Anne Denizot

Morbidity of prophylactic lymph node dissection in the central neck area in patients with papillary thyroid carcinoma

Abstract The benefits of prophylactic central neck dissection (PCND) in patients with papillary thyroid carcinoma (PTC) have not been clearly demonstrated so far and should be weighed against the potential risks of the procedure. The aim of the study was to assess the recurrent laryngeal nerve and parathyroid risks of PCND after total thyroidectomy in patients with PTC and to compare the results with those obtained in patients who underwent total thyroidectomy only. Methods: We selected 100 patients who underwent a total thyroidectomy: 50 for nontoxic benign multinodular goiter (Group 1) and 50 for PTC (Group 2). Patients with PTC had no evidence of macroscopic lymph node invasion during surgery and underwent, in addition to the total thyroidectomy, a PCND. All of the 100 patients were operated on by two experienced endocrine surgeons. All patients had pre- and postoperative investigations of vocal cord movements. Calcemia and phosphoremia were systematically evaluated preoperatively and on day 1 and day 2 after surgery. All patients presenting a postoperative calcemia below 1.90 mmol/l were considered to present an early postoperative hypoparathyroidism and received calcium-vitamin D therapy. The hypoparathyroidism was considered permanent when calcium-vitamin D therapy was still necessary 1 year after surgery. Results: None of the patients presented permanent nerve palsy. There were three cases of transient nerve palsy (6%) in Group 1 and two (4%) in Group 2. In Group 1 there was no permanent hypoparathyroidism and four cases of transient hypoparathyroidism (8%). In Group 2, seven patients presented transient hypoparathyroidism (14%) and two patients (4%) remained with definitive hypoparathyroidism. Conclusion: After total thyroidectomy for PTC, PCND does not increase recurrent laryngeal nerve morbidity but it is responsible for a high rate of hypoparathyroidism, especially in the early postoperative course. Even taking into account the possible benefits, the results make it difficult to advocate PCND as a routine procedure in all patients presenting a PTC.

Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type IIa: Retrospective French Multicentric Study

Abstract. Primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia (MEN) type IIa is rare, occurring in 20% to 30% of the patients. The aim of this study was to evaluate clinical findings, surgical therapy, and outcome for 56 patients affected by PHPT among 249 MEN-IIa patients collected from 84 families assembled by the Groupe d’Etude des Tumeurs á Calcitonine (GETC, French Calcitonin Tumors Study Group). This retrospective study was based on cases registered by the GETC (20 participating centers) from 1969 to 1994. Characteristics of PHPT in 56 patients (31 women, 25 men) with MEN-IIa were reviewed. All but two underwent cervicotomy. The median age at diagnosis was 37.6 years. PHPT was found concomitantly with medullary thyroid carcinoma (MTC) or pheochromocytoma in 43 patients (77%). PHPT was asymptomatic in 68% of the patients. Serum calcium levels ranged from 2.20 to 3.70 mmol/L (median 2.82 mmol/L; normal 2.10–2.60 mmol/L). The number of parathyroid glands removed at surgery was 0 (n = 2), 1 (n = 24), 2 (n = 5), > 2 (n = 12), 4 (n = 11). Pathology (initial surgery) consisted of 24 adenomas, 4 double adenomas, and 25 hyperplasia. Cure after initial surgery was obtained in 89%, including a 22% incidence of hypoparathyroidism. There were 6 cases (11%) with persistent PHPT. With a mean follow-up of 6.4 years, five patients (9%) had recurrent PHPT. The results indicate that MEN-IIa-related PHPT is generally associated with mild, often asymptomatic hypercalcemia. Despite recurrences encountered 5 to 15 years after the first cervicotomy, resection of only macroscopically enlarged glands generally appears sufficient. Subtotal or total parathyroidectomy with autotransplantation is associated with a high rate of hypoparathyroidism.

latent subclinical medullary thyroid carcinoma: diagnosis and treatment

Abstract. Sporadic medullary thyroid carcinoma (SMTC) is usually diagnosed at a clinical stage often associated with lymph node involvement. Hence surgical treatment does not result in definitive cure in many patients. Studies have demonstrated that routine measurement of serum basal calcitonin (CT) in patients with nodular thyroid disease allows preoperative, early diagnosis of unsuspected SMTC. The aim of this work was to assess the results of surgery in patients operated on for subclinical SMTC detected preoperatively by measurement of serum CT. Results were compared with those obtained in patients with SMTCs diagnosed at a clinical stage and operated on during the same period. During a 4-year period (1993–1996) 24 SMTCs were diagnosed and treated in our department. They were diagnosed at a clinical stage in 13 patients (group 1): palpable thyroid tumor (n= 11), palpable metastatic lymph node (n= 6), distant metastases (n= 4). In nine cases the diagnosis was made by both fine-needle aspiration cytology and serum CT measurement. In the four other cases the initial cytology was incorrect, but the diagnosis was revised on the basis of elevated basal CT values. In 11 patients (group 2) presenting with nodular thyroid disease, SMTC was not clinically detectable. SMTC was preoperatively suspected by elevated CT levels: basal CT > 10 pg/ml and pentagastrin-stimulated CT peak > 100 pg/ml. One patient in group 1 with distant metastases was not operated on. All of the other 12 patients underwent total thyroidectomy and extensive lymph node dissection. The mean size of the tumors was 27 mm. Lymph node involvement was found in nine patients. After surgery, CT levels returned to normal in five patients but remained elevated in five others; the two remaining patients died of distant metastases. All 11 patients in group 2 underwent total thyroidectomy and central neck dissection. None of the 11 patients had nodal extension. All 11 patients are biochemically cured. It was concluded that routine measurement of basal serum CT in those with nodular thyroid disease allows early, preoperative diagnosis of subclinical SMTC and improves the results of surgery.

normocalcemia with elevated parathyroid hormone levels after surgical treatment of primary hyperparathyroidism

BACKGROUND Thirty percent of patients who undergo successful parathyroidectomy for primary hyperparathyroidism show unexplained elevated postoperative serum parathyroid hormone (PTH) levels despite normocalcemia. METHODS PTH levels were measured monthly in 97 patients for 6 months after parathyroidectomy. Renal function, 25-OH-vitamin D levels, serum alkaline phosphatase levels, osteocalcin, and bone densitometry were evaluated before and 6 months after surgery. PTH reactivity to calcium loading was tested at the sixth month. RESULTS Thirty patients had elevated PTH levels despite normocalcemia after parathyroidectomy. Before surgery, these 30 patients had higher PTH and creatinine levels, lower vitamin D levels, and more extensive bone involvement than those with normal postoperative PTH levels. In patients with normal renal function and normal vitamin D levels, postoperative PTH values correlated with preoperative PTH levels but not with bone disease. CONCLUSION In most cases, elevated PTH levels after surgery is an adaptive reaction to renal dysfunction or vitamin D deficiency. If no adaptive cause can be found, persistent hyperparathyroidism must be suspected.

κ1-Opioid binding sites are the dominant opioid binding sites in surgical specimens of human pheochromocytomas and in a human pheochromocytoma (KAT45) cell line

The adrenal medulla produces opioids which exert paracrine effects on adrenal cortical and chromaffin cells and on adrenal splanchnic nerves, via specific binding sites. The opioid binding sites in the adrenals are detectable mainly in the medullary part of it and differ in type between species. Thus, the bovine adrenal medulla contains mostly kappa-opioid binding sites and fewer delta- and mu-opioid binding sites while primate adrenals contain mainly delta sites and few kappa-opioid binding sites. Most chromaffin cell tumors, the pheochromocytomas, produce opioids which suppress catecholamine production by the tumor. The aim of the present work was to identify the types of opioid binding sites in human pheochromocytomas. For this purpose, we characterized the opioid binding sites on crude membrane fractions prepared from 14 surgically excised pheohromocytomas and on whole KAT45 cells, a recently characterized human pheochromocytoma cell line. Our data showed that human pheohromocytomas are heterogeneous, as expected, with regard to the production of catecholamines and the distribution and profile of their opioid binding sites. Indeed, only one out of the 14 pheochromocytomas expressed exclusively delta and mu opioid sites, while in the remaining 13 tumors kappa-type binding sites were dominant. The KAT45 cell line possessed a significant number of kappa1 binding sites, fewer kappa2-opioid binding sites and kappa3-opioid binding sites, and minimal binding capacity for delta- and mu-opioid receptor agonists sites. More specifically, the kappa1 sites/cell were approximately 18,000, the kappa2 4500/cell and the kappa3 sites 2000/cell. Our findings for the surgical specimens and the cell line combined with previously published pharmacological data obtained from KAT45 cells suggest that kappa sites appear to be the most prevalent opioid binding sites in pheochromocytomas. Finally, in normal bovine adrenals the profile of opioid binding sites differs in adrenaline and noradrenaline producing chromaffin cells. To test the hypothesis that the type of catecholamine produced by a pheochromocytoma depends on its cell of origin, we compared our binding data with the catecholamine content of each pheochromocytoma examined. We found no correlation between the type of the predominant catecholamine produced and the opioid binding profile of each tumor suggesting that this hypothesis may not be valid.

Surgical Management of Primary Hyperparathyroidism in Older Adults

To compare the feasibility, safety, and outcome of parathyroidectomy in the management of primary hyperparathyroidism (PHPT) in individuals aged 75 and older with that of those younger than 50.

Impact of autofluorescence-based identification of parathyroids during total thyroidectomy on postoperative hypocalcemia: a before and after controlled study

Background. The clinical impact of intraoperative autofluorescence‐based identification of parathyroids using a near‐infrared camera remains unknown. Methods. In a before and after controlled study, we compared all patients who underwent total thyroidectomy by the same surgeon during Period 1 (January 2015 to January 2016) without near‐infrared (near‐infrared− group) and those operated on during Period 2 (February 2016 to September 2016) using a near‐infrared camera (near‐infrared+ group). In parallel, we also compared all patients who underwent surgery without near‐infrared during those same periods by another surgeon in the same unit (control groups). Main outcomes included postoperative hypocalcemia, parathyroid identification, autotransplantation, and inadvertent resection. Results. The near‐infrared+ group displayed significantly lower postoperative hypocalcemia rates (5.2%) than the near‐infrared− group (20.9%; P < .001). Compared with the near‐infrared− patients, the near‐infrared+ group exhibited an increased mean number of identified parathyroids and reduced parathyroid autotransplantation rates, although no difference was observed in inadvertent resection rates. Parathyroids were identified via near‐infrared before they were visualized by the surgeon in 68% patients. In the control groups, parathyroid identification improved significantly from Period 1 to Period 2, although autotransplantation, inadvertent resection and postoperative hypocalcemia rates did not differ. Conclusion. Near‐infrared use during total thyroidectomy significantly reduced postoperative hypocalcemia, improved parathyroid identification and reduced their autotransplantation rate.