Masanori Murayama

Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects

OBJECTIVE The standard ACTH test in clinical use employs a pharmacological dose of ACTH which assesses the maximum secretory capacity of the adrenal cortex. We have investigated the responses of plasma adrenocortical steroids including cortisol, aldosterone and dehydroepiandrosterone (DHEA) to physiological doses of ACTH (ACTH 1–24, tetracosactide, Cortrosyn) and determined the minimal dose which induces a response equivalent to that induced by a pharmacological dose of ACTH.

Successful Treatment with Cyclosporin A in Tocilizumab-resistant TAFRO Syndrome.

Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is a unique clinicopathologic variant of multicentric Castlemans disease that has recently been identified in Japan. Previous reports have shown that affected patients typically respond to immunosuppressive therapy, such as prednisolone and tocilizumab. However, the optimal treatment for refractory TAFRO syndrome, which can be fatal, remains unclear. We herein report a case of tocilizumab-resistant TAFRO syndrome successfully treated with cyclosporin A, indicating that cyclosporine A may be an alternative therapy for refractory TAFRO syndrome.

Evidence for disulfide bonds in membrane-bound and solubilized opioid receptors

The effects of pretreatment with dithiothreitol (DTT) on opioid binding activities of membrane‐bound and digitonin‐solubilized opioid receptors from bovine adrenal medulla were studied. Pretreatment of membranes with DTT or mercaptoethanol inhibited [3H]diprenorphine binding by reducing the number of binding sites. The inhibitory action of DTT was time and dose dependent. The binding of [3H]D‐Ala2‐D‐Leu5‐enkephalin was also inhibited by DTT pretreatment. Pretreatment of digitonin‐solubilized binding sites with DTT also reduced the number of [3H]diprenorphine binding sites. The action of DTT was diminished by preincubating the DTT solution with H2O2, [3H]Diprenorphine protected the opioid binding sites from the inhibitory action of DTT. The present results provide evidence that disulfide bonds are implicated in opioid binding activity of the opioid receptor system.

Opioid and non-opioid binding of β-endorphin to bovine adrenal medullary membranes

Binding of human beta-endorphin (beta h-EP) to bovine adrenal medullary membranes was characterized using [125I]Tyr27-beta h-EP [( 125I]beta h-EP) as a primary ligand. The specific binding of [125I]beta h-EP was time-dependent, saturable and stereospecific. Analysis of a saturation isotherm revealed two apparent classes of specific binding sites with dissociation constants of 2.4 and 34 nM. The extent of maximum inhibition of specific [125I]beta h-EP binding by either levorphanol, morphine, naloxone, dynorphin A (1-13) or D-Ala2-D-Leu5-enkephalin was similar to each other and remained partial (60-70%). Levorphanol eliminated the high affinity component but showed no effect on the low affinity component of [125I]beta h-EP binding. beta h-EP(1-31) displaced completely the [125I]beta h-EP binding. However, beta h-EP(1-23) only partially (approximately 80%) inhibited the [125I]beta h-EP binding. beta h-EP(6-31) showed inhibitory activity on [125I]beta h-EP binding. These results suggest that [125I]beta h-EP binding to bovine adrenal medullary membranes consists of a high affinity opioid-sensitive component and a low affinity non-opioid component. The non-opioid component of [125I]beta h-EP binding may be related to COOH-terminal of the beta h-EP molecule.

Elevated plasma 19‐hydroxyandrostenedione levels in Cushing's disease: stimulation with ACTH and inhibition with metyrapone

OBJECTIVE The regulation of 19‐hydroxyandrostenedione secretion has been suggested to be under the control of both the ACTH‐adrenal axis and renin‐angiotensin system. We undertook the present study to evaluate the effect of the chronic excess of ACTH, or the short‐term excess of ACTH due to metyrapone, on 19‐hydroxyandrostenedione secretion in patients with Cushings disease

COMPARATIVE ASSESSMENT OF ULTRASONOGRAPHY AND COMPUTED TOMOGRAPHY IN ADRENAL DISORDERS

Comparative diagnostic assessment by ultrasonography (US) and computed tomography (CT) was performed in each of 17 patients with adrenal disorders. US is better than CT for demonstrating the intratumorous characteristics, the relationship between the tumor and the surrounding organs, and the organ from which large tumors arise, such as pheochromocytoma. On the other hand, CT is better able to detect small adrenal tumors in primary aldosteronism, although US with a sector or linear scanner can also detect small tumors in some cases. Adrenal hyperplasia in both Cushings disease and congenital adrenogenital syndrome was more easily demonstrated by CT than by US. Of the two US instruments, a sector scanner was more useful in the delineation of the enlarged right nontumorous adrenal by scanning from the right intercostal region, but both scanners were of no use in the delineation of the enlarged nontumorous left adrenal in patients with obesity.

Acidosis-Induced Hypochloremic Alkalosis in Diabetic Ketoacidosis Confirmed by The Modified Base Excess Method

CONTEXT AND OBJECTIVE Diabetic ketoacidosis (DKA) is associated with a metabolic alkalosis, which is thought to be due to vomiting. However, alkalosis can occur in DKA without vomiting. We retrospectively reviewed the acid-base disturbances in DKA admissions without vomiting. PARTICIPANTS AND METHODS We included admissions of the patients with blood glucose and beta-hydroxybutyrate (βOHB) levels > 250 mg/dL and > 1.0 mmol/L, respectively. Admissions without vomiting were classified into a group with a βOHB > 3.0 mmol/L (DKA group) and a group with βOHB of 1.0-3.0 mmol/L (pre-DKA group). The acid-base status was analyzed by the modified base excess (BE) method. BE effects were calculated by changes in sodium (BE free water, [BEFW]), and chloride (BECl). Positive and negative values for each parameter suggested alkalosis and acidosis, respectively. RESULTS Forty-five included admissions were divided into DKA (n = 34) and pre-DKA (n =11) groups. Sodium-corrected chloride level and the chloride/sodium ratio were significantly lower in the DKA group than in the pre-DKA group. In both groups, BEFW values were modestly negative. The mean BECl values were positive in both groups, but significantly higher in the DKA group. The alkalinizing effects by hypochloremia diminished the base deficit in the DKA group by approximately 25%. The BECl value significantly correlated with serum total ketone levels (r = 0.66; P < .0001). CONCLUSION The modified BE method successfully proved the presence of hypochloremic alkalosis in DKA without vomiting. This suggests the direct participation of serum ketoacids in the pathogenesis of hypochloremic alkalosis.

Cushing's Syndrome Caused by an Ectopic Pituitary Adenoma of the Sphenoid Sinus: Adrenal Crisis After Partial Resections of the Adenoma

A 60-year-old woman with an 8-year history of Cushing’s syndrome was evaluated. Biochemical data were consistent with those of Cushing’s disease. Plasma ACTH levels responded paradoxically to GnRH. MRI demonstrated a large tumor occupying the sphenoid sinus, which was enhanced by gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The pituitary gland was normal in shape and was located in the sella turcica without dislocation. The pituitary gland and the sphenoid tumor could be distinguished by the obvious difference in their MRI intensities. Three consecutive partial resections of the sphenoid tumor were performed, but plasma ACTH and cortisol levels remained high just after the third operation. Histological studies revealed a chromophobe adenoma immunohistochemically positive for ACTH. However, adrenal crisis occurred 3 months after the third operation during reserpine administration ( 1.5 mg/day for approximately 2 mo) for the treatment of Cushing’s syndrome due to the residual tumor in the sphenoid sinus. Subsequent MRI showed no change in the tumor shadow, and the paradoxical response of plasma ACTH levels to GnRH remained unchanged. The fourth operation reconfirmed the existence of the ACTH-producing adenoma in the sphenoid sinus. There was no anatomical interaction between the sphenoid tumor and the pituitary gland, and, histologically, no tumor cells were present in the pituitary gland. These findings suggest that the tumor is an ACTH-producing ectopic pituitary adenoma arising from the sphenoid sinus. The patient has been in remission for 4 years on glucocorticoid replacement therapy. The factors responsible for the adrenal crisis were not well understood, although reserpine administration might have had some role.

Perigraft Abscess Subsequent to Aortoesophageal Fistula

A 79-year-old man with appetite loss and nausea for 1 month was admitted to our hospital. His thoracic aortic aneurysm had gradually increased in size due to perigraft endoleak after the previous aneurysm repair surgery. Although he showed no hematemesis, melena, or a fever, gastrointestinal endoscopy and contrast-enhanced computed tomography (CT) revealed an aortoesophageal fistula (AEF). He developed septic shock due to a perigraft abscess and eventually died, although aortic graft replacement and esophageal transection were performed. Clinical suspicion is the most important factor for obtaining an accurate diagnosis and improving the prognosis in cases of AEF.

Giant cell phlebitis: a potentially lethal clinical entity

An 83-year-old woman presented to us with a 4-week history of general malaise, subjective fever and lower abdominal pain. Despite the intravenous infusion of antibiotics, her blood results and physical condition worsened, resulting in her sudden death. Autopsy study revealed that the medium-sized veins of the mesentery were infiltrated by eosinophil granulocytes, lymphocytes, macrophages and multinucleated giant cells; however, the arteries were not involved. Microscopically, venous giant cell infiltration was observed in the gastrointestinal tract, bladder, retroperitoneal tissues and myocardium. The final diagnosis was giant cell phlebitis, a rare disease of unknown aetiology. This case demonstrates for the first time that giant cell phlebitis involving extra-abdominal organs, including hearts, can cause serious morbidity.