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Endocrine Care: Gianluca Aimaretti, Maria Rosaria Ambrosio, Carolina Di Somma, Maurizio Gasperi, Salvatore Cannavò, Carla Scaroni, Alessandra Fusco, Patrizia Del Monte, Ernesto De Menis, Marco Faustini-Fustini, Franco Grimaldi, Francesco Logoluso, Paola Razzore, Silvia Rovere, Salvatore Benvenga, Ettore Ciro degli Uberti, Laura De Marinis, Gaetano Lombardi, Franco Mantero, Enio Martino, Giulio Giordano, and Ezio Ghigo Residual Pituitary Function after Brain Injury-Induced Hypopituitarism: A Prospective 12-Month Study J Clin Endocrinol Metab 2005; 90: 6085-6092 [Abstract] [Full text] [PDF]

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Growth hormone deficiency after brain injury-induced hypopituitarism: how should it be diagnosed?

Ilonka Kreitschmann-Andermahr, Harald J Schneider and Bernhard Saller   (21 December 2005)

Growth hormone deficiency after brain injury-induced hypopituitarism: how should it be diagnosed? 21 December 2005
Ilonka Kreitschmann-Andermahr, Neurologist Department of Neurosurgery, University of Technology Aachen, Pauwelsstrasse 30, 52074 Aachen, Harald J Schneider and Bernhard Saller Send letter to journal: Re: Growth hormone deficiency after brain injury-induced hypopituitarism: how should it be diagnosed? ikreitschmann-andermahr{at}ukaachen.de Ilonka Kreitschmann-Andermahr, et al.	In their article “Residual Pituitary Function after Brain Injury-Induced Hypopituitarism: A Prospective 12-Month Study”, Aimaretti et al. (1) report severe growth hormone deficiency (GHD) as the most common deficit in 20% of traumatic brain injury (TBI) and 22% of subarachnoid hemorrhage (SAH) patients, as diagnosed with the growth hormone releasing hormone (GHRH) + arginine (ARG) test. The authors state that the insulin tolerance test (ITT) is contraindicated after brain injuries. In view of some recently published data and our experiences, we would like to invite discussion on this matter. In TBI/SAH patients, isolated or dual pituitary hormone deficits outweigh multiple hormone deficits by far. Neuropathological studies have shown a high degree of hypothalamic damage in TBI/SAH casualties. The ITT, which assesses hypothalamic function with respect to both the GH- and corticotroph axes, has been used in several studies for diagnosis of hypopituitarism after TBI/SAH without adverse events. Moreover, to our knowledge, no case of seizures connected to ITT is documented in the literature. For the GHRH+ARG test, the high false-negative diagnostic rate has been demonstrated for severe GHD in children in the early years after cranial irradiation (2) in whom the cause of GHD is predominantly hypothalamic. Moreover, the ITT is less susceptible to body mass index (BMI)-dependent alterations of GH levels (3). Recently, Corneli et al. (4) proposed BMI-adjusted reference ranges for the GHRH+ARG-test; for an overweight population (BMI 25-30 kg/m2) a GH cut-off of 8 µg/l for severe GHD had a sensitivity of 97% and a specificity of 76%. Taking this cut-off and assuming a prevalence of 15% isolated GHD in the TBI/SAH population, the GHRH+ARG- test would have a high negative predictive value of 99%, but a low positive predictive value of only 41%. This means that almost 60% of overweight TBI/SAH patients with a GH-peak below the cut-off would not have GHD. In a prospective study on hypopituitarism after TBI, we saw significant negative correlations of GH response to GHRH+ARG stimulation with both BMI and age in patients and controls, even though obese subjects were excluded (5). Furthermore, in clinical practice, we have observed discordant results in 6/11 TBI patients tested with both the ITT and GHRH+ARG test. Five patients had no adequate GH response to GHRH+ARG, but a normal response to the ITT (mean BMI 36.0, range 29-40); and one patient with total hypopituitarism (BMI 17) had a normal GH response to GHRH+ARG, but no response to the ITT, probably indicating hypothalamic damage. For these reasons, we conclude that for the purpose of clinical decision making, diagnosis of GHD after TBI/SAH with the GHRH+ARG test alone may be inadequate, even if BMI-adjusted reference ranges are used. Before excluding the ITT for use in brain trauma patients, we believe it is necessary to gather more comparative data on the safety and efficacy of the different stimulation tests for GH secretory status in this patient population. References 1. Aimaretti G, Ambrosio MR, Di Somma C, Gasperi M, Cannavo S, Scaroni C, Fusco A, Del Monte P, De Menis E, Faustini-Fustini M, Grimaldi F, Logoluso F, Razzore P, Rovere S, Benvenga S, Ciro degli Uberti E, De Marinis L, Lombardi G, Mantero F, Martino E, Giordano G, Ghigo E. 2005 Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J Clin Endocrinol Metab 90:6085-6092 2. Darzy KH, Aimaretti G, Wieringa G, Gattamaneni HR, Ghigo E, Shalet SM. 2003 The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post-irradiation time interval. J Clin Endocrinol Metab 88:95-102. 3. Biller BMK, Samuels MH, Zagar A, Cook DM, Arafah BM, Bonert V, Stavrou S, Kleinberg DL, Chipman JJ, Hartman, ML. 2002 Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 87:2067-2079. 4. Corneli G, Di Somma C, Baldelli R, Rovere S, Gasco V, Croce CG, Grottoli S, Maccario M, Colao A, Lombardi G, Ghigo E, Camanni F, Aimaretti G. 2005 The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. Eur J Endocrinol 153:257-264. 5. Schneider HJ, Schneider M, Saller B, et al. Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury. Eur J Endocrinol. In press.