Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 47-year-old woman was evaluated for congenital dwarfism, primary amenorrhoea due to hypogonadotrophic hypogonadism, severe hyperlipidaemia with pancreatitis, and overt diabetes mellitus associated with severe insulin resistance requiring 2.5-3 units of insulin per kilogram body weight. Chromosomal analysis with trypsin banding was normal and biochemical evaluation revealed low oestrogen levels, inappropriately low gonadotrophins, very low IGF-I concentrations and GH concentrations unresponsive to insulin or L-dopa administration. Prolactin, pituitary-adrenal and pituitary-thyroid axes were normal. Dynamic testing with GnRH and GHRH produced increases in FSH, LH and GH concentrations. A MRI of the brain revealed no discernible hypothalamic abnormalities and a small pituitary. The presence of congenital combined growth hormone and gonadotrophin deficiency on the basis of a suprapituitary defect suggests the existence of common or related pathways regulating GnRH and GHRH synthesis or secretion and may have contributed to the ultimate development of insulin resistance and hyperlipidaemia.
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PMID:Isolated combined growth hormone and gonadotrophin deficiency due to hypothalamic dysfunction, associated with insulin resistance. 755 20

Glucocorticoids, when administered over prolonged periods of time, cause protein wasting, osteoporosis, elevation of total cholesterol, and carbohydrate intolerance. Human GH is a potent anabolic agent known to stimulate protein synthesis and osteoblast activity. Chronic hypercortisolemia is associated with impaired GH secretion. The aim of our study was to evaluate the effects of short term administration of human recombinant GH on bone and fuel metabolism in patients receiving chronic glucocorticoid treatment and with suppressed GHRH-stimulated GH peaks (< 10 micrograms/L). We studied nine nonobese adult patients more than 70 yr of age (seven females and two males; age range, 41-68 yr; body mass index, 26 +/- 1.3 kg/m2) undergoing long term glucocorticoid therapy for nonendocrine diseases. After a 3-day stabilization period in the hospital, several parameters were evaluated in all patients: 1) protein, 2) bone, 3) lipid, 4) carbohydrate metabolism, and 5) immune system function under baseline conditions. At 1800 h on the fifth day of hospitalization, the patients began treatment with a daily sc injection of 0.1 IU/kg (0.037 mg/kg) recombinant human GH (Humatrope, Eli Lilly Co.) for 7 days. GH administration caused a significant increase in nitrogen balance (from -0.12 +/- 0.04 to -0.03 +/- 0.02 g/kg.day; P < 0.05), osteocalcin, carboxy-terminal propeptide of type I procollagen, and carboxy-terminal telopeptide of type I collagen with respect to basal levels. After GH administration, total, high density lipoprotein, and low density lipoprotein cholesterol levels were significantly lowered, and serum triglyceride levels were increased in all patients. Normal blood glucose levels during GH administration were observed in our patients concomitantly with a slight increase in insulin secretion. After GH treatment, the T-helper/T-suppressor cell ratio significantly increased with respect to basal levels (2.5 +/- 0.4 vs. 2.2 +/- 0.3; P < 0.05). Our data suggest that in patients receiving chronic glucocorticoid treatment, GH administration may significantly antagonize several side-effects of long term glucocorticoid administration, such as protein wasting, osteoporosis, and hyperlipidemia.
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PMID:Effects of recombinant human growth hormone (GH) on bone and intermediary metabolism in patients receiving chronic glucocorticoid treatment with suppressed endogenous GH response to GH-releasing hormone. 782

Attenuation of the GH and insulin-like growth factor I (IGF-I) axis in aging may be responsible for changes in body composition and metabolism. This relationship has been confirmed by studies of recombinant human GH replacement in aging men and women, but the adverse effects encountered limit its clinical utility. The use of GHRH or its analogs may be an alternative mode for restoring the GH-IGF-I axis in aging individuals. Here we report the endocrine-metabolic changes in response to a GHRH analog in age-advanced men and women. A single blind, randomized, placebo-controlled trial of 5 months duration was conducted. Ten women and 9 men between the ages of 55-71 yr self-injected placebo (saline) s.c. nightly for 4 weeks followed by 16 weeks of [Nle27]GHRH-(1-29)-NH2 at a dose of 10 microg/kg. Subjects underwent 12-h nocturnal (2000-0800 h) frequent blood sampling (10-min intervals) and 24-h urine collection at baseline, after 4 weeks of placebo injections, and after 16 weeks of GHRH analog administration. GH responses to GHRH analog and spontaneous GH pulsatility were assessed. Subjects were also monitored 2, 4, 8, and 12 weeks after commencement of GHRH analog treatment. Blood pressure, body weight, and fasting insulin and glucose levels were recorded at each visit. Serum concentrations of IGF-I, IGF binding protein-1 (IGFBP-1), IGFBP-3, GH-binding protein (GHBP), lipids, and safety laboratory tests (complete blood count and chemistry profile) were measured in fasting samples (0800-0900 h). Body composition was determined by dual energy x-ray absorptiometry scan, and skin thickness was measured at four sites, including the right and left hand and volar forearm, by Harpenden skin calipers. Insulin sensitivity was assessed by a frequently sampled i.v. glucose tolerance test. Quality of life parameters, including sleep, were evaluated through self-administered questionnaires. Nightly GHRH analog administration at 2100 h induced, within 10 min, an acute release of GH, which lasted for 2 h. The GH-releasing effect of GHRH analog was sustained during the course of the study. Compared with placebo, GHRH analog induced a significant increase in 12-h integrated nocturnal GH levels in women (P < 0.01) and men (P < 0.05). This was accompanied, within 2 weeks, by increased serum levels of IGF-I (P < 0.05) and IGFBP-3 (P < 0.001), but not IGFBP-1, which remained elevated for 12 weeks, returning toward baseline by 16 weeks in both genders. Within 4 weeks, GHBP concentrations were significantly increased (P < 0.01) in women, but not in men. Although blood pressure and body weight were unaffected, GHRH analog treatment resulted in a significant increase in skin thickness (P < 0.05) in both genders and increased lean body mass in men only (P < 0.05), with no other changes in body composition or bone mineral density in either gender. There was a trend for a positive nitrogen balance in both genders, which became significant (P = 0.03) when the data were combined. Fasting insulin and glucose levels were unaltered, but a significant increase in insulin sensitivity occurred in men (P < 0.05), but not in women. Assessment of quality of life parameters revealed a significant improvement in general well-being (P < 0.05) and libido (P < 0.01) in men, but not in women, and sleep quality was unaffected in both genders. The only adverse side-effect was transient hyperlipidemia, which resolved by the end of the study. We conclude that nightly administration of GHRH analog for 4 months in age-advanced men and women activated the somatotropic axis. Although an increase in skin thickness was found in both genders, increases in lean body mass, insulin sensitivity, general well-being, and libido occurred in men but not in women. These observations suggest that GHRH analog administration induced anabolic effects favoring men more than women. Further studies are needed to define the gender differences observed in response to GHRH analog administration.
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PMID:Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. 914 36