Sublethal hyperthermia transiently disrupts Cortisol steroidogenesis in adrenocortical cells.

Primary Aldosteronism is the most common cause of secondary hypertension. First-line treatment; adrenalectomy resects adrenal nodules and adjacent normal tissue, limiting suitability to those who present with unilateral disease. Use of thermal ablation represents an emerging approach as a possible minimally invasive therapy for unilateral and bilateral disease, to target and disrupt hypersecreting aldosterone producing adenomas, while preserving adjacent normal adrenal cortex. To determine the extent of damage to adrenal cells upon exposure to hyperthermia; the steroidogenic adrenocortical cell lines, H295R and HAC15 were treated with hyperthermia at temperatures between 37-50 °C with the effects of hyperthermia on steroidogenesis evaluated following stimulation with forskolin (FSK) and angiotensin II (ANGII). Cell death, protein/mRNA expression of steroidogenic enzymes and damage markers (HSP70/90), and steroid secretion were analysed immediately and 7-days post-treatment. Following treatment with hyperthermia, 42 °C & 45 °C, did not induce cell death and were deemed sublethal doses while ≥50 °C caused excess cell death in adrenal cells. Sublethal hyperthermia (45 °C) caused a significant reduction in cortisol secretion immediately following treatment while differentially affecting the expression of various steroidogenic enzymes, although recovery of steroidogenesis was evident 7-days post-treatment. As such, sublethal hyperthermia, which occurs in the transitional zone during thermal ablation induces a short-lived, un-sustained inhibition of cortisol steroidogenesis in adrenocortical cells in vitro.