Using microwave thermal ablation to develop a subtotal, cortical-sparing approach to the management of primary aldosteronism.

Objective: To investigate the feasibility and efficacy of localized, subtotal, cortical-sparing microwave thermal ablation (MTA) as a potential curative management for primary aldosteronism. The study investigated with equal importance the selected ablation of small volumes of adrenal cortex while sparing adjacent cortex. Method: An in-vivo study was carried out in swine (n = 8) where MTA was applied under direct visualization, to the adrenal glands at 45 W or 70 W for 60 s, using a lateral, side-firing probe and a non-penetrative approach. Animals were survived for 48 h post-procedurally. Animals were investigated for markers of histological, immunohistochemical and biochemical evidence of adrenal function and adrenal damage by assessing samples drawn intra-operatively and at the time of euthanasia. Results: Selected MTA (70 W for 60 s) successfully ablated small adrenocortical volumes (∼0.8 cm3) characterized by coagulative necrosis and abnormal expression of functional markers (CYP11B1 and CYP17). Non-ablated, adjacent cortex was not affected and preserved normal expression of functional markers, without increased expression of markers of heat damage (HSP-70 and HMGB-1). Limited adrenal medullary damage was demonstrated histologically, clinically and biochemically. Conclusion: MTA offers potential as an efficient methodology for delivering targeted subtotal cortical-sparing adrenal ablation. Image-guided targeted MTA may also represent a safe future modality for curative management of PA, in the setting of both unilateral and bilateral disease.

A Mercury Toxicity Case Complicated by Hyponatremia and Abnormal Endocrinological Test Results.

Mercury (Hg) poisoning is considered a rare disease by the National Institutes of Health and the diagnosis can present great challenges to clinicians. Children who are exposed to Hg can present with a wide variety of symptoms, including acrodynia, tremor, excessive salivation, and psychiatric symptoms, including insomnia. However, endocrinologic manifestations from Hg exposure are less well known. This is a case report of a 12-year-old boy who presented with body rash, irritability, insomnia, and profuse sweating after returning from a summer camp. The child was initially managed in the outpatient setting, and the investigation was mainly targeted toward infectious etiology, including Rocky Mountain spotted fever and Lyme disease. He was eventually admitted to the hospital with altered mental status and was noted to have hyponatremia with serum sodium of 121 mEq/L. Thyroid studies also revealed elevated free thyroxine levels in the presence of normal triiodothyronine and thyrotropin. The patient developed hypertension and tachycardia, and was found to have elevated 24-hour vanillylmandelic acid and metanephrines. Finally, heavy metal measurements revealed a blood Hg level that was greater than the reference values of 0 to 9 ng/mL. Chelation treatment with 2,3-dimercaptopropane-1-sulfonate was subsequently initiated and over a period of 8 months his symptoms resolved and his thyroid function test returned to normal. This case highlights some of the challenges commonly encountered in identifying Hg exposure. More importantly, it illustrates that exposure to Hg should be considered in children who present with the symptoms and abnormal endocrinologic test results described in this report.

Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels.

AIM: The present study was to compare the effects of nicotinic acid and nicotinamide on the plasma methyl donors, choline and betaine. METHODS: Thirty adult subjects were randomly divided into three groups of equal size, and orally received purified water (C group), nicotinic acid (300 mg, NA group) or nicotinamide (300 mg, NM group). Plasma nicotinamide, N1-methylnicotinamide, homocysteine, betaine and choline levels before and 1.5-h and 3-h post-dosing, plasma normetanephrine and metanephrine concentrations at 3-h post-dosing, and the urinary excretion of N1-methyl-2-pyridone-5-carboxamide during the test period were examined. RESULTS: The level of 3-h plasma nicotinamide, N1-methylnicotinamide, homocysteine, the urinary excretion of N1-methyl-2-pyridone-5-carboxamide and pulse pressure (PP) in the NM group was 221%, 3972%, 61%, 1728% and 21.2% higher than that of the control group (P < 0.01, except homocysteine and PP P < 0.05), while the 3-h plasma betaine, normetanephrine and metanephrine level in the NM group was 24.4%, 9.4% and 11.7% lower (P < 0.05, except betaine P < 0.01), without significant difference in choline levels. Similar but less pronounced changes were observed in the NA group, with a lower level of 3-h plasma N1-methylnicotinamide (1.90 ± 0.20 µmol/l vs. 3.62 ± 0.27 µmol/l, P < 0.01) and homocysteine (12.85 ± 1.39 µmol/l vs. 18.08 ± 1.02 µmol/l, P < 0.05) but a higher level of betaine (27.44 ± 0.71 µmol/l vs. 23.52 ± 0.61 µmol/l, P < 0.05) than that of the NM group. CONCLUSION: The degradation of nicotinamide consumes more betaine than that of nicotinic acid at identical doses. This difference should be taken into consideration in niacin fortification.

Orexinergic activation of medullary premotor neurons modulates the adrenal sympathoexcitation to hypothalamic glucoprivation.

Glucoprivation activates neurons in the perifornical hypothalamus (PeH) and in the rostral ventrolateral medulla (RVLM), which results in the release of adrenaline. The current study aimed to establish 1) whether neuroglucoprivation in the PeH or in the RVLM elicits adrenaline release in vivo and 2) whether direct activation by glucoprivation or orexin release in the RVLM modulates the adrenaline release. Neuroglucoprivation in the PeH or RVLM was elicited by microinjections of 2-deoxy-D-glucose or 5-thio-D-glucose in anesthetized, euglycemic rats. Firstly, inhibition of neurons in the PeH abolished the increase in adrenal sympathetic nerve activity (ASNA) to systemic glucoprivation. Secondly, glucoprivation of neurons in the PeH increased ASNA. Thirdly, in vivo or in vitro glucoprivation did not affect the activity of RVLM adrenal premotor neurons. Finally, blockade of orexin receptors in the RVLM abolished the increase in ASNA to neuroglucoprivation in the PeH. The evoked changes in ASNA were directly correlated to levels of plasma metanephrine but not to normetanephrine. These findings suggest that orexin release modulates the activation of adrenal presympathetic neurons in the RVLM.

Exogenous and endogenous plasma levels of epinephrine during dental treatment under local anesthesia.

BACKGROUND AND OBJECTIVES: To determine serum levels of catecholamines after local anesthesia for dental treatment, we used tritium-labeled epinephrine as a vasoconstrictor for dental local anesthesia. METHODS: Twenty healthy male outpatients undergoing standardized dental treatment (deep scaling) were studied. In all patients, only one quadrant was anesthetized even though the treatment was performed on all teeth. Two milliliters of articaine 4% (amide anesthetic) with 20 micrograms epinephrine was used as local anesthetic. Of the total epinephrine administered, 1.2% (100 microCi) consisted of tritium-labeled epinephrine. Blood samples were drawn through a central venous catheter before and at frequent intervals after the local anesthetic solution was administered. RESULTS: A dramatic increase in exogenous epinephrine was observed in four patients during injection (up to 6937 pg/mL). The other 16 patients demonstrated a continuous increase in applied epinephrine that peaked on average at the 7th minute (631.5 +/- 41.4 pg/mL). A second increase occurred after the beginning of the dental procedure. The mean total epinephrine levels were always higher than those of the applied epinephrine. Extrasystoles were observed in two of four and tachycardia in three of four patients with high plasma levels of applied epinephrine. Increases in total epinephrine were associated with exogenous catecholamine administration, whereas the dental treatment did not significantly influence the plasma levels. CONCLUSION: Despite aspiration in 20% of the patients, an unintended intravascular injection occurred. Although healthy young men tolerated large increases in central plasma epinephrine levels surprisingly well, this may not be the case in patients with concurrent cardiovascular disease. Patients at cardiovascular risk should be under continuous monitoring when an epinephrine-containing solution is applied.