Publications by authors named "Antonio Sitges-Serra"

73 Publications

Late Recovery of Parathyroid Function after Total Thyroidectomy in Children and Adults: Is There a Difference?

Horm Res Paediatr 2021 Mar 11:1-9. Epub 2021 Mar 11.

Centre for Endocrine Surgery, University College London Hospitals NHS Foundation Trust and Great Ormond Street Hospital, London, United Kingdom.

Background: Parathyroid failure after total thyroidectomy is the commonest adverse event amongst both children and adults. The phenomenon of late recovery of parathyroid function, especially in young patients with persistent hypoparathyroidism, is not well understood. This study investigated differences in rates of parathyroid recovery in children and adults and factors influencing this.

Methods: A joint dual-centre database of patients who underwent a total thyroidectomy between 1998 and 2018 was searched for patients with persistent hypoparathyroidism, defined as dependence on oral calcium and vitamin D supplementation at 6 months. Demographic, surgical, pathological, and biochemical data were collected and analysed. Parathyroid Glands Remaining in Situ (PGRIS) score was calculated.

Results: Out of 960 patients who had total thyroidectomy, 94 (9.8%) had persistent hypoparathyroidism at 6 months, 23 (24.5%) children with a median [range] age 10 [0-17], and 71 (75.5%) adults aged 55 [25-82] years, respectively. Both groups were comparable regarding sex, indication, extent of surgery, and PGRIS score. After a median follow-up of 20 months, the parathyroid recovery rate was identical for children and adults (11 [47.8%] vs. 34 [47.9%]; p = 0.92). Sex, extent, and indication for surgery had no effect on recovery (all p > 0.05). PGRIS score = 4 (HR = 0.48) and serum calcium >2.25 mmol/L (HR = 0.24) at 1 month were associated with a decreased risk of persistent hypoparathyroidism on multivariate analysis (p < 0.05).

Conclusion: Almost half of patients recovered from persistent hypoparathyroidism after 6 months; therefore, the term persistent instead of permanent hypoparathyroidism should be used. Recovery rates of parathyroid function in children and adults were similar. Regardless of age, predictive factors for recovery were PGRIS score = 4 and a serum calcium >2.25 mmol/L at 1 month.
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http://dx.doi.org/10.1159/000513768DOI Listing
March 2021

Etiology and Diagnosis of Permanent Hypoparathyroidism after Total Thyroidectomy.

J Clin Med 2021 Feb 2;10(3). Epub 2021 Feb 2.

Endocrine Surgery, Hospital del Mar, 08003 Barcelona, Spain.

Postoperative parathyroid failure is the commonest adverse effect of total thyroidectomy, which is a widely used surgical procedure to treat both benign and malignant thyroid disorders. The present review focuses on the scientific gap and lack of data regarding the time period elapsed between the immediate postoperative period, when hypocalcemia is usually detected by the surgeon, and permanent hypoparathyroidism often seen by an endocrinologist months or years later. Parathyroid failure after thyroidectomy results from a combination of trauma, devascularization, inadvertent resection, and/or autotransplantation, all resulting in an early drop of iPTH (intact parathyroid hormone) requiring replacement therapy with calcium and calcitriol. There is very little or no role for other factors such as vitamin D deficiency, calcitonin, or magnesium. Recovery of the parathyroid function is a dynamic process evolving over months and cannot be predicted on the basis of early serum calcium and iPTH measurements; it depends on the number of parathyroid glands remaining in situ (PGRIS)-not autotransplanted nor inadvertently excised-and on early administration of full-dose replacement therapy to avoid hypocalcemia during the first days/weeks after thyroidectomy.
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http://dx.doi.org/10.3390/jcm10030543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867256PMC
February 2021

Muscle strength, physical performance, and metabolic changes after subtotal parathyroidectomy for secondary hyperparathyroidism.

Surgery 2021 Apr 17;169(4):846-851. Epub 2020 Nov 17.

Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Background: Hyperparathyroidism in patients on chronic hemodialysis presents with bone pain, pruritus, and extra-skeletal calcifications. Little attention has been paid to low plasma protein concentrations and muscle weakness in these patients. The present study was undertaken to characterize the impact of subtotal parathyroidectomy for chronic hemodialysis on body composition, muscle strength, plasma proteins, quality of life, and long-term clinical course.

Methods: We performed a prospective observational before-after assessment study of consecutive chronic hemodialysis patients referred for parathyroidectomy. Patients were investigated at baseline before parathyroidectomy and then at 1 and 6 months after surgery, with the aim to assess changes in metabolic parameters, body composition by bioimpedance, muscle strength, and quality of life (36-items Short Form Health Survey questionnaire). Follow-up was terminated when patients reached 1 of the 3 pre-defined end points: recurrence of secondary hyperparathyroidism, transplantation, or death.

Results: A group of 23 patients on hemodialysis were included. Preoperative handgrip strength was diminished by 52.4 ± 17%. After parathyroidectomy, a drop of immunoreactive parathyroid hormone concentrations (1,153 vs 237 pg/mL; P < .001) was observed together with increases in plasma protein (total: 6.8 vs7.8 g/dL, s-albumin 3.7 vs 4.4 g/dL and prealbumin: 31.7 vs 35.2 mg/dL; P < .001), handgrip strength (18.3 vs 22.9 kg: P = .001) as well as an improvement in physical dimension (32.9 vs 35.6; P = .004) and vitality (32.3 vs 47.1; P = .002) domains of the 36-items Short Form Health Survey questionnaire. After10 years, one-third of the patients had died, one-third of the patients had a recurrence of secondary hyperparathyroidism, and one-third of patients had received a kidney transplant and maintained a normal parathyroid function.

Conclusion: Subtotal parathyroidectomy improves protein metabolic markers, muscle strength, and physical performance in chronic hemodialysis patients.
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http://dx.doi.org/10.1016/j.surg.2020.10.002DOI Listing
April 2021

Prevalence of basal ganglia and carotid artery calcifications in patients with permanent hypoparathyroidism after total thyroidectomy.

Endocr Connect 2020 Oct;9(10):955-962

Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Objective: Permanent hypoparathyroidism is an uncommon disease resulting most frequently from neck surgery. It has been associated with visceral calcifications but few studies have specifically this in patients with post-surgical hypoparathyroidism. The aim of the present study was to assess the prevalence of basal ganglia and carotid artery calcifications in patients with long-term post-thyroidectomy hypoparathyroidism compared with a control population.

Design: Case-control study.

Methods: A cross-sectional review comparing 29 consecutive patients with permanent postoperative hypoparathyroidism followed-up in a tertiary reference unit for Endocrine Surgery with a contemporary control group of 501 patients who had an emergency brain CT scan. Clinical variables and prevalence of basal ganglia and carotid artery calcifications were recorded.

Results: From a cohort of 46 patients diagnosed with permanent hypoparathyroidism, 29 were included in the study. The mean duration of disease was 9.2 ± 7 years. Age, diabetes, hypertension, smoking and dyslipidemia were similarly distributed in case and control groups. The prevalence of carotid artery and basal ganglia calcifications was 4 and 20 times more frequent in patients with permanent hypoparathyroidism, respectively. After propensity score matching of the 28 the female patients, 68 controls were matched for age and presence of cardiovascular factors. Cases showed a four-fold prevalence of basal ganglia calcifications, whereas that of carotid calcifications was similar between cases and controls.

Conclusion: A high prevalence of basal ganglia calcifications was observed in patients with post-surgical permanent hypoparathyroidism. It remains unclear whether carotid artery calcification may also be increased.
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http://dx.doi.org/10.1530/EC-20-0387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576655PMC
October 2020

Local relapse of parathyroid adenomas: an uncommon cause of recurrent primary hyperparathyroidism.

Cir Esp 2021 Feb 31;99(2):161-164. Epub 2020 May 31.

Unidad de Cirugía Endocrina, Departamento de Cirugía General, Hospital del Mar, Barcelona, España.

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http://dx.doi.org/10.1016/j.ciresp.2020.04.019DOI Listing
February 2021

Influence of gender and women's age on the prevalence of parathyroid failure after total thyroidectomy for multinodular goiter.

Gland Surg 2020 Apr;9(2):245-251

Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Background: Female gender, particularly of a young age, has been reported as a risk factor for hypocalcemia after total thyroidectomy. There are no studies, however, addressing specifically the influence of women's age and menstrual status on postoperative parathyroid function.

Methods: Cohort study of consecutive patients undergoing total thyroidectomy for benign goiter between 2000-2017, excluding those with associated hyperparathyroidism, reoperation or conservative procedures. Prevalence of postoperative hypocalcemia (s-Ca <8 mg/dL at 24 hours), protracted (1-month) and permanent hypoparathyroidism (>1 year) were the main variables studied. Complete >1-year follow-up was achieved for all patients developing post-thyroidectomy hypocalcemia. Demographic, disease-related, number of parathyroid glands remaining in situ (PGRIS), biochemical and surgical variables were recorded. The impact of menstrual status on parathyroid function was analyzed by comparing two groups of women using a cut-off age of 45 years.

Results: A total of 811 patients were included: 14 percent were males and 86 percent females with a mean age of 53.2 years. The prevalence of postoperative hypocalcemia was ten points higher in women than in men (23.7% 36.4%; P=0.008). Permanent hypoparathyroidism was more common in women than in men (5% 0.9%; P=0.048). Compared to females ≥45 years, young women presented higher rates of all three parathyroid failure syndromes despite similar PGRIS scores. Age <45 years and low PGRIS scores were the only independent variables predicting postoperative hypocalcemia in females.

Conclusions: Premenopausal patients presented a higher prevalence of parathyroid failure and permanent hypoparathyroidism with similar PGRIS scores suggesting the presence of a sex-hormone factor influencing post-thyroidectomy parathyroid function.
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http://dx.doi.org/10.21037/gs.2020.02.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225482PMC
April 2020

Fashions in General Surgery.

Cir Esp 2020 Mar 8;98(3):117-118. Epub 2019 Jul 8.

Departamento de Cirugía, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, España. Electronic address:

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http://dx.doi.org/10.1016/j.ciresp.2019.06.005DOI Listing
March 2020

MANAGEMENT OF ENDOCRINE DISEASE: Unmet therapeutic, educational and scientific needs in parathyroid disorders.

Eur J Endocrinol 2019 09 1;181(3):P1-P19. Epub 2019 Jun 1.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

PARAT, a new European Society of Endocrinology program, aims to identify unmet scientific and educational needs of parathyroid disorders, such as primary hyperparathyroidism (PHPT), including parathyroid cancer (PC), and hypoparathyroidism (HypoPT). The discussions and consensus statements from the first PARAT workshop (September 2018) are reviewed. PHPT has a high prevalence in Western communities, PHPT has a high prevalence in Western communities, yet evidence is sparse concerning the natural history and whether morbidity and long-term outcomes are related to hypercalcemia or plasma PTH concentrations, or both. Cardiovascular mortality and prevalence of low energy fractures are increased, whereas Quality of Life is decreased, although their reversibility by treatment of PHPT has not been convincingly demonstrated. PC is a rare cause of PHPT, with an increasing incidence, and international collaborative studies are required to advance knowledge of the genetic mechanisms, biomarkers for disease activity, and optimal treatments. For example, ~20% of PCs demonstrate high mutational burden, and identifying targetable DNA variations, gene amplifications and gene fusions may facilitate personalized care, such as different forms of immunotherapy or targeted therapy. HypoPT, a designated orphan disease, is associated with a high risk of symptoms and complications. Most cases are secondary to neck surgery. However, there is a need to better understand the relation between disease biomarkers and intellectual function, and to establish the role of PTH in target tissues, as these may facilitate the appropriate use of PTH substitution therapy. Management of parathyroid disorders is challenging, and PARAT has highlighted the need for international transdisciplinary scientific and educational studies in advancing in this field.
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http://dx.doi.org/10.1530/EJE-19-0316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598862PMC
September 2019

Parathyroid autotransplantation in thyroid surgery.

Langenbecks Arch Surg 2018 May 10;403(3):309-315. Epub 2018 Feb 10.

Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Background: Careful parathyroid gland dissection and in situ preservation was the time-honored approach to prevent parathyroid failure after total thyroidectomy. The relative success of parathyroid autotransplantation of hyperplastic parathyroid tissue in patients with renal or hereditary hyperparathyroidism did popularize the use of normal parathyroid tissue autografts during thyroidectomy to prevent permanent hypoparathyroidism. Proof of autograft function in this setting, however, is controversial.

Purpose: This narrative review aims at reviewing critically the current status of parathyroid autotransplantation during total thyroidectomy. It is also meant to analyze from the historical, methodological, and clinical points of view the claimed benefit of normal parathyroid gland autotransplantation. A focus is placed on the prevention of permanent hypoparathyroidism by parathyroid autotransplantation.

Conclusions: Liberal parathyroid autotransplantation was proposed in the mid 1970s but evidence of function is scarce. Proofs are accumulating that parathyroid autografts not only increase the rate of postoperative hypocalcemia, but may be also contribute to permanent hypoparathyroidism.
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http://dx.doi.org/10.1007/s00423-018-1654-5DOI Listing
May 2018

The PGRIS and parathyroid splinting concepts for the analysis and prognosis of protracted hypoparathyroidism.

Gland Surg 2017 Dec;6(Suppl 1):S86-S93

Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Most patients with hypocalcemia after total thyroidectomy will recover the parathyroid function in a few weeks, but some 20-30% of them will still be in the need for replacement therapy one month after surgery and about 5-10% of those will develop permanent hypoparathyroidism. Although postoperative hypocalcemia has been related to several demographic and metabolic causes, parathyroid hormone (PTH) decline, resulting from autotransplantation, inadvertent excision or devascularization of the parathyroid glands, is the common final pathway. The number of parathyroid glands remaining in situ (PGRIS) is a key variable to understand the pathogenesis of protracted hypoparathyroidism and the chances for restoration of the parathyroid function. Normal-high serum calcium concentration, probably achieved by a more intensive medical treatment at the time of hospital discharge, has been identified as an independent variable favoring recovery of the parathyroid function. This we refer to as parathyroid splinting, a hypothesis holding that putting the injured parathyroid parenchyma at rest after thyroidectomy may improve long-term outcome of protracted hypoparathyroidism.
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http://dx.doi.org/10.21037/gs.2017.07.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756749PMC
December 2017

A nomogram to predict the likelihood of permanent hypoparathyroidism after total thyroidectomy based on delayed serum calcium and iPTH measurements.

Gland Surg 2017 Dec;6(Suppl 1):S11-S19

Endocrine Surgery Unit, University Hospital del Mar, Barcelona, Spain.

Background: Retrospective studies have shown that delayed high-normal serum calcium and detectable iPTH are independent variables positively influencing outcome of prolonged parathyroid failure after total thyroidectomy (TT). The aim of the present study was to examine prospectively the ability of these two variables to predict permanent hypoparathyroidism in patients under replacement therapy for postoperative hypocalcemia.

Methods: Prospective observational multicenter study of patients undergoing TT followed by postoperative parathyroid failure (serum calcium <8 mg/dL within 24 h and PTH <15 pg/mL 4 h after surgery). Serum calcium, vitamin D and iPTH were determined before thyroidectomy, 24 h after surgery, at 1 month and then periodically until recovery of the parathyroid function or permanent hypoparathyroidism was diagnosed after at least 1 year follow-up.

Results: Some 145 patients with postoperative hypocalcemia were investigated [s-Ca 7.5 (0.5) mg/dL]. Hypocalcemia recovered within 30 days in 91 (63%) patients and 54 (37%) developed protracted hypoparathyroidism {iPTH 5.8 [4] pg/mL at 1 month}, of whom 32 recovered within 1 year and 22 developed permanent hypoparathyroidism. Protracted hypoparathyroidism was related to few parathyroid glands remaining in situ (PGRIS). Serum calcium concentration (mg/dL) at 1 postoperative month correlated positively with the rate of recovery (percent) from protracted hypoparathyroidism: <8.5 (20%); 8.5-9 (29%); 9.1-9.5 (70%); 9.6-10 (89%); >10 (83%) (P=0.013). Serum iPTH at 1 month was also higher (7.3 . 3.7 pg/mL; P=0.002) in recovered protracted hypoparathyroidism. The combination of both variables predicts the likelihood of recovery of the parathyroid function with >90% accuracy.

Conclusions: High-normal serum calcium and low but detectable iPTH concentrations at 1 month after TT were associated with better outcome of protracted hypoparathyroidism. A nomogram combining both variables may guide medical treatment and monitoring of post-thyroidectomy prolonged hypoparathyroidism.
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http://dx.doi.org/10.21037/gs.2017.10.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756757PMC
December 2017

Clinical profile and long-term follow-up of 32 patients with postoperative permanent hypoparathyroidism.

Gland Surg 2017 Dec;6(Suppl 1):S3-S10

Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Background: Parathyroid failure is the most common complication after total thyroidectomy but permanent impairment of the parathyroid function is unusual. Limited data is available assessing long-term follow-up, quality of life and complications occurring in patients with permanent hypoparathyroidism (PH). We aimed to assess the incidence of complications derived from PH status, their influence on the quality of life perceived by PH patients and its relation to standard medical treatment with calcium salts and active vitamin D analogues.

Methods: Cross-sectional observational study of consecutive patients undergoing total thyroidectomy who developed PH and were followed at least twice a year at a referral endocrine surgery unit. PH was defined as intact parathyroid hormone (iPTH) levels <13 pg/mL and the need for replacement therapy with calcium and/or vitamin D for at least 1 year after surgery. Quality of life was assessed using the SF-36 questionnaire. Data regarding doses and type of vitamin D analogues and calcium supplementation, serum calcium fluctuations, bone densitometry and renal ultrasound were recorded.

Results: The cohort included 32 patients (3 male/29 female) with a mean age of 51.2±15.2 years. The mean follow-up was 78±68 months and the total follow-up length was 70,080 PH patient/days. Five (15.6%) patients showed a decreased renal function. At least one clinical adverse event was observed in 18 (56.3%) patients. There was a slight decrease of the punctuation in the SF-36 questionnaire for the perceived quality of life that was only significant for the emotional role.

Conclusions: PH and its treatment carry a mild to moderate burden of illness if followed closely. During a mean follow-up of nearly 6 years, only half of the patients suffered a relevant clinical event with little impact on their quality of life.
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http://dx.doi.org/10.21037/gs.2017.11.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756756PMC
December 2017

Time to parathyroid function recovery in patients with protracted hypoparathyroidism after total thyroidectomy.

Eur J Endocrinol 2018 Jan 24;178(1):103-111. Epub 2017 Oct 24.

Endocrine Surgery Unit, Hospital del Mar, Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain.

Objective: Hypocalcaemia is the most common adverse effect after total thyroidectomy. It recovers in about two-thirds of the patients within the first postoperative month. Little is known, however, about recovery of the parathyroid function (RPF) after this time period. The aim of the present study was to investigate the time to RPF in patients with protracted (>1 month) hypoparathyroidism after total thyroidectomy.

Design: Cohort prospective observational study.

Methods: Adult patients undergoing total thyroidectomy for goitre or thyroid cancer. Cases with protracted hypoparathyroidism were studied for RPF during the following months. Time to RPF and variables associated with RPF or permanent hypoparathyroidism were recorded.

Results: Out of 854 patients undergoing total thyroidectomy, 142 developed protracted hypoparathyroidism. Of these, 36 (4.2% of the entire cohort) developed permanent hypoparathyroidism and 106 recovered: 73 before 6 months, 21 within 6-12 months and 12 after 1 year follow-up. Variables significantly associated with RPF were the number of parathyroid glands remaining (not autografted nor inadvertently resected) and a serum calcium concentration >2.25 mmol/L at one postoperative month. Late RPF (>6 months) was associated with surgery for thyroid cancer. RPF was still possible after one year in patients with four parathyroid glands preserved and serum calcium concentration at one month >2.25 mmol/L.

Conclusions: Permanent hypoparathyroidism should not be diagnosed in patients requiring replacement therapy for more than six months, especially if the four parathyroid glands were preserved.
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http://dx.doi.org/10.1530/EJE-17-0589DOI Listing
January 2018

Short and Long-Term Outcomes After Surgical Procedures Lasting for More Than Six Hours.

Sci Rep 2017 08 23;7(1):9221. Epub 2017 Aug 23.

Department of Surgery, Hospital del Mar, Barcelona, 08003, Spain.

Long-term all-cause mortality and dependency after complex surgical procedures have not been assessed in the framework of value-based medicine. The aim of this study was to investigate the postoperative and long-term outcomes after surgical procedures lasting for more than six hours. Retrospective cohort study of patients undergoing a first elective complex surgical procedure between 2004 and 2013. Heart and transplant surgery was excluded. Mortality and dependency from the healthcare system were selected as outcome variables. Gender, age, ASA, creatinine, albumin kinetics, complications, benign vs malignant underlying condition, number of drugs at discharge, and admission and length of stay in the ICU were recorded as predictive variables. Some 620 adult patients were included in the study. Postoperative, <1year and <5years cumulative mortality was 6.8%, 17.6% and 45%, respectively. Of patients discharged from hospital after surgery, 76% remained dependent on the healthcare system. In multivariate analysis for postoperative, <1year and <5years mortality, postoperative albumin concentration, ASA score and an ICU stay >7days, were the most significant independent predictive variables. Prolonged surgery carries a significant short and long-term mortality and disability. These data may contribute to more informed decisions taken concerning major surgery in the framework of value-based medicine.
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http://dx.doi.org/10.1038/s41598-017-09833-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569056PMC
August 2017

Failure of fragmented parathyroid gland autotransplantation to prevent permanent hypoparathyroidism after total thyroidectomy.

Langenbecks Arch Surg 2017 Mar 7;402(2):281-287. Epub 2017 Jan 7.

Endocrine Surgery Unit, Hospital del Mar, Passeig Marítim 25-29, 08003, Barcelona, Spain.

Purpose: Parathyroid autotransplantation during total thyroidectomy leads to higher rates of postoperative hypocalcaemia. It has been argued, however, that it prevents permanent hypoparathyroidism. The impact of autografted normal parathyroid gland fragments on long-term parathyroid status has not been assessed properly. To clarify this, the short- and long-term parathyroid function was assessed in patients with three glands remaining in situ after total thyroidectomy, in whom the fourth gland was either autotransplanted (Tx) or accidentally resected (AR).

Methods: Consecutive patients (n = 669) undergoing first-time total thyroidectomy were prospectively studied recording the number of parathyroid glands remaining in situ: PGRIS =4-(glands autografted + glands in the specimen). The study was focused on the subgroup of 186 patients with three parathyroid glands remaining in situ as a result of either accidental resection (AR, n = 76) or autotransplantation into the sternocleidomastoid muscle (Tx, n = 110). Prevalence of postoperative hypocalcaemia, protracted, and permanent hypoparathyroidism were compared between the two groups. Demographic, disease-related, laboratory, and surgical variables were recorded. All patients were followed for at least 1 year.

Results: Both groups were comparable in terms of disease and extent of surgery. Mean postoperative serum calcium was the same (AR: 1.97 ± 0.2 vs Tx: 1.97 ± 0.22 mmol/L). Rates of protracted (AR: 24% vs Tx: 25.5%) and permanent hypoparathyroidism (AR: 5.3% vs Tx: 7.3%) were similar in both groups.

Conclusions: The prevalence of parathyroid failure syndromes after total thyroidectomy was similar whether a parathyroid gland was inadvertently excised or autotransplanted. Autotransplantation did not influence the permanent hypoparathyroidism rate.
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http://dx.doi.org/10.1007/s00423-016-1548-3DOI Listing
March 2017

Compliance with recommendations on surgery for primary hyperparathyroidism-from guidelines to real practice: results from an Iberian survey.

Langenbecks Arch Surg 2016 Nov 19;401(7):953-963. Epub 2015 Dec 19.

Hospital Santo Antonio, Largo Professor Abel Salazar, 4099-001, Porto, Portugal.

Purpose: Knowledge about compliance with recommendations derived from the positional statement of the European Society of Endocrine Surgeons on modern techniques in primary hyperparathyroidism surgery and the Third International Workshop on management of asymptomatic primary hyperparathyroidism is scarce. Our purpose was to check it on a bi-national basis and determine whether management differences may have impact on surgical outcomes.

Methods: An online survey including questions about indications, preoperative workup, surgical approach, intraoperative adjuncts, and outcomes was sent to institutions affiliated to the endocrine surgery divisions of the National Surgical Societies from Spain and Portugal. A descriptive evaluation of the responses was performed. Finally, we assessed the correlation between the different types of management with the achievement of optimal results, defined as a cure rate equal or greater than the median of all interviewed institutions.

Results: Fifty-seven hospitals (41 Spanish, 16 Portuguese) answered the survey. First-ordered imaging tests were neck ultrasound and sestamibi scan. Facing negative or non-concordant results, 44 % of surgeons ordered additional tests before first-time surgery, and 84 % before reoperations. When indicated, selective parathyroidectomy was an acceptable option for 95 % of institutions as first-time surgery and for 51 % in reoperations. Intraoperative parathormone measurements were used by 92 % of departments. The surgical outcomes were good in most institutions (median cure rate 97 %) and were influenced mostly by the presence of an endocrine surgery unit in the surgical department (p = 0.038).

Conclusions: Practice of Iberian endocrine surgeons is consistent with current recommendations on surgery for primary hyperparathyroidism, with variability in some areas.
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http://dx.doi.org/10.1007/s00423-015-1362-3DOI Listing
November 2016

Inadvertent parathyroidectomy during total thyroidectomy and central neck dissection for papillary thyroid carcinoma.

Surgery 2017 03 13;161(3):712-719. Epub 2016 Oct 13.

Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Background: The main drawback of central neck lymph node dissection is postoperative parathyroid failure. Little information is available concerning inadvertent resection of the parathyroid glands in this setting and its relationship to postoperative hypoparathyroidism. Our aim was to determine the prevalence of inadvertent parathyroidectomy during total thyroidectomy and central neck dissection for papillary thyroid cancer and its impact on short-and long-term parathyroid function.

Methods: This was a prospective observational study of consecutive patients undergoing first-time total thyroidectomy with a central neck dissection for papillary carcinoma >10 mm. Prevalence and risk factors for inadvertent parathyroidectomy were recorded. Serum calcium and intact parathyroid hormone concentrations were determined 24 hours after operation and then periodically in patients developing postoperative hypocalcemia. All patients were followed for a minimum of one year.

Results: Whole gland (n = 33) or microscopic parathyroid fragments (n = 14) were identified in 47/170 (28%) operative specimens. The lower parathyroid glands were involved more often. Variables influencing inadvertent parathyroidectomy were extrathyroidal extension of the tumor and therapeutic lymphadenectomy. Neither lateral neck dissection nor the number of lymph nodes retrieved affected the rate of inadvertent parathyroid resection. Postoperative hypocalcemia and permanent hypoparathyroidism were more frequent after inadvertent parathyroidectomy (64% vs 46% and 15% vs 4%; P ≤ .03 each).

Conclusion: Inadvertent parathyroidectomy during total thyroidectomy with central neck dissection for papillary thyroid carcinoma is common and involves the inferior glands more frequently in patients with extended resections and clinical N1a disease. Inadvertent resection of parathyroid glands is associated with greater rates of postoperative hypocalcemia and permanent hypoparathyroidism.
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http://dx.doi.org/10.1016/j.surg.2016.08.021DOI Listing
March 2017

Current dilemmas in the diagnosis and management of follicular thyroid tumors.

Expert Rev Endocrinol Metab 2016 Sep 18;11(5):379-385. Epub 2016 Aug 18.

c Department of Surgery , Universitat Autònoma de Barcelona, Hospital del Mar , Barcelona , Spain.

Follicular carcinoma (FTC) is a relatively uncommon type of differentiated thyroid carcinoma. Guidelines have often dealt with FTC and papillary thyroid cancer as a single disease. Over the last decade, however, a better understanding of these two types of thyroid cancer indicates that they cannot be analysed together. Neither ultrasonography nor fine-needle aspiration cytology can provide a clear distinction between FTC and follicular adenoma. New molecular diagnostic techniques may be used to identify a subpopulation of follicular neoplasms with a low probability of being malignant. Diagnostic surgery-usually hemithyroidectomy- is recommended for most thyroid follicular lesions without a certain preoperative diagnosis. If FTC is diagnosed most-perhaps not all- patients will require a completion thyroidectomy. While widely invasive FTC usually does not pose diagnostic or therapeutic doubts, consensus on the diagnosis of non-invasive follicular lesions is still lacking. Prognosis of FTC is mostly dependent on local invasion and distant metastasis that, in turn, correlate with tumor size.
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http://dx.doi.org/10.1080/17446651.2016.1218760DOI Listing
September 2016

Multigland primary hyperparathyroidism--frequently considered, seldom encountered.

Langenbecks Arch Surg 2015 Dec 20;400(8):863-6. Epub 2016 Jan 20.

Department of Surgery, Hospital Del Mar, Barcelona, Spain.

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http://dx.doi.org/10.1007/s00423-016-1373-8DOI Listing
December 2015

Esophageal recurrence of medullary thyroid carcinoma.

Gland Surg 2015 Dec;4(6):564-6

1 Department of General Surgery, Hospital de la Princesa, Madrid, Spain ; 2 Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Medullary thyroid carcinoma (MTC) metastasizes to the regional lymph nodes and to the lungs, liver and bones. Only one case of recurrence of MTC involving the upper gastrointestinal tract has been reported so far. We describe the case of a 38-year-old woman with MTC, who developed an upper esophageal submucosal recurrence after two previous local recurrences treated surgically and one ethanol injection. After resection of the right lateral esophageal wall, calcitonin dropped by 60% and showed a doubling time >1 year. We cannot rule out the role of deep ethanol injection in the involvement of the cervical esophagus wall.
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http://dx.doi.org/10.3978/j.issn.2227-684X.2015.03.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647017PMC
December 2015

Undescended parathyroid adenomas as cause of persistent hyperparathyroidism.

Gland Surg 2015 Aug;4(4):295-300

Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Background: Undescended glands are a rare cause of primary and secondary hyperparathyroidism (HPT), but they are more common, however, among patients with recurrent HPT or those who have undergone a failed initial cervical exploration. The currently development of more precise noninvasive imaging techniques has improved the results of preoperative diagnosis of these ectopic lesions.

Methods: The operative reports of patients undergoing parathyroidectomy at our institution were reviewed to identify patients with an undescended parathyroid gland adenomas. Demographic, clinical, imaging and surgical variables were recorded.

Results: Three patients were included: 2/598 parathyroidectomies performed for primary HPT and 1/93 performed for secondary HPT. One case is presented as jaw tumor syndrome (JTS). All the patients had undergone at least one operation before the definitive focused surgery and represented 6% of our parathyroid reoperations. No significant complications and no recurrences were observed in the long-term follow up.

Conclusions: Accurate preoperative localization of these lesions was possible with noninvasive studies. High cure rate is possible through selective approach when accurate preoperative localization. Thorough knowledge of parathyroid embryology and meticulous surgical technique are essential, particularly in patients with previous unsuccessful explorations.
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http://dx.doi.org/10.3978/j.issn.2227-684X.2015.04.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523623PMC
August 2015

European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults.

Eur J Endocrinol 2015 Aug;173(2):G1-20

Section of Specialized EndocrinologyClinic of Medicine, Oslo University Hospital, Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus, DenmarkDepartment of Clinical and Experimental MedicineUniversity of Pisa, Pisa, ItalyEndocrine Research UnitDepartment of Veterans Affairs, San Francisco VA Medical Center, University of California, San Francisco, California, USAEndocrine Surgery UnitHospital Universitari del Mar, Barcelona, SpainRenal DivisionGhent University Hospital, Ghent, BelgiumDivision of EndocrinologyDepartment of MedicineDepartment of Clinical EpidemiologyLeiden University Medical Center, Leiden, The NetherlandsDepartment of Clinical EpidemiologyAarhus University Hospital, Aarhus, Denmark Section of Specialized EndocrinologyClinic of Medicine, Oslo University Hospital, Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus, DenmarkDepartment of Clinical and Experimental MedicineUniversity of Pisa, Pisa, ItalyEndocrine Research UnitDepartment of Veterans Affairs, San Francisco VA Medical Center, University of California, San Francisco, California, USAEndocrine Surgery UnitHospital Universitari del Mar, Barcelona, SpainRenal DivisionGhent University Hospital, Ghent, BelgiumDivision of EndocrinologyDepartment of MedicineDepartment of Clinical EpidemiologyLeiden University Medical Center, Leiden, The NetherlandsDepartment of Clinical EpidemiologyAarhus University Hospital, Aarhus, Denmark Section of Specialized EndocrinologyClinic of Medicine, Oslo University Hospital, Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus, DenmarkDepartment of Clinical and Experimental MedicineUniversity of Pisa, Pisa, ItalyEndocrine Research UnitDepartment of Veterans Affairs, San Francisco VA Medical

Hypoparathyroidism (HypoPT) is a rare (orphan) endocrine disease with low calcium and inappropriately low (insufficient) circulating parathyroid hormone levels, most often in adults secondary to thyroid surgery. Standard treatment is activated vitamin D analogues and calcium supplementation and not replacement of the lacking hormone, as in other hormonal deficiency states. The purpose of this guideline is to provide clinicians with guidance on the treatment and monitoring of chronic HypoPT in adults who do not have end-stage renal disease. We intend to draft a practical guideline, focusing on operationalized recommendations deemed to be useful in the daily management of patients. This guideline was developed and solely sponsored by The European Society of Endocrinology, supported by CBO (Dutch Institute for Health Care Improvement) and based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) principles as a methodological base. The clinical question on which the systematic literature search was based and for which available evidence was synthesized was: what is the best treatment for adult patients with chronic HypoPT? This systematic search found 1100 articles, which was reduced to 312 based on title and abstract. The working group assessed these for eligibility in more detail, and 32 full-text articles were assessed. For the final recommendations, other literature was also taken into account. Little evidence is available on how best to treat HypoPT. Data on quality of life and the risk of complications have just started to emerge, and clinical trials on how to optimize therapy are essentially non-existent. Most studies are of limited sample size, hampering firm conclusions. No studies are available relating target calcium levels with clinically relevant endpoints. Hence it is not possible to formulate recommendations based on strict evidence. This guideline is therefore mainly based on how patients are managed in clinical practice, as reported in small case series and based on the experiences of the authors.
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http://dx.doi.org/10.1530/EJE-15-0628DOI Listing
August 2015

Local recurrence of papillary thyroid cancer.

Expert Rev Endocrinol Metab 2015 Jul 7;10(4):349-352. Epub 2015 Jun 7.

a Hospital del Mar, Endocrine Surgery Unit Barcelona, Barcelona, Spain.

Management of advanced papillary thyroid cancer (PTC >10 mm) is changing its focus. Mortality was the main outcome measure for patients treated before the 90s. In the past two decades, however, most patients diagnosed with PTC belong to the very low risk of death group. On the other hand, local recurrence of PTC remains a clinical problem, with rates up to 25% depending on the presence of nodal metastasis, tumor diameter, and the skill of the surgeon to completely remove the primary tumor and the associated lymph node metastasis at first-time thyroidectomy. After optimized surgery (total thyroidectomy plus central neck dissection), radioiodine ablation has very little influence on lymph node recurrence that now presents mostly as lateral neck node metastasis that was overlooked or incompletely resected at the time of initial surgery.
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http://dx.doi.org/10.1586/17446651.2015.1053870DOI Listing
July 2015

THERAPY OF ENDOCRINE DISEASE: Central neck dissection: a step forward in the treatment of papillary thyroid cancer.

Eur J Endocrinol 2015 Dec 18;173(6):R199-206. Epub 2015 Jun 18.

Endocrine Surgery UnitDepartment of Surgery, Hospital del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain.

Since its introduction in the '70s and '80s, CND for papillary cancer is here to stay. Compartment VI should always be explored during surgery for papillary thyroid carcinoma (PTC) for obvious lymph node metastases. These can be easily spotted by an experienced surgeon or, eventually, by frozen section. No doubt, obvious nodal disease in the Delphian, paratracheal and subithsmic areas should be dissected in a comprehensive manner (therapeutic central neck dissection), avoiding the selective removal of suspicious nodes. Available evidence for routine prophylactic CND is not completely satisfactory. Our group's opinion, however, is that it reduces or even eliminates the need for repeat surgery in the central neck, better defines the extent (and stage) of the disease and provides a further argument against routine radioiodine ablation. Thus, PTC is becoming more and more a surgical disease that can be cured by optimized surgery alone in the majority of cases. Prophylactic CND, however, involves a higher risk for the parathyroid function and should be skilfully performed, preferably only on the same side as the primary tumour and preserving the cervical portion of the thymus.
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http://dx.doi.org/10.1530/EJE-15-0481DOI Listing
December 2015

Mortality after thyroid surgery, insignificant or still an issue?

Langenbecks Arch Surg 2015 May 23;400(4):517-22. Epub 2015 Apr 23.

Neck and Breast Surgery Unit, Department of Surgery, Hospital Fundación Jiménez Díaz, Avda Reyes Católicos, 2, 28040, Madrid, Spain,

Background: Thyroidectomy is considered to be a safe procedure. Although very uncommon, death may occur after thyroid resection. The aim of this study was to investigate the prevalence and causes of death after thyroidectomy and the associated risk factors in the modern era of thyroid surgery.

Patients And Methods: A structured questionnaire was sent to all endocrine surgery units in Spain to report all deaths that occurred after thyroidectomy in recent years.

Results: Twenty-six surgical units, encompassing 30.495 thyroidectomies, returned the questionnaire. A total of 20 deaths (0.065%) were recorded: 12 women (60%) and 8 men (40%) with a median age of 65 years (range 32-86). Half of the patients had a retrosternal goiter with a median weight of 210 g. The median operative time was 185 min. Histological diagnoses were benign goiter (35%) or thyroid carcinoma (65%): differentiated (30%), medullary (20%), poorly differentiated/anaplastic (10%), and colorectal cancer metastasis (5%). Causes of death were cervical hematoma (30%), respiratory distress/pneumonia due to prolonged endotracheal intubation (25%), tracheal injury (15%), heart failure (15%), sepsis (wound infection/esophageal perforation) (10%) and mycotic aneurysm (5%). The median time from surgery to death was 14 days (range 1-85).

Conclusions: Death after thyroidectomy is very uncommon, and most often results from a combination of advanced age, giant goiters, and upper airway complications.
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http://dx.doi.org/10.1007/s00423-015-1303-1DOI Listing
May 2015

Defining the syndromes of parathyroid failure after total thyroidectomy.

Gland Surg 2015 Feb;4(1):82-90

1 Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain ; 2 Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain ; 3 General and Digestive Surgery Department, Hospital de la Princesa, Madrid, Spain.

Acute and chronic parathyroid insufficiency syndromes are the most common complication after total thyroidectomy. Permanent hypoparathyroidism imposes an important medical burden on patient lifestyle due to the need for lifetime medication, regular visits and significant long-term costs. Its true prevalence has been underestimated due to lack of clear definitions, inadequate follow-up and conflicts of interest when reporting individual patient series. The aim of this review is to propose precise definitions for the different syndromes associated to parathyroid failure based on the follow-up and management of patients developing hypocalcemia (<8 mg/dL at 24 hours) after first-time total thyroidectomy for cancer or goiter at our unit. Short and long-term post-thyroidectomy parathyroid failure presents as three different metabolic syndromes: (I) postoperative hypocalcemia is defined as a s-Ca <8 mg/dL (<2 mmol/L) within 24 hours after surgery requiring calcium/vit D replacement therapy at the time of hospital discharge; (II) protracted hypoparathyroidism as a subnormal iPTH concentration (<13 pg/mL) and/or need for calcium/vit D replacement at 4-6 weeks; and (III) permanent hypoparathyroidism as a subnormal iPTH concentration (<13 pg/mL) and/or need for calcium/vit D replacement 1 year after total thyroidectomy. Each of these syndromes has its own pattern of recovery and should be approached with different therapeutic strategies.
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http://dx.doi.org/10.3978/j.issn.2227-684X.2014.12.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321048PMC
February 2015

Effect of initial empiric antibiotic therapy combined with control of the infection focus on the prognosis of patients with secondary peritonitis.

Surg Infect (Larchmt) 2014 Dec;15(6):806-14

1 Unit of Emergency Surgery and Service of General and Digestive Surgery, Universitat Autònoma de Barcelona , Barcelona, Spain .

Background: In patients with intra-abdominal infection, inappropriate initial empiric antibiotic therapy is associated with greater morbidity. We evaluated the impact of adequate empiric antibiotic treatment together with control of the infection focus on the morbidity and mortality rates of patients with secondary peritonitis.

Methods: This was a prospective, observational study with the participation of 24 Spanish hospitals and 362 patients with secondary peritonitis (262 community-acquired, 100 post-operative). Therapeutic failure (infectious complications or death) was classified into four categories according to whether empiric antibiotic treatment was appropriate and the infection focus was controlled.

Results: The rates of therapeutic failure, re-operation, and mortality were 48%, 13%, and 8%, respectively. Empiric antibiotic treatment was inappropriate in 39% of cases, which was associated with a higher rate of surgical site infection (53% vs. 40%; p=0.031) and death (12% vs. 5%; p=0.021) than was observed in patients receiving appropriate initial empiric therapy. Eight percent of patients in whom control of the infection focus was not obtained suffered from more infectious complications (76% vs. 52%; p=0.01) and surgical site infections (69% vs. 44%; p=0.01); and in this group, both therapeutic failure and mortality rates were similar, independent of whether the empiric antibiotic therapy was appropriate.

Conclusion: Inappropriate initial empiric antibiotic therapy was associated with higher rates of therapeutic failure, surgical site infection, re-operation, and death. Classification of therapeutic failure into four categories according to the appropriateness of empiric antibiotic therapy and the success of infection control provided excellent discrimination of morbidity and death.
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http://dx.doi.org/10.1089/sur.2013.240DOI Listing
December 2014

Technical hints and potential pitfalls in modified radical neck dissection for thyroid cancer.

Gland Surg 2013 Nov;2(4):174-9

Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

Modified radical neck dissection (MRND) is often performed in conjunction with total thyroidectomy for the management of thyroid cancer. Prevention of postoperative sequelae after MRND is closely dependent on the avoidance of technical mistakes that may lead to significant complications and long-term morbidity. A thorough technical discussion with emphasis on potential pitfalls is made of the most relevant steps of MRND using the extrafascial approach: fascial dissection, approach to the accessory nerve, posterior limits, upper internal jugular vein (IJV), transverse cervical vessels, thoracic duct and compartment V dissection. Some anatomical hints are emphasized to help the novice surgeon to develop a refined surgical technique, the key to an uneventful postoperative course.
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http://dx.doi.org/10.3978/j.issn.2227-684X.2013.07.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115752PMC
November 2013

Clinical guidelines at stake.

J Epidemiol Community Health 2014 Oct 3;68(10):906-8. Epub 2014 Apr 3.

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http://dx.doi.org/10.1136/jech-2014-203862DOI Listing
October 2014

Reply to Letter: "Surgery for Asymmetrical Multinodular Goiter".

Ann Surg 2015 Jul;262(1):e24-5

Department of Surgery, Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain.

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http://dx.doi.org/10.1097/SLA.0000000000000379DOI Listing
July 2015