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 (ie, "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 magnetic resonance imaging 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.

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.

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.

Assessing Postoperative Phosphate and Calcium/Phosphate Ratio as Surrogates for Parathyroid Hormone Following Total Thyroidectomy.

OBJECTIVE: Evaluate utility of postoperative phosphate and calcium/phosphate ratio (Ca/P) as surrogates for parathyroid hormone (PTH) following total thyroidectomy. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital. METHODS: We retrospectively reviewed patients 18 years or older who underwent total thyroidectomy in a tertiary care hospital by a single surgeon from 2015 through 2021. Patients with incomplete data, pre-existing hypoparathyroidism, vitamin D deficiency, or renal failure were excluded. All patients had PTH drawn within 4 hours of surgery and serum calcium, albumin, and phosphate levels on postoperative Day 1. Corrected calcium was used to calculate a Ca/P. Receiver operating characteristic (ROC) curves were generated to compare phosphate level or Ca/P with PTH. Each possible surrogate was assessed relative to PTH cutoffs of less than 5, 10, 15, and 20 pg/mL. A good screening test was defined as having an area under the curve (AUC) greater than 0.8. RESULTS: A total of 185 patients underwent total thyroidectomy with 1 fellowship-trained otolaryngologist. Most patients were female (62%), median age 48 years. Most surgeries were performed for cancer (68%). Six (3.2%) patients required IV calcium supplementation and 2 (1.1%) required readmission for symptomatic hypocalcemia. ROC curves comparing phosphate and Ca/P to PTH at the listed cutoffs demonstrated AUC ranging from 0.55 to 0.66 and 0.61 to 0.79, respectively. None met the threshold for a good screening test. CONCLUSION: Postoperative phosphate and Ca/P ratio are not surrogates for PTH levels following total thyroidectomy. More research is needed to identify cost-effective strategies for postoperative calcium monitoring in patients undergoing total thyroidectomy. LEVEL OF EVIDENCE: Retrospective cohort study.

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.

The application of autofluorescence system contributes to the preservation of parathyroid function during thyroid surgery.

PURPOSE: The purpose of this study was to investigate the impact of autofluorescence technology on postoperative parathyroid function and short-term outcomes in patients undergoing thyroid surgery. METHODS: A total of 546 patients were included in the study, with 287 in the conventional treatment group and 259 in the autofluorescence group. Both groups underwent central lymph node dissection, which is known to affect parathyroid function. Short-term outcomes, including rates of postoperative hypocalcemia and parathyroid dysfunction, serum calcium and PTH levels on the first postoperative day, as well as the need for calcium supplementation, were analyzed. A multivariable analysis was also conducted to assess the impact of autofluorescence on postoperative parathyroid dysfunction, considering factors such as age, BMI, and preoperative calcium levels. RESULTS: The autofluorescence group demonstrated significantly lower rates of postoperative hypocalcemia and parathyroid dysfunction compared to the conventional treatment group. The autofluorescence group also had better serum calcium and PTH levels on the first postoperative day, and a reduced need for calcium supplementation. Surprisingly, the use of autofluorescence technology did not prolong surgical time; instead, it led to a shorter hospitalization duration. The multivariable analysis showed that autofluorescence significantly reduced the risk of postoperative parathyroid dysfunction, while factors such as age, BMI, and preoperative calcium levels did not show a significant correlation. CONCLUSION: This study provides evidence that autofluorescence technology can improve the preservation of parathyroid function during thyroid surgery, leading to better short-term outcomes and reduced postoperative complications. The findings highlight the potential of autofluorescence as a valuable tool in the management of parathyroid hypofunction. Further research and validation are needed to establish the routine use of autofluorescence technology in the thyroid.

Endocrine manifestations in adults with 22q11.2 deletion syndrome: a retrospective single-center cohort study.

INTRODUCTION AND OBJECTIVE: Patients with the 22q11.2 deletion syndrome (22q11DS) frequently display cardiological and psychiatric diseases, but are also at increased risk for endocrine manifestations. The aim of this study was to evaluate the screening, prevalence, and management of hypoparathyroidism and thyroid disease in patients with 22q11DS, to evaluate the metabolic profile, and to compare these results with current literature and guidelines. DESIGN: We performed a retrospective study of patients with genetically confirmed 22q11DS, followed at the center for human genetics of the University Hospitals Leuven, resulting in a cohort of 75 patients. Medical history, medication, and laboratory results concerning hypoparathyroidism, thyroid dysfunction, and the metabolic profile were collected. RESULTS: Of the total cohort, 26 patients (35%) had at least one hypocalcaemic episode. During hypocalcaemia, parathyroid hormone (PTH) was measured in only 12 patients with 11 having normal or low PTH, confirming a diagnosis of hypoparathyroidism. Recurrent episodes of hypocalcaemia occurred in seventeen patients (23%). Adherence to the guidelines was low, with 13% of patients having a yearly serum calcium evaluation, 12% receiving daily calcium supplements, and 20% receiving non-active vitamin D. Hypothyroidism was present in 31 patients (44%) and hyperthyroidism in 6 patients (8%). Information on body mass index (BMI) was available in 52 patients (69%), of which 38% were obese (BMI ≥ 30 kg/m2). CONCLUSION: Hypoparathyroidism, hypothyroidism, and obesity are common endocrine manifestations in patients with 22q11DS but are probably underdiagnosed and undertreated, indicating the need for multidisciplinary follow-up including an endocrinologist.

Comparison of indocyanine green angiography vs intraoperative parathyroid hormone in early prediction of risk of post-thyroidectomy hypocalcemia: a prospective cohort study.

Introduction: Indocyanine green (ICG) angiography is the 'real-time intraoperative imaging' technique used to reduce the chances of hypoparathyroidism in post-thyroidectomy patients. In our study, the authors predicted the risk of early post-thyroidectomy hypocalcemia by intraoperative evaluation of parathyroid gland perfusion by ICG angiography. Materials and methods: In patients who underwent total thyroidectomy, ICG angiography was done using the SPY PHI imaging system (Stryker). Post-thyroid specimen removal, scoring of parathyroids was done in spy contrast mode. All 4 or <4 visualized parathyroids were scored for vascularity with the highest score of 8. Serum ionized calcium was done 6 h postsurgery and on the morning and evening of postoperative days 1 and 2. Calcium supplements were given to only those who developed clinical or severe biochemical hypocalcemia. Results: Out of 60, postoperative hypocalcemia was noted in 41 patients. Total ICG score ≤5 was seen in 34 patients, out of which 28 developed postoperative hypocalcemia showing PPV 82.3% and diagnostic accuracy of 68.3% while iPTH (4.28 pmol/l) showed PPV 76.7 and diagnostic accuracy 70 %. In eight patients, none of the glands was scored as 2 (White) and all these patients developed hypocalcemia requiring calcium infusion. Conclusion: The absence of visualization of at least 1 well-perfused (score 2) gland on ICG angiography is highly predictive of hypocalcemia and the majority of patients with total ICG score ≤5 developed hypocalcemia in the immediate postoperative period. ICG is a good predictor of the absence of hypoparathyroidism after thyroidectomy and is comparable to iPTH in the prediction of post-thyroidectomy hypocalcemia.

Dilated cardiomyopathy in patients with hypoparathyroidism: A narrative review.

Background: Hypoparathyroidism is a rare endocrine disorder characterized by low blood calcium levels, elevated phosphorus levels, and insufficient parathyroid hormone production. It can lead to dilated cardiomyopathy (DCM), a cardiac condition characterized by enlarged ventricles and reduced heart function. This review aims to explore the relationship between hypoparathyroidism and DCM, the impact of calcium on cardiac function, and the potential for DCM reversal with calcium supplementation. Methods: A comprehensive literature search was conducted using PubMed, Google Scholar, and relevant keywords and Mesh terms. Case reports evaluating dilated cardiomyopathy in patients with Hypoparathyroidism were included in the study. Additionally, references cited in each study were carefully examined to identify relevant reports. The cases included in the review were analyzed, and common cardiac manifestations, diagnostic approaches, and management were identified. Results: DCM in hypoparathyroidism presents with symptoms of heart failure, reduced ejection fraction, and impaired left ventricular function. Laboratory tests show low serum calcium levels and elevated phosphate levels. Prompt diagnosis and treatment with calcium and vitamin D supplementation can lead to improvements in cardiac function. Conclusion: Hypoparathyroidism-induced DCM is reversible with timely calcium and vitamin D supplementation. Patient compliance with prescribed medications and supplements is crucial to prevent and manage cardiac complications. Regular follow-up check-ups and monitoring of calcium levels can aid in early detection and improve patient outcomes. Educating patients about the importance of treatment adherence can significantly reduce the risk of developing DCM and other cardiac symptoms associated with hypoparathyroidism. Routine follow-up of DCM among patients with endocrine disorders is recommended.

Hypocalcemia in combination with hyperphosphatemia impairs muscle cell differentiation in vitro.

PURPOSE: Hypoparathyroidism is a rare endocrine disorder characterized by low or absent secretion of parathyroid hormone (PTH), which leads to decreased calcium and increased phosphorus levels in the serum. The diagnosis of hypoparathyroidism is based on the identification of the aforementioned biochemical abnormalities, which may be accompanied by clinical manifestations. Symptoms of hypoparathyroidism, primarily attributed to hypocalcemia, include muscle cramps or spasms, facial, leg, and foot pain, seizures, and tingling in the lips or fingers. The treatment of hypoparathyroidism depends on the severity of symptoms and the underlying pathology. Over the long term, calcium supplements, active vitamin D analogs, and thiazide diuretics may be needed. In fact, in patient cohorts in which optimal disease control still remains elusive, replacement therapy with recombinant parathyroid hormone analogs may be contemplated. Despite the predominantly neuromuscular symptoms of hypoparathyroidism, further effects of parathyroid hormone deficiency at the muscle cell level remain poorly understood. Thus, the aim of our study was to evaluate the effects of hypocalcemia in combination with hyperphosphatemia on muscle cells differentiation in vitro. METHODS: C2C12 cells, an in vitro model of muscle cells, were differentiated for 2 or 6 days in the presence of hypocalcemia (CaCl2 0.9 mmol/l) and moderate (PO4 1.4 mmol/l) or severe (PO4 2.9 mmol/l) hyperphosphatemia, or combinations of both conditions. Cell differentiation and expression of genes linked to muscle differentiation were evaluated. RESULTS: The combination of hypocalcemia with hyperphosphatemia induced a significant reduction (50%) in differentiation marker levels, such as MyoD (protein 1 for myoblast determination) and myogenin on the 1st day of differentiation, and MHC (myosin heavy chains) after 6 days of differentiation compared to control. Furthermore, this condition induced a statistically significant reduction of insulin-like growth factor-1 (IGF-1) mRNA expression and inhibition of IGF signaling and decrease in ERK phosphorylation compared to control cells. CONCLUSIONS: Our results showed that a condition of hypocalcemia with hyperphosphatemia induced an alteration of muscle cell differentiation in vitro. In particular, we observed the reduction of myogenic differentiation markers, IGF-1 signaling pathway, and ERK phosphorylation in differentiated skeletal myoblasts. These data suggest that this altered extracellular condition might contribute to the mechanisms causing persistence of symptoms in patients affected by hypoparathyroidism.

Extended Treatment With Recombinant Human Parathyroid Hormone (1-84) in Adult Patients With Chronic Hypoparathyroidism.

OBJECTIVE: Recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) is efficacious in patients with hypoparathyroidism but additional data supporting its prolonged use are needed. We evaluated whether efficacy, safety, and tolerability are maintained during long-term rhPTH(1-84) treatment of patients with chronic hypoparathyroidism. METHODS: This was a phase 4, single-center, open-label, single-arm, 3-year extension (NCT02910466) of the phase 3 Hypo Extended (HEXT) study (NCT01199614). Patients self-administered rhPTH(1-84) once daily by subcutaneous injection, with doses individualized based on clinical parameters. Albumin-adjusted serum calcium levels (primary outcome measure), other disease biomarkers, health-related quality of life, and safety of rhPTH(1-84) were assessed using descriptive statistics. RESULTS: All patients (n = 39) had been exposed to rhPTH(1-84) (mean exposure [SD] 8.5 [3.5] years) before the start of the study, resulting in a mean exposure of 10.8 years including the present study. Mean patient age was 51.9 years, 79.5% were female, and 97.4% were White. Mean albumin-adjusted serum calcium concentrations were within the target range, and mean serum phosphate, serum calcium-phosphate product, and 24-hour urinary calcium excretion levels were within reference ranges at end of treatment. Mean doses of supplemental calcium and active vitamin D were maintained throughout the study. Bone turnover marker levels were maintained from baseline to end of treatment. No clinically relevant changes in bone mineral density were observed. Patient-reported health-related quality-of-life scores were generally maintained throughout the study. Four adverse events were considered treatment related and no new safety signals were identified. CONCLUSION: The effects of rhPTH(1-84) on biochemical, skeletal, and health-related quality-of-life parameters did not wane with extended use.

Management of Postthyroidectomy Hypoparathyroidism and Its Effect on Hypocalcemia-Related Complications: A Meta-Analysis.

OBJECTIVE: The aim of this Meta-analysis is to evaluate the impact of different treatment strategies for early postoperative hypoparathyroidism on hypocalcemia-related complications and long-term hypoparathyroidism. DATA SOURCES: Embase.com, MEDLINE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and the top 100 references of Google Scholar were searched to September 20, 2022. REVIEW METHODS: Articles reporting on adult patients who underwent total thyroidectomy which specified a treatment strategy for postthyroidectomy hypoparathyroidism were included. Random effect models were applied to obtain pooled proportions and 95% confidence intervals. Primary outcome was the occurrence of major hypocalcemia-related complications. Secondary outcome was long-term hypoparathyroidism. RESULTS: Sixty-six studies comprising 67 treatment protocols and 51,096 patients were included in this Meta-analysis. In 8 protocols (3806 patients), routine calcium and/or active vitamin D medication was given to all patients directly after thyroidectomy. In 49 protocols (44,012 patients), calcium and/or active vitamin D medication was only given to patients with biochemically proven postthyroidectomy hypoparathyroidism. In 10 protocols (3278 patients), calcium and/or active vitamin D supplementation was only initiated in case of clinical symptoms of hypocalcemia. No patient had a major complication due to postoperative hypocalcemia. The pooled proportion of long-term hypoparathyroidism was 2.4% (95% confidence interval, 1.9-3.0). There was no significant difference in the incidence of long-term hypoparathyroidism between the 3 supplementation groups. CONCLUSIONS: All treatment strategies for postoperative hypocalcemia prevent major complications of hypocalcemia. The early postoperative treatment protocol for postthyroidectomy hypoparathyroidism does not seem to influence recovery of parathyroid function in the long term.

Coronary calcium score in patients with post-surgical hypoparathyroidism

ABSTRACT Objective: This study aimed to evaluate the cardiovascular risk of patients with post-surgical hypoparathyroidism through coronary calcium score (CACS) evaluation and cardiovascular 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.

Endocrinopathies in beta thalassemia: a narrative review.

Beta thalassemia is the most common genetic blood disorder, characterized by reduced production or complete absence of beta-globin chains. The combination of systematic red blood cell transfusion and iron chelation therapy is the most readily available supportive treatment and one that has considerably prolonged the survival of thalassemia patients. Despite this, the development of endocrine abnormalities correlated with beta thalassemia still exists and is mostly associated with iron overload, chronic anemia, and hypoxia. A multifactorial approach has been employed to investigate other factors involved in the pathogenesis of endocrinopathies, including genotype, liver disease, HCV, splenectomy, socioeconomic factors, chelation therapy, and deficiency of elements. The development of specific biomarkers for predicting endocrinopathy risk has been the subject of extensive discussion. The objective of the present narrative review is to present recent data on endocrinopathies in beta thalassemia patients, including the prevalence, the proposed pathogenetic mechanisms, the risk factors, the diagnostic methods applied, and finally the recommended treatment options.

Early-onset Chronic Keratitis as the First Presenting Component of Autoimmune Polyendocrinopathy Syndrome Type 1 (APS-1): A Case Report and Review of the Literature.

Autoimmune polyendocrine syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare monogenic autosomal recessive autoimmune disease. It is caused by mutations in the autoimmune regulator (AIRE) gene. APS-1 is diagnosed clinically by the presence of two of the three major components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and primary adrenocortical insufficiency. A 3.3-year-old girl was presented with a carpopedal spasm to the pediatric emergency clinic. She had a history of recurrent keratitis, and chronic candidiasis as urinary tract infections and oral thrashes. Hypoparathyroidism (HPT) was diagnosed based on low serum concentrations of calcium and parathyroid hormone and elevated serum concentrations of phosphate, and treatment with calcium and calcitriol supplementation was started. Genetic testing revealed homozygosity for nonsense c.769C>T (p.R257X) mutation in exon 6 in the AIRE gene which was reported previously. At the age of 5.6 years, she was presented with an adrenal crisis, and treatment with hydrocortisone and fludrocortisone was started. The reported case highlights that unexplained chronic keratitis in children may be the first and most severe component of this syndrome. The classic triad of APS-1 may also appear in the first decade of life.

Incidence of post-surgical hypoparathyroidism (POSH) after total thyroidectomy.

Post-surgical hypoparathyroidism (POSH) is a recognised complication of total thyroidectomy, leading to hypocalcaemia and its associated adverse effects. This retrospective study aimed to determine the incidence of POSH and identify perioperative predictors for its development. Data from patients who underwent total or completion thyroidectomy between January 2017 and July 2022 were retrospectively analysed. The incidence of POSH was assessed, and patients were categorised into transient or prolonged POSH at six months postoperatively. Potential predictors for POSH were investigated including gender, histological diagnosis, and preoperative thyroid function. A total of 133 adult patients were included in the study. The incidence of patients recovering from transient POSH within six months was 15%, and 5% had prolonged POSH beyond six months of surgery. Parathyroid hormone (PTH) levels normalised in 83% of prolonged POSH patients within 14-33 months, reducing the incidence of persistent POSH to 0.75%. Despite normal PTH levels, overall, 3% had persistent marginally low calcium levels (mean 2.11 mmol/L) in keeping with relative parathyroid insufficiency. Histological diagnosis of malignancy was the only significant risk factor for both transient and prolonged POSH (RR 2.95, CI 1.54 to 5.67, p = 0.001) in this cohort. Cautious capsular dissection during thyroidectomy and protection of the parathyroid glands and vascular supply produce a low incidence of POSH. Although the vast majority of patients with POSH recover after six months, hypocalcaemia may persist due to relative parathyroid insufficiency, requiring long-term calcium supplementation. Further research is needed to determine the best strategies for preventing and treating this condition.

Fahr Syndrome Presenting With Status Epilepticus After COVID-19 Infection.

Hypoparathyroidism is a rare metabolic disease. In addition to symptoms of hypocalcemia, chronic hypoparathyroidism can result in brain calcifications leading to Fahr syndrome. Hypoparathyroidism most commonly results as a postsurgical complication, with autoimmune disease the second most common etiology. Here we report a 48-year-old man with symptoms of chronic hypocalcemia who presented with status epilepticus following severe coronavirus disease 2019 (COVID-19) infection. In addition to severe hypocalcemia, he was found to have an inappropriately low serum parathyroid hormone level and basal ganglia calcifications visualized on head computed tomography scan. He was treated with intravenous calcium infusion prior to transition to orally administered calcium, calcitriol, and high-dose cholecalciferol (vitamin D3).

Application of calcium-to-phosphorus (Ca/P) ratio in the diagnosis of pseudohypoparathyroidism: another piece in the puzzle of diagnosis of Ca-P metabolism disorders.

Objective: The serum calcium (Ca)-to-phosphorus (P) ratio has been proposed to identify patients with primary hyperparathyroidism and chronic hypoparathyroidism (HPT), but it has never been tested in pseudohypoparathyroidism (PHP). The aim of this study was to test the performance of Ca/P ratio in PHP diagnosis compared with that in healthy subjects and patients with HPT for differential diagnosis. Design: A retrospective, cross-sectional, and observational study was carried out. Methods: Serum Ca, P, creatinine, parathyroid hormone (PTH), and albumin were collected. Ca and P were expressed in mmol/L. Ca/P diagnostic performance was evaluated by receiver operating characteristic curve, sensitivity, specificity, and accuracy. Results: A total of 60 patients with PHP, 60 patients with HPT, and 120 controls were enrolled. The Ca/P ratio was lower in patients with PHP and HPT than that in controls (p < 0.0001). The cutoff of 1.78 (2.32 if Ca and P measured in mg/dL) for Ca/P ratio could identify patients with PHP and HPT among the entire cohort (sensitivity and specificity of 76%). No valid cutoff of Ca/P was found to distinguish patients with PHP from patients with HPT; in this case, PTH above 53.0 ng/dL identified patients with PHP (sensitivity and specificity of 100%). The index (Ca/P × PTH) above 116 ng/L recognized patients with PHP from controls (sensitivity of 84.7% and specificity of 87.4%), whereas (Ca/P × PTH) below 34 ng/L recognized patients with HPT from controls (sensitivity of 88.9% and specificity of 90.8%). Conclusions: The Ca/P ratio below 1.78 (2.32 CU) is highly accurate to identify patients with PHP and HPT, although it is not reliable to differentiate these two conditions. The index (Ca/P × PTH) is excellent to specifically recognize PHP or HPT from healthy subjects.

A Scoping Review of the Apparent Phenomenon of the Improvement in Hypoparathyroidism in Pregnant and Postpartum Females.

Hypoparathyroidism requires management with both calcium supplementation and active vitamin D to avert a state of hypocalcemia. During late gestation and the postpartum period (specifically lactation), there is an under-recognized, yet intriguing occurrence of apparent 'pseudohyperparathyroidism', whereby supplementation dosages may need to either be reduced or discontinued, to prevent hypercalcemia. The explanation for this apparent phenomenon of improved parathyroid status ('remission' or 'resolution') is incompletely understood; the purpose of this review is to analyze the case reports of this enigma within the medical (and grey) literature, providing an overall pathophysiological explanation and recommendation for the management of such patients. A literature search was conducted through PubMed/Medline, CINAHL, Cochrane Library Database, Scopus, UpToDate, Google Scholar, and the grey literature without a time-restricted period, analyzing all available articles within the literature describing an apparent improvement in parathyroid status in late-gestation and postpartum (lactating) females. Non-hypoparathyroid case reports were also included to further analyze and synthesize an overall likely pathophysiological explanation. Through the literature search, 24 papers were identified covering such a phenomenon in patients with hypoparathyroidism, alongside multiple additional reports of a similar occurrence in patients without underlying hypoparathyroidism. The pathophysiology is believed to occur due to the placental production of parathyroid hormone-related peptide (PTHrP) during gestation, with further production from the lactating mammary glands during the postpartum period. A typical pattern is observed, with increased PTHrP and suppressed PTH throughout both gestation and lactation (present in both normal and hypoparathyroid subjects). The concept of PTHrP-induced hypercalcemia is further demonstrated in patients without hypoparathyroidism, including subjects with placental hypersecretion and mammary gland enlargement. It is evident that patients with hypoparathyroidism may require a dosage reduction during late gestation and lactation, due to the risk for hypercalcemia. In addition to patients with hypoparathyroidism, this pathophysiological phenomenon occurs in unsuspecting patients, demonstrating the need for all clinicians in contact with pregnant females to be aware of this uncommon - yet perilous - occurrence.

A Case Report on Hypocalcemic Cardiomyopathy: A Rare Cause of Cardiac Failure.

We discuss a case of a 48-year-old man who presented with symptoms of breathlessness, orthopnea, and paroxysmal nocturnal dyspnea. Echocardiogram showed severe left ventricular dysfunction with an ejection fraction of 20% and a coronary angiogram performed later was normal. He was initiated on standard medical management for heart failure. Further blood tests showed that he had severe hypocalcemia secondary to hypoparathyroidism. After the correction of hypoparathyroidism using calcium supplementation and alfacalcidol, his ejection fraction improved to 59%, and 12 weeks later, all anti-failure medications were stopped. A clinical diagnosis of hypocalcemic cardiomyopathy due to hypoparathyroidism was made. The literature review reveals only a few reported cases of heart failure as the initial presentation of dilated cardiomyopathy due to underlying hypocalcemia.