Acromegaly: pathogenesis, diagnosis, and management

Fleseriu, Maria; Langlois, Fabienne; Lim, Dawn Shao Ting; Varlamov, Elena V.; Melmed, Shlomo

doi:10.1016/s2213-8587(22)00244-3

Cited by 111 publications

(70 citation statements)

References 225 publications

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“…Patients with radiological thoracic vertebral fractures and COVID-19 had worse outcomes when hospitalized for pneumonia [87] thus potentially predicting cardiorespiratory risk. As patients with acromegaly have higher prevalence of vertebral fractures [88] , close monitoring for cardiac and respiratory complications is warranted.…”

Section: Pituitary Pathology In the Context Of Covid-19mentioning

confidence: 99%

Pituitary and SARS CoV-2: An unremitting conundrum

Căpățînă

Poiană

Fleseriu

2023

Best Practice & Research Clinical Endocrinology & Metab

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Section: Pituitary Pathology In the Context Of Covid-19mentioning

confidence: 99%

Pituitary and SARS CoV-2: An unremitting conundrum

Căpățînă

Poiană

Fleseriu

2023

Best Practice & Research Clinical Endocrinology & Metab

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“…Growth Hormone Releasing Hormone (GHRH), IGF1 (Insulin Like Growth Factor 1) 1 and Potassium Voltage‐Gated Channel Interacting Protein 3 (KCNIP3) 14 are widely believed to be associated with the occurrence of GHPA. To assess the potential role of SPHK1 in GHPA, we first analysed SPHK1 expression in transcriptome data of pituitary tissue from patients with GHPA by using the Gene Expression Omnibus (GEO) database (GSE46311, GHPA, n = 16).…”

Section: Resultsmentioning

confidence: 99%

“…Patients diagnosed with growth hormone-secreting pituitary adenoma (GHPA) or acromegaly are at a heightened risk of morbidity and mortality over the medium-and long-term. 1 The severe complications associated with this condition, including but not limited to insulin resistance, cardiac hypertrophy, headaches, sleep apnea syndrome, visual disturbances, hypertension, and various other kinds of tumours, contribute to the increased risk compared to the general population. 2 In addition to these complications, patients affected with these pathologically benign tumours may also face tumour recurrence, elevated levels of insulin-like growth factors-1 (IGF-1) and/or GH, and deterioration in glucose control despite undergoing conventional therapies such as surgery, medication (such as somatostatin analogs), or radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…Patients diagnosed with growth hormone‐secreting pituitary adenoma (GHPA) or acromegaly are at a heightened risk of morbidity and mortality over the medium‐ and long‐term 1 . The severe complications associated with this condition, including but not limited to insulin resistance, cardiac hypertrophy, headaches, sleep apnea syndrome, visual disturbances, hypertension, and various other kinds of tumours, contribute to the increased risk compared to the general population 2 .…”

Section: Introductionmentioning

confidence: 99%

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Targeting the SPHK1/S1P/S1PR2 axis ameliorates GH‐secreted pituitary adenoma progression

Sun,

Hu,

et al. 2023

Eur J Clin Investigation

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BackgroundGrowth hormone‐secreted pituitary adenoma (GHPA) is a prominent subtype of pituitary adenoma (PA) associated with progressive somatic disfigurement, various complications, and elevated mortality rates. Existing treatment options have limited efficacy, highlighting the urgent need for novel pharmacological interventions. Previous studies have revealed that sphingosine kinase 1 (SphK1)/sphingosine‐1‐phosphate (S1P)/S1P receptors (S1PRs) signalling have critical roles in the tumour microenvironment, but their role in GHPA remains unclear.MethodsWe performed integrative analyses including bioinformatics analyses, functional studies, and clinical validation to investigate the pathological roles of SPHK1/S1P and evaluated the effectiveness of the S1P receptor 2 (S1PR2) inhibitor JTE‐013 in GHPA treatment.ResultsSPHK1/S1P signalling is abnormally expressed in patients with GHPA. Knockdown of SPHK1 suppresses S1P‐mediated cell proliferation in GH3 Cells. Mechanistically, S1P inhibits apoptosis and autophagy while promoting the secretion of Growth Hormone (GH) by binding to the S1P receptor subtype 2 (S1PR2) in GH3 cells. Moreover, the function of S1PR2 in GH3 cells is mediated by the downstream Akt‐Creb pathway. We then identify the S1PR2 as a novel target for therapeutic intervention in GHPA. Systemic administration of the potent and selective S1PR2 antagonist, JTE‐013, significantly reduces both tumour size and GH secretion. Importantly, we identify preoperative serum S1P levels as a biomarker predicting poor prognosis in GHPA patients at follow‐up.ConclusionOur study shows that blocking SPHK1/S1P/S1PR2 axis can ameliorate the progression of GHPA, providing evidence of a promising therapeutic target for GHPA.

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“…Furthermore, debulking pituitary surgery may result in a greater response rate to octreotide (OCT) than in those who received OCT as primary medical therapy. 80 The clinical outcome of surgery is measured in terms of its effectiveness in achieving “clinical remission” according to a universally agreed “consensus” criteria for biochemical remission, namely a random GH level of less than 1 μg/L and a GH nadir level post-OGTT less than 0.4 μg/L and a normalized level of IGF-1 for age and gender. 81 Success rates are affected by various factors, including tumor size, preoperative GH concentration, and surgeon experience.…”

Section: Managementmentioning

confidence: 99%

Contemporary Management of Acromegaly: A Practical Approach

Almalki

Ahmad

Alqahtani

et al. 2022

Journal of Diabetes and Endocrine Practice

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Acromegaly is a rare, chronic disease that is, in more than 95% of cases, caused by a growth hormone (GH)-secreting pituitary adenoma. Overproduction of insulin-like growth factor-1 (IGF-1) due to GH hypersecretion leads to various clinical features characterized by somatic overgrowth, physical changes, multiple comorbidities, and increased mortality. The average age at diagnosis is 40 to 50 years, with no sex predilection. The mean delay in diagnosis is 4.5 to 5 years due to the insidious onset and slow clinical progression of the disease. The diagnosis is confirmed by increased levels of IGF-1 and insuppressible GH measured by an oral glucose tolerance test. Treatment is aimed at normalizing GH/IGF-1 levels and controlling tumor volume. Medical treatment and radiotherapy can be utilized when surgery fails to control GH/IGF-1 hypersecretion. This article aims to review recent updates in acromegaly diagnosis and treatment to raise awareness about acromegaly clinical presentation and management.

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Acromegaly: pathogenesis, diagnosis, and management

Cited by 111 publications

References 225 publications

Pituitary and SARS CoV-2: An unremitting conundrum

Pituitary and SARS CoV-2: An unremitting conundrum

Targeting the SPHK1/S1P/S1PR2 axis ameliorates GH‐secreted pituitary adenoma progression

Contemporary Management of Acromegaly: A Practical Approach

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