Hobnail Papillary Thyroid Carcinoma, A Systematic Review and Meta-Analysis.

Although papillary thyroid carcinoma (PTC) is considered to have an excellent prognosis, some recently identified more aggressive variants show reduced overall survival rates. Hobnail PTC (HPTC) was newly recognized as one of these aggressive forms, affecting recurrence, metastasis, and overall survival rates. Herein, we performed a systematic review and meta-analysis of studies including cases or case series with patients with HPTC. Furthermore, we included our individual case series consisting of six patients. The pooled mortality rate in the cohort, consisting of 290 patients, was 3.57 (95% CI 1.67−7.65) per 100 person/years. No sex differences could be observed concerning mortality (p = 0.62), but older age and tumor size significantly affected mortality (p = 0.004 and p = 0.02, respectively). The percentage of hobnail cells did not affect mortality (p = 0.97), neither did the presence of BRAF mutations. Classical characteristics such as the presence of extrathyroidal extension (p = 0.001), distant metastases (p < 0.001), and lymph node metastases (p < 0.001) all had a significant impact on mortality. Thus, HPTC appears to correlate with worse overall survival, and all PTC cases should be carefully assessed for this variant.

Simple Prediction Score for Developing Surgical Site Infection after Clean Neck Operation.

Background: Clean neck operations (thyroidectomies, parathyroidectomies, and lymph node resection) are among the most common procedures performed in the United States. Surgical site infections (SSIs) after clean neck operations are rare, but the consequences are devastating and often life-threatening. The aim of this study was to develop a score that will identify patients at high risk for developing a SSI after a clean neck procedure. Materials and Methods: Patients with either thyroidectomies, parathyroidectomies, or lymph node resection of the neck were identified from the 2016 and 2017 databases of the American College of Surgeons National Surgical Quality Improvement Program and were used for this analysis. Our primary goal was to build a scoring system with which we will be able to identify patients at high risk for SSI after a clean neck operation. Results: Of a total of 99,877 patients, 72,719 patients had a thyroidectomy, 22,043 patients had parathyroidectomy, and 5,115 patients had lymph node resection of the neck. Multivariable logistic regression identified the following independent risk factors associated with post-operative SSI: male gender (adjusted odds ratio [aOR], 1.25; 95% confidence interval [CI], 1.03-1.51), diabetes mellitus (aOR, 1.34; 95% CI, 1.07-1.67), smoking (aOR, 1.66; 95% CI, 1.36-2.04), pre-operative steroid use (aOR, 1.75; 95% CI, 1.21-2.53), cancer diagnosis (aOR, 1.44; 95% CI, 1.17-1.77), radical lymphadenectomies (aOR, 2.94; 95% CI, 2.16-4), and total operative time ≥198 minutes (aOR, 2.25; 95% CI, 1.82-2.78). Afterward, we developed a prognostic score for calculating the odds of having post-operative SSI. One point was allotted for each of the aforementioned factors, except lymphadenectomies where two points were allotted, and operative time was excluded. Our score was associated with a stepwise higher risk of post-operative SSI after a clean neck operation. Conclusions: Pre-operative and intra-operative factors can predict which patients undergoing a clean neck surgery may develop SSI. Our prognostic score may help guide surgeons identify patients at high-risk for SSI after clean neck surgery and these patients might benefit from prophylactic use of antibiotic agents.

Management of endocrine surgical disorders during COVID-19 pandemic: expert opinion for non-surgical options.

PURPOSE: The COVID-19 pandemic brought unprecedented conditions for overall health care systems by restricting resources for non-COVID-19 patients. As the burden of the disease escalates, routine elective surgeries are being cancelled. The aim of this paper was to provide a guideline for management of endocrine surgical disorders during a pandemic. METHODS: We used Delphi method with a nine-scale Likert scale on two rounds of voting involving 64 experienced eminent surgeons and endocrinologists who had the necessary experience to provide insight on endocrine disorder management. All voting was done by email using a standard questionnaire. RESULTS: Overall, 37 recommendations were voted on. In two rounds, all recommendations reached an agreement and were either endorsed or rejected. Endorsed statements include dietary change in primary hyperparathyroidism, Cinacalcet treatment in secondary hyperparathyroidism, alpha-blocker administration for pheochromocytoma, methimazole ± ß-blocker combination for Graves' disease, and follow-up for fine-needle aspiration results of thyroid nodules indicated as Bethesda 3-4 cytological results and papillary microcarcinoma. CONCLUSION: This survey summarizes expert opinion for the management of endocrine surgical conditions during unprecedented times when access to surgical treatment is severely disrupted. The statements are not applicable in circumstances in which surgical treatment is possible.

Varied Recurrent Laryngeal Nerve Course Is Associated with Increased Risk of Nerve Dysfunction During Thyroidectomy: Results of the Surgical Anatomy of the Recurrent Laryngeal Nerve in Thyroid Surgery Study, an International Multicenter Prospective Anatomic and Electrophysiologic Study of 1000 Monitored Nerves at Risk from the International Neural Monitoring Study Group.

Background: The recurrent laryngeal nerve (RLN) can be injured during thyroid surgery, which can negatively affect a patient's quality of life. The impact of intraoperative anatomic variations of the RLN on nerve injury remains unclear. Objectives of this study were to (1) better understand the detailed surgical anatomic variability of the RLN with a worldwide perspective; (2) establish potential correlates between intraoperative RLN anatomy and electrophysiologic responses; and (3) use the information to minimize complications and assure accurate and safe intraoperative neuromonitoring (IONM). Methods: A large international registry database study with prospectively collected data was conducted through the International Neural Monitoring Study Group (INMSG) evaluating 1000 RLNs at risk during thyroid surgery using a specially designed online data repository. Monitored thyroid surgeries following standardized IONM guidelines were included. Cases with bulky lymphadenopathy, IONM failure, and failed RLN visualization were excluded. Systematic evaluation of the surgical anatomy of the RLN was performed using the International RLN Anatomic Classification System. In cases of loss of signal (LOS), the mechanism of neural injury was identified, and functional evaluation of the vocal cord was performed. Results: A total of 1000 nerves at risk (NARs) were evaluated from 574 patients undergoing thyroid surgery at 17 centers from 12 countries and 5 continents. A higher than expected percentage of nerves followed an abnormal intraoperative trajectory (23%). LOS was identified in 3.5% of NARs, with 34% of LOS nerves following an abnormal intraoperative trajectory. LOS was more likely in cases of abnormal nerve trajectory, fixed splayed or entrapped nerves (including at the ligament of Berry), extensive neural dissection, cases of cancer invasion, or when lateral lymph node dissection was needed. Traction injury was found to be the most common form of RLN injury and to be less recoverable than previous reports. Conclusions: Multicenter international studies enrolling diverse patient populations can help reshape our understanding of surgical anatomy during thyroid surgery. There can be significant variability in the anatomic and intraoperative characteristics of the RLN, which can impact the risk of neural injury.

Successful management of tertiary hyperparathyroidism associated with hypophosphataemic rickets in an adult.

Tertiary hyperparathyroidism (THP) is a rare complication in patients with hypophosphataemic rickets (HR), usually related to long-term management with active vitamin D analogues and oral phosphate salts. If left untreated, THP may aggravate bone and renal disease. We report a case of THP, which developed during the course of HR. Preoperatively, cinacalcet administration along with gradual increase in alphacalcidol dose, led to almost normalization of serum calcium and decrease in parathyroid hormone (PTH) concentrations. The patient underwent an uneventful subtotal parathyroidectomy, resulting in PTH normalization and stabilization of eucalcaemia during 18 months of follow-up. We conclude that, except for optimal dosage of elementary phosphate and alphacalcidol, cinacalcet prior to parathyroidectomy may be an effective option in patients with HR complicated with THP.

Surgical treatment in patients with single and multiple gland primary hyperparathyroidism with the use of intraoperative parathyroid hormone monitoring: extensive single-center experience.

PURPOSE: To evaluate a single-center extensive experience and effectiveness in surgical treatment of primary hyperparathyroidism (pHPT) with the use of rapid intraoperative parathyroid hormone (ioPTH) monitoring in patients with single gland (SGpH) or multiple gland (MGpH) disease. METHODS: This retrospective, single-center cohort study included 214 patients with pHPT treated from January 2010 to June 2017. In total, 172 patients fulfilled the inclusion criteria having at least one preoperative localization image study and measurement of ioPTH. Statistical analysis was made by the chi-square test and Student's t tests. RESULTS: Of the 172 patients, 146 were women (85%) and 26 men (15%), with a mean age of 56.9 years; 153 (89%) had SGpH and 19 (11%) MGpH. The mean follow-up was 41.8 months. A total of 153 surgical procedures were performed as minimal invasive parathyroidectomy (MIP) based on a SGpH diagnosis; operative success was achieved in 150 cases (98%), according to ioPTH concentrations. The remainder (19 procedures) were performed as bilateral neck exploration (BNE) based on a MGpH diagnosis; operative success was achieved in 16 cases (84%). ioPTH correctly modified the initially planned operation in 26.3% of patients with MGpH. CONCLUSIONS: ioPTH enables the surgical treatment of patients with pHPT with focused approaches and excellent results, as it helps the surgeon to identify cases of MGpH. ioPTH adds value to cases where preoperative imaging failed to detect the affected gland or the results are inconclusive. According to the literature, its application seems to be of marginal benefit in cases in which there are two concordant preoperative imaging studies.

Two-stage thyroidectomy in the era of intraoperative neuromonitoring.

BACKGROUND: The use of intraoperative neuromonitoring (IONM) provides surgeons with real time information about recurrent laryngeal nerves (RLN) functional integrity. Hence, allowing them to modify the initially scheduled bilateral procedure, to a two-stage thyroidectomy in cases of loss of signal (LOS) on the first side of resection resulting in minimization of bilateral RLN injury. The purpose of our study was to present our results since the implementation of the above mentioned process in both malignant and benign thyroid disease. METHODS: We conducted a retrospective, observational cohort study of prospectively collected data from all patients who underwent a scheduled total thyroidectomy with or without neck dissection in our Department over the last 4 years [2013-2016]. From the 1,138 patients who received surgical treatment during that period, 284 were excluded since they did not meet the criteria. Exclusion criteria involved previous neck operation, parathyroid surgery, pre-existing vocal cord palsy (VCP) and unilateral surgery. A total of 854 patients were eligible for our study. All patients were subjected to pre- and postoperative indirect laryngoscopy by the same experienced ENT specialist team and all the surgeries were performed by the same experienced team. The whole procedure followed the International Neural Monitoring Study Group's (INMSG) Guideline Statement. RESULTS: We experienced 70 cases (70/854, 8.2%) with postoperative VCP. Two of them (0.23%) had permanent VCP and the rest of those patients (7.97%) experienced transient VCP. Twenty-three (2.7%) patients were candidates for staged thyroidectomy after LOS on the first side of resection, including ten patients with papillary or medullary thyroid carcinoma and one with toxic multinodular goiter (MNG). Of those patients, 22 incidents of VCP (95.7%) have recovered within two months and one of them persisted for more than six months (permanent VCP). We did not experience any permanent bilateral RLN palsy after the implementation of the staged procedure. CONCLUSIONS: Staged thyroidectomy seems a very attractive and promising procedure for both patient and surgeon, since it nearly eliminates one of the most fearful complications in thyroid surgery. We suggest staged thyroidectomy in all cases with first side of resection signal loss, even in malignancies, since the benefits are much more than the disabilities in a patient's morbidity and quality of life.

Prospective study of vocal fold function after loss of the neuromonitoring signal in thyroid surgery: The International Neural Monitoring Study Group's POLT study.

OBJECTIVES/HYPOTHESIS: Intraoperative neuromonitoring identifies recurrent laryngeal nerve (RLN) injury and gives prognostic information regarding postoperative glottic function. Loss of the neuromonitoring signal (LOS) signifies segmental type 1 or global type 2 RLN injury. This study aimed at identifying risk factors for RLN injury and determining vocal fold (VF) function initially and 6 months after definitive LOS. STUDY DESIGN: Prospective study encompassing 21 hospitals from 13 countries. METHODS: Included in this study were patients with persistent intraoperative LOS. RESULTS: At first postoperative laryngoscopy, early VF palsy was present in 94 of all 115 patients with LOS (81.7%): in 53 of 56 patients (94.6%) with type 1 injury and 41 of 59 patients (69.5%) with type 2 injury. In LOS type 1, women outnumbered men >5-fold. Traction produced LOS type 1 in 38 of 56 patients (67.9%) and LOS type 2 in 54 of 59 patients (91.5%). Course of the RLN posterior and/or anterior to the inferior thyroid artery, extralaryngeal branching, or tuberculum of Zuckerkandl did not increase VF palsy rates. Permanent VF palsy rates were also lower (P = .661) after LOS type 2 than after LOS type 1: 6.8% (four of 59 patients) versus 10.7% (six of 56 patients). Intraoperative administration of steroids did not diminish postoperative VF palsy rates. CONCLUSIONS: LOS type 1 entails more severe nerve damage than LOS type 2, affecting women disproportionately. Both LOS types, being primarily associated with traction injury, are unaffected by variant neck anatomy in expert hands and unresponsive to steroids. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:1260-1266, 2016.

Pattern of adrenal hormonal secretion in patients with adrenal adenomas: the relevance of aldosterone in arterial hypertension.

CONTEXT: Approximately 10% of hypertensives are considered to exhibit autonomous aldosterone secretion (AAS). Although adrenal incidentalomas (AI) can be found in up to 19% of hypertensive individuals, data on the incidence of AAS in hypertensive patients with AI remain scarce. OBJECTIVE: The aim was to study adrenal aldosterone (ALD) secretory pattern in patients with adrenal adenomas with and without arterial hypertension. DESIGN AND SETTING: We conducted a case-control study in a tertiary general hospital. PATIENTS AND MAIN OUTCOME MEASURES: We investigated 72 normotensive subjects with normal adrenal morphology and 191 subjects divided in three groups: 46 normotensive individuals with an AI (NAI), 89 hypertensive patients with an AI (HAI), and 56 hypertensive patients with an adrenal adenoma identified after investigation for arterial hypertension (HAA). Evaluation of autonomous cortisol secretion was based on a low-dose dexamethasone suppression test. Autonomous ALD secretion was based on a modified saline infusion test (MSI). Normal cutoff levels were obtained from the control matched population. RESULTS: Post-MSI ALD levels and the ALD/renin (REN) ratios were significantly elevated in HAI and HAA patients compared to NAI subjects. To evaluate the prevalence of AAS, we applied the combination of post-MSI ALD level and the ALD/REN ratio simultaneously (post-MSI cutoffs, ALD levels, 2.41 ng/dl; ALD/REN ratio, 0.35 ng/dl/µU/ml). Based on these cutoffs, 12% of NAI, 36.4% of HAI, and 54.2% of HAA patients had AAS. The prevalence of autonomous cortisol secretion did not differ among the three groups. CONCLUSIONS: Using a MSI test, we found a remarkably increased prevalence of AAS in hypertensive patients with adrenal adenomas, even when the latter represented an incidental finding.

High prevalence of autonomous aldosterone secretion among patients with essential hypertension.

BACKGROUND: Previous studies based on standard endocrine testing have generally shown a low prevalence of primary aldosteronism, a form of autonomous aldosterone secretion (AAS), in hypertensive individuals. The purpose of this case-control study was to evaluate whether use of appropriately defined controls and combined testing reveal previously undetected AAS in hypertensives. MATERIALS AND METHODS: We investigated aldosterone secretion in 180 hypertensives with (n = 44) and without (n = 136) adrenal adenomas on computerized tomography (CT) and 72 matched nonhypertensive individuals with normal adrenal CT. Serum aldosterone and active renin were measured, and the aldosterone/active renin ratio was calculated before and after a modified fludrocortisone-suppression test (FST). In the latter, to eliminate any stimulatory effect of endogenous stress-induced adrenocorticotrophin hormone on aldosterone secretion, we administered 1 mg of dexamethasone on the last day of the classical FST fludrocortisone/dexamethasone suppression test (FDST). RESULTS: Using the 97·5 percentiles of serum aldosterone (74 pM L(-1)) and the aldosterone/renin ratio (32 pM L(-1) mU(-1) L(-1)) values obtained from the controls following the FDST, normal cut-off values indicative of adequate aldosterone suppression were established. Using the combination of these cut-offs, the estimated prevalence of AAS in patients with hypertension was 31%. Multiple linear regression analysis revealed a significant correlation between systolic and/or diastolic arterial blood pressure and the aldosterone value (P < 0·0001 and P < 0·01, respectively) and/or the aldosterone/renin ratio (P < 0·0001 and P < 0·01, respectively), which were obtained following the FDST. CONCLUSIONS: By applying new cut-offs obtained following modification of standard testing, AAS is quite prevalent in hypertensive individuals and correlates highly with arterial blood pressure. This may have relevance for both the aetiology of the hypertension and its optimal therapy.

High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas.

OBJECTIVES: Previous studies based on standard endocrine testing have shown a variable incidence of autonomous cortisol secretion (ACS) or autonomous aldosterone secretion (AAS) in patients with single adrenal adenomas (SAA). We tested whether the use of appropriate controls and modification of standard testing, aiming at eliminating interference from endogenous ACTH, reveals previously undetected subtle ACS and AAS by SAA. DESIGN: Case control study. Patients We investigated 151 patients with SAA and 72 matched controls with normal adrenal computerized tomography. MEASUREMENTS: All participants had arterial blood pressure recorded, and serum cortisol and aldosterone measured before and after intravenous administration of 250 mug of ACTH, and following dexamethasone administration. Eighty-three patients and all the controls had serum aldosterone and renin measured before and after saline infusion, and after a second saline infusion following dexamethasone administration. RESULTS: Using the mean + 2 SD values obtained from controls after dexamethasone administration and saline infusion following dexamethasone administration, normal cut-off values for cortisol (30.11 nM), aldosterone (67.59 pM), and aldosterone/renin ratio (9.74 pM/mU/l) were developed. Using these cut-off values, the estimated incidence of ACS and AAS in patients with SAA was 56.63% and 24.10%, respectively, whereas 12.05% had autonomous secretion of both cortisol and aldosterone. Systolic and diastolic arterial blood pressure correlated significantly with the aldosterone/renin ratio following AlphaCTH stimulation (P < 0.0002 and P < 0.001, respectively), and after saline infusion following dexamethasone administration (P < 0.003 and P < 0.002, respectively). CONCLUSIONS: By applying new cut-offs, ACS and AAS in patients with a SAA is very common, and aldosterone secretion correlates with arterial blood pressure.

A unique case of a benign adrenocortical tumor with triple secretion of cortisol, androgens, and aldosterone: development of multiple sclerosis after surgical removal of the tumor.

We present a 39-year old female with a benign adrenal tumor characterized by autonomous secretion of cortisol, androgens, and aldosterone. The patient presented with a 4-year history of hypertension and severe hirsutism. Baseline investigations revealed elevated testosterone, androstendione, and 17OH progesterone with normal levels of dehydroepi androsterone sulfate. CT of the adrenals revealed a 2.5 x 3.0 cm tumor with characteristics of an adenoma on the left adrenal gland. Pelvic ultrasound was normal. Further investigations revealed suppressed basal ACTH levels, loss of diurnal rhythm of cortisol, and failure to suppress on low dose dexamethasone suppression test, suggesting autonomous cortisol secretion by the tumor. She had an exaggerated response of 17OH progesterone to ACTH, implying reduced 21-hydroxylase activity. An elevated plasma aldosterone concentration to plasma renin activity ratio was suggestive of hyperaldosteronism, which was confirmed by failure of aldosterone to suppress to a formal saline infusion test. Complete clinical and biochemical remission of the disease was observed after left adrenalectomy. Histology confirmed the presence of an adrenocortical adenoma. The patient developed multiple sclerosis 6 months after the operation. The flare-up of an autoimmune disease (multiple sclerosis) postoperatively could be coincidental or possibly related to the high normalization of the high cortisol levels acting as a precipitating factor.