Chronic Hypocalcemia Research Articles

The Concurrent Association of Magnesium and Calcium Deficiencies with Cognitive Function in Older Hospitalized Adults.

Background/Objectives: Hypomagnesemia and hypocalcemia are common conditions among older adults that may contribute to cognitive decline. However, most of the existing research has focused primarily on dietary intake rather than the actual serum levels of these nutrients or examined them separately. This study aims to investigate the relationship between hypomagnesemia, hypocalcemia, and the concurrent presence of both deficiencies in relation to cognitive performance among seniors. Methods: A total of 1220 hospitalized patients aged 60 and older were included in the analysis. The participants were categorized into four groups: those with normal serum levels of magnesium and calcium, those with hypomagnesemia, those with hypocalcemia, and those with both serum magnesium and calcium deficiencies. To evaluate the potential influence of age, sex, common comorbidities, and disturbances in magnesium and calcium levels on cognitive performance, two general linear models were employed, using the Mini-Mental State Examination (MMSE) and Clock-Drawing Test (CDT) as dependent variables. Results: After adjusting for age, sex, body mass index, and comorbidities, the mean values for the MMSE and CDT were 23.33 (95%CI: 22.89-23.79) and 5.56 (95%CI: 5.29-5.83) for the group with normomagnesemia and normocalcemia, 22.59 (95%CI: 21.94-23.24) and 5.16 (95%CI: 4.77-5.54) for the group with hypomagnesemia, 19.53 (95%CI: 18.36-20.70) and 4.52 (95%CI: 3.83-5.21) for the group with hypocalcemia, and 21.14 (95%CI 19.99-22.29) and 4.28 (95%CI 3.61-4.95) for the group with both hypomagnesemia and hypocalcemia, respectively. Magnesium and calcium deficiencies contributed to MMSE and CDT variance in the general linear models. Conclusions: Our findings indicate that in addition to age, body mass index, and chronic heart failure, both hypomagnesemia and hypocalcemia are associated with reduced cognitive performance.

Impaired Quality of Life in Patients with Post-Surgical Hypoparathyroidism.

Hypoparathyroidism is characterized by chronic hypocalcemia with low or abnormal parathyroid hormone levels. Thyroid surgery remains a predominant cause of hypoparathyroidism, often preventable by partial thyroidectomy. Although hypoparathyroidism can impair quality of life (QOL), data remain limited for Latin America. We aimed to characterize clinical manifestations and QOL in patients with postsurgical hypoparathyroidism. This case-control study included patients (>18 years) who underwent total thyroidectomy (TT) for differentiated thyroid cancer (DTC) with postsurgical hypoparathyroidism (Group 1, Cases) and those with DTC who underwent TT without postsurgical hypoparathyroidism (Group 2, Controls). Clinical records were collected, and the SF-36v2 QOL survey and a structured symptom survey were applied. A logistic multivariate regression analysis was performed. This study included 106 subjects (Group 1, N=41; Group 2, N=65). Group 1 patients were younger, had a higher frequency of lymph node resection, and more frequently received Ι-131 than Group 2 patients (p<0.05). In the SF-36v2 survey, Group 1 had fewer physical-functioning scores (odds ratio, 3.8; 95% confidence interval, 1.2-11.7) and lower scores in mental and physical components than Group 2 and national records. Commonly reported symptoms include paresthesia, daily fatigue, and memory alterations. Treatment adherence rates were 56% and 71% for calcium and calcitriol, respectively. Furthermore, 24% of patients experienced one or more hypoparathyroidism drug-related adverse effects. Patients with postsurgical hypoparathyroidism had an impaired QOL, a high frequency of disease-associated symptoms, and limited treatment adherence. These results should be considered when deciding the best surgical alternative for DTC.

Exploring Chronic Hypocalcemia: Insights into Autoimmune Polyglandular Syndrome Type 1-A Case Study and Literature Review.

Hypocalcemia is a common occurrence in pediatric patients, attributed to various causes and presenting with diverse clinical manifestations. A prompt evaluation is necessary to determine its underlying cause, whether it presents acutely or chronically, and to tailor treatment based on its severity. Among the potential causes of chronic hypocalcemia, primary hypoparathyroidism stands out. The case of a seven-year-old male patient with hypocalcemia reported in this article serves as an illustration, wherein targeted next-generation sequencing revealed a homozygous p.R257X mutation in the AIRE gene, indicative of autoimmune polyendocrine syndrome type 1 (APS-1). It poses challenges due to its multisystemic nature and involvement of specific autoantibodies, often leading to underdiagnosis, owing to its rarity, varied manifestations, and incomplete penetrance. A comprehensive review of the APS-1 literature was conducted to provide insights into the clinical manifestations, genetic spectrum, potential immunological mechanisms, and current medical strategies. Additionally, the recognition of AIRE gene mutations is crucial for facilitating genetic diagnosis, prognosis, and potential treatment strategies for APS-1. The management of such cases involves individualized approaches to treatment, regular monitoring, medication adjustments, and the early identification of associated conditions.

Comparative Performance Assessment of Novel Fluorescence Immunoassay POCTs for Measuring Circulating Levels of Vitamin-D.

Vitamin D (Vit D) is a fat-soluble molecule acting like a hormone, and it is involved in several biological mechanisms such as gene expression, calcium homeostasis, bone metabolism, immune modulation, viral protection, and neuromuscular functions. Vit D deficiency can lead to chronic hypocalcemia, hyperparathyroidism, and many other pathological conditions; in this context, low and very low levels of 25-hydroxy-vitamin D (25-OH-D) were found to be associated with an increased risk of COVID-19 infection and the likelihood of many severe diseases. For all these reasons, it is important to quantify and monitor 25-OH-D levels to ensure that the serum/blood concentrations are not clinically suboptimal. Serum concentration of 25-OH-D is currently the main indicator of Vit D status, and it is currently performed by different assays, but the most common quantitation techniques involve immunometric methods or chromatography. Nevertheless, other quantitation techniques and instruments are now emerging, such as AFIAS-1® and AFIAS-10® (Boditech and Menarini) based on the immunofluorescence analyzer, that guarantee an automated system with cartridges able to give quick and reliable results as a point-of-care test (POCT). This work aims to compare AFIAS-1® and AFIAS-10® (Boditech and Menarini) Vit D quantitation with Ultra High-Performance Liquid Chromatography coupled with tandem mass spectrometry that currently represents the gold standard technique for Vit D quantitation. The analyses were performed in parallel on 56 samples and in different conditions (from fresh and frozen plasma) to assess the reliability of the results. Any statistically significant differences in methods, the fixed error, and the error proportional to concentration were reported. Results obtained in all conditions showed a good correlation between both AFIAS® instruments and LC-MS/MS, and we can affirm that AFIAS-1® and AFIAS-10® are reliable instruments for measuring 25-OH-D with accuracy and in a fast manner.

Functional evaluation of a novel nonsense variant of the calcium-sensing receptor gene leading to hypocalcemia.

The calcium-sensing receptor (CASR) gene encodes a G protein-coupled receptor crucial for calcium homeostasis. Gain-of-function CASR variants result in hypocalcemia, while loss-of-function variants lead to hypercalcemia. This study aims to assess the functional consequences of the novel nonsense CASR variant [c.2897_2898insCTGA, p.(Gln967*) (Q967*)] identified in adolescent patient with chronic hypocalcemia, a phenotype expected for a gain-of-function variants. To functionally characterize the Q967* mutant receptor, both wild-type (WT) and mutant CASR were transiently transfected into HEK293T cells and calcium-sensing receptor (CaSR) protein expression and functions were comparatively evaluated using multiple read-outs. Western blot analysis revealed that the CaSR mutant protein displayed a lower molecular weight compared with the WT, consistent with the loss of the last 122 amino acids in the intracellular domain. Mitogen-activated protein kinase activation and serum responsive element luciferase assays demonstrated that the mutant receptor had higher baseline activity than the WT. Extracellular-signal-regulated kinase/c-Jun N-terminal kinase phosphorylation, however, remained consistently high in the mutant, without significant modulations following exposure to increasing extracellular calcium (Ca2+o) levels, suggesting that the mutant receptor is more sensitive to Ca2+o compared with the WT. This study provides functional validation of the pathogenicity of a novel nonsense CASR variant, resulting in an abnormally hyperfunctioning protein consistent with the patient's phenotype. Functional analyses indicate that mutant receptor is constitutively active and poorly sensitive to increasing concentrations of extracellular calcium, suggesting that the cytoplasmic tail may contain elements regulating signal transduction.

Compressive myelopathy from diffuse spinal dural calcifications in a patient with end-stage renal disease: illustrative case.

Diffuse spinal dural calcification is a rare disorder associated with hyperparathyroidism, including the secondary forms associated with renal failure, osteodystrophy, and chronic hypocalcemia. Here, the authors report a rare case of diffuse dural calcification causing spinal cord compression with myelopathy, requiring decompressive surgery with duraplasty to achieve adequate decompression. A 46-year-old male with a history of renal failure on dialysis presented with 2 months of progressive neuropathic pain, lower-extremity weakness, and nonsustained clonus. Spine imaging showed severe renal osteodystrophy with multilevel compression fractures and diffuse dural calcifications with areas of invagination causing severe spinal cord compression. Decompressive surgery was recommended. In surgery, a thickened and calcified dura was encountered with areas of buckling causing spinal cord compression. The invaginated area of the dura was resected and reconstructed with patch duraplasty. The patient's neurological status remained unchanged postoperatively, and at the 6-month follow-up, the patient reported significant improvement in pain and muscle spasms. Diffuse dural calcifications are a rare complication of prolonged dialysis and secondary hyperparathyroidism. When there is resultant spinal cord compression, this condition requires an intradural approach that addresses the thickened, calcified dura directly to obtain adequate spinal cord decompression.

Bilateral Hypocalemic Cataract Post Thyroidectomi : A Case Report

Introduction : Young adult cataracts are negligible, and their prevalence is rarely reported in Indonesia. We reporta rapidly developing cataract in a 25-year-old woman due to secondary hypoparathyroidism. Cataracts in this case, progress remarkably fast compared to primary cataracts.
 Case Illustration : A twenty-five-year-old female patient presented bilateral vision loss and a history of a total thyroidectomy caused by diffused toxic goiter 7 years before admission. Postoperative calcium levels were extremely depleted. The uncorrected visual acuity examination measured 1/300 in the right eye and 20/200 in the left. Slit lamp examination revealed cortical opacities in both eyes. We diagnosedit as bilateral hypocalcemia cataracts. Patient has undergone bilateral phacoemulsification and intraocular lens implantation. The day following surgery visual acuity in the right eye was 20/30 and the left eye was 20/30 without correction. After one year of evaluation the visual acuity in RE become RE was 20/20 with a correction of -0.50 D sphere and the LE was 20/20 with a correction of -1.0 D sphere.
 Discussion : Patients with hypoparathyroidism risk developing cataracts due to chronic hypocalcemia, which inhibits the lenticular Na/K pump and induces intracellular sodium flux. This high sodium level triggers the osmosis process, followed by swelling of the lens fibers to form dystrophic calcifications. Thyroid surgery procedures suspectedly involving the parathyroid gland may cause hypocalcemia, thus leading to development of cataract.
 Conclusion : Clinicians should always consider hypoparathyroidism as the cause of bilateral cataracts in patients with a previous total thyroidectomy.

C-Cell Hyperplasia and Cystic Papillary Thyroid Carcinoma in a Patient with Type 1B Pseudohypoparathyroidism and Hypercalcitoninaemia: Case Report and Review of the Literature.

Hypercalcitoninaemia has been described in patients with pseudohypoparathyroidism (PHP) type 1A and 1B. Elevated calcitonin levels are thought to result from impaired Gsα receptor signaling, leading to multiple hormone resistance. Evidence on the risk of medullary thyroid carcinoma (MTC) or C-cell hyperplasia in PHP patients with hypercalcitoninaemia is lacking. A 43-year-old Caucasian man was referred to our endocrinology clinic for chronic hypocalcemia associated with elevated serum parathormone levels and a single cystic thyroid nodule. The patient did not show skeletal deformities, and screening for concomitant hormone resistances was negative, except for the presence of elevated serum calcitonin levels. The workup led to a molecular diagnosis of sporadic PHP1B. Fine needle aspiration of the thyroid nodule was not diagnostic. The calcium stimulation test yielded an abnormal calcitonin response. Given the scarcity of data on the risk of thyroid malignancy in PHP and calcium stimulation test results, total thyroidectomy was performed. Histological examination revealed cystic papillary thyroid cancer in a background of diffuse C-cell hyperplasia. To our knowledge, we are the first to describe a rare form of thyroid cancer combined with C-cell hyperplasia in a patient with PHP and hypercalcitoninaemia. In the present case, a mere receptor resistance might not fully explain the elevated calcitonin levels, suggesting that hypercalcitoninaemia should be carefully evaluated in PHP patients, especially in the case of concomitant thyroid nodules. Further studies on larger cohorts are needed to elucidate this topic.

SAT217 Chronic Asymptomatic Hypoparathyroidism Due To Two Separate Single Nucleotide Heterozygous Mutations In The CaSR Gene

Abstract Disclosure: M. Antony: None. S. Gundlapally: None. S. Storm: None. P. Russell: None. V. Verma: None. R. Kant: None. Introduction: The most common cause for acquired hypoparathyroidism is either post-surgical or autoimmune destruction of the parathyroid glands. The clinical presentation can range from an asymptomatic state to severe life-threatening symptoms that require intensive therapeutic management with intravenous and/or oral calcium, calcitriol and in some cases, recombinant parathyroid hormone therapy. Hypoparathyroidism secondary to CASR (calcium sensing gene receptor) gene mutation is an uncommon etiology that can also have a varied clinical presentation as above. Clinical Case: A 60-year-old Caucasian male with no significant past medical history was found to have chronic hypocalcemia. He denied experiencing symptoms such as numbness, tingling or cramping sensation around face, lips, or upper extremities. He denied a history of movement disorder or dental problems. He denied a history of neck surgeries or neck radiation exposure. He denied a family history of calcium disorders. He was on calcium carbonate/Vitamin D3 600 mg/400 I.U once daily. The first documented low corrected serum calcium was 6.9 mg/dl (8.6-10.0 mg/dl) in November of 2017. Since then, there have been multiple low corrected serum calcium levels ranging between 7 to 7.6 mg/dl. Patient underwent endocrinology work-up after withholding the above calcium/Vitamin D3 supplementation and it revealed a low corrected serum calcium of 7.6 mg/dl with an inappropriately normal serum PTH level of 37 pg/ml (15-65 pg/ml), normal vitamin D level of 45.1 ng/ml (> 30.0 ng/ml), normal serum phosphorus 3.8 mg/dl (2.5-4.5 mg/dl), and normal serum magnesium 1.8 mg/dl (1.6-2.6 mg/dl). The 24-hour urine calcium was 93 mg/24 hour with a corresponding 24-hour urine creatinine of 1836 mg (1040-2350 mg/24hour) and urine volume of 1625 ml. CASR gene analysis revealed two separate single nucleotide heterozygous mutations. The first mutation was at Exon 4/7, nucleotide position was c.614G>A and Amino Acid position was p.Arg205His. The second mutation was at Exon 7/7, nucleotide position was c.2546T>C and Amino Acid Position is p.lle849Thr. Due to lack of specific symptoms, patient was not initiated on specific therapies such as calcitriol or Natpara (recombinant PTH) and was advised to continue taking the daily calcium/vitamin D3 supplementation. He is being currently monitored every 4 to 6 months to assess for any clinical symptoms along with pertinent laboratory work-up. Conclusion: Hypoparathyroidism due to CASR gene mutation has a varied clinical presentation. One-third of cases do not develop any clinical symptoms, such as our patient and hence do not warrant any specific treatment other than periodic clinical and biochemical assessment. Presentation: Saturday, June 17, 2023

Desipramine induces eryptosis in human erythrocytes, an effect blunted by nitric oxide donor sodium nitroprusside and N-acetyl-L-cysteine but enhanced by Calcium depletion

ABSTRACT Background: Desipramine a representative of tricyclic antidepressants (TCAs) promotes recovery of depressed patients by inhibition of reuptake of neurotransmitters serotonin (SER) and norepinephrine (NE) in the presynaptic membrane by directly blocking their respective transporters SERT and NET. Aims: To study the effect of desipramine on programmed erythrocyte death (eryptosis) and explore the underlying mechanisms. Methods: Phosphatidylserine (PS) exposure on the cell surface as marker of cell death was estimated from annexin-V-binding, cell volume from forward scatter in flow cytometry. Hemolysis was determined photometrically, and intracellular glutathione [GSH]i from high performance liquid chromatography. Results: Desipramine dose-dependently significantly enhanced the percentage of annexin-V-binding cells and didn´t impact glutathione (GSH) synthesis. Desipramine-induced eryptosis was significantly reversed by pre-treatment of erythrocytes with either nitric oxide (NO) donor sodium nitroprusside (SNP) or N-acetyl-L-cysteine (NAC). The highest inhibitory effect was obtained by using both inhibitors together. Calcium (Ca2+) depletion aggravated desipramine-induced eryptosis. Changing the order of treatment, i.e. desipramine first followed by inhibitors, could not influence the inhibitory effect of SNP or NAC. Conclusion: Antidepressants-caused intoxication can be treated by SNP and NAC, respectively. B) Patients with chronic hypocalcemia should not be treated with tricyclic anti-depressants or their dose should be noticeably reduced.

Cellular and molecular mechanisms of the organogenesis and development, and function of the mammalian parathyroid gland.

Serum calcium homeostasis is mainly regulated by parathormone (PTH) secreted by the parathyroid gland. Besides PTH and Gcm2, a master gene for parathyroid differentiation, many genes are expressed in the gland. Especially, calcium-sensing receptor (CaSR), vitamin D receptor (VDR), and Klotho function to prevent increased secretion of PTH and hyperplasia of the parathyroid gland under chronic hypocalcemia. Parathyroid-specific dual deletion of Klotho and CaSR induces a marked enlargement of the glandular size. The parathyroid develops from the third and fourth pharyngeal pouches except murine species in which the gland is derived from the third pouch only. The development of the murine parathyroid gland is categorized as follows: (1) formation and differentiation of the pharyngeal pouches, (2) appearance of parathyroid domain in the third pharyngeal pouch together with thymus domain, (3) migration of parathyroid primordium attached to the top of thymus, and (4) contact with the thyroid lobe and separation from the thymus. The transcription factors and signaling molecules involved in each of these developmental stages are elaborated. In addition, mesenchymal neural crest cells surrounding the pharyngeal pouches and parathyroid primordium and invading the parathyroid parenchyma participate in the development of the gland.

Fahr’s Syndrome Secondary to Hypoparathyroidism Presenting with Paralysis and Recurrent Seizures: A Case Report

Aim: To describe a rare case of Fahr’s syndrome (FS) associated with chronic post-surgical hypoparathyroidism and hypocalcemia.
 Case Presentation: A 63-year-old female with a previous history of total thyroidectomy and hemiplegia presented to our hospital with altered mentation and recurrent generalized tonic-clonic seizures. Laboratory evaluation revealed hypoparathyroidism, hypocalcemia, and hypokalemia. Head computed tomography (CT) scan was consistent with FS, demonstrating extensive, bilateral, and symmetrical calcified deposits in the brain, predominantly in basal ganglia, corona radiata, and cerebellar hemispheres. The association with post-surgical hypoparathyroidism and relevant biochemical indices determined the suspected etiology of the pathologic process of ectopic calcification.
 Discussion: FS is a rare, neurodegenerative disorder characterized by abnormal bilateral ectopic calcified deposits in the basal ganglia and other brain structures. FS presents with a wide variety of neurological and psychiatric manifestations. The diagnosis is confirmed by neuroimaging studies such as a head CT scan or magnetic resonance imaging, which displays the calcification of BG and other structures in a bilateral and symmetrical pattern. Biochemical analysis may adjunctively identify the underlying risk factor of the disease.
 Conclusion: Our case represents a long-term severe consequence of untreated post-surgical hypoparathyroidism, which has consequently led to irreversible secondary FS. Maintenance of eucalcemic and euphosphatemic states is essential to prevent the progression of ectopic cerebral calcification.

Challenges in the management of chronic hypoparathyroidism and severe hypocalcaemia in post thyroidectomy- is there a rationale in using recombinant human parathyroid hormone?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Subtotal Thyroidectomy Postoperative Complications with Unplanned Thyroid Surgery

Background: The surgical treatment for bilateral multinodular nontoxic goiter (BMNG) is still debatable. Avoiding RLN harm during thyroid surgery if the pathology is not identified. Reduce the incidence of hypoparathyroidism by reducing the rate of parathyroid gland damage during excision. Objective: To see the complications of subtotal thyroidectomy in random thyroid surgery. Materials and Methods: This was a prospective, observational study conducted in the Department of ENT & Head- Neck surgery, Rangamati Medical College, Rangamati for a period of 2 years from January 2019 and December 2020. Total 100 patients were operated for benign and malignant thyroid disorders. This study was done to assess complications after various types of thyroid surgeries indicated for benign as well as malignant thyroid lesions. Results: Ten (10.0%) patients had transient hypocalcemia followed by 4(4.0%) had transient recurrent nerve palsy, 1(1.0%) had permanent hypocalcemia, 1(1.0%) had permanent recurrent nerve palsy and 1(1.0%) had neck hematoma. Mean weight of the resected thyroid was found 62.4±14.1 gram in euthyroidism group and 74.2±26.4 gram in hypothyroidism group. Mean proportion of weight of the thyroid remnant in total weight of the thyroid was found 5.1±2.2 percent in euthyroidism group and 3.9±2.1 percent in hypothyroidism group. Conclusion: Transient hypocalcemia, transient recurrent nerve palsy, chronic hypocalcemia, permanent recurrent nerve palsy, and neck hematoma were the most frequent postoperative complications.

Vitamin D in hypoparathyroidism: insight into pathophysiology and perspectives in clinical practice.

Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by the absence or insufficient parathyroid hormone production resulting in chronic hypocalcemia. Complications of HypoPT include perturbation of several target organs. The conventional treatment consists of the administration of active vitamin D, namely calcitriol. Regarding vitamin D status, few data are available, mostly in HypoPT subjects supplemented with parent vitamin D. In addition, perturbation of vitamin D metabolism has been poorly investigated, as well as the contribution of altered vitamin D status on the clinical expression of the disease. The most recent consensus on the management of chronic HypoPT suggests the baseline evaluation of serum 25-hydroxy-vitamin D [25(OH)D] and supplementation with parent vitamin D with the aim to achieve and maintain serum 25(OH)D levels in the range of 30-50 ng/mL. The rationale for using supplementation with parent vitamin D (either ergocalciferol or cholecalciferol) in HypoPT would be to provide sufficient 25(OH)D substrate to the residual 1-α-hydroxylase activity, thus ensuring its conversion to active vitamin D in renal and extra-renal tissues. More data from experimental and clinical studies are needed for better assessing how these mechanisms may significantly influence metabolic control in HypoPT and eventually skeletal and extra-skeletal manifestation of the disease. Finally, future data will clarify how the currently available parent vitamin D compounds (ergocalciferol, cholecalciferol, calcifediol) would perform in addressing these specific issues.

Advanced MR imaging features of uncontrolled phenylketonuria in an adult patient

A 29-year-old male was brought to the neurology department with a complaint of vomiting for one month. He had known mental retardation, epilepsy, and chronic hypocalcemia. His relatives said that the patient was diagnosed with phenylketonuria in childhood. As a result of further radiological examination, cranial MR images were compatible with phenylketonuria ([Figure 1A-F]). Although our case is very rare, it is worth reminding that phenylketonuria can be diagnosed in adulthood[1] and to emphasize that phenylketonuria is also present in the differential diagnosis of leukoencephalopathy.

Fahr´s Syndrome; Pseudohypoparathyroidism Type Ib Masquerading as Epileptic Seizures

Hypocalcaemia of various origin can be manifested by paresthesia, muscle cramps, muscle weakness, syncope, convulsions and even severe psychomotor retardation. Such symptoms can be initially considered as signs of epilepsy. We present a 12-year old boy with partial seizures and basal ganglia calcifications, initially diagnosed as having Fahr´s disease and epilepsy, where severe hypocalcaemia, due to genetically confirmed pseudohypoparathyroidism type Ib was the underlying cause. Excellent clinical improvement was observed after calcium and vitamin D therapy. The basal ganglia calcifications were secondary due to chronic hypocalcaemia, therefore the appropriate diagnosis was pseudohypoparathyroidism type Ib with Fahr´s syndrome, but not Fahr´s disease. In conclusion, the serum evaluation of minerals, especially calcium and phosphate, should be performed in all patients with convulsions, cramps and psychomotor retardation. This is essential in arriving at a proper diagnosis and early initiation of appropriate treatment.

Recurrent seizures as manifestation of hypoparathyroidism-related hypocalcemia in a patient with post-subtotal thyroidectomy

Background: Hypocalcemia, a condition where the serum calcium concentration or total serum calcium is below normal, could be associated with various manifestations including severe symptoms requiring immediate hospitalization. The condition can cause by several causes including iatrogenic thyroidectomy. Here, we report a patient of hypocalcemia associated with hypoparathyroidism due to post-thyroidectomy. Case presentation: A 32-year-old woman admitted to the hospital complained of stiffness and tingling in the extremities accompanied by recurrent seizures. The serum calcium level was low and this hypocalcemia condition was associated with low parathyroid hormone levels after subtotal thyroidectomy surgery. Laboratory examination indicated calcium 4.8 mg/dL and parathyroid hormone 2.21 pg/ml. The patient had bradycardia with prolonged QT on electrocardiography (ECG) and developed cataracts in both eyes which could be associated with chronic hypocalcemia. The patient's condition improved after correction of hypocalcemia. After discharge, the patient was given calcium and levothyroxine supplementation due to hypothyroid conditions. Conclusion: The hypocalcemia condition in the patient was associated with low parathyroid hormone level post-subtotal thyroidectomy surgery. This case highlights the impotence of detailed analyses of hormonal, radiological and histological investigations of patients with thyroid gland diseases to diagnose such conditions early and to ensure timely management.

PSAT183 Severe Hypocalcemia Precipitated by COVID-19 Infection in a Patient with Albright Hereditary Osteodystrophy and Pseudohypoparathyroidism

Abstract Background Hypocalcemia is a common endocrine manifestation of COVID 19 infection. We present a rare case of severe hypocalcemia in a patient with a history of Pseudohypoparathyroidism (PHP) type 1A after COVID-19 infection. PHP is a genetic disorder that presents with hypocalcemia, hyperphosphatemia, and secondary hyperparathyroidism due to marked target-organ unresponsiveness to parathyroid hormone (PTH). PHP type 1A also has a characteristic somatic phenotype known as Albright Hereditary Osteodystrophy (AHO), including short stature, brachydactyly, shortened metatarsals, and often reduced intelligence. Case Presentation This is a 53-year-old female with PHP type 1A, diabetes mellitus type 2, hypothyroidism, vitamin D deficiency, mild intellectual disability, and hypertension. She presented with new onset of seizures. She was also found to be positive for COVID-19 infection. On Review of systems, she had diarrhea but denied perioral or extremity paresthesia, palpitations, muscle spasms and bone pain. She reported compliance with calcitriol and calcium supplements at home. She had short stature, round face, short neck, obesity, brachydactyly (short digits of right 4th and 5th fingers) and shortened left 4th metacarpal. Labs revealed corrected serum calcium from baseline of 7.8 mg/dL to 4.4 mg/dL, ionized calcium 2.9 mg/dL, vitamin D 12.8ng/ml, PTH 142pg/ml and phosphorus 6.2mg/dl. EKG showed T wave inversions and prolonged QT interval. She did not have tetany, carpopedal spasm, paresthesia, Chvostek's sign, or Trousseau's sign. After receiving a total of 11 grams of elemental calcium, calcitriol, and ergocalciferol, her corrected calcium level improved to 7.4 mg/dL and EKG normalized. She was discharged home with calcium carbonate 1,250 mg twice a day and calcitriol 0.5 mcg daily. Discussion PHP type 1A is an autosomal dominant mutation of the stimulatory G protein alpha subunit (G alpha or GNAS) derived from the mother due to genomic imprinting which leads to PTH resistance in the kidneys and parathyroid glands. Our patient had a long-standing history of mild hypocalcemia with calcium and calcitriol supplements. Sudden worsening of hypocalcemia was likely related poor calcium and calcitriol absorption induced by COVID-19 infection. Patient with chronic hypocalcemia may not present with typical hypocalcemia signs or symptoms due to their tolerance. Conclusion Clinicians should be aware of the risk of developing severe hypocalcemia in patients who are calcium dependent or vitamin D deficient, malnourished during critical illness, or have COVID-19 infection which may decrease serum albumin and reduce total serum calcium level. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT210 A Case of Asymptomatic Severe Hypocalcemia: Consideration of Genetic Causes

Abstract Calcium sensing receptor (CaSR) activating mutations are a rare etiology of calcium dyscrasias in the general population. Of these, hypocalciuric hypocalcemia and autosomal dominant hypocalcemia (ADH) type 1 are the most common subtypes, with a prevalence of 74.1 and 3.9 per 100,000, respectively. Although rare, these mutations should be considered in patients with a family history of hypocalcemia, particularly if asymptomatic, as the treatment goals and replacement strategies differ from typical primary hypoparathyroidism, with which they are often mistaken. We present a case of a 41-year-old male with a history of treated vitamin D deficiency and anxiety who presented to endocrinology clinic for severe asymptomatic hypocalcemia (serum calcium 6.0-7.0). Family history pertinent for a mother, sister, and brother also with hypocalcemia, and brother with single childhood hypocalcemic seizure at age 4. Patient reported being on and off calcium, calcitriol, and ergocalciferol for years and has never had any symptoms regardless of his regimen or serum calcium. Specifically, he had no personal history of paresthesia, muscle cramping, or kidney stones. No family history of osteoporosis, fracture, kidney stone, or renal disease. Laboratory evaluation over the last 30 years most pertinent for serum calcium 6.0-9.5 on varying supplement/medication regimens, low-normal PTH, initially elevated and now normal serum phosphorous, low-normal serum magnesium, and 24h urinary calcium quite variable but as high as >300mg/d (when serum calcium within normal limits). Genetic testing revealed a heterozygous DNA sequence change detected on exon 7 of the CaSR gene, which has been previously found to be a pathogenic cause of ADH. Activating mutations of the CaSR (typically ADH type 1) clinically present as hypocalcemia, low or low-normal PTH, hyperphosphatemia, hypomagnesemia, and increased urinary calcium. When starting the evaluation for these mutations, it is important to note that there are two types of ADH. Type 1 mutations occur as an activating mutation at the CaSR causing hypersensitivity to calcium, while type 2 activating mutations occur at a different locale (G alpha 11 subunit). Despite mutations at different sites, each type leads to a similar gain-of-function mutation and a very similar clinical presentation. The clinical significance of differentiating these diagnoses from primary hypoparathyroidism (PHP) lies in the goals of treatment and in the adverse effects of over-supplementation of calcium in ADH. In PHP, patients generally have symptomatic hypocalcemia, and calcium can and should be supplemented to prevent adverse events of chronic hypocalcemia. Contrastingly, in CaSR mutation conditions, mild and even significant hypocalcemia is well tolerated. If patients’ serum calcium is normalized, they often experience significant hypercalciuria and renal manifestations therein, such has nephrocalcinosis and nephrolithiasis. Therefore, treatment of patients with CaSR activating mutations should be aimed at relieving hypocalcemia symptoms, if any are present. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.