The recurrence of prolactinoma after withdrawal of dopamine agonist: a systematic review and meta-analysis

Zou, Yunzhi; Li, Depei; Gu, Jiayu; Chen, Siyu; Wen, Xia; Dong, Jiajun; Jiang, Xiaobing

doi:10.1186/s12902-021-00889-1

BMC Endocrine Disorders

Table 1 The characteristics of included studies

From: The recurrence of prolactinoma after withdrawal of dopamine agonist: a systematic review and meta-analysis

First Author	Year	Region	No. patients	Drug types and dosage	duration (months)	age (yr)	M/F	Pre intervention	Tumor detection	PRL measurement methods	Initial tumor diameter (mm)	Initial PRL concentration (ng/ml)	Regression of tumor	Normalize serum prolactin before withdrawal	Prolactinoma recurrence (n)	Follow-up (months)
Moriondo, P [11]	1985	Italy	6	BRC: 4 was 10 mg/d 2 was 5 mg/d	24	Mean: 35.33 SEM: 5.07	0/6	No	CT	RIA	NA	Mean: 84.5 SEM: 22.7	All	All but one	1	16
Cannavo` S [15]	1999	Italy	9 MAC 18 MIC	“A”	24	Mean ± SD (range) MAC: 28.9 ± 3.2 (18–45) MIC: 29.6 ± 2.0 (18–62)	NA	No	MRI	IA	Mean ± SEM. MAC: 15.64 ± 3.98 MIC: 6.58 ± 1.96	Mean ± SEM MAC: 404.09 ± 281.53 MIC: 192.88 ± 112.35	Mean ± SEM (p value) MAC: 6.9 ± 1.8 mm (p < 0.001) MIC: 3.0 ± 0.5 mm (p < 0.001)	All but three	0	12
Johnston, D G [16]	1984	UK	15	BRC: 7.5-20 mg daily (9 was 20 mg daily)	Mean: 44.4 SEM: 4.68	Mean: 40.87 SEM: 3.29	8/7	2 with surgery before	CT	RIA	NA	Range: 49.1–38,333	All	All but one	1	Mean: 3.14 SEM: 0.66
Wu, Z B [17]	2008	China	14	“B”	NA	Mean: 36 SEM: 12	NA	No	MRI	NA	Mean: 45 Range: 20–97	NA	All	All	0	Mean 18 (at least 3 mo)
Anagnostis, P [18]	2012	Greece	20 MIC 6 MAC	CAB & BRC	NA	Mean ± SEM MIC: 32 ± 1 MAC: 41 ± 3 Total: 35 ± 2	ND	No	NA	ICMA	Mean ± SEM MIC: 7.4 ± 1 MAC: 24.1 ± 0.39 Total: 13.7 ± 2	Mean ± SEM MIC: 112 ± 19 MAC: 263 ± 59 Total: 165 ± 26	Mean ± SEM (mm) MIC: 1.6 ± 0.6 MAC: 6 ± 4.2 Total: 2.6 ± 0.7	Mean: 12.2 SEM: 2.3 Range: 0.5–44.7	2 (1 MIC and 1 MAC)	Mean: 79 SEM: 11 Range: 12–240
V.Q. Passos [19]	2002	Brazil	16 MIC 11 MAC	BRC (mg/week) median: 5 range: 1.25–25	NA	Median 28 Range 15–31 Mean 29.85 SD 8.94	4/23	Yes	CT & MRI	RIA	NA	Median: 257 Range: 36–2000 Mean: 417 SD: 473	NA	All	0	Median 44; Range 3–240.
Watanabe, S [20]	2017	Japan	11	CAB (mg/week) Maximum: 1 (range 0.25–12); Maintenance: 0.5 (range 0.25–3.0).	60	Mena: 36 range: 16–64	ND	No	MRI	IA	Mean: 21 Range: 10–76	Mean: 486.9 Range: 1–23,500	All	Unit: ng/ml Mean: 7.2 Range: 1.0–71.9	0	12
Colao, A [21]	2007	Italy	115 MIC 79 MAC	CAB (mg/week) mean ± SD (median) MIC: 1.2 ± 0.5 (1.0) MAC: 1.2 ± 0.4 (1.0)	mean ± SD (median) MICs: 43 ± 15 (45) MACs: 42 ± 13 (36)	Mean ± SD (median) MIC: 32 ± 11 (29) MAC: 44 ± 15 (46)	MIC: 12/103 MAC: 36/43	NA	MRI	NA	Mean ± SD (range) MIC: 6.8 ± 1.5 (3.3–10) MAC: 17.2 ± 6.2 (10.3–50)	Mean ± SD (range) MIC: 157.2 ± 50 (67–300) MAC: 891.67 ± 1341 (197–9715)	Mean ± SD (range)(mm): MIC: 1.5 ± 2.0 (0–5.6) MAC: 2.4 ± 3.5 (0–9.5)	Mean ± SD (range)(ng/ml) MIC: 24.8 ± 17.93 (3–78) MAC: 31.6 ± 22.3 (10.3–90)	0	Mean ± SD (median) MIC: 47 ± 29 (48) MAC: 44 ± 28 (48)
Kharlip, J [22]	2009	USA	31 MIC 11 MAC	“C”	Median (range) MIC: 43 (23–119) MAC: 56 (26–205)	Median (range) MIC: 44 (18–68) MAC: 54 (36–75)	MIC: 5/26 MAC: 7/4	8 MIC & 4 MAC had BRC before	MRI	NA	Median (range) MIC: 8 (5–10) MAC: 15 (11–29)	Mean (range) MIC: 73 (27.2–182.3) MAC: 310 (103–1122)	Mean (range)(mm) MIC: 3 (0–9) MAC: 0 (0–7)	Median (range)(ng/ml) MIC: 3.6 (0.1–17) MAC: 1.9 (0.1–6.2)	0	3
Sala, E [12]	2016	Italy	32	CAB (mean ± SD) (1) Week dosage (mg): MIC: 0.96 ± 0.41 MAC: 0.97 ± 0.37 (2) Total amount (mg): MIC: 397.4 ± 274.6 MAC: 313 ± 198.6	Mean ± SD: MICs: 66 ± 39.6 MACs: 79.2 ± 30	Mean ± SD MIC: 42.4 ± 9.9 MAC: 70 ± 10.9	NA	Yes	CT & MRI	FIA	NA	Mean ± SD MIC: 113.5 ± 54.12 MAC: 258.9 ± 211.3	76% in MIC; 92% in MAC.	mean ± SD (ng/ml) MIC: 7.3 ± 4.3 MAC: 13.4 ± 14.1	0	12
Muratori, M [13]	1997	Italy	6	“D”	12	Range 25–48	NA	NA	CT	IFMA	NA	Mean ± SEM 89.83 ± 12.76	All	Unit: ng/ml Mean: 9 SEM: 1.81	1	Mean: 52.83 SEM: 4.53
Dogansen, S C [7]	2016	Turkey	36	“E”	Mean ± SD (range) 66.7 ± 30.4 (27–138)	Mean: 32.1 SD: 10.9 Range: 17–66	12/24	No	MRI	IA	Mean: 19.4 SD: 12.4 Range: 6–52	Mean: 2303 SD: 4190 Range: 112–18,500	Disappearance (n, %): 11 (31%) mean ± SD (range) Diameter (mm): 3.3 ± 3.1 (0–10) Percentage of tumor shrinkage (%): 76.5 ± 18.6 (50–100)	mean ± SD (range) PRL level (ng/ml): 8.4 ± 6.7 (0.4–21) Percentage reduction (%): 95.1 ± 5.3 (81–99)	0	Mean: 28.6 Range: 7–26
Colao, A [14]	2003	Italy	105 MIC 70 MAC	CAB (mg/week) Median (range) MIC: 1 (0.5–3.5) MAC: 1 (1–2)	Median (range) MIC: 48 (24–75) MAC: 42 (24–72)	Median (range) MIC: 30 (15–66) MAC: 40 (19–70)	MIC: 11/94 MAC: 33/37	No	MRI	RIA	Mean ± SD. MIC: 6.9 ± 1.6; MAC: 17.1 ± 6.4.	Mean ± SD MIC: 162.2 ± 48.2 MAC: 915.6 ± 1413	Mean ± SD (mm) MIC: 1.2 ± 1.6 MAC: 2.3 ± 3.3	Mean ± SD (ng/ml) MICs: 6.0 ± 5.2 MAC: 5.3 ± 3.0	0	At least 24 months

M/F: Male/Female
SD: standard deviation; SEM: standard error of mean
MIC: microprolactinoma; MAC: macroprolactinoma; PRL: prolactin
BRC: bromocriptine; CAB: cabergoline
IA: Immunoassay; RIA: radioimmunoassay; FIA: fluorimmunoassay; ICMA: Immunochemiluminencent assay; IFMA: Immunofluorimetric assay
“A”: 0.25 mg CAB twice a week for 4 weeks. The dose was increased stepwise in 0.5 mg increments until reaching lowest maximally effective and tolerated dose
“B”: Started with BRC 2.5 mg/d. Increased to 7.5 mg/d within 2 or 3 weeks. Increased to 15 mg/d if serum PRL levels were not controlled. Reduced to no more than 5.0 mg/d once prolactin level was within the normal range for 3 months
“C”: CAB (mg/week). Max dose and number of patients: MIC: 0.25 (3), 0.5 (9), 1.0 (17), 1.5 (2), MAC: 0.25 (0), 0.5 (2), 1.0 (7), 1.5 (2); Dose before stopping treatment and number of patients: MIC: 0.25 (13), 0.5 (7), 1.0 (9), 1.5 (1), missing (1), MAC: 0.25 (4), 0.5 (6), 1.0 (1), 1.5 (0)
“D”: Cabergoline. Started with 0.5 mg/week. Further dose increments by 0.25–0.5 mg. The maximum dose was 3 mg/week
“E”: Mean ± SD (range). Unit: mg/week. For CAB: Max dose: 0.8 ± 0.3 (0.5–1.5), Min dose before withdrawal: 0.3 ± 0.1 (0.25–0.5). For BRC: Max dose: 7.4 ± 4.3 (2.5–20), Min dose before withdrawal: 4.2 ± 2.6 (1.25–7.5)

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