GH deficiency (GHD) in adults has to be shown by a single provocative test, provided that it is validated. Insulin tolerance test (ITT) has been indicated as the test of choice; now also glucagon test is validated and represents an alternative. The GHRH plus arginine (ARG) test and testing with GHRH plus a GH secretagogue are equally reliable diagnostic tools, and are now considered as ‘golden’ standards as ITT. Childhood-onset (CO) GHD needs retesting in late adolescence or young adulthood; this is a major clinical challenge and raises questions about the most appropriate method and cut-off value. Appropriate re-evaluation of GH status is represented by simple measurement of IGF1 concentration off rhGH treatment. Clearly, low IGF1 levels are evidence of persistent severe GHD in subjects with genetic GHD or panhypopituitarism. However, normal IGF1 levels never rule out severe GHD and CO-GHD with normal IGF1 levels must undergo a provocative test. The appropriate GH cut-off limit is specific for each provocative test. As shown by the ROC curve analysis, in late adolescents and young adults, the lowest normal GH peak response to ITT is 6.1 μg/l while that to GHRH+ARG test is 19.0 μg/l. These cut-off limits, however, are just indicative as being variable as a function of the assay used. No other test is validated for retesting. As GHRH+ARG test mostly explores the GH-releasable pool, normal GH response would be verified by a second ITT in order to rule out subtle hypothalamic defect.
V Gasco, G Corneli, G Beccuti, F Prodam, S Rovere, J Bellone, S Grottoli, G Aimaretti and E Ghigo
H J Schneider, S Rovere, G Corneli, C G Croce, V Gasco, R Rudà, S Grottoli, G K Stalla, R Soffietti, E Ghigo and G Aimaretti
Objective: Hypopituitarism frequently follows pituitary neurosurgery (NS) and/or irradiation. However, the frequency of hypothalamic–pituitary dysfunction after NS of non-pituitary intracranial tumors is unclear. The aim of this study was to assess the presence of endocrine alterations in patients operated on for intracranial tumors.
Design: This is a retrospective study.
Methods: We studied 68 consecutive adult patients (28 female, 40 male, age 45.0 ± 1.8 years; body mass index (BMI): 26.5 ± 0.6) with intracranial tumors who underwent NS only (n = 17) or in combination with radiotherapy (RT) and/or chemotherapy (CT) (n = 51). In all subjects, basal endocrine parameters and the GH response to GHRH + arginine test (using BMI-dependent cut offs) were evaluated.
Results: In 20.6% of the patients, peripheral endocrinopathy related to CT and/or RT was present. Hypopituitarism was found in 38.2% of the patients. Total pituitary hormone, multiple pituitary hormone, and isolated pituitary hormone deficits were present in 16.2, 5.8, and 16.2% respectively. The most common pituitary deficits were, in decreasing order: LH/FSH 29.4%, GH 27.9%, ACTH 19.1%, TSH 17.7%, and diabetes insipidus 4.4%. Hyperprolactinemia was present in 13.2%. The prevalence of hypopituitarism was higher in patients who underwent NS only and with tumors located closely to the sella turcica, but a substantial proportion of patients with tumors not directly neighboring the sella also showed hypopituitarism.
Conclusions: Hypopituitarism frequently occurs after NS for intracranial tumors. Also, exposure of these patients to CT and/or RT is frequently associated with peripheral endocrinopathies. Thus, endocrine evaluation and follow-up of patients treated for intracranial tumors should be performed on a regular basis.
M Filopanti, A M Barbieri, G Mantovani, S Corbetta, V Gasco, M Ragonese, C Martini, F Bogazzi, A Colao, D Ferone, A Peri, F Pigliaru, G Angeletti, M Arosio, P Beck-Peccoz, A G Lania and A Spada
Hepatotoxicity is one of the most serious adverse effects in acromegalic patients treated with pegvisomant (PEG-V). Recent studies have found an association between this adverse event and the UGT1A1 allele 28 polymorphism associated with Gilbert's syndrome.
To determine whether UGT1A1*28 and alcohol dehydrogenase (ADH) polymorphisms influence liver toxicity during PEG-V treatment.
Design and setting
Multicenter observational retrospective study conducted in 13 tertiary care endocrinology units in Italy.
A total of 112 patients with active disease resistant to somatostatin analogs (SSTa) and 108 controls were enrolled.
Clinical and biochemical data were recorded by electronic clinical reporting forms. Blood or DNA samples were sent to the coordinating center for genotyping.
No differences in genotypes between patients and controls were found. During PEG-V therapy liver function tests (LFT), abnormalities and overt hepatotoxicity developed in 17 and 4.5% of patients respectively. Logistic and linear regression analyses showed an association between LFT abnormalities during the follow-up visit and prior events of LFT abnormalities in medical history (odds ratio=1.25; P=0.04) and the number of concomitant medications, other than SSTa (B=3.9; P=0.03). No correlation between LFT alterations and UGT1A1 allele 28 as well as ADH1C and B polymorphisms was found.
UGT1A1 allele 28 and ADH1C and B polymorphisms do not predict increased risk of hepatotoxicity during PEG-V therapy. Conversely, patients with multi-therapies and with previous episodes of liver disease should be carefully managed, due to the observed association between these conditions and LFT abnormalities during PEG-V therapy.