Normal Serum Calcium Research Articles

Persistent elevation of parathyroid hormone after curative parathyroidectomy: A risk factor for recurrent hyperparathyroidism

AbstractBackgroundUp to 45% of patients may have persistently elevated parathyroid hormone (PTH) levels after curative parathyroidectomy for primary hyperparathyroidism (PHPT), although the clinical significance is unclear. We aimed to assess the long‐term clinical significance of persistently elevated PTH early after parathyroidectomy.MethodsA prospectively collected institutional database was queried for patients who underwent parathyroidectomy for sporadic PHPT between 12/99 and 6/22 and had normal serum calcium levels at 6 months postoperatively. Demographic and clinical data were collected, including diagnoses associated with secondary HPT (gastrointestinal malabsorptive diseases, kidney disease, and vitamin D deficiency). Patients were divided into two groups: normal PTH or elevated PTH at 6 months postoperatively. The rate of persistently elevated PTH, average time to PTH normalization, and time to recurrence were determined.ResultsThe final cohort included 1146 patients; 849 (91%) had normal PTH levels and 194 (17%) had early postoperative normocalcemia with elevated PTH at 6 months postoperatively. Among 194 patients (mean follow‐up: 50 ± 53 months), 14 (7.2%) developed recurrent pHPT and 86 (44.3%) had normalization of PTH levels (median time to normalization: 12 months) (IQR: 9 and 15). There was no difference in the presence of diagnoses associated with secondary HPT between patients who had recurrent PHPT, normalization of PTH levels, or remained normocalcemic with persistently elevated PTH levels. The median time to recurrence was 22 months (IQR: 11 and 48) for the 7.2% of patients who developed recurrent PHPT compared to 2.4% in the 849 patients with normal calcium and PTH levels at 6 months (p < 0.001).ConclusionsFollowing curative parathyroidectomy, persistent elevation of PTH levels is not uncommon. Although most patients have a durable cure, it may be an early sign of persistent/recurrent PHPT. Long‐term surveillance for recurrence is necessary.

Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial.

Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels. Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism. Phase 3 trial with a 26-week double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE). 21 sites across North America and Europe. 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52. All OLE participants received TransCon PTH administered once daily. Multi-component efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes (PROs) and bone mineral density (BMD). Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events (TEAEs). At week 52, 81% (63/78) met the multi-component efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. PROs showed sustained improvements in quality of life, physical functioning, and well-being. Mean BMD Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most TEAEs were mild or moderate and none led to trial discontinuation during the OLE. At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.

7331 A Rare Case Of Familial Hypoparathyroidism

Abstract Disclosure: N. Sekhon: None. K.Z. Win: None. Background: Autosomal dominant hypoparathyroidism disorders are very rare and mostly asymptomatic. We present an interesting case of autosomal hypoparathyroidism with a new variant of gene defect on genetic analysis. Case: A 66-year-old female was referred to the endocrinology clinic for familial hypoparathyroidism and calcium oxalate nephrolithiasis. She had onset of seizures at age 16. She was diagnosed with hypocalcemia and hypoparathyroidism at age 30 when she had her first episode of nephrolithiasis. She had recurrent nephrolithiasis and lithotripsies, ultimately developing chronic kidney impairment that was at stage 3b at the time of evaluation. Renal Ultrasound revealed bilateral nephrolithiasis, and nephrocalcinosis. There was a history of hypoparathyroidism in her father, paternal uncle, and son. Her medications included calcium carbonate-vitamin D3 600-400 mg-unit oral 2 tablets daily and calcitriol 0.5 mcg daily. The pertinent physical examination finding was a short stature with height 4’11” and calluses in fingers. Her recent serum chemistry showed calcium 8.8 mg/dL (reference range 8.3 - 10.6 mg/dL), PTH < 6.3 pg/mL (reference range 18.4 - 80.1 pg/ mL), and phosphorus 3.3 mg/dL (reference range 2.4 - 5.5 mg/dL). 24 hr urine calcium was 96 mg (reference range 50-300 mg/24h). She was treated with hydrochlorothiazide for nephrolithiasis but was discontinued due to hypokalemia. We performed genetic testing that resulted positive for CASR NM_001178065.1 with heterozygosity and damaging missense predictions inherited as autosomal dominant or recessive. Discussion: The calcium-sensing receptor (CaSR) has an important role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion and urinary calcium excretion. Familial hypoparathyroidism disorders are divided into Autosomal dominant hypocalcemia (ADH) type 1 and Autosomal dominant hypocalcemia (ADH) type 2. ADH1 is caused by an activating mutation of calcium-sensing receptor (CASR). The estimated prevalence of ADH1 ranges from 1 per 70,000 to 3.9 per 100,000. It is characterized by mild to moderate hypocalcemia, hyperphosphatemia, hypercalciuria, and inappropriately low but detectable PTH levels. It can be associated with Bartter syndrome Type 5. ADH2 is due to mutations in the alpha subunit of the G protein G11 (Gα11). Our patient had classic symptoms of hypocalcemia including short stature, seizures, kidney stones and its sequelae. Her 24-hour urine analysis showed inappropriately normal urine calcium with low normal serum calcium, undetectable serum PTH, and normal phosphorus. Our patient’s genetic analysis revealed a heterozygous defect in gene CASR with DNA variants c.2564G>A with damaging missense predictions. There is no such variant reported or listed in the ClinVar database. To our knowledge, this is the first such case of an autosomal dominant hypoparathyroidism with this gene defect. Presentation: 6/1/2024

12410 Intra-operative Parathyroid Hormone Monitoring: Comparative Evaluation Of Sampling Sites And Assay Methods

Abstract Disclosure: R. Kwayess: None. S. Ajjour: None. M. Rahme: None. M. Assaad: None. J. Abbas: None. S. Jabbour-Khoury: None. R. Daher: None. E. Cavalier: None. O. Kreidieh: None. M. Chakhtoura: None. G. El-Hajj Fuleihan: None. Background: Primary hyperparathyroidism is a common endocrine disorder increasingly managed by minimally invasive parathyroidectomy (MIP) with intra-operative parathyroid hormone (IOPTH) monitoring using 2nd generation parathyroid hormone (PTH) assay. Objective: Compare the use of central sampling versus peripheral sampling, and of 3rd as opposed to 2nd generation PTH assays’ performance. Methods: We collected preoperative baseline characteristics and laboratory values for consenting participants undergoing parathyroidectomy at our center. We then measured IOPTH levels from peripheral and central venous sites using 2nd and 3rd generation assays at various intraoperative time points. We calculated the maximal intraoperative PTH drop from highest baseline (pre-incision or pre-excision) at peripheral site and pre-excision at central site for participants who were normocalcemic at ≥ 6 months post-operatively. We used paired t-test to compare the mean % drop in IOPTH by 2nd vs 3rd generation assays, and peripheral vs central sampling. Results: Out of 88 participants enrolled, 63 had follow-up data at 6 months or beyond and normal serum calcium level (9.41 ± 0.43 mg/dL). Mean age was 56.16 ± 11.5 years, 77.8% females and 47.6% had osteoporosis or osteopenia. Pre-operative mean values were: serum calcium 10.94 ± 0.73 mg/dL, ionized calcium 5.6 ± 0.68 mg/dL, PTH 131.93 ± 120.1 pg/mL and creatinine 0.77 ± 0.19 mg/dL. The majority of patients underwent excision of one abnormal gland (79.4%). On average, 57.3% of patients had the highest PTH drop at 10 mins, 32.7% beyond 10 minutes, and 9.7% at 5 minutes, regardless of assay type and site. Median PTH decrements were 81% and 83.8% for 2nd generation assay, and 86.5% and 89% for 3rd generation assays, at peripheral and central sites, respectively. There was no significant difference in the PTH drop comparing central to peripheral sites using either assay. However, 3rd generation assays displayed a higher drop compared to 2nd generation assay, for both central and peripheral sites (p-value <0.001). Discussion/Conclusion: Our study shows no difference in % drop between peripheral and central sampling, using either 2nd or 3rd generation assays. Central PTH sampling is commonly used by surgeons because of ease of access, while applying the Miami criterion. However, the drop in median 3rd generation PTH level was higher compared to the 2nd generation assay, regardless of the sampling site. Our findings suggest the necessity of defining larger PTH drop cut-off values for 3rd generation PTH assay than the commonly used Miami criterion.

7293 An Unusual Case Of Adult-Onset Heterozygous HHRH In A Male With Normal Phosphorus And Severe Osteoporosis

Abstract Disclosure: M. El Najjar: None. A. Sabet: None. D. Willard: None. Introduction: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by renal phosphate wasting, which can affect bone metabolism. Although onset is typically in childhood, adult-onset forms have been described, and the manifestation depends on the zygosity of each patient. Most commonly, adults with HHRH demonstrate markedly reduced bone density and multiple fractures. Heterozygotes have milder presentations with mild hypophosphatemia, hypercalciuria, and nephrolithiasis, usually without bone disease; however, it is less well characterized. Case report: A 73-year-old man suffered an L1 vertebral compression fracture while playing golf. Bone mineral density testing revealed T-scores of -0.9 at the lumbar spine and -3.4 at the femoral neck (Z-score -2.6). He started alendronate 70 mg weekly for osteoporosis treatment. A year later, the patient sustained an L3 vertebral compression fracture while on treatment with no improvement in his bone density. His family history was remarkable for osteoporosis in his mother but no nephrolithiasis or hypercalcemia. Physical examination was unremarkable. Laboratory evaluation was notable for a 1,25-dihydroxyvitamin D of 87 pg/mL (18-72 pg/mL) , a 24-hour urine calcium of 240 mg/g Cr (30-210 mg/g),a serum PTH of 9 pg/mL (16-77 pg/ml) , but otherwise a normal serum calcium level of 9.4 mg/dL (8.6-10.3 mg/dL) and serum phosphate level of 2.2 mg/dl (2.1-4.3 mg/dl). Genetic testing revealed heterozygosity for SLC34A3 mutation, which is associated with HHRH. The patient discontinued alendronate and started 250 mg phosphorus supplementation 4 times daily. At 6 months follow up, he reported improvement in his body aches, and biochemical testing showed normalization of his 24-hour urine calcium to 171 mg/g Cr and serum PTH to 21 pg/mL. Repeat bone density scan after 1 year of phosphorus supplementation showed T-scores of -0.3 at the lumbar spine (5.8% increase) and -2.6 at the femoral neck (15.5% increase). Clinical Lesson: HHRH is an autosomal recessive hypophosphatemic rickets associated with mutations of the SLC34A3 sodium-phosphate cotransporter, where it is believed that selective phosphate wasting leads to increased calcitriol, in contrast to other forms of hypophosphatemic rickets, causing increased intestinal calcium absorption and resulting hypercalciuria. Adult-onset forms of HHRH have been described in heterozygous carriers of the SLC34A3 mutation and usually present with low to low-normal phosphate levels, hypercalciuria, and nephrolithiasis but without bone disease. However, clinical variations of heterozygous carriers have also been recognized, and therefore are likely underdiagnosed. Our patient’s serum phosphorus level was within the normal range, and hypophosphatemic rickets could have been missed if a more extensive laboratory evaluation had not been performed. Presentation: 6/1/2024

12556 Medullary Thyroid Cancer With Persistent Elevation Of Carcinoembryonic Antigen: Case Report

Abstract Disclosure: M.S. Campana: None. Introduction: Medullary thyroid Cancer (MTC) is a rare neuroendocrine tumor that originates from thyroid parafollicular C-cells and represents 5 % of all thyroid cancers. MTC can be sporadic (75%) or hereditary (25%) associated with multiple endocrine neoplasia type 2 syndrome (MEN2). Serum calcitonin (Ctn) and carcinoembryonic antigen (CEA) are its tumor markers. We report a case of persistently elevated CEA levels despite an undetectable Ctn in a patient with MTC after initial thyroid lobectomy. Description of the case: A 42-year-old woman self-identified a neck lump after intentional weight loss. A neck US showed a right lobe thyroid nodule which resulted as suspicious for malignancy (Bethesda V) with subsequent right lobectomy. Pathology reported a 2.6 cm unexpected MTC with negative surgical margins, extrathyroidal extension, angioinvasion, and lymphatic invasion. No cervical lymph nodes (LNs) were removed. Immunohistochemistry was positive for CEA, chromogranin A, synaptophysin, and Ctn. T2 Nx. One month after lobectomy, the Ctn was 10.5 (0-3.0 pg/mL) and CEA 205.2 (0-3.0 ng/mL Non-smoker; 0-5.0 ng/mL smoker). The patient was then referred to our clinic for further management. Laboratories showed normal serum calcium, PTH, and fractionated plasma metanephrine/normetanephrine. A 2-month post-operative Ctn was undetectable, but CEA was elevated at 24.5. Subsequently, we broaden imaging studies to include neck US, CT neck /chest with contrast, and MRI abdomen pelvis with contrast. The only remarkable finding was a 6.7 cm pelvic mass with normal Ca-125. Genetic testing was negative for germline RET, ruling out MEN2. Patient underwent completion left lobectomy with prophylactic bilateral central neck dissection. Pathology showed benign thyroid parenchyma with multinodular hyperplasia and 0/12 LNs. Because of concerning pelvic mass, the patient was referred to OB/GYN. She underwent a laparoscopic bilateral salpingo-oophorectomy. Pathology showed a follicular ovarian cyst, negative for malignancy. A year post-completion total thyroidectomy Ctn remains undetectable, and a CEA is normal at 1.3. Discussion: Because Ctn was already undetectable 1 month after lobectomy with persistent elevated CEA a complete total thyroidectomy with prophylactic bilateral central neck dissection was indicated to achieve operative cure. Ctn is specific to MTC but variable. CEA is more reproducible with less variability; however, it is not specific to MTC and can also be elevated in smokers, benign breast and genitourinary disease, emphysema, cirrhosis, and cancer of colon, rectum, liver, genitourinary, and lung. If residual disease is present, Ctn tends to be proportionally more elevated than CEA. When the opposite occurs, poorly differentiated MTC with possibility of distant metastases vs. a second primary malignancy vs. a distant benign neoplasm known to elevate CEA need to be ruled out. Presentation: 6/2/2024

7761 Unmasking The Uncommon: A Case Of Primary Adrenal Insufficiency Presenting As Severe Hypercalcemia

Abstract Disclosure: A. Misbah: None. Z. Al-Hiti: None. A. Saleh: None. M. Joda: None. K. Rajamani: None. Adrenal insufficiency is a recognized but uncommon cause of hypercalcemia. The exact mechanism remains unknown; however, it is thought to be a combination of the hypovolemic state in adrenal insufficiency leading to decreased urinary clearance, as well as increased bone resorption. We present a case of primary adrenal insufficiency presenting with severe hypercalcemia. A 41 year old female with a past medical history of osteopenia, recently diagnosed postural orthostatic tachycardia syndrome (POTS), and hyponatremia attributed to SIADH presented with complaints of weakness and poor oral intake. She also reported a history of nausea, vomiting, weight loss, fatigue, and dizziness, for the last few months. She reported feeling well prior to a COVID-19 infection a few months back. At presentation, she was hypotensive with a blood pressure of 70/50 mmHg, while her other vital signs were stable. She appeared ill, and was noted to have dry oral mucous membranes. There was no increased pigmentation noted on exam. Initial laboratory evaluation revealed sodium of 130 (135-145 mmol/L), potassium of 5.3 (3.5-5.1 mmol/L), and creatinine of 1.7 (0.5-0.8 mg/dL). She had severe hypercalcemia with a calcium level of 15.5 (8.3-10.6 mg/dL) and had a blood glucose level of 53 (70-100 mg/dL). Venous blood gas indicated metabolic acidosis. Morning cortisol was low at 1 (3-23 ug/dL). Serum ACTH was elevated at 775 (0-46 pg/mL). Cosyntropin stimulation test confirmed primary adrenal insufficiency. She underwent work-up for hypercalcemia, which revealed a suppressed PTH, normal levels of PTHrP, vitamin D, and vitamin A. Serum and urine protein electrophoresis was normal. She was initially managed in the ICU and received aggressive fluid resuscitation. She was started on stress dose of hydrocortisone, which was then tapered to physiological doses of oral hydrocortisone and fludrocortisone. Subsequent improvements were observed in blood pressure, laboratory abnormalities, and normalized serum calcium levels. She was discharged home on hydrocortisone and fludrocortisone. On follow-up, she was doing well with the resolution of her symptoms. This case highlights the importance of recognizing adrenal insufficiency as one of the causes of hypercalcemia. Although hypercalcemia as a consequence of adrenal insufficiency is well-documented, the exact prevalence is not known but is estimated to be around 6%. After excluding more common diseases such as primary hyperparathyroidism and malignancy, the possibility of adrenal insufficiency should be considered as a cause of hypercalcemia. Treatment involves hormone replacement as well as hydration, bringing resolution to symptoms. Her presentation was unique, also due to the fact that her initial symptoms were diagnosed as POTS as well as SIADH. Given the onset of symptoms after a COVID-19 infection a few months ago, there could also be a potential link between the two. Presentation: 6/3/2024

Prevalence of chronic postsurgical hypoparathyroidism not adequately controlled: an analysis of a nationwide cohort of 337 patients.

The identification of patients with chronic hypoparathyroidism who are adequately (AC) or not adequately controlled (NAC) has clinical interest, since poor disease control is related to complications and mortality. We aimed to assess the prevalence of NAC patients in a cohort of subjects with postsurgical hypoparathyroidism. We performed a multicenter, retrospective, cohort study including patients from 16 Spanish hospitals with chronic hypoparathyroidism lasting ≥3 years. We analyzed disease control including biochemical profile and clinical wellness. For biochemical assessment we considered three criteria: criterion 1, normal serum calcium, phosphorus and calcium x phosphorus product; criterion 2, the above plus estimated glomerular filtration rate ≥60 ml/min/1.73 m2; and criterion 3, the above plus normal 24-hour urinary calcium excretion. A patient was considered AC if he or she met the biochemical criteria and was clinically well. We included 337 patients with postsurgical hypoparathyroidism (84.3% women, median age 45[36-56] years, median time of follow-up 8.9[6.0-13.0] years). The proportions of NAC patients with criteria 1, 2 and 3 were, respectively, 45.9%, 49.2% and 63.1%. Patients who had dyslipidemia at the time of diagnosis presented a significantly higher risk of NAC disease (criterion 3; OR 7.05[1.44-34.45]; P=0.016). NAC patients (criterion 2) had a higher proportion of subjects with incident chronic kidney disease and eye disorders, and NAC patients (criterion 3) had a higher proportion of incident chronic kidney disease, nephrolithiasis and dyslipidemia than AC patients. The present study shows a strikingly high prevalence of NAC patients in the clinical practice of Spanish endocrinologists. Results suggest that NAC disease might be associated with some prevalent and incident comorbidities.

Association of serum calcium, vitamin D, and C-reactive protein with all-cause and cause-specific mortality in an osteoarthritis population in the UK: a prospective cohort study

BackgroundOsteoarthritis is a prevalent musculoskeletal condition, but the role of specific serum biomarkers, such as calcium, vitamin D, and C-reactive protein (CRP), in predicting mortality among individuals with osteoarthritis remains unclear.MethodsThis observational study analyzed longitudinal data from over 500,000 participants in the UK Biobank, identifying those with osteoarthritis using ICD-9/10 codes or self-reported history. We performed multivariable cox-regression and flexible parametric survival model (FPSM) for survival analysis, with adjustments made through the inverse probability of treatment weight (IPTW) for baseline covariates identified by directed acyclic graphs (DAGs).ResultsOf the 49,082 osteoarthritis population, the average age was 60.69 years, with 58.7% being female. During the follow-up period exceeding 15 years, a total of 5,522 people with osteoarthritis died. High serum calcium levels, compared to normal serum calcium levels, were significantly associated with all-cause mortality (hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11, 1.59), cardiovascular diseases (CVD)-related deaths (HR 1.55, 95% CI 1.05, 2.29), and other deaths (HR 1.59, 95% CI 1.20, 2.11). Low serum calcium levels, compared to normal serum calcium levels, was linked with CVD-related deaths (HR 2.06, 95% CI 1.02, 4.14). Vitamin D insufficiency, compared to sufficient vitamin D levels, was correlated with all-cause mortality (HR 1.22, 95% CI 1.13, 1.33), CVD-related deaths (HR 1.43, 95% CI 1.20, 1.72), and other deaths (HR 1.26, 95% CI 1.09, 1.45) but not with cancer-related deaths. High serum CRP levels, compared to normal CRP levels, were associated with all outcomes (all-cause mortality: HR 1.22, 95% CI 1.12, 1.33; CVD-related death: HR 1.24, 95%CI 1.03, 1.49; cancer-related death: HR 1.23, 95% CI 1.09, 1.40; other deaths: HR 1.19, 95%CI 1.03, 1.38).ConclusionsBoth high and low serum calcium levels, elevated CRP, and vitamin D insufficiency are potential predictors of increased mortality risk in the osteoarthritis population. These findings emphasize the importance of monitoring and possibly addressing these serum biomarkers in osteoarthritis populations to improve long-term outcomes. Further studies are needed to understand the underlying mechanisms and to propose therapeutic interventions.

Serum calcium as a candidate marker in detecting stunting in toddler

<p><strong><em>Background: </em></strong><em>Monitoring the nutritional status of toddlers is a very important thing to do. Calcium is one of the blood parameters that can be assessed, because calcium deficiency will affect the child's linear growth. So far, monitoring of nutritional status is only based on anthropometry and is not followed by assessment of blood parameters. </em><strong><em>Objectives:</em></strong><strong><em> </em></strong><em>This study aims to measure serum calcium levels as a candidate marker in detecting stunting in toddlers. </em></p><p><strong><em>Method:</em></strong><em> The design of this research is cross sectional with 62 samples of toddlers aged 2-5 years. Data on sample characteristics was obtained through a questionnaire, as for serum calcium levels measurement, venous blood samples were taken and measured with the colorimetric method. The incidence of stunting is obtained based on TB/U measurements and Z-score was calculated using Anthro 1.02 software. Data were then analyzed univariately (frequency distribution) and bivariately (</em><em>independent t-test and </em><em>chi-square) using SPSS version 22. </em></p><p><strong><em>Results:</em></strong><em> Based on anthropometric measurements, it was found that 21 (33.9%) toddlers had stunting, 28 (45.1%) toddlers had low Serum calcium levels and the majority of toddlers (54.9%) had normal serum calcium levels. There was no significant difference (p=0.989) in mean serum calcium levels between stunting and non-stunting toddlers (1.961 ± 0.223 µq/dL vs 1.960 ± 0.175 µq/dL). Bivariate results also showed that there was no significant relationship (p=0.414) between serum calcium levels and the incidence of stunting. </em></p><p><strong><em>Conclusion:</em></strong><em> Measuring serum calcium levels cannot be used as a candidate marker for detecting stunting in toddlers. Further research is needed with a larger number of samples and measurements of various parameters related to calcium balance.</em><strong></strong></p>

Role of Postoperative Intact Parathyroid Hormone Levels in Predicting Hypocalcaemia after Thyroidectomy.

To determine the sensitivity and specificity of intact parathyroid hormone (iPTH) levels in predicting hypocalcaemia after thyroidectomy. A descriptive cross-sectional study. Place and Duration of the Study: Department of General Surgery, Shifa International Hospital and Shifa Foundation, Islamabad, from May 2021 to 2022. The sample size was calculated to be 205 with consecutive non-probability sampling. Serum iPTH levels and serum calcium levels were measured postoperatively at 6 hours and 24 hours and recorded in a proforma for analysis. After collection, the data were entered and analysed using SPSS version 24.0. Among 205 patients, 157 (76.6%) were females and 48 (23.4%) were males. At 6 hours postoperatively, 121 (59%) patients had normal iPTH levels and 123 (60%) patients had normal serum calcium levels (p = 0.15). At 24-hour, 130 (63.4%) patients had normal iPTH levels and 92 (44.9%) patients had normal serum calcium levels (p = 0.001). Overall, 8 (3.9%) patients developed symptomatic hypocalcaemia (p = <0.001). The sensitivity and specificity of iPTH levels at ≤15 pg/ml were 100% and 70%, respectively, but at 24 pg/ml cut-off level, the specificity increased to 90% with sensitivity of 100%. Low serum iPTH levels at 6 hours after surgery can predict hypocalcaemia in patients undergoing thyroidectomy, even if serum calcium levels appear normal at that time. Parathyroid hormone, Serum calcium, Hypocalcaemia, Total thyroidectomy, Calcium homeostasis.

#191 An unusual cause of hypocalcemia in a young patient

Abstract Background and Aims A 33-year-old man visited the Nephrology Department outpatient clinic with abnormal laboratory findings: his serum calcium level was 5.9 mg/dL in a recent health examination. He denied any underlying disease and was on no medications. He complained of a tingling sensation in his hands and of eyelid twitching. On physical examination, he showed Chvostek's sign. His laboratory findings including serum calcium level are shown in Table 1. He did not have any morphological abnormalities, such as a round face, brachydactyly, or dental anomalies. Method Since he showed hypocalcemia, normal 25-hydroxyvitamin D, and elevated parathyroid hormone (PTH) levels, the presence of PTH resistance was presumed. Under strong suspicion of pseudohypoparathyroidism (PHP) in this patient, DNA sequence analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of GNAS and STX16, genetic regions that are often affected by mutations or imprinting changes in PHP, was performed. No pathogenic mutations in GNAS and STX16 were detected by sequencing. Results Results of MS-MLPA of the GNAS locus demonstrated abnormal methylation patterns in the patient after HhaI restriction enzyme treatment. The methylation ratio showed a gain of methylation in the NESP55 region and loss of methylation in the AS, XL, and A/B differentially methylated regions (DMRs) in the patient as compared to a healthy control (Fig. 1). The patient was diagnosed with PHP type 1B (PHP1B) due to the methylation abnormalities in multiple DMRs. His parents both showed normal serum calcium levels; thus, no further genetic testing was conducted. He is on outpatient follow-up with adequate calcium replacement and no specific symptoms. Conclusion PHP is a rare disorder of unknown prevalence. It is characterized by hypocalcemia, hyperphosphatemia, and increased PTH levels. PHP1B is a subtype of PHP characterized by isolated renal PTH resistance, usually without physical abnormalities such as Albright hereditary osteodystrophy or other endocrine abnormalities. PHP1B can be sporadic or familial. The genetic characteristics of most sporadic PHP1B remains unclear, but GNAS imprinting abnormalities and hypomethylation at the A/B DMRs have been reported. Symptoms of PHP1B usually begin in childhood due to low calcium levels and may include numbness, seizures, tetany, cataracts, and dental problems. However, as in our case, specific symptoms may not occur until adulthood. Therefore, when evaluating the cause of hypocalcemia, it is necessary to differentiate PHP1B, even in adults, and particularly in cases with hyperphosphatemia and high PTH levels.

Acute kidney injury and hypercalcemia associated with veterinary supplements applications in adult man

The compound “ADE” is an injectable oil for veterinary use which contains large amounts of vitamins A, D and E. The parenteral application in humans leads to a granuloma reaction which triggers hypercalcemia. A 42-year-old man was admitted with lower limb pain, nephrolithiasis and nephrocalcinosis. Laboratory tests revealed creatinine 4.59 mg/dl, calcium 13.3 mg/dl and parathormone 13.8 pg/ml. He underwent an ureterolithotripsy, stent placement, intravenous crystalloid fluids, and corticosteroid. He improved symptoms, kidney function and normalized serum calcium. The “ADE”-induced hypercalcemia diagnosis can be challenging. The early diagnosis may avoid negative outcomes.

Biallelic and monoallelic pathogenic variants in CYP24A1 and SLC34A1 genes cause idiopathic infantile hypercalcemia

ObjectiveIdiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated.MethodsThe clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively.ResultsFive of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients.ConclusionsA monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults.

Biochemical characteristics and clinical manifestation of normocalcemic primary hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (nPHPT) is a condition characterized by persistently high levels of parathyroid hormone (PTH) and normal serum calcium levels in the absence of other causes for secondary hyperparathyroidism. The aim of the present study was to assess the clinical presentation and the biochemical characteristics in patients with nPHPT and to compare them with those in patients with hypercalcemic PHPT (hPHPT). The study included 316 patients (277 women and 39 men, average age 58.7 ± 12.1) diagnosed with PHPT. Total serum calcium, inorganic phosphates (PO4), PTH, urinary Ca (uCa), albumin, creatinine, 25(OH)D and bone markers (b-CTX and ALP) were examined in all of them. BMD of the lumbar spine (LS), distal third of the radius (DR), femoral neck (FN) and total proximal femur (TF) were measured by a dual-energy X-ray absorptiometry (DXA). The patients were divided into two groups according to albumin-corrected calcium (Ca) level - with hPHPT (Ca>2.62 mmol/L) and with nPHPT (Ca 2.12-2.62 mmol/l), without other causes for secondary hyperparathyroidism. The frequency of nPHPT was 15.2%. Normocalcemic patients had lower levels of PTH, higher PO4 and 25(OH)D, and smaller parathyroid adenomas. No significant difference in the frequency of osteoporosis, low-energy fractures, nephrolithiasis and gastrointestinal disorders was found between nPHPT and hPHPT. There was no difference in BMD between the two groups. The patients with nPHPT show a more favorable biochemical profile compared to those with hPHPT. Nevertheless, clinical manifestations and complications are similar, without a significant difference in the frequency of osteoporosis, nephrolithiasis, gastrointestinal disorders and low-energy fractures.

Reference values for serum calcium in neonates should be established in a population of vitamin D-replete subjects.

Serum calcium is frequently measured during the neonatal period, and is known to be influenced by the vitamin D status. We hypothesized that the 25OHD concentration may influence the lower limit of the serum calcium normal range in neonates. We included in our prospective cohort study 1002 mother-newborn pair recruited from April 2012 to July 2014, in two centers located in the neighborhoods of Paris, France, whose serum calcium was measured at 3 days of life. We established, after exclusion of outliers, a 95% confidence interval (CI) for serum calcium 1) in our whole population of 1002 neonates, 2) in neonates with a cord blood 25OHD concentration ≥ 30 nmol/L, and 3) in those with a 25OHD ≥ 50 nmol/L. The mean serum total calcium was 2.46 ± 0.13 nmol/L [95% CI: 2.19-2.72 mmol/L], 2.47 ± 0.25 mmol/L [95% CI: 2.22-2.72 mmol/L], and 2.50 ± 0.25 mmol/L [95% CI: 2.25-2.75 mmol/L] in the whole group, in the 514 neonates with 25OHD ≥ 30 nmol/L, and in the 202 neonates with 25OHD ≥ 50 nmol/L respectively. The lower limit of the 95% range was significantly higher in neonates with 25 OHD ≥ 30 nmol/L (p<0.05) and ≥ 50 nmol/L (p<0.001) than in the entire cohort. We show that the lower limit of the normal serum calcium range is higher in groups with a higher 25OHD than in unselected subjects. We propose that the reference range for serum calcium in neonates is 2.25 to 2.75 mmol/L.

Diagnosis and management of pruritus associated with chronic kidney disease in hemodialyzed patients

Chronic kidney disease-associated pruritus (CKD-aP) is a disabling symptom which is frequent and often underestimated. Pa-MRC has a negative impact on quality of life, and is frequently accompanied by sleep disorders and depression. The approval of difelikefalin – a kappa opioid receptor agonist – in this indication requires updated recommendations. As a first step, secondary causes of pruritus without skin lesions must be ruled out, and general measures taken (emollients, psychological support, optimization of dialysis, normalization of serum calcium, phosphate and PTH in the range proposed by the KGIDO guidelines, treatment of iron deficiency). A therapeutic test with a non-sedating oral antihistamine may be proposed. If this test is negative, Pa-MRC must be strongly suspected, and its intensity (WI-NRS scale) and impact on quality of life assessed. In the case of mild Pa-MRC (WI-NRS ≤ 3), only general measures are implemented. If Pa-MRC is moderate to severe (WI-NRS ≥ 4), specific treatment with difelikefaline can be initiated for 6 months in addition to general measures. At 3 months, if the response is complete (WI-NRS score ≤ 1) or partial (decline ≥ 3 points), treatment is continued. At 6 months, if the response is complete, treatment may be discontinued with the patient’s agreement; treatment is maintained if the response is partial. At 3 or 6 months, if response is insufficient (decline < 3 points) and/or in the event of intolerance, treatment is discontinued and an alternative treatment (e.g., gabapentinoids, UVB) may be considered after dermatological consultation.

Urine immunofixation electrophoresis and serum free light chain analyses benefit diagnosis of multiple myeloma in orthopedic patients with normal serum total proteins, creatinine, calcium, and hemoglobin.

A substantial number of patients with multiple myeloma (MM) who have bone destruction are initially admitted into the orthopedic service at the hospital. However, routine laboratory testing usually fails to identify these patients, thus delaying optimal therapy. Therefore, there is a clear medical need for early diagnosis of MM in these patients. Between 2019 and 2021, 42 patients receiving treatment for orthopedic conditions had normal hemoglobin (Hb), total protein (TP), albumin (ALB), creatinine (CREA), and blood calcium (Ca) levels before their surgical procedure(s) but were subsequently pathologically confirmed to have MM, based on their presenting orthopedic symptoms. During the same period, 52 patients with orthopedic conditions were pathologically excluded from the diagnosis of MM and were recruited into our control group. Serum free light chain (sFLC) testing was performed in 94 consecutive patients in the orthopedic service using Siemens N Latex FLC kits. The levels of Hb, TP, ALB, CREA, and Ca were also measured. All 42 patients with MM were divided into group A (n = 25: κ proliferation) and group B (n = 17: λ proliferation) by the pathology department. There were no significant differences in levels of Hb, TP, ALB, CREA, and Ca between group A and group B and the control group. However, the sFLC κ/λ ratio of group A and B was also significantly different from that of the control group (P < .001). The results of serum immunofixation electrophoresis (IFE) testing demonstrated negative results in 14 cases (58.3%) in group A and 4 cases (25.0%) in group B. Some patients with orthopedic conditions who do not have typical MM laboratory results, such as those with abnormal Hb, TP, ALB, CREA, and Ca levels before their operation(s), actually have MM. MM should be highly suspected in patients with unexplained bone lesions and with an abnormal sFLC κ/λ ratio. Further tissue or bone marrow biopsy is needed in these patients even if serum and urine IFE results are negative and light chain ratio is normal.

Factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients.

Parathyroidectomy (PTX) is an effective treatment for primary hyperparathyroidism (PHPT) patients. Postoperative hypocalcemia is a common complication after PTX. This study aimed to analyze the factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients. The retrospective study included 270 PHPT patients treated with PTX and collected their demographic and clinical information and their laboratory indices. Factors influencing serum calcium levels and hypocalcemia after PTX in PHPT patients were analyzed using univariate and multifactorial analyses. First, in patients with normal preoperative serum calcium levels (2.20-2.74 mmol/L), the higher the preoperative alkaline phosphatase and serum phosphorus levels, the lower the postoperative serum calcium levels. Furthermore, the higher the preoperative serum calcium levels and the accompanying clinical symptoms, the higher the postoperative serum calcium levels. Low preoperative serum calcium levels were shown to be a risk factor for postoperative hypocalcemia (OR=0.022), and the optimal preoperative serum calcium threshold was 2.625 mmol/L (sensitivity and specificity were 0.587 and 0.712, respectively). Second, in the mild preoperative hypercalcemia group (2.75-3.00 mmol/L), the older the patient, the higher the preoperative and postoperative serum calcium levels, the higher the postoperative serum calcium; the lower the alkaline phosphatase and calcitonin levels, the higher the postoperative serum calcium levels. On the other hand, the younger the patient was, the more likely hypocalcemia blood was (OR=0.947), with an optimal age threshold of 47.5 years (sensitivity and specificity were 0.543 and 0.754, respectively). Third, in the preoperative moderate to severe hypercalcemia group (>3.0mmol/L), patients undergoing a combined contralateral thyroidectomy and a total thyroidectomy had low postoperative serum calcium levels. Patients with different preoperative serum calcium levels had various factors influencing their postoperative serum calcium levels and postoperative hypocalcemia, which facilitated the assessment of their prognosis.

Phosphaturic mesenchymal tumor: Clinicopathological features with outcomes in 10 patients with review of literature.

Phosphaturic mesenchymal tumors (PMTs) are rare mesenchymal tumors, associated with long-standing, non-specific but often debilitating symptoms in the affected patients. These tumors display characteristic histopathological features and in case, identified timely, can be a boon for patients, given an excision is completely curative. To evaluate the clinical and histopathological features of 10 PMTs, diagnosed at our institution, along with clinical outcomes in those patients. This was a retrospective study, wherein 10 PMTs, diagnosed from January 2013 to July 2022, were included. The average age at the time of diagnosis was 40 years with an M:F ratio of 4:1. Clinical features included lumps, weakness, bone pain, difficulty in moving and walking, and pathologic fractures. The biochemical analysis showed normal serum calcium levels (average = 9.5 mg/dL), with low serum phosphorus (average = 2.2 mg/dL) and raised serum fibroblast growth factor 23 (FGF23) levels, in all the cases, wherever available. On histopathology, all tumors showed cells arranged in a hemangiopericytomatous pattern, including oval to short spindle forms. Multinucleate giant cells were present in nine tumors, and characteristic "grungy calcifications" was observed in eight tumors. Prominent pseudo cystic spaces were seen in eight tumors. A significant number of mitotic figures and tumor necrosis were not seen in any tumor. In five cases where follow-up was available, there was complete resolution of symptoms post-resection with no recurrence or metastasis. All those patients were free of disease until the last follow-up. This constitutes the first largest comprehensive study on these rare tumors from our country. PMTs can be diagnosed based on certain histopathological features and correlation with clinicoradiological and biochemical findings. These are invariably benign neoplasms. Patients are relieved of their debilitating symptoms after adequate surgical tumor resection. Therefore, their correct and timely diagnosis is crucial.