Background
Methods
Case presentation
Date | PRL (3.4–19.1 ug/L) | FT4 (9.0–19.0 pmol/L) | Total testosterone (4.9–32.0 nmol/L) | Tumor size (cm) | Medication |
---|---|---|---|---|---|
December 2014 | > 470 | 10.7 | 5.16 | CC: 2.4 TR: 2.0 AP: 2.0 | CAB 0.5 mg 2×/week LT4 25 mcg OM |
June 2015 | 121.9 | – | – | CC: 1.3 TR: 1.5 AP: 1.8 | CAB 0.75 mg 2×/week LT4 75 mcg OM |
July 2016 | 24.1 | 13.0 | 4.6 | CC: 1.4 TR: 1.7 AP: 1.8 | CAB 0.75 mg 2×/week LT4 75 mcg OM |
December 2017 | > 197.4 | 12.0 | 2.2 | CC: 1.5 TR: 1.7 AP: 2.1 | CAB 0.75 mg 2×/week LT4 75 mcg EOD LT4 100 mcg EOD |
February 2020 | 93.8 | 10.5 | 1.4 | CC: 2.5 TR: 1.8 AP: 1.7 | CAB 0.75 mg 2×/week LT4 50 mcg M-F LT4 25 mcg S,S T 100 mg q28 days |
February 2021 | 160.8 | – | – | CC: 2.2 TR: 1.6 AP: 1.7 | CAB 0.75 mg 2×/week LT4 25 mcg M-T LT4 50 mcg F-S T 100 mg q28 days |
December 2021 | 271.1 | 10.2 | - | CC: 2.8 TR: 2.0 AP: 1.9 | CAB 1.5 mg, 1.5 mg, 1 mg LT4 25 mcg M-T LT4 50 mcg F-S T 100 mg q28 days |
April 2022 | 280.8 | - | - | CC: 2.9 TR: 1.9 AP: 1.6 | CAB 1.5 mg 3×/week LT4 25 mcg M-T LT4 50 mcg F-S T 100 mg q28 days |
September 2022 (preoperative) | 236.6 | 9.3 | 20.6 | CC: 2.7 TR: 1.9 AP: 1.7 | CAB 2 mg 3×/week LT4 50 mcg OM T 100 mg q28 days |
September 2022 (postoperative) | 133.2 | – | – | – | CAB 1 mg 2×/week LT4 50 mcg OM T 100 mg q28 days |
October 2022 | 99.9 | 12.5 | – | Intrasellar component: CC: 0.7 TR: 0.9 AP: 1.3 Suprasellar component: CC: 0.9 TR: 2.0 AP: 0.8 | CAB 2 mg 3×/week LT4 100 mcg OM T 100 mg q28 days |
Discussion
Results of literature search
No. | Details at presentation | Progress before secondary DA resistance | Details at secondary DA resistance | Progress after secondary DA resistance | Diagnosis |
---|---|---|---|---|---|
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 |
Characteristic | Value |
---|---|
Gender, male | 12 |
Gender, female | 11 |
Gender, unknown | 8 |
Age (range), years | 22–70 |
Androgen/estrogen replacement therapy | 4 |
Macroadenoma | 15 |
Microadenoma | 3 |
Tumor size not reported | 13 |
Time to secondary resistance (range), years | 0.8–15 |
Malignant prolactinomas | 10 |