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Article ; Online: Real-world value of cabergoline in the treatment of acromegaly.

Shimon, Ilan

Best practice & research. Clinical endocrinology & metabolism

2024 , Page(s) 101887

Abstract: Cabergoline is an ergot derivative long-acting dopamine receptor 2 (DR2) selective agonist administered orally and widely used for the treatment of prolactin-secreting adenomas and Parkinson's disease. DR2 is expressed in most somatotroph adenomas. In ... ...

Abstract	Cabergoline is an ergot derivative long-acting dopamine receptor 2 (DR2) selective agonist administered orally and widely used for the treatment of prolactin-secreting adenomas and Parkinson's disease. DR2 is expressed in most somatotroph adenomas. In acromegaly, cabergoline is used off-label and its role is limited by the relatively modest efficacy for achieving hormonal remission and thus, it is largely indicated in patients with mild elevation of GH/IGF-I postoperatively. It can be given as monotherapy, usually at a higher weekly dose than usually required to treat prolactinomas, but also as an add-on treatment in patients partially responding to the somatostatin receptor ligands octreotide or lanreotide. IGF-1 normalization with cabergoline can be achieved in about a third of the patients. Low baseline IGF-1 level (below 1.5 x ULN) before cabergoline initiation is a good predictor for remission. Combination treatment with the GH receptor antagonist pegvisomant can also be beneficial. The inexpensive, well-tolerated and convenient oral administration of cabergoline makes it an attractive medical therapy for active acromegaly.
Language	English
Publishing date	2024-02-28
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2052339-7
ISSN	1878-1594 ; 1532-1908 ; 1521-690X
ISSN (online)	1878-1594 ; 1532-1908
ISSN	1521-690X
DOI	10.1016/j.beem.2024.101887
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Article ; Online: Prolactinomas Resistant to Dopamine Agonists: Pathophysiology and Treatment.

Shimon, Ilan

Archives of medical research

2023 Volume 54, Issue 8, Page(s) 102883

Abstract: Prolactinomas are the most common functional pituitary tumors, accounting for 40% of all pituitary adenomas. Medical treatment with dopamine agonists (DA), mainly cabergoline, is considered the primary therapy for these patients. Prolactin normalization ... ...

Abstract	Prolactinomas are the most common functional pituitary tumors, accounting for 40% of all pituitary adenomas. Medical treatment with dopamine agonists (DA), mainly cabergoline, is considered the primary therapy for these patients. Prolactin normalization is achieved in 80-90% of prolactinomas treated with cabergoline. Patients resistant to the standard dose can escalate the dose of cabergoline up to the maximum tolerated dose. The expression of dopamine (D2) receptors and dopamine affinity is decreased in aggressive and resistant prolactinomas. Patients with aggressive and DA-resistant adenomas or with rare PRL-secreting carcinomas can be treated off-label with temozolomide (TMZ), a DNA alkylating agent. TMZ is effective in 40-50% of treated lactotroph tumors showing at least a partial response. However, patients tend to escape from the effect of TMZ after a limited time of response. Other therapeutic options include aromatase inhibitors, the somatostatin receptor ligand pasireotide, peptide receptor radionuclide therapy (PRRT), immune-checkpoint inhibitors, tyrosine-kinase inhibitors, or everolimus, the mammalian target of rapamycin inhibitor. These experimental treatments were effective in some patients carrying refractory prolactinomas showing usually partial tumor control. However, the number of treated patients with any of these new therapeutic options is very limited and treatment results are inconsistent, thus additional experience with more patients is required.
MeSH term(s)	Humans ; Prolactinoma/drug therapy ; Prolactinoma/metabolism ; Prolactinoma/pathology ; Dopamine Agonists/therapeutic use ; Cabergoline/therapeutic use ; Dopamine ; Pituitary Neoplasms/drug therapy ; Pituitary Neoplasms/metabolism ; Pituitary Neoplasms/pathology ; Temozolomide/therapeutic use ; Prolactin/therapeutic use
Chemical Substances	Dopamine Agonists ; Cabergoline (LL60K9J05T) ; Dopamine (VTD58H1Z2X) ; Temozolomide (YF1K15M17Y) ; Prolactin (9002-62-4)
Language	English
Publishing date	2023-09-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1156844-6
ISSN	1873-5487 ; 0188-4409 ; 0188-0128
ISSN (online)	1873-5487
ISSN	0188-4409 ; 0188-0128
DOI	10.1016/j.arcmed.2023.102883
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Article ; Online: Metastatic Spread to the Pituitary.

Shimon, Ilan

Neuroendocrinology

2020 Volume 110, Issue 9-10, Page(s) 805–808

Abstract: The pituitary fossa is an uncommon site for metastatic tumor spread. Metastatic lesions to the sellar area derived mostly from breast, lung, renal, prostate, and colon cancers, and rarely from other solid and hematologic malignancies. Almost every cancer ...

Abstract	The pituitary fossa is an uncommon site for metastatic tumor spread. Metastatic lesions to the sellar area derived mostly from breast, lung, renal, prostate, and colon cancers, and rarely from other solid and hematologic malignancies. Almost every cancer has been reported as a source of pituitary metastasis. Pituitary metastasis can involve both the anterior and posterior lobes, but the neuro-hypophysis is mainly involved. Clinical manifestations include diabetes insipidus, hypopituitarism, headache, visual disturbances, ophthalmoplegia, and also compression of adjacent structures by aggressive tumor masses. Metastatic spread to the pituitary from a distant primary malignancy is commonly associated with metastases to other tissues and poor prognosis, unless efficient systemic targeted medical treatment is available for the primary cancer (melanoma, lymphoma).
MeSH term(s)	Humans ; Pituitary Neoplasms/diagnosis ; Pituitary Neoplasms/pathology ; Pituitary Neoplasms/secondary ; Pituitary Neoplasms/therapy
Language	English
Publishing date	2020-02-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000506810
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Article ; Online: Giant prolactinomas: Multi-modal approach to achieve tumor control.

Shimon, Ilan

Endocrine

2017 Volume 56, Issue 2, Page(s) 227–228

Language	English
Publishing date	2017-05
Publishing country	United States
Document type	Editorial
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-016-1225-x
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Article ; Online: Giant Prolactinomas.

Shimon, Ilan

Neuroendocrinology

2018 Volume 109, Issue 1, Page(s) 51–56

Abstract: Prolactin-secreting adenomas (prolactinomas) are the most common secreting adenomas of the pituitary. Microprolactinomas (diameter <10 mm) are frequently diagnosed in women, whereas macroprolactinomas (maximum diameter ≥10 mm) are generally seen in men. ... ...

Abstract	Prolactin-secreting adenomas (prolactinomas) are the most common secreting adenomas of the pituitary. Microprolactinomas (diameter <10 mm) are frequently diagnosed in women, whereas macroprolactinomas (maximum diameter ≥10 mm) are generally seen in men. Most macroprolactinomas measure between 10 and 40 mm. Giant prolactinomas, measuring >40 mm, are rare, accounting for only 1-5% of all prolactinomas. Although generally benign, giant prolactinomas are aggressive and invasive, extending into the suprasellar region and also involving the cavernous sinuses. The optic chiasm is frequently involved, which leads to visual damage, and patients occasionally suffer from ophthalmoplegia. Long-term (usually lifetime) therapy with high-dose dopamine agonists (cabergoline or bromocriptine), together with pituitary surgery in some cases and radiotherapy if required, can achieve biochemical remission, tumor control, and clinical improvement in most patients.
MeSH term(s)	Female ; Humans ; Male ; Pituitary Neoplasms/pathology ; Pituitary Neoplasms/therapy ; Prolactinoma/pathology ; Prolactinoma/therapy
Language	English
Publishing date	2018-11-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000495184
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Article ; Online: Management of Pituitary Disease.

Shimon, Ilan

Minerva endocrinologica

2016 Volume 41, Issue 3, Page(s) 314–315

MeSH term(s)	Adenoma/therapy ; Humans ; Pituitary Diseases/therapy ; Pituitary Neoplasms/therapy
Language	English
Publishing date	2016-09
Publishing country	Italy
Document type	Journal Article
ZDB-ID	423687-7
ISSN	1827-1634 ; 0391-1977
ISSN (online)	1827-1634
ISSN	0391-1977
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Article ; Online: Pituitary acting drugs: cabergoline and pasireotide.

Gadelha, Mônica R / Wildemberg, Luiz Eduardo / Shimon, Ilan

Pituitary

2022 Volume 25, Issue 5, Page(s) 722–725

Abstract: First-line treatment for Cushing´s disease is transsphenoidal surgery. But in cases of persistent or recurrent disease after surgery, contraindications to surgery, severe hypercortisolism control before surgery, or for patients waiting for radiotherapy ... ...

Abstract	First-line treatment for Cushing´s disease is transsphenoidal surgery. But in cases of persistent or recurrent disease after surgery, contraindications to surgery, severe hypercortisolism control before surgery, or for patients waiting for radiotherapy effects, medical therapy may be indicated. Pituitary-directed agents include cabergoline and pasireotide. Both drugs present similar potential for biochemical control and pasireotide has additionally been proved to reduce tumor volume. Moreover, pasireotide was evaluated in high quality studies. In respect to safety, both drugs are well tolerated and safe, but special attention should be given for cardiac valve disease and psychiatric disorder for cabergoline, and hyperglycemia for pasireotide.
MeSH term(s)	Humans ; Cabergoline/therapeutic use ; Pituitary ACTH Hypersecretion/drug therapy ; Pituitary ACTH Hypersecretion/pathology ; Pituitary Gland/pathology ; Somatostatin/therapeutic use
Chemical Substances	Cabergoline (LL60K9J05T) ; pasireotide (98H1T17066) ; Somatostatin (51110-01-1)
Language	English
Publishing date	2022-06-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1385151-2
ISSN	1573-7403 ; 1386-341X
ISSN (online)	1573-7403
ISSN	1386-341X
DOI	10.1007/s11102-022-01238-8
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Article ; Online: PICT-1 regulates p53 splicing and sensitivity of medullary thyroid carcinoma cells to everolimus.

Bareli, Yifat / Shimon, Ilan / Tobar, Ana / Rubinfeld, Hadara

Journal of neuroendocrinology

2022 Volume 34, Issue 10, Page(s) e13187

Abstract: Protein interacting with carboxyl terminus 1 (PICT-1) is a nucleolar protein shown to act as a tumor suppressor that interacts with PTEN, or in a contrasting manner to facilitate the accessibility of p53 to ubiquitination and degradation, thus to ... ...

Abstract	Protein interacting with carboxyl terminus 1 (PICT-1) is a nucleolar protein shown to act as a tumor suppressor that interacts with PTEN, or in a contrasting manner to facilitate the accessibility of p53 to ubiquitination and degradation, thus to function as an oncogene. The aim of the study was to examine the potential role of PICT-1 in neuroendocrine neoplasm (NEN) tumorigenesis and response to mTOR inhibitor treatment. PICT-1 was overexpressed in medullary thyroid (TT) and pancreatic (BON1) NEN cell lines using lentiviral vector. Whereas in BON1 cells PICT-1 overexpression exhibited no significant impact, in TT cells it induced the appearance of p53β lacking the C-terminus end. This was accompanied by a robust decrease in p21 expression and elevation of cell viability. Remarkably, PICT-1 overexpression completely reversed the reduction in cell viability of medullary thyroid neoplasm cells induced by everolimus, a therapeutic option for patients with progressive NENs. mTOR pathway investigations revealed that PICT-1 overexpression induced a reduction in PTEN expression and a robust increase in the expression level of phospho-Akt-Ser47 only partially inhibited by everolimus. These findings suggest a possible role of PICT-1 in the spliceosome machinery and provide functional involvement of PICT-1 in the complex network of mTOR.
MeSH term(s)	Humans ; Cell Line, Tumor ; Everolimus/pharmacology ; Thyroid Neoplasms/drug therapy ; Thyroid Neoplasms/genetics ; TOR Serine-Threonine Kinases/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Everolimus (9HW64Q8G6G) ; NOP53 protein, human ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Tumor Suppressor Protein p53 ; Tumor Suppressor Proteins
Language	English
Publishing date	2022-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1007517-3
ISSN	1365-2826 ; 0953-8194
ISSN (online)	1365-2826
ISSN	0953-8194
DOI	10.1111/jne.13187
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Article: Giant Prolactinomas

Shimon, Ilan

Neuroendocrinology

2018 Volume 109, Issue 1, Page(s) 51–56

Institution	Institute of Endocrinology, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Abstract	Prolactin-secreting adenomas (prolactinomas) are the most common secreting adenomas of the pituitary. Microprolactinomas (diameter <10 mm) are frequently diagnosed in women, whereas macroprolactinomas (maximum diameter ≥10 mm) are generally seen in men. Most macroprolactinomas measure between 10 and 40 mm. Giant prolactinomas, measuring >40 mm, are rare, accounting for only 1–5% of all prolactinomas. Although generally benign, giant prolactinomas are aggressive and invasive, extending into the suprasellar region and also involving the cavernous sinuses. The optic chiasm is frequently involved, which leads to visual damage, and patients occasionally suffer from ophthalmoplegia. Long-term (usually lifetime) therapy with high-dose dopamine agonists (cabergoline or bromocriptine), together with pituitary surgery in some cases and radiotherapy if required, can achieve biochemical remission, tumor control, and clinical improvement in most patients.
Keywords	Cabergoline ; Dopamine agonist ; Giant prolactinoma ; Prolactin ; Prolactinoma
Language	English
Publishing date	2018-11-07
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	At the Cutting Edge
ZDB-ID	123303-8
ISBN	978-3-318-06568-8 ; 3-318-06568-4
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000495184
Database	Karger publisher's database

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Article ; Online: Screening for Cushing's syndrome: is it worthwhile?

Shimon, Ilan

Pituitary

2015 Volume 18, Issue 2, Page(s) 201–205

Abstract: Introduction: Cushing's syndrome (CS) is a rare disease characterized by a collection of signs and symptoms, also common in the general population without elevated cortisol secretion. During the last years more patients with CS are identified earlier ... ...

Abstract	Introduction: Cushing's syndrome (CS) is a rare disease characterized by a collection of signs and symptoms, also common in the general population without elevated cortisol secretion. During the last years more patients with CS are identified earlier and with milder disease. Many of these patients are diagnosed during screening efforts performed for certain or isolated complaints like weight gain, diabetes mellitus (DM), hypertension, osteoporosis, elevated white blood cell counts and more. Methods: In this review article the most popular screening test performed in the studies cited was the 1-mg dexamethasone suppression test. Conclusions: Cushing is not frequent enough to support the use of routine screening in patients with morbid obesity and type 2 DM. Also only 1% of hypertensive patients have secondary hypertension due to CS. However, screening should be considered in young patients with resistant DM and/or hypertension. Among patients with osteoporosis and vertebral fractures up to 5% were diagnosed with subclinical hypercortisolism; most of these had adrenal adenoma. Screening for CS is important in subjects with adrenal incidentaloma, and many studies show a high prevalence (~10%) of Cushing or subclinical CS in these patients.
MeSH term(s)	ACTH-Secreting Pituitary Adenoma/diagnosis ; ACTH-Secreting Pituitary Adenoma/epidemiology ; ACTH-Secreting Pituitary Adenoma/therapy ; Adenoma/diagnosis ; Adenoma/epidemiology ; Adenoma/therapy ; Adrenal Cortex Function Tests ; Comorbidity ; Dexamethasone/administration & dosage ; Humans ; Mass Screening/methods ; Patient Selection ; Pituitary ACTH Hypersecretion/diagnosis ; Pituitary ACTH Hypersecretion/epidemiology ; Pituitary ACTH Hypersecretion/therapy ; Predictive Value of Tests ; Prognosis ; Risk Assessment ; Risk Factors
Chemical Substances	Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2015-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1385151-2
ISSN	1573-7403 ; 1386-341X
ISSN (online)	1573-7403
ISSN	1386-341X
DOI	10.1007/s11102-015-0634-9
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