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The role of calcitonin and parathyroid hormone in the pathogenesis of post-thyroidectomy hypocalcemia.

Permanent hypocalcemia complicating thyroidectomy is a rare complication, whereas transient post-thyroidectomy hypocalcemia occurs frequently. Ten patients were studied in an attempt to elucidate the underlying mechanisms. An early and transient postoperative rise in calcitonin (CT) corresponding to a decline in calcium levels was demonstrated. Though there was no significant depression of parathyroid hormone (PTH) levels, the failure of the parathyroids to respond to hypocalcemic stimuli suggests a degree of at least transient parathyroid insufficiency. Transiently elevated CT levels appear to play a significant role in the commonly observed early, transient post-thyroidectomy hypocalcemia following subtotal and total thyroidectomy.

Calcitonin↗

Effects of short- and long-term thyroidectomy on mitochondrial and nuclear activity in adult rat brain.

We compared subcellular activities in brain and liver at various times after thyroidectomy. Male S.D. rats were used on days 5, 10 or 60 after surgery. Mitochondrial properties were estimated by determining the respective activities of oxidative phosphorylation, succinate oxidase, succinate and beta-hydroxybutyrate cytochrome c reductase and alpha-glycerophosphate dehydrogenase. Nuclear activity was estimated by measuring the RNA polymerase I activity. In brain, RNA polymerase I activity already declined at 5 days after thyroidectomy, whereas mitochondrial respiratory enzymes decreased significantly only after 60 days. In liver, nuclear RNA polymerase I and mitochondrial enzyme activities were observed to drop simultaneously by the 5th day after thyroid removal. On the other hand, daily T3 s.c. injections, 0.25 microgram/100 g B.W., were given for 10 days to rats immediately after thyroidectomy (10 days Tx) or to chronically hypothyroid rats (60 days Hth). Hormonal treatment either maintained or restored subcellular activities to their normal level, both in brain and liver. These data suggest that the metabolic properties of brain mitochondria are sensitive to thyroid hormones, but that the brain needs less iodothyronines than other organs. The fast reduction of RNA polymerase I by thyroidectomy and its subsequent restoration by T3 suggest that the nuclear activity greatly depends on thyroid status.

Animals↗

Postoperative complications of thyroidectomy for differentiated thyroid carcinoma.

OBJECTIVE: This study evaluates the incidence and risk factors of complications in patients submitted to thyroidectomy for differentiated thyroid carcinoma in a cancer hospital with residency training. STUDY DESIGN: A retrospective chart and complications review of 316 consecutive patients who underwent thyroidectomy for differentiated thyroid carcinoma. RESULTS: Of the 316 patients, the main postoperative complications were transient hypocalcemia in 87 (27.5%), permanent hypocalcemia in 16 (5.1%), transient vocal cord palsy in 4 (1.2%), and permanent vocal cord palsy in 2 (0.6%). Neck dissection and paratracheal lymph node dissection when associated with total thyroidectomy were significantly related to transitory and permanent hypocalcemia. CONCLUSION: Thyroid surgery can be performed safely in a hospital with medical residency training program under direct supervision of an experienced surgeon with acceptable morbidity. Hypocalcemia is the most significant complication. Neck and paratracheal lymph node dissections were the most significant predictors of hypocalcemia in patients submitted to total thyroidectomy.

Adolescent↗

Randomized study on oral administration of calcitriol to prevent symptomatic hypocalcemia after total thyroidectomy.

BACKGROUND: Symptomatic hypocalcemia remains the main postoperative complication after total thyroidectomy. The aim of the present study was to evaluate the role of oral supplementation of calcitriol and calcium salts in preventing severe postoperative hypocalcemia after total thyroidectomy. METHODS: A consecutive series of patients undergoing total thyroidectomy followed by administration of 500 mg of calcium salts 3 times per day were randomized to 3 different postoperative medical treatments: in group A, .5 microg of calcitriol twice per day was administered to 104 patients; in group B, 1 mmicrog of calcitriol twice per day was administered to 111 patients; and in group C, 202 patients did not receive calcitriol. RESULTS: The rate of postoperative tetany in group A was 2.9%, in group B was 0%, and in group C was 7.4% (P=.03) and the rate of paresthesias was 28.8%, 17.1%, and 22.3%, respectively (P=.19). At discontinuation of calcitriol/calcium salts treatment, intact parathyroid hormone levels did not significantly differ from the preoperative levels. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve for serum concentration of calcium in predicting postoperative tetany was .749, .858 and .862 on the first, second, and third postoperative day, respectively. The best cut-off value of calcemia for prediction tetany was 7.5 mg/dL, and the rate of severe hypocalcemia on the third postoperative day was 23.1% in group A, 9.9% in group B, and 27.2% in group C (P=.001). CONCLUSIONS: Oral administration of 1 microg of calcitriol twice per day and 500 mg of calcium salts 3 times per day after total thyroidectomy significantly decreases the risk of severe postoperative hypocalcemia.

Administration, Oral↗

Large remnant 131I ablation as an alternative to completion/total thyroidectomy in the treatment of well-differentiated thyroid cancer.

BACKGROUND: An alternative to completion thyroidectomy for well-differentiated thyroid carcinoma is to ablate the remnant lobe with 131 I. The purpose of this study is to review our own experience with large remnant ablation. METHODS: A retrospective review of 169 patients with well-differentiated thyroid cancer treated at one institution over a 14-year period was undertaken. Seventy-one patients who underwent partial thyroidectomy (PT) followed by 131 I ablation were identified. This group was compared to 98 patients treated with total thyroidectomy (TT). RESULTS: Mean follow-up was 6.2 years for the 71 PT + 131 I versus 4.7 years for the 98 TT patients (P = .184). Recurrence occurred in 4 of 71 PT + I 131 patients (5.6%) versus 9 of 98 TT patients (9.2%) (P = .393). Other than a tendency for the size of the primary to be slightly larger and for the histology to be follicular carcinoma in the PT + 131 I patients, the 2 groups were nearly identical in age, gender, and other prognostic factors such as capsular invasion and metastases. CONCLUSIONS: Large-dose ablation with 131 I is a viable alternative to completion thyroidectomy. Recurrence rates over an average 6-year period are similar to TT. Long-term monitoring of these cohorts is required.

Adenocarcinoma↗

A randomized, prospective, parallel group study comparing the Harmonic Scalpel to electrocautery in thyroidectomy.

BACKGROUND: Exhaustive hemostasis is essential to successful thyroidectomy. Electrocoagulation to control bleeding has the potential risk of injuring the surrounding structures from lateral dispersion of heat. The Harmonic Scalpel (HS) cuts and coagulates simultaneously using mechanical vibration rather than high temperatures. Because its use in thyroidectomies has been limited, we sought to compare procedure parameters and complications of thyroidectomies performed using the HS with those using electrocoagulation. METHODS: Sixty patients were randomized into 2 surgical groups, HS and the standard technique using electrocautery and ligatures as the primary hemostatic method. A sample t test or Wilcoxon rank sum test was used to compare the following parameters: operative time, number of ligatures, blood loss, pain intensity, need for extra dose(s) of analgesic, incidence of recurrent laryngeal nerve palsy, and hypoparathyroidism. RESULTS: Both groups of 30 patients were comparable in age, gender, and nature of disease. In 38 patients (63%), surgery was performed for benign disease, and in 22 (37%), for differentiated carcinoma. Operative time (arithmetic mean +/- SD) was 25 minutes less in the HS group (96 +/- 23 vs 121 +/- 34, P = .005). Median number of ligatures in the HS group was 1 (range, 0-7) versus 17 (range, 6-28) ( P < .001). Mean blood loss, estimated by gauze weight, was less with HS (35 +/- 27 mL vs 54 +/- 51 mL, P = .06). Drainage during the first 24 postoperative hours and pain intensity during the first postoperative week were similar in both groups. There were no episodes of persistent nerve palsy or hypoparathyroidism in either group. CONCLUSION: The use of HS in thyroidectomies requires less operative time than does electrocoagulation.

Adult↗

Contralateral papillary thyroid cancer at completion thyroidectomy has no impact on recurrence or survival after radioiodine treatment.

BACKGROUND: This study investigated the rate of contralateral papillary thyroid cancer (PTC) in low-risk PTC patients who had completion thyroidectomy, and were referred for radioactive iodine (RAI) therapy. The study sought predictors of contralateral disease and examined the impact of contralateral disease in RAI-treated patients. METHODS: We reviewed 20 years of data from a prospective registry for 150 patients with PTC. These patients had undergone thyroid lobectomy, followed by completion thyroidectomy, and had been referred for RAI. RESULTS: Of the 150 patients, 41% had PTC in the contralateral lobe. There was no difference in the rate of contralateral disease in low-risk patients (age <45 years, T1 tumors, lymph node-negative) compared with the remainder. There were no significant differences between patients with or without contralateral disease with respect to primary tumor size, mean age, time to completion thyroidectomy, or metastatic lymph node disease. Logistic regression analyses showed no histologic parameters that correlated with contralateral disease. There were no recurrence or survival differences in patients with or without contralateral disease after resection and RAI. CONCLUSIONS: The prevalence of tumor in the contralateral lobe of low-risk patients with PTC is significant and warrants consideration for completion thyroidectomy and radioiodine treatment. Our results, however, suggest that contralateral disease does not have an impact on recurrence or survival after treatment.

Adolescent↗

Safety and efficacy of total thyroidectomy in hands of endocrine surgery trainees.

BACKGROUND: Fear of a high complication rate of total thyroidectomy, especially in the hands of less experienced surgeons, limits its routine use. The results of total thyroidectomy in the hands of endocrine surgery trainees and consultants were compared to know whether this procedure can be performed effectively and safely by trainees. METHODS: Medical records of 232 patients who underwent total thyroidectomy from 1990 to 1997 were reviewed. Patients were put into groups A (operated by consultants) and B (trainees). Safety (postoperative hypoparathyroidism, recurrent laryngeal nerve palsy, and hemorrhage) and efficacy (postoperative radioactive iodine uptake) in the two groups were compared. RESULTS: There were 127 patients in group A and 105 in group B. Rates of occurrence of permanent hypoparathyroidism and recurrent laryngeal nerve palsy were comparable in the two groups. Postoperative radioactive iodine uptake in the two groups was not significantly different. CONCLUSIONS: Total thyroidectomy can be safely and effectively performed by endocrine surgical trainees.

Adult↗

Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome.

BACKGROUND/PURPOSE: Although medullary thyroid carcinoma (MTC) can occur sporadically, in the pediatric population it is most often associated with the multiple endocrine neoplasia syndrome (MEN type 2). Traditional screening was based on evaluation of basal and stimulated serum calcitonin levels. The recent cloning of the MEN2 gene on the RET proto-oncogene of chromosome 10 now allows for testing of gene carrier status in individuals at risk who could benefit from prophylactic treatment. The current study was undertaken to determine the appropriate age for safe total prophylactic thyroidectomy. METHODS: Over a 16-year period, 12 patients with a family history of MEN2A and one with a MEN2B underwent total thyroidectomy and central neck dissection without parathyroid autotransplantation. Four patients (31%) were treated previously for Hirschsprung's disease. RESULTS: In seven patients (mean age, 11.8 years) undergoing biochemical screening for diagnosis, multifocal MTC and C cell hyperplasia (CCH) were found in all the resected specimens. Of six patients identified with genetic screening (mean age, 9.1 years), two had elevated stimulated calcitonin levels, one (age 14) had evidence of MTC, and one (age 6) had CCH. Four patients with normal calcitonin levels had no evidence of MTC (ages 6, 8, 10) but there was one occurrence of CCH (age 11). No permanent postoperative hypoparathyroidism or recurrent laryngeal nerve damage occurred in this series. With a mean follow-up of 4 years (range, 1 to 14 years), the overall disease-free survival is 100%. CONCLUSIONS: From this study the authors conclude that total thyroidectomy can be performed safely in children and should be the treatment of choice in patients with a family history of MEN2A carrying a germinal RET mutation even if the serum basal or stimulated serum calcitonin level is normal. Total thyroidectomy should be performed as early as 5 years of age before the occurrence of CCH or MTC.

Adolescent↗

Predictive DNA testing for multiple endocrine neoplasia 2: a therapeutic challenge of prophylactic thyroidectomy in very young children.

BACKGROUND: Patients with multiple endocrine neoplasia (MEN) type 2 are at risk for early medullary thyroid carcinoma (MTC). Recently, the cloning of the ret oncogene has made it possible to identify patients at risk for MEN 2 syndrome with a high degree of reliability before presenting any symptoms. METHODS: Children of families with MEN 2 were screened genetically if one of the parents was a known gene carrier of the RET proto-oncogene. If they were carriers, thyroidectomy was performed. RESULTS: The authors report five children with MEN 2 who underwent prophylactic thyroidectomy irrespective of the results of calcitonin screening tests after genetic screening had shown that they were carrier of the RET proto-oncogene. Apart from a temporary hypocalcemia in one, the operations were uneventful. Pathology results showed MTC in three children of one family with MEN 2A at age 2, 3, and 6 years. In two families with MEN 2B the thyroidectomy specimen showed bilateral MTC in a 1-year-old and a 3-year-old child. CONCLUSIONS: These findings show that MTC occurs at very young age in children with MEN 2. The authors advocate performing prophylactic thyroidectomy in the first year of life in children with MEN 2B and at age 2 years in children with MEN 2A to obtain an optimal cure rate.

Carcinoma, Medullary↗

Post-thyroidectomy hypocalcaemia: A feature of the operation or the thyroid disorder?

It has been suggested that post-thyroidectomy hypocalcaemia is related to the presence of a thyrotoxic osteodystrophy for which a high serum concentration of bone alkaline phosphatase is a marker. Changes in serum-calcium (corrected to a standard albumin concentration of 40 g/l), alkaline phosphatase (A.P.), inorganic phosphate, and albumin were studied prospectively in 54 euthyroid patients with drug-treated Graves' disease, and in 17 controls with simple non-toxic goitre, before and serially after partial thyroidectomy. All data were paired and results indicate that the pattern of biochemical change was the same in both types of patient and that the degree of change was not related to the serum-A.P. concentration in the Graves'-disease patients. Of the patients studied within the first 24 h of operation, 5 out of 12 with Graves' disease and raised serum-A.P. (group I), 9 of 20 with Graves' disease and normal serum-A.P. (group II), and 7 of 15 controls (group III) showed a fall in serum-calcium below the lower limit of the reference range. In all three groups there was a highly significant fall in serum-calcium 24 h after operation but there was no significant difference in serum-calcium between the groups either immediately before or 24 h after operation. Serum-calcium returned to pre-surgical concentrations within 7 days of thyroidectomy and serum-A.P. concentrations by 4 to 6 weeks in all groups. There was no evidence that post-thyroidectomy hypocalcaemia is related to thyrotoxic osteodystrophy and the pattern of the biochemical changes was thought to be consistent with release of thyrocalcitonin at operation.

Adult↗

Double-blind, placebo-controlled, dose-ranging study of ramosetron for the prevention of nausea and vomiting after thyroidectomy.

BACKGROUND: Patients receiving general anesthesia during thyroidectomy have a high risk for postoperative nausea and vomiting. OBJECTIVE: This prospective, randomized, double-blind, placebo-controlled, dose-ranging study was undertaken to assess the efficacy and safety of ramosetron, a selective 5-hydroxytryptamine type 3-receptor antagonist, in preventing nausea and vomiting after thyroidectomy. METHODS: Standard general anesthetic technique and postoperative analgesia were employed. Patients undergoing thyroidectomy were randomized to receive IV ramosetron 0.15, 0.3, or 0.6 mg or placebo at completion of the procedure. During the first 48 hours after anesthesia, episodes of emesis and adverse events were assessed by nursing staff who were blinded to patients' treatment assignment. RESULTS: Eighty patients (22 men, 58 women; age range, 28-63 years; weight range, 37-91 kg) were enrolled in the study. There were no differences in demographic characteristics between treatment groups. The numbers of patients who were emesis free (no nausea, retching, or vomiting) 0 to 24 hours after anesthesia were 10 of 20 (50%) with ramosetron 0.15 mg, 17 of 20 (85%) with ramosetron 0.3 mg, 18 of 20 (90%) with ramosetron 0.6 mg, and 8 of 20 (40%) with placebo. The corresponding numbers 24 to 48 hours after anesthesia were 11 of 20 (55%), 18 of 20 (90%), 18 of 20 (90%), and 9 of 20 (45%). At both time points, only the values for ramosetron 0.3 and 0.6 mg were statistically significant versus placebo (P < or = 0.001). No clinically serious adverse events were observed in any group. CONCLUSIONS: In this population of patients receiving general anesthesia while undergoing thyroidectomy, ramosetron 0.3 mg was effective in preventing postoperative nausea and vomiting 0 to 48 hours after anesthesia. Increasing the dose to 0.6 mg provided no demonstrable benefit.

Adult↗

Comparison of granisetron and ramosetron for the prevention of nausea and vomiting after thyroidectomy.

BACKGROUND: Postoperative nausea and vomiting (PONV) are common after thyroidectomy. Granisetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, is more effective than the traditional antiemetics droperidol and metoclopramide for the prevention of PONV after thyroidectomy. Ramosetron, another new selective antagonist of 5-HT3 receptor, has been shown to have more potent and longer-acting properties than granisetron against cisplatin-induced emesis in ferrets. OBJECTIVE: This study was undertaken to compare the efficacy and tolerability of granisetron and ramosetron for the prevention of PONV after thyroidectomy. METHODS: In this randomized, double-blind study, patients received granisetron 3 mg or ramosetron 0.3 mg intravenously at the end of surgery. A standard general anesthetic technique and postoperative analgesia were used. Emetic episodes and safety were assessed during the first 24 hours and the second 24 hours after anesthesia. RESULTS: Eighty patients (15 men, 65 women) aged 33 to 58 years were included in the study. Each study group consisted of 40 patients. There were no differences between groups with regard to patient demographics. The percentage of patients who were emesis free (no nausea, no retching, no vomiting) 0 to 24 hours after anesthesia was 83% (33 of 40) with granisetron and 88% (35 of 40) with ramosetron; the corresponding rates 24 to 48 hours after anesthesia were 63% (25 of 40) and 90% (36 of 40), respectively (P = 0.004). The safety profile of the two 5-HT3 receptor antagonists was comparable, as no clinically serious adverse effects caused by the study drug were observed in either of the groups. CONCLUSIONS: Prophylactic antiemetic therapy with ramosetron was comparable to therapy with granisetron for the prevention of PONV 0 to 24 hours after anesthesia in patients who underwent thyroidectomy; 24 to 48 hours after anesthesia, ramosetron was more ef- fective than granisetron for prophylaxis against PONV in this population.

Adult↗

[Effects of thyroidectomy of the rat on the structure and functions of skeletal muscle mitochondria].

Mitochondria used in the present study were isolated from skeletal muscle of normal and thyroidectomized rats. The preparations were controlled by electron microscopy. It was not possible to find any morphological change induced by thyroidectomy, nevertheless, some difference appeared in the cytochrome contents which were slightly decreased. Oxygen consumption rates of thyroidectomized rat mitochondria were decreased when the particles were maintained in states 3 and 4 in the presence of various substrates, but the P/O ratios were not modified. The activities of mitochondrial enzymes were in general slightly affected by thyroidectomy except for glycerol-1-phosphate cytochrome c reductase and NADH rotenone sensitive cytochrome c reductase which were decreased and for glutamate dehydrogenase activity which was increased. The tRNA nucleotidyltransferase activity found in the mitochondrial matrix was not influenced by the absence of thyroid secretion. Normal rat muscle mitochondria incorporate 14C-leucine with an artificial ATP-generating system or with a respiratory substrate. The amino acid incorporation was decreased by thyroidectomy. Muscle mitochondria analyzed by polyacrylamide gel electrophoresis contained more than 30 protein components with MW ranging from 10.000 to 135.000. Thyroidectomy lowered the amount of a fraction of about 54.000 MW. It is not impossible that all the data observed in the absence of thyroid secretion are in relation with changes induced in the mitochondrial genome as previously shown in mitochondria isolated from liver or thyroidectomized rats.

Animals↗

The spectrum of emergency admissions for thyroidectomy.

Emergency physicians frequently encounter patients with thyroid disease. However, it is unusual for these thyroid disorders to create acute, life-threatening situations. Critical airway compression attributable to benign or malignant thyroid enlargement may occur suddenly. Similarly, venous obstruction from thyroid tumors or severe physiological compromise from thyrotoxicosis may require urgent treatment. We reviewed a group of patients who were evaluated by emergency physicians for acute thyroid pathology and subsequently admitted for urgent thyroidectomy. Over a 7-year period, 13 patients had acute airway compressive symptoms, and 1 had acute venous compressive symptoms. Six patients had thyrotoxicosis with physiological compromise. Common airway management techniques were successfully used. Nineteen patients underwent thyroidectomy. One patient suffered a cardiopulmonary arrest before thyroidectomy could be performed. Surgical morbidity may be increased for patients undergoing thyroidectomy for urgent indications.

Adult↗

The cricothyroid space: a guide for successful thyroidectomy.

OBJECTIVE: The frequent complications of thyroid surgery are mostly related to the anatomy of the region. This stimulated us to look for a starting point that makes exploration of the region easier and consequently reduces complications. We aimed to explore and define the anatomy of the cricothyroid [CT] region from cadaveric dissection and to present the outcome of 73 consecutive thyroidectomies starting from a space in the CT region. METHODS: Dissection in the thyroid gland region and creating a space in the CT region was performed on five cadavers [10 spaces], followed by 73 consecutive thyroidectomies through a standard approach beginning from the CT space. RESULTS: In all cadavers, a space was easily created in the CT region. Vessels, nerves and the parathyroid glands were identified. Standard thyroidectomy starting from the CT space was performed on 73 patients. The external laryngeal nerve was seen in 40% of the cases. The recurrent laryngeal nerve was identified and preserved in all patients. Six patients had temporary hypocalcaemia and eight had a temporary voice change. None of the patients had permanent hypoparathyroidism or recurrent laryngeal nerve palsy. CONCLUSION: The CT space is an avascular space medial to the thyroid lobe and is a good starting point for thyroidectomy that allows easy and safe exploration of the region.

Adult↗

Use of the electrothermal vessel sealing system versus standard vessel ligation in thyroidectomy.

OBJECTIVE: The electrothermal vessel sealing system (LigaSure) facilitates operative haemostasis by fusing blood vessel walls to form a collagen seal. The LigaSure is currently used in a variety of gastrointestinal, gynaecological and urological operations. We report our experience with LigaSure for thyroidectomy to test the hypothesis that it reduces operating time without increasing complications compared with standard vessel ligation. METHODS: This non-randomized, retrospective review included 234 consecutive patients who underwent thyroidectomy by one surgeon. Standard vessel ligation was used in 99 patients between 1997 and 2000, and the LigaSure was used in 135 patients between 2001 and 2003. The following data were collected: patient demographics, thyroid pathology, type of operation (total thyroidectomy vs lobectomy), operating time, complications (transient or permanent hypocalcaemia, <or=8 mg/dL), recurrent or superior laryngeal nerve injury, neck haematoma, wound complications, prolonged intubation), incision length and hospital stay. RESULTS: The two groups had similar demographics, thyroid pathology, types of operations and complication rates. The LigaSure group had lower operating times and incision lengths. CONCLUSION: We found that the LigaSure was as safe as standard vessel ligation for thyroidectomy, with the benefit of reduced operating time. A future prospective study has been designed.

Adult↗

Improvements in health care for patients undergoing thyroidectomy.

OBJECTIVE: In this study, we evaluated the effect on cost and clinical outcome of the implementation of departmental subspecialization and a clinical care pathway for patients undergoing thyroidectomy. METHODS: Subspecialization and a clinical thyroidectomy pathway were implemented in 2001 at the Department of Surgery, National University Hospital, Singapore. A total of 150 patients (Group A) who served as controls were compared with 143 patients who were managed after implementation of subspecialization and the clinical thyroidectomy pathway (Group B). Length of stay, postoperative complications and cost per patient were compared between the two groups. RESULTS: The mean age was 46 years and females comprised 77% of all patients. The mean length of hospital stay was shorter in Group B (1.9 days) compared with Group A (3.3 days; p < 0.001). The mean hospital charges also fell significantly after implementation, at 3,524 dollars per patient in Group B compared with 3,929 dollars in Group A (p = 0.003). There was no difference in morbidity between the two groups (2.0% and 1.4% in Groups A and B, respectively). CONCLUSION: This study confirms that length of hospital stay and hospital costs are effectively reduced through the combination of subspecialization and a clinical pathway for patients undergoing thyroidectomy. Subspecialty units and pathways reduce variation in patient care. This effectively leads to better-quality outcomes, more efficient discharge planning and improved cost-effectiveness of clinical services.

Cost-Benefit Analysis↗