Lavin Chapter 12

134   Section 2 • Hypothalamic-Pituitary Dysfunction

X. FIBROMYALGIA A. Fibromyalgia syndrome is an idiopathic condition in which patients experience intense pain in specific tender points, as well as profound fatigue and sleep disturbances. B. GHD that occurs in a subset of patients with fibromyalgia is of clinical relevance because it is a possibly treatable disorder utilizing GH with demonstrated benefits to patients. Dinser et al. reported that approximately 30% of patients with fibro- myalgia had an abnormally low response to insulin-induced hypoglycemia and arginine-stimulation testing. C. In a study by Cuatrecasas in BMC Musculoskeletal Disorders , GH treatment in fibromyalgia patients with low GH levels reduced the number of tender points within a few months. GH also improved fatigue, pain, and mental health without causing negative reactions. D. The decision to treat patients with fibromyalgia by GH supplementation awaits confirmatory long-term studies of its efficacy and side effects profile. E. One study suggested that low levels of IGF-1 cannot be explained by clinical associations, but suggests that low IGF-1 levels in patients with fibromyalgia are a secondary phenomenon because of hypothalamic–pituitary–GH axis dysfunction. F. At present, there are no definitive conclusions as to the link between hypotha- lamic–pituitary–adrenal axis dysfunction and GHD in fibromyalgia. Nevertheless, the presence of clinically significant GHD in a subpopulation of patients with fibromyalgia seems well established. Understanding its links with chronic stress may provide some insights into mechanisms, whereby environmental stressors and developmental factors interact with inherited susceptibility to modify gene expression and ultimately generate symptoms. XI. CARDIOVASCULAR A. A study from the French Registry of Acute ST-Elevation or Non-ST Elevation Myo Cardial Infarction (FAST-MI) Registry evaluated IGF-1 at hospital admissions for acute myocardial infarction (MI), recurrent MI, and stroke over a 2-year follow-up. They concluded that low IGF-1 scores are associated with an increased risk of all-cause death, recurrent MI, and stroke in MI patients. IGF-1 induces vasodilatation by nitric oxide production, reduces endothelial dysfunction, promotes mRNA expression for specific contractile proteins, improves myocardial contractility, stimulates ischemic preconditioning, and limits ischemia-reperfusion injuries. B. Low serum levels of IGF-1 have been associated with carotid intima-media thick- ness, the presence of congestive heart failure, and angiographically documented coronary disease. Low IGF-1 levels have also been associated with an increased risk of ischemic heart disease. Low IGF-1 concentrations were also associated with higher mortality after acute MI. C. This study is the largest study that reports the relationship between serum levels of age-adjusted IGF-1 and long-term cardiovascular outcomes after an acute MI. The results show that low levels of age-adjusted IGF-1 at time of admission in acute MI patients are associated with an increased 2-year risk of death, recurrent MI, or stroke. Patients with acute MI had reduced serum levels of IGF-1 compared with healthy controls, and among the acute MI patients, those with lower IGF-1 levels hit a higher frequency of 90-day events, such as recurrent ischemia, reinfarction, revascularization, sustained ventricular tachycardia, and, after discharge, even death. These authors’ results are interesting to consider with regard to a potential role for acute administration of IGF-1 at the acute phase of MI. D. General benefits of GH. GH has both direct effects on vascular function and also effects mediated through IGF-1 itself. The cardiovascular risk associated with GHD appears to be related to several factors, including hypertension, inflammation, dyslipidemia, and insulin resistance. After administration of GH, there is an increase in flow-mediated dilatation and reduction of arterial stiffness. There is also a slight decrease in blood pressure. E. Heart and vessel anatomy. Increased intima-media thickness and abnormal arterial wall dynamics have been documented in GHD. GH treatment has reversed these dis- orders. Some studies show reduced left ventricular posterior wall, and interventricular