Resistance to drug treatment of acromegaly and ways to overcome it

Golounina, Olga; Dzeranova, Larisa; Pigarova, Ekaterina; Belaya, Zh E

doi:10.14341/omet12710

Cited by 5 publications

(1 citation statement)

References 107 publications

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“…Индекс пролиферации Ki-67 является прогностическим маркером эффективности лечения акромегалии, однако оценку данного показателя можно провести только после хирургического вмешательства. Полиморфизмы гена ИФР-1 и рецептора гормона роста относятся к генетическим предикторам эффективности оперативного лечения [ 3 ][ 4 ].…”

Section: обоснованиеunclassified

Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly

Lutsenko

Belaya

Przhiyalkovskaya

et al. 2022

Probl Endokrinol (Mosk)

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BACKGROUND. Neurosurgery is the most effective treatment for acromegaly. As most of the patients present with macroadenomas, surgical treatment is not always successful, even with the expert level of a neurosurgeon. Assessment of the postoperative remission rates in acromegaly preoperative predictors of treatment efficacy is an urgent task of modern research. AIM: To assess the short-term and long-term remission of acromegaly after endoscopic transnasal adenomectomy in a tertiary medical center and assess preoperative predictors of the treatment effectiveness.MATERIALS AND METHODS: A single-center, prospective, uncontrolled study was conducted. We included patients with active acromegaly who did not receive medical therapy with somatostatin analogues and were referred for endoscopic transsphenoidal adenomectomy. Plasma miRNA expression was assessed by quantitative reverse transcription PCR. Postoperative samples of adenomas were sent for study, with the determination of the immunohistochemical staining for somatostatin receptors 2 and 5 subtypes and morphology was performed on postoperative adenoma samples.RESULTS: The study included 44 patients: 32.8% men, median age 47.0 [34.0; 55.0], IGF-1 744.75 ng/ml [548.83;889.85], growth hormone 9.5 ng/ml [4.94; 17.07]. Tumor volume 832 mm3 [419.25; 2532.38]. Early postoperative remission was achieved in 35 patients (79.5%). Patients who achieved short-term remission had higher IGF-1 and basal growth hormone levels. Median follow-up was 19.0 months [12.5;29.0]. Long-term remission was achieved in 61.4% (27 patients), no remission in 9 (20.5%), recurrency in 2 patients (4.5%), 6 patients were to follow-up (13.6%). In patients with long-term remission, we observed lower growth hormone and IGF-1 levels. No differences in miRNA expression was observesd. The predictive value of basal GH before surgery for long-term remission was assessed: area under the curve 0.811 (95% CI: 0.649; 0.973). A cut-off value of 15.55 ng/mL corresponded to a sensitivity of 70.0% (34.8%; 93.3%), a specificity of 85.7% (67.3%; 96.0%), an accuracy of 81.6% (65 .7%; 92.3%), PPV 63.6% (39.3%; 82.5%), NPV 88.9% (75.4%; 95.4%).CONCLUSION: Rates of short-term and long-term remission after endoscopic transsphenoidal adenomectomy in our cohort is 79,5% и 61,4%, respectively, and is comparable with literature data for expert pituitary centers. Preoperative GH shows potential value in predicting the long-term remission of acromegaly, but further studies in a larger sample are needed to obtain more accurate cut-off values.

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Section: обоснованиеunclassified

Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly

Lutsenko

Belaya

Przhiyalkovskaya

et al. 2022

Probl Endokrinol (Mosk)

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Guidelines on diagnostics and treatment of acromegaly (draft)

Przhiyalkovskaya,

Mokrysheva,

Troshina

et al. 2024

Obes. metabol.

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We recommend acromegaly to be ruled in all patients with characteristic changes in appearance (A3). In all patients without characteristic changes in appearance, we recommend to rule out acromegaly, if several clinical signs suspicious for acromegaly are present (B3). We recommend acromegaly to be ruled out in all patients with pituitary adenoma (B3). We recommend to rule out acromegaly in all patients with prolactin-secreting adenomas (C4). For laboratory confirmation of acromegaly, we recommend to measure serum insulin-like growth factor-1 (IGF-1, somatomedin C) level (A3). In patients without obvious clinical signs of acromegaly and/or with a moderate increase in IGF-1 levels (IGF-1 index less than 1.3), we recommend to assess the response of somatotropic hormone (GH) to hyperglycemia (GH during an oral glucose tolerance test) (B3). In all patients with biochemically confirmed acromegaly, magnetic resonance imaging of the pituitary gland with intravenous contrast is recommended to assess pituitary adenoma size, location and growth pattern (A3). We recommend to measure blood glucose and glycated hemoglobin in all patients with confirmed acromegaly (B3). We recommend to measure serum prolactin levels in all patients with acromegaly (B3).In all patients with acromegaly and pituitary adenoma, transnasal transsphenoidal adenomectomy is recommended as first-line treatment if the patient’s consent is given and there are no contraindications (A1). For all patients with acromegaly for whom neurosurgical treatment is indicated, surgical intervention is recommended in medical centers, specializing in pituitary diseases, by neurosurgeons who perform at least 50 such operations per year (A3). We recommend that morphological and immunohistochemical examination of the removed pituitary adenoma is performed in all patients with acromegaly (A3). We do not recommend routine medical therapy for acromegaly before surgery as a mean to reduce tumor size (B2).For patients with acromegaly in whom neurosurgical treatment is not indicated or ineffective or while patient awaiting for the effect of radiation therapy, we recommend medical therapy (A1). Long-acting first-generation somatostatin analogues are recommended as first-line drug therapy for acromegaly. In case of partial/complete resistance to or intolerance to somatostatin analogs, pegvisomant is recommended as a second-line medical therapy for acromegaly (A1). We recommend starting pegvisomant from a single dose of 40–80 mg per day subcutaneously, then continue injections at a starting dose of 10 or 15 mg per day with IGF-1 monitoring after 4–6 weeks and dose adjustment if necessary (B2). In patients with acromegaly and a moderate increase in IGF-1 levels, we recommend to initiate cabergoline as medical monotherapy or, if somatostatin analogs are ineffective, in combination with them (B2).In patients with acromegaly, if the disease remains active after surgical treatment, if drug treatment is unavailable, intolerable or ineffective, and repeated neurosurgical intervention is inappropriate, it is we recommend radiation therapy (A1). A multidisciplinary approach is recommended in the management of acromegaly complications (C3).

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Clinical characteristics and efficacy of acromegaly treatment in the Udmurt Republic

Nurullina

Ахмадуллина

Maslova

et al. 2022

Almanac of Clinical Medicine

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Background: Acromegaly is a severe neuroendocrine disorder caused by chronic overproduction of growth hormone and insulin-like growth factor 1 and associated with a variety of clinical manifestations, debilitating complications and progressive disability, if no biochemical control has been achieved. The Russian registry of hypothalamic-pituitary tumors allows for evaluation of the epidemiological, demographic and clinical characteristics of patients with acromegaly, as well as of the effectiveness of various treatment methods. Aim: To identify epidemiological and clinical characteristics and treatment efficacy for acromegaly in the patients in the Udmurt Republic. Materials and methods: We performed a cross-sectional study based on the registry of hypothalamic-pituitary tumors of the Udmurt Republic as per June 2022. It contains data from 77 patients with acromegaly. The study included 59 (76.62%) patients with the information sufficient for evaluation of the disease stage and its complications. Results: According to the registry of hypothalamic-pituitary tumors, the prevalence of acromegaly in the Udmurt Republic was 6.71 cases per 100,000 of the population. Patients with acromegaly in Udmurt Republic had a high prevalence of arthralgia, abnormally large feet and hands, weakness/fatigue, snoring / sleep apnea, increased sweating, dizziness, peripheral edema, obesity, menstrual cycle abnormalities, diabetes mellitus, nodular goiter, pathological fractures and hypopituitarism. Neurosurgery has been performed in 74.57% (n = 44) of the patients, with a remission of acromegaly achieved in 18 (40.9%). Medical treatment was given to 25/59 (42.37%) of the patients, with 22 of them being treated with 1st generation long-acting somatostatin analogues. Radiation therapy has been administered to 13 patients (22.03%). Biochemical control was achieved in 40/59 (67.8%) of patients with acromegaly, related to neurosurgery in most patients, as well as to the use of a growth hormone receptor antagonist and/or combined medical treatment. Conclusion: The prevalence of acromegaly in the Udmurt Republic is consistent with international data. Clinical characteristics of acromegaly generally correspond to the classic disease course, although a number of symptoms are more commonly found in the Udmurt Republic patients than in the Russian Federation registry; this might be related to the quality of the registry management. The effectiveness of treatment for acromegaly in Udmurt Republic is comparable to the international data.

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Resistance to drug treatment of acromegaly and ways to overcome it

Cited by 5 publications

References 107 publications

Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly

Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly

Guidelines on diagnostics and treatment of acromegaly (draft)

Clinical characteristics and efficacy of acromegaly treatment in the Udmurt Republic

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