Table 1 Summary of the included studies for systematic review

Ross [19] 1988

5

Random GH<5ng/ml

Biochemical and/or clinical signs of active acromegaly after a period of time with normal GH levels

Surgery

NR

1

Surgery

1

2

Radiotherapy

2

1

Medical

1

1

Expired

Salinger [20] 1992

3

Relief of presenting symptoms and favorable changes in radiologic and serum endocrine studies

Second presentation of symptoms or regrowth of tumor after initial response

Surgery + Radiotherapy

NR

1

Surgery

1

2

Surgery + Radiotherapy

2

Long [21] 1996

1

Random GH<5µg/L and OGTT<2µg/L

NR

Surgery

4.83

1

Surgery

1

Abosch [22] 1998

9

GH<5ng/mL within the first 30 days following surgery

An initial remission followed by a rise in GH levels + recurrent symptoms

Surgery

3.3

3

Radiotherapy

2

2

Medical

2

4

No treatment

Freda [23] 1998

10

A normal IGF-I level or OGTT<2ng/mL

An elevation of IGF-I or OGTT>2ng/ml subsequent to postoperative documentation of normalization

Surgery

NR

10

Surgery

4

Swearingen [24] 1998

5

Random GH<2.5ng/mL, OGTT<2ng/mL, Serum IGF-I normalization

Biochemical recurrence

Surgery

5

3

Surgery

1

1

Medical

1

1

Expired

Biermasz [25] 2000

5

Random GH<2.5ng/mL, OGTT<1ng/mL, Serum IGF-I normalization

Biochemical recurrence

Surgery

6

2

Radiotherapy

2

3

Medical

3

Pollock [26] 2002

1

Random GH<2ng/mL, Serum IGF-I normalization

Abnormal IGF-1 after normalization

Radiotherapy

1

1

Medical

1

Acosta-Gomez [27] 2005

3

Normalization of clinical sings (including basal and dynamic responses of GH) at 1 year after therapy with no evidence of residual tumor on CT or MRI

Clinical, biochemical and/or neuroradiological signs of tumor activity detected after therapy

Surgery

NR

1

Radiotherapy

1

1

Medical

1

1

No treatment

Landolt [28] 2006

1

GH and IGF-I normalization

NR

Surgery + Radiotherapy

20

1

Radiotherapy

1

Petit [29] 2007

1

Serum IGF-I normalization

Abnormal IGF-I after remission

Surgery

12

1

Radiotherapy

0

Jagannathan [30] 2008

3

Serum IGF-I normalization

NR

Radiotherapy

NR

1

Radiotherapy

1

2

Medical

2

Losa [31] 2008

1

Serum IGF-I normalization, Basal GH<2.5µg/L

Basal GH>2.5µg/L, Abnormal IGF-1

Surgery

NR

1

Medical

1

Yamada [32] 2010

2

Basal GH<2.5µg/L, OGTT<1ng/mL, Serum IGF-I normalization

NR

Surgery

NR

2

Medical

2

Albarel [33] 2013

10

Serum IGF-I normalization, OGTT<0.4µg/L 3 months post-surgery

Elevated IGF-1 levels or OGTT>0.4µg/L during follow-up.

Surgery

More than 0.5

2

Radiotherapy

2

5

Medical

5

3

No treatment

1

Van Rompaey [34] 2013

6

Serum IGF-I normalization, OGTT<1 ng/ml

NR

Surgery

NR

1

Surgery

1

1

Radiotherapy

1

4

Medical

4

Sankhla [35] 2013

1

NR

NR

Surgery + Radiotherapy

NR

1

Surgery

1

Shirvani [36] 2014

14

Basal GH<2.5µg/L, Serum IGF-I normalization

NR

Surgery

2.62

6

Surgery

4

5

Radiotherapy

5

3

Medical

3

Sun [37] 2014

4

Random GH<1μg/L, OGTT<0.4μg/L

NR

Surgery

NR

4

Surgery

1

Sinha [38] 2014

2

basal serum Growth Hormone<1 g/L

Hypersecretion after normalization

Surgery + Radiotherapy

NR

2

Surgery

2

Paluzzi [39] 2014

2

Serum IGF-I normalization

NR

Surgery

1.25

2

Surgery

2

Losa [40] 2017

4

NR

NR

Radiotherapy

NR

1

Surgery

1

2

Radiotherapy + Medical

2

1

Medical

1

Ismail [41] 2020

2

Serum hormone level normalization

NR

Surgery

NR

2

Surgery

2