Eleven-Year Experience with Selective Adrenal Vein Sampling in Management of Primary Adrenal Hormonal Hypersecretion.

Introduction: Nearly half of the adult population in the United States has been diagnosed with hypertension. Adrenal hormonal hypersecretion is a leading cause of secondary hypertension. Adrenal vein sampling (AVS) may assist in differentiating between unilateral and bilateral adrenal hormonal hypersecretion to identify patients who are candidates for adrenalectomy. We reviewed the use of AVS at our institution along with associated outcomes after adrenalectomy. Materials and Methods: A retrospective chart review was conducted of patients with a diagnosis of primary hyperaldosteronism (PA) or adrenocorticotropic hormone-independent Cushing syndrome (AICS) and who underwent adrenalectomy between January 1, 2010, and December 1, 2021. Patient data of baseline characteristics, preoperative workup, including AVS, and postoperative outcomes were collected and analyzed. Results: Seventy-one patients were identified in the study period (48 PA and 23 AICS). Computed tomography scan identified unilateral adrenal nodules in 52 patients (29 left; and 23 right), bilateral nodules in 13 patients, and no nodules in 6 patients. AVS was performed in 45 patients with PA (93%) and 5 patients with AICS (21%). After surgery, the number of PA patients with hypokalemia or requiring potassium supplementation significantly decreased after adrenalectomy (before surgery: 33 [68.7%]; and after surgery: 5 [10.4%], P < .01). The number of medications required for hypertension in AICS patients also significantly decreased. No major adverse events were noted. Conclusions: Our long-term experience demonstrates the ongoing use of AVS during workup of patients with primary hyperaldosteronism and for select patients with adrenocorticotropic hormone-independent Cushing syndrome. However, a low level of discordance between imaging and AVS findings in PA patients suggests that there may be a subset of patients in whom preoperative AVS is not necessary.

Successful percutaneous CT-guided microwave ablation of adrenal gland for ectopic Cushing syndrome.

Adrenocorticotropic hormone production by pancreatic neuroendocrine tumor (PNET) is rare and results in hyperstimulation of the adrenal gland to produce ectopic Cushing syndrome. Our case showcases the safety and effectiveness of percutaneous CT-guided microwave ablation of the adrenal gland in a 49-year-old female with PNET and hepatic metastases who presented with ectopic Cushing syndrome despite surgical resection of the primary pancreatic tumor and left adrenal gland. Prior to ablation, the right adrenal gland measured 4.3×1.6×2.0cm and the patient had malignant hypertension with elevated morning serum cortisol level (1976nmol/L). After microwave ablation of the right adrenal gland, the hypertension resolved and the cortisol level decreased dramatically (74nmol/L). As expected after successful treatment, the patient developed adrenal insufficiency and was placed on glucocorticoid and mineralocorticoid supplementation.

Comparison of different postoperative pain managements in patients submitted to transperitoneal laparoscopic renal and adrenal surgery.

PURPOSE: We compared the effects of local levobupivacaine infiltration, intravenous paracetamol, intravenous lornoxicam treatments on postoperative analgesia in patients submitted to transperitoneal laparoscopic renal and adrenal surgery. MATERIALS AND METHODS: Sixty adult patients 26 and 70 years who underwent laparoscopic renal and adrenal surgery were randomized into three groups with 20 patients each: Group 1 received local 20 mL of levobupivacaine 0.25% infiltration to the trocar incisions before skin closure. In group 2, 1g paracetamol was given to the patients intravenously 30 minutes before extubation and 5 g paracetamol was given intravenously in the 24 postoperative period. In group 3, 8 mg lornoxicam i.v. was given 30 minutes before extubation and 8 mg lornoxicam i.v. was given in the 24 postoperative period. In the postoperative period, pain scores, cumulative tramadol, and additional pethidine consumption were evaluated. RESULTS: Postoperative pain scores significantly reduced in each group (p < 0.05). Although pain levels of the groups were not significantly different at 1, 2, 4, 8, 12 and 24 hours postoperatively, cumulative tramadol consumptions were higher in group 1 than the others. (Group 1 = 370.6 ± 121.6 mg, Group 2: 220.9 ± 92.5mg, Group 3 = 240.7 ± 100.4 mg.) (p < 0.005). The average dose of pethidine administered was significantly lower in groups 2 and 3 compared with group 1 (Group 1: 145 mg, Group 2: 100mg, Group 3: 100mg) (p = 0.024). CONCLUSIONS: Levobupivacaine treated group required significantly more intravenous tramadol when compared with paracetamol and lornoxicam groups in patients submitted to transperitoneal laparoscopic renal and adrenal surgery.

Comparison of different postoperative paın managements in patients submitted to transperitoneal laparoscopic renal and adrenal surgery

ABSTRACTPurpose:We compared the effects of local levobupivacaine infiltration, intravenous paracetamol, intravenous lornoxicam treatments on postoperative analgesia in patients submitted to transperitoneal laparoscopic renal and adrenal surgery.Materials and Methods:Sixty adult patients 26 and 70 years who underwent laparoscopic renal and adrenal surgery were randomized into three groups with 20 patients each: Group 1 received local 20mL of levobupivacaine 0.25% infiltration to the trocar incisions before skin closure. In group 2, 1g paracetamol was given to the patients intravenously 30 minutes before extubation and 5g paracetamol was given intravenoulsy in the 24 postoperative period. In group 3, 8mg lornoxicam i.v. was given 30 minutes before extubation and 8mg lornoxicam i.v. was given in the 24 postoperative period. In the postoperative period, pain scores, cumulative tramadol, and additional pethidine consumption were evaluated.Results:Postoperative pain scores significantly reduced in each group (p < 0.05). Although pain levels of the groups were not significantly different at 1, 2, 4, 8, 12 and 24 hours postoperatively, cumulative tramadol consumptions were higher in group 1 than the others. (Group 1 = 370.6 ± 121.6mg, Group 2: 220.9 ± 92.5mg, Group 3 = 240.7 ± 100.4mg.) (p < 0.005). The average dose of pethidine administered was significantly lower in groups 2 and 3 compared with group 1 (Group 1: 145mg, Group 2: 100mg, Group 3: 100mg) (p = 0.024).Conclusions:Levobupivacaine treated group required significantly more intravenous tramadol when compared with paracetamol and lornoxicam groups in patients submitted to transperitoneal laparoscopic renal and adrenal surgery.

Influence of the HPA axis on the inflammatory response in cutaneous wounds with the use of 670-nm laser photobiomodulation.

This study evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis in cutaneous wounds subjected to laser biomodulation. A total of 48 rats were divided into two groups: Group I (GI) with 24 adrenalectomized animals and Group II (GII) with 24 non-adrenalectomized animals. Each group was divided into two subgroups: the irradiated subgroup which laser was applied to four points at the edges of the wound (670 nm laser, 9 mW) and control subgroup. Rats in each subgroup were sacrificed at 24 or 72 h. Adrenal glands were only removed from GI rats. Three days after adrenalectomy, a cutaneous wound was made. An immunohistochemical analysis was performed using anti-CD45 and anti-CD8 antibodies. Flow cytometry was used to count T lymphocytes and their subpopulations in blood. Decreases in the number of CD45-positive inflammatory cells and in the total numbers of CD8- and CD45-positive cells were observed in histological sections of adrenalectomized animals subjected to laser biomodulation at 24h. Similar results were observed for distribution of total lymphocytes in blood (p<0.05). The action of 670 nm laser does not depend exclusively on HPA axis. It is believed that corticosteroid-promoting enzymes liberated in non-adrenal tissues may influence immune response under the influence of this type of phototherapy.

Adrenal influences on the inhibitory effects of procaterol, a selective Beta-two-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in Guinea pigs.

While the guinea pig has been the preferred choice for use as a model of allergic bronchial asthma in the evaluation of anti-asthmatic drugs, it has been shown that antigen-induced bronchoconstriction in guinea pigs is attenuated by epinephrine released from the adrenal gland. In order to investigate the possible influence of the adrenal gland on the effects of antiexudative and bronchodilative drugs on antigen-induced airway responses, we examined the inhibitory effects of procaterol, a selective beta(2)-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in adrenalectomized guinea pigs and compared them with the drug's effects in sham-operated animals. Guinea pigs sensitized passively with anti-ovalbumin (OA) guinea-pig serum were adrenalectomized or sham-operated under urethane anesthesia and examined 30 min after surgery in the following experiments. (1) Animals were intravenously administered Evans blue dye to quantify airway plasma exudation, and then OA was inhaled for 10 min while measuring pulmonary inflation pressure, a parameter of bronchoconstriction. Procaterol (1, 3, 10, or 30 microg/kg) or saline (control) was administered into the airways 10 min prior to OA inhalation. The amount of extravasated Evans blue dye in the airways was calculated. (2) Venous blood samples were collected during OA or saline inhalation and plasma catecholamine levels were compared. In control animals, OA-induced increases in both the amount of Evans blue dye and in pulmonary inflation pressure were markedly greater in adrenalectomized animals than in sham-operated animals. Procaterol dose-dependently inhibited OA-induced airway microvascular leakage and bronchoconstriction, and its effects were more potent in adrenalectomized animals (significant at 1 microg/kg and higher) than in sham-operated animals (significant at 10 microg/kg and higher). Although the plasma concentration of epinephrine during OA inhalation was approximately 3 times higher than that during saline inhalation in sham-operated animals, no difference was seen in adrenalectomized animals. In conclusion, while procaterol essentially possesses pronounced inhibitory effects on antigen-induced airway microvascular leakage and bronchoconstriction in guinea pigs, the effects are considerably masked by epinephrine released from the adrenal gland.

Intraoperative local anesthesia decreases postoperative parenteral opioid requirements for transperitoneal laparoscopic renal and adrenal surgery: a randomized, double-blind, placebo controlled investigation.

PURPOSE: To determine if local anesthesia decreases discomfort following laparoscopic upper retroperitoneal surgery, we performed a randomized, double-blind, placebo controlled study in which the port sites and hand assist incision were infiltrated with bupivacaine or placebo prior to surgery. MATERIALS AND METHODS: A total of 72 patients undergoing transperitoneal laparoscopic renal or adrenal surgery were randomly assigned to the treatment (0.5% bupivacaine) or placebo (0.9% normal saline) arm. Port and hand assist port sites were infiltrated at the outset of the procedure. Postoperative pain and opioid use were measured at consistent intervals. RESULTS: A total of 37 individuals were treated with placebo (standard laparoscopy [SL] in 15 and hand assisted laparoscopy [HALS] in 22) and 35 were treated with bupivacaine (SL in 16 and HALS in 19). Mean parenteral morphine equivalents use for the placebo vs bupivacaine groups were 29.6 vs 20.0 mg at 12 hours, 50.2 vs 34.5 mg at 24 hours and 57.1 vs 36.6 mg for the total hospital stay (all p <0.05). Parenteral opioid use was decreased in the bupivacaine group in the SL and HALS subgroups with a significant effect at 12 hours in the latter subgroup. On multivariate ANOVA bupivacaine use but not SL vs HALS was associated with decreased parenteral opioid use at all time points (p <0.05). CONCLUSIONS: At the outset of transperitoneal laparoscopic urological surgery in the upper retroperitoneum, port site and other incision infiltration with long acting local anesthesia decreases postoperative parenteral opioid requirements compared with placebo controls. The effect was seen with SL and HALS and it was greater than any effect of SL vs HALS.

Regulation of hippocampal glucocorticoid receptor gene transcription and protein expression in vivo.

Glucocorticoid receptors (GRs) are glucocorticoid-activated transcription factors that modulate expression of a variety of neuronal genes. Appropriate control of GR expression is therefore critical for maintenance of cellular and organismic homeostasis. The present study assessed glucocorticoid regulation of the GR at the gene, mRNA, and protein level. Removal of circulating glucocorticoids (adrenalectomy) increased GR mRNA expression in CA1 and dentate gyrus (DG). Corticosterone (CORT) replacement normalized GR mRNA expression, whereas high doses slightly decreased GR mRNA in CA1. Parallel increases were observed using a probe complementary to the distal 3' untranslated region, indicating that mRNA changes were not attributable to selection of alternative polyadenylation site. Expression of a GR intronic sequence was also increased by adrenalectomy, consistent with increased gene transcription. Analysis of regional GR protein expression by immunoautoradiography did not reveal changes in GR protein in pyramidal cell layers; however, increased GR signal was seen in the stratum radiatum, indicating redistribution of GR to the cytosol. Western blot analysis confirmed adrenalectomy-induced increases in hippocampal GR levels. Administration of the mineralocorticoid receptor (MR) antagonist spironolactone increased both GR mRNA and protein in CA1 and DG, consistent with MR-mediated inhibition of GR transcription. However, high-dose CORT treatment did not decrease GR mRNA or protein levels. Chronic stress exposure did not downregulate GR mRNA or protein in hippocampus. The results suggest that the hippocampal GR is subject to heterologous regulation by the MR. In contrast, GR autoregulation is only evident during prolonged exposure to high-circulating glucocorticoid levels.

Distribution and concentration of urocortin, and effect of adrenalectomy on its content in rat hypothalamus.

We developed a specific and sensitive radioimmunoassay (RIA) for rat urocortin (rUcn) and investigated the tissue distribution and concentration of immunoreactive (IR-)Ucn in rats. Antiserum was obtained by immunizing rabbits with synthetic rUcn21-35 coupled with bovine thyroglobulin. 125I-[Tyr]18-rUcn19-37 was used as the tracer. The RIA detected synthetic rUcn1-40 as low as 0.4 fmol/tube, and did not cross-react with other corticotropin-releasing factor-related peptides. IR-Ucn was widely distributed in central nervous system, endocrine organs, and digestive system. Its concentration was highest in pituitary (11.0 +/- 1.36 pmol/g.w.w., mean +/- SEM, n=4). Reverse-phase HPLC revealed that hypothalamic IR-Ucn had similar chromatographic mobility to synthetic rUcn1-40. However, bilateral adrenalectomy did not influence the hypothalamic IR-Ucn content. Our results suggest that Ucn may play important roles in various tissues in normal rats, but not behave as a hypothalamic hypophysiotropic factor in mediating adrenocorticotropin secretion in adrenalectomized rats.

Primary hyperaldosteronism in pregnancy. A case report.

BACKGROUND: Primary hyperaldosteronism is an uncommon disorder, and there are few reports of its occurrence and management in pregnancy. CASE: Primary hyperaldosteronism was suspected before pregnancy in a 31-year-old women with refractory hypertension and hypokalemia. Pregnancy evaluation revealed suppressed renin levels and high aldosterone levels; computed tomography revealed a 1-cm mass in the left adrenal gland. The patient became pregnant before completion of evaluation and treatment. On high doses of nifedipine and nadolol, the first-trimester blood pressure was 130/98 mm Hg and remained high in the early second trimester. In view of the risks of poorly controlled hypertension, adrenalectomy was performed at 15 weeks' gestation, with rapid improvement in blood pressure and elimination of the patient's requirement for large doses of potassium daily. Antihypertensive medication was withdrawn, with maintenance of normal blood pressure until 36 weeks' gestation. At that time the blood pressure rose slightly but responded to bed rest. A healthy female infant was delivered at term by cesarean section. CONCLUSION: Previous reports of emergency preterm delivery and a case of neonatal mortality in the setting of hyperaldosteronism in pregnancy confirm the significant risks associated with this condition. In our patient, adrenalectomy in the early second trimester resulted in a rapid and sustained improvement in hypertension, reversal of hypokalemia and a good pregnancy outcome.

Hypertension in disguise--a trap for the unwary.

A 36-year-old asymptomatic Chinese male with polycystic kidney disease (PKD) developed hypertension 1 year after the diagnosis of PKD. The patient was treated initially as for hypertension associated with PKD. However, over a 6-year period his hypertension became progressively difficult to control and he developed severe symptomatic hypokalemia. Subsequent investigations confirmed the presence of primary hyperaldosteronism. The initial computed tomographic scans of the adrenals did not reveal any definite adenomas. The patient subsequently underwent bilateral adrenal venous sampling, which suggested a left-sided source of aldosterone excess. A repeat computed tomography of the adrenals with fine cuts revealed a 6-mm diameter adenoma of the left adrenal gland. He underwent an uncomplicated left adrenalectomy. All antihypertensive and potassium supplements were stopped on the 5th postoperative day. Two and half years after the adrenalectomy he remains normotensive and normokalaemic without any medication. The case illustrates the importance of measuring serum potassium before initiation of any therapy and the need to consider secondary causes even if a primary association is known. It also reinforces the fact that when hypertension becomes difficult to control, a secondary cause has to be searched actively. The association between primary aldosteronism and renal cysts has been highlighted only recently. The association of polycystic kidneys and primary aldosteronism has been reported in the literature only once previously.

[On the influence of thiocyanates on the delayed immune response in intact and epinephrectomised guinea pigs (author's transl)]. / Uber die Beeinflussbarkeit der Sensibilisierung beim nebennierenintakten und nebennierenexstirpierten Meerschweinchen durch Rhodanide.

Daily application of 32 mg/kg sodium thiocynate from 1--11th respectively 12th--21st experimental day causes in epinephrectomised guinea pigs at the 26th experimental day an inhibition of cell-mediated immune response (sensitization was induced by intraperitoneal injection of horse serum at the 5th and 7th experimental day). The inhibition of cell-mediated immune response could be demonstrated by means of migration inhibition of spleen cells. Epinephrectomy was performed by operation procedures twice a week. Gluco- and mineralocorticoids were applied supplementary. -- Also other proved thiocyanates respectively compounds with thiocyanate groups such as potassium thiocyanate, ammonium thiocyanate and d,1-2-imino-3.4-dimethyl-5-phenyl-thiacolidinhydrothiocyanate showed the same effect. The results are only pointed out in intact animals, but distinct in epinephrectomised guinea pigs. Finally a significant weaker effect, but of the same kind was observed by potassium- and sodium iodate. Every used dose of prednisolone and cyclophosphamide suppress the migration inhibition. The influence of 2-iminothiacolidin-4-carbon acid and desoxycorticosteronacetat on the migration inhibition is different and depends on the antigen dose applied for sensitization. -- Simulated daily injections undertaken in form of stitches and application of aqua destillata are inefficacious.

[Primary hyperparthyroidism. Analysis of 152 patients with special reference to acute life threatening complications (acute hyperparathyroidism)]. / Primärer Hyperparathyreoidismus Eine Analyse von 152 Patienten unter besonderer Berücksichtigung akuter lebensbedrohlicher Komplikationen (akuter Hyperparathyreiodismus).

The findings of 152 patients with proven primary hyperparathyroidism are reportedmthe purpose of the analysis was to find difference between the various clinical manifestations of the disease. Furthermore the occurrence of acute hyperparathyroid crisis in our series as well as in the literature are described. 65.8% of the patients were females, 34.2% were males. The leading symptom in 98 patients (group I) were kidney stones and in 23 patients (group II) cystic bone disease. Both manifestations of the disease occurred in only 7 patients (group III) and no symptoms related to the kidneys or to the bones occurred in 24 patients (group IV). Because of the difference of the clinical manifestations the additional data were analyzed for each group separately and compared with each other. There was no difference in the mean serum calcium levels for all four groups, however, patients of group I were on the average younger, the duration of the disease was longer and the weight of the parathyroid adenoma was lower compared to the other three groups, Data are presented regarding calcium excretion, phosphate clearance and tubular reabsorption of phosphate for each group. At operation single or multiple adenoma formation was present in 133 patients, whereas diffuse hyperplasia was found in 17 and carcinoma in 2 other patients. 46 of the adenomas were found in an atypical anatomical localisation. This observation is responsible for the many unsuccessful or second explorations of the neck; The weight of the adenomas varied between 0.1 and 23.5 g. The most difficult diagnosis was that of diffuse hyperplasia. The sucess of the surgical intervention was usually established in over 80% of the cases within 24 to 48 hours after the operation with a significant fall of serum calcium. There ist still no definite explanation for the variability of the clinical manifestations of primary hyperparathyroidism. Parathyroid hormone determinations on larger numbers of patients are not yet published. The assumption, that different hormones or peptide fragments are reposible for the different action on bone and kidney is discussed; In our series of 152 patients acute hyperparathyroid crisis occurred eight times. Our findings are compared to the other well documented cases in the literature. Main symptoms were nausea, vomiting, abdominal pain and different states of cerebral dysfunction. Most of the patients had calcium levels over 16 mg/100 ml. Partial renal insufficiency with elevated blood urea and phosphate retention was found in over 50% of the cases. Overall mortality of all cases with acute parathyroid crisis is 52.5%. The pathogenesis of acute hyperparathyroidism and the implications of high calcium levels are discussed. According to our own experience hypercalcenia can be controlled with an intensive therapeutic program and emergency operation for acute parathyroid crisis is no longer necessary.