Thyroid surgery in obese patients: A review of the literature.

The incidence of obesity in the general population has tripled in the past four decades. The number of bariatric surgeries performed annually has quadrupled in the past ten years due to this obesity epidemic. Concomitantly, the number of patients who are obese or who have undergone bariatric surgery and have become candidates for thyroid surgery has also increased considerably. Among patients undergoing thyroidectomy in the French population, the proportion of obese patients currently represents 10 to 20%. In addition, the frequency of benign and malignant thyroid pathologies seems to be increased by obesity, with a Hazard Ratio of around 1.8 for thyroid cancers in obese women. While obesity does not seem to influence the specific post-operative morbidity of thyroidectomy, a history of malabsorptive bariatric surgery should encourage the greatest caution in patients who need to undergo thyroid surgery since it is associated with a significant risk of severe hypocalcemia (>60% in some studies) requiring intravenous calcium supplementation in about 20% of cases. In the latter situation, peri-operative vitamin D-calcium supplementation is essential. In addition, the replacement dose of Levothyroxine (T4) intended for replacement must also be adapted in obese patients, calculated not from the actual weight but from the ideal weight. The objective of this review is to discuss the influence of obesity on the evolution of nodular and neoplastic thyroid pathologies, on the morbidity of thyroid surgery as well as on post-operative drug treatments. The impact of bariatric surgery on these different aspects is also discussed.

Non-adrenal tumors of the adrenal area; what are the pitfalls?

Discovery of an adrenal mass is nowadays a frequent situation. While adrenal tumors can cause a variety of symptoms, more often than not they are diagnosed incidentally on imaging exams such as CT-scan or MRI performed for another purpose. However, any retroperitoneal supra-renal mass can have an extra-adrenal origin. Indeed, operated non-adrenal masses initially but wrongly diagnosed as an adrenal disease represent about 3.5% of adrenalectomies. These differential diagnoses principally include retroperitoneal tumors that are malignant in two thirds of cases (lymphomas, sarcomas, neurogenic or germinal tumors), and more rarely vascular anomalies or congenital malformations, which are most frequently left-sided due to the wide variety of anatomical structures surrounding the left adrenal gland. Several lesions can originate from the adrenal gland or be located near the gland (paraganglioma, ganglioneuroma). Even though unilateral adrenalectomy is associated with low morbidity, ignorance of these differential diagnoses can cause ill-adapted management; overly conservative surgery in case of sarcoma is one example. Some of these lesions have characteristic clinical or imaging features (cystic lymphangioma, angiomyolipoma…). In other cases, assessment of hormonal secretion is required and additional exams (MRI, percutaneous biopsy, PET-scan with 18-Fluorodeoxyglucose) can correct an erroneous diagnosis. The above diagnostic approach allows appropriate management (with or without surgery). The purpose of this review was to highlight the main differential diagnoses of adrenal masses, to describe their characteristics, and to discuss their therapeutic management.

Correction to: Pheochromocytoma diagnosed during pregnancy: lessons learned from a series of ten patients.

The original article was updated to correct the listing of A. Hamy's name; it is correct as displayed above.

Pheochromocytoma diagnosed during pregnancy: lessons learned from a series of ten patients.

BACKGROUND: Pheochromocytoma (PHEO) in pregnancy is a life-threatening condition. Its management is challenging with regards to the timing and type of surgery. METHODS: A retrospective review of the management of ten patients diagnosed with pheochromocytoma during pregnancy was performed. Data were collected on the initial diagnostic workup, symptoms, treatment, and follow-up. RESULTS: PHEO was diagnosed in ten patients who were between the 10th and the 29th weeks of pregnancy. Six patients had none to mild symptoms, while four had complications of paroxysmal hypertension. Imaging investigations consisted of MRI, CT scan and ultrasounds. All had urinary metanephrines, measured as part of their workup. Three patients had MEN 2A, one VHL syndrome, one suspected SDH mutation. All patients were treated either with α/ß blockers or calcium channel blockers to stabilize their clinical conditions. Seven patients underwent a laparoscopic adrenalectomy before delivery. Three out of these seven patients had a bilateral PHEO and underwent a unilateral adrenalectomy of the larger tumor during pregnancy, followed by a planned cesarean section and a subsequent contralateral adrenalectomy within a few months after delivery. Three patients had emergency surgery for maternal or fetal complications, with C-section followed by concomitant or delayed adrenalectomy. All newborns from the group of planned surgery were healthy, while two out three newborns within the emergency surgery group died shortly after delivery secondary to cardiac and pulmonary complications. CONCLUSIONS: PHEO in pregnancy is a rare condition. Maternal and fetal prognosis improved over the last decades, but still lethal consequences may be present if misdiagnosed or mistreated. A thorough multidisciplinary team approach should be tailored on an individual basis to better manage the pathology. Unilateral adrenalectomy in a pregnant patient with bilateral PHEO may be an option to avoid the risk of adrenal insufficiency after bilateral adrenalectomy.

Effect of parathyroidectomy on quality of life and non-specific symptoms in normocalcaemic primary hyperparathyroidism.

BACKGROUND: Normocalcaemic primary hyperparathyroidism (NcPHPT) is a new clinical entity being diagnosed increasingly among patients with mild primary hyperparathyroidism (PHPT). The aim of this study was to evaluate quality of life and non-specific symptoms before and after parathyroidectomy in patients with NcPHPT compared with those with hypercalcaemic mild PHPT (Hc-m-PHPT). METHODS: This was a prospective multicentre study of patients with mild PHPT from four university hospitals. Patients were evaluated before operation, and 3, 6 and 12 months after surgery for quality of life using the SF-36-v2® questionnaire, as well as for 25 non-specific symptoms. RESULTS: Before operation, the only statistically significant difference between the NcPHPT and Hc-m-PHPT groups was in the mean(s.d.) blood calcium level (2·54 versus 2·73 mmol; P < 0·001). At 1 year after surgery, the blood calcium level had improved significantly in both groups, with no significant difference between them. Quality of life improved significantly in each group compared with its preoperative score, with regard to the physical component summary (P = 0·040 and P = 0·016 respectively), whereas the mental component summary improved significantly in the Hc-m-PHPT group only (P = 0·043). Only two non-specific symptoms improved significantly in the NcPHPT group compared with nine in the Hc-m-PHPT group. CONCLUSION: Parathyroidectomy mildly improves quality of life and some non-specific symptoms in patients with NcPHPT.

Randomized clinical trial of ultrasonic scissors versus conventional haemostasis to compare complications and economics after total thyroidectomy (FOThyr).

BACKGROUND: The benefits of single-use ultrasonic scissors in thyroid surgery are still debated. Although this device has been shown to reduce operating time compared with conventional haemostasis, its cost-effectiveness has never been demonstrated. The aim of this study was to evaluate the efficacy, cost-effectiveness and safety of ultrasonic scissors for total thyroidectomy. METHODS: This was a prospective, randomized, multicentre trial conducted at 13 hospital sites. The primary endpoint was the percentage of patients with hypocalcaemia (serum calcium level below 2 mmol/l) on day 2. Secondary endpoints included postoperative complications and costs, with calculation of incremental cost differences and cost-effectiveness ratios. RESULTS: In total, 1329 patients who underwent total thyroidectomy were included in the analysis: 670 were randomized to treatment with ultrasonic scissors and 659 to conventional haemostasis. There was no difference between groups in the rate of complications, including hypocalcaemia on day 2 (19.7 per cent in ultrasonic scissors group versus 20.3 per cent in conventional haemostasis group; P = 0·743). Median operating times were significantly shorter with ultrasonic scissors (90 versus 100 min with conventional haemostasis; P < 0·001). Total mean(s.d.) direct costs at 6 months were €4311(1547) and €4011(1596) respectively (P < 0·001). CONCLUSION: Ultrasonic scissors were no more clinically effective than conventional haemostasis, but use of these devices was more costly. Registration number: NCT01551914 (http://www.clinicaltrials.gov).

Pheochromocytoma revealed by acute heart failure. When should we operate? Presented at the ESES Congress, Gothenburg May 25-26, 2012.

PURPOSE: The aim of this study was to assess the safety and efficacy of adrenalectomy on patients with pheochromocytoma diagnosed at the time of an acute heart failure (AHF). METHODS: We reported cases of patients who presented an AHF secondary to a pheochromocytoma during a period of 10 years. The diagnosis of AHF was defined by a left ventricular ejection fraction of less than 30 % or the use of circulatory assistance. They had adrenalectomy as emergency surgery or later. Morbidity and mortality of surgery were studied. RESULTS: Thirteen patients required an adrenalectomy for AHF secondary to pheochromocytoma. Four patients (31 %) had an adrenalectomy in emergency. Nine patients (69 %) had a delayed surgery with a median delay of 25 days (7-180). Eight patients had circulatory assistance (61 %). Five of them had a circulatory assistance and a delayed surgery (38 %), two of them had a circulatory assistance followed by emergency surgery (at 1.5 and 3 days) and one had emergency surgery immediately followed by circulatory assistance. Emergency surgery was performed by laparotomy in all cases and delayed surgery by laparoscopy for seven patients (54 %). Perioperative complications consisted in: one circulatory arrest, two bleedings requiring transfusion, one intestinal ischaemia, one haemoperitoneum with re-operation (day 8). One patient died on day 5. Post-operative course of patients with delayed surgery was uneventful. CONCLUSIONS: AHF revealing a pheochromocytoma is a rare and serious event. Patients with emergency surgery have more complications than those with delayed surgery.

[CCAFU's contribution to the French National Cancer Institute's reference frame: Adrenal malignant tumors]. / Contribution 2013 du CCAFU au référentiel INCa : Tumeurs malignes de la surrénale.

INTRODUCTION: Malignant tumours of the adrenal gland are adrenocortical carcinomas (ACC), malignant phaeochromocytomas (MPC) or metastatic tumours. The objective of this article is to propose guidelines for the management of these tumours. MATERIAL AND METHODS: A review of the literature was performed by selecting articles on malignant tumours of the adrenal gland published in PUBMED. RESULTS: Abdominal computed tomography is the reference first-line examination. A diameter > 6 cm, a heterogeneous appearance, irregular margins, spontaneous high density (> 20 HU) and delayed wash-out are radiological signs of malignancy. MRI can be used to characterize the tumour with a sensitivity of 89% and a specificity of 99%. Hormone assays and an endocrinology consultation are recommended before any management. When ACC is suspected, (18)FDG-PET is the reference scintigraphic examination, while the isotope of choice for MPC is (18)F-DOPA, which is more sensitive than MIBG. These scintigraphic examinations have a sensitivity close to 100% and allow staging of distant metastases. Percutaneous biopsy has a limited place in the diagnostic work-up. It is only indicated in the case of suspected adrenal metastasis after having excluded phaeochromocytoma and must not be performed in the case of suspected adrenocortical carcinoma. Surgery is first-line treatment for localized and resectable tumours, but is rarely curative due to the high recurrence rate. For ACC, adjuvant therapy by mitotane or adjuvant radiotherapy can be proposed. Metabolic radiotherapy with (131)I-MIBG can be proposed for the treatment of MPC. First-line chemotherapy is indicated in the case of advanced disease or unresectable tumour. Surgical treatment of adrenal metastasis by adrenalectomy is recommended depending on the type and prognosis of the primary cancer. CONCLUSION: Preoperative laboratory, morphological and scintigraphic assessment is essential before any management. First-line treatment is surgical when the tumour is resectable, but must be completed by adjuvant therapy to limit the risk of recurrence.

[Acute pancreatitis and primary hyperparathyroidism: a multicentric study by the Francophone Association of Endocrine Surgeons]. / Pancréatite aiguë et hyperparathyroïdie primaire: étude multicentrique de l'Association francophone de chirurgie endocrinienne.

BACKGROUND: Primary hyperparathyroidism is an unusual cause of acute pancreatitis. The aim of this study was to analyse data from multiple centers concerning patients with primary hyperparathyroidism and associated acute pancreatitis and to analyze potential predictive factors. METHODS: In this retrospective multicentric study, 19 patients were identified (Group A) with the associated diagnoses of acute pancreatitis and primary hyperparathyroidism. Their clinical data was compared to that of a control group of 65 patients (group B) with primary hyperparathyroidism without acute pancreatitis. RESULTS: Age, parathormone levels and pathology (uni/multiglandular disease) were similar between the two groups. The mean plasma calcium level was significantly higher in group A (12.64 mg/100ml) than in group B patients without pancreatitis (11.28 mg/100ml) (p<0.0001). CONCLUSION: This study confirms the causal relationship between primary hyperparathyroidism and acute pancreatitis. The degree of hypercalcemia may play an important role in this association. Calcium levels should be measured in all patients with acute pancreatitis.

Statins and the stroke-cholesterol paradox.

Although strokes belong to the group of cardiovascular disorders, there is no clear association between LDL and/or HDL levels and 'stroke' as an entity. However, there is ample evidence that statins reduce stroke risk in selected patient groups such as survivors of myocardial infarction. This apparent paradox can be explained on the one hand by the heterogeneity of strokes as a group and on the other hand by the specific characteristics of statins. There are strong indications for a relationship between blood lipid profiles and types of stroke that have atherosclerosis as the underlying pathogenetic mechanism. Apart from their ability to reduce LDL levels significantly, statins have a number of other properties, which influence the process of atherosclerosis at various stages. Future and ongoing trials have to prove which patients at risk for stroke will benefit most from the preventive use of statins.

High performance liquid chromatographic method for routine monitoring of amiodarone and desethylamiodarone plasma levels.

The authors describe a normal phase liquid-chromatographic assay suitable for therapeutic monitoring of amiodarone and desethylamiodarone in human plasma. The compounds were extracted at pH 3.8 into methyl tert-butyl ether containing [2-ethyl-3-3.5-dibromo-4-dipropylaminoproxybenzoyl)benzothiophe ne] as internal standard. The separation was obtained by using a mobile phase of methanol-methyl tert butyl ether-sulfuric acid (60-40-0.015; v/v/v). The absorbance of the compounds was monitored at 254 nm with a sensitivity limit of 0.05 mg/l for amiodarone and 0.02 mg/l for desethylamiodarone. The mean overall recovery from plasma samples was greater than 90 p. cent for both compounds. This method was applied to therapeutic and pharmacokinetic studies.

Effect of size and dosage strength on the bioavailability of two diltiazem formulations during repeated administrations in humans.

In angina pectoris, diltiazem is usually prescribed as two 60 mg tablets in the morning and two 60 mg tablets in the evening. In the course of the pharmaceutical development of this drug, it was therefore planned to study an experimental formulation containing 120 mg of diltiazem. On the basis of dissolution tests in vitro, a bioavailability study was initiated to compare the 120 mg experimental formulation to the standard 60 mg tablet. The study was conducted in 12 healthy volunteers who received the 2 treatments (one 120 mg tablet bid for 7 days versus two 60 mg standard tablets bid for 7 days) according to a cross-over design. Blood and urine samples were analysed by HPLC method with a UV spectrophotometric detection (sensitivity: 5 ng/ml). Analysis of variance did not show any significant difference between the two formulations for the following parameters: maximum plasma levels observed at steady-state, area under the curves and unchanged urinary diltiazem. From these results the extent of absorption of the 120 mg experimental formulation can be considered as bioequivalent to the administration of 2 tablets of the 60 mg commercially available diltiazem formulation. The time to peak, however, was delayed in 75% of the subjects with the 120 mg diltiazem tablet, showing that the surface area of the pharmaceutical preparation is of primary importance for drug dissolution and rate of absorption.

Pharmacokinetics and bioavailability of doxycycline in humans.

The bioavailability of a new tablet of 6-deoxy-5-hydroxytetracycline (doxycycline, Doxycline Plantier) was estimated relatively to an oral solution and a commercially available capsule. Each form was administered to 12 healthy volunteers according to a replicated latin square. Statistical analysis of non-compartmental pharmacokinetic parameters - maximum concentrations, corresponding time, area under the plasma concentrations curve and unchanged amounts recovered in the urine - failed to show any difference between the tested pharmaceutical forms, although the new tablet allows to reach higher concentrations.

[Antiarrhythmic properties of 3-(2-hydroxy-3 isopropylamino-propoxy)-3 phenyl-2 isoindolinone-1, (RS, SR) in the dog]. / Propriétés anti-arythmiques de l'(hydroxy-2 isopropylamino-3 propoxy)-3 phényl-2 isoindolinone-1, (RS, SR) chez le chien.

In the Dog, 3-(2-hydroxy-3 isopropylamino-proxy)-2-phenyl-1-isoindolinone (RS, SR) possesses an anti-arrhythmic activity similar to that of quinidine but at dose levels 2 to 6 times lower than in the case of the latter compound. Furthermore, in contrast to quinidine, at the dose levels where the antiarrhythmic activity is well observed, the compound is devoid of hypotensive activity and of depressive action on cardiac contractility. The first clinical studies of this compound have shown its usefulness in the treatment of ventricular and supraventricular arrhythmias.