Table 1.

Characteristics of the Included Studies

Study Identification (Design)	Patients, n	Age, y (Mean)	Male, %	Location/Settings	Intervention, Patients, n	Follow-Up Period, mo	Inclusion Criteria
Karaca et al (12), 2011 (RCT)	22	45	63.5	Outpatient clinic of Endocrinology, at Erciyes University Medical School, Turkey	Oct-LAR	12	1) Newly diagnosed patients with acromegaly.
Medical arm					N1 = 11
Surgical arm					TSS N2 = 11
Colao et al (13), 2009 (RCT)     Medical arm	81	48.2	49	Multicenter study conducted at 46 neuroendocrinology clinics in seven countries (Australia, Belgium, Brazil, France, Germany, Italy, and the United Kingdom)	Oct-LAR	12	1) Patients aged 18–80 y with newly diagnosed or previously untreated acromegaly. 2) Patients were required to have a biochemical diagnosis comprising both a lack of GH suppression to <1 μg/L after a 75-g oral glucose load and serum IGF-1 levels >97th percentile (adjusted for age and gender).
Surgical arm					TSS n = 41
Luque-Ramirez et al (14), 2011 (case series)	74	49	49	Outpatient clinic of multiendocrinology center in Spain	Somatostatin analogs	28	1) The patient was aged 18–80 y with acromegaly.
					Dopamine agonists		2) The patient had recently been diagnosed or had undergone surgery in the previous 6 mo with or without drug treatment any longer than 3 mo prior to surgery.
Medical arm					N1 = 18		3) There was a minimum follow-up of 20 mo.
Surgical arm					TSS		4) Informed consent.
					N2 = 56		5) The patient had not participated in any clinical trial or other studies with drugs.
Abe and Ludecke (15), 1999 (case series)	78	47	42	Hamburg University, Germany	Primary transnasal surgery n = 78	52	1) Consecutive acromegalic patients with intraoperative GH measurement who had not previously undergone surgery.
Gondim et al (16), 2010 (cohort)	67	54	49	Department of neurosurgery of the general hospital in Brazil	Endoscopic TSS n = 67	24	1) Clinical diagnosis compatible with acromegaly (GH > 1 mU/L, IGF-1 level > the normal age and sex adjusted level), presence of GH-secreting pituitary adenoma, tumor determined to be positive for GH marker through histological examination, no previous treatment, surgery performed by the senior author (J.A.G.), and at least 1 y of follow-up.
Salvatori et al (17), 2010 (cohort)	59	53	49	Multicenter study conducted on 13 endocrinology clinics in the United States	Somatostatin analog and dopamine drugs n = 59	6	1) Suitably motivated patients with a clinical diagnosis of acromegaly due to a pituitary tumor and age >18 y. Switch patients also had to have taken a constant dose of Oct-LAR for ≥3 mo, with serum IGF-1 no > 10% > normal. Switch patients had to have their last Oct-LAR injection 28–35 d prior to study enrollment.
Gondim et al (18), 2009 (cohort)	33	44	27	Outpatient clinic of the neuroendocrine department of the General Hospital of Fortaleza, Brazil	TSS n = 33	29	1) Patient with acromegaly (GH >1 μg/L , IGF-1 > normal age and sex matcher), compatible imaging with intrasellar tumor, no cavernous sinus invasion, positive immune reactivity of GH, no previous treatment, surgery at the HGF, and ≥1 y of follow-up.
Lombardi et al (19), 2009 (cohort)	51	50	45	Outpatient clinic in 24 centers in Italy	Somatostatin analogs Lanreotide-autogel 120 mg n = 39	13	1) Patients aged >18 y with active acromegaly (serum GH levels >5 μg/L and/or >1 μg/L after OGTI and abnormal IGF-1 values) who signed the written informed consent form. Patients should not have undergone pituitary surgery <3 mo before selection, somatostatin analogs (except for a presurgical treatment of <3 mo) or radiotherapy.
Kreutzer et al (20), 2001 (cohort)	57	44	35	Outpatient clinics at the neuroendocrine pituitary service at the University of Virginia Health Sciences Center, Charlottesville, Virginia	TSS n = 57	37.7	1) Patients with active acromegaly who received surgical intervention as initial treatment.
Arita et al (21), 2008 (cohort)	9	74	56	Outpatient clinic of Hiroshima and Kagoshima university hospitals	TSS n = 9	66	1) Patients with acromegaly who are >70 y old.
Sheaves (22), 1996 (case series)	101	46	54	Single center, St Bartholomew's Hospital, London, United Kingdom	TSS n = 101	45.6	1) Patients assessed preoperatively in the center according to a consistent protocol.
Colao (23), 2008 (case series)	67	20–81	51	Single center in Naples, Italy	Oct-LAR	12	1) Patients with active acromegaly to somatostatin analogs as first-line therapy in all macroadenomas with extrasellar extension.
					n = 67		2) Patients with proven cardiomyopathy, hypertension, sleep apnea or other respiratory disorders, and/or other systemic complications potentially making anesthesia less safe than in other patients.
							3) Written consent at the time of hospitalization agreeing with diagnostic procedures and treatment strategy.
Erturk et al (24), 2005 (case series)	30	43	NR	Multicenter, Department of Endocrinology Uludag University, School of Medicine, Bursa, Turkey	TSS	42	1) Patients with clinical symptoms.
					n = 30		2) Basal GH levels > 25 μg/L. 3) Patients had MRI showed intrasellar adenomas.
Grottoli et al (25), 2005 (case series)	21	46	62	Departments of Endocrinology of Multicenter (15 centers) in Italy (outpatient clinics)	Oct-LAR n = 21	12	1) Newly diagnosed patients with acromegaly.
Mangupli et al (26), 2003 (cohort)	11	41	55	Outpatient clinic of Caracas University Hospital, Caracas, Venezuela	Oct-LAR n = 11	12	1) Newly diagnosed acromegaly patients.
Lucas et al (27), 2003 (case series)	104	48	40.4	Departments of Endocrinology of Multicenter, Spain	Somatostatin analogs, lanreotide n = 104	6	1) Diagnosis of acromegaly was made using clinical criteria, with high serum GH levels not suppressible < 2 μg/L (4 mU/L) after an oral glucose test (75 g) and serum IGF-1 levels > 450 μg/L.
Beauregard et al (28), 2003 (cohort)	103	42	58	Outpatient clinic of the Norte Dame Hospital, Montréal, Canada	TSS	12–360	1) Patients with acromegaly and received TSS during period of 1970–1999 as primary treatment.
					n = 103		2) Patients with at least 1 y of follow-up.
							3) Operation was done by the same surgeon.
Bevan et al (29), 2002 (case series)	27	53	62.96	Multicenter, nine endocrine centers in the United Kingdom	Oct-LAR	12	1) Patients with newly diagnosed acromegaly with biochemically active disease.
					n = 27		2) Mean serum GH concentration > 5 mU/L (2 μg/L) that failed to suppress < 2 mU/L (0.8 μg/L ) after oral 75-g glucose administration.
							3) Visible adenoma on pituitary imaging.
							4) No patient had received previous surgery, radiotherapy, or medical therapy with somatostatin analogs or dopamine agonists.
Biermasz et al (30), 2000 (cohort)	59	44	58	Outpatient clinic for the Department of Endocrinology and Neurosurgery Leiden University, Leiden, The Netherlands	TSS n = 59	86	1) Acromegalic patients who underwent TSS by the same neurosurgeon during the study period. 2) Patient with no previous treatment.
Albarel et al (31), 2013 (case series)	115	45.5	Reported as ratio of women to men, 1.2/1	Single center in Timone University Hospital, Marseille, France	TSS n = 115	120	1) Patients underwent sublabial or nasal TSS, with the exception of two who were operated on by the transfrontal route.
Giordano et al (32), 2012 (cohort)	231	NR	35	Single center University of Naples, Naples, Italy.	Lanreotide	12	1) Untreated patients with acromegaly.
Medical arm					N1 = 151
Surgical arm					TSS N2 = 80
Ronchi et al (33), 2005 (cohort)	146	57	42	Department of Endocrinology, University of Milan, Milan, Italy	TSS	228	1) Patient with acromegaly who underwent TSS between 1985 and 1996.
					n = 40		2) Patient with record documented imaging studying with their records. 3) All patients who had been considered as in remission.
Bex et al (34), 2007 (case series)	418	NR	51	64 endocrinologists from 37 different hospital settings in Belgium and GD-Luxembourg	Short- and long-acting somatostatin analogs, dopamine drugs, bromocriptine, and/or cabergoline	132	1) Newly diagnosed patients with acromegaly who primarily received medical therapy.
					n = 95
Baldys-Waligorska et al (35), 2011 (cohort)	26	58	15	Department of Endocrinology, Jagiellonian University Hospital, Krakow, Poland	Oct-LAR	12	1) The diagnosis of acromegaly was based on the Cortina criteria: IGF-1 concentration > normal range for age and gender, human GH nadir during OGTT >1.0 μg/L. Pituitary adenoma was verified by MRI.
					N1 = 26		2) Written consent was obtained from each patient.
Colao et al (36), 2009 (cohort)	45	NR	60	Outpatient clinic of the Federico II University of Naples, Naples, Italy	Somatostatin analogs	60	1) Patients with active acromegaly primarily treated with octreotide or lanreotide for 5 y.
					n = 45		2) Written consent.
Gilbert et al (37), 2003 (case series)a	39	NR	NR	Outpatient clinic in London, United Kingdom	Oct-LAR n = 39	6	1) Newly diagnosed patients with acromegaly. 2)
Mercado et al (38), 2007 (cohort)	68	50	41	Outpatient clinic of 31centers in 15 countries	Somatostatin analogs	12	1) Male or female patients aged 18–80 y with previously untreated acromegaly who provided their written informed consent were eligible to participate in the study.
					n = 68		2) Biochemical diagnosis of acromegaly required both a lack of GH suppression to <1 μg/L after a 75-g oral glucose load and an elevated IGF-1 >97th percentile of the normal range adjusted for age and gender.
Cozzi et al (4), 2006 (cohort)	67	55	46	Outpatients clinic of Divisions of Endocrinology Ospedale Niguarda, Milan, Italy, and Division of Endocrinology, Ospedali Riuniti, Bergamo, Italy	Oct-LAR n = 67	48	1) Consecutive patients with active acromegaly, according to clinical picture, elevated GH levels not suppressible <1 μg/L after OGTT, and high age-adjusted IGF-1 levels, macroadenoma or invasive microadenoma at MRI scans, and no previous neurosurgery or radiotherapy.
Colao et al (39), 2006 (cohort)	34	50	59	Outpatient clinic of the Department of Clinical and Molecular Endocrinology and Oncology, University 'Federico II' of Naples, Naples, Italy	Somatostatin analogs n = 34	6	1) Patient's age ≥18 y. 2) Newly diagnosed acromegalic patients or those previously untreated. 3) Presence of a pituitary tumor (microadenoma or macroadenoma) on pituitary MRI within 8 wk before enrollment. 4) Lack of suppression of GH nadir to <1 μg/L after oral administration of 75 g of glucose. 5) IGF-1 levels > upper limits of normal. 6) Tolerance to a test dose of 50 μg sandostatin.
Luque-Ramirez (40), 2010 (cohort)	19	52	45	Outpatient clinic of multiendocrinology center in Spain	Oct-LAR n = 19	12	1) Age >18 y. 2) Newly diagnosed previously untreated acromegalic patients. 3) Presence of a pituitary tumor on pituitary MRI within 12 wk before enrollment. 4) Fail to suppress GH levels <1 μg/L after oral administration of 75 mg of glucose. 5) IGF-1 levels > upper limits of normality (ie, > 95th percentile adjusted for age). 6) Demonstrated tolerance and response to an acute test of Oct-LAR sc 7) Written informed consent of all patients to participate in this study and for the scientific use of their data.
Jenkins et al (41), 2004 (cohort)	6	53	NR	Outpatient clinic of the Department of Endocrinology at St Bartholomew's Hospital, London, United Kingdom	Oct-LAR n = 6	6	1) Patients newly diagnosed with acromegaly. 2) Patient who do not receive any previous treatment.
Newman et al (42), 1998 (NRT)	26	50	38	Outpatient clinic of the 14 participating centers, United States	Oct-LAR	NR	1) Newly diagnosed patients with acromegaly.
Carlsen et al (43), 2011 (cohort)	32	50	66	Acromegalic patients in Norway diagnosed as part of POTA (Preoperative Oct-LAR Treatment of Acromegaly) study	Oct-LAR n = 32	6	1) Newly diagnosed, previously untreated patients with GH nadir >5 μg/L during a standard 75-g, 2-h OGTT. 2) Pituitary adenoma verified by a pituitary MRI scan. 3) Age between 18 and 80 y.
Biermasz et al (44), 2004 (cohort)	164	46	55	Outpatient clinic for the Department of Endocrinology and Neurosurgery, Leiden, The Netherlands	TSS n = 164	NR	1) Patients newly diagnosed with acromegaly. 2) Patient who do not receive any previous treatment.
Ahmed et al (45) 1999 (cohort)	139	45	49	Single center, United Kingdom	TSS n = 139	67	1) Patients who agreed to receiving surgery as the first line of treatment.

Abbreviations: MRI, magnetic resonance imaging; NR, nonrandomized; NRT, nonrandomized trial; Oct-LAR, octreotide long-acting release; RCT, randomized controlled trial; TSS, Transspehnoidal Surgery; GH, growth hormone; IGF-1, Insulin-like growth factor 1; Oct-LAR, Octreotide long-acting repeatable.

^aAbstract only.