After RT, we recommend periodic withdrawal of medical therapy for 1 to 3 months (depending on the specific drug) for reassessment of GH and IGF-1 levels. Significant Financial Interest or Leadership Position: none declared. The role of pretreatment echocardiography has not been defined; however, in the setting of suggestive clinical findings, particularly in perioperative patients, a thorough cardiac evaluation may be indicated. Pokrajac A, Wark G, Ellis AR, Wear J, Wieringa GE, Trainer PJ. The risk of cerebrovascular disease in patients with acromegaly is increased after conventional RT (44). . Found inside – Page 183An audit of outcome of treatment in acromegaly. Q J Med 1993;86:293–9. 5. Giustina A, Barkan A, Casanueva FF, et al. Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 2000;85:526–9. 6. Bonadonna S, Doga M, ... Circulating IGF-1 half-life is approximately 15 hours, and serum levels are relatively stable (19), but the presence of IGF-1 binding proteins extends the IGF-1 half-life significantly. Side effects also include occasional local skin irritation and pain at the injection site. RT may even be considered in the setting of an aggressive tumor, including the presence of high Ki-67 staining, although there are no studies that address this (179). 2014 Nov99(11):3933-51. doi: 10.1210/jc.2014-2700. Symptoms of gallbladder obstruction may occur after cessation of the SRL (148). The 2004 guidelines agreed that the gold standard check for acromegaly was an oral glucose tolerance test, with a normal result being a growth hormone level of less than 1 ng/mL. For information on the diagnosis of PCOS, see the section on Diagnosis in the CKS topic on Polycystic ovary syndrome. (1|⊕⊕⊕⊕), 5.2 In a patient with significant disease (ie, with moderate-to-severe signs and symptoms of GH excess and without local mass effects), we suggest use of either a SRL or pegvisomant as the initial adjuvant medical therapy. (1|⊕⊕○○), 7.4 During pregnancy, we suggest serial visual field testing in patients with macroadenomas. Hormones (Athens). Hypertension, coronary heart disease, cardiac failure, cerebrovascular disease. Hypertension occurs in 33–46%, with a predominance of diastolic blood pressure elevation that increases in prevalence with age (44, 55, 56, 58). Schopohl J, Strasburger CJ, Caird D, et al. Technique chosen depends on the expertise and preference of the surgical team and on patient choice. (2|⊕⊕○○), 6.2 We suggest use of stereotactic radiotherapy (SRT) over conventional radiation therapy in patients with acromegaly, unless the technique is not available, there is significant residual tumor burden, or the tumor is too close to the optic chiasm resulting in an exposure of more than 8 Gy. Medical therapy should be considered in the setting of worsening headaches and/or evidence of tumor growth (216). Postoperative imaging should be performed no sooner than 12 weeks after surgery to allow for involution of gel foam and fat packing (127). Capatina C, Wass JA; 60 Years of Neuroendocrinology: Acromegaly. Found insideThis book will take the reader behind the myths of GH and into the real world of clinical endocrinology. The contributions stem from recognized clinicians and scientists who have been working in the field for decades. Grynberg M, Salenave S, Young J, Chanson P. Abu Dabrh AM, Asi N, Farah W, et al. Due to the insidious onset and slow progression, diagnosis is often delayed, particularly in adults, by on average 4-7 years or longer, after the onset of excessive GH secretion, There are several familial causes, including those associated with other endocrine disorders (multiple endocrine neoplasia type 1, McCune-Albright syndrome and Carney complex) or as an isolated disorder, called familial isolated pituitary adenoma (FIPA). Meij BP, Lopes MB, Ellegala DB, Alden TD, Laws ER Jr. Kreutzer J, Vance ML, Lopes MB, Laws ER Jr. Petrossians P, Borges-Martins L, Espinoza C, et al. Additionally, we do not recommend performance of somatostatin receptor scintigraphy or an acute GH response to a sc octreotide injection as a determinant of SRL response because they are not routinely helpful (93, 136). Sleep apnea syndrome is frequent in active acromegaly, with a prevalence of approximately 69%; it is primarily obstructive due to soft tissue thickening and edema of the tongue, pharynx, and upper airways, and less frequently due to a central sleep apnea mechanism (60). Find out about acromegaly, a rare condition where the body produces too much growth hormone causing tissue and bone to grow more quickly. Melmed S, Casanueva FF, Klibanski A, et al. Quality of life (175) and tumor size control (172) may be enhanced. Hyperprolactinemia from tumor cosecretion (73, 85) or stalk effect can contribute to hypogonadism in acromegaly (86). However, if the GH is detectable (ie, >0.4 μg/L), measurement of GH after a glucose load may yield important information. This guideline is cosponsored by the European Society of Endocrinology. We suggest MRI as the imaging modality of choice followed by CT scan when MRI is contraindicated or unavailable. Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. Bangham DR, Gaines Das RE, Schulster D. Karavitaki N, Turner HE, Adams CB, et al. Highly sensitive, such that a normal level usually excludes acromegaly. Freda PU, Nuruzzaman AT, Reyes CM, Sundeen RE, Post KD. Read about symptoms, causes, diagnosis and treatment. Assessment for an underlying cause, Diagnosis, Hirsutism, CKS. . . Melmed S, Casanueva FF, Klibanski A, et al; A consensus on the diagnosis and treatment of acromegaly complications. . Hypertension, cardiovascular disease, diabetes and long duration of symptoms are also poor prognostic factors. False positives for a diagnosis of acromegaly may occur in pregnancy and late-stage adolescence. Ghazi A, Khosla S, Becker K; Acromegaloid facial appearance: case report and literature review. It has been identified as the cause of several historical giants and possibly the source of descriptions of giants in Irish folklore. Caron P, Broussaud S, Bertherat J, et al; Acromegaly and pregnancy: a retrospective multicenter study of 59 pregnancies in 46 women. . In terms of the strength of the recommendation, strong recommendations use the phrase “we recommend” and the number 1, and weak recommendations use the phrase “we suggest” and the number 2. Zada G, Cavallo LM, Esposito F, et al. Acromegaly may be associated with an increased risk of vertebral compression fractures despite normal bone density, and fracture risk may be accelerated by hypogonadism (76). The diseases are discussed in a uniform, easy-to-follow format--a brief description, signs and symptoms, etiology, related disorders, epidemiology, standard treatment, investigational treatment, resources, and references.The book includes a ... Pollock BE, Jacob JT, Brown PD, Nippoldt TB. Therefore, patients with acromegaly with macroadenomas should be monitored clinically for headaches and visual symptoms. However, in the USA, it has recently been estimated to be around 11 per million population per year. (2|⊕⊕⊕○). After treatment, repeat colonoscopy is suggested every 5 years in those found to have a polyp or with persistently elevated IGF-1 and every 10 years in those without a polyp and with normal IGF-1 (67). Thyroid cancer is the most common cancer associated with acromegaly[4]: Because of the increased prevalence of colorectal adenomas and cancer, it is recommended that patients with acromegaly should be offered regular colonoscopy screening, starting at the age of 40 years[5], although screening at diagnosis has also been suggested regardless of age (however, this is controversial). These include: evidence-based approaches to assessing the cause of hyperprolactinemia. Increased mortality rates are reported in patients who have undergone RT in some studies, and the presence of comorbidities including diabetes mellitus and hypertension may contribute as well (38, 51). In one study, the presence of Gilbert syndrome with a UGT1A1*28 genotype was predictive of increased hepatotoxicity caused by pegvisomant (165), although another study did not support this finding (166). Combining medical therapies may improve efficacy, reduce side effects associated with an individual medication, decrease the frequency of injections and total drug dose, and, potentially offer a cost benefit and improved compliance during long-term treatment (172). Adequate replacement of central adrenal, gonadal, and thyroid insufficiency is recommended. . Kopchick JJ, Parkinson C, Stevens EC, Trainer PJ. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. The second review included 31 noncomparative studies. A multidisciplinary approach is critical for the management of acromegaly (3, 4). Published by Frontiers In Endocrinology, 01 January 2017. (1|⊕⊕⊕○), 6.4 We recommend annual hormonal testing of patients following RT for hypopituitarism and other delayed radiation effects. Despite initial efficacy of cabergoline, the response to cabergoline appears to decrease with time. Practice guidelines are presented for diagnosis and treatment of patients with elevated prolactin levels. Buhk JH, Jung S, Psychogios MN, et al. Often an insidious onset and symptoms may precede the diagnosis by several years. A serum GH < 0.14 μg/L suggests “surgical remission,” and a level < 1 μg/L indicates “control” and normalization of the mortality risk (126). FDA on Acromegaly. Sorted by 2011 Jul-Aug. 17(4):636-46. . Growth hormone (GH) stimulates the production of insulin-like growth factor 1 (IGF-1), which is produced in the liver and many other tissues. Ultrasound should be performed if the patient has signs and symptoms of gallstone disease. Pituitary. The prevalence of hypopituitarism with SRT appears similar to that after conventional RT (190–192). Given the variability between GH and IGF-1 assays, it is critical to maintain the use of the same assay in the same patient if possible throughout management (32, 33, 93). Pasireotide is a novel SRL that has enhanced binding to more SSTs and has been shown to normalize IGF-1 in 35% of patients in a phase 3 trial (140). Excessive perspiration and seborrhea occur in up to 80% of subjects (72). GH hypersecretion increases insulin resistance, producing impaired glucose tolerance and diabetes mellitus in 15–38% of patients (44, 55–57). Because of hypertrophic upper airway structures, fiber-optic intubation may be necessary, and careful perioperative airway management is essential (99, 104). Measuring an IGF-1 level is recommended as the initial screen for acromegaly because it is a marker of integrated GH secretion (17). Found insideA consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 2010:3141–3148. Giustina A, Chanson P, Kleinberg D, et al. Expert consensus document: a consensus on the medical treatment of acromegaly. . Higham CE, Atkinson AB, Aylwin S, et al. Melmed S, Cook D, Schopohl J, Goth MI, Lam KS, Marek J. Mercado M, Borges F, Bouterfa H, et al. Found insideMelmed S., Jackson I., Kleinberg D., Klibanski A. Current treatment guidelines for acromegaly. J Clin Endocrinol Metab1998; 83:2646–2652. 9. Ferone D., Colao A., van der Lely AJ., Lamberts S.W.J. Pharmacotherapy or Surgery as Primary ... CDC on Acromegaly. © Egton Medical Information Systems Limited. In less than 5% of cases, excess GHRH secretion from a hypothalamic tumor or a neuroendocrine tumor (usually from lung or pancreas origin) may lead to somatotroph hyperplasia and acromegaly (10). Read about symptoms, causes, diagnosis and treatment. Acromegaly is a chronic, progressive, multi-systemic disease associated with significant morbidity and increased mortality. Although the overall efficacy of SRT may be similar to conventional RT, time to remission may be shorter with SRT (186). Based on these evidence synthesis summaries and the Task Force's own review of the individual studies, an algorithm for integrated multidisciplinary therapeutic approach was developed to aid practitioners in the care of patients with acromegaly (Figure 1). Epub 2010 Jul 21. Cabergoline is most likely to be useful in patients with just modest elevations of GH and IGF-1 levels, with or without concomitant hyperprolactinemia (168). Less common are reversible hair loss and, rarely, alopecia. This handbook in endocrinology and diabetes discusses clinical investigation and management in a convenient way, including both the protocols and explicit clinical information necessary for the management of individual patients. Sherlock M, Aragon Alonso A, Reulen RC, et al. Three controlled prospective studies showed that up to 6 months of preoperative SRLs resulted in improved surgical outcomes in patients with macroadenomas (112–114). Found inside – Page 220Melmed S, Jackson I, Kleinberg D, Klibanski A. Current treatment guidelines for acromegaly. J Clin Endocrinol Metab. 1998;83(8):2646-2652. 8. Swearingen B, Barker FG, Kaznelson L, et al. Long-term mortality after transsphenoidal surgery ... with acromegaly prescribed a somatostatin analogue. Weak recommendations require more careful consideration of the person's circumstances, values, and preferences to determine the best course of action. This suggests that cabergoline may be added to a SRL, particularly if the GH/IGF-1 levels are mildly elevated. . Found inside – Page 1074Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. 8. Grinspoon S, Clemmons D, Swearingen B, et al. Serum insulin-like growth factor-binding protein-3 levels in the diagnosis of ... Thyroid cancer is one of the more commonly detected cancers in acromegaly (69). SRLs may provide headache relief through direct mechanisms beyond those of GH suppression and tumor size reduction (138). Completed forms are available through the Endocrine Society office. | PEG and cabergoline can both be used in addition to a somatostatin analogue if there has been an inadequate response. GH-secreting adenomas with a hypointense T2-weighted MRI signal (45) have been shown to exhibit enhanced SRL responsiveness (46). During long-term follow-up, joint complaints persisted in 77% of those with biochemical remission and negatively impacted quality of life (75). Acromegaly is a chronic disorder caused by GH hypersecretion. Epub 2014 Oct 30. Visceral hypertrophy - eg, heart, thyroid (with a multinodular goitre), liver and spleen. Found inside – Page iiThis text addresses the need for a book specifically aimed at obstetric anesthesia and covers topics such as pulmonary, cardiac renal, hepatic, hematologic, neurologic, endocrine and other diseases. SRT includes a number of modalities, ie, gamma knife, CyberKnife, and a linear accelerator, which all deliver high-energy photons. The commonly held view that tumours that also secrete prolactin have a better response rate to dopamine agonists is not supported. There are two equally effective long-acting available preparations: im octreotide long-acting release (LAR), and deep sc lanreotide depot/autogel (128–131). In the UK, PEG is licensed for the treatment of acromegaly in patients with inadequate response to surgery, radiotherapy or somatostatin analogues. NICE has issued rapid update guidelines in relation to many of these. Biermasz NR, van Dulken H, Roelfsema F. Erfurth EM, Bülow B, Mikoczy Z, Svahn-Tapper G, Hagmar L. Minniti G, Traish D, Ashley S, Gonsalves A, Brada M. Noad R, Narayanan KR, Howlett T, Lincoln NB, Page RC. If there is no size change at 1 year, then yearly imaging is suggested. ACE inhibitors or ARBs) The co-prescription of two (or more) RAS blocking agents (e.g. Despite the use of international reference preparations of GH (30, 31), the commercially available immunoassays produce heterogeneous values, and results from one laboratory cannot be compared with findings from another (32, 33). A meta-analysis of studies has shown that the risk of colonic polyps is increased in acromegaly (65), although the true risk is unknown. Sort by Date. As pegvisomant exhibits a favorable benefit for glycemic control, this medication may be useful when comorbid diabetes mellitus is present with acromegaly (158). . Shlomo Melmed, MD—Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: Novartis, Roche, Pfizer, Ipsen. Type 2 diabetes mellitus (40-52%) and glucose intolerance (28-46%) due to insulin resistance. Ezzat S, Kontogeorgos G, Redelmeier DA, Horvath E, Harris AG, Kovacs K. Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S. Howlett TA, Willis D, Walker G, Wass JA, Trainer PJ. It is important for the clinician to have knowledge of the specific assay used. Fifty percent tumor shrinkage has been found in approximately 59% of subjects after SRL administration and correlates with biochemical response (178). Filopanti M, Barbieri AM, Mantovani G, et al. The prevalence of hypertension, insulin resistance, dyslipidemia, hypertrophic cardiomyopathy, and endothelial dysfunction is increased; however, the prevalence of coronary artery disease in acromegaly is unclear (54). In a patient with persistent disease after surgery, repeat surgery may be useful when the tumor is accessible (ie, not invading the cavernous sinus). Proteinuria high (i.e. Acromegaly causes an overgrowth of all organ systems, bones, joints and soft tissues. an ACE inhibitor and an ARB) should generally be avoided. (2|⊕⊕○○), 4.1 We recommend transsphenoidal surgery as the primary therapy in most patients. . Laurence Katznelson, Edward R. Laws, Jr, Shlomo Melmed, Mark E. Molitch, Mohammad Hassan Murad, Andrea Utz, John A. H. Wass, Acromegaly: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 11, 1 November 2014, Pages 3933–3951, https://doi.org/10.1210/jc.2014-2700. Although lowering GH/IGF-1 improves sleep apnea severity, up to 40% of those with controlled acromegaly have persistent sleep apnea, and initiation or titration of positive airway pressure treatment may be necessary (60–62). Found inside – Page 19ACROMEGALY. First Line Somatostain analogs (3): r Mechanism of action: Inhibit GH secretion r Forms: –Octreotide: Initial ... sleep apnea, colon polyps) should be followed appropriately according to guidelines for these conditions. Biermasz NR, Dekker FW, Pereira AM, et al. (2|⊕⊕○○), 4.3 We suggest against the routine use of preoperative medical therapy to improve biochemical control after surgery. Effectiveness of treatment is based on measurement of serum IGF-1 and GH, which should be measured after 12 weeks just prior to the next dose. Smaller tumors and lower baseline GH and IGF-1 levels are important predictors of response (134, 135). The lanreotide autogel/depot 120-mg dose may be administered in up to 8-week intervals depending on biochemical response (132). American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Acromegaly--2011 update: executive summary.
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