[Cardiovascular symptoms and risks of subclinical dysthyroidism]. / Manifestations et risques cardiovasculaires des dysthyroïdies infracliniques.

PURPOSE: To clarify the importance of cardiovascular symptoms and risks in subclinical dysthyroidism in order to define the best way of treatment and follow-up. CURRENT KNOWLEDGE AND KEY POINTS: Subclinical dysthyroidism is defined by abnormal circulating TSH values in face and normal free thyroid hormones levels, in asymptomatic individuals. If the cardiovascular effects of overt hyperthyroidism are well documented, the relation between subclinical dysthyroidism and the heart is not well established. Subclinical hyperthyroidism may be caused by the same thyroid disorders that results in overt hyperthyroidism, but the most common cause is excessive dosage in levothyroxine. The most frequent cardias complication of subclinical hyperthyroidism is atrial fibrillation. Recently minimal alterations of myocardial function have also been described. In most patients, one tries to return to euthyroidism in order to prevent cardiovascular complications. Subclinical hypothyroidism is 3 to 10 times more frequent, especially in women after 60 years. Subtle modifications of cardiac function and lipid metabolism and an increased risk of atherosclerosis have been described in this condition. There is still debate about the decision to treat or not to treat these patients. FUTURE PROSPECTS AND PROJECTS: Until now, treatment of subclinical dysthyroidism is mainly based upon experiences and convictions to physicians. Prospective studies are necessary to assess the true benefits and risks of either early treatment or therapeutic abstention with regular clinical and biological follow up. In such studies, patients should be separated according to age and the nature (endogenous or exogenous) of dysthyroidism.

Marinosomes, marine lipid-based liposomes: physical characterization and potential application in cosmetics.

Marinosomes are liposomes based on a natural marine lipid extract containing a high polyunsaturated fatty acid (PUFA) ratio. They were prepared and characterized in conditions that mimic that of topical application in terms of pH, temperature and calcium. Marinosomes were stable in storage conditions for 1 month. At low pH (pH 4) or in presence of high calcium concentrations (9 mM), complex structural rearrangements, such as aggregation and size reduction, occurred which were kinetically dependant.

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.

Excessive concern with physical appearance leading to a diagnosis of adrenal adenoma.

We report an unusual case of Cushing's syndrome manifested by anxiety over body image in a 26-year-old nurse. Initial presentation was a 'dermatological non-disease'. Clinical signs became increasingly evident during the course of the disease, justifying an adrenal gland evaluation which showed a secreting adrenocortical adenoma. Surgical treatment led to recovery with return to normal appearance and cessation of her aesthetic complaints. Our observation shows that persistent aesthetic complaints may sometimes reveal early hypercorticism.

Kappa1-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.

Latent subclinical medullary thyroid carcinoma: diagnosis and treatment.

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.

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

UNLABELLED: 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.

[Early diagnosis of sporadic medullary cancers of the thyroid: value of systematic assay of calcitonin]. / Diagnostic précoce des cancers médullaires sporadiques de la thyroïde: intérêt du dosage systématique de la calcitonine.

OBJECTIVE: Sporadic medullary cancer of the thyroid is often diagnosed late beyond the surgically curable stage. The aim of this work was to assess the capacity of routine calcitonin assay as an early diagnosis test for medullary cancer in patients with a thyroid lesion. METHODS: Calcitonin was assayed (normal < 10 pg/ml) as a routine test from 1993-1995 in a series of 2975 patients seen for thyroid exploration. When baseline level was above 10 pg/ml, a pentagastrine test was performed (normal < 30 pg/ml). All patients with a calcitonin peak > or = 100 pg/ml after pentagastrin underwent surgery for suspected medullary cancer. Surgery for suspected malignancy, hyperthyroidism or locoregional functional disorders was also performed in 1494 of the included patients, independent of calcitonin level. Patients with personal or familial history of multiple endocrine disease were excluded. Fine needle aspiration was done in all patients with an unique or predominant thyroid nodule. RESULTS: Medullary cancer of the thyroid was demonstrated in 14 patients (0.47%). Among 8 patients with clinically patent tumor, the diagnosis was established in 3 on the basis of cytology results and elevated calcitonin level; in the 5 other cases, initial cytology was incorrect (anaplastic, papillary, thyroiditis) but correct diagnosis was established on the basis of high calcitonin levels. Diagnosis was suspected preoperatively in the 6 others solely because of high calcitonin; these patients had microlesions measuring 1.2-9 mm. None of the 7 patients with a medullary cancer measuring < 10 mm had node extension at surgery and all 7 attained biological cure. Among the 7 other patients with a lesion > 10 mm, calcitonin level returned to normal level in 3 and remained high in 2; the 2 others died with distant metastasis. CONCLUSION: Routine assay of calcitonin in all patients with a thyroid nodule can improve preoperative diagnosis of medullary cancer of the thyroid and allows early diagnosis of latent infraclinical tumors.

Primary hyperparathyroidism in multiple endocrine neoplasia type IIa: retrospective French multicentric study. Groupe d'Etude des Tumeurs á Calcitonine (GETC, French Calcitonin Tumors Study Group), French Association of Endocrine Surgeons.

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.

Bone insufficiency fractures as an inaugural manifestation of primary hyperparathyroidism.

Primary hyperparathyroidism causes excessive bone resorption with a decrease in bone mineral density. Fractures of the vertebras and appendicular bones, however, seem uncommon, even in the long term. We report three patients who presented with bone insufficiency fractures as the inaugural symptom of primary hyperparathyroidism. The three patients were women, aged 62, 65 and 86 years, respectively, who presented with fractures of the medial tibial plateau, femoral neck of femoral neck and tarsus. Laboratory tests showed hypercalcemia, hypophosphatemia and elevated parathyroid hormone levels. Apart from confusion in the 86-year-old patient, there were no clinical manifestations. A bone biopsy obtained in one patient showed increased resorption parameters with no loss of bone trabecular volume; the two other patients underwent absorptiometry, which disclosed a marked decrease in bone mineral density at the spine and femoral neck. There were no risk factors for osteopenia apart from advanced age and female gender. A parathyroid adenoma was removed surgically in all three cases. Vitamin D deficiency was a concomitant abnormality that probably exacerbated the adverse effects of hyperparathyroidism on the skeleton.

[Role of laparoscopy in surgery of the adrenal glands]. / Place de la coelioscopie dans la chirurgie des surrénales.

It has been recently demonstrated that resection of the adrenal glands can be performed laparoscopically, providing certain advantages over conventional open surgery. The aim of this work was to determine the role of laparoscopy in the surgical approach to the adrenal glands. From June 1994 to December 1995, transperitoneal laparoscopic procedures were proposed in patients with a unilateral 8 cm or less non-malignant tumors of the adrenal gland. For tumors under 4 cm in diameter, only secreting tumors were removed. One patient had Cushing's disease and underwent bilateral resection. Among 58 patients requiring ablation of the adrenal gland; 37 (64%) underwent a laparoscopic procedure: 20 Conn adenomas, 8 Cushing adenomas, 1 Cushing's disease, 5 pheochromocytomas, 3 incidentalomas. Mean tumor size was 26 mm (7-75 mm). Two tumors were found to be malignant: one cortisone-secreting tumor and one leiomyosarcoma. Conversion was required in 4 cases (11%) due to difficulties in exposing the dissection in 3 cases and due to malignancy in 1. Mean operative time for unilateral operations was 159 minutes (75-300 minutes). There were no deaths. Morbidity included one hemorrhage via the trocar orifice requiring reoperation, one infarction of the spleen which regressed spontaneously, one parietal hematoma, and one case of phlebitis of the lower limb. The endocrinopathy was successfully cured in all patients with secreting tumors. The 21 other patients underwent open surgery. Laparoscopic access was contraindicated due to suspected malignancy in 10 cases, past surgical history in 7 and bilateral or extra-adrenal lesions in 4. Laparoscopic resection of the adrenal glands is the preferred technique in patients with Conn adenomas, Cushing adenomas and in most cases of pheochromocytoma. It is not indicated for malignant and/or very large tumor (> 8 cm). In our experience, the laparoscopic approach has replaced open posterior approach which is now only used exceptionally. Currently two-thirds of our patients with an indication for resection of the adrenal glands are operated laparoscopically.

[Basedow disease following metastatic thyroid cancer]. / Maladie de Basedow secondaire à un cancer thyroïdien métastatique.

OBJECTIVES: Metastatic thyroid carcinoma rarely provokes hyperthyroidism. We describe here the main characteristics of this association observed in a 48-year-old woman. CASE REPORT: The patient had presented signs of hyperthyroidism for one year. Clinical examination revealed severe Graves' disease with nodular goiter. Presurgery investigations demonstrated thyroid carcinoma and lung metastasis. Thyroid stimulating immunoglobulins were elevated. After total thyroidectomy, hyperthyroidism persisted, indicating the functional nature of the lung metastases. DISCUSSION: The effect of thyroid stimulating immunoglobulins on the clinical course of thyroid carcinoma and distant metastases remains unknown.

[Laparoscopic surgery of adrenal glands: indications and limits]. / Coeliochirurgie des glandes surrénales: indications et limites.

Over the last four years it has been demonstrated that laparoscopy can be used successfully for adrenalectomy, providing certain advantages over conventional open surgery. The aim of this study was to determine the indications for laparoscopic approach in adrenal surgery. From June 1994 to June 1996 laparoscopic transabdominal flank approaches were proposed in patients with a unilateral 8 cm or less, non-malignant tumors of the adrenal gland. For tumors under 4 cm in diameter only secreting tumors were removed. Among 77 patients requiring ablation of the adrenal gland, 50 (65%) underwent a laparoscopic procedure: 29 Conn adenomas, 10 Cushing adenomas, 6 Pheochromocytomas, 4 incidentalomas. One patient had Cushing's disease and underwent bilateral resection. Mean tumor size was 26 mm (7-75 mm). Malignancy was demonstrated in 2 tumors: one cortisone secreting tumor and one leiomyosarcoma. Conversion was required in 4 cases (8%). Mean operative time for unilateral adrenalectomies was 147 minutes (50-300'). There were no deaths. Morbidity included: one hemorrhage via the trocar orifice requiring reoperation, one infarction of the spleen which regressed spontaneously, one parietal hematoma, and one case of phebitis of the lower limb. The endocrinopathy was successfully cured in all patients with secreting tumors. The 27 other patients underwent open adrenalectomy. Laparoscopic approach was not proposed due to suspected malignancy in 13 cases, previous surgery in 8 cases and multiple, bilateral and/or extra adrenal tumors in 6 cases. Laparoscopic approach to the adrenal gland is the procedure of choice in patients with Conn adenomas, Cushing adenomas and in most cases of pheochromocytomas. It is not indicated for malignant and large tumor (> 8 cm). Currently two-thirds of our patients requiring and adrenalectomy are operated laparoscopically.

[Intraoperative parathormone assay. The value of assessment of primary hyperparathyroidism in surgery]. / Dosage peropératoire de parathormone. Intérêt dans la chirurgie de l'hyperparathyroïdie primaire.

Peroperative assay of intact parathormone has been proposed to improve the surgical results, either by confirming cure peroperatively or to indicate the need for further search in case of persistent pathological secretion. Between October 1992 and July 1994 parathormone was assay peroperatively during 136 operations for primary hyperparathyroidism in 135 patients. Seven samples were made for each patient in the operating theatre: at intubation, at skin incision (ti), at ablation of the pathological gland, then 15 (t15), 30 (t30) and 60 (t60) minutes later. All samples were assayed with the rapid technique and controlled the next day with the standard method. The correlation coefficient between the two methods was 0.97. Comparing the drop in intact parathormone levels between cured patients and those with persistent hyperparathyroidism after surgery showed statistically significant differences. We retained a dramatic drop in hormone level by 80% between t1 and t15 with persistent low levels between t15 and t30 (ratio t30 over t15 < 1) as the criteria of cure: the drop off between t1 and t15 is not sufficient to confirm cure. Peroperative assay of intact parathormone can be used to demonstrate the presence of remaining pathological parathyroid tissue, especially important in case of highly ectopic localizations. This assay technique is not particularly well adapted to routine parathyroid surgery for primary hyperthyroidism but has been reserved for cases planned for limited dissection (operations conducted under local anaesthesia and reoperations).

Fine-needle aspiration of thyroid follicular neoplasm: diagnostic use of thyroid peroxidase immunocytochemistry with monoclonal antibody 47.

BACKGROUND: We previously demonstrated that thyroid peroxidase (TPO) immunocytochemistry with monoclonal antibody 47 can help to differentiate benign (staining score, 80% or more) from malignant (staining score, less than 80%) thyroid nodules on fine-needle aspiration (FNA) samples. In the present study we assessed the use of TPO immunocytochemistry in the cytologic diagnosis of thyroid follicular neoplasms. METHODS: A total of 109 histologically proven follicular tumors were studied. There were 60 microfollicular adenomas, 23 atypical adenomas, 17 oncocytic adenomas, and 9 follicular carcinomas. Adequate preoperative FNA samples were available in all cases. TPO immunocytochemistry was performed on one half of the slides. RESULTS: The staining score was less than 80% in all follicular carcinomas, whereas it was 80% or more in 68 of 100 benign tumors. There was no false negative and 32 false positives for diagnosis of malignancy. The false positives were 10 microfollicular adenomas, 13 atypical adenomas, and 9 oncocytic adenomas. TPO immunocytochemistry has a sensitivity of 100% and a specificity of 68% for screening of follicular cancer. CONCLUSIONS: TPO immunocytochemistry with monoclonal antibody 47 on FNA samples is a highly sensitive and fairly specific method to distinguish benign from malignant follicular neoplasms. This technique can help to reduce the number of surgical procedures for benign thyroid nodules without increased risk of overlooking malignancy.

Thyroperoxidase immunodetection for the diagnosis of malignancy on fine-needle aspiration of thyroid nodules.

We have previously demonstrated that in 95.6% of malignant thyroid tumors the enzyme thyroid peroxidase (TPO) presents antigenic changes detectable by a monoclonal antibody termed MoAb47. The aim of this study was to investigate the interest of TPO immunodetection for the diagnosis of malignancy on fine-needle aspiration biopsy (FNAB) of thyroid nodules. The study was performed on 300 patients. Slides of FNAB aspirate were air-dried and stained by anti-TPO-MoAb47. According to the percentage of TPO-positive epithelial cells, patients were divided into two groups: benign (> 80%) and malignant (< 80%). In 279 cases additional slides were available for Giemsa stain and standard cytology. All the patients were operated on, and the final diagnosis was recorded as benign in 248 cases (183 macrofollicular nodules, 23 microfollicular adenomas, 18 atypical adenomas, 11 oncocytomas, 11 thyroiditis, 2 Graves' disease) and malignant in 52 cases (44 papillary carcinomas and 8 follicular carcinomas). Samples from 215 of 248 benign nodules yielded 80% to 100% TPO-positive cells, whereas samples from all malignant tumors yielded less than 80% positive cells. The sensitivity of TPO staining for diagnosis of malignancy was thus 100%, its specificity 86.7%, and its overall accuracy 89%. With conventional cytology, sensitivity, specificity, and accuracy were 91.6%, 79.2%, and 81.0%, respectively. We conclude from this study that TPO staining with MoAb47 should become an essential adjunct in the preoperative cytologic diagnosis of thyroid nodules.