GP3-5: Thyroid hormone activation regulates exercise induced growth hormone release

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S38 Posters / Growth Hormone & IGF Research 22S1 (2014) S25–S52 rosiglitazone treatment were similar in patients with and with- out active acromegaly Rosiglitazone treatment did not alter the GH or IGF-1 levels in patients with acromegaly Conclusion: In patients with type 2 DM, rosiglitazone treatment restored the dynamics between IGFBP-1 and insulin during eug- lycemic clamp The effect of rosiglitazone is not influenced by the presence of active acromegaly Rosiglitazone does not alter the GH-IGF1 axis in patients with acromegaly GP3-3 The diagnostic accuracy of pegvisomant-primed glucagon stimulation test (PV-GST) compared to insulin tolerance (ITT) and glucagon stimulation (GST) tests in evaluating adult growth hormone (GH) reserve KCJ Yuen 1 , J Frystyk 2 , SA Rhoads 1 , SE Legg 1 , M Bidlingmaier 3 1 Medicine, Oregon Health & Science University, Portland, United States, 2 Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark, 3 Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany Introduction: The GST has been proposed as the alternative test to the ITT in diagnosing adult GH deficiency, but may not be reliable in patients with underlying glucose intolerance and/or obesity As acute GH blockade with high dose pegvisomant (PV) (1 mg/kg) increases endogenous GH secretion, we hypothesized that PV primed to the GST (PV-GST) will improve the diagnostic accuracy of the GST in assessing adult GH reserve Aims: We assessed the PV-GST on the characteristics of peak GH levels compared to the ITT and GST, the correlation between serum PV and peak GH levels, and the effects of PV on IGF-I levels in adults suspected of GH deficiency Methods: In this proof-of-concept pilot study, 10 adults sus- pected of adult GH deficiency underwent the PV-GST, ITT and GST in random order at least 3 weeks apart For the PV-GST, SC PV (1 mg/kg) was administered 3 days before the GST Results: Following PV administration, IGF-I decreased and GHBP increased compared to pre-PV administration, baseline GST and baseline ITT levels Serum PV levels correlated positively with peak GH, baseline GH, and changes in baseline GH (Dbaseline GH) and peak GH levels (Dpeak GH) Five patients failed (GH-deficient, 50%) and the other 5 patients passed (GH-sufficient, 50%) all 3 tests In the GH-deficient patients, serum PV levels correlated positively with peak GH levels, whereas in the GH-sufficient patients, serum PV levels correlated positively with Dbaseline GH and Dpeak GH Three patients preferred the PV-GST, 4 to the ITT and 3 to the GST Conclusion: High dose weight-based PV priming may be used to improve the diagnostic accuracy of the GST in evaluating for adult GH deficiency, but further larger studies are needed to verify the PV-GST before it can be widely recommended to evaluate adult GH reserve GP3-4 Discordance of post-surgical nadir GH during OGTT and serum IGF-I levels in patients with acromegaly I Fukuda 1 , N Hizuka 1 , T Muraoka 1 , K Amano 2 , T Kawamata 2 , Y Okada 2 , A Ichihara 1 1 Department of Medicine II, Tokyo Women’s Medical University, Tokyo, Japan, 2 Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan Introduction: Since 2010, post-surgical remission criteria of acromegaly is defined as nadir GH levels during 75 g OGTT less than 04 mg/L and normal IGF-I levels It is recommended that serum IGF-I levels are evaluated 3-6 months, when the levels stabilize, after transsphenoidal surgery (TSS) However, it is not unified with respect to timing when post-surgical OGTT should be performed In this study, we investigated post-operative nadir GH levels dur- ing OGTT in patients with acromegaly to clarify a concordance with post-surgical IGF-I levels and nadir GH Patients and methods: Fifty six naïve patients with acromegaly (M/F 21/35, age range: 23~72 years old) whose serum IGF-I normalized by 12 months after TSS were studied Time course of serum IGF-I levels was investigated 1, 3, and 12 months after TSS OGTT was performed within one month after TSS (range: 6~28 days) Results: Serum IGF-I was elevated in 26 and 4 patients at 1 and 3 months but normalized in all patients by 12 months following TSS Post-operative nadir GH during OGTT reached < 04 mg/L in 33 patients (59%) (remission group: group R) Nadir GH ranged from 04 to 137 mg/L in 23 patients (discordant group: group D) There was no significant difference in IGF-I SD at 12 months after TSS between group D and R (033 vs 041, p=068) Retest of OGTT was performed in 15 patients classified into group D within 4 years after TSS Nadir GH became < 04 mg/L in 10 patients, whereas nadir GH ranged from 069 to 142 in 5 patients Conclusions: These data suggested that if one-year post-surgical IGF-I levels normalize without any adjunctive therapy, complete restoration of GH suppression to glucose administration is pre- sumably expected in most patients However, incomplete sup- pression of GH persisted in 33% of the patients (5/15) classified into group D GP3-5 Thyroid hormone activation regulates exercise induced growth hormone release DL Ignacio, DHS Silvestre, JP Cavalcanti-de-Albuquerque, RAL Neto, ACC Ferreira, DP Carvalho, JPS Werneck-de- Castro Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Introduction: Women at the menopause phase are prone to develop obesity, overfeeding and less active This phenotype has been related to decreased thyroid hormones (TH) and estrogen (E2) Together with exercise, TH and E2 regulate growth hormone (GH) release, which is a potent regulator of body metabolism However, the relationship between exercise-induced TH activa- tion by type 1 deiodinase (D1), estrogen deficiency and GH secre- tion was not addressed so far Methods: To answer this question we used female Wistar rats submitted to bilateral ovariectomy (Ovx) and acute aerobic exer- cise session (20 min at 75% of maximal aerobic exercise capacity) Results: Acute exercise induced GH release peaking at 30 min (increased 150%) after exercise and increased D1 activity by 51% right after exercise Ovx blunted both GH and D1 response suggesting that intact gonadal function is vital for exercise modulation of pituitary function Pituitary GH protein content was similar in all groups after exercise Next, we pharmacologi- cally blocked D1 activity by administration of propylthiouracil (2 mg/100 g bw) 4 h and immediately before exercise in intact animals Conclusions: PTU administration decreased exercise-induced GH release mimicking Ovx effects In conclusion, TH activation in pituitary gland by exercise modulates exercise-induced GH secretion as well as estrogen

Transcript of GP3-5: Thyroid hormone activation regulates exercise induced growth hormone release

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S38 Posters / Growth Hormone & IGF Research 22S1 (2014) S25–S52

rosiglitazone treatment were similar in patients with and with-out active acromegaly . Rosiglitazone treatment did not alter the GH or IGF-1 levels in patients with acromegaly .Conclusion: In patients with type 2 DM, rosiglitazone treatment restored the dynamics between IGFBP-1 and insulin during eug-lycemic clamp . The effect of rosiglitazone is not influenced by the presence of active acromegaly . Rosiglitazone does not alter the GH-IGF1 axis in patients with acromegaly .

GP3-3The diagnostic accuracy of pegvisomant-primed glucagon stimulation test (PV-GST) compared to insulin tolerance (ITT) and glucagon stimulation (GST) tests in evaluating adult growth hormone (GH) reserve

K .C .J . Yuen1, J . Frystyk2, S .A . Rhoads1, S .E . Legg1, M . Bidlingmaier3 . 1Medicine, Oregon Health & Science University, Portland, United States, 2Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark, 3Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany

Introduction: The GST has been proposed as the alternative test to the ITT in diagnosing adult GH deficiency, but may not be reliable in patients with underlying glucose intolerance and/or obesity . As acute GH blockade with high dose pegvisomant (PV) (1 mg/kg) increases endogenous GH secretion, we hypothesized that PV primed to the GST (PV-GST) will improve the diagnostic accuracy of the GST in assessing adult GH reserve .Aims: We assessed the PV-GST on the characteristics of peak GH levels compared to the ITT and GST, the correlation between serum PV and peak GH levels, and the effects of PV on IGF-I levels in adults suspected of GH deficiency .Methods: In this proof-of-concept pilot study, 10 adults sus-pected of adult GH deficiency underwent the PV-GST, ITT and GST in random order at least 3 weeks apart . For the PV-GST, SC PV (1 mg/kg) was administered 3 days before the GST .Results: Following PV administration, IGF-I decreased and GHBP increased compared to pre-PV administration, baseline GST and baseline ITT levels . Serum PV levels correlated positively with peak GH, baseline GH, and changes in baseline GH (Dbaseline GH) and peak GH levels (Dpeak GH) . Five patients failed (GH-deficient, 50%) and the other 5 patients passed (GH-sufficient, 50%) all 3 tests . In the GH-deficient patients, serum PV levels correlated positively with peak GH levels, whereas in the GH-sufficient patients, serum PV levels correlated positively with Dbaseline GH and Dpeak GH . Three patients preferred the PV-GST, 4 to the ITT and 3 to the GST .Conclusion: High dose weight-based PV priming may be used to improve the diagnostic accuracy of the GST in evaluating for adult GH deficiency, but further larger studies are needed to verify the PV-GST before it can be widely recommended to evaluate adult GH reserve .

GP3-4Discordance of post-surgical nadir GH during OGTT and serum IGF-I levels in patients with acromegaly

I . Fukuda1, N . Hizuka1, T . Muraoka1, K . Amano2, T . Kawamata2, Y . Okada2, A . Ichihara1 . 1Department of Medicine II, Tokyo Women’s Medical University, Tokyo, Japan, 2Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan

Introduction: Since 2010, post-surgical remission criteria of acromegaly is defined as nadir GH levels during 75 g OGTT less than 0 .4 mg/L and normal IGF-I levels . It is recommended that serum IGF-I levels are evaluated 3-6 months, when the levels stabilize, after transsphenoidal surgery (TSS) . However, it is not unified with respect to timing when post-surgical OGTT should be performed .

In this study, we investigated post-operative nadir GH levels dur-ing OGTT in patients with acromegaly to clarify a concordance with post-surgical IGF-I levels and nadir GH .Patients and methods: Fifty six naïve patients with acromegaly (M/F 21/35, age range: 23~72 years old) whose serum IGF-I normalized by 12 months after TSS were studied . Time course of serum IGF-I levels was investigated 1, 3, and 12 months after TSS . OGTT was performed within one month after TSS (range: 6~28 days) .Results: Serum IGF-I was elevated in 26 and 4 patients at 1 and 3 months but normalized in all patients by 12 months following TSS . Post-operative nadir GH during OGTT reached < 0 .4 mg/L in 33 patients (59%) (remission group: group R) . Nadir GH ranged from 0 .4 to 1 .37 mg/L in 23 patients (discordant group: group D) . There was no significant difference in IGF-I SD at 12 months after TSS between group D and R (0 .33 vs 0 .41, p=0 .68) . Retest of OGTT was performed in 15 patients classified into group D within 4 years after TSS . Nadir GH became < 0 .4 mg/L in 10 patients, whereas nadir GH ranged from 0 .69 to 1 .42 in 5 patients .Conclusions: These data suggested that if one-year post-surgical IGF-I levels normalize without any adjunctive therapy, complete restoration of GH suppression to glucose administration is pre-sumably expected in most patients . However, incomplete sup-pression of GH persisted in 33% of the patients (5/15) classified into group D .

GP3-5Thyroid hormone activation regulates exercise induced growth hormone release

D .L . Ignacio, D .H .S . Silvestre, J .P . Cavalcanti-de-Albuquerque, R .A .L . Neto, A .C .C . Ferreira, D .P . Carvalho, J .P .S . Werneck-de-Castro . Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Introduction: Women at the menopause phase are prone to develop obesity, overfeeding and less active . This phenotype has been related to decreased thyroid hormones (TH) and estrogen (E2) . Together with exercise, TH and E2 regulate growth hormone (GH) release, which is a potent regulator of body metabolism . However, the relationship between exercise-induced TH activa-tion by type 1 deiodinase (D1), estrogen deficiency and GH secre-tion was not addressed so far .Methods: To answer this question we used female Wistar rats submitted to bilateral ovariectomy (Ovx) and acute aerobic exer-cise session (20 min at 75% of maximal aerobic exercise capacity) .Results: Acute exercise induced GH release peaking at 30 min (increased 150%) after exercise and increased D1 activity by 51% right after exercise . Ovx blunted both GH and D1 response suggesting that intact gonadal function is vital for exercise modulation of pituitary function . Pituitary GH protein content was similar in all groups after exercise . Next, we pharmacologi-cally blocked D1 activity by administration of propylthiouracil (2 mg/100 g b .w .) 4 h and immediately before exercise in intact animals .Conclusions: PTU administration decreased exercise-induced GH release mimicking Ovx effects . In conclusion, TH activation in pituitary gland by exercise modulates exercise-induced GH secretion as well as estrogen .