Signs And Symptoms of Adult Growth Hormone Deficiency
Diagnosis of AGHD
Until several years ago, the growth hormone stimulation test (GHST), which measures the capacity of the pituitary to produce growth, was considered the principal criteria for the diagnosis of AGHD. During the past several years, the accuracy of the GHST to determine whether a person has AGHD has been increasingly questioned because of test variability and and increasing acceptance of IGF-I being of significant diagnostic value in combination with the GHST, the phenotype (physical and mental characteristics, the medical history, as described above; and, increased understanding that, in the absence of a clearly defined organic cause for AGHD, the unique physiology of each person being evaluated, makes the diagnosis of AGHD complex and varied.
Adult growth hormone deficiency (GHD) is a multifactorial disorder in which pituitary dysfunction associated with pituitary adenomas or their treatment plays a major role. The concept of partial GHD, recognized by paediatric endocrinologists for many years, is being now being examined in adults for an association between hypothalamic-pituitary disease and metabolic and anthropometric abnormalities in persons whose GH range from severe GHD to non-GHD levels. Partial GHD, however, becomes more difficult to diagnosis in the presence of obesity, increasing age, and in the absence of additional pituitary hormone deficits.
Adults with GHD can have a variety of signs and symptoms, which include abnormality body composition with increased fat mass (especially central adiposity), decreased lean muscle mass, extracellular fluid volumn, dimished muscle strength, physical energy and stamina, lack of motivation, lethargy, lability (changes in mood), depression, and impairment of congitive functions.
Comprehensive biochemical testing may reveal the following conditions that are also markers for AGHD: lipid imbalance, athersclerosis, obesity, increased LDL cholesterol and reduced insulin sensitivity, and metabolic syndrome. An MRI scan may reveal a structural abnormality or tumor in the brain. A pulmonary function test may reveal dimished lung respiratory muscle capacity. A DEXA dual-energy X-ray absorptiometry) scan may reveal osteoporosis and increased risk of fracture. All those conditions are consistent with AGHD. Hypopituitarism and GHD are associated with an increased mortality.
Comprehensive biochemical testing initally includes, but is not limited to: complete blood count (CBC) with differential platelets, comprehensive metabolic panel, thyroid panel, IGF-I, HbA1c, lutenizing hormone, follicle stimulating horomone, testosterone, estrogen (for women only), DHEAS, androstenedione. Biochemical testing can also reveal deficiences in thyroxin, testosterone, and androgenic steriods (DHEAS and androstenedione), diseases and disorders of metabolism, and genetic defects that can interfere with the secretion, uptake, and utilization of GH and IGF-I.
When the IGF-I is low, further investigation is warranted to determine the cause of the low IGF-I, which can include (1) the testing of IGF-II, and the IGF binding proteins; (2) growth hormone stimulation tests to determine whether the pituitary has the capacity to produce growth hormone; (3) the levels of zinc, magnesium, and selenium, which minerals are necessary for the proper functioning of certain enzymes that are essential for the metabolic processes involved in with IGF-I and its various binding proteins; and, possibly testing for metabolic diseases and disorders.
The diagnosis of AGHD is often challenging because of the absence of growth parameters as diagnostic factors in addition factor, and the effects of other disorders that adults acquire over time. Other markers are therefore needed to identify adults who have GHD and could potentially benefit from GH replacement therapy. Consensus guidelines for the diagnosis and treatment of adult GHD include patients who have evidence of hypothalamic-pituitary disease or disorder, patients with childhood-onset GHD, and patients who have undergone cranial ablation, or have a history of head trauma. Suspicion of GHD is also heightened in the presence of other pituitary hormone deficits. Tests for GHD include measurement of GH upon conducting growth hormone stimulation tests (GHSTs) with provoking agents that have high sensitivity and sensitivity including, but not limited to, the insulin tolerance test (ITT), GHRH plus arginine or GHRH and GHRP-6. The results of several studies have found that non-stimulated serum or urine measurements of GH levels do not reliably predict deficiency in adults. Also, the ITT has some potential risks involved its administration and is of questionable reproducibility, which have prompted the development of the previously mentioned tests. Thus, in cases where ITT is contraindicated or inconclusive, the combination of arginine and GHRH is an effective alternative.
The signs and symptoms of growth hormone deficiency can be masked by testosterone or thyroxin; or caused by deficiencies in those hormones or by other hormone dysfunction or by metabolic disorders. In such cases, rhGH can cause other hormone deficiencies (e.g., cortisol), or in combination with testosterone in males can cause (1) secondary polycythemia via the hormone erythropietin, resulting in serious and even grave conditions (i.e. hemochromotosis, cardiac infarction, stroke and paralysis, liver damage). rhGH can also stimulate coagulation of prothrombin and activated partial thromboplastin time in GHD adults. Excessive GH/rhGH also causes a significant increase in the risk of cancer and the recurrance of cancer, and diabetes mellitus. It is, therefore, important to identify and rule out any such conditions before diagnosing and treating GHD/AGHD. The patient’s medical history, as well as physical examination, biochemical testing and appropriate scans of the brain are critical to the diagnosis and treatment of the patient for AGHD.