Regeneration of Functional Adrenal Tissue Following Bilateral Adrenalectomy

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Abstract
It is assumed that following complete bilateral adrenalectomy, no adrenal tissue will re-develop, and adrenal hormone levels would remain low and unaffected by stress. However, anecdotal observations in animals and in patients suggest that under some unknown circumstances the opposite can occur. Herein we studied whether adrenalectomized rats can develop an alternative source of systemic corticosterone after complete bilateral adrenalectomy with minimal replacement therapy. Male and female rats underwent either a standard adrenalectomy, in which the glands were removed with minimal surrounding adipose tissue, or an extensive adrenalectomy, in which glands were removed with most surrounding adipose tissue. Excised glands were histologically tested for completeness, and corticosterone replacement was nullified within 1-3 weeks postoperatively. In four experiments and in both excision approaches, some rats gradually reestablished corticosterone baseline levels and stress response in a time-dependent manner, but differences were observed in the reestablishing rates: 80% in standard adrenalectomy vs. 20% in the extensive adrenalectomy. Upon searching for the source of corticosterone secretion, we were surprised to find functional macroscopic foci of adrenocortical tissue, without medullary tissue, mostly proximal to the original location. Chronic stress accelerated corticosterone levels reestablishment. We hypothesize that underlying this phenomenon are pre-existing ectopic microscopic foci of adrenocortical-like tissue, or few adrenal cells that were pre-embedded in surrounding tissue or detached from the excised gland upon removal. We conclude that ADX animals may develop compensatory mechanisms, and suggest that studies employing ADX consider additional corticosterone supplementation, minimize stress, and verify absence of circulating corticosterone.
Funding Information
  • National Institutes of Health
  • National Cancer Institute (CA172138, CA125456)

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