First-generation somatostatin receptors ligands (SRL) are the mainstay in the medical treatment of acromegaly, however the percentage of patients controlled with these drugs significantly varies in ...the different studies. Many factors are involved in the resistance to SRL. In this review, we update the physiology of somatostatin and its receptors (sst), the use of SRL in the treatment of acromegaly and the factors involved in the response to these drugs. The SRL act through interaction with the sst, which up to now have been characterized as five subtypes. The first-generation SRL, octreotide and lanreotide, are considered sst2 specific and have biochemical response rates varying from 20 to 70%. Tumor volume reduction can be found in 36–75% of patients. Several factors may determine the response to these drugs, such as sst, AIP, E-cadherin, ZAC1, filamin A and β-arrestin expression in the somatotropinomas. In patients resistant to first-generation SRL, alternative medical treatment options include: SRL high dose regimens, SRL in combination with cabergoline or pegvisomant, or the use of pasireotide. Pasireotide is a next-generation SRL with a broader pattern of interaction with sst. In the light of the recent increase of treatment options in acromegaly and the deeper knowledge of the determinants of response to the current first-line therapy, a shift from a trial-and-error treatment to a personalized one could be possible.
Prolactinomas are the most common pituitary tumors and pathological hyperprolactinemia. Therefore, women harboring prolactinomas frequently present infertility due to the gonadal axis impairment. The ...gold-standard treatment is dopamine agonist (DA) which can reverse hyperprolactinemia and hypogonadism, and promote tumor shrinkage in the majority of cases. Therefore, reports of pregnancy in such cohort become more common. In this scenario, bromocriptine is still the DA of choice due to its shorter half-life and larger experience as compared to cabergoline. In DA resistant cases, transsphenoidal pituitary surgery is indicated. However, potential risks of DA-induced pregnancies include fetal exposition and symptomatic tumor growth. Dopamine agonist should be discontinued as soon as pregnancy is confirmed in microprolactinomas and intrasellar macroprolactinomas (MAC). Concerning expansive/invasive MAC, DA maintenance should be considered. Periodically clinical evaluation should be performed during pregnancy, being sellar imaging indicated if tumor symptomatic growth is suspected. In such cases, if DA treatment fails, neurosurgery is indicated.
Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more ...than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.
Objective In the Phase III PAOLA study (clinicaltrials.gov: NCT01137682), enrolled patients had uncontrolled acromegaly despite ≥6 months of octreotide/lanreotide treatment before study start. More ...patients achieved biochemical control with long-acting pasireotide versus continued treatment with octreotide/lanreotide (active control) at month 6. The current work assessed the extent of comorbidities at baseline and outcomes during a long-term extension. Design/methods Patients receiving pasireotide 40 or 60 mg at core study end could continue on the same dose in an extension phase if biochemically controlled or receive pasireotide 60 mg if uncontrolled. Uncontrolled patients on active control were switched to pasireotide 40 mg, with the dose increased at week 16 of the extension if still uncontrolled (crossover group). Efficacy and safety are reported to 304 weeks (~5.8 years) for patients randomized to pasireotide (core + extension), and 268 weeks for patients in the crossover group (extension only). Results Almost half (49.5%; 98/198) of patients had ≥3 comorbidities at core baseline. During the extension, 173 patients received pasireotide. Pasireotide effectively and consistently reduced GH and IGF-I levels for up to 5.8 years’ treatment; 37.0% of patients achieved GH <1.0 µg/L and normal IGF-I at some point during the core or extension. Improvements were observed in key symptoms. The long-term safety profile was similar to that in the core study; 23/173 patients discontinued treatment because of adverse events. Conclusions In this patient population with a high burden of comorbid illness, pasireotide was well tolerated and efficacious, providing prolonged maintenance of biochemical control and improving symptoms.
In March 2013, the Acromegaly Consensus Group met to revise and update guidelines for the medical treatment of acromegaly. The meeting comprised experts skilled in the medical management of ...acromegaly. The group considered treatment goals covering biochemical, clinical and tumour volume outcomes, and the place in guidelines of somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists, and alternative modalities for treatment including combination therapy and novel treatments. This document represents the conclusions of the workshop consensus.
Multidisciplinary management of acromegaly: A consensus Giustina, Andrea; Barkhoudarian, Garni; Beckers, Albert ...
Reviews in endocrine & metabolic disorders,
12/2020, Letnik:
21, Številka:
4
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal ...approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.
Background:
A novel oral octreotide formulation was tested for efficacy and safety in a phase III, multicenter, open-label, dose-titration, baseline-controlled study in patients with acromegaly.
...Methods:
We enrolled 155 complete or partially controlled patients (IGF-1 <1.3 × upper limit of normal ULN, and 2-h integrated GH <2.5 ng/mL) receiving injectable somatostatin receptor ligand (SRL) for ≥3 months. Subjects were switched to 40 mg/d oral octreotide capsules (OOCs), and the dose escalated to 60 and then up to 80 mg/d to control IGF-1. Subsequent fixed doses were maintained for a 7-month core treatment, followed by a voluntary 6-month extension.
Results:
Of 151 evaluable subjects initiating OOCs, 65% maintained response and achieved the primary endpoint of IGF-1 <1.3 × ULN and mean integrated GH <2.5 ng/mL at the end of the core treatment period and 62% at the end of treatment (up to 13 mo). The effect was durable, and 85 % of subjects initially controlled on OOCs maintained this response up to 13 months. When controlled on OOCs, GH levels were reduced compared to baseline, and acromegaly-related symptoms improved. Of 102 subjects completing the core treatment, 86% elected to enroll in the 6-month extension. Twenty-six subjects who were considered treatment failures (IGF-1 ≥1.3 × ULN) terminated early, and 23 withdrew for adverse events, consistent with those known for octreotide or disease related.
Conclusions:
OOC, an oral therapeutic peptide, achieves efficacy in controlling IGF-1 and GH after switching from injectable SRLs for up to 13 months, with a safety profile consistent with approved SRLs. OOC appears to be effective and safe as an acromegaly monotherapy.
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