Neurosarcoidosis presenting as hypopituitarism and a cystic pituitary mass.

We report a young woman with clinical hypopituitarism and systemic sarcoidosis involving the lung, gastrointestinal tract, and peripheral lymph nodes. Laboratory evaluation confirmed that cortisol, thyroid indices, insulin-like growth factor 1, follicle-stimulating hormone, luteinizing hormone, and estradiol levels were low, with a normal prolactin. Magnetic resonance imaging revealed a large cystic pituitary lesion compressing the optic chiasm and exhibiting rim but not hypothalamic enhancement. The differential diagnosis included cystic macroadenoma, Rathke's cleft cyst, craniopharyngioma, and simple cyst. A transsphenoidal procedure provided decompression and diagnosis: pathology was consistent with sarcoidosis. Postoperatively, the patient's neurosarcoid disease markedly worsened, requiring hypothalamic irradiation. To our knowledge, this is the first report of intracranial sarcoidosis presenting solely as a cystic pituitary mass. An awareness of this possibility is important to prevent inappropriate neurosurgical intervention and subsequent potential exacerbation of neurosarcoidosis.

Cell surface vitamin D-binding protein (GC-globulin) is acquired from plasma.

Vitamin D-binding protein (DBP) is an abundant plasma protein. The observation of immunodetectable, cell-associated DBP on peripheral blood mononuclear cells and placental cytotrophoblasts had presented the question of the origin, function, and precise subcellular localization of cell-associated DBP. Using anti-human DBP F(ab')2 with fluorescence-activated cytometric analysis and immunogold electron microscopy, we detected DBP on the plasmalemma of U937 cells, a monoblastic, histiocytic cell line grown in media supplemented with fetal calf serum (FCS). DBP was then removed from FCS by actin affinity chromatography followed by anti-DBP immunoaffinity chromatography. U937 cells in this DBP-free medium exhibited nearly identical growth rates to cells grown in medium containing native FCS. However, in contrast to cells grown with native FCS, those grown for seven to eight generations with DBP-free FCS exhibited less cell-surface DBP as quantified by fluorescence-activated cytometric analysis (73% decrease) and immunoelectron microscopy (88% decrease). DBP mRNA could not be detected in U937 cells, placental tissues, freshly prepared resting and stimulated B and T lymphocytes, or lymphocyte-derived cell lines by Northern analysis. In addition, using the sensitive reverse transcriptase/polymerase chain reaction assay no DBP fragments were detectable in U937 cells. We conclude that U937 cell-associated DBP is exogenously derived from plasma and is located on the plasmalemma. Based upon this conclusion, we postulate that specific binding sites for DBP may exist on the plasma membranes of certain cell types.

Angiopathic consequences of saturating the plasma scavenger system for actin.

Two plasma proteins, vitamin D-binding protein (actin monomer sequestrant) and gelsolin (actin polymer severing), have been found in association with actin in plasma from ill humans and during experimental injury. In vitro, these are the only plasma proteins that display a high affinity for actin. We infused increasing amounts of globular actin intravenously to rats to evaluate its disposition in plasma and tissues. Intravascular filament formation, microthrombi, and endothelial injury were observed, especially in the pulmonary circulation. These pathological changes were not observed when the globular actin in the infusate had been preincubated with the vitamin D-binding protein in vitro. Complexes of actin with both proteins were found in the plasma, suggesting a saturable, plasma actin-binding system in vivo. Our findings suggest that in vivo saturation of these proteins' actin-binding capacities may serve as a paradigm for pulmonary vascular disorders seen during widespread tissue trauma and cell lysis.

Evidence for transformation of glucagon-like immunoreactivity of gut into pancreatic glucagon in vivo.

The effect of gut glucagon-like immunoreactivity (GLI) devoid of pancreatic glucagon was studied in piglets. All glucagon-like peptides with an accessible C-terminal were removed from the gut extract by specific antibodies reacting with the C-terminal of the glucagon molecule. Endogenous secretion of pancreatic and gut glucagon was blocked by somatostatin infusion, and then the purified gut glucagon preparation was infused. The latter prevented the hypoglycemia resulting from somatostatin infusion, and increased the glucagon level detectable by C-terminal specific antibodies in the blood of the animals. This rise was significant statistically from the 30th min of GLI administration (26.7 +/- 7.2 pg/ml versus 137.0 +/- 67.0 pg/ml; P less than 0.05) and increased until the end of the infusion (90th min, 218 +/- 60 pg/ml; P less than 0.005). It has been suggested that, owing to the in vivo enzymatic degradation of the infused gut glucagon, biologically active "pancreatic" glucagon fractions are formed extracellularly.