The effect of body mass index on the diagnosis of GH deficiency in patients at risk due to a pituitary insult

ObjectivesDiminished GH response to stimulation has been demonstrated in obesity, leading to erroneous diagnosis of GH deficiency. The aim of this study was to evaluate the influence of body mass index (BMI) on GH responsiveness in patients at risk for pituitary function deficits.MethodsA total of 59 healthy subjects and 75 patients with a pituitary insult underwent insulin tolerance test or pyridostigmine+GHRH test in order to assess GH secretory reserve. Normal subjects and patients were classified as normal weight (BMI <24.9 kg/m2), overweight (BMI 25–29.9 kg/m2), and obese (BMI >30 kg/m2).ResultsAll normal individuals with BMI <24.9 kg/m2 demonstrated adequate GH responses, while three of the 21 overweight (14.3%) and nine of the 28 obese subjects (32.1%) did not respond to GH stimulation. Among patients, four of 14 (28.6%) with BMI <24.9 kg/m2, 18 of 22 (81.8%) who were overweight, and 28 of 39 (71.7%) who were obese did not respond to GH stimulation. Of the 46 nonresponder patients with increased BMI, nine (19.6%) had normal insulin-like growth factor 1 (IGF1) values and no other pituitary hormone deficits, raising questions about the accuracy of somatotroph function assessment, while all nonresponders with BMI <24.9 kg/m2 had low IGF1 values and panhypopituitarism.ConclusionsOur results indicate that BMI >25 kg/m2 has a negative effect on GH response not only in normal healthy subjects but also in patients at risk for pituitary function deficit as well. Parameters such as IGF1 levels and anterior pituitary deficits should be taken into account to accurately assess GH status in these patients.

Hypopituitarism following traumatic brain injury: prevalence is affected by the use of different dynamic tests and different normal values

ObjectiveTraumatic brain injury (TBI) has emerged as an important cause of hypopituitarism. However, considerable variations in the prevalence of hypopituitarism are reported. These can partly be explained by severity of trauma and timing of hormonal evaluation, but may also be dependent on endocrine tests and criteria used for diagnosis of hypopituitarism.MethodsSystematic review of studies reporting prevalence of hypopituitarism in adults ≥1 year after TBI focusing on used (dynamic) tests and biochemical criteria.ResultsWe included data from 14 studies with a total of 931 patients. There was considerable variation in definition of hypopituitarism. Overall, reported prevalences of severe GH deficiency varied between 2 and 39%. Prevalences were 8–20% using the GHRH–arginine test (cutoff <9 μg/l), 11–39% using the glucagon test (cutoff 1–5 μg/l), 2% using the GHRH test (no cutoff), and 15–18% using the insulin tolerance test (ITT; cutoff <3 μg/l).Overall, the reported prevalence of secondary adrenal insufficiency had a broad range from 0 to 60%. This prevalence was 0–60% with basal cortisol (cutoff <220 or <440 nmol/l), 7–19% using the ACTH test, and 5% with the ITT as first test (cutoff <500 or <550 nmol/l). Secondary hypothyroidism was present in 0–19% (free thyroxine) or 5–15% (thyroid-releasing hormone stimulation). Secondary hypogonadism was present in 0–29%.ConclusionThe reported variations in the prevalence rates of hypopituitarism after TBI are in part caused by differences in definitions, endocrine assessments of hypopituitarism, and confounding factors. These methodological issues prohibit simple generalizations of results of original studies on TBI-associated hypopituitarism in the perspective of meta-analyses or reviews.

Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or in combination with GHRH: comparison with the insulin tolerance test

OBJECTIVE: The diagnosis of GH deficiency in adults should be made using provocative testing of GH secretion. The insulin tolerance test (ITT) is recommended as the gold standard investigation. Because of the risk of serious complications, patients with epilepsy or known ischemic heart disease should not undergo this test. GHRP-6 is a synthetic hexapeptide that releases GH by binding to specific hypothalamic and pituitary receptors. We assessed the diagnostic capability of GH stimulation by GHRP-6 alone or in combination with GHRH in comparison to the results of an ITT. DESIGN: Twenty patients underwent an ITT for suspected pituitary or adrenal disease. Either GHRP-6 (1 microg/kg) alone, or GHRP-6 in combination with GHRH (1 microg/kg) were administered on different days. Blood samples were obtained during a subsequent 90-min period for measurement of GH. RESULTS: Ten patients had a GH peak response of less than 3 microg/l during ITT and were considered growth hormone deficient (GHD). The GH mean peak (+/-S.E.M., range) in this group was 0.7 microg/l (+/-0.3, 0.1-2.9) compared with 14.5 microg/l (+/-3.5, 3.8-40.8) in the group of patients with a GH peak response of more than 3 microg/l (growth hormone sufficient (GS)). For the GHRP-6 test, the GH mean peak was 1.3 microg/l (+/-0.6, 0.1-6.7) in the GHD group versus 25.7 microg/l (+/-5.5, 7.7-54.2) in the GS group. After GHRP-6+GHRH, the GH mean peaks were 4.0 microg/l (+/-1.3, 0.2-11.9) versus 54.7 microg/l (+/-11.1, 13.9-136.0) respectively. During administration of GHRP-6, the only side effects observed were flush symptoms. CONCLUSIONS: Peak GH levels below 7 microg/l for the GHRP-6 test and below 13 microg/l for the combined GHRP-6+GHRH test identified all patients with GH deficiency correctly as defined by ITT. The results suggest that testing with GHRP-6 or GHRP-6+GHRH is as sensitive and specific as an ITT for the diagnosis of adult GH deficiency.

Integrity of the Growth Hormone/Insulin-Like Growth Factor System Is Maintained in Patients with Chronic Fatigue Syndrome1

GH deficiency states and chronic fatigue syndrome (CFS) share several characteristics, and preliminary studies have revealed aspects of GH dysfunction in CFS. This study assessed indexes of GH function in 37 medication-free CFS patients without comorbid psychiatric illness and 37 matched healthy controls. We also assessed GH function before and after treatment with low dose hydrocortisone, which has been shown recently to reduce fatigue in CFS. We measured basal levels of serum insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2 and IGFBP-3 together with 24-h urinary GH excretion. We also performed 2 dynamic tests of GH function: a 100-μg GHRH test and an insulin stress test using 0.15 U/kg BW insulin. There were no differences between patients and controls in basal levels of IGF/IGFBP or in urinary GH excretion. GH responses to both the GHRH test and the insulin stress test were no different in patients and controls. CFS patients did have a marginally reduced suppression of IGFBP-1 during the insulin stress test. Hydrocortisone treatment had no significant effect on any of these parameters. There is no evidence of GH deficiency in CFS. At the doses used, hydrocortisone treatment appears to have little impact on GH function.