Impact of a Head Covering on Photo-Therapy Induced Hypo-calcaemia in Full-term Neonates with Hyper-bilirubinemia

Background: Hyper-bilirubinemia causes yellowish discoloration of the sclera and skin in newborns and is one of the most common disorders that neonatologists face daily. In the first week of life, 60 percent of term and 80 percent of preterm babies have jaundice. In neonates with unconjugated hyper-bilirubinemia, phototherapy is the most common treatment. Objective: To compare the occurrence of hypocalcemia in full-term icteric neonates with and without head covering during phototherapy. Materials and Methodology: Two hundred and eight full-term neonates were split into two groups for photo-therapy for hyper-bilirubinemia. The heads of the participants in the study group were covered with a hat. Before beginning photo-therapy, serum bilirubin and serum calcium levels were assessed, as well as after 48 hours of photo-therapy. SPSS software was used to tabulate and analyze the data. Results: Ninety-four (45%) of the 208 neonates in the sample were males, while 114 (55%) were females. The average age was 5.56 +2.78 days, and the average weight was 3.04 +0.58 kilograms. Out of 208 neonates, 44 (21%) had hypocalcemia. Hypocalcemia occurred in 28 neonates in the control group and 16 neonates in the study group. There was no symptomatic hypocalcemia in any of the newborns. The p-value for the Chi square test was 0.2. Since this value is greater than 0.05, it is not statistically important. Conclusion: In comparison to neonates whose heads were not covered, fewer neonates with covered heads experienced hypocalcemia in our research. However, these findings were not statistically important. However, Research in other countries found that neonatal head cover at phototherapy had a substantial impact. As a result, we propose that a major multicenter study be performed in our country to determine the exact significance.

Intermittent Bi-Daily Sub-cutaneous Teriparatide Administration in Children With Hypoparathyroidism: A Single-Center Experience

Introduction: The use of teriparatide has been reported in children with hypoparathyroidism as an investigational physiologic replacement therapy.Methods: We aimed to retrospectively report our pediatric experience of bi-daily sub-cutaneous teriparatide. Results are presented as median (25th−75th quartile). As part of the routine follow-up of these patients with hypoparathyroidism, total calcium at H0 (i.e., just before injection) and H4 (i.e., 4 h after teriparatide injection) and other biomarker parameters were regularly assessed.Results: At a median age of 10.7 (8.1–12.6) years, an estimated glomerular filtration rate (eGFR) of 110 (95–118) mL/min/1.73 m2, calcium levels of 1.87 (1.81–1.96) mmol/L and an age-standardized phosphate of 3.8 (2.5–4.9) SDS, teriparatide therapy was introduced in 10 patients at the dose of 1.1 (0.7–1.5) μg/kg/day (20 μg twice daily), with further adjustment depending on calcium levels. Six patients already displayed nephrocalcinosis. Severe side effects were reported in one child: two episodes of symptomatic hypocalcemia and one of iatrogenic hypercalcemia; one teenager displayed dysgueusia. Calcium levels at H0 did not significantly increase whilst calcium at H4 and phosphate levels significantly increased and decreased, respectively. After 12 months, eGFR, calcium and age-standardized phosphate levels were 108 (90–122) mL/min/1.73 m2, 2.36 (2.23–2.48) mmol/L, 0.5 (−0.1 to 1.5), and 68 (63–74) nmol/L, respectively, with a significant decrease in phosphate levels (p = 0.01). Urinary calcium and calcium/creatinine ratio remained stable; no nephrolithiasis was observed but two moderate nephrocalcinosis appeared.Conclusion: Intermittent teriparatide therapy significantly improves calcium and phosphate control, without increasing calciuria. It appears to be safe and well-tolerated in children.

Incidence of hypocalcaemia among post-thyroidectomy patients at a tertiary care hospital at Trivandrum, Kerala, South India

Background: Hypocalcemia is one of the most common complications of thyroid surgery. It is usually temporary, but it may rarely take several months to resolve. The aim of this study was to determine the incidence of hypocalcaemia after total thyroidectomy and assess the biochemical factors that may be predictive of hypocalcemia.Methods: An observational study was conducted in 98 patients at the general surgery department of a tertiary care medical college hospital for a period of one year. Convenient method of sampling was done. All the patients undergoing total thyroidectomy were included in this study. The serum calcium level was evaluated at different times in the post-operative period as a part of the routine post-operative care at the hospital. During the postoperative period patients were carefully watched for clinical symptoms and signs of hypocalcemia.Results: In the study group, 19 (19.4%) had hypocalcemia. In the study group, 14 (14.3%) had symptomatic hypocalcemia and 5 patients (5.1%) had asymptomatic hypocalcemia. 18 patients (18.4%) had temporary hypocalcemia and 1 patient (1%) had permanent hypocalcemia. Among the patients with hypocalcemia, 18 (95%) were females and 1 (5%) patient was male. 13 (68%) patients were euthyroid, 5 (26%) patients were hyperthyroid and 1 (5%) patient was hypothyroid. Significant association was seen between diagnosis of thyroid disorders and hypocalcemia, thyroid function and hypocalcemia and between operating time and hypocalcemia.Conclusions: Incidence of hypocalcemia in patients who had undergone total thyroidectomy was found to be less. Majority of them had temporary hypocalcemia and permanent hypocalcemia was seen only in one patient.

Pseudohypoparathyroidism-Ib due to novel heterozygous stop gain mutation in exon 8 of STX16 gene: A case report

We report a case of pseudohypoparathyroidism type 1b (PHP1b) manifesting in childhood with hypocalcemic seizures. Symptomatic hypocalcemia is a common emergency in the pediatric age group with vitamin D deficiency being a frequent underlying etiology and PHP is rare. Patients with PHP1b do not depict the Albright’s hereditary osteodystrophy (AHO) phenotype typical of patients with PHP1a and pseudopseudohypoparathyroidism (PPHP). The resistance to parathyroid hormone (PTH) is documented mostly at renal tubular site of action in patients with PHP1b. Hypothyroidism is reported occasionally, signifying resistance to thyroid-stimulating hormone (TSH). Individuals with autosomal dominant and maternally inherited form of PHP harbor methylation defects at GNAS exon A/B, while sporadic and non-familial cases harbor methylation defects at other locus sites, including differentially methylated regions (GNAS-DMR). A novel heterozygous stop gain mutation c.C910T/p.Arg304X in exon 8 of the STX16 gene (Syntaxin 16) was observed in our case. Resistance seems limited to the renal action of PTH alone as currently, TSH level is normal. Maternal STX16 gene analysis results confirmed the modality of inheritance.

Measurement of serum intact parathyroid hormone (iPTH) at the end of total thyroidectomy: A reliable parameter for hypocalcemia?

Objective Total thyroidectomy represents the gold standard surgical procedure for patients with malignant thyroid disease. Over the past decades, the total thyroidectomy gradually replaced the subtotal thyroidectomy for benign thyroid disorders as well. Postoperative hypocalcemia remains the most frequent complication. The close proximity of parathyroid glands to the thyroid capsule leads often to devascularization or adventitious removal of parathyroid tissue. Clinical symptoms like paresthesia, tingling, muscle cramps or seizures often occur. Combined measurement of intact parathyroid hormone (iPTH) and calcium after the operation are used worldwide to predict postoperative hypoparathyroidism. The purpose of this study was to find out the incidence of decreased iPTH at the end of surgery and its reliability in predicting hypocalcemia. Methods We performed a retrospective analysis of 534 patients who underwent total thyroidectomy at our institution between 2000 and 2019. Medical records were reviewed to analyze the patient characteristics, indication of the procedure, laboratory and histological results, postoperative management and complications. The iPTH was measured before and at the end of the surgery, while the calcium was measured at the first postoperative day. The iPTH assay at our hospital has a normal range between 15.0 and 80.0 pg/ml. Meanwhile hypocalcemia was defined as a calcium measurement < 2.2 mmol/l. Results The mean age of the patients was 55.34 years. The female to male ratio was 4.6:1. The mean preoperative iPTH of our cohort was 48.35 pg/ml, while the postoperative iPTH was 31.74 pg/ml, indicating a mean reduction of 35.75%. A total of 174 patients (32.6%) had a iPTH < 15.0 pg/ml at the end of the surgery, indicating a reduction of 75.6%. 22 of these 174 patients (12.6%) developed clinical symptoms of hypocalcemia. In contrast only 3 patients (0.08%) with normal iPTH developed symptoms. Whole parathyroid glands were identified in 95/534 (17.8%), whereas from the 174 patients with iPTH < 15.0 pg/ml, 56 (32.2%) had at least one parathyroid gland in the operative specimens. Conclusion Measurement of iPTH at the end of total thyroidectomy is a good predictor to detect patient who are at risk for developing symptomatic hypocalcemia and calcium substitution can be started at the same day. A normal iPTH almost excludes symptomatic hypocalcemia.

The Unusual Suspect: Hypocalcemia in Preeclampsia After Magnesium Infusion

Background: Magnesium plays a vital role in calcium homeostasis. Magnesium sulfate is used in obstetric populations for the management of preeclampsia and eclampsia. Hypocalcemia secondary to iatrogenic hypermagnesemia is an uncommon complication. We report a case of symptomatic hypocalcemia due to hypermagnesemia. Clinical Case: A 26-year-old female with type 1 diabetes at 33 weeks gestation was admitted for preeclampsia. She had severe hypertension and proteinuria, and the decision to induce labor was made. She was started on a magnesium sulfate drip and remained on the drip for 33 hours. Magnesium levels peaked at 7.5 mg/dL (1.7–2.5 mg/dL). The magnesium drip was suspended after delivery. She complained of mild tingling and numbness in her hands, feet, and perioral area. Shortly after delivery, she had a pre-syncopal event. The laboratory evaluation revealed a calcium of 5.9 mg/dL (8.4–10.4) with an albumin of 2.2 g/dL (3.7–5.5), magnesium of 4.2 mg/dL, phosphorus 2.2 mg/dL (2.3–4.6) and GFR above 60 mL/min/1.73m2 . Spot urine calcium to creatinine ratio was 0.17 mg/dL. The 25-hydroxy vitamin D level was low at 12 ng/mL (20–100). The parathyroid hormone (PTH) level was inappropriately normal at 21.7 pg/mL (12–88). She had no history of hypocalcemia, and calcium level obtained six months before the presentation was normal. She received one calcium gluconate infusion, was then started on a continuous calcium gluconate infusion for symptomatic hypocalcemia. She also received oral supplementation of calcium and vitamin D. The calcium levels normalized within 24 hours as the hypermagnesemia resolved from the discontinuation of the magnesium drip. The subsequent PTH level was 38.8 pg/mL. She was discharged on vitamin D supplements. She had no recurrence of hypocalcemia. Conclusion: Our case highlights the effect of magnesium infusion on the parathyroid gland leading to profound symptomatic hypocalcemia. Magnesium plays an essential role in the secretion of PTH. Transient hypoparathyroidism can occur due to hypomagnesemia and hypermagnesemia (tocolytic therapy). In hypomagnesemia, the parathyroid gland secretes insufficient PTH, and the renal and skeletal response to PTH is reduced. In hypermagnesemia, the magnesium activates the extracellular calcium-sensing receptor, subsequently causing inhibition of the parathyroid gland. Amelioration of hypermagnesemia leads to the normalization of parathyroid function. Health care providers should be aware of this phenomenon, especially in the obstetric population receiving magnesium infusion. The monitoring of calcium levels may be necessary for this patient population. The laboratory testing should include magnesium in the evaluation of hypocalcemia. References: 1. Shoback, D. (2008). Hypoparathyroidism. New England Journal of Medicine, 359(4), 391–403.

Extreme Secretion of PTHrP From a Pancreatic Neuroendocrine Tumor, A Shift From Severe Hypercalcemia to Hypocalcemia

Background: PTHrP-secreting pancreatic neuroendocrine tumors (PNET) are a recognized cause of malignancy associated hypercalcemia. Herein, we report a case of severe hypercalcemia due to an extreme elevation of PTHrP from a PNET, where after treatment of the hypercalcemia, symptomatic hypocalcemia occurred. Clinical Case: A 59 year-old-woman with a recurrent PNET with liver metastases undergoing an evaluation for multi-visceral transplant presented with acute confusion, nausea and vomiting. Diagnostic testing identified an extreme elevation of total calcium (Ca) [>20.1 mg/dL (8.5 - 10.2)] from two different samples [serum albumin 4.1 g/dL (3.9 - 4.9)]. The total Ca level one month earlier was 8.3 mg/dL with a serum albumin of 3.1 g/dL. Total Ca measurements were performed with the Ca Gen.2 assay on a cobas c702 chemistry analyzer (Roche Diagnostics). Results greater than the analytical measurement range (0.8 – 20.1 mg/dL) were diluted with saline and confirmed (22.6 mg/dL). A Radiometer ABL 800 Flex blood gas analyzer was used to determine the ionized Ca concentration [2.94 mmol/L (1.08 - 1.30)]. Upon presentation the serum creatinine (Cr) was 2.07 mg/dL (0.58 - 0.96); eGFR utilizing the MDRD equation 24 mL/min/1.73m2; baseline serum Cr 0.78 mg/dL. Her serum 25-OH vitamin D was 31 ng/mL (31.0 - 80.0), PTH 12 pg/mL (15 - 65), phosphate 4.3 mg/dL (2.7 - 4.8) and 1, 25-OH vitamin D 39.1 (15.0 - 60.0). PTHrP measurements were performed by ARUP Laboratories via liquid chromatography tandem mass spectrometry (LC-MS/MS) and resulted in a reported value of >2500 pmol/L (0.0 - 3.4). Her symptoms resolved and the corrected Ca gradually decreased to 8 mg/dL after treatment with IV fluids, calcitonin 200 units sc every 12 hours for 48 hours, 60 mg IV pamidronate, and five sessions of hemodialysis. Within thirteen days of receiving pamidronate, her corrected Ca slowly increased to 12mg/dL; thus, she received a single dose of 120 mg sc denosumab. Nine days later, the patient developed symptomatic hypocalcemia (7.3 mg/dL) manifested by paresthesia in the hands and feet and perioral numbness. She then received multiple doses of oral and intravenous Ca along with 50,000 units of oral ergocalciferol twice weekly. The corrected Ca normalized (8.1 mg/dL) and symptoms resolved. The patient was discharged with plans for future treatment of her underlying malignancy. Conclusion: This is the first report of a PNET producing an extreme elevation of PTHrP of higher than 2500 pmol/L, resulting in a concordant extreme elevation of total calcium within a month of documented normocalcemia. Treatment of hypercalcemia with denosumab may result in the development of hypocalcemia requiring treatment.

P32: POST-OPERATIVE RELATIVE PARATHORMONE DECLINE (ΔPTH%) AND ABSOLUTE PARATHORMONE DECLINE (ΔPTH) LEVELS ARE BETTER MARKERS OF SYMPTOMATIC HYPOCALCEMIA FOLLOWING TOTAL THYROIDECTOMY THAN POST-OPERATIVE PTH ALONE

Introduction Hypocalcemia is a frequent complication following thyroidectomy which can delay discharge and increase overall treatment expenditure. We aimed to assess the predictive value of absolute and relative intact Parathormone(iPTH) decline levels as reliable markers of post-operative hypocalcemia. Method This prospective study included 95 consecutive patients at our tertiary care centre. Patients underwent either Total Thyroidectomy(TT), TT+Central Neck Dissection(CND) or TT+CND+Modified Radical Neck Dissection(MRND). iPTH levels were measured four hours after surgery and the following morning after surgery(POD 1). iPTH, absolute iPTH decline(ΔPTH) and relative iPTH decline(ΔPTH%) were calculated and correlated with hypocalcemia. Comparisons between groups were measured by chi-square test, Fischer's exact test and Mann-Whitney U test. Result Of the 95 patients, 59 had malignant disease, while 36 patients had benign histopathology. TT was performed in 69 patients, TT+CCLND in 7, and TT+CCLND+MRND in 19. 32.6% of patients(n=31) had biochemical hypocalcemia and 20%(n=19) had symptomatic hypocalcemia. The mean calcium of the cohort on Post-operative day(POD)-1 was 8.3±0.66(range=6.5-9.9) and POD-3 was 8.4±0.69(range=6.3–10.7). Median PTH, measured 4 hours after surgery was 24pg/ml(IQR–23.4;range 2.5–85.5), and measured on POD-1 was 28pg/ml(IQR–27.6;range=2-79). The ΔPTH(U=206;p<0.001) & ΔPTH% (U=127;p<0.001) were significantly higher in patients with symptomatic hypocalcemia. A ΔPTH% of 20%(sensitivity=84%;specificity=91%) and ΔPTH of 3.75 pg/ml(sensitivity = 74%; specificity=87%) were good predictors of symptomatic hypocalcemia. Conclusion Post-operative ΔPTH and ΔPTH% are reliable predictors of hypocalcemia following thyroid surgery and have the potential to facilitate a safe early discharge for patients undergoing TT. 20% fall in the PTH level(ΔPTH%) can be useful as a marker of hypocalcemia. Take-home message Post-operative ΔPTH and ΔPTH% are better predictors of hypocalcemia following thyroid surgery than a single value of post-operative PTH alone.

Differential activation of parathyroid and renal Ca2+-sensing receptors underlies the renal phenotype in autosomal dominant hypocalcemia 1

BackgroundParathyroid Ca2+-sensing receptor (CaSR) activation inhibits parathyroid hormone (PTH) release, while activation of CaSRs in kidneys and intestine attenuates local transepithelial Ca2+ transport. In patients with autosomal dominant hypocalcemia 1 (ADH1) due to activating CASR mutations, treatment of symptomatic hypocalcemia can be complicated by treatment-induced hypercalciuria, resulting in nephrocalcinosis and renal insufficiency. Although CaSRs throughout the body are activated by increased extracellular Ca2+ concentrations, it is not understood why some ADH1 patients have reduced PTH, but not hypercalciuria at presentation, despite CaSR expression in both kidney and parathyroid.MethodsActivation of the CaSR was studied in mouse models and a ADH1 patient. In vitro CaSR activation was studied in HEK293 cells.ResultsMice with a gain-of-function mutation in Casr are hypocalcemic with reduced plasma PTH levels. However, renal CaSRs are not activated as indicated by normal urinary calcium handling and unaltered renal Cldn14 expression. Activation of renal CaSRs only occurred after increasing plasma Ca2+ levels. Similarly, calcimimetic administration to wildtype mice induced hypocalcemia without activating renal CaSRs. Moreover, significant hypercalciuria was not observed in an ADH1 patient until blood Ca2+ was normalized. In vitro experiments suggest that increased CaSR levels in the parathyroid relative to the kidney contribute tissue-specific CaSR activation thresholds.ConclusionHere we delineate tissue-specific CaSR activation thresholds, where parathyroid CaSR overactivity can reduce plasma Ca2+ to levels insufficient to activate renal CaSRs, even with overactivating mutations. These findings may aid in the management of ADH1 patients.