Minimally invasive parathyroid exploration for solitary adenoma. Initial experience with an open, 'short incision' approach.

BACKGROUND: In the vast majority of patients with primary hyperparathyroidism (HPT) the causative pathology is a benign solitary adenoma. The conventional surgical approach for HPT has involved bilateral cervical exploration with attempted identification of all four parathyroids and resection of enlarged glands. However, in recent years new techniques have permitted accurate preoperative localisation of the single parathyroid tumour in many patients. This has facilitated a focused unilateral operation to be performed in patients with a solitary parathyroid adenoma. More recently we have progressed to a minimally invasive surgical approach for such individuals in whom the tumour has been localised preoperatively. PATIENTS & METHODS: Between September 2004 and July 2006, 24 patients with proven HPT, underwent focused, unilateral cervical exploration through a short (2.5-3 cm) incision placed low on the appropriate side of the neck. Preoperatively, each patient had been shown to have a single focus of activity after parathyroid isotope scanning. RESULTS: There were 21 females and 3 males in the study group with a mean age of 61.5 years (range 25 - 84 years) at the time of operation. The approach was successful in 22 patients with a mean operating time of 49 minutes (range 22-85 minutes). Postoperatively, the serum calcium level returned to normal in every patient and has remained so during a mean follow up period of 11.5 months (range 1-22 months). No individual developed postoperative hypocalcaemia although one patient developed a temporary unilateral vocal cord paralysis. CONCLUSION: A short incision cervical approach for HPT due to solitary adenoma is a viable alternative for appropriately selected patients.

The RET mutation E768D confers a late-onset familial medullary thyroid carcinoma -- only phenotype with incomplete penetrance: implications for screening and management of carrier status.

OBJECTIVE: We describe a 4-generation family with familial medullary thyroid carcinoma (FMTC) -- a variant of multiple endocrine neoplasia type 2 (MEN 2) without extra-thyroid features. RET mutation analysis confirmed an E768D mutation in exon 13 in 8 family members, 3 affected with medullary thyroid cancer alone while the other 5 were detected to be mutation carriers. This mutation has been described in very few families worldwide and the spectrum of disease and natural history is unclear. RESULTS: Three affected members had medullary thyroid cancer (MTC) confirmed histologically at ages 25, 50 and 56 years, respectively. The E768D mutation appears to have a less aggressive clinical course compared to other high risk RET mutations with no evidence of clinical recurrence up to 11 years after initial therapy. Of five gene carriers identified, two are asymptomatic at the age of 70 and 61, and three had raised calcitonin levels at 46, 39, and 45 years. Following total thyroidectomy, one gene carrier had a histologically normal thyroid at age 46, following a mildly elevated calcitonin, one had C-cell hyperplasia at the age of 39, and one had a frank focus of carcinoma in the left thyroid lobe at the age of 45. No members had evidence of phaeochromocytoma or parathyroid disease on screening. CONCLUSION: The RET E768D mutation is associated with MTC with a later age at presentation, incomplete penetrance and less aggressive course compared with other high risk RET mutations. To date in this family the E768D mutation has not been associated with either phaeochromocytoma or hyperparathyroidism. The appropriate screening strategy for and management of E768D carriers is difficult reflecting the phenotypic heterogeneity.

Long-term outcome of unilateral parathyroid exploration for primary hyperparathyroidism due to presumed solitary adenoma.

Unilateral cervical exploration for primary hyperparathyroidism (PHPT) remains controversial. Critics of unilateral exploration have argued that this surgical strategy results in an unacceptably large number of patients with persistent or recurrent hypercalcemia following the initial operation due to undetected additional parathyroid pathology on the contralateral, unexplored side of the neck. We have reviewed retrospectively a large cohort of patients who were submitted to scan-directed unilateral cervical exploration for PHPT following dual-isotope subtraction scintigraphy and according to a standard protocol. Between January 1, 1985 and June 30, 1999 a series of 184 patients underwent scan-directed unilateral neck exploration for PHPT. Following the initial operation three individuals (1.6%) demonstrated persistent hypercalcemia. At a mean follow-up of 59 months (range 6-168 months) none of the patients had developed recurrent hypercalcemia. Scan-directed unilateral cervical exploration represents a valid surgical strategy for a significant proportion of patients with PHPT; and in this group of patients it does not lead to an increased incidence of persistent or recurrent hypercalcemia.

Comparative genomic hybridization analysis of adrenocortical tumors.

Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that allows the entire genome of a tumor to be surveyed for gains and losses of DNA copy sequences. A limited number of studies reporting the use of this technique in adult adrenocortical tumors have yielded conflicting results. In this study we performed CGH analysis on 13 malignant, 18 benign, and 1 tumor of indeterminate malignant potential with the aim of identifying genetic loci consistently implicated in the development and progression of adrenocortical tumors. Tissue samples from 32 patients with histologically proven adrenocortical tumors were available for CGH analysis. CGH changes were seen in all cancers, 11 of 18 (61%) adenomas, and the 1 tumor of indeterminate malignant potential. Of the adrenal cancers, the most common gains were seen on chromosomes 5 (46%), 12 (38%), 19 (31%), and 4 (31%). Losses were most frequently seen at 1p (62%), 17p (54%), 22 (38%), 2q (31%), and 11q (31%). Of the benign adenomas, the most common change was gain of 4q (22%). Mann-Whitney analysis showed a highly significant difference between the cancer group (mean changes, 7.6) and the adenoma group (mean changes, 1.1) for the number of observed CGH changes (P < 0.01). Logistic regression analysis showed that the number of CGH changes was highly predictive of tumor type (P < 0.01). This study has identified several chromosomal loci implicated in adrenocortical tumorigenesis. Activation of a protooncogene(s) on chromosome 4 may be an early event, with progression from adenoma to carcinoma involving activation of oncogenes on chromosomes 5 and 12 and inactivation of tumor suppressor genes on chromosome arms 1p and 17p.