Masako Shimojo

Human ACTH hypersensitivity syndrome associated with abnormalities of the ACTH receptor gene

Activating mutations of the ACTH receptor have not been previously described. We investigated a 69‐year‐old woman with normal blood cortisol but undetectable blood ACTH concentrations. The aim of this study was to evaluate her hypothalamo–pituitary–adrenal axis by measuring circadian variation in blood ACTH and cortisol, and by performing CRH and ACTH stimulation and dexamethasone suppression tests. We also examined biological activity of her circulating blood ACTH using bovine adrenocortical cell suspensions and ACTH receptor gene structure by Northern blotting analysis.

Glutest Neo Super--a new handheld blood glucose meter-corrects for the effects of the hematocrit values in both hematocrit-adjusted samples and samples obtained from anemic patients.

BACKGROUND Handheld blood glucose (BG) meters are convenient tools that are widely used to measure the BG levels. However, the hematocrit (Hct) value has been identified as a confounding factor for accurate BG measurement. Some BG meters are equipped with an Hct-correcting feature, whose effectiveness has been tested previously. Nevertheless, the measurements yielded by many BG meters are confounded by the Hct values. Recently, a new BG meter equipped with an Hct-correcting feature has been developed; however, its effectiveness has not yet been confirmed. STUDY DESIGN Venous blood samples were collected from two healthy volunteers, and the Hct values in the samples were adjusted to approximately 0%, 10%, 20%, 30%, 40%, 50%, and 60%. Further, venous blood samples were collected from 10 anemic patients (Hct <40%). The whole BG (WBG) levels in the samples were measured using two devices-the new BG meter (Glutest Neo Super [Sanwa Kagaku Kenkyusho Co. Ltd., Nagoya, Japan]) and a standard BG meter (OneTouch Ultra [Life Scan Inc., Milpitas, CA]). For reference, plasma glucose (PG) levels were measured using a machine at our hospital laboratory (GA08 [A&T Co., Kanagawa, Japan]). The bias in the measurements was calculated as follows: bias = ([WBG - PG]/PG) x 100. Further, the correlation between the Hct values and the bias was assessed by performing linear regression analysis. RESULTS In both the Hct-adjusted samples and the samples obtained from anemic patients, the WBG levels measured using Glutest Neo Super were minimally affected by the Hct values, while those measured using OneTouch Ultra were affected by the Hct values to a statistically significant extent. CONCLUSIONS The Hct-correcting feature of the new BG meter Glutest Neo Super was effective. The use of this new device for BG measurements may lead to more appropriate treatment selection.

Establishment and characterization of a novel cell line derived from a human small cell lung carcinoma that secretes parathyroid hormone, parathyroid hormone-related protein, and pro-opiomelanocortin.

There are few case reports describing small cell lung carcinoma (SCLC), which secrete parathyroid hormone (PTH)-related protein (PTHrP) and result in hypercalcemia. We have established a novel cell line, derived from a 37-year-old woman with SCLC, which produced PTH, PTH-rP, and a part of proopiomelanocortin (POMC), and led to hypercalcemia. The cell line, named SS-1, was grown as floating cell clusters in DMEM/F12 medium supplemented with 10% fetal bovine serum and had a population doubling time of 72 h. The modal chromosome number was 47 (88%); marker chromosomes were not observed. The SS-1 cell line secreted not only PTHrP but also PTH, and both were decreased by CaCl2 administration. Decreasing the concentration of Ca++ in the growth medium stimulated the secretion of both PTHrP and PTH. The cell line had calcium sensing receptor (Cas-R). Since PTHrP and PTH secretion from the SS-1 cells was related to Ca++ concentration in the growth medium, the cell line might be useful for the study of PTH-rP and PTH regulation as well as for SCLC analysis. In addition, the cells secreted N terminal POMC, the precursor of adrenocorticotropic hormone, in response to stimulation with corticotropin releasing hormone. In summary, we established a novel cell line, SS-1 from SCLC, which produced PTHrP, PTH and N terminal POMC.

18-Hydroxycortisol and 18-oxocortisol in Cushing's syndrome

In patients with primary aldosteronism due to an aldosterone-producing adenoma and glucocorticoid-suppressible aldosteronism, 18-hydroxycortisol and 18-oxocortisol excretions are elevated. Both steroids are synthesized in the transitional zone between the zona glomerulosa and zona fasciculata. There are no reports concerning production of these steroids in Cushings syndrome due to adrenal adenoma or hyperplasia, as far as we know. We determined the urinary excretion and serum concentration of 18-hydroxycortisol and 18-oxocortisol in eight patients with Cushings syndrome (four due to adrenal adenoma, and four due to adrenal hyperplasia). Two of the four patients with adrenal adenoma had high levels of urinary and serum 18-hydroxycortisol and 18-oxocortisol; on the other hand all the patients with adrenal hyperplasia had normal urinary and serum levels of both steroids. Patients with high concentrations of 18-hydroxycortisol and 18-oxocortisol, however, showed no differences in clinical features, routine laboratory findings and hormonal data compared to patients with normal concentrations of 18-hydroxycortisol and 18-oxocortisol. Our data suggest that some adrenal adenomas causing Cushings syndrome originate from transitional cells.