The impact of operative duration and intraoperative fluid dynamics on postoperative hypocalcemia after total thyroidectomy: a prospective non-randomized study.

BACKGROUND: Postoperative hypocalcemia after total thyroidectomy (TT) still remains common. This prospective observation study examined the role of intraoperative time period (IOP) and intravenous fluids (IVF) in transient and permanent (> 6 months) hypocalcemia post-TT. SUBJECTS AND METHOD: Consecutive patients (n = 328; age = median (IQR); 34 (15) years; M:F = 65:263) with benign or malignant thyroid disease undergoing TT were evaluated for IOP, intraoperative IVF, serum corrected calcium, intact parathormone (iPTH), and 25-hydroxyvitamin D (25OHD) levels at baseline, 48 h, and 6 months post-TT. RESULTS: The incidence of symptomatic transient and permanent hypocalcemia post-TT was 33.5% and 7.9% respectively. In multivariate logistic regression analysis, the independent risk factors for transient hypocalcemia were IOP (odds ratio: 11.6), 48-h iPTH (4.8), IVF (2.9), hyperthyroidism (2.8), and percent calcium decline (1.07), while 25OHD deficiency increased the risk by 10.5 odds in subset with preoperative hypocalcemia. In receiver operating characteristic analysis, IOP, and IVF strongly predicted transient hypocalcemia with a threshold of 123 min and 1085 mL. Area under the curve, sensitivity, and specificity were 0.883 (95% CI: 0.838-0.928), 88.1%, and 74.4% and 0.883 (0.840-0.926; each P = 0.001), 84.4%, and 74.4% respectively. Serum 48-h calcium < 7.8 mg/dL was the only reliable predictor of permanent hypocalcemia. CONCLUSION: Operative duration > 123 min and IVF > 1085 mL increased the risk of transient hypocalcemia post-TT manyfold but not permanent hypocalcemia. Routine intraoperative identification, preservation of viable in situ parathyroid glands, and laryngeal nerves increased IOP and rates of transient hypocalcemia but improved long-term outcome.

Is there adenoma-carcinoma sequence between benign adenoma and papillary cancer of thyroid: A genomic linkage study.

BACKGROUND: The adenoma-carcinoma sequence in thyroid nodules is an enigmatic phenomenon. Genomics is the only definitive modality to resolve this hypothesis. Adenomas and papillary carcinomas tend to have mutations in RAS and highly specific BRAF gene respectively. In this context, we set out study the prevalence and clinical significance of these somatic mutations in surgical tissue samples. MATERIAL AND METHODS: This retrospective study was conducted on surgically managed thyroid nodule patients. Institutional ethical committee approval was obtained. Diagnosis was based on biochemical confirmation, imaging, fine needle aspiration cytology and later confirmed by histopathology. We selected 100 benign thyroid adenomas (BTA) and 100 papillary thyroid carcinoma (PTC) cases. Archived tumour tissue samples of selected cases were retrieved. After appropriate processing of samples, DNA extraction, cDNA preparation, PCR amplification, application of 4 sets of Primers were performed as part of mutational analysis of RAS (H-,K-,N-) and BRAF genes. RESULTS: Homozygous mutations in N-RAS were found in 36/100 (36%) of BTA and 7/100 (7%) of PTC cases. No H-RAS or K-RAS mutations were found in both groups. Homozygous mutations were found in BRAF gene in 4/100 (4%) of BTA cases and 52/100 (52%) of PTC cases. The differences were statistically significant. CONCLUSIONS: Similar N-RAS and BRAF mutations were prevalent in both benign and malignant thyroid nodules giving some evidence for linkage between them. Though not robust, we opine that there is possibility of adenoma-carcinoma sequence in thyroid nodules.

The Effect of Hypomagnesemia on Refractory Hypocalcemia after Total Thyroidectomy: A Single-Center Prospective Cohort Study.

BACKGROUND: Hypomagnesemia is known to impede hypocalcemia correction. This prospective observational study aimed to evaluate the impact of serum magnesium levels on the development of refractory hypocalcemia, which remains a concerning problem after total thyroidectomy (TT). SUBJECTS AND METHODS: Consecutive subjects (n = 312; mean age = 38.4 [range: 13-83] years; M:F = 62:250) undergoing TT for benign or malignant thyroid diseases were evaluated for serum corrected-calcium (8.4-10.4 mg/dL), magnesium (1.7-2.4 mg/dL), intact parathormone (iPTH), and 25-hydroxycholecalciferol (25OHD) levels preoperatively, at 48-h and 6-month post-TT. RESULTS: Postoperatively, 98 subjects (31.4%) exhibited transient hypocalcemia, 96 (30.8%) had hypomagnesemia, and 52 (16.7%) had refractory hypocalcemia. Preoperatively, 38 subjects (12.2%) had asymptomatic hypocalcemia and 77 (24.7%) had hypomagnesemia. In multivariate logistic regression analysis, independent risk factors of transient hypocalcemia were hyperthyroidism (odd's ratio [OR]: 5.6), 48-h iPTH (OR: 3.2), 48-h magnesium (OR: 2.7), preoperative 25OHD (OR: 0.96), and preoperative calcium (OR: 0.5; each P < 0.01). In receiver-operating characteristic analysis, percent calcium decline and 48-h magnesium reliably predicted transient hypocalcemia with a threshold of 10.5% and 1.9 mg/dL, respectively. Area under curve, sensitivity, and specificity were 0.822, 82.7%, and 72.9%; and 0.649 (each P < 0.001), 68.4%, and 63.1%, respectively. CONCLUSION: Serum magnesium below 1.9 mg/dL had 2.7 times higher odds of developing transient hypocalcemia post-TT. Hypomagnesemia and percent calcium decline >10.5% within 48-h post-TT are associated with refractory hypocalcemia, which necessitates correction of both the deficiencies for prompt resolution of symptoms.

The effect of total thyroidectomy on the recovery of bone mineral density in subjects with hyperthyroidism.

BACKGROUND: Although hyperthyroidism is associated with high turnover osteopenia and its recovery after treatment, the extent of recovery with different forms of therapy remains controversial. This prospective study evaluated the bone mineral density in thyrotoxic subjects undergoing total thyroidectomy and 131I radioactive iodine therapy. METHODS: Newly diagnosed subjects with hyperthyroidism undergoing total thyroidectomy (group 1; n = 127) and 131I radioactive iodine therapy (group 2; n = 30) were evaluated for bone mineral density by dual energy x-ray absorptiometry at the time of diagnosis (point A), on achieving euthyroidism with antithyroid drugs (point B), and 6 months after definitive treatment (point C). RESULTS: In group 1, bone mineral density (expressed as g/sq cm; mean ± standard deviation) in the hip (0.842 ± 0.157) and spine (0.97 ± 0.155) at point A, improved at point B (hip, 0.853 ± 0.157 and spine, 0.982 ± 0.155), and further improved at point C (hip, 0.91 ± 0.158 and spine, 1.053 ± 0.161, each P < .001). In group 2, at point C, bone mineral density in the hip (0.761 ± 0.168 versus point A, 0.741 ± 0.146) and spine (0.831 ± 0.159 versus point A, 0.823 ± 0.158) were less than group 1 (each P < .01). CONCLUSION: Bone mineral density improved significantly after all forms of treatment of hyperthyroidism and was greatest in lumbar vertebrae (8.6%) as early as 6 months after total thyroidectomy. The delayed recovery of bone mineral density after 131I radioactive iodine therapy needs long-term evaluation.

Is hungry bone syndrome a cause of postoperative hypocalcemia after total thyroidectomy in thyrotoxicosis? A prospective study with bone mineral density correlation.

BACKGROUND: Hungry bone syndrome is a well-established cause of postoperative hypocalcemia in thyrotoxicosis. To date, the incidence of hungry bone syndrome after total thyroidectomy is unclear. This prospective study examined the incidence of postthyroidectomy hungry bone syndrome and its correlation with preoperative bone mineral density. METHODS: Forty thyrotoxic subjects (Group A; age: mean ± SD; 36.5 ± 9.8 years) and 40 euthyroid controls with benign thyroid nodules (Group B) undergoing total thyroidectomy were evaluated for preoperative bone mineral density and serum calcium, magnesium, phosphorus, parathyroid hormone, alkaline phosphatase, and 25-Hydroxy Vitamin D serially. At least 3 parathyroid glands were preserved. RESULTS: Both groups were age and sex matched. Thyrotoxic subjects had higher postoperative hypocalcemia (82.5% vs controls 22.5%, 95% confidence interval 37.9 to 75.4), low preoperative bone mineral density and raised alkaline phosphatase (each, P = .001). Among thyrotoxic subjects experiencing hypocalcemia (n = 33), 39.4% (13/33) exhibited hungry bone syndrome (characterized by simultaneous fall in serum calcium, magnesium, and phosphorus), 18.1% (6/33) had hypoparathyroidism and 12% had hypomagnesemia. Hypocalcemic subjects exhibiting hungry bone syndrome displayed further decreased preoperative bone mineral density in the spine (0.875 ± 0.138 vs 1.024 ± 0.149 g/cm2, P = .004) and low serum magnesium 72-hour postsurgery (0.57 ± 0.23 vs 0.88 ± 0.25 mmol/L, P = .013) than those not exhibiting hungry bone syndrome. Postoperative serum calcium correlated with preoperative bone mineral density in the spine (P = .013). In group B subjects experiencing hypocalcemia (n = 9), none exhibited hungry bone syndrome but 77.78% (7/9) had hypoparathyroidism. All but one was eucalcemic after 6 months. CONCLUSION: Hungry bone syndrome occurs exclusively in thyrotoxic subjects and constitutes the major cause of postoperative hypocalcemia after total thyroidectomy. Vertebral osteoporosis and hypomagnesemia within 72 hours after total thyroidectomy is associated with the risk of hungry bone syndrome.

Rapid restoration of bone mass after surgical management of hyperthyroidism: A prospective case control study in Southern India.

CONTEXT: The rate and the extent of bone remineralization at cancellous versus cortical sites after treatment of hyperthyroidism is unclear. Few studies have examined the effect of operative management of hyperthyroidism on recovery of bone mass. OBJECTIVE: To evaluate prospectively the bone mineral density (BMD), bone mineral content (BMC), and bone areal size at the spine, hip, and forearm before and after total thyroidectomy. DESIGN AND SETTING: A prospective case control observational study from August 2011 to July 2014 in a single center. PARTICIPANTS: This study evaluated 40 overt hyperthyroid patients and 31 age-matched euthyroid controls who were operative candidates. MAIN OUTCOME MEASURES: Bone indices were measured at baseline and 6-month postoperatively using dual energy x-ray absorptiometry. Serum levels of alkaline phosphatase and 25-hydroxy vitamin D3 (25OHD) were assessed. RESULTS: Baseline BMD of hyperthyroid subjects at the spine, hip, and forearm were less than euthyroid controls (P = .001) with concomitant increases in serum alkaline phosphatase (mean ± SD, 143 ± 72 vs 72 ± 23 IU/L control; P < .001). The 25OHD level was 24.3 ± 10.6 and 26.1 ± 14.6 ng/mL in patients and controls, respectively. Among hyperthyroid patients, posttreatment BMD expressed as g/cm(2) were 0.97 ± 0.12 (vs pretreatment 0.91 ± 0.14; P = .001) at the spine, 0.87 ± 0.12 (vs pretreatment 0.80 ± 0.13; P = .001) at the hip, and 0.67 ± 0.09 (vs pretreatment 0.64 ± 0.11; P = .191) at the forearm. The percent change in BMD was greatest at spine (8.3%) followed by the hip (7.6%) and forearm (3.0%). CONCLUSION: Operative management with total thyroidectomy improved the bone loss associated with hyperthyroidism as early as 6 months postoperatively at the hip and spine despite concomitant vitamin D deficiency. Delayed recovery of bone indices at the forearm, a cortical bone, requires further long-term evaluation.