A case of acquired deficiency of pituitary GH, PRL and TSH, associated with type 1 diabetes mellitus.

A 75-year-old male showed combined anterior pituitary hormone deficiency (CPHD). Basal and TRH-stimulated PRL levels were undetectable. Basal and GRH-stimulated GH levels were very low, and could barely be measured by means of an ultrasensitive enzyme immunoassay. In addition, basal TSH levels were under the normal limit, and TRH-stimulated TSH secretions were impaired. On the other hand, the secretions of ACTH, LH and FSH remained intact. There was no mutation of Pit-1 gene in this patient, and immunohistochemical studies using human pituitary and the patient's serum showed no positive staining. The HLA types frequently detected in lymphocytic hypophysitis were recognized, supporting the view that the CPHD in this case may be caused by lymphocytic hypophysitis, although magnetic resonance imaging of the pituitary gland showed no specific findings. Interestingly, a high titer of anti-glutamic acid decarboxylase antibody, suggested that the patient suffered from type 1 diabetes mellitus (DM). Five years ago, his thyroid function was normal and the treatment of DM with oral hypoglycemic agent was effective, indicating that the onset of both diseases at least occurred within the last half decade. We report here a rare case of SPIDDM with CPHD which might be caused by lymphocytic hypophysitis.

Cocaine- and amphetamine-regulated transcript peptide in the rat anterior pituitary gland is localized in gonadotrophs and suppresses prolactin secretion.

Cocaine- and amphetamine-regulated transcript (CART) mRNA and CART peptide are abundant in the hypothalamic nuclei that control anterior pituitary function. CART peptide has also been localized in the anterior pituitary gland itself, although its role in pituitary function has not as yet been elucidated. In the present study, we investigated the localization and function of CART peptide in the anterior pituitary gland. Immunohistochemical observations revealed that CART peptide colocalized with FSH and LH in gonadotroph cells but that it was absent from the other hormone-producing cells. Immunoelectronmicroscopy suggested that CART peptide and gonadotropin were colocalized in the same secretory granules. CART peptide suppressed prolactin release from dispersed anterior pituitary cells 15 min after its addition into the media [basal production, 234.9 +/- 14.6 ng/ml vs. CART 55-102 peptide 100 nm, 125.0 +/- 18.2 ng/ml (P < 0.01, n = 5)]. Prolactin release was suppressed by CART in a dose-related manner; on the other hand, CART peptide did not affect the secretion of other anterior pituitary hormones. CART peptide synthesis by these cells was elevated 15 min after the addition of leptin to the media (100 nm), as determined by immunoblotting, but LHRH (10 nm) did not significantly affect CART peptide expression. These findings suggest that CART synthesis in the anterior pituitary may be stimulated by leptin and that CART peptide may play a role in the regulation of anterior pituitary hormone secretion in the rat.

Effects of nateglinide on the elevation of postprandial remnant-like particle triglyceride levels in Japanese patients with type 2 diabetes assessment by meal tolerance test.

To elucidate the role of early insulin response in post-prandial hyperlipidemia, we examined triglyceride (TG) and remnant-like particle triglyceride (RLP-TG) levels, using a meal tolerance test (MTT) with or without the administration of nateglinide (NAT). The MTTs were performed 2 d apart in 36 drug-naive patients with type 2 diabetes who had been hospitalized for glycemic control while receiving diet therapy. Before the second MTT, patients were treated with 90 mg NAT. Treatment with NAT was associated with a significant increase in insulin levels in the treated patients 1 h after the test meal, compared to levels in non-treatment. NAT treatment was also associated with a significant decrease in the level of free fatty acids 1 and 2 h after the meal, and with a significant decrease in plasma glucose levels 1, 2, and 4 h after the meal, compared to those in non-treatment. During the first MTT with NAT non-treatment, 13 patients showed serum TG levels of 200 mg/dL or greater when measured 2 h after the meal. In these 13 patients, NAT administration produced a significant decrease in TG levels 1, 2, and 6 h after the meal, as well as a significant reduction in RLP-TG levels 1 and 2 h after the meal. NAT administration was also associated with significant reductions in area under the curve (DeltaAUC) for TG and RLP-TG. These results suggest that, in a clinical setting, the early insulin response is closely associated with both postprandial glucose and postprandial lipid metabolism in Japanese patients with type 2 diabetes.