Pitfalls in the diagnosis and treatment of a hypertensive patient with unilateral primary aldosteronism and contralateral pheochromocytoma: a case report.

BACKGROUND: Primary aldosteronism (PA) is a common cause of secondary hypertension, whereas pheochromocytoma is a rare cause of it. Thus, concomitant PA and pheochromocytoma is a very rare condition. CASE PRESENTATION: A 52-year-old woman was admitted to our hospital with suspected PA based on the presence of hypertension, spontaneous hypokalemia, and a high aldosterone-to-renin ratio. She had no catecholamine excess symptoms other than hypertension. Abdominal computed tomography (CT) showed a right lipid-rich adrenal mass and a left lipid-poor adrenal mass. PA was diagnosed by the captopril challenge test. The 24-h urinary fractionated metanephrines were slightly elevated. Adrenal vein sampling (AVS) confirmed that the right adrenal gland was responsible for aldosterone hypersecretion. Medical therapy with eplerenone was started because the patient refused surgery. Five years later, she requested surgery for PA. The second AVS confirmed right unilateral hyperaldosteronism, as expected. Repeated abdominal CT showed the enlargement of the left adrenal mass. The 24-h urinary fractionated metanephrines had risen to the diagnostic level. 123I- metaiodobenzylguanidine (MIBG) scintigraphy showed a marked tracer uptake in the left adrenal mass with no metastatic lesion. After preoperative management with α-blockade, laparoscopic left partial adrenalectomy was performed. Immunohistochemical examination of the tumor showed chromogranin A positivity leading to the diagnosis of left pheochromocytoma. CONCLUSIONS: We report an extremely rare case of concomitant unilateral PA and contralateral pheochromocytoma. When diagnosing unilateral PA by AVS, especially in cases with a lipid-poor adrenal mass, clinicians should rule out the possibility of the presence of pheochromocytoma before proceeding to undergo unilateral adrenalectomy. Although there is no standard treatment for this rare condition, it is essential to select personalized treatment from the perspective of conserving the adrenal gland.

Re-Assessment of the Oral Salt Loading Test Using a New Chemiluminescent Enzyme Immunoassay Based on a Two-Step Sandwich Method to Measure 24-Hour Urine Aldosterone Excretion.

Since April 2021, the plasma aldosterone concentration has been measured by chemiluminescent enzyme immunoassay (CLEIA) in Japan. In the present study, we developed a new CLEIA using a two-step sandwich method to measure the 24-hour urine aldosterone level. We collected 115 urine samples and measured 24-hour urine aldosterone levels employing radioimmunoassay (RIA), CLEIA, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that the 24-hour urine aldosterone levels measured using CLEIA and LC-MS/MS were significantly correlated (ρ = 0.992, P < 0.0001). Based on the results of Passing-Bablok regression analysis, the slope was 0.992 and the intercept -19.3. The 24-hour urine aldosterone levels measured using CLEIA and RIA were also significantly correlated (ρ = 0.905, P < 0.0001). However, the aldosterone level measured by CLEIA was lower than that measured by RIA (slope, 0.729; intercept, 120.9). In Japan, a new guideline for primary aldosteronism has been announced, with changes in the aldosterone measurement method. The cutoff values for oral sodium loading test (OSLT) were changed, but clinical verification using real-world urine samples has not been performed. Therefore, we examined the cut-off value of the 24-hour urine aldosterone level after the OSLT. Receiver operating characteristic analysis revealed a cut-off value for primary aldosteronism of 3 µg/day.

Adrenal Vein Sampling With Gadolinium Contrast Medium in a Patient With Florid Primary Aldosteronism and Iodine Allergy.

We describe a 35-year-old woman who was allergic to iodine contrast medium and was diagnosed with primary aldosteronism (PA) based on functional confirmatory tests. She was suspected to have unilateral PA because of marked hypertension, spontaneous hypokalemia, high plasma aldosterone, reduced plasma renin activity, and a right hypodense adrenal tumor. She wanted to become pregnant and requested adrenalectomy instead of medical treatment with mineralocorticoid receptor antagonists. Localization of PA by adrenal vein sampling (AVS) was necessary, but angiography with iodine contrast medium was not possible because of her allergy. AVS was performed using gadolinium contrast agent (gadoterate meglumine) instead of iodine, in combination with computed tomography angiography (CTA). In AVS, before and after adrenocorticotropin (ACTH) loading, 12 blood samples were drawn from the right adrenal vein, left adrenal central vein, left adrenal common duct, left and right renal veins, and the lower inferior vena cava with only 5 mL of gadolinium medium. There were no complications during AVS. Examination revealed an elevated aldosterone/cortisol ratio on the right side, lateralized ratio of 7.4, and contralateral ratio of 0.76; the patient was diagnosed with right unilateral PA. She underwent right adrenalectomy and showed improvements in aldosterone level from 312.4 pg/mL to 83.0 pg/mL, potassium from 3.0 mEq/L to 3.9 mEq/L, and systolic blood pressure from 138 mm Hg to 117 mm Hg. In PA patients with iodine allergy, AVS can be performed safely and precisely using gadolinium contrast combined with CTA.

Dopamine-Secreting Pheochromocytoma and Paraganglioma.

Predominantly or exclusively dopamine-secreting pheochromocytoma and paraganglioma are very rare. We report a 64-year-old woman with an adrenal incidentaloma. She was normotensive and had no symptoms of catecholamine excess. The 24-hour urine catecholamine level showed normal norepinephrine (122.9 µg/day), normal epinephrine (24.3 µg/day), and markedly elevated dopamine (148 212.4 µg/day). 123I-metaiodobenzylguanidine (MIBG) scintigraphy revealed tumor uptake. After α-blockade as preoperative management, she successfully underwent laparoscopic left adrenalectomy and was finally diagnosed with an exclusively dopamine-secreting pheochromocytoma. The tumor was histologically comprised of small polygonal cells with high cellularity and was immunohistochemically positive for all 3 catecholamine-synthesizing enzymes: tyrosine hydroxylase (very weak), dopamine ß-hydroxylase (heterogeneous), and phenylethanolamine N-methyltransferase (very weak). Electron microscopy revealed very few catecholamine-containing small vesicles with a few organelles, which reflected immature cells. No biochemical or imaging evidence of recurrence or metastasis were evident 1 year after the surgery. We conducted a literature search in the PubMed database. A total of 33 cases were collected. Our case had the second-highest 24-hour urinary dopamine excretion and was the first in which immunostaining for catecholamine synthase and electron microscopy were performed together. Histological findings in our case give a possible hypothesis that the mechanism underlying a dopamine-secreting pheochromocytoma is associated with immature catecholamine vesicles in which dopamine ß-hydroxylase is localized, thus resulting in inhibited conversion from dopamine to norepinephrine. We also discuss the reasons for the lack of catecholamine excess symptoms, whether preoperative management of α-blockade is needed, and the association between the prognosis and genetic mutation, with an extensive literature review.

Improvement of non-alcoholic fatty liver disease after laparoscopic sleeve gastrectomy in Japanese obese patients.

PURPOSE: The purpose of this study was to evaluate changes in non-alcoholic fatty liver disease (NAFLD) after laparoscopic sleeve gastrectomy (LSG) using computed tomography (CT) images. METHODS: We analyzed data from 57 patients who underwent LSG and had CTs performed before and after surgery. The patients included 34 women and 23 men (with an average age of 43 years); their mean preoperative weight and body mass index were 120 kg and 46 kg/m2, respectively. Obesity-related health disorders included type 2 diabetes mellitus (T2DM) in 33 patients, hypertension in 33 and dyslipidemia in 32. We diagnosed NAFLD in cases with liver to spleen ratios (L/S ratio) <0.9 on non-contrast CT images. We evaluated changes in body weights, BMIs, comorbidities, metabolic parameters, L/S ratios, and liver volumes after surgery. RESULTS: The mean interval between CT scans before and after surgery was 26 months. The total weight loss and % excess weight loss were 35 kg and 72%, respectively. The remission rates for T2DM, hypertension, and dyslipidemia were 85%, 76% and 84%, respectively. After LSG, the L/S ratio increased in all the patients, while all except for one had L/S ratio >0.9. We diagnosed 33 out of 57 patients (58%) as having NAFLD before the operation. After the operation, the L/S ratios and liver volumes were not statistically different between the patients with previous NAFLD and those without it. CONCLUSION: Laparoscopic sleeve gastrectomy is an effective treatment for obesity-related health disorders including NAFLD in Japanese obese patients.

Relationships between computed tomography-assessed density, abdominal fat volume, and glucose metabolism after sleeve gastrectomy in Japanese patients with obesity.

In this study, we investigated the relationships between body weight (BW), computed tomography (CT)-assessed abdominal adipose tissue, and the glycemic metabolic profile in obese Japanese patients following laparoscopic sleeve gastrectomy (LSG). This study analyzed adipose tissue compartments using CT methods before and 1 year after LSG. Thirty obese patients were studied, and variables measured included visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), density of VAT (VAT-D), and density of SAT (SAT-D). We also examined the parameters in patients according to whether they had type-2 diabetes (T2DM). LSG induced significant losses in BW, SAT, and VAT after LSG. Additionally, SAT-D and VAT-D both increased and fasting plasma glucose (FPG) and HbA1c, but not C-peptide, decreased after surgery. ΔSAT and ΔVAT were positively related, and ΔSAT-D and ΔVAT-D were negatively related to ΔBW and/or FPG. Furthermore, a multivariate regression model showed that total BW loss (TBWL) was closely related to ΔSAT (ß = 0.84; p < 0.001) and ΔVAT-D (ß = -0.45; p < 0.05) and improvement of FPG was related to ΔVAT (ß = 0.61; p < 0.05) after LSG. Finally, ΔFPG was correlated with ΔVAT in 16 T2DM patients (r = 0.58; p < 0.05) but not in non-T2DM patients. TBWL was related to ΔSAT and ΔVAT-D, and improvement of FPG was related to ΔVAT in obese Japanese patients after LSG.

Effects of Sleeve Gastrectomy on Blood Pressure and the Renal Renin-Angiotensin System in Rats with Diet-Induced Obesity.

OBJECTIVE: Sleeve gastrectomy (SG) has been reported to decrease blood pressure (BP), although the reason has not been revealed. The present study aimed to establish the reason why SG decreases BP. METHODS: Male Sprague-Dawley rats were subjected to surgical (sham operation or SG) and dietary interventions (fed a normal diet or high-fat diet ad libitum or fed by pair-feeding [PF]). Systolic BP (SBP), urinary sodium excretion, and endocrine parameters were examined 4 weeks after surgery. RESULTS: Both SG and PF rats had reduced body weight compared with SO rats fed normal diet or high-fat diet ad libitum. SG rats exhibited a reduction in SBP compared with PF, which was associated with a reduction in renal renin, angiotensin II, and catechol-O-methyltransferase levels (P < 0.01 for each). SG increased plasma cholecystokinin (CCK) levels compared with PF (P < 0.0001 for each), whereas glucagon-like peptide 1 and peptide YY were not changed in fasting. Exogenous administration of CCK reduced renal catechol-O-methyltransferase (P = 0.0233), renin (P < 0.0001), and angiotensin II (P < 0.0001) levels and SBP (P = 0.0053). CONCLUSIONS: SG reduced SBP, at least in part, through suppression of sympathetic nerve action by elevation of CCK, which was followed by suppression of the intrarenal renin-angiotensin system.

Bioelectrical Impedance Analysis Results for Estimating Body Composition Are Associated with Glucose Metabolism Following Laparoscopic Sleeve Gastrectomy in Obese Japanese Patients.

We investigated the association between body composition and changes in glucose metabolism following laparoscopic sleeve gastrectomy (LSG) in obese Japanese patients. Thirty-two Class III obese patients were assessed before LSG and 3, 6, and 12 months postoperatively. Variables including fat mass (FM), % body fat (%FM), total and skeletal muscle mass (MM), the ratio of lower extremity MM to body weight (BW) (L/W), and the ratio of upper extremity MM to BW (U/W) were measured while using bioelectrical impedance analysis (BIA). LSG significantly decreased BW, FM, and %FM in all time periods observed after surgery with concomitant improvements in metabolic markers. MM was decreased at three months but maintained from 3⁻12 months post-surgery. Importantly, %MM, U/W, and the L/W ratio increased after LSG. Furthermore, change in FM was positively correlated with change in BW 12 months after LSG, whereas changes in %MM were negatively correlated with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Finally, multivariable stepwise regression analyses showed that changes in % total MM was an independent determinant of FPG and change in % skeletal MM was a significant independent determinant of HbA1c in Class III obese Japanese patients after LSG.

Fulminant type 1 diabetes mellitus with anti-programmed cell death-1 therapy.

Anti-programmed cell death-1 (PD-1) antibodies are regarded as a risk factor for insulin-dependent diabetes mellitus as a side-effect. While a small number of cases have been reported, evidence remains limited. This is the first report of an Asian patient developing insulin-dependent diabetes during anti-PD-1 therapy. A 55-year-old euglycemic woman receiving nivolumab for malignant melanoma showed abrupt onset of ketonuria, and elevated levels of plasma glucose (580 mg/dL) and hemoglobin A1c (7.0%). Over the next 2 weeks, serum C-peptide levels fell below the limit of detection. Islet autoantibodies were negative, and the patient showed a human leukocyte antigen haplotype associated with type 1 diabetes. Anti-PD-1 therapy can cause rapid onset of insulin-dependent diabetes, possibly because of inappropriate activation of T cells. Human leukocyte antigen haplotypes might be related to the onset of this disease. Physicians should be aware of this serious adverse event and carry out routine blood glucose testing during anti-PD-1 therapy.