The diagnosis of severe growth hormone deficiency in elderly patients with hypothalamic–pituitary disease

Toogood, Andrew; Jones, Jim R.; O’Neill, Paul; Thorner, Michael O.; Shalet, Stephen M

doi:10.1046/j.1365-2265.1998.00440.x

Cited by 67 publications

(35 citation statements)

References 53 publications

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“…There are discrepancies between the studies on the cut-off values of the combined GHRHCarginine test and of the arginine test. In previous studies, age seemed to be of no influence when using these tests (32,33). However, there is a significantly lower peak GH response in elderly compared with younger patients in the GHRHC arginine test (34).…”

Section: Discussionmentioning

confidence: 99%

GH replacement therapy in elderly GH-deficient patients: a systematic review

Kokshoorn

Biermasz

Roelfsema

et al. 2011

European Journal of Endocrinology

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Context: Recombinant human GH (rhGH) is prescribed for the treatment of adults with GH deficiency (GHD). However, conflicting data are available on the efficacy of rhGH treatment in elderly GHD patients. Objective: To assess the efficacy of rhGH treatment in elderly GHD subjects. Methods: We searched the available literature in PubMed, Cochrane Library, Web of Science and EMBASE. Study selection: Studies on GHD patients, aged O60 years, treated with rhGH were eligible for inclusion. Data extraction was performed by two reviewers independently. Results: We found 11 eligible studies with a total of 534 patients. Only two studies had prospective, randomized, placebo-controlled study designs of rhGH treatment with a duration of 6 (nZ15) and 12 months (nZ62), respectively. Treatment with rhGH decreased total and low density lipoprotein (LDL) cholesterol levels by 4-8 and 11-16%, respectively, but did not alter high density lipoprotein or triglyceride levels. RhGH did not affect body mass index, but decreased waist circumference (by w3 cm) and waist/hip ratio. RhGh did not consistently affect blood pressure or bone mineral density. RhGH increased lean body mass by 2-5% and decreased total fat mass by 7-10% in four studies, but did not affect body composition in two other studies. RhGH consistently improved quality of life (QoL) parameters reflected in AGHDA-scores. There were no explicit data on elderly GHD patients aged O80 years. Conclusion: RhGH replacement in elderly subjects with GHD decreases LDL cholesterol levels and improves QoL, but the effects on other parameters are not unequivocal. There were no data on the efficacy and safety of rhGH treatment in octogenarians with GHD.

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Section: Discussionmentioning

confidence: 99%

GH replacement therapy in elderly GH-deficient patients: a systematic review

Kokshoorn

Biermasz

Roelfsema

et al. 2011

European Journal of Endocrinology

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“…It has previously been shown that elderly subjects with organic GH deficiency are characterised by changes in body fat mass, plasma lipids and bone metabolism, and may benefit from GH substitution therapy (10,24). Previously, the arginine stimulation test was shown to be a reliable test for the diagnosis of GH deficiency in elderly subjects (25). From the present and previously published data, we conclude that the GHRH/GHRP-6 test is a useful and validated tool for the diagnosis of GH deficiency in the elderly, as it is not affected by age and can be performed without risk in this patient group.…”

Section: Discussionmentioning

confidence: 99%

The GHRH/GHRP-6 test for the diagnosis of GH deficiency in elderly or severely obese men

Haijma

Dam²,

Vries³

et al. 2005

eur j endocrinol

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Objective and design: Ageing and obesity result in decreased activity of the GH/IGF-I axis and concomitant impaired GH responses to secretory stimuli. We therefore determined the validity of the GH cut-off value of 15.0 mg/l in the GH-releasing hormone (GHRH)/GH releasing peptide-6 (GHRP-6) test for the diagnosis of GH deficiency in elderly or severely obese men. Methods: We performed a combined GHRH/GHRP-6 test in ten elderly men (mean age 74 years; mean body mass index (BMI) 24.6 kg/m 2 ), nine obese men (mean age 47 years; mean BMI 40.6 kg/m 2 ) and seven healthy male controls (mean age 51 years, mean BMI 24.3 kg/m 2 ). After assessment of fasting plasma GH, IGF-I and IGF-binding protein-3 (IGFBP-3), GHRH (100 mg) and GHRP-6 (93 mg) were given intravenously as a bolus injection. Repeated GH measurements were performed for two hours. Results: Both peak GH levels and areas under the curve (AUC) were significantly lower in the obese than in the controls (peak 13.2 vs 53.4 mg/l, P ¼ 0.001; AUC 707 vs 3250 mg/l £ 120 min; P ¼ 0.001). Mean GH response in the elderly was lower than in the controls (peak 35.0 mg/l; AUC 2274 mg/l £ 120 min), but this was not statistically significant. In contrast, GH peak levels in seven obese men remained below the cut-off level of 15.0 mg/l associated with severe GH deficiency. All others had GH peak levels exceeding this threshold. IGFBP-3 levels were significantly lower in the elderly than in the controls (1.35 vs 2.05 mg/l, P ¼ 0.001). Baseline GH or IGF-I did not differ significantly between groups. Conclusions: GH responses following GHRH/GHRP-6 administration were significantly reduced in severely obese men, but were not significantly reduced in elderly men, despite a negative trend. Our data indicate that the cut-off GH level of 15.0 mg/l after GHRH þ GHRP-6 administration for the diagnosis of severe GH deficiency cannot be used in severely obese men.European Journal of Endocrinology 152 575-580

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“…This suggested that the impact of pituitary disease overrode the subtle changes that occur in the regulation of GH secretion with aging and need not be taken into account when diagnosing GHD in this clinical scenario (16,38). On the other hand, in the current study on hypopituitary patients with GHD, older age negatively predicted the response to GH in weight, BMI, waist circumference, and total and LDL-cholesterol, in keeping with a previous description of GH replacement in the elderly (39), while others have identified elderly GHD patients as a GH-sensitive group (40,41).…”

Section: Discussionmentioning

confidence: 99%

Response to GH treatment in adult GH deficiency is predicted by gender, age, and IGF1 SDS but not by stimulated GH-peak

Feldt‐Rasmussen

Brabant

Maiter

et al. 2013

European Journal of Endocrinology

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Objective: We studied whether the severity of GH deficiency (GHD) defined as i) GH-peak on stimulation tests (insulin tolerance test (ITT), arginine, and glucagon), ii) number of additional pituitary deficits, or iii) baseline IGF1 SDS could impact the response to GH treatment. We further explored whether iv) IGF1 SDS after 24 months of GH replacement or v) DIGF1 SDS from baseline to 24 months was related to the phenotypic response to GH treatment. Design, patients, and measurements: The patient cohort (nZ1752; 50% women) was obtained from KIMS (Pfizer International Metabolic Database). The patients were divided into three groups of approximately equal size (tertiles) according to the stimulated GH-peak values and baseline IGF1 SDS and were studied at baseline, 12, and 24 months of GH therapy. Results: Lower baseline IGF1 SDS predicted better response in weight, BMI, total cholesterol, and triglycerides, while IGF1 SDS after 24 months was associated with reduction in waist/hip ratio, total cholesterol, and improved quality of life (QoL). Age-correlated negatively with the response in body weight, BMI, waist, IGF1 SDS, and total and LDL-cholesterol.Response in weight and BMI was greater in men than in women, whereas women showed greater improvement in QoL than men. Patients with more severe GHD as assessed by lower GH-peaks and more pituitary hormone deficiencies had a greater increase in IGF1 SDS. The increase in IGF1 SDS was associated with a reduction in waist/hip ratio and an increase in weight, BMI, and triglycerides. There was no correlation with other lipids, blood pressure, or glucose. Conclusion: Our findings indicate that baseline and 24 months, IGF1 and its degree of increase during GH replacement were more important than stimulated peak GH to predict the phenotypic response.

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The diagnosis of severe growth hormone deficiency in elderly patients with hypothalamic–pituitary disease

Cited by 67 publications

References 53 publications

GH replacement therapy in elderly GH-deficient patients: a systematic review

GH replacement therapy in elderly GH-deficient patients: a systematic review

The GHRH/GHRP-6 test for the diagnosis of GH deficiency in elderly or severely obese men

Response to GH treatment in adult GH deficiency is predicted by gender, age, and IGF1 SDS but not by stimulated GH-peak

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