Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature

Kızılgül, Muhammed; Duger, Hakan; Nasiroglu, Narin; Sencar, Muhammed Erkam; Hepşen, Sema; Akhanlı, Pınar; Berker, Dilek; Çakal, Erman; Bostan, Hayri; Uçan, Bekir

doi:10.20945/2359-3997000000481

Cited by 4 publications

(2 citation statements)

References 42 publications

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“…Immunohistochemical staining for other pituitary hormones is a useful practice for the evaluation of acromegaly patients as it can identify tumors with hormonal cosecretion, the most frequent one being GH–prolactin cosecretion. While the exact relationship between GH–prolactin cosecretion and other clinical and HP characteristics is not clear, several studies found that these types of tumors present a better response to DA in terms of IGF-1 decrease, thus prolactin staining could potentially have a role in choosing the optimal medical treatment for patients with active acromegaly [ 77 , 78 ] (Figure 1 ; Table 1 ).…”

Section: Cytoskeleton: Filamin a Beta-arrestinsmentioning

confidence: 99%

Immunohistochemical evaluation of biomarkers with predictive role in acromegaly: a literature review

Gliga¹,

Tătăranu²,

Popescu³

et al. 2023

Rom J Morphol Embryol

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Acromegaly is a rare endocrine disorder, which despite the recent advances in diagnosis and management, remains a significant burden in terms of morbidity and mortality for patients because of the frequent aggressive evolution and lack of response to available first-line pharmacological therapy. A switch from the classical “trial and error” management to a personalized therapy approach has been proposed through early identification of biomarkers that could predict treatment response and biological behavior. Several such molecular markers have been extensively studied through immunohistochemistry (IHC), among them the somatostatin receptors type 2 (SSTR-2) and type 5 (SSTR-5), which are known to correlate with response to somatostatin analogues treatment, the SSTR-2 negative tumors usually being resistant to first-generation analogues, while SSTR-5 potentially being a predictive marker for the novel agent, Pasireotide. Based on cytokeratin (CK) immunostaining pattern, somatotropinomas have been classified into densely granulated adenomas (DGAs), which present a milder evolution and favorable outcomes after therapy, and sparsely granulated adenomas (SGAs), known to be more aggressive and frequently resistant to first-line treatment options. Other novel markers, such as the E-cadherin cell-adhesion protein, the aryl hydrocarbon receptor-interacting protein (AIP), the cytoskeleton molecule filamin A (FLNA) and the Ki-67 nuclear antigen have also been the highlight of IHC studies on growth hormone (GH)-producing tumors, with promising results regarding their predictive roles for the outcome of acromegalic patients. In this review, we aimed to summarize the current knowledge on the role of IHC for acromegaly, highlighting the most important biomarkers that could offer valuable information for predicting treatment response, biological behavior, and prognosis.

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Section: Cytoskeleton: Filamin a Beta-arrestinsmentioning

confidence: 99%

Immunohistochemical evaluation of biomarkers with predictive role in acromegaly: a literature review

Gliga¹,

Tătăranu²,

Popescu³

et al. 2023

Rom J Morphol Embryol

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“…To sum up, the publication by Kizilgul and cols. (1) showing once more the efficacy of cabergoline in the treatment of acromegaly is a timely reminder that dopaminergic treatment still has an important role, at a relatively low cost, in the current management of acromegaly. It is noteworthy that cabergoline is included in the drugs' list for the treatment of acromegaly in our public health system.…”

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Dopaminergic treatment of patients with acromegaly: still kicking after all these years

Abucham¹

2022

Archives of Endocrinology and Metabolism

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I n this issue of the Archives of Endocrinology and Metabolism, the article "Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature", by Kizilgul and cols. (1), shares an excellent opportunity to review the history and to reappraise the role of dopaminergic treatment in acromegaly.It all started 50 years ago, when Liuzzi and cols.(2) reported in The Journal of Clinical Endocrinology and Metabolism an inhibitory effect of L-Dopa in patients with acromegaly. That observation was particularly intriguing because L-Dopa, a dopamine precursor, was known to stimulate GH secretion in healthy subjects (3).Here is a quote from the discussion in that seminal paper: On the basis of clinical and experimental knowledge we are unable to explain these results.... we believe that the paradoxical fall of plasma GH we observed in some patients affected by acromegaly is of interest and needs more extensive studies. It suggests a new therapeutic approach to the treatment of acromegaly.Indeed, in the following years, that same group of investigators showed that a new ergot derivative, 2-Br-alpha-ergocryptine (bromocriptine), a dopamine agonist, was also able to reduce growth hormone secretion in patients with acromegaly (4). Soon after, bromocriptine proved to be even more effective in reducing prolactin secretion in various physiological and pathological conditions and became the first choice treatment for prolactinomas (5). The effect of bromocriptine on growth hormone secretion and tumor growth in acromegaly was later shown to be mediated by dopaminergic receptors (particularly type 2), which are usually expressed in growth hormone and other pituitary adenomas (6). Notwithstanding its modest efficacy and several side effects, bromocriptine remained, for a whole decade, as the only pharmacological treatment available for acromegaly.In the mid-eighties, treatment of acromegaly changed dramatically with the development of octreotide, a somatostatin analogue much more effective than bromocriptine in controlling growth hormone secretion and tumor growth in patients with acromegaly (7). Thereafter, octreotide and, also, lanreotide (another first generation somatostatin analog), became the first line of pharmacological treatment for that disease. Nevertheless, almost half of patients do not attain disease control under treatment with those somatostatin analogs even with higher than usual doses (8).At about the same time, cabergoline, another ergot-derivative with a more potent dopaminergic activity and less side effects than bromocriptine, showed a remarkable superiority in relation to bromocriptine in the treatment of prolactinomas (9). Later, in the late 90's, two preliminary reports of treatment of acromegaly with cabergoline, alone or in combination with somatostatin analogues, showed promising outcomes

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Clinical presentation and recurrence of pituitary neuroendocrine tumors: results from a single referral center in Colombia

Jiménez-Cañizales

Rojas

Alonso

et al. 2023

J Endocrinol Invest

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Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature

Cited by 4 publications

References 42 publications

Immunohistochemical evaluation of biomarkers with predictive role in acromegaly: a literature review

Immunohistochemical evaluation of biomarkers with predictive role in acromegaly: a literature review

Dopaminergic treatment of patients with acromegaly: still kicking after all these years

Clinical presentation and recurrence of pituitary neuroendocrine tumors: results from a single referral center in Colombia

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