Two cases of renal hypouricemia in which dopamine infusion produced a good recovery from exercise-induced acute kidney injury.

We report 2 cases with a good recovery from acute kidney injury (AKI) due to exercise-induced AKI associated with renal hypouricemia. Case 1 involves a 20-yearold man who had a similar episode 1 year earlier. He complained of nausea, vomiting and loin pain after playing football. On admission, his serum creatinine was 3.27 mg/dl and he was treated with intravenous fluid infusion (2 l/d). His renal function deteriorated and creatinine rose to 9.82 mg/dl. A renal hemodynamic evaluation using duplex Doppler ultrasound showed a high arterial resistance index (RI). After we changed his treatment to intravenous continuous infusion of 2 µg/kg/min dopamine, RI decreased sequentially and creatinine decreased without hemodialysis. A renal biopsy performed 7 days after dopamine infusion showed no changes in glomeruli and tubules, suggesting the absence of acute tubular necrosis, and no uric acid crystals or myoglobin casts in tubules. Case 2 involves a 42-year-old man who complained of loin pain after riding a motorcycle. On admission, his creatinine and creatine phosphokinase (CPK) were 3.93 mg/dl and 59 mU/ml, respectively. His RI was also high and he was treated immediately with an intravenous continuous infusion of 2 µg/kg/min dopamine. RI and creatinine decreased sequentially. Both cases suggest the effectiveness of dopamine infusion for AKI due to renal hypouricemia in which the RI of the renal arteries is high.

Primary sclerosing cholangitis associated with increased peripheral eosinophils and serum IgE.

Symptoms of cholestasis, including epigastralgia, fever, and jaundice, with marked increases in peripheral eosinophils and serum IgE in a 20-year-old man are reported here. Endoscopic retrograde cholangio-pancreatography (ERCP) detected constrictions of the bile ducts, compatible with primary sclerosing cholangitis (PSC). The symptoms and blood parameters of liver dysfunction were associated with the degree of eosinophilia and high serum IgE levels. During corticosteroid therapy, all of these parameters improved, and morphologic improvements of the bile ducts were also observed. The pathogenesis of PSC may be explained, in part, by the concept of hypereosinophilic syndrome or allergic reaction.

Synchronous fluctuation of interleukin-6 and platelet count in cyclic thrombocytopenia and thrombocytosis.

We describe a case of cyclic thrombocytopenia and thrombocytosis, whose cytokine levels, granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-6 (IL-6) in plasma, fluctuated in synchrony with platelet count. The levels of the two cytokines correlated significantly with the platelet count for 11 observations over an 8-month period (r = 0.79, p < 0.01 for GM-CSF and r = 0.87, p < 0.001 for IL-6). No inverse relationship between platelet-associated immunoglobulin G (PAIgG) and platelet count was observed (r = 0.39, p > 0.20). These findings suggest that the fluctuation of platelet count in this case may result from an aberration of the cytokine network regulating megakaryopoiesis and platelet formation.

[TSH-secreting fibrous pituitary adenoma showing calcification: a case report].

TSH-secreting pituitary adenoma with calcification and proliferation of the collagen fibers was presented. A 42-year-old man had shown general fatigue and thyroid hypertrophy caused by hyperthyroidism for 3 years. CT and MRI revealed pituitary adenoma with calcification extending into the cavernous sinus and sphenoid sinus. The patient was operated on using the transsphenoidal route twice, but the tumor was not able to be removed totally, partly due to the hardness of the tumor. The tumor in- and around the left cavernous sinus as well as the hardest part of the tumor itself due to the calcification could not be removed. Histopathological examination revealed chromophobe adenoma with proliferation of the collagen fibers. Immunohistological and electronmicroscopic examination demonstrated TSH-secreting adenoma. Postoperatively, thyroid function improved and the patient's symptoms due to hyperthyroidism disappeared.

Endocrine function in a case of beta-adrenergic hyperdynamic circulatory state.

Endocrine functions were investigated in a case of "beta-adrenergic hyperdynamic circulatory state". This state was diagnosed by (1) typical symptoms of cardiac awareness, (2) physical findings (increments of pulse rate and blood pressure by changing positions or walking), (3) increase in cardiac output (5.25 l/min leads to 14.03 l/min) and decrease in circulatory time (10.8 sec leads to 5.5 sec) by isoproterenol infusion (0.02 mug/min/kg body weight), (4) rapid loss of symptoms and above findings by propranolol treatment (30 mg per os daily) and reappearance by discontinuing medication. The mechanism of insulin response to glucose has been a controversy as to whether the secretion is transmitted by beta-receptor or independent glucose receptor. And in this physiologic beta-adrenergic state, it was found that insulin responses in IVGTT and OGTT were within normal limit. When beta-adrenergic condition was corrected by propranolol treatment, insulin responses were shown lowered, though in the normal range. This could be reproduced by discontinuing medication. Insulin, glucagon and growth hormone secretions caused by arginine were also found normal, but during the period the patient was on propranolol therapy, all responses were decreased, within the normal range. These results do not positively support the idea that glucose receptor is linked to beta-receptor. They do not either agree with the contention that secretions of insulin, glucagon and growth hormone induced by arginine are mediated through beta-receptors.

Comparison of the changes in plasma human growth hormone (HGH) and immuno-reactive glucagon (IRG) after intravenous and subcutaneous injection of glucagon.

Ten healthy male volunteers were studied to compare the effectiveness of intravenous and subcutaneous injections of 1 mg of glucagon on HG secretion. Plasma HGH level rose to a peak of 6 ng/ml or greater 120 minutes after the subcutaneous injection of glucagon (sc glucagon) in all subjects, whereas the intravenous injection of glucagon (iv glucagon) caused comparable increments in plasma HGH in only six out of ten subjects. Furthermore, in comparison to those in sc glucagon the periods required to show maximum responses were less consistent in iv glucagon. Plasma IRG levels reached a peak of 102.4+/-22.6 ng/ml at two minutes following iv glucagon, and a peak of 3.33+/-1.08 ng/ml at 15 minutes following sc glucagon. These fell to initial levels at 60 minutes and at 180 minutes, respectively. There was no definite correlation either between the magnitudes of changes in plasma IRG and HGH levels or between the velocities of decrement in blood sugar and HGH responsiveness. Judging from its simplicity and reproducibility it may be concluded that sc glucagon is more suitable for a clinical provocative test of HGH release than is iv glucagon. In regards to the mechanism of glucagon-induced HGH release, neither glucagon per se nor the fall of blood sugar after hyperglycemia was assumed to play any major role. The sustained elevation of plasma IRG for a certain period might be responsible for the glucagon-induced HGH release.

[Studies on the responsiveness of human adrenocortical tumors to ACTH the clinical and experimental observations (author's transl)].

Six cases of Cushing's syndrome with adrenocortical tumors which showed a variety of responsiveness to ACTH were investigated in relation to their clinical pictures and laboratory findings. Abnormal responses to ACTH in tumors was analyzed by in vitro experiments with surgically obtained tumor tissues, and the ACTH responsive mechanism of the tumors was discussed. An 8 hour intravenous ACTH infusion test showed that three of these patients were ACTH responsive, and the other three unresponsive. Histological observation of the tumors revealed that ACTH responsive tumors were adenomas and that ACTH unresponsive tumors were "black adenomas" in two and a carcinoma in one. To investigate possible factors which might account for these differences in ACTH responsiveness, tumor specimens of each one of the responsive and unresponsive adenomas, and a carcinoma were subjected to in vitro studies. When incubated with ACTH or cyclic AMP, tissue sections of a responsive adenoma enhanced cortisol secretion, while that of a black adenoma failed to show any change. Steroidogenesis by carcinoma sections were significantly suppressed in the presence of ACTH or cyclic AMP. Cycloheximide abolished a stimulatory effect of ACTH and cyclic AMP on steroidogenesis in a responsive adenoma without affecting its basal secretion of cortisol. Steroidogenesis by unresponsive tumors (an adenoma and a carcinoma) were decreased by cycloheximide. Since the conversion of cholesterol to pregnenolone, the rate limiting step in steroidogenesis, takes place in adrenal mitochondria, the effect of cyclic AMP on pregnenolone formation from 14C-cholesterol by mitochondrial fractions of these tumors was examined. Cyclic AMP stimulated pregnenolone formation by mitochondrial fraction of an ACTH responsive adenoma, while with that of an unresponsive adenoma pregnenolone formation was not affected. Pregnenolone formation by cancer mitochondria was significantly suppressed by cyclic AMP. These results suggest that the unresponsiveness to ACTH of these tumors might be explained by the ineffectiveness of cyclic AMP to stimulate pregnenolone formation by tumor mitochondria, and that the steroidogenic pathway in unresponsive tumors are in an enhanced state even without cyclic AMP. It should be mentioned that all unresponsive adenomas gave a characteristic appearance of a "black adenoma". Histologically, tumors were composed of compact cells with abundant lipofuscin granules. The possible relationship between the ACTH responsiveness of adrenocortical tumors and some clinical pictures caused by them was also noticed. ACTH unresponsive adenomas resulted in shorter duration, severer conditions of the disease and higher 17-ketosteroid excretion than responsive adenomas. The growth of unresponsive tumors seemed faster than that of responsive ones.

Rapid radioimmunoassay for guanosine 3',5'-cyclic monophosphate using tritiated ligand.

A radioimmunoassay procedure for guanosine 3',5'-cyclic monophosphate (CGMP) is described. The procedure is based on competitive binding between [3H]CGMP and non-radioactive CGMP, with separation of bound and unbound CGMP by Millipore filtration. The binding reaction showed very high specificity to CGMP, had a broad pH optimum, and reached equilibrium within a short time. A simple procedure for the pruification of assay samples using Dowex AG 50W-X2 resin is also described. CGMP contents in urine samples were assayed without purification. Injection of glucagon into healthy human volunteers resulted in a small but significant reduction in urinary CGMP level, whereas CAMP excretion increased dramatically.