Table 1.
Literature review of acromegaly recurrence
| Population | Time period and nature of study | Surgical Series | Recurrence Rate (%) | Mean/median follow-up time | Criteria for remission | Time of first evaluation after surgery | Time of recurrence | Risk factors for recurrence | |
|---|---|---|---|---|---|---|---|---|---|
| Nomikos et al. [13] | 668 |
1982–2001 retrospective |
Yes | 0,4 | Mean 126 ± 74 months |
GHr < 2,5 μg/L + GHn < 1 μg/L + IGF1 |
7 days; 3 months | 3 and 6 years | Remission criteria used |
| Freda et al. [14] | 97 |
1996–2020 Prospective |
No | 14 | Mean 9,34 ± 6.4 years |
GHn < 0,4 μg/L + IGF1 |
3 months | Median of 4.5 year (range 2,8–24 year) | Abnormal GH levels at OGTT (GH 0,14–0,4) |
| Cunha et al. [5] | 54 |
2001–2019 retrospective |
Yes |
0 in cured 13 (8,3 BDI; 33,3 in BDII*) discrepancies |
Median of 39 (range 12–126) months |
GHr < 1 μg/L + IGF1 (Discrepancy if only 1 criteria) |
3 months | NA |
IGF1 < 1,25 ULN ° |
| Biermasz et al. [15] | 59 |
1977–1988 retrospective |
Yes | 18,5 | Mean 16 ± 0.8 years |
IGF1 + mean GH day-profile or GHr < 2,5 μg/L + GHn |
7–10 days; 6 months | 6 months – 3 / 4 years – 10 years | Preoperative mean GH concentration |
| Beauregard et al. [16] | 103 |
1970–1999 retrospective |
No | 6,8 | Mean 13,4 (range 10–29) years |
GHr < 2,5 μg/L ± GHn < 1 μg/L ± IGF1 |
NA | Mean of 4 years | – |
| Krieger et al. [17] | 181 |
1973–1990 retrospective |
Yes | 0,8 | Mean 5 years | GHr < 2 μg/L | 1 day | NA | – |
| Ronchi et al. [6] | 40 |
2000–2004 retrospective |
No | 2 | Mean 14,3 ± 4,2 years | IGF1 + GHr < 2,5 ± TRH and GnRH test | Median 3 months (range 3–9 months) | NA | – |
| Banerji et al. [18] | 101 |
1992–2005 prospective |
Yes | 7 | Median 84 (range 3–132) months |
GHr < 2,5 μg/L + GHn < 1 μg/L No IGF1 |
6 weeks | NA | Tumor size |
| Roelfsema et al. [19] | 3548 | Review | Mixed |
4,5 0,007 pts/yrs |
Mean 6,36 ± 0,58 years | Mixed | Mixed | 1–10 years | Postoperative GHr and GHn; Paradoxical GH increase after TRH infusion |
| Liang Lv et al [20] | 94 |
2008–2017 retrospective |
Yes | 10 | Median 35 (range 13–129) months |
GHn < 0,4 μg/L + IGF1 |
3 months | NA | Postoperative GHn levels (1 week after surgery) |
| Shen et al. [21] | 133 |
2013–2014 retrospective |
Yes | 6,5 | Median 48 (range 12–84) months | GHn < 1 μg/L + IGF1 | 3 months | 12, 36 and 54 months |
tumor proliferation (Ki-67); GHn at surgical remission |
| Kristof et al. [22] | 102 | retrospective | Yes | 2,08 | Mean 5,06 years (range 3 months-16.9 years) | GHn < 1 μg/L + IGF1 | 3 months | 4,6 and 4,9 years | – |
| De et al. [23] | 90 |
1980–2001 retrospective |
No | 0 | Mean 10,9 years (range 6 months – 20 years) |
GHr < 2,5 μg/L + GHn < 1 μg/L + IGF1 |
4–6 weeks | – | – |
| Rotermund et al. [24] | 280 |
2008–2015 retrospective |
Yes | 12,2 | Median 29 (range 1–120) months |
IGF1 + GHr < 1 μg/L or GHn < 1 μg/L |
1 and 3 days | NA | – |
| Sun et al. [25] | 86 |
2006–2011 retrospective |
Yes | 25 | Mean 13,4 ± 15,8 months | GHr < 1 μg/L or GHn < 0,4 μg/L | NA | 38 and 22 months | SSTR2A expression |
| Shimon et al. [26] | 98 |
1990–1999 retrospective |
No | 8 | Mean 3,9 ± 2,5 years | GHn < 2 μg/L + IGF1 | NA | 1 year | – |
| Babu et al. [27] | 58 |
2005–2013 retrospective |
Yes | 2,3 | Mean 64 ± 32,2 months | GHn < 1 μg/L + IGF1 | 6–12 weeks | < 12 months | – |
| Fernandez Mateos et al. [28] | 548 |
1975–2015 retrospective |
Yes | 6,5# | Mean 3,3 ± 2,3 years |
GHr < 2 μg/L + GHn < 1 μg/L + IGF1 |
3–6 months | 4, 7, 8 and 12 years | – |
| Diri et al. [29] | 108 | Retrospective | No | 14,9 | Mean 44,8 (range 24–59) months | GHn < 1 μg/L + IGF1 | 3 months | NA | Initial tumor size; compression of optic chiasm; diagnosis IGF1 levels |
| Kreutzer et al. [30] | 57 |
1992–1998 retrospective |
Yes | 2,4 | Mean 37,7 (range 12–88) months |
GHr < 2,5 μg/L + GHn < 1 μg/L + IGF1 |
6 weeks (range 1–12 months) | NA | – |
| Shirvani et al. [31] | 130 |
1992–2010 retrospective |
Yes | 10,8 | Mean 35,9 (range 6–169) months |
GHr < 2,5 μg/L + IGF1 |
1 day | Mean 31,4 (range 10–100) months | – |
IGF1 levels in age- and sex-adjusted normal range, GHr GH random levels, GHn nadir GH levels after OGTT
* BDI: Biochemical discrepancy type I (normal IGF1 levels + random serum GH ≥ 1.0 μg/L); BDII: Biochemical discrepancy type II (high IGF-I + random serum GH < 1.0 μg/L)
° IGF-I levels up to 1,25-fold the ULN determined 3 months after TNS in acromegaly patients was associated with long-term remission, regardless of GH levels, even in patients initially considered as surgical failure. IGF-I ≤ 1,25-fold the ULN had 100% sensitivity and 96% specificity to predict long-term remission
# Recurrence rate was calculated on 61 patients initially in remission with available data 15 years after surgery (4/61)