The acute effect of a single application of cabergoline on endogenous GH levels in patients with acromegaly on pegvisomant treatment

Roemmler, J.; Steffin, B.; Gutt, B.; Schneider, Harald J.; Sievers, Caroline; Bidlingmaier, Martin; Schopohl, Jochen

doi:10.1016/j.ghir.2010.05.004

Cited by 10 publications

(4 citation statements)

References 41 publications

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“…Few data are available on the combination of cabergoline and pegvisomant ( 58 – 60 ). Cross-sectional studies show significantly decreased IGF-I with long-term combination treatment in patients with mildly elevated IGF-I despite pegvisomant monotherapy ( 60 ).…”

Section: Acromegalymentioning

confidence: 99%

Dopamine Agonists for Pituitary Adenomas

Cooper

Greenman

2018

Front. Endocrinol.

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Dopamine agonists (DA) are well established as first-line therapy for prolactinomas. These tumors express high levels of dopamine 2 receptors (D2R), leading to the strong efficacy of DA in reducing tumor size and hormonal secretion. Other pituitary tumor subtypes express D2R to varying degrees, leading to an extensive body of research into potential off-label use of DA in non-prolactinoma pituitary tumors. Preclinical models of Cushing's disease, acromegaly, and nonfunctioning pituitary tumors (NFPT) demonstrate D2R expression in cell lines and cultured tumors as well as effectiveness of DA in reducing hormonal secretion in functioning tumors and arresting tumor proliferation. Clinical studies have shown some efficacy of DA in treatment of these tumors. In Cushing's disease, DA therapy results in normalization of urinary cortisol levels in approximately 25% of patients, but reported rates of tumor shrinkage are very low; in acromegaly, DA therapy leads to normalization of insulin-like growth factor I and tumor shrinkage in approximately one-third of patients, and improved responses when used in combination with somatostatin receptor ligands. Among patients with NFPT, pooled results show 30% experience reduction of tumor size and 58% show stabilization of disease. DA therapy appears to have some clinical benefit in patients with non-prolactinoma pituitary tumors, and may be an option for medical therapy in some clinical scenarios.

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Section: Acromegalymentioning

confidence: 99%

Dopamine Agonists for Pituitary Adenomas

Cooper

Greenman

2018

Front. Endocrinol.

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“…Experimental data suggest that response to cabergoline is preserved in acromegalic patients treated with the GHreceptor antagonist PEG [30]. The anti-secretory and antiproliferative effects of cabergoline could complement the action of PEG [8] and improve biochemical and tumor control [18].…”

Section: Cabergoline As An Add-on Therapy To Pegmentioning

confidence: 99%

Cabergoline treatment in acromegaly: pros

et al. 2014

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Cabergoline is an ergot-derived dopamine D2 receptor agonist which may be effective for the medical management of acromegaly. Its efficacy in reducing growth hormone and IGF-I levels, as well as its antiproliferative and pro-apoptotic effects on pituitary tumor cells, has been observed in several studies. Cabergoline may be used alone or as an add-on therapy to patients who are partially resistant to somatostatin analogs (SSA), or who do not achieve complete control with maximum doses of pegvisomant (PEG). Additionally, the convenience of its oral administration, allowing better compliance, and its lower economic cost, in comparison with SSA and PEG, favor cabergoline as an attractive option for acromegalic patients, who frequently require long-life medical treatment to achieve disease control. The few adverse events observed with prolonged DA therapy, mainly regarding cardiac valve disease, are not frequent at the doses generally used in acromegaly.

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“…In particular, bromocriptine improves glucose tolerance [ 131 – 133 ] and decreases insulin [ 131 , 133 ] and glucagon [ 132 ] levels in patients with acromegaly [ 133 ]. Similarly, the addition of cabergoline to PEGV decreases the postprandial glucose rise [ 134 ].…”

Section: The Impact Of Medical Treatment Of Acromegaly In Glucose Met...mentioning

confidence: 99%

Secondary diabetes mellitus in acromegaly

et al. 2023

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Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher in cohorts of patients with type 2 DM (T2DM). The presence of secondary DM depends primarily on acromegaly status and is associated with increased cardiovascular morbidity, malignancy rate and overall mortality. The principal pathophysiologic mechanism is increased insulin resistance due to excessive lipolysis and altered fat distribution, reflected at the presence of intermuscular fat and attenuated, dysfunctional adipose tissue. Insulin resistance is ascribed to the direct, diabetogenic effects of growth hormone (GH), which prevail over the insulin-sensitizing effects of insulin-like growth factor 1 (IGF-1), probably due to higher glucometabolic potency of GH, IGF-1 resistance, or both. Inversely, GH and IGF-1 act synergistically in increasing insulin secretion. Hyperinsulinemia in portal vein leads to enhanced responsiveness of liver GH receptors and IGF-1 production, pointing towards a mutually amplifying loop between GH-IGF-1 axis and insulin. Secondary DM occurs upon beta cell exhaustion, principally due to gluco-lipo-toxicity. Somatostatin analogues inhibit insulin secretion; especially pasireotide (PASI) impairs glycaemic profile in up to 75% of cases, establishing a separate pathophysiologic entity, PASI-induced DM. In contrast, pegvisomant and dopamine agonizts improve insulin sensitivity. In turn, metformin, pioglitazone and sodium-glucose transporters 2 inhibitors might be disease-modifying by counteracting hyperinsulinemia or acting pleiotropically. Large, prospective cohort studies are needed to validate the above notions and define optimal DM management in acromegaly.

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The acute effect of a single application of cabergoline on endogenous GH levels in patients with acromegaly on pegvisomant treatment

Cited by 10 publications

References 41 publications

Dopamine Agonists for Pituitary Adenomas

Dopamine Agonists for Pituitary Adenomas

Cabergoline treatment in acromegaly: pros

Secondary diabetes mellitus in acromegaly

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