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Background: Multiglandular parathyroid disease, which is particularly frequent in patients with mild primary hyperparathyroidism, is a surgical challenge requiring bilateral cervicotomy with 4-gland exploration. Near-infrared autofluorescence of the parathyroid is increasingly used to prevent hypocalcemia after total thyroidectomy. However, its utility in decreasing operating time and aiding parathyroid identification during bilateral 4-gland exploration remains debated., Methods: In our prospective trial, we enrolled consecutive patients with sporadic mild primary hyperparathyroidism (serum calcium <2.85 mmol/L with elevated or nonadapted serum parathyroid hormone levels). With randomization, we assigned patients to classic parathyroidectomy or parathyroidectomy with near-infrared autofluorescence using the Fluobeam 800 device (near-infrared autofluorescence group). All procedures involved planned bilateral neck exploration conducted by 2 experienced surgeons. The primary outcome was mean operating time. Secondary outcomes included the number of visualized and excised glands, complication rates, and cure rates., Results: In total, 132 patients were included (66 per group). Mean age was 64.0 ± 12.0 years, with 85.6% female. Mean preoperative serum calcium level was 2.63 ± 0.11 mmol/L, and median serum PTH level 86.1 [65.6-109.8] pg/mL. The mean operating time did not significantly differ between the classic parathyroidectomy and near-infrared autofluorescence groups (46.9 ± 15.3 minutes and 51.2 ± 22.9 minutes, respectively, P = .21). The use of near-infrared autofluorescence did not significantly modify the number of identified or resected glands nor the rate of complications. Cure rates were similar between groups (92.2% and 94.8%; P = .72)., Conclusion: In this study, near-infrared autofluorescence, in the hands of experienced surgeons, did not reduce operating time for parathyroidectomy during bilateral neck exploration in mild primary hyperparathyroidism. Although not increasing operating time, further evaluation is needed, particularly regarding its role in the surgeon's training., Competing Interests: Conflict of Interest/Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hypocalcemia after total thyroidectomy is a frequent complication that can be predicted and best managed by the postoperative measurement of parathyroid hormone levels., Methods: This study included consecutive patients who underwent total thyroidectomy between 2017 and 2022. Hypocalcemia was defined as serum calcium <8.0 mg/dL and hypoparathyroidism as parathyroid hormone <15 pg/mL. After comparing serum calcium levels on postoperative day 1 and intraoperative parathyroid hormone levels 20 minutes after total thyroidectomy in the first period, an algorithm involving routine postoperative oral calcium and alfacalcidol administration in patients with intraoperative parathyroid hormone levels 20 minutes after total thyroidectomy <20 pg/mL was developed and tested during the second period. The rates of symptomatic hypocalcemia, readmission for hypocalcemia, and permanent hypoparathyroidism were compared between the 2 periods., Results: In the first period, 1,965 total thyroidectomies (1,548 women; mean age, 51 years) were performed, including 617 patients (31%) with central neck dissection for thyroid carcinoma. Of 314 patients (16%) who experienced symptomatic hypocalcemia, only 183 (58%) could be predicted using serum calcium levels on postoperative day 1 <8.0 mg/dL. This rate increased to 96% (301 patients) when using intraoperative parathyroid hormone levels 20 minutes after total thyroidectomy and serum calcium levels on postoperative day 1 (P < .001). Intraoperative parathyroid hormone levels 20 minutes after total thyroidectomy alone could predict symptomatic hypocalcemia in 90% (282) of patients. Hypoparathyroidism was permanent in 20 patients (1%), with a greater predictive value of intraoperative parathyroid hormone levels 20 minutes after total thyroidectomy over serum calcium levels on postoperative day 1 (18/20 [90%] vs 8/20 [40%], P < .01). Using the intraoperative parathyroid hormone levels 20 minutes after total thyroidectomy-based algorithm and preventive calcium supplementation in the second period of the study, 1,420 total thyroidectomies (1,106 women; mean age, 50 years) were performed, including 392 (28%) cases with central neck dissection for thyroid carcinoma. Only 2.3% (32) patients developed a symptomatic hypocalcemia compared with 16% during the first period (P < .001). Thirty-eight patients (2.7%) experienced readmission after total thyroidectomy before implementation of the supplementation protocol in our study compared with 2 patients (0.01%) after we began using the protocol (P < .001). There was no significant difference in permanent hypoparathyroidism between the 2 periods (1.3% vs 1%) (P = .8)., Conclusions: The parathyroid hormone-based algorithm determined by intraoperative parathyroid hormone levels 20 minutes after total thyroidectomy and routine preventive administration of oral calcium/calcitriol reduced the risk of symptomatic hypocalcemia and readmission after total thyroidectomy., Competing Interests: Conflict of Interest/Disclosure The authors have no relevant financial disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Near-infrared autofluorescence and indocyanine green fluorescence are 2 recent tools introduced to improve postoperative parathyroid function during thyroid surgery., Methods: We conducted a randomized prospective study. Patients undergoing total thyroidectomy were randomly assigned either to the fluorescence group, in which near-infrared autofluorescence and indocyanine green fluorescence were used, or to the control group. The primary outcomes of the study were the rate of postoperative transient and symptomatic hypocalcemia., Results: A significantly higher number of parathyroid glands were identified in the fluorescence group (3.83 vs 3.64, P = .028). The rate of postoperative symptomatic hypocalcemia was significantly lower in the fluorescence group (6% vs 17%, P = .015), as was the dosage (1.53 vs 1.91 g, P = .007) and the duration of calcium therapy (32.30 vs 45.66 days, P = .003). Having at least 2 well-vascularized parathyroid glands correlates to lower rates of transient hypocalcemia (7.4% vs 21.9%, P = .037) as well as to higher serum calcium (8.70 vs 8.42 mg/dL, P = .027) and parathyroid hormone levels (19.15 vs 11.4 pg/mL, P = .0002) on postoperative day 1., Conclusion: Near-infrared autofluorescence and indocyanine green fluorescence are novel tools that may support the endocrine surgeon in preserving and predicting post-thyroidectomy parathyroid gland function., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The risk of postoperative hungry bone syndrome after parathyroidectomy for secondary hyperparathyroidism of renal origin may alter the course of treatment, including the hospital length of stay and readmission rates. We sought to identify additional patient or hospital factors that might contribute to hungry bone syndrome after parathyroidectomy in patients with secondary hyperparathyroidism of renal origin., Methods: Patients who underwent a parathyroidectomy for secondary hyperparathyroidism of renal origin were identified in a geographically diverse, 10-state, discharge data set. Covariates included demographic data, payer status, 31 comorbidities, and hospital characteristics. The primary outcome variable of interest was hospital length of stay. Secondary outcomes were complications and 30-day readmission., Results: Of 796 patients studied, 164 patients (20.6%) were diagnosed with hungry bone syndrome. There were no differences in the rates of hungry bone syndrome by race or number of comorbidities. The average age of hungry bone syndrome patients (45.7 years ± 13.9) was younger than that of non-hungry bone syndrome patients (50.7 ± 14.8; P < .001). Hungry bone syndrome was more common among obese patients than nonobese patients (25.0% vs 15.8%; P < .001). Parathyroid autotransplant was performed at similar rates in hungry bone syndrome and non-hungry bone syndrome patients (23.8% vs 23.1%; P = .821). Median length of stay was significantly longer for hungry bone syndrome patients (6 days, interquartile range: [4, 8] versus 3 days, interquartile range: [2-6]; P < .001). Similar 30-day readmission rates were observed (hungry bone syndrome: 41 (25%) versus non-hungry bone syndrome: 147 (23%); P = .640)., Conclusion: Hungry bone syndrome occurs in 1 of 5 patients after parathyroidectomy for secondary hyperparathyroidism of renal origin. Patients should be informed of the possibility of a relatively long (6 days) length of stay after surgery as well as the moderate possibility (>20%) of another hospitalization within the 30-day postdischarge period., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Symptomatic hypocalcemia is a common complication of total thyroidectomy. Management strategies include responsive treatment initiation for symptoms or prevention by routine or parathyroid hormone-directed calcium supplementation. The comparative cost-effectiveness of even the most often utilized strategies is unclear., Methods: A Markov cohort model was created to compare routine supplementation with calcium alone (RS), postoperative parathyroid hormone-based selective supplementation with calcium and calcitriol (SS), and no supplementation (NS) in asymptomatic patients. Patients could remain asymptomatic or develop symptomatic hypocalcemia, managed with outpatient oral supplementation or intravenous calcium infusion and administered either inpatient or outpatient. Effectiveness was measured in quality-adjusted life years. Sensitivity analyses were performed to test model parameter assumptions., Results: RS was the preferred strategy, costing $329/patient and resulting in 0.497 quality-adjusted life years, which was only marginally better compared to SS ($373 for 0.495 quality-adjusted life years). NS was most costly at $4,955 for 0.491 quality-adjusted life years. Preference for RS over SS was sensitive to the probability of developing symptoms and the probability of symptom treatment with intravenous supplementation. On probabilistic sensitivity analysis, RS was preferred in 75.4% of scenarios., Conclusion: After total thyroidectomy, a preventative calcium supplementation strategy should be strongly considered. In this data-driven theoretical model, RS was the least costly option and resulted in an incremental gain in quality-adjusted life years., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Overnight hospitalization after thyroid surgery has been a widely adopted practice because of the concern for complications such as hypocalcemia and hematoma. Same-day discharge, however, has become popular in recent years., Methods: The American College of Surgeons National Surgical Quality Improvement Program Targeted Thyroidectomy database (2016-2017) was used to identify patients who underwent thyroid resections. A 1:1 propensity score matching was used to match patients who were discharged on postoperative day 0 and those discharged on postoperative days 1 or 2. Multivariable logistic regression models were constructed to assess the association between discharge timing and postoperative outcomes., Results: Of the 10,502 patients, 2,776 (26.4%) were discharged on postoperative day 0, and 7,726 (73.6%) were discharged on postoperative days 1 or 2. After propensity score matching, 1,977 matched pairs were created. In this matched cohort, the rates of readmission were similar when comparing patients discharged on postoperative day 0 with those discharged on postoperative days 1 or 2 (odds ratio 1.26, 95% confidence interval 0.78-2.05). Likewise, no differences were observed in the rates of surgical site infection, clinically severe hypocalcemia, neck hematoma, or recurrent laryngeal nerve injury., Conclusion: In a national cohort of patients undergoing thyroid surgery, same-day discharge was not associated with greater rates of readmission or complications when compared with discharge 1 or 2 days after thyroid surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: An institutional protocol for selective calcium/calcitriol supplementation after completion/total thyroidectomy was established based on the 4-hour postoperative parathyroid hormone level. The aim of this study was to evaluate the outcomes of this protocol 5 years after implementation., Methods: All patients who underwent completion/total thyroidectomy from January 2012 to December 2016 were reviewed. Predictors of a 4-hour parathyroid hormone level <10 pg/mL and symptomatic hypocalcemia were assessed., Results: Of 591 patients, 448 (76%) had a 4-hour parathyroid hormone ≥10, 72 (12%) had a 4-hour parathyroid hormone of 5-10, and 71 (12%) had a 4-hour parathyroid hormone <5. Hypocalcemic symptoms were infrequent (30/448, 7%) if the 4-hour parathyroid hormone was ≥10; 56% (40/71) of those with a 4-hour parathyroid hormone <5 reported symptoms. With 4-hour parathyroid hormone of 5-10, symptoms were reported in 32 of 72 (44%) patients; supplementation at discharge included calcium (n = 55, 76%), calcium and calcitriol (n = 12, 17%), or none (n = 5, 7%). Ten patients subsequently received calcitriol for persistent symptoms. On multivariate analysis, predictors of 4-hour parathyroid hormone <10 included incidental parathyroidectomy, malignancy, and thyroiditis; predictors of hypocalcemic symptoms included age <55 and 4-hour parathyroid hormone <10., Conclusion: After completion/total thyroidectomy, patients with a 4-hour parathyroid hormone ≥10 can be safely discharged without routine supplementation. The addition of calcitriol to calcium supplementation should be strongly considered for patients with a 4-hour parathyroid hormone of 5-10., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The clinical impact of intraoperative autofluorescence-based identification of parathyroids using a near-infrared camera remains unknown., Methods: In a before and after controlled study, we compared all patients who underwent total thyroidectomy by the same surgeon during Period 1 (January 2015 to January 2016) without near-infrared (near-infrared- group) and those operated on during Period 2 (February 2016 to September 2016) using a near-infrared camera (near-infrared+ group). In parallel, we also compared all patients who underwent surgery without near-infrared during those same periods by another surgeon in the same unit (control groups). Main outcomes included postoperative hypocalcemia, parathyroid identification, autotransplantation, and inadvertent resection., Results: The near-infrared+ group displayed significantly lower postoperative hypocalcemia rates (5.2%) than the near-infrared- group (20.9%; P < .001). Compared with the near-infrared- patients, the near-infrared+ group exhibited an increased mean number of identified parathyroids and reduced parathyroid autotransplantation rates, although no difference was observed in inadvertent resection rates. Parathyroids were identified via near-infrared before they were visualized by the surgeon in 68% patients. In the control groups, parathyroid identification improved significantly from Period 1 to Period 2, although autotransplantation, inadvertent resection and postoperative hypocalcemia rates did not differ., Conclusion: Near-infrared use during total thyroidectomy significantly reduced postoperative hypocalcemia, improved parathyroid identification and reduced their autotransplantation rate., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Because the fluorescent light intensity on an indocyanine green fluorescence angiography reflects the blood perfusion within a focused area, the fluorescent light intensity in the remaining in situ parathyroid glands may predict postoperative hypocalcemia risk after total thyroidectomy., Methods: Seventy patients underwent intraoperative indocyanine green fluorescence angiography after total thyroidectomy. Any parathyroid glands with a vascular pedicle was left in situ while any parathyroid glands without pedicle or inadvertently removed was autotransplanted. After total thyroidectomy, an intravenous 2.5 mg indocyanine green fluorescence angiography was given and real-time fluorescent images of the thyroid bed were recorded using the SPY imaging system (Novadaq, Ontario, Canada). The fluorescent light intensity of each indocyanine green fluorescence angiography as well as the average and greatest fluorescent light intensity in each patient were calculated. Postoperative hypocalcemia was defined as adjusted calcium <2.00 mmol/L within 24 hours., Results: The fluorescent light intensity between discolored and normal-looking indocyanine green fluorescence angiographies was similar (P = .479). No patients with a greatest fluorescent light intensity >150% developed postoperative hypocalcemia while 9 (81.8%) patients with a greatest fluorescent light intensity ≤150% did. Similarly, no patients with an average fluorescent light intensity >109% developed PH while 9 (30%) with an average fluorescent light intensity ≤109% did. The greatest fluorescent light intensity was more predictive than day-0 postoperative hypocalcemia (P = .027) and % PTH drop day-0 to 1 (P < .001)., Conclusion: Indocyanine green fluorescence angiography is a promising operative adjunct in determining residual parathyroid glands function and predicting postoperative hypocalcemia risk after total thyroidectomy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: In papillary thyroid microcarcinoma (PTMC), regional lymph node metastasis (LNM) is associated with a increased locoregional recurrence rate. Yet, prophylactic central lymph node dissection (CLND) targeting subclinical central LNM continues to be a matter of debate in the treatment of PTMC, which generally carries an excellent prognosis. The aim of our study was to investigate the benefits and risks of prophylactic CLND in patients with clinically node-negative PTMC., Methods: This study included 232 patients who underwent surgery for clinically node-negative PTMC from 1999 to 2006. Of these 232 patients, 113 underwent only total thyroidectomy (TT) and 119 underwent TT in conjunction with prophylactic bilateral CLND (TT with CLND). We then compared serum thyroglobulin (Tg) levels, recurrence rates, and postoperative complications between the 2 groups (TT only and TT with CLND)., Results: The postoperative stimulated serum Tg level was significantly less in the TT with CLND group than in the TT only group (1.07 vs. 2.24 ng/mL, respectively; P = .022). The stimulated Tg levels in the 2 groups became similar, however, after low-dose radioactive iodine treatment (0.44 ng/mL vs. 0.69 ng/mL, respectively; P = 0.341). There was no significant difference in 3-year locoregional control rates after TT with CLND and TT only (98.3% vs. 96.5%, respectively; P = .368). Although the frequency of permanent hypocalcemia was approximately 3 times greater in the TT with CLND group (5.6%) than in the TT only group (1.8%), this finding did not reach statistical significance., Conclusion: With prophylactic CLND, the postoperative Tg level can significantly decrease. However, prophylactic CLND is not helpful in decreasing short-term locoregional recurrence in patients with clinically node-negative PTMC. Finally, the risk of permanent hypocalcemia may increase after CLND., (Copyright © 2012. Published by Mosby, Inc.)

Background: Our goal was to determine whether routine oral calcium (OC) and vitamin D (VD) administration can effectively prevent symptoms of hypocalcemia after total thyroidectomy., Methods: Seventy-nine patients who underwent total thyroidectomy were randomly allotted to one of the following groups: (1) group A, no treatment; (2) group B, OC 3 g per day; (3) group C, OC 3 g + VD 1 mg per day. Treatment was started on postoperative (PO) day 1 in groups B and C., Results: Fewer patients in groups B and C experienced symptoms when compared with group A (P =.005). Patients in groups B and C had only minor symptoms, whereas 2 patients in group A experienced major symptoms and 6 required intravenous calcium (P <.01). The rate of hypocalcemia was slightly lower in group C (P = not significant). Treatment was discontinued by PO day 7 in all but 8 patients. Two patients still required treatment 6 months after operation (2.5%). PO parathyroid hormone levels did not differ in the 3 groups (P = not significant)., Conclusions: Routine supplementation therapy with OC or VD effectively prevents symptomatic hypocalcemia after total thyroidectomy and may allow for a safe early discharge. Further studies are necessary to determine the best treatment. The combination of OC and VD may further reduce the rate of PO hypocalcemia, without inhibiting parathyroid hormone secretion.

Background: Although use of histamine H2 antagonists for chronic treatment of primary hyperparathyroidism (PHP) is ineffective, pretreatment with cimetidine has been reported to reduce the incidence of postoperative hypocalcemia in patients with PHP undergoing neck exploratory operation. The current investigation was conducted to determine the validity of this assertion., Methods: In a randomized, double-blind, placebo-controlled trial, 20 patients with PHP were treated with either cimetidine or placebo for 10 to 14 days before neck exploratory operation. Clinical outcome and biochemical indexes before and after drug treatment in both groups were compared., Results: Cimetidine treatment resulted in a modest increase in preoperative parathyroid hormone level but did not affect any other parameter, including serum calcium level or renal tubular reabsorption of phosphate. Intraoperative time was similar in both groups. Mean postoperative calcium nadir was identical regardless of therapy (8.3 mg/dl), and seven (70%) patients from each group had at least one serum calcium measurement less than 8.5 mg/dl., Conclusions: Cimetidine treatment before neck exploratory operation for PHP does not diminish the frequency or severity of postoperative hypocalcemia.

Biochemical and hormonal effects of oral calcium supplementation in premature and asphyxiated neonates during the first few days of life are described. Eight pairs of infants were matched for gestational age and one-minute Apgar score. One member of each pair served as a control and the other was given supplemental oral calcium (75 mg/kg/24 hr) beginning at 12 and ending at 72 hours of age. The supplemental infants had significantly higher serum calcium values both during the time of supplementation and for 36 hours after supplementation was stopped. The oral calcium supplements had no significant effect on serum concentrations of phosphate, magnesium, 25-hydroxy-vitamin D3, or parathyroid hormone, The incidence of hypocalcemia after 12 hours of age was 0 in eight supplemented infants and three in eight control infants. In patients at risk for hypocalcemia, prospective use of oral calcium supplements during the period when there is inadequate calcium intake from feedings may prevent hypocalcemia, appears to be without deleterious effect on measurable chemical and hormonal factors important in calcium homeostasis, and results in maintenance of higher serum calcium levels after supplementation has been discontinued.

Despite experimental evidence that myocardial depression resulting from rapid transfusion of ACD blood (citrate binds ionic calcium) is avoidable by simultaneous calcium administration, most hypovolemic patients receive calcium either after transfusion or not at all. Similar iatrogenic hypocalcemic myocardial depression occurs in normovolemic patients with known myocardial damage who are dialyzed for acute uremia when ACD blood prime is used at high initial flow rates (350 c.c. per minute) and when dialysis is performed against low calcium dialysate (2.5 mEq. per liter or less). This study tests the hypotheses that (1) rapid transfusion of as little as one unit of CPD blood causes a significant reduction in ionized calcium, (2) the depressive effect of CPD blood is significant and similar to that of ACD blood, (3) rapid blood transfusion (ACD or CPD) is safe if calcium is given simultaneously, (4) addition of calcium to the extracorporeal heparinized blood prime used in dialysis prevents initial depression, and (5) hemodynamic instability during dialysis is prevented when the dialysate is normocalcemic. From the results of our study, we made the following conclusions: (1) Ionized calcium is reduced significantly by rapid transfusion of CPD blood; (2) acute myocardial depression noted with CPD blood is similar to that previously observed with ACD blood and is prevented during transfusion of either type of blood by simultaneous calcium administration; and (3) hemodialysis in patients who have had cardiac surgery is safe if calcium is added to blood prime and dialysate is made normocalcemic.

Adult rats underwent end-to-side portacaval shunt either 30 days prior to or 12 days following parathyroidectomy. When portacaval shunt was performed initially, the serum calcium failed to decrease following subsequent parathyroidectomy and remained within normal levels up to 110 days. When parathyroidectomy first was done, the significant hypocalcemia was corrected subsequently by portacaval shunt and serum calcium remained close to the normal level up to 75 days. The effect of portacaval shunt depended on the calcium content of the food and was obtained only when rats were fed by a regular diet. Rats on a calcium-deficient diet were hypocalcemic, similar to the parathyroidectomized rats without the portacaval shunt. Prolonged calcium-deficient diet alone, without parathyroidectomy, did not by itself result in hypocalcemia either in the intact rat or in the portacaval shunted rat. The data indicate that portacaval shunt prevents and corrects hypocalcemia in the parathyroidectomized Lewis rat as long as sufficient calcium is available in the diet.

Forty-eight low-birth-weight infants with varying degrees of respiratory distress were studied with respect to serum calcium concentration and urinary calcium excretion. Serum calcium decreased over the 24-hour study period in infants who did not receive calcium infusion. The decrease was greater in those receiving bicarbonate therapy for acidosis. Continuous calcium infusion at 1 mg/kg/hr sustained relatively normal serum calcium concentration, even in those infants who required bicarbonate. Since the changes in estimated extracellular calcium could not be accounted for by urinary excretion, a shift of calcium into bone was postulated.