Expression of pituitary hormones in the Pax8-/- mouse model of congenital hypothyroidism

Signaling mechanisms in pituitary morphogenesis as well as pituitary cell fate determination during early embryonic development are relatively well characterized. In contrast, the cues that determine the progression of the various anterior pituitary cell types during postnatal periods are poorly defined. Pax8-/- mice, which are born without a thyroid gland, were used to study the influence of thyroid hormones on the expression of pituitary hormones during early postnatal life. Serum pituitary hormones were determined by RIAs, and the pituitaries were analyzed by Northern blotting, in situ hybridization histochemistry, and immunocytochemistry. In 21-d-old Pax8-/- mice, the cellular composition of the anterior pituitary was dramatically distorted. Thyrotropes exhibited hypertrophy and hyperplasia, the number of detectable somatotropes was drastically reduced, and lactotropes were almost undetectable. Expression of LH and FSH was also reduced, but ACTH and proopiomelanocortin expression was not significantly different. Serum pituitary hormone levels were changed correspondingly. T(4) replacement therapy for variable time periods normalized TSH and GH mRNA expression within 3 d but not prolactin expression, not even when T(4) was administered for 6 d in combination with estradiol. These findings reveal the importance of thyroid hormones in developing the appropriate proportions of anterior pituitary cell types, especially with regard to lactotropes.     

Targeted overexpression of luteinizing hormone causes ovary-dependent functional adenomas restricted to cells of the Pit-1 lineage

The majority of pituitary adenomas in humans are nonmetastasizing, monoclonal neoplasms that occur in approximately 20% of the general population. Their development has been linked to a combination of extrinsic factors and intrinsic defects. We now demonstrate with transgenic mice that targeted and chronic overexpression of LH causes ovarian hyperstimulation and subsequent hyperproliferation of Pit-1-positive cells that culminates in the appearance of functional pituitary adenomas ranging from focal to multifocal expansion of lactotropes, somatotropes, and thyrotropes. Tumors fail to develop in ovariectomized mice, indicating that contributions from the ovary are necessary for adenoma development. Although the link between chronic ovarian hyperstimulation and PRL-secreting adenomas was expected, the involvement of somatotropes and thyrotropes was surprising and suggests that multiple ovarian hormones may contribute to this unusual pathological consequence. In support of this idea, we have found that ovariectomy followed by estrogen replacement results in the expansion of lactotropes selectively in LH overexpressing mice, but not somatotropes and thyrotropes. Collectively, these data indicate that estrogen is sufficient for the formation of lactotrope adenomas only in animals with a hyperstimulated ovary, whereas the appearance of GH- and TSH-secreting adenomas depends on multiple ovarian hormones. Together, our data expand current models of pituitary tumorigenesis by suggesting that chronic ovarian hyperstimulation may underlie the formation of a subset of pituitary adenomas containing lactotropes, somatotropes, and thyrotropes.     

Preoperative beta blocker use associated with cerebral ischemia during carotid endarterectomy

Purpose

Cerebral ischemia is a known complication of carotid cross-clamping during carotid endarterectomy. Selective intraluminal shunting for cerebral protection is not always effective and carries risks. The purpose of this study was to identify potentially modifiable risk factors for intraoperative cerebral ischemia and shunting during carotid endarterectomy.

Methods

We performed an historical case-control chart review of primary carotid endarterectomies with electroencephalographic (EEG) monitoring and selective shunting. Randomized controls and cases that showed ischemic EEG changes and required shunting were matched by year of surgery and the presence or absence of a contralateral carotid occlusion. Detailed perioperative data were collected for all cases. Results were analyzed using the Mantel-Haenszel test, analysis of variance, and a multivariate logistic regression model.

Results

Of 523 charts screened, 69 patients had experienced evidence of cerebral ischemia on clamping of the carotid and required shunting. These patients were more likely than their matched controls to have been receiving regular preoperative beta blockers (33/69 vs 18/69, respectively; P = 0.01; odds ratio [OR] 2.5; 95% confidence interval [CI] 1.2 to 5.1). Ipsilateral moderate carotid stenosis (60-80%) was also associated with increased risk. An adjusted multivariate regression model estimated an OR of 3.6 (95% CI 1.5 to 8.9; P = 0.005) for the association between use of a beta blocker and shunting. Intraoperative hemodynamic values were similar for the shunt and control groups as well as for patients receiving and not receiving preoperative beta blockers.

Conclusion

The current study found an association between regular preoperative use of beta blockers and intraoperative cerebral ischemia in patients undergoing carotid endarterectomy. This effect did not relate to intraoperative hemodynamics.     

In Canada, anesthesiologists are less likely to respond to an electronic, compared to a paper questionnaire

PURPOSE: A randomized unblinded controlled trial was used to assess the utility of electronic questionnaires in a survey of Canadian anesthesiologists. METHODS: Postal or electronic questionnaires were sent between November 2001 and March 2002 to 1,333 anesthesiologists registered with the Canadian Anesthesiologists' Society. The primary outcome measure was the difference in response rates between electronic and postal questionnaires. Secondary outcome measures included a comparison of demographic characteristics, cost, and knowledge and practice regarding prophylactic perioperative beta blockade. RESULTS: The overall response rate was 52%. E-mail participants were half as likely as postal participants to respond to the questionnaire (35% vs 69%, relative risk = 0.51, 95% confidence interval 0.45-0.58). Respondents who provided an e-mail address were younger and more likely to be affiliated with an academic institution. There were no significant differences in responses to knowledge and practice questions. The electronic arm was faster than the postal arm and the cost per reply was one-third the cost of the postal arm (2.50 dollars vs 8.02 dollars). CONCLUSIONS: Electronic surveys are a means of acquiring information from a large number of individuals in a rapid, efficient and cost-effective manner. This methodology may be particularly valid and useful in surveys of participants with similar backgrounds and internet access. However the lower response rates achieved as compared with postal surveys indicates a need to use vigilance when generalizing results to a broader population.