Primary hepatic carcinoid tumor presenting as Cushing's syndrome.

Hepatic carcinoid tumors are very uncommon; most are clinically non-functional and very few present with the symptoms of carcinoid syndrome. ACTH-producing carcinoid tumors most commonly originate in the lung or thymus and present insidiously with bronchospasm and/or chest mass. Occasionally, ectopic ACTH syndromes have been reported in association with pancreatic islet cell tumors, medullary thyroid cancer, pheochromocytoma, small-cell lung carcinoma, and rarely, ovarian and prostate tumors. We report here a patient with an ectopic ACTH-secreting primary hepatic carcinoid tumor who presented with cushingoid appearance, profound proximal muscle weakness, severe lower extremity edema, and markedly elevated urinary free cortisol. ACTH levels were in the low normal range. A solitary vascular hepatic lesion was found on magnetic resonance imaging, which was isodense with the surrounding liver on octreotide scan and photopenic on an 18-fluorodeoxyglucose (18FDG)-positron emission tomography (PET) scan. Following surgical resection of the hepatic tumor, histopathology confirmed an ACTH-secreting neuroendocrine tumor (NET), the patient had complete resolution of hypercortisolemic symptoms and remains in remission, now 4 yr after hepatic tumor resection. This case reports the first ACTH-secreting primary hepatic NET presenting as ectopic Cushing's syndrome. Interesting aspects of this case include the presence of a pituitary incidentaloma, the low normal ACTH, and photopenia on 18FDG-PET imaging.

Aortic root infection in a prosthetic valve demonstrated by gallium-67 citrate SPECT.

A 70-year-old man presented with 6 weeks of worsening low back pain, fever, sweating, and weight loss with known severe lumbosacral osteoarthritis. His history included CABG in 1992, porcine aortic valve replacement, and permanent pacemaker implantation in 2002. CT of the chest, abdomen, and pelvis did not demonstrate a cause for the symptoms. Blood cultures grew penicillin-sensitive enterococcus and he was referred for evaluation of possible osteodiskitis or epidural abscess. Gallium planar imaging demonstrated increased activity in the lumbar spine, suspicious for the presence of infection, and activity was noted in the mid mediastinum as well. SPECT clearly showed increased Ga-67 activity in the region of the aortic root, suspicious for infection. A perivalvular aortic root abscess was subsequently demonstrated by transesophageal echo. This case illustrates the value of Ga-67 chest SPECT in patients with prosthetic valves for detection of endocarditis.

Effects of ischemia on sarcoplasmic reticulum and contractile myofilament activity in human myocardium.

The effects of global ischemia on the contractile system and on sarcoplasmic reticulum (SR) function were studied by measuring the isometric tension and the SR Ca2+ release activity of chemically skinned cardiac fiber preparations from seven patients undergoing open-heart surgery. Ten minutes of ischemia caused 1) a decrease in the myofilament sensitivity to Ca2+ (expected Ca2+ concentration giving half-maximal tension; from 0.69 +/- 0.04 to 1.38 +/- 0.06 microM, n = 7) and in the cooperativity index (Hill coefficient; from 2.61 +/- 0.45 to 0.92 +/- 0.15, n = 7), 2) a decrease in myosin light chain phosphorylation, and 3) a 300% increase in the threshold caffeine concentration for SR Ca2+ efflux channel activation, with a 30% reduction in the rate of Ca2+ release by caffeine at threshold concentrations and a 23% reduction in the rate of release by 20 mM caffeine. After preincubation with 5 microM trifluoperazine, a calmodulin antagonist, the caffeine threshold of ischemic and control cardiac muscle became comparable. Most changes were reversed by reperfusion, while the caffeine threshold was still two times greater than control. These results indicate that ischemia caused alterations of the cardiac muscle contractile apparatus and the SR that were reversed only after reperfusion.

Contractile properties and Ca2+ release activity of the sarcoplasmic reticulum in dilated cardiomyopathy.

BACKGROUND: We performed a comparative study on Ca2+ release activity of the sarcoplasmic reticulum and calcium sensitivity of contractile apparatus of chemically skinned myocardial fibers obtained from four nonfailing human hearts and 13 excised hearts from patients with idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Ca2+ sensitivity of contractile apparatus was studied by following the isometric tension developed by chemically skinned myocardial fibers challenged with solutions of decreasing pCa. Ca2+ release from sarcoplasmic reticulum was monitored indirectly by measurement of the isometric tension developed by skinned fibers challenged with caffeine. We observed no significant difference of Ca2+ sensitivity and cooperativity between normal myocardium (pCa50 = 6.00 +/- 0.05; Hill coefficient, nHill = 2.07 +/- 0.10) and dilated cardiomyopathy (pCa50 = 6.03 +/- 0.07; nHill = 2.72 +/- 0.30) when the fibers were stretched to 130% of the resting length. We also found that both in normal myocardium and dilated cardiomyopathy, stretching to 150% of the resting length increased the Ca2+ sensitivity of the contractile system; pCa50 = 6.21 +/- 0.01 and 6.13 +/- 0.04 in normal and dilated cardiomyopathy, respectively, whereas in dilated cardiomyopathy there was a decrease of Hill coefficient with stretching that was not observed in the control group. The caffeine threshold in idiopathic dilated cardiomyopathy was markedly increased compared with the control group, 1.94 +/- 0.27 mmol/l and 0.29 +/- 0.04 mmol/l caffeine, respectively, whereas there were no significant differences in the extent and rate of caffeine-induced Ca2+ release. CONCLUSIONS: These results indicate that in idiopathic dilated cardiomyopathy there is no alteration of contractile and regulatory proteins; on the contrary, the gating mechanism of the Ca2+ release channel of sarcoplasmic reticulum is abnormal, suggesting a possible involvement of the excitation-contraction coupling in the pathogenesis of this disease. It should also be taken into account, however, that the increased caffeine threshold in dilated cardiomyopathy would be a result of the enhanced resistance to the skinning procedure secondary to the modification of lipid species and/or content in sarcoplasmic reticulum membrane.