploratory study warrants further studies of the neurobiological impact of PTH and of the impact of PTH replacements therapy on patients' cognitive functioning.

Hypoparathyroidism (HypoPT) is a disease with insufficient or no production of Parathyroid hormone (PTH) from the parathyroid glands resulting in low plasma levels of PTH and calcium. One of the reported symptoms and complications of HypoPT is low quality of life (QOL) and mild impaired cognitive function, often described as "brain fog". We have compared patients with HypoPT and healthy controls in regard to QOL, cognitive function, and brain structure. We have used QOL questionnaires, neuropsychological tests, and Magnetic resonance imaging (MRI). We found a reduced QOL and cognitive function in patients with HypoPT. Furthermore, MRI showed a difference in brain structure, with a reduced volume of the hippocampus area, especially in those reporting severe symptoms of "brain fog". Disease duration was found to be associated with the size of the thalamus. Our study suggests that there might be an association between HypoPT patients' symptoms of cognitive deficits and changes in brain structure.

New insights into the vitamin D/PTH axis in endocrine-driven metabolic bone diseases.

BACKGROUND: Endocrine regulation of bone metabolisms is the focus of the "Skeletal Endocrinology" series of meetings. AIMS: To report on the outcome of the discussion on the role of vitamin D/PTH axis in endocrine osteopathies held during the 10th Skeletal Endocrinology Meeting which took place in Stresa (Italy) in March 2023. OUTCOMES: Vitamin D/PTH axis has relevant influence on several outcomes in the general population and in patients affected by endocrinopathies such as hypoparathyroidism and secreting pituitary adenomas. CONCLUSIONS: Assessing the status of the vitamin D/PTH axis and using vitamin D and PTH as therapeutic agents is mandatory in several endocrine-related bone metabolic conditions.

PTH and adiposity.

Although PTH is best known for its role as a regulator of skeletal remodelling and calcium homeostasis, more recent evidence supports a role for it in energy metabolism and other non-classical targets. In this report, we summarize evidence for an effect of PTH on adipocytes. This review is based upon all peer-reviewed papers, published in the English language with PubMed as the primary search engine. Recent preclinical studies have documented an effect of PTH to stimulate lipolysis in both adipocytes and liver cells and to cause browning of adipocytes. PTH also reduces bone marrow adiposity and hepatic steatosis. Although clinical studies are limited, disease models of PTH excess and PTH deficiency lend support to these preclinical findings. This review supports the concept of PTH as a polyfunctional hormone that influences energy metabolism as well as bone metabolism.

Parathyroid hormone controls skeletal and circulating calcium levels. Its secretion by the 4 parathyroid glands is regulated primarily by the concentration of the ionized calcium level. The other major target organ for parathyroid hormone is the kidney where it conserves filtered calcium by effects on the renal tubules. While bone and the kidney are indisputably the main target organs for PTH, recent studies are pointing to systems and organs that can be shown also to respond to PTH. One of these systems that PTH appears to target is fat cells, an important storehouse for energy. This review summarizes what is known about PTH's effects to stimulate the production of energy from fat cells when present in excess or to reduce the production of energy when deficient.

Continuous Subcutaneous Delivery of rhPTH(1-84) and rhPTH(1-34) by Pump in Adults With Hypoparathyroidism.

Context: Continuous subcutaneous infusion of recombinant parathyroid hormone (rhPTH) through a pump has been proposed as a therapeutic alternative for patients with chronic hypoparathyroidism who remain symptomatic or hypercalciuric on conventional treatment (calcium and active vitamin D) or daily injections of rhPTH(1-84) or rhPTH(1-34). However, the real-world evidence of the outcome of this novel therapy is limited. Case Descriptions: We report the clinical and biochemical outcomes of 12 adults with hypoparathyroidism (11 women, age 30-70 years, and 1 man, age 30 years) from 3 different clinical sites in the United States who were transitioned from conventional therapy to daily injections of rhPTH(1-84) or rhPTH(1-34) and then switched to continuous administration of rhPTH(1-84)/rhPTH(1-34) via pump therapy. In most patients, mean serum calcium concentrations increased while on PTH pump therapy compared with both conventional therapy (in 11 patients) and single/multiple daily rhPTH injections (in 8 patients). Despite this, 10 patients had lower median 24-hour urinary calcium levels while on PTH pump therapy compared with prior therapy (mean ± SD difference: -130 ± 222 mg/24 hours). All patients reported a qualitative decrease in hypocalcemic symptoms while receiving pump therapy. Three patients had pod failure at least once, and 1 patient developed an infusion site reaction. Conclusion: In this case series of 12 patients with chronic hypoparathyroidism treated with rhPTH(1-84)/rhPTH(1-34) administered via a pump, improvement in clinical and biochemical parameters were observed in the majority of the patients. Our observations indicate benefits of pump administration of rhPTH that warrant further investigation.

Hypomagnesemia with Secondary Hypoparathyroidism and Hypocalcemia due to Novel Variants in the Transient Receptor Potential Cation Channel Subfamily M Member 6 ( TRPM6 ) Gene.

HOMG1 (hypomagnesemia 1, intestinal) or hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder of magnesium metabolism, characterized by impaired magnesium absorption. This disorder may mimic other conditions presenting with neonatal seizures. Here, we report an infant diagnosed to have hypomagnesemia with secondary hypocalcemia due to novel variants in TRPM6 gene.

Quality of life in patients with hypoparathyroidism receiving standard treatment: an updated systematic review.

PURPOSE: Hypoparathyroidism is defined by hypocalcemia with inappropriately normal or low parathyroid hormone levels. The current standard treatment consists of lifelong calcium and/ or vitamin D supplementation. Even while on stable treatment regimens, hypoparathyroid patients might still suffer from symptoms that can negatively impact their quality of life. METHODS: A systematic literature review to identify the current knowledge regarding quality of life in patients with hypoparathyroidism receiving standard treatment was performed on November 1st, 2023. PubMed as well as Web of Science were searched. The systematic review is registered in PROSPERO (#CRD42023470924). RESULTS: After removal of duplicates, 398 studies remained for title and abstract screening, after which 30 were included for full-text screening. After exclusion of seven studies with five studies lacking a control population, one using a non-validated questionnaire, and one being a subsample of the larger included study, 23 studies were included in this systematic review. The majority of the included studies used a guideline-conform definition of hypoparathyroidism, and the SF-36 was the most often applied tool. Almost all studies (87%) reported statistically significantly lower scores in at least one quality of life domain compared to a norm population or controls. CONCLUSION: Patients with hypoparathyroidism receiving standard treatment report impairments in quality of life. The reasons for these impairments are probably multifaceted, making regular monitoring and the inclusion of various professionals necessary.

Further delineation of phenotype and genotype of Kenny-Caffey syndrome type 2 (phenotype and genotype of KCS type 2).

BACKGROUND: Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare inherited disorder characterized by proportionate short stature, skeletal defects, ocular and dental abnormalities, and transient hypocalcemia. It is caused by variants in FAM111A gene. Diagnosis of KCS2 can be challenging because of its similarities to other syndromes, the absence of clear hallmarks and the deficient number of genetically confirmed cases. Here, we aimed to further delineate and summarize the genotype and phenotype of KCS2, in order to get a better understanding of this rare disorder, and promote early diagnosis and intervention. METHODS: We present clinical and genetic characteristics of eight newly affected individuals with KCS2 from six families, including one family with three individuals found to be a father-to-daughter transmission, adding to the limited literature. Furthermore, we performed a review of genetically confirmed KCS2 cases in PubMed, MEDLINE and CNKI databases. RESULTS: There were six females and two males in our cohort. All the patients presented with short stature (100.0%). Clinical manifestations included ocular defects such as hypermetropia (5/8), dental problems such as defective dentition (3/8) and dental caries (3/8), skeletal and brain anomalies such as delayed closure of anterior fontanelle (6/8), cerebral calcification (3/8), cortical thickening (3/8) and medullary stenosis (4/8) of tubular bones. Endocrinologic abnormalities included hypoparathyroidism (5/8) and hypocalcemia (3/8). One male patient had micropenis and microorchidism. All cases harboured missense variants of FAM111A, and nucleotides c.1706 arose as a mutational hotspot, with seven individuals harbouring a c.1706G>A (p.Arg569His) variant, and one child harbouring a c.1531T>C (p.Tyr511His) variant. Literature review yielded a total of 46 patients from 20 papers. Data analysis showed that short stature, hypoparathyroidism and hypocalcemia, ocular and dental defects, skeletal features including cortical thickening and medullary stenosis of tubular bones, and seizures/spasms were present in more than 70% of the reported KCS2 cases. CONCLUSION: We provide detailed characteristics of the largest KCS2 group in China and present the first genetically confirmed instance of father-to-daughter transmission of KCS2. Our study confirms that Arg569His is the hot spot variant and summarizes the typical phenotypes of KCS2, which would help early diagnosis and intervention.

Coronary calcium score in patients with post-surgical hypoparathyroidism.

Objective: This study aimed to evaluate the cardiovascular risk of patients with post-surgical hypoparathyroidism through coronary calcium score (CACS) evaluation andcardiovascular risk calculators. Subjects and methods: Patients with post-surgical hypoparathyroidism (HG = 29) were compared to a control group (CG = 29), matched by sex and age. Demographic and clinical data were captured by a questionnaire or patient files. Both groups performed a thoracic-computed tomography to evaluate the CACS and the cardiovascular risk was calculated by two risk calculators. Results: In the HG, the supplementation of calcium varied between 500 to 2,000 mg/day and the mean calcitriol was 0.5 ± 0.29 mcg/day. The mean serum calcium and phosphorus were 8.32 ± 0.68 and 4.92 ± 0.87 mg/dL, respectively, and in the range recommended for hypoparathyroidism. The Brazilian Society of Cardiology's risk calculator showed a difference among groups, with no patient in the HG with low risk, but the CACS was similar. A positive CACS in the HG was associated with obesity and high BMI but not with calcium and/or vitamin D supplementation. Conclusion: In conclusion, patients with hypoparathyroidism did not show increased CACS, and it was not related to supplementation.

Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone.

The conventional treatment of hypoparathyroidism (HypoPT) includes active vitamin D and calcium. Despite normalization of calcium levels, the conventional treatment is associated with fluctuations in calcium levels, hypercalciuria, renal impairment, and decreased quality of life (QoL). Replacement therapy with parathyroid hormone (PTH)(1-84) is an option in some countries. However, convincing beneficial effects have not been demonstrated, which may be due to the short duration of action of this treatment. Recently, palopegteriparatide (also known as TransCon PTH) has been marketed in Europe and is expected also to be approved in other countries. Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable physiological PTH levels for 24 hours/day. A phase 3 study demonstrated maintenance of normocalcemia in patients with chronic HypoPT, with no need for conventional therapy. Furthermore, this treatment lowers urinary calcium and improves QoL. Another long-acting PTH analog with effects on the parathyroid hormone receptor (eneboparatide) is currently being tested in a phase 3 trial. Furthermore, the treatment of autosomal dominant hypocalcemia type 1 with a calcilytic (encaleret) is also being tested. All in all, improved treatment options are on the way that will likely take the treatment of HypoPT to the next level.

Recalcitrant Hypocalcemia: Postsurgical Hypoparathyroidism Exacerbated by a Chyle Leak Treated With Octreotide.

Background/Objective: To report a case of recalcitrant post-surgical hypocalcemia caused by hypoparathyroidism complicated by a chyle leak and octreotide use. Case Report: A man in his 60s with a 4-month history of voice changes, 10-pound weight loss, and a right-sided neck mass presented with difficulty breathing for 1 week. He had a right laryngeal/hypopharyngeal mass, which was biopsied. Pathology results were positive for invasive squamous cell carcinoma. He underwent an extensive neck surgery, including total thyroidectomy. Postsurgical laboratory results revealed serum corrected calcium of 7.6 mg/dL (ref 8.0-10.2 mg/dL) and parathyroid hormone <6.3 pg/mL (ref. 10-65). Despite treatment with calcium carbonate 12 g (elemental) daily, calcitriol and hydrochlorothiazide, his corrected serum calcium levels remained low. Patient also had a chyle leak that was treated with octreotide. Resolution of his hypocalcemia occurred after substitution of calcium carbonate with calcium citrate, cessation of octreotide, and management of the chyle leak. Discussion: Our patient likely developed recalcitrant hypocalcemia from: 1) postsurgical hypoparathyroidism, 2) a chyle leak, and 3) the use of octreotide. Administration of octreotide to seal the chyle leak most likely decreased gastric acid production and contributed to decrease in absorption of calcium carbonate. Oral calcium citrate may be better absorbed in this case. Conclusion: Postsurgical hypoparathyroidism can lead to hypocalcemia. This case is unique in that the patient's chyle leak and the use of octreotide contributed to recalcitrant hypocalcemia.

Exploring Multiple Endocrinological Issues and Dysautonomia in a Rare Case: Hypoparathyroidism in MIRAGE Syndrome.

MIRAGE syndrome is a rare multisystemic disorder characterized by various manifestations, such as myelodysplasia, susceptibility to infections, growth retardation, adrenal hypoplasia, genital anomalies, and enteropathy. In the literature, there have been rare cases of dysautonomia. We present a 6.5-year-old girl, who was first admitted to our department with short stature. On follow up, she exhibited multiple endocrinological issues, including transient hypothyroidism, primary hypoparathyroidism and dysautonomia, along with multisystem involvement. Further investigations revealed recurrent moniliasis, low IgM levels, and transient monosomy 7 in the bone marrow. Whole exome sequencing revealed a heterozygous pathogenic variant of SAMD9 (c.2159del; p.Asn720ThrfsTer35). Additional complications observed during follow-up included medullary nephrocalcinosis, hypomagnesemia, hypermagnesiuria, hypophosphatemia, decreased glomerular filtration rate, and nephrotic proteinuria. The patient also developed hyperglycemia, which was managed with low-dose insulin. This case highlights the diagnostic challenges and the diverse phenotypic presentation observed in MIRAGE syndrome.

Brain Calcifications Secondary to Idiopathic Hyperthyroidism and Hypoparathyroidism.

Background: Thyroid and parathyroid hormones are essential components of the metabolic system and its regulation. Concurrent hyperthyroidism with hypoparathyroidism is an extremely rare finding and is not considered a common etiology of brain calcifications seen on imaging. Brain calcifications can cause a range of neurologic symptoms, including movement disorders, cognitive impairment, and seizures. Prompt recognition and treatment of hypoparathyroidism are essential to prevent or minimize the development of brain calcifications and associated neurologic symptoms. Case Report: A 39-year-old female presented to the emergency department in an unconscious state with generalized weakness and tonic-clonic seizures for 1 day. On clinical examination, she had jerky movements of her upper limbs, and her Glasgow Coma Scale score was 4/15. Supporting hypoparathyroidism, she had low levels of serum parathyroid hormone, calcium, and vitamin D and a high level of serum phosphorus. Her magnesium level was normal. Thyroid profile revealed hyperthyroidism. Noncontrast-enhanced computed tomography scan at the midbrain level showed multiple bilateral hyperintense areas in the basal ganglia and thalami suggestive of calcifications. The patient was treated with calcium and vitamin D supplements and antithyroid agents that successfully resolved her symptoms. Conclusion: This case provides important documentation for including hypocalcemia as a result of hypoparathyroidism in the differential diagnosis of patients with seizures. The treatment approach used with our patient can be considered for managing seizures in cases where the underlying cause is challenging to identify. This case highlights the importance of a thorough evaluation and individualized treatment plan for patients with seizures.

Hypoparathyroidism Revealed by Unsuccessful Anti-epileptic Therapy.

Pediatric hypoparathyroidism is an uncommon endocrine disease that can be either isolated or syndromic. It occurs when the secretion of parathormone is insufficient to maintain normal levels of ionized calcium. Patients with hypoparathyroidism can exhibit cerebral calcifications and metabolic disorders, and the severity of such features is inversely correlated with hypocalcemia. We report a case of a 13-year-old patient who was initially diagnosed with epilepsy by another medical team two years before her admission to our hospital and who was subjected to oral valproate therapy. The anti-epileptic therapy proved to be unsuccessful even with increasing doses. The diagnosis was corrected when we performed adequate biological investigations. This case is underlying the importance of the electrolytes profile, especially the serum phosphocalcic test, in the management of patients with new onset or recurrent epileptic seizures.