- Email: [email protected]
insulin-like growth factor-I (IGF-I) axis: A clinical and utrasonographic study in patients with acromegaly and hypopituitarism
350
GRS'98 Abstracts
P-S0 EFFECTS OF 1 Y E A R TREATMENT W I T H GH I N A N OLD PATIENT W I T H CHRONIC CONGESTIVE HEART FAILURE A N D G H D
GP Ceda:, B Calbim:i2, V Fontana% M Maggio:, L Lena:, N Benedetti :, S Perelli-Ercolini% S Caporotundo% G Ugolotti2, G ValentiL :Chair of Geriatrics, Univ. of Parma; 2Nuclear Medicine Service, Parma Hosp. Parma, Italy. GH deficiency is characterized by an impaired cardiac performance susceptible of marked improvement with GH therapy. Since GH has also been shown to increase myocardial contractility and to induce a decrease of peripheral vascular resistance, we studied the effects of GH treatment on the cardiac function of an old patient with chronic heart failure (CHF) and GHD. A male patient (81 years) with adult-onset GHD, CHF and atrial fibrillation was treated with rhGH (12IU/week) for 1 year together with conventional HRT. The following parameters were evaluated: body composition analysis (by BIA and abdominal CT scan), glycolipid metabolism values, biochemical parameters (IGF-I, thyroid horm., Te, PSA) and cardiac evaluation with ECG, Eco B-mode and 99Tc scyntigraphy every 3 months. Soon after therapy, a marked improvement of exertional dyspnea and sense of well being was recorded. IGF-I levels increased from 18 to 150 ng/ml. FM was reduced, FFM increased and body weight decreased after treatment, without major modifications of glycolipid metabolism values. Cardiac performance evaluation showed no modification of systolic function, but consistent improvement of diastolic funtion parameters and disappearance at the radionuclide ventriculography of a paradoxical movement of distal anteroseptal wall with improvement of PFR and TPFR values. It remains to be established if these beneficial effects of GH are seen also in CHF of aging, a condition of relative GH deficiency. P - S 1 HEMOSTATIC VARIABLES IN PATIENTS W I T H GH EXCESS OR DEFICIENCY
A Sartorio% M Arosio 2, B Bottasso 3, P BucciarellP, M .Cattaneo 3, G Faglia2, S Ferrero:, PM Mannucci 3, S Porretti 2. ~Italian Institute for Auxology, Milan; 2Institute of Endocrine Sciences, 3Hemophilia & Thrombosis Ctr, Institute of Internal Medicine, Maggiore Hosp, Univ. of Milan, Italy. Both GH excess (acromegaly, A) and GH deficiency (GHD) are reported to be associated with increased morbidity and mortality.for cardiovascular diseases. Mthough several factors may contribute to raise the cardiovascular risk, recent studies have shown an impairment of coagulation and fibrinolytic system in both diseases. In order to assess the importance of GH in modulating hemostatic variables, we measured tissue-type plasminogen activator antigen (t-PA), its endothelial inhibitor (PAI-I), prothrombin activation peptide (F1 + 2) and fibrinogen in 10 non-diabetic acromegalic patients (age _+SD: 39 + 13 years, GH: 18.4 _+23.0 gg/1, IGF-I: 109.0 _+3Z0 nmol/1), 24 adults with GHD (8 childhood- and 16 adult-onset, age: 41 + 13 years, IGFI: 6.7 + 4.1 nmol/1) and 64 sex- and age-matched normal controls (C). GHD patients had higher PAI-I compared with C (12.7 _+ 16.7 vs 4.8 +_5.3 U/ml, P < 0.001), while t-PA antigen was not different from C. On the contrary, patients with A had lower t-PA antigen than C (3.6 + 2.0 vs 6.3 _+2.5 ng/ml, P < 0.01), while PAII did not differ from C (4.0 _+ 5.0 U/ml). A negative correlation between t-PA and both GH and IGF-I was found. No significant differences in F1 + 2 among the three groups were observed. Fibrinogen was higher in GHD and A in respect to C (A: 398 _+ 11t mg/dl; GHD: 363 _+ 105 mg/dl; C: 291 _+ 71 mg/dl A vs C: P < 0.001; GHD vs C: P < 0.01; A vs GHD: NS). In conclusion, GHD is associated with hyperfibrinogenemia and increased PM-I, while only hyperfibrinogenemia was found in A. The finding of low t-PA antigen in A confirms the GH-inhibitory effects on this parameter, previously observed during rec-GH therapy.
P - 8 2 T H Y R O I D A N D G R O W T H H O R M O N E (GH)/INSULINLIKE G R O W T H FACTOR-I (IGF-I) AXIS: A CLINICAL A N D U T R A S O N O G R A P H I C STUDY IN PATIENTS W I T H ACROMEGALY A N D H Y P O P I T U I T A R I S M
A Colao% D Ferone:, N Panza 2, G Esposito 2, P Marzullol, R Pivonello:, G Cerbone:, G Lombardil. :Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples; 2Division of Oncology, "Cardarelli" Hospital, Naples, Italy. We studied thyroid size and function, and tumor prevalence in 90 acromegalics and compared the results with those obtained in 120 patients with hypopituitarism and in 200 healthy subjects, sex, age and body mass index matched, coming from the same geographic area. Thyroid size was evaluated on palpation and ultrasonography. Circulating TSH and f-T4 levels were assayed in all 410 subjects. Goiter was found on palpation and ultrasonography in 75.6 and 95.5% of acromegalics, 13.3 and 32.5% of hypopituitaric patients, 19.5 and 33.5% of controls, respectively. Average thyroid volume was significantly greater in acromegalics (36.9 + 1.6 ml) than in hypopituitaric patients or controls (15.3 +_ 0.7 and 1Z1 + 0.5 ml, P < 0.05). Hyperthyroid goiter was found in 11 acromegalics, three hypopituitaric patients and five controls. Serum TSH levels were similar in acromegalic and hypopituitaric patients, but they were significantly reduced as compared to controls (0.9 _+0.1 vs 1.0 + 0.3 vs 1.7 + 0.2 mIU/l; P < 0.05). The prevalence of benign and malignant tumors was not significantly different in the three groups. In conclusion, a high prevalence of goiter but not of thyroid malignancies was found in acromegaly, despite the evidence of significantly reduced TSH levels. This finding confirms that thyroid enlargement in acromegaly seems to occur independently of TSH. P - S 3 EVALUATION OF THE OUTCOME OF NEUROSURGICAL TREATMENT OF ACROMEGALY: RELATIONSHIP BETWEEN IGF-I A N D G R O W T H HORMONE AT BASELINE A N D AFTER ORAL GLUCOSE TOLERANCE TEST (OGTT) LEVELS
M Doga, C Mascadri, A Bollati, G Milani, B Bfignoli, G Francia:, A Velardo2, L De Marinis3, E De Menis4, E Degli Uberti 5, A Giustina. Endocrinology and Neurosurge W University of Brescia, Endocrinology4 University of Ferrara, 3Rome and 2Modena, Internal Medicine :University of Verona and 4Treviso, Italy. The aim of our study was to investigate in 85 acromegalic patients (44 M, 41 F, mean age 48 +_ 1.8; BMI 2Z9 _+ 0.8 kg/m 2) the biochemical pattern of active disease, comparing GH and IGF-I at baseline with GH levels after OGTT after neurosurgical treatment. IGF-I and GH levels were determined respectively by IRMA (Nichols, USA). Quantitative correlations: there was a significant correlation between post-neurosurgical basal levels and GH nadir value during OGTT (P< 0.001, r = 0.980); a significant correlation between post-neurosurgical IGF-I and GH nadir during OGTT (P = 0.032, r = 0.273) and between post-neurosurgical IGF-I and basal GH levels (P = 0.033, r = 0.270) was found. Qualitative correlations: considering as cure criteria basal GH levels and GH nadir after OGTT respectively <1 ng/ml and of IGF-I _<300 ng/ml, only 65.1% of acromegalic patients had basal GH and IGF-I levels both in the normal range (9.5% were considered cured, 55.6% were not considered cured); conversely 34.9% of patients had GH and IGF-I basal levels, respectively, _>1 ng/ml and <300 ng/ml. Moreover, in the 76.5% of patients GH nadir after OGTT and IGF-1 gave the same informations (11.8% were considered cured, 64.7% were considered not cured); 18.8% of remaining patients had GH nadir and IGF-I, respectively, > 1 ng/ml and <300ng/ml, although 4.7% of patients had GH nadir and IGF-I levels after OGTT, respectively, _<1 ng/ml and _<300ng/ml. Our data suggest that baseline random GH levels have a very good degree of correlation with GH post-OGTT and therefore may be very useful in first-step evaluation of outcome of neurosurgery in acromegaly.
GRS'98 Abstracts
P-S0 EFFECTS OF 1 Y E A R TREATMENT W I T H GH I N A N OLD PATIENT W I T H CHRONIC CONGESTIVE HEART FAILURE A N D G H D
GP Ceda:, B Calbim:i2, V Fontana% M Maggio:, L Lena:, N Benedetti :, S Perelli-Ercolini% S Caporotundo% G Ugolotti2, G ValentiL :Chair of Geriatrics, Univ. of Parma; 2Nuclear Medicine Service, Parma Hosp. Parma, Italy. GH deficiency is characterized by an impaired cardiac performance susceptible of marked improvement with GH therapy. Since GH has also been shown to increase myocardial contractility and to induce a decrease of peripheral vascular resistance, we studied the effects of GH treatment on the cardiac function of an old patient with chronic heart failure (CHF) and GHD. A male patient (81 years) with adult-onset GHD, CHF and atrial fibrillation was treated with rhGH (12IU/week) for 1 year together with conventional HRT. The following parameters were evaluated: body composition analysis (by BIA and abdominal CT scan), glycolipid metabolism values, biochemical parameters (IGF-I, thyroid horm., Te, PSA) and cardiac evaluation with ECG, Eco B-mode and 99Tc scyntigraphy every 3 months. Soon after therapy, a marked improvement of exertional dyspnea and sense of well being was recorded. IGF-I levels increased from 18 to 150 ng/ml. FM was reduced, FFM increased and body weight decreased after treatment, without major modifications of glycolipid metabolism values. Cardiac performance evaluation showed no modification of systolic function, but consistent improvement of diastolic funtion parameters and disappearance at the radionuclide ventriculography of a paradoxical movement of distal anteroseptal wall with improvement of PFR and TPFR values. It remains to be established if these beneficial effects of GH are seen also in CHF of aging, a condition of relative GH deficiency. P - S 1 HEMOSTATIC VARIABLES IN PATIENTS W I T H GH EXCESS OR DEFICIENCY
A Sartorio% M Arosio 2, B Bottasso 3, P BucciarellP, M .Cattaneo 3, G Faglia2, S Ferrero:, PM Mannucci 3, S Porretti 2. ~Italian Institute for Auxology, Milan; 2Institute of Endocrine Sciences, 3Hemophilia & Thrombosis Ctr, Institute of Internal Medicine, Maggiore Hosp, Univ. of Milan, Italy. Both GH excess (acromegaly, A) and GH deficiency (GHD) are reported to be associated with increased morbidity and mortality.for cardiovascular diseases. Mthough several factors may contribute to raise the cardiovascular risk, recent studies have shown an impairment of coagulation and fibrinolytic system in both diseases. In order to assess the importance of GH in modulating hemostatic variables, we measured tissue-type plasminogen activator antigen (t-PA), its endothelial inhibitor (PAI-I), prothrombin activation peptide (F1 + 2) and fibrinogen in 10 non-diabetic acromegalic patients (age _+SD: 39 + 13 years, GH: 18.4 _+23.0 gg/1, IGF-I: 109.0 _+3Z0 nmol/1), 24 adults with GHD (8 childhood- and 16 adult-onset, age: 41 + 13 years, IGFI: 6.7 + 4.1 nmol/1) and 64 sex- and age-matched normal controls (C). GHD patients had higher PAI-I compared with C (12.7 _+ 16.7 vs 4.8 +_5.3 U/ml, P < 0.001), while t-PA antigen was not different from C. On the contrary, patients with A had lower t-PA antigen than C (3.6 + 2.0 vs 6.3 _+2.5 ng/ml, P < 0.01), while PAII did not differ from C (4.0 _+ 5.0 U/ml). A negative correlation between t-PA and both GH and IGF-I was found. No significant differences in F1 + 2 among the three groups were observed. Fibrinogen was higher in GHD and A in respect to C (A: 398 _+ 11t mg/dl; GHD: 363 _+ 105 mg/dl; C: 291 _+ 71 mg/dl A vs C: P < 0.001; GHD vs C: P < 0.01; A vs GHD: NS). In conclusion, GHD is associated with hyperfibrinogenemia and increased PM-I, while only hyperfibrinogenemia was found in A. The finding of low t-PA antigen in A confirms the GH-inhibitory effects on this parameter, previously observed during rec-GH therapy.
P - 8 2 T H Y R O I D A N D G R O W T H H O R M O N E (GH)/INSULINLIKE G R O W T H FACTOR-I (IGF-I) AXIS: A CLINICAL A N D U T R A S O N O G R A P H I C STUDY IN PATIENTS W I T H ACROMEGALY A N D H Y P O P I T U I T A R I S M
A Colao% D Ferone:, N Panza 2, G Esposito 2, P Marzullol, R Pivonello:, G Cerbone:, G Lombardil. :Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples; 2Division of Oncology, "Cardarelli" Hospital, Naples, Italy. We studied thyroid size and function, and tumor prevalence in 90 acromegalics and compared the results with those obtained in 120 patients with hypopituitarism and in 200 healthy subjects, sex, age and body mass index matched, coming from the same geographic area. Thyroid size was evaluated on palpation and ultrasonography. Circulating TSH and f-T4 levels were assayed in all 410 subjects. Goiter was found on palpation and ultrasonography in 75.6 and 95.5% of acromegalics, 13.3 and 32.5% of hypopituitaric patients, 19.5 and 33.5% of controls, respectively. Average thyroid volume was significantly greater in acromegalics (36.9 + 1.6 ml) than in hypopituitaric patients or controls (15.3 +_ 0.7 and 1Z1 + 0.5 ml, P < 0.05). Hyperthyroid goiter was found in 11 acromegalics, three hypopituitaric patients and five controls. Serum TSH levels were similar in acromegalic and hypopituitaric patients, but they were significantly reduced as compared to controls (0.9 _+0.1 vs 1.0 + 0.3 vs 1.7 + 0.2 mIU/l; P < 0.05). The prevalence of benign and malignant tumors was not significantly different in the three groups. In conclusion, a high prevalence of goiter but not of thyroid malignancies was found in acromegaly, despite the evidence of significantly reduced TSH levels. This finding confirms that thyroid enlargement in acromegaly seems to occur independently of TSH. P - S 3 EVALUATION OF THE OUTCOME OF NEUROSURGICAL TREATMENT OF ACROMEGALY: RELATIONSHIP BETWEEN IGF-I A N D G R O W T H HORMONE AT BASELINE A N D AFTER ORAL GLUCOSE TOLERANCE TEST (OGTT) LEVELS
M Doga, C Mascadri, A Bollati, G Milani, B Bfignoli, G Francia:, A Velardo2, L De Marinis3, E De Menis4, E Degli Uberti 5, A Giustina. Endocrinology and Neurosurge W University of Brescia, Endocrinology4 University of Ferrara, 3Rome and 2Modena, Internal Medicine :University of Verona and 4Treviso, Italy. The aim of our study was to investigate in 85 acromegalic patients (44 M, 41 F, mean age 48 +_ 1.8; BMI 2Z9 _+ 0.8 kg/m 2) the biochemical pattern of active disease, comparing GH and IGF-I at baseline with GH levels after OGTT after neurosurgical treatment. IGF-I and GH levels were determined respectively by IRMA (Nichols, USA). Quantitative correlations: there was a significant correlation between post-neurosurgical basal levels and GH nadir value during OGTT (P< 0.001, r = 0.980); a significant correlation between post-neurosurgical IGF-I and GH nadir during OGTT (P = 0.032, r = 0.273) and between post-neurosurgical IGF-I and basal GH levels (P = 0.033, r = 0.270) was found. Qualitative correlations: considering as cure criteria basal GH levels and GH nadir after OGTT respectively <1 ng/ml and of IGF-I _<300 ng/ml, only 65.1% of acromegalic patients had basal GH and IGF-I levels both in the normal range (9.5% were considered cured, 55.6% were not considered cured); conversely 34.9% of patients had GH and IGF-I basal levels, respectively, _>1 ng/ml and <300 ng/ml. Moreover, in the 76.5% of patients GH nadir after OGTT and IGF-1 gave the same informations (11.8% were considered cured, 64.7% were considered not cured); 18.8% of remaining patients had GH nadir and IGF-I, respectively, > 1 ng/ml and <300ng/ml, although 4.7% of patients had GH nadir and IGF-I levels after OGTT, respectively, _<1 ng/ml and _<300ng/ml. Our data suggest that baseline random GH levels have a very good degree of correlation with GH post-OGTT and therefore may be very useful in first-step evaluation of outcome of neurosurgery in acromegaly.