In vivo and in vitro effects of octreotide, quinagolide and cabergoline in four hyperprolactinaemic acromegalics: correlation with somatostatin and dopamine D2 receptor scintigraphy

Abstract

Objective: GH and PRL cosecretion frequently occurs in acromegaly and the sensitivity of both hormones to somatostatin analogs (SA) and dopamine agonists (DA) alone or in combination, is still debated. This study was designed to evaluate the in vivo and in vitro sensitivity to SA and/or DA and correlate the response in terms of hormone suppression to the results of in vivo somatostatin and dopamine receptor scintigraphy and to the immunohistochemical findings.

Design and patients: Scintigraphy using 111In-DTPA-D-Phe(1)-OCT (111In-OCT) and 123I-methoxybenzamide (123I-IBZM) was performed in four patients with acromegaly and high circulating GH, PRL and IGF-I levels. The results were correlated with the response to long-term treatment with octreotide (OCT), quinagolide (QN) and/or cabergoline (CAB), to the in vitro hormone suppression by OCT and DA in primary cultures from the pituitary tumors and to the immunohistochemical findings.

Results: The first patient showed high tumour uptake of 111In-OCT and 123I-IBZM, the second high uptake of only 111In-OCT, while the third one showed faint tumour uptake of only 123I-IBZM, and the fourth a faint uptake of 111In-OCT. In the first and in the fourth patients OCT or CAB administered alone failed to normalize hormone levels while the combined treatment induced circulating GH, IGF-I and PRL normalization. In the second patient OCT administered alone normalized hormone levels while QN reduced PRL levels only. In the third patient both OCT and QN, alone or in combination, failed to normalize hormone levels. However, in this patient GH and PRL suppression was significantly greater after QN than OCT treatment. After medical therapy, all the patients were operated on. Immunohistochemistry showed diffuse GH and focal PRL staining in the first patient, while diffuse GH and PRL staining in the remaining three. In vitro, OCT significantly suppressed GH secretion in the four primary pituitary tumor cultures, while PRL secretion was significantly suppressed only in the second and the fourth cases. Dopamine agonists (DA) significantly suppressed PRL release in all the cultures, while GH secretion was significantly suppressed in three out of four.

Conclusions: These four acromegalics, presenting similar clinical findings and comparable peripheral hormone levels, showed different responsiveness to SA and DA. Moreover, during the in vitro study on primary tumor cell cultures, OCT and DA displayed an inhibiting activity on GH and PRL secretion positively correlated with the response observed in vivo. This evidence together with the in vivo receptor imaging study suggest the existence of somatostatin and/or dopamine D2 receptor heterogeneity in this class of pituitary tumors. The new potent DA might be primarily considered in the medical treatment of hyperprolactinemic acromegalics, while SA alone or in combination with DA in case of ineffective hormone suppression.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;

- Malignant pleural mesothelioma, stage T3-T4. Consideration of a case study;

- Excellent result in a Mesothelioma case treated exclusively with Di Bella Method for over 4 years and still treatment with positive results;

- A case of advanced Multiple Myeloma treated with Di Bella Method (DBM) into total remission for 13 years;

- Neuroblastoma: Complete objective response to biological treatment;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;

- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- A retrospective observational study on cases of Osteosarcomas treated with a multitherapy: The rationale and effectiveness;

- A Retrospective Observational Study on Cases of Sarcoma Treated with the Di Bella Method: Rationale and Effectiveness;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up.