scholarly journals Medical Therapy of Acromegaly

2012 ◽  
Vol 2012 ◽  
pp. 1-22 ◽  
Author(s):  
U. Plöckinger

This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs—somatostatin receptor ligands (SRLs), dopamine agonists, and the GH antagonist Pegvisomant—is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included. Special emphasis is given to the difficulties to define remission criteria of acromegaly due to technical assay problems. An algorithm for medical therapy in acromegaly is provided.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Elena V Varlamov ◽  
José Miguel Hinojosa-Amaya ◽  
Dawn Lim Shao Ting ◽  
Maria Fleseriu ◽  
Joao Prola

Abstract Background MRI T2 hypointensity of growth hormone (GH) secreting pituitary adenomas (PA) has been associated with better biochemical response to somatostatin receptor ligands and has been suggested to be useful in selecting patients with expected favorable response for pre- and post-surgery medical therapy. However, in most imaging centers, T2 intensity measurement is not part of standard neuroradiologist (NR) reporting. Objective To assess whether endocrinologists (Es) can reliably measure PA T2 signal intensity by calculating inter-rater reliability between Es and NR. Methods Retrospective review of MRI in 20 patients with pituitary somatotroph macroadenoma randomly selected from an IRB-approved PA database who had preoperative MRI available. T2 MRI intensity of the solid portion of the PA was compared to the temporal gray matter (GM) and white matter (WM): hypo- (PA< WM), hyper- (PA> GM), and isointense (WM <PA <GM). Measurements were performed separately by a NR and by two Es trained to take measurements by the same NR. Statistics: SPSS 25; Cohen kappa (κ). Results Patient mean age was 47 ± 20 years, with 12 females; mean largest PA diameter was 22.6 mm (range 11-45 mm). NR measured 12 hyper-, 7 iso- and 1 hypo-intense PA. Agreement was moderate between NR and E#1 (κ 0.72, 95%CI 0.751-1.0, p<0.001) and NR and E#2 (κ 0.638, 95%CI 0.351-0976, p<0.001) and strong between E#1 and E#2 (κ=0.90, 95%CI 0.309-0.903, p=0.001). Hypointense PA (by NR) was read by both Es as isointense. One hyperintense PA (by NR) was read by both Es as isointense. One isointense PA was read by E#2 as hypointense. Overall adenomas were; 9 densely granulated GH, 5 sparsely granulated GH, 3 mixed GH and prolactin, 1 plurihormonal, 1 not classified, and 1 no surgical intervention. Discussion Inter-rater reliability between the 2 Es was strong, however, it was moderate between each E and the NR. Factors that likely contributed to difference in measurement are heterogeneity of the PA, MRI quality, selection bias in choosing “most appropriate” site to measure intensity of adenoma, gray and white matter. Es could be trained to interpret the T2 intensity, although reliability with NR is only moderate. Interestingly, in this sample majority of T2 PA were hyperintense, but densely granulated, suggesting that preoperative identification of densely granulated tumors, which are also predictive of favorable SRL response, might be limited. More studies are needed to assess T2 correlation with pathology. Conclusion As T2 intensity (hyper-, hypo- or iso-) on MRI might be predictive of biochemical response to medical therapy in some patients with PA, we recommend T2 intensity to be part of neuroradiology reporting protocol. Our pilot study showed that endocrinologists could read MRIs after adequate training, but there is only moderate correlation with neuroradiologists.


2011 ◽  
Vol 152 (18) ◽  
pp. 715-721 ◽  
Author(s):  
Orsolya Nemes ◽  
Emese Mezősi

Acromegaly is a rare disease with typical clinical manifestations. Untreated acromegaly carries a 2-4-fold increase in mortality in long-term outcome. The goal of treatment is double, including biochemical control of the disease (normalization of serum IGF1 levels compared to age and gender matched controls, GH levels below 1 ng/ml after oral glucose load, or random GH below 2.5 ng/ml) and control of the tumor mass. The therapeutic modalities currently available for the treatment of acromegaly are: surgery, medical therapy, radiation therapy and their combinations. The cornerstones of medical therapy in acromegaly are the somatostatin receptor ligands due to their effectiveness in controlling GH excess in 60-70 % of patients and their beneficial effects on tumor volume. Somatostatin analogues have an established role as adjuvant therapy after non-curative surgery, and evidence suggests their use as primary treatment for selected patients. The long-term use of somatostatin receptor ligands is safe and they are well tolerated. Future medical therapy consists of pasireotide, a novel, universal somatostatin receptor agonist, and a new class of drugs named dopastatins. The latter so-called chimeric molecules have strong affinity for somatostatin receptors and dopamine-2 receptors, resulting in a more effective blocking of GH secretion, according to preliminary data. The authors of this paper review the current medical therapy of acromegaly, focusing on the role of somatostatin receptor ligands. Orv. Hetil., 2011, 152, 715–721.


2020 ◽  
Vol 182 (6) ◽  
pp. D17-D29 ◽  
Author(s):  
Aart J van der Lely ◽  
Emmanuelle Kuhn ◽  
Ammar Muhammad ◽  
Eva C Coopmans ◽  
Sebastian J Neggers ◽  
...  

Current guidelines recommend the use of long-acting somatostatin receptor ligands (SRLs) first when surgery fails to correct GH/IGF-I hypersecretion in patients with acromegaly. In this issue of the journal, a pro- and contra debate will outline which arguments are in favour and which are against positioning pegvisomant (PEGV), a GH receptor antagonist, as the first-line treatment modality of acromegaly. The task of the pros was to promote a paradigm shift towards repositioning PEGV as first-line treatment as PEGV is safe and more effective than the first- and second-generation of SRLs. SRLs, when prescribed together with PEGV can still reduce tumour size when necessary, while they decrease the necessary dose of PEGV by around 50% in the average patient. They conclude that PEGV must move up towards the first-line treatment. For the cons, SRLs remain the first-line medical treatment. Indeed, even if, in recent studies, the remission rate is lower than initially claimed, SRLs are still effective not only for normalizing GH/IGF-I levels in half of the patients but also for inducing tumour shrinkage, improving comorbidities and headaches and reversing excess mortality. They are more convenient for use with their monthly administration and have a remarkable safety profile as demonstrated by the very prolonged experience acquired by more than 30 years of use. Finally, the cost-effectiveness of first-generation SRLs is better than that of PEGV. For all these reasons, cons consider that SRLs remain the best first medical treatment in patients requiring medical therapy.


2004 ◽  
Vol 1 (2) ◽  
pp. 121-125 ◽  
Author(s):  
Alexander Pasternak ◽  
Yanping Pan ◽  
Ralph Mosley ◽  
Susan Rohrer ◽  
Elizabeth Birzin ◽  
...  

2021 ◽  
Author(s):  
Naia Grandgeorge ◽  
Giovanni Barchetti ◽  
Solange Grunenwald ◽  
Fabrice Bonneville ◽  
Philippe Caron

2021 ◽  
Vol 12 ◽  
Author(s):  
Odelia Cooper ◽  
Vivien Bonert ◽  
Ning-Ai Liu ◽  
Adam N. Mamelak

Management of aggressive pituitary adenomas is challenging due to a paucity of rigorous evidence supporting available treatment approaches. Recent guidelines emphasize the need to maximize standard therapies as well as the use of temozolomide and radiation therapy to treat disease recurrence. However, often these adenomas continue to progress over time, necessitating the use of additional targeted therapies which also impact quality of life and long-term outcomes. In this review, we present 9 cases of aggressive pituitary adenomas to illustrate the importance of a multidisciplinary, individualized approach. The timing and rationale for surgery, radiation therapy, temozolomide, somatostatin receptor ligands, and EGFR, VEGF, and mTOR inhibitors in each case are discussed within the context of evidence-based guidelines and clarify strategies for implementing an individualized approach in the management of these difficult-to-treat-adenomas.


2020 ◽  
Author(s):  
Joan Gil ◽  
Montserrat Marqués‐Pamies ◽  
Mireia Jordà ◽  
Carmen Fajardo‐Montañana ◽  
Araceli García‐Martínez ◽  
...  

2020 ◽  
Vol 105 (10) ◽  
pp. e3785-e3797 ◽  
Author(s):  
Susan L Samson ◽  
Lisa B Nachtigall ◽  
Maria Fleseriu ◽  
Murray B Gordon ◽  
Marek Bolanowski ◽  
...  

Abstract Purpose The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs). Methods In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 [IGF-1] ≤ 1.0 × upper limit of normal [ULN]; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures. Results Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (< 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 > 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P < .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience. Conclusions OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.


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