Replacement therapy with levothyroxine modulates platelet activation in recent-onset post-thyroidectomy subclinical hypothyroidism.

BACKGROUND AND AIM: Subclinical hypothyroidism has been linked to increased risk of atherosclerotic disease. Soluble CD40 ligand (sCD40L), mainly derived from activated platelets, and the lipid peroxidation product 8-iso-prostaglandin F2α (8-iso-PGF2α) are known to play a relevant pathophysiological role in atherogenesis. In this study, we analyzed the relationship between thyroid hormones and circulating levels of sCD40L and 8-iso-PGF2α in patient with recent-onset post-thyroidectomy subclinical hypothyroidism under replacement therapy. METHODS AND RESULTS: Circulating levels of thyroid hormones, sCD40L, and 8-iso-PGF2α were assessed in 40 recently thyroidectomized patients (33 females, mean age 52.0 ± 11.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine (LT-4). At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 7.7 ± 3.9 µU/mL, FT3 1.8 ± 0.6 pg/mL, and FT3 8.9 ± 3.0 pg/mL). Circulating levels of sCD40L and 8-iso-PGF2α were directly correlated with each other (r = 0.360, p = 0.023) and with TSH levels (r = 0.322, p = 0.043 and r = 0.329 p = 0.038, respectively). After 2 months under the replacement therapy with LT-4 circulating levels of TSH (from 7.7 ± 3.9 to 2.7 ± 2.8 µU/mL, p < 0.0001), sCD40L (from 6.11 ± 2.41 to 2.43 ± 2.00 ng/mL, p < 0.0001) and 8-iso-PGF2α (from 45.33 ± 6.94 to 40.36 ± 6.20, p < 0.0001) significantly decreased. Changes in circulating levels of sCD40L and 8-iso-PGF2α were directly correlated with each other (r = 0.349 p = 0.028) and with changes in TSH levels (r = 0.367 p = 0.020 and r = 0.339 p = 0.032, respectively). CONCLUSION: Our study suggests an influential role of TSH on proatherogenic activation of platelets, probably through enhanced lipid peroxidation. These findings could partially explain the increased susceptibility of patients with subclinical hypothyroidism to develop atherosclerotic disease.

[Laparoscopic adrenalectomy in the treatment of malignant adrenal lesions]. / La surrenectomia laparoscopica nel trattamento delle lesioni surrenaliche maligne.

The role of laparoscopic approach for the treatment of malignant adrenal diseases is still controversial. The aim of this study was to verify the results of laparoscopic adrenalectomy in the management of adrenal malignancies. The medical records of all the patients who underwent laparoscopic procedures for adrenal diseases and in whom malignancy was demonstrated at final histology were reviewed. Nine patients were included (3 malignant pheochromocytomas, 4 adrenocortical carcinomas and 2 adrenal metastases). At a mean follow-up of 17.0 +/- 12.8 months (range, 2-36), all but two patients were alive and disease free. One patient died for unrelated causes. No patient developed local or port site recurrence. The results of this study demonstrate that laparoscopic adrenalectomy can be safe and effective also in case of adrenal malignancies. Conversion to open surgery in mandatory in case of local invasion and when the dissection cannot be as accurate as in conventional operations. A preliminary laparoscopic exploration can be planned in case of suspected malignant lesions to confirm the diagnosis and to evaluate their operability.

Validity of thyroglobulin mRNA assay in peripheral blood of postoperative thyroid carcinoma patients in predicting tumor recurrences varies according to the histologic type: results of a prospective study.

BACKGROUND: The objective of the current study was to evaluate the ability of serum thyroglobulin mRNA assay in detecting local and distant recurrences in patients who underwent surgery for thyroid carcinoma. METHODS: Sixty-six consecutive patients were studied. One year after surgery, all patients underwent clinical examination and radioiodine scan, and a blood sample was taken for serum thyroglobulin (Tg) immunoassay and for Tg mRNA assay by reverse transcription-polymerase chain reaction (RT-PCR). RNA was extracted from cells pellet and analyzed by RT-PCR using specific primers for Tg. RESULTS: Thyroglobulin mRNA was detected in 14 (21.2%) patients. Seven of 16 patients with elevated serum thyroglobulin had detectable Tg mRNA. Six of 30 (20%) patients with absent or minimal thyroid bed radioiodine uptake and 7 of 36 (19.4%) patients with significant thyroid bed uptake had detectable Tg mRNA. Among 5 patients with metastases, only 1 (20%) showed circulating Tg mRNA. Overall, the sensitivity, specificity, and accuracy of Tg mRNA assay in predicting the results of the (131)I whole-body scans was 25%, 80%, 25%, respectively. Fourteen of 53 (26.4%) patients with papillary thyroid carcinoma had detectable thyroglobulin mRNA whereas none of the patients with other histologic types did. The sensitivity, specificity, and accuracy of Tg mRNA assay in predicting the results of the (131)I whole-body scans in patients with papillary thyroid carcinoma was 100%, 75%, and 100%, respectively. Of note, the percentage of cases with detectable Tg mRNA was similar among patients who did not receive postoperative (131)I and those who had postoperative radioiodine treatment. CONCLUSIONS: The current study suggests that the validity of the Tg mRNA assay varies according to the histologic type of thyroid carcinoma and that this assay may play a role in the identification of metastatic disease in the subgroup of patients affected by papillary thyroid carcinoma but does not appear to be sensitive or active enough to direct clinical management.

Is the identification of the external branch of the superior laryngeal nerve mandatory in thyroid operation? Results of a prospective randomized study.

BACKGROUND: The aim of this study was to investigate the incidence of injury to the external branch of the superior laryngeal nerve (EBSLN) with 2 different surgical approaches. METHODS: From 1998 to 2000, 289 consecutive patients undergoing thyroidectomy were randomly divided into 2 groups. In group A (137 patients [215 upper pole ligations]), the superior thyroid artery was ligated after identification of the EBSLN. In group B (152 patients [244 upper pole ligations]), the superior thyroid artery's branches were ligated separately close to the gland. In all patients, a phoniatric evaluation with videostrobolaryngoscopy and spectrographic examination was performed. RESULTS: The 2 groups were well matched regarding age, sex, thyroid pathological findings, and type of operation. In group A, the EBSLN was not clearly identified in 11.6% of cases. Alterations of EBSLN function were absent in both groups of patients, either postoperatively or 1 and 6 months after operation. Group B showed statistically significant shorter operative time compared with that for group A. CONCLUSIONS: Even if the EBSLN often crosses the superior thyroid pedicle, especially in large goiters, this study demonstrated that accurate distal ligation of the branches of the superior thyroid artery is a safe technique to prevent EBSLN injury.

Medullary thyroid carcinoma: surgical management of primary tumor and locoregional recurrence.

Medullary thyroid carcinoma is a rare neoplasm (3-9% of all thyroid tumors). Surgery represents the only strategy for potential cure of the disease in whichi. Medullary thyroid carcinoma in which locoregional lymph node metastases are an early occurrence cannot be treated with radioiodine therapy and it is minimally sensitive to chemotherapy and external beam radiation therapy. Therefore total thyroidectomy with lymphadenectomy is the treatment of choice. Ipsilateral laterocervical lymphadenectomy is essential for neoplasms > 10 mm in size in case of central and ipsilateral laterocervical lymph node involvement; bilateral laterocervical lymphadenectomy should be performed in all patients with bilateral lymphadenopathy and in some cases of MEN 2B. In recurrence, reoperation is the single possible treatment with satisfactory results in terms of prognosis.

Minimally invasive, totally gasless video-assisted thyroid lobectomy.

BACKGROUND: Neck surgery is one of the newest fields of application of video-assisted surgery. We developed a technique for minimally invasive, totally gasless video-assisted thyroid lobectomy. METHODS: The procedure was accepted by a patient with a follicular nodule of the left lobe of the thyroid. We performed a left thyroid lobectomy through a single 20-mm horizontal skin incision, just above the sternal notch, after inserting a 5-mm 30 degrees laparoscope, by using both endoscopic and conventional instrumentation. RESULTS: The recurrent laryngeal nerve and the parathyroid glands were easily identified and preserved. The operating time was 2.5 hours. No complication occurred. The postoperative stay was 2 days. The cosmetic result was excellent CONCLUSIONS: We concluded that our technique is feasible and safe. This makes us optimistic about the future of minimally invasive, video-assisted thyroid surgery.

Hemorrhagic adrenal cyst: an unusual reason of acute hypovolemia.

Adrenal cysts are often asymptomatic and included in the larger "incidentaloma" group. They may reach significant size without onset of compressive symptoms and are often left undiagnosed until an ultrasound or CT scan are performed for a vague lumbar or flank discomfort. Intracystic hemorrhage is a rare but life-threatening complication since a sudden and significant blood loss may occur without any evident clinical source, hypovolemic shock resulting as the first symptom. The authors report their personal experience in two patients along with a review of the literature on this insidious emergency, its diagnosis and therapeutic approach.

Prognostic factors in differentiated thyroid carcinoma: a multivariate analysis of 234 consecutive patients.

BACKGROUND AND OBJECTIVES: The clinical characteristics and patient outcome of a group of patients treated for differentiated thyroid carcinoma (DTC) were analyzed in order to assess the relative influence of different prognostic factors. MATERIALS AND METHODS: We retrospectively reviewed data about sex, age, size and histologic behavior of the tumor, extrathyroid extension of the tumor, lymph node status, distant metastasis at diagnosis, surgical procedures, and overall survival from 234 patients treated for DTC. Data were submitted to a statistical analysis. RESULTS: Using a univariate analysis, we found that survival rates were significantly influenced by age (P = 0.0001), size (P = 0.018), extrathyroidal extension (P = 0.000001), lymph node involvement (P = 0.03), and distant metastases (P = 0.049). Age and size were independent prognostic factors at multivariate analysis (t = 2.694 and t = 2.443, respectively). CONCLUSIONS: On the basis of our results and of a review of the literature, we conclude that total thyroidectomy is the treatment of choice in DTC, except for small (<1 cm) papillary carcinoma, that could be treated by lobectomy plus isthmectomy, while lymphadenectomy is indicated only in case of macroscopic involvement.

Adrenal cystic lesions: report of 12 surgically treated cases and review of the literature.

Adrenal cysts are rare (0,064%-0,18% in autopsy series) and less than 500 cases have been reported in the western literature. Incidental diagnosis of adrenal cysts, however, is reported with increasing rates. We observed 12 patients with adrenal cyst. Each of them had a careful laboratory and instrumental evaluation; all the patients were operated. In our series about 67% of the patients were symptomatic (6 patients with abdominal pain, 1 with palpable mass, 1 with hemorrhagic shock). No biochemical alteration was observed. Conversely we observed an unusual subclinically hyperfunctioning cystic adenoma, potentially progressive to a clinically recognizable endocrine syndrome. US, CT and MRI had a sensitivity of 66,7%, 80% and 100% respectively. Adrenalectomy was performed in all patients. The pathological findings were: 1 epithelial cyst (cystic adenoma), 2 endothelial cysts (vascular cystic ectasia with adenomatous adrenocortical hyperplasia and 1 vascular cyst) and 9 pseudocysts. On the basis of these results, we conclude that a careful hormonal, morpho-functional and instrumental evaluation is indicated in all adrenal cysts, even if the available diagnostic procedures, even when combined, cannot always define their nature. Surgical excision, when possible by laparoscopic approach, is indicated in presence of symptoms, endocrine abnormalities (even when subclinic), complications, suspicion of malignancy and/or large size (>5 cm). Adrenal gland must be excised en bloc, also because of the possible presence of other adrenal lesions.

Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma.

BACKGROUND: Recurrence of adrenal cortical carcinoma (ACC) after radical surgery is a common finding. Although successful reoperations have been reported with encouraging results, most published experiences are anecdotal and based on few cases. We report the results of surgical treatment for recurrent ACC in a multiinstitutional series. METHODS: One hundred eighty-eight cases of ACC were collected in a national registry. A complete follow-up was obtained in 179 cases. At initial diagnosis 92 patients had local disease (stage I or II). One hundred seventy patients underwent surgical treatment, considered radical in 140; in this group, recurrent disease was observed in 52 cases (37%) after a mean disease-free interval of 21.7 months. RESULTS: Adjuvant chemotherapy was ineffective in ameliorating the prognosis. The mean survival in 20 patients who underwent reoperation was significantly higher (15.85 +/- 14.9 months) than in nonreoperated cases (3.2 +/- 2.9 months). Five-year actuarial survival in reoperated patients is significantly better than in nonreoperated patients (49.7% versus 8.3%, respectively). CONCLUSIONS: Although the prognosis of this tumor is still poor, surgery is the only effective therapy; reoperation allows survival comparable to that observed in patients without recurrent disease. An aggressive strategy for recurrent ACC is advisable until prospective studies demonstrate a real effectiveness for chemotherapy.

The Italian Registry for Adrenal Cortical Carcinoma: analysis of a multiinstitutional series of 129 patients. The ACC Italian Registry Study Group.

BACKGROUND: Adrenal cortical carcinoma is an uncommon tumor with a poor prognosis. The low incidence of this tumor makes it difficult to achieve reliable data on clinical manifestations, natural history, and the impact of therapies. The purpose of this study was to evaluate such aspects in a large series. METHODS: A retrospective series of 129 cases (55 men and 74 women, mean age of 49 years) was collected from 18 surgical institutions. At the time of diagnosis 45.7% of patients had endocrine symptoms. One hundred twenty-four patients underwent surgery, which was considered curative in 91 cases and palliative in 33. Sixty-three patients had local disease, 48 had regional disease, and 43 had distant metastases. RESULTS: This study confirmed a higher incidence in the 40- to 50-year-old population with a female prevalence; hormonal hyperincretion was more common in women, but it was not caused by advanced disease. The overall 5-year survival rate was 35%. Tumor stage and curative resection affected prognosis significantly. The influence of gender, side, age, and hormonal function has not been confirmed. Adjuvant therapies were ineffective in prolonging survival. Reoperated patients experienced better survival (mean, 41.5 months) than nonreoperated cases (mean, 15.6 months). CONCLUSIONS: The poor prognosis of adrenal cortical carcinoma may be improved by early diagnosis and complete resection. Radical surgery is the sole effective therapy, particularly in early stages. Surgical treatment of recurrence seems to improve survival and should be attempted systematically. Adjuvant therapies obtained contrasting results, and their role should be evaluated in prospective multicentric trials.

[Incidental discovery of adrenal neoplasms: our experience]. / Gli incidentalomi surrenalici: la nostra esperienza.

Incidental radiologic diagnosis of clinically silent adrenal masses is reported with increasing rates. Between 1981 and 1994 we observed 30 patients with "incidentaloma": for each of them a careful hormonal and instrumental evaluation was obtained. 24 patients were surgically treated. No significant biochemical alterations were observed; ETG, TC and RMN had a sensitivity of 86%, 93% and 83%, respectively. At seleno-cholesterol scintigraphy 5 incidentalomas (all adenomas) had a concordant pattern and 5 (none of these adenoma) had a discordant pattern. MIBG scintigraphy showed an uptaking ganglioneuroma. The observed histotypes were: 10 adenomas, 3 cysts, 1 hematoma, 1 myelolipoma, 1 angiomyolipoma, 1 ganglioneuroma, 1 ganglioneurofibroma, 1 paraganglioma, 1 aspecific granulomatous necrosis, 4 cortical carcinoma and 3 metastatic lesions. We did not observe any postoperative acute adrenal failure. The main problem raised by incidentalomas is to define their nature; hence the need of a careful hormonometabolic, morpho-functional and instrumental evaluation. The available diagnostic procedures, even when combined, cannot always define if an incidentaloma is a benign or a malignant lesion: in the current clinical practice, the size of the mass is still the most important criterion to define a therapeutic approach. Surgical excision is mandatory in presence of an hormonal production, even subclinic, and/or a large size of the mass (over 5 cm). If the tumor size is less than 5 cm, an aggressive strategy may be chosen in selected low-risk patients, because of the low morbidity of adrenalectomy. In our experience, the transperitoneal subcostal approach has been adopted routinely with good results.

[Complications in thyroid surgery]. / Complicanze in chirurgia tiroidea.

Since the first years of the century, the improvement in surgical techniques has drastically reduced the main postoperative complication, profuse bleeding. More experience in thyroidectomy has highlighted other specific problems of the procedure, which has received substantial benefits by the adoption of targeted surgical techniques. The Authors describe the most important topics reported for each complication, on the basis of the latest literature and their own experience, with particular reference to the oncologic surgery of the thyroid.