Protracted critical illness is marked by protein wasting resistant to feeding, by accumulation of fat stores, and by suppressed pulsatile release of GH and TSH. We previously showed that the latter can be reactivated by brief infusion of GH-releasing peptide (GHRP-2) and TRH. Here, we studied combined GHRP-2 and TRH infusion for 5 days, which allowed a limited evaluation of the metabolic effectiveness of this novel trophic endocrine strategy. Fourteen patients (mean +/- SD age, 68 +/- 11 yr), critically ill for 40 +/- 28 days, were compared to a matched group of community-living control subjects at baseline and subsequently received 5 days of placebo and 5 days of GHRP-2 plus TRH (1 + 1 microg/kg x h) infusion in random order. At baseline, impaired anabolism, as indicated by biochemical markers (osteocalcin and leptin), was linked to hyposomatotropism [reduced pulsatile GH secretion, as determined by deconvolution analysis, and low GH-dependent insulin-like growth factor and binding protein (IGFBP) levels]. Biochemical markers of accelerated catabolism (increased protein degradation and bone resorption) were related to tertiary hypothyroidism and the serum concentration of IGFBP-1, but not to hyposomatotropism. Metabolic markers were independent of elevated serum cortisol. After 5 days of GHRP-2 plus TRH infusion, osteocalcin concentrations increased 19% vs. -6% with placebo, and leptin had rose 32% vs. -15% with placebo. These anabolic effects were linked to increased IGF-I and GH-dependent IGFBP, which reached near-normal levels from day 2 onward. In addition, protein degradation was reduced, as indicated by a drop in the urea/creatinine ratio, an effect that was related to the correction of tertiary hypothyroidism, with near-normal thyroid hormone levels reached and maintained from day 2 onward. Concomitantly, a spontaneous tendency of IGFBP-1 to rise and of insulin to decrease was reversed. Cortisol concentrations were not detectably altered. In conclusion, 5-day infusion of GHRP-2 plus TRH in protracted critical illness reactivates blunted GH and TSH secretion, with preserved pulsatility, peripheral responsiveness, and feedback inhibition and without affecting serum cortisol, and induces a shift toward anabolic metabolism. This provides the first evidence of the metabolic effectiveness of short term GHRP-2 plus TRH agonism in this particular wasting condition.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1210/jcem.84.4.5636 | DOI Listing |
AACE Clin Case Rep
February 2021
Department of Endocrinology, Hematology and Gerontology, Chiba University Hospital, Chiba, Japan.
Objective: Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive type of B-cell lymphoma with large cells growing within the lumen of blood vessels. Although previous reports revealed highly variable symptoms resulting from small-vessel occlusion by neoplastic cells in a variety of organs, there are few reports of IVLBCL with pituitary involvement.
Method: We present a case of IVLBCL with pituitary infiltration from our institution together with a literature review of similar cases to better understand this rare case of IVLBCL involving the pituitary gland.
Endocr J
October 2018
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan.
Thyrotropin (TSH)-producing adenomas are a rare cause of hyperthyroidism and are a type of functional pituitary adenoma. The diagnosis of TSH-producing adenoma is a challenging problem in clinical endocrinology. Since growth hormone-releasing peptide-2 (GHRP-2) fails to induce TSH secretion in normal subjects, the effect of GHRP-2 on TSH levels was therefore examined in patients with TSH-producing adenomas.
View Article and Find Full Text PDFTokai J Exp Clin Med
September 2017
Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Iseharashi, Kanagawa 259-1193, Japan.
Currently, nivolumab (an anti-programmed cell death-1 receptor monoclonal antibody) is available for many types of advanced cancers in Japan. However, there have been few detailed case reports about endocrine-related adverse events of this therapy. Here, we report a patient with metastatic renal cell carcinoma who presented with secondary adrenal insufficiency following nivolumab therapy.
View Article and Find Full Text PDFEndocr J
April 2011
The Center of Diabetes and Endocrine & Metabolism Disease, Nagaoka Red Cross Hospital, Nagaoka, Japan.
GH secretion is mainly regulated at the hypothalamus by a dual interplay between growth hormone releasing hormone (GHRH) and somatostatin, which are modulated by various factors. We examined the regulatory mechanism of GH secretion in an apparently healthy young man without decreased IGF-1 concentration and nocturnal GH secretion, but who showed low responses to insulin tolerance (ITT) and to GHRP-2 tests. The patient also had no GH response to acute aerobic exercise.
View Article and Find Full Text PDFEndocrinology
December 2005
Department of Intensive Care Medicine, Catholic University of Leuven, Belgium.
Prolonged critical illness is characterized by reduced pulsatile TSH secretion, causing reduced thyroid hormone release and profound changes in thyroid hormone metabolism, resulting in low circulating T(3) and elevated rT(3) levels. To further unravel the underlying mechanisms, we investigated the effects of exogenous TRH and GH-releasing peptide-2 (GHRP-2) in an in vivo model of prolonged critical illness. Burn-injured, parenterally fed rabbits were randomized to receive 4-d treatment with saline, 60 microg/kg.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!