The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. The Weiss score is the most widely accepted method for distinguishing an ACC from an adrenocortical adenoma (ACA); however, in borderline cases, accurate diagnosis remains problematic. We recently discovered that the glucocorticoid receptor (GR) gene NR3C1 is significantly up-regulated in ACCs compared with ACAs in global gene expression studies. OBJECTIVE: Our objective was to study GR expression in adrenocortical tumors (ACTs) and to assess its utility as an adjunct to the Weiss score. DESIGN: Microarray analysis, real-time quantitative RT-PCR (qPCR), immunohistochemistry, Western blot, and direct sequencing were performed. RESULTS: Analysis of 28 ACTs by microarray and 49 ACTs by qPCR found NR3C1 expression to be up-regulated in ACCs compared with ACAs (P < 0.001). Western blotting and RT-PCR confirmed the presence of the GRalpha isoform in ACCs, and no mutations were detected on direct sequencing. Immunohistochemistry for GR in an overlapping cohort of ACTs demonstrated strongly positive nuclear staining in 31 of 33 ACCs (94%), with negative staining in 40 of 41 ACAs (98%) (P < 0.001). This finding was validated in an external cohort of ACTs, such that 14 of 18 ACCs (78%) demonstrated positive nuclear staining whereas 32 of 33 ACAs (94%) were negative (P < 0.001). CONCLUSIONS: The immunohistochemical finding of nuclear GR staining identified ACCs with high diagnostic accuracy. We propose that GR immunohistochemistry may complement the Weiss score in the diagnosis of ACC in cases that display borderline histology. The possibility that GR is transcriptionally active in these tumors, and may therefore be a therapeutic target, requires further study.

Nerve stimulation in thyroid surgery: is it really useful?

BACKGROUND: Monitoring of the recurrent laryngeal nerve (RLN) has been claimed in some studies to reduce rates of nerve injury during thyroid surgery compared with anatomical dissection and visual identification of the RLN alone, whereas other studies have found no benefit. Continuous monitoring with endotracheal electrodes is expensive whereas discontinuous monitoring by laryngeal palpation with nerve stimulation is a simple and inexpensive technique. This study aimed to assess the value of nerve stimulation with laryngeal palpation as a means of identifying and assessing the function of the RLN and external branch of the superior laryngeal nerve (EBSLN) during thyroid surgery. METHODS: This was a prospective case series comprising 50 consecutive patients undergoing total thyroidectomy providing 100 RLN and 100 EBSLN for examination. All patients underwent preoperative and postoperative vocal cord and voice assessment by an independent ear, nose and throat surgeon, laryngeal examination at extubation and all were asked to complete a postoperative dysphagia score sheet. Dysphagia scores in the study group were compared with a control group (n = 20) undergoing total thyroidectomy without nerve stimulation. RESULTS: One hundred of 100 (100%) RLN were located without the use of the nerve stimulator. A negative twitch response occurred in seven (7%) RLN stimulated (two bilateral, three unilateral). Postoperative testing, however, only showed one true unilateral RLN palsy postoperatively (1%), which recovered in 7 weeks giving six false-positive and one true-positive results. Eighty-six of 100 (86%) EBSLN were located without the nerve stimulator. Thirteen of 100 (13%) EBSLN could not be identified and 1 of 100 (1%) was located with the use of the nerve stimulator. Fourteen per cent of EBSLN showed no cricothyroid twitch on EBSLN stimulation. Postoperative vocal function in these patients was normal. There were no instances of equipment malfunction. Dysphagia scores did not differ significantly between the study and control groups. CONCLUSION: Use of a nerve stimulator did not aid in anatomical dissection of the RLN and was useful in identifying only one EBSLN. Discontinuous nerve monitoring by stimulation during total thyroidectomy confers no obvious benefit for the experienced surgeon in nerve identification, functional testing or injury prevention.

Recurrence after total thyroidectomy for benign multinodular goiter.

BACKGROUND: Total thyroidectomy is now the preferred option for the management of benign multinodular goiter (BMNG), and it ought not be associated with recurrent disease. The aim of the present study was to examine the efficacy of total thyroidectomy for BMNG and to review reasons for recurrence. MATERIAL AND METHODS: The study group comprised all patients from January 1980 to December 2005 who underwent a definitive procedure to remove all thyroid tissue for BMNG, and who were subsequently identified as having developed a recurrence. Included were patients who underwent primary total thyroidectomy at our unit, or a two or more stage procedure where a definitive secondary total thyroidectomy was performed at our unit. RESULTS: There were 3,044 total or secondary total thyroidectomies performed for BMNG during the study period. Ten patients were identified as having developed recurrent BMNG requiring reoperation despite previous complete "total" thyroidectomy. There were 11 sites of recurrence in 10 patients. Only one was a true local recurrence in the thyroid bed. Another 9 recurrences related to the embryology of the thyroid gland, 4 in the pyramidal tract and 5 in the thyrothymic tract. There was one recurrence at another site (submandibular) in a patient with presumed metastatic thyroid cancer despite benign histology. There were no complications in any of the 10 patients. CONCLUSIONS: Total thyroidectomy for BMNG is not only a safe procedure but is efficacious in preventing recurrent disease. Failure to remove embryological remnants such as thyrothymic residue or pyramidal remnants during total thyroidectomy is the major cause of recurrence.