The 11th Acromegaly Consensus Conference in April 2017 was convened to update recommendations on therapeutic outcomes for patients with acromegaly. Consensus guidelines on the medical management of ...acromegaly were last published in 2014; since then, new pharmacological agents have been developed and new approaches to treatment sequencing have been considered. Thirty-seven experts in the management of patients with acromegaly reviewed the current literature and assessed changes in drug approvals, clinical practice standards and clinical opinion. They considered current treatment outcome goals with a focus on the impact of current and emerging somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists on biochemical, clinical, tumour mass and surgical outcomes. The participants discussed factors that would determine pharmacological choices as well as the proposed place of each agent in the guidelines. We present consensus recommendations highlighting how acromegaly management could be optimized in clinical practice.
Non-functioning pituitary adenomas (NFPA) usually present with symptoms of mass effect. Thus, the first-line treatment generally consists of transsphenoidal surgery. Since these tumors are usually ...large and invasive, post-surgical tumor remnants are common. Active surveillance is the follow-up strategy adopted by most pituitary centers, although the prevalence of residual tumor growth may reach 50% in 5–10 years, often leading to repeat surgery, radiation therapy, or both. NFPA remain the only pituitary tumor type for which no medical therapy has been approved. In this debate, we consider the evidence in favor and against using cabergoline to treat progressing NFPA.
Abstract
Objective
The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.
Participants
The ...Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.
Evidence
This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.
Consensus Process
Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.
Conclusions
Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.
Pituitary apoplexy is characterized by sudden increase in pituitary gland volume secondary to ischemia and/or necrosis, usually in a pituitary adenoma. Most cases occur during the 5th decade of life, ...predominantly in males and in previously unknown clinically non-functioning pituitary adenomas. There are some predisposing factors as arterial hypertension, anticoagulant therapy and major surgery. Clinical picture comprises headache, visual impairment, cranial nerve palsies and hypopituitarism. Most cases improve with both surgical and expectant management and the best approach in the acute phase is still controversial. Surgery, usually by transsphenoidal route, is indicated if consciousness and/or vision are impaired, despite glucocorticoid replacement and electrolyte support. Pituitary function is impaired in most patients before apoplexy and ACTH deficiency is common, which makes glucocorticoid replacement needed in most cases. Pituitary deficiencies, once established, usually do not recover, regardless the treatment. Sellar imaging and endocrinological function must be periodic reevaluated.
The SAGIT® instrument (SAGIT) has been developed to enable accurate characterization of acromegaly disease activity.
We evaluated the ability of SAGIT to discriminate acromegaly disease control ...status.
This multicenter, noninterventional, prospective and retrospective, longitudinal study, conducted at academic and private clinical practice sites, included patients aged ≥ 18 years with a diagnosis of controlled (n = 109) or non-controlled (n = 105) acromegaly, assessed by clinical global evaluation of disease control (CGE-DC) questionnaire, investigator therapeutic decision, and international guidelines. Control status was not determined at baseline for 13 patients. Since 9 patients were enrolled retrospectively, all presented analyses are based on the prospective population (N = 227). Patients were assessed over a 2-year follow-up period. Classification and regression tree (CART) analyses were performed to investigate how SAGIT components at baseline (signs/symptoms S, associated comorbidities A, growth hormone levels G, insulin-like growth factor 1 levels I, tumor features T) discriminate between controlled and non-controlled acromegaly.
Baseline mean subscores S, G, I, and T were significantly lower in patients with CGE-DC controlled vs CGE-DC non-controlled acromegaly. SAGIT components I and G for CGE-DC and S, A, G, I, and T for the clinician's therapeutic decision were retained by CART analyses. For international guidelines, only SAGIT component I was retained. The risk for undergoing ≥ 1 treatment change during the study was 3.44 times greater for CGE-DC non-controlled acromegaly relative to CGE-DC controlled acromegaly.
The SAGIT instrument is a valid and sensitive tool to comprehensively and accurately assess acromegaly severity.
Many patients with acromegaly do not achieve biochemical control despite receiving high doses of the first-generation somatostatin analogues octreotide or lanreotide. In the PAOLA trial, we aimed to ...assess the efficacy and safety of two different doses of the somatostatin analogue pasireotide long-acting release compared with active control (octreotide or lanreotide) in patients with inadequately controlled acromegaly.
In a multicentre, randomised, phase 3 trial, we enrolled eligible patients aged 18 years or older with acromegaly who were inadequately controlled (5-point, 2 h mean growth hormone concentration >2·5 μg/L and insulin-like growth factor 1 IGF-1 concentration >1·3 times the upper normal limit) and had received 30 mg octreotide long-acting repeatable or 120 mg lanreotide (Somatuline Autogel; Ipsen, UK) as monotherapy for 6 months or longer. We randomly assigned patients in a 1:1:1 ratio with an interactive voice-web response system to receive 40 mg pasireotide long-acting release once every 28 days for 24 weeks, 60 mg pasireotide long-acting release once every 28 days for 24 weeks, or continued treatment with octreotide or lanreotide (active control). Patients were stratified according to previous treatment (octreotide or lanreotide) and growth hormone concentrations at screening (2·5-10 μg/L and >10 μg/L). Patients and study investigators were not masked to study drug assignment but were masked to pasireotide dose allocation. The primary endpoint was number of patients achieving biochemical control, defined as mean growth hormone concentration less than 2·5 μg/L and normalised IGF-1 concentration. Efficacy analyses were based on intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01137682.
Between Dec 17, 2010, and Aug 6, 2012, 198 patients were enrolled and randomly assigned to pasireotide 40 mg (n=65), pasireotide 60 mg (n=65), or active control (n=68) groups. At 24 weeks, ten (15%) patients in the pasireotide 40 mg group and 13 (20%) patients in the pasireotide 60 mg group achieved biochemical control, compared with no patients in the active control group (absolute difference from control group 15·4%, 95% CI 7·6-26·5, p=0·0006 for pasireotide 40 mg group, 20·0%, 11·1-31·8, p<0·0001 for pasireotide 60 mg group). The most common adverse events were hyperglycaemia (21 33% for treatment with 40 mg pasireotide, 19 31% with 60 mg pasireotide, and nine 14% with active control), diabetes (13 21%, 16 26%, and five 8%), and diarrhoea (ten 16%, 12 19%, and three 5%); most were grade 1 or 2 in severity. Serious adverse events were reported in six (10%) patients in the pasireotide 40 mg group, two (3%) in the pasireotide 60 mg group, and three (5%) in the active control group.
Pasireotide provides superior efficacy compared with continued treatment with octreotide or lanreotide, and could become the new standard pituitary-directed treatment in patients with acromegaly who are inadequately controlled using first-generation somatostatin analogues.
Novartis Pharma AG. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation.
Prolactinomas Glezer, Andrea; Bronstein, Marcello D
Endocrinology and metabolism clinics of North America,
03/2015, Letnik:
44, Številka:
1
Journal Article
Recenzirano
Identifying the correct cause of hyperprolactinemia is crucial for treatment. Prolactinoma is the most common pathologic cause of hyperprolactinemia. Dopamine agonists are efficacious in about 80% to ...90% of patients with prolactinoma, leading to reduction of serum prolactin levels and tumor dimensions. Neurosurgery, mainly by the transsphenoidal route, is indicated in cases of intolerant and resistant dopamine agonists. Radiotherapy is rarely used because of its side effects and low efficacy. The alkylating agent temozolomide showed efficacy for treatment of aggressive and resistant prolactinomas. Other approaches, such as thyrosine kinase inhibitors, are currently being tested and could be an additional tool for these troublesome tumors.
Hyperprolactinemia can be caused by several conditions and its effects on the hypothalamic-pituitary-gonadal axis are understood in more detail. Nevertheless, in recent decades, other metabolic ...effects have been studied and data pointed to a potential increased cardiovascular disease (CVD) risk. A recent study showed a decrease in total and LDL- cholesterol only in men with prolactinoma treated with dopamine agonists (DA) supporting the previous results of a population study with increased CVD risk in men harboring prolactinoma. However, other population studies did not find a correlation between prolactin (PRL) levels and CVD risk or mortality. There is also data pointing to an increase in high-density lipoprotein levels, and decreases in triglycerides, carotid-intima-media thickness, C-reactive protein, and homocysteine levels in patients with prolactinoma on DA treatment. PRL was also implicated in endothelial dysfunction in pre and postmenopausal women. Withdrawal of DA resulted in negative changes in vascular parameters and an increase in plasma fibrinogen. It has been shown that PRL levels were positively correlated with blood pressure and inversely correlated with dilatation of the brachial artery and insulin sensitivity, increased homocysteine levels, and elevated D-dimer levels. Regarding possible mechanisms for the association between hyperprolactinemia and CVD risk, they include a possible direct effect of PRL, hypogonadism, and even effects of DA treatment, independently of changes in PRL levels. In conclusion, hyperprolactinemia seems to be associated with impaired endothelial function and DA treatment could improve CVD risk. More studies evaluating CVD risk in hyperprolactinemic patients are important to define a potential indication of treatment beyond hypogonadism.
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