Table 2 Reported cases of prolactinomas with secondary DA resistance

1 [20]

40, F

Symptoms: galactorrhea, secondary amenorrhea

Pituitary deficiency: gonadal

PRL: 171 ug/L (RI: 6–29.9)

Imaging: microadenoma

Treatment: CAB 0.75 mg/week

PRL: normalized

Imaging: NA

Onset: 3.5 years

PRL: 128 ug/L

Imaging: macroadenoma

Treatment: CAB 3 mg/week, S

PRL: slightly above ULN

Imaging: no residual tumor

PRLoma

Ki-67: < 5%

p53: negative

2 [11]

63, M

Symptoms: impotence

Pituitary deficiency: gonadal, thyroid, adrenal

PRL: 4531 ug/L (RI: NA)

Imaging: macroadenoma

Treatment: S, DXT, BRC 7.5 mg/d

PRL: normalized

Imaging: NA

Onset: 7 years

PRL: 1758 ug/L

Imaging: slight growth + right frontal metastasis

Treatment: BRC 15 mg/d, Q 600 ug/d, tamoxifen 20 mg/d, S, DXT

PRL: 4531 ug/L

Imaging: frontal residual metastasis + cyst

Malignant PRLoma

3 [21]

57, F

Symptoms: headache, blurred vision, secondary amenorrhea

Pituitary deficiency: gonadal, GHD

PRL: 6580 ug/L (RI: 3.3–26.6)

Imaging: macroadenoma

Treatment: BRC 40 mg/d, CAB 1 mg/week

PRL: 59 ug/L (99% reduction)

Imaging: NA

Onset: 8 years

PRL: 1692 ug/L

Imaging: macroadenoma

Treatment: CAB 6 mg/week, S, DXT, CAB 2 mg/week

PRL: 118 ug/L (93% reduction)

Imaging: stable remnant

PRLoma, no mitosis or cellular atypia

Ki-67: < 3%

p53: negative

4 [26]

47, M

Symptoms: headache, blurred vision, impotence

Pituitary deficiency: panhypopituitarism

PRL: 6345 ug/L (RI: < 23.5)

Imaging: macroadenoma

Treatment: BRC 15 mg/d

PRL: 236 ug/L (96% reduction)

Imaging: size reduction

Onset: 10 months

PRL: 1974 ug/L

Imaging: tumor growth

Treatment: BRC 40 mg/d, S, BRC 20 mg/d

PRL: 564 ug/L (71% reduction)

Imaging: NA

PRLoma

5 [7]

53, M

Symptoms: headache, impotence

Pituitary deficiency: panhypopituitarism

PRL: 1477 ug/L (RI: NA)

Imaging: macroadenoma

Treatment: BRC 10 mg/d

PRL: normalized

Imaging: remnant in left cavernous sinus

Onset: 7 years

PRL: NA

Imaging: stable remnant

Treatment: BRC 25 mg/d, Q 600 ug/d, CAB 4.5 mg/week

PRL: normalized

Imaging: stable remnant

PRLoma

6 [12]

63, F

Symptoms: diplopia, blurred vision

Pituitary deficiency: none

PRL: 490 ug/L (RI: < 22)

Imaging: macroadenoma

Treatment: BRC 3.75 mg/d

PRL: 56 ug/L (89% reduction)

Onset: 1.5 years

PRL: 206 ug/L

Imaging: tumor growth

Treatment: Q 300 ug/d, CAB (dose: NA), S, DXT, S (spinal metastases), DXT (spinal metastases)

PRL: 6000 ug/L

Imaging: spinal metastases

Malignant PRLoma, no mitotic activity

Ki-67: 10–15%

7 [50]

22, M

Symptoms: blurred vision

Pituitary deficiency: NA

PRL: 1260 ug/L (RI: NA)

Imaging: macroadenoma

Treatment: S, BRC 7.5 mg/d

PRL: normalized

Imaging: NA

Onset: 1 year

PRL: 42 ug/L

Imaging: macroadenoma

Treatment: S, DXT, BRC 7.5 mg/d

PRL: 5.4 ug/L (87% reduction)

Imaging: NA

PRLoma

8 [17]

70, M

Symptoms: headache

Pituitary deficiency: gonadal

PRL: 8800 ug/L (RI: 2.5–13)

Imaging: macroadenoma

Treatment: CAB 3.5 mg/week

PRL: 25 ug/L (99.7% reduction)

Imaging: size reduction

Onset: 46 months

PRL: 16,000 ug/L

Imaging: tumor growth

Treatment: CAB 5 mg/week, S, octreotide 20 mg/month

PRL: 16,800 ug/L

Imaging: tumor growth

Somatolactotrophoma, no mitotic figures

Ki-67: 4%

p53: negative

9 [13]

31, F

Symptoms: blurred vision, secondary amenorrhea

Pituitary deficiency: panhypopituitarism

PRL: NA

Imaging: macroadenoma

Treatment: S, DXT

PRL: 412 ug/L

Imaging: stable remnant

Onset: 4 years

PRL: 2417 ug/L

Imaging: tumor growth

Treatment: S, BRC 20 mg/d, DXT, S (metastasis)

PRL: 1604 ug/L

Imaging: cerebellar metastasis

Malignant PRLoma, no mitotic activity in pituitary tumor, numerous mitoses in cerebellar metastasis

10 [18]

57, F

Symptoms: secondary amenorrhea

Pituitary deficiency: gonadal

PRL: 75 ug/L (RI: NA)

Imaging: microadenoma

Treatment: BRC 5 mg/d, CAB 1 mg/week

PRL: normalized

Imaging: tumor resolution

Onset: 15 years

PRL: 2392 ug/L

Imaging: macroadenoma

Treatment: CAB 4 mg/week, S, CAB 1.5 mg/week, DXT

PRL: normalized

Imaging: stable remnant

PRLoma

Ki-67: 11%

p53: negative

11 [18]

38, F

Symptoms: secondary amenorrhea

Pituitary deficiency: gonadal

PRL: 124 ug/L (RI: NA)

Imaging: microadenoma

Treatment: CAB 1 mg/week

PRL: normalized

Imaging: NA

Onset: 5 years

PRL: 250 ug/L

Imaging: macroadenoma

Treatment: CAB 7 mg/week, S, CAB 1.5 mg/week

PRL: normalized

Imaging: no residual tumor

PRLoma

p53: negative

12 [14]

43, M

Symptoms: NA

Pituitary deficiency: NA

PRL: NA

Imaging: macroadenoma

Treatment: S, S, S, BRC 55 mg/d

PRL: 57 ug/L

Imaging: NA

Onset: 4 years

PRL: 1000 ug/L

Imaging: macroadenoma

Treatment: Q 0.8 mg/d, S, DXT, CAB 14 mg/week, DXT × 4, S × 2, DXT (spinal metastases)

PRL: 18,000 ug/L

Imaging: no residual tumor, spinal metastases

Malignant PRLoma

13 [15]

40, M

Symptoms: headache, blurred vision

Pituitary deficiency: panhypopituitarism

PRL: > 188 ug/L (RI: < 18.9)

Imaging: macroadenoma

Treatment: S, DXT, BRC 40 mg/d

PRL: 23.5 ug/L (> 87% reduction)

Imaging: no residual tumor

Onset: 5 years

PRL: 3807 ug/L

Imaging: tumor recurrence

Treatment: S, BRC 40 mg/d, S, chemotherapy, S, chemotherapy

PRL: 23,500 ug/L

Imaging: tumor growth, left vertebral artery metastasis

Malignant PRLoma

14 [8]

62, M

Symptoms: visual loss, weight loss, loss of pubic hair

Pituitary deficiency: panhypopituitarism

PRL: 2,598,489 ug/L (RI: 2115–17,625)

Imaging: macroadenoma

Treatment: S, CAB 3 mg/week

PRL: normalized

Imaging: 0.5 cm remnant

Onset: 5 years

PRL: 143,350 ug/L

Imaging: macroadenoma

Treatment: CAB 7 mg/week, S, S, DXT

PRL: 5,041,643 ug/L

Imaging: tumor growth

PRLoma, rare mitotic figures in first two resections, 9–10 mitoses/10 HPF in third resection

Ki-67: 3% in first two resections, 20–30% in third resection

p53: negative in first two resections, positive in third resection

15 [9]

42, F

Symptoms: headache, blurred vision

Pituitary deficiency: panhypopituitarism

PRL: 728 ug/L (RI: < 23)

Imaging: macroadenoma

Treatment: DXT, S, S, S, BRC 15 mg/d

PRL: 43 ug/L (94% reduction)

Imaging: NA

Onset: 2 years

PRL: 313 ug/L

Imaging: macroadenoma

Treatment: BRC 30 mg/d, DXT, BRC 37.5 mg/d, DXT, P 25 ug/d

PRL: 12,800 ug/L

Imaging: scalp metastases

Malignant PRLoma

16 [19]

45, M

Symptoms: NA

Pituitary deficiency: NA

PRL: 3000 ug/L (RI: NA)

Imaging: macroadenoma

Treatment: CAB 1 mg/week

PRL: 54 ug/L (98% reduction)

Imaging: NA

Onset: 9 years

PRL: 1519 ug/L

Imaging: macroadenoma

Treatment: S

PRL: NA

Imaging: size reduction

PRLoma

MIB-1: > 3%

p53: positive

17 [19]

58, F

Symptoms: NA

Pituitary deficiency: NA

PRL: 240 ug/L (RI: NA)

Imaging: macroadenoma

Treatment: BRC 15 mg/d, CAB 9 mg/week

PRL: 29 ug/L (88% reduction)

Imaging: NA

Onset: 6 years

PRL: 909 ug/L

Imaging: macroadenoma

Treatment: S

PRL: NA

Imaging: size reduction

PRLoma

MIB-1: > 3%

p53: positive

18 [10]

55, M

Symptoms: diplopia, visual loss, impotence

Pituitary deficiency: gonadal, thyroid

PRL: 364 ug/L (RI: 2.8–17.9)

Imaging: macroadenoma

Treatment: BRC 15 mg/d

PRL: normalized

Imaging: residual tumor

Onset: 5 years

PRL: 229 ug/L

Imaging: macroadenoma

Treatment: CAB 5 mg/week, S, CAB 14 mg/week + BRC 10 mg/d, S, S, DXT

PRL: 470 ug/L

Imaging: residual tumor

PRLoma

Ki-67: 10–15% in first resection, 20–25% in second resection, > 25% in third resection

19–24 [51]

Brue et al. described six patients with PRLomas with secondary DA resistance. All patients had normalized PRL within 1 year of treatment with subsequent increase in PRL. The onset of secondary DA resistance was 2–6 years. All patients were treated with BRC and none were treated with CAB or S. No further details were provided

25 [52]

Laboy-Ortiz et al. described at 42-year-old male with PRLoma who developed secondary DA resistance after 13 months. No further details were provided

26–29 [16]

Pernicone et al. described four patients with malignant PRLomas with secondary DA resistance. All patients had early response to DA followed by escape from control. No further details were provided

30–31 [53]

Astaf’eva et al. described two patients with PRLomas with secondary DA resistance. One patient achieved disease control after DXT. No further details were provided

32–39 [24]

Vroonen et al. described eight patients with late resistance to DA but did not provide details on these cases