Clinical Management of Acromegaly: Therapeutic Frontiers and New Perspectives for Somatostatin Receptor Ligands (SRLs)

Brunetti, A.; Antonini, Simone; Saladino, Andrea; Lavezzi, Elisabetta; Zampetti, Benedetta; Cozzi, Renato

doi:10.3390/medicina58060794

Cited by 3 publications

(3 citation statements)

References 54 publications

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“…No report of the second-generation SSA pasireotide was identified amid gestation. The drug was introduced into daily practice later than first-generation SSAs targeting tumors with a higher expression of SSTR5 rather than type 2; thus, it found its way in acromegaly management considering that 24–65% of acromegaly cases might not achieve optimal control under first-generation SSAs [ 104 , 105 , 106 , 107 ]. Not all tumors display the same configuration SSTS, which may indicate SSA response; the immunohistochemistry report after selective hypofisectomy provides a useful assessment of the SSTR2/5 ratio [ 108 ].…”

Section: Specific Medical Therapy For Acromegaly During Pregnancymentioning

confidence: 99%

Approach of Acromegaly during Pregnancy

et al. 2022

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Acromegaly-related sub/infertility, tidily related to suboptimal disease control (1/2 of cases), correlates with hyperprolactinemia (1/3 of patients), hypogonadotropic hypogonadism—mostly affecting the pituitary axis in hypopituitarism (10–80%), and negative effects of glucose profile (GP) anomalies (10–70%); thus, pregnancy is an exceptional event. Placental GH (Growth Hormone) increases from weeks 5–15 with a peak at week 37, stimulating liver IGF1 and inhibiting pituitary GH secreted by normal hypophysis, not by somatotropinoma. However, estrogens induce a GH resistance status, protecting the fetus form GH excess; thus a full-term, healthy pregnancy may be possible. This is a narrative review of acromegaly that approaches cardio-metabolic features (CMFs), somatotropinoma expansion (STE), management adjustment (MNA) and maternal-fetal outcomes (MFOs) during pregnancy. Based on our method (original, in extenso, English—published articles on PubMed, between January 2012 and September 2022), we identified 24 original papers—13 studies (3 to 141 acromegalic pregnancies per study), and 11 single cases reports (a total of 344 pregnancies and an additional prior unpublished report). With respect to maternal acromegaly, pregnancies are spontaneous or due to therapy for infertility (clomiphene, gonadotropins or GnRH) and, lately, assisted reproduction techniques (ARTs); there are no consistent data on pregnancies with paternal acromegaly. CMFs are the most important complications (7.7–50%), especially concerning worsening of HBP (including pre/eclampsia) and GP anomalies, including gestational diabetes mellitus (DM); the best predictor is the level of disease control at conception (IGF1), and, probably, family history of 2DM, and body mass index. STE occurs rarely (a rate of 0 to 9%); some of it symptoms are headache and visual field anomalies; it is treated with somatostatin analogues (SSAs) or alternatively dopamine agonists (DAs); lately, second trimester selective hypophysectomy has been used less, since pharmaco-therapy (PT) has proven safe. MNA: PT that, theoretically, needs to be stopped before conception—continued if there was STE or an inoperable tumor (no clear period of exposure, preferably, only first trimester). Most data are on octreotide > lanreotide, followed by DAs and pegvisomant, and there are none on pasireotide. Further follow-up is required: a prompt postpartum re-assessment of the mother’s disease; we only have a few data confirming the safety of SSAs during lactation and long-term normal growth and developmental of the newborn (a maximum of 15 years). MFO seem similar between PT+ve and PT-ve, regardless of PT duration; the additional risk is actually due to CMF. One study showed a 2-year median between hypophysectomy and pregnancy. Conclusion: Close surveillance of disease burden is required, particularly, concerning CMF; a personalized approach is useful; the level of statistical evidence is expected to expand due to recent progress in MNA and ART.

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Section: Specific Medical Therapy For Acromegaly During Pregnancymentioning

confidence: 99%

Approach of Acromegaly during Pregnancy

et al. 2022

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“…A acromegalia é um distúrbio endócrino crônico resultante da hipersecreção prolongada do hormônio do crescimento (GH) após o fechamento das epífises ósseas. A principal causa da acromegalia é a presença de um adenoma hipofisário secretor de GH, que estimula a produção excessiva desse hormônio (Brunetti et al, 2022).…”

Section: Introductionunclassified

Acromegalia: uma análise dos impactos em regulações neuroendócrinas

Queiroz,

Campos,

Duarte

et al. 2024

Braz. J. Implantol. Health Sci.

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A acromegalia é um distúrbio endócrino crônico caracterizado pelo aumento progressivo dos tecidos devido à hipersecreção do hormônio do crescimento (GH) após o fechamento das epífises ósseas, resultando em características fenotípicas distintas, como prognatismo mandibular, acromegalia das extremidades, bossa frontal proeminente, alterações na voz, entre outras manifestações. Sendo assim, é importante avaliar como os processos neuroendócrinos estão relacionados com o desenvolvimento da acromegalia, a fim de estabelecer um entendimento claro sobre como os processos de tratamento são desenvolvidos. A revisão sistemática realizada nos últimos 10 anos analisou os mecanismos neuroendócrinos no manejo da doença, com critérios de inclusão específicos e pesquisa em diversas bases de dados. Dos 31 resultados iniciais, 6 estudos foram selecionados, evidenciando a relevância dos tratamentos utilizados e suas respostas. Os achados ressaltam a necessidade de compreender as características moleculares da acromegalia para direcionar estratégias terapêuticas mais eficazes, visando a normalização dos níveis de GH e IGF-1 para controlar os sintomas e melhorar os desfechos clínicos dos pacientes afetados por esse distúrbio endócrino. Portanto, novos estudos são essenciais para elucidar melhor esses mecanismos e orientar estratégias terapêuticas mais precisas e eficazes para pacientes com acromegalia.

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“…The most common practice is to start treatment “blindly” with fg-SRLs and switch to Pasireotide, GH-blockers or combination therapy in case of resistance to fg-SRL, which was reported to occur in between 20–70% of cases, with a mean of 45% [ 14 , 15 ]. While some of these medications share common mechanisms of action, there are also clear differences in how different classes of drugs act on inducing acromegaly disease control, from receptor-type activation to post-receptor signaling pathways and cytoskeleton involvement [ 16 , 17 , 18 ]. For patients with aggressive and invasive tumors resistant to first- and second-line therapies, sometimes the only option left is surgical reintervention or radiotherapy, both of which are frequently associated with poor prognosis, secondary side-effects, such as hypopituitarism, and high morbidity [ 7 , 19 ].…”

Section: Introductionmentioning

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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Clinical Management of Acromegaly: Therapeutic Frontiers and New Perspectives for Somatostatin Receptor Ligands (SRLs)

Cited by 3 publications

References 54 publications

Approach of Acromegaly during Pregnancy

Approach of Acromegaly during Pregnancy

Acromegalia: uma análise dos impactos em regulações neuroendócrinas

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

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