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1.  Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients 
Pituitary  2011;14(3):253-258.
The efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the individual beneficial and adverse effects, in two acromegaly patients, who only normalized their insulin like growth factor (IGF-I) levels with high-dose pegvisomant therapy. We present two cases of a 31 and 44 years old male with gigantism and acromegaly that were controlled subsequently by surgery, radiotherapy, SRIF analogs and daily PEG-V treatment. They were converted to combined treatment of monthly SSA and (twice) weekly PEG-V. High dose SSA treatment was added while the PEG-V dose was decreased during carful monitoring of the IGF-I. After switching from PEG-V monotherapy to SRIF analogs plus pegvisomant combination therapy IGF-I remained normal. However, the necessary PEG-V dose, to normalize IGF-I differed significantly between these two patients. One patient needed twice weekly 100 mg, the second needed 60 mg once weekly on top of their monthly lanreotide Autosolution injections of 120 mg. The weekly dose reduction was 80 and 150 mg. After the introducing of lanreotide, fasting glucose and glycosylated haemoglobin concentrations increased. Diabetic medication had to be introduced or increased. No changes in liver tests or in pituitary adenoma size were observed. In these two patients, PEG-V in combination with long-acting SRIF analogs was as effective as PEG-V monotherapy in normalizing IGF-I levels, although significant dose-reductions in PEG-V could be achieved. However, there seems to be a wide variation in the reduction of PEG-V dose, which can be obtained after conversion to combined treatment.
PMCID: PMC3146981  PMID: 21221818
Pituitary tumor; Acromegaly; Acromegaly treatment; Pegvisomant; Combined treatment; Somatostatin analogs
2.  Nanomedicines in the treatment of acromegaly: focus on pegvisomant 
This article examines the role of pegvisomant in the treatment of acromegaly. This syndrome, caused by excessive growth hormone (GH) secretion by a pituitary adenoma, is associated with a doubled mortality rate and poor quality of life. Pituitary microsurgery has long been the first choice of treatment since it cures many patients, especially those with localized tumors. Adjuvant irradiation was given if insulin-like growth factor-I (IGF-I) or GH did not normalize. The introduction of long-acting slow- release somatostatin analogs was a breakthrough for adjuvant treatment, although not always effective. Rather, targeting excessive GH production, muting the GH signal at its receptor, was a totally different approach. The development of GH antagonists (by mutation of glycine at position 120) and other modifications to enhance receptor binding, and subsequent pegylation of the molecule led to the development of B2036. After pegylation of B2036 at 5 positions the distribution volume is restricted and its serum half-life considerably increased. In short-term clinical studies performed in selected, mostly pretreated, acromegalic patients, IGF-I normalized in the majority of cases. Combination therapy with long-acting somatostatin analogs and weekly rather than daily pegvisomant injections appears to be successful in one clinical study and might limit the high cost of pegvisomant. Long-term efficacy and safety has to be demonstrated. The drug does not cross the blood–brain barrier, and whether it distributes freely into the extracellular space of other organs than the liver has not been investigated, which might have implications for persistent local IGF-I production under unrestrained GH concentrations.
PMCID: PMC2676637  PMID: 17722273
pegvisomant; Somavert; receptor antagonist; growth hormone; insulin-like growth factor-I; treatment
3.  Acromegaly: Beyond surgery 
Acromegaly is characterized by chronic, excess secretion of growth hormone (GH) from a pituitary adenoma, and elevated hepatic insulin-like growth factor 1 (IGF-1) levels. Significant progress has been made in the development of medical therapies to achieve biochemical and symptomatic control in acromegaly. In this review we discuss the three currently available medical therapies, which include somatostatin analogs, dopamine agonists and pegvisomant. We describe a step-wise approach in which a somatostatin analog is followed by the addition of a dopamine agonist, and then if required the addition of or replacement by pegvisomant. New somatostatin agonists such as pasireotide, and the introduction of new orally-acting somatostatin agonists, should increase the therapeutic choices available in the near future.
PMCID: PMC3743354  PMID: 23961470
Acromegaly; cabergoline; lanreotide; medical therapy; octreotide; pasireotide; pegvisomant; somatostatin analogs
4.  The endocrine tumor summit 2008: appraising therapeutic approaches for acromegaly and carcinoid syndrome 
Pituitary  2009;13(3):266-286.
The Endocrine Tumor Summit convened in December 2008 to address 6 statements prepared by panel members that reflect important questions in the treatment of acromegaly and carcinoid syndrome. Data pertinent to each of the statements were identified through review of pertinent literature by one of the 9-member panel, enabling a critical evaluation of the statements and the evidence supporting or refuting them. Three statements addressed the validity of serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations as indicators or predictors of disease in acromegaly. Statements regarding the effects of preoperative somatostatin analog use on pituitary surgical outcomes, their effects on hormone and symptom control in carcinoid syndrome, and the efficacy of extended dosing intervals were reviewed. Panel opinions, based on the level of available scientific evidence, were polled. Finally, their views were compared with those of surveyed community-based endocrinologists and neurosurgeons.
PMCID: PMC2913001  PMID: 20012914
Acromegaly; Carcinoid syndrome; Neuroendocrine tumor; NET; Somatostatin analogs; Somatostatin analogues; Lanreotide; Octreotide; Insulin-like growth factor-I; IGF-I; Growth hormone; GH
5.  A practical approach to acromegaly management in Latin America 
Pituitary  2013;17:30-35.
Evidence-based treatment guidelines have undoubtedly advanced medical practice and supported optimal management of acromegaly, but their application may be hampered by limited access to the latest treatment options.
In this retrospective, narrative review, the authors revisited existing treatment guidelines for acromegaly in Latin America. These were considered in conjunction with published evidence chosen at the authors’ discretion.
In a socially and economically diverse region, such as Latin America, any regional practice guidelines need to appreciate that recommended treatment options, such as surgery by expert pituitary surgical teams and drug therapies, especially somatostatin analogs, are often not available due to limited resources. In these instances, physicians may be obliged to apply less effective therapeutic options.
The current article looks at the practical aspects of acromegaly management in Latin America and discusses this in the context of existing guidelines. Furthermore, we consider potential strategies to make better use of resources through combination and multimodal approaches to treatment.
PMCID: PMC3906557  PMID: 23334809
Acromegaly; Latin America; Somatostatin analogs; Dopamine agonists; Pegvisomant; Guidelines
6.  Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006; Acromegaly remains under-recognized and under-diagnosed 
Clinical endocrinology  2009;72(2):203-208.
Traditionally, acromegaly evaded diagnosis until in its clinically obvious later stages when treatment is more difficult. Over the last 25 years diagnostic tests have improved, but whether clinical disease detection also improved was unknown so we tested if disease severity at diagnosis had changed from 1981 to 2006.
Data on 324 consecutive acromegaly patients presenting from 1981–2006 at two New York City hospitals were collected by retrospective review (n=324) and by interview (n=200). The main complaint, acromegaly-associated co-morbidities, signs, symptoms, healthcare providers visited, pre-operative growth hormone (GH) and insulin-like growth factor I (IGF-I) levels and pituitary tumor size at diagnosis were compared in patients presenting in the earlier vs. later halves of the time period.
Times from symptom onset to diagnosis were 5.9 yr. (early) vs. 5.2 yr. (late)(p=ns). At diagnosis, 96% of early and late groups had facial feature changes and/or hand/foot enlargement. Co-morbidities included hypertension (HTN) 37 % (early) vs. 36% (late), carpal tunnel syndrome (24 vs. 24%), sleep apnea (13 vs. 29%)(p <0.01), osteoarthritis (25 vs. 23%), and diabetes mellitus (DM) (18 vs.15%); each patient had 1.2 (early) vs. 1.3 (late) (p=0.53) co-morbidities. Groups were similar in signs, symptoms, tumor size, GH and IGF-I.
Clinical, biochemical and tumor size characteristics at diagnosis of acromegaly patients were unchanged from 1981–2006. Most patients still have marked manifestations of acromegaly at diagnosis suggesting that acromegaly remains clinically under-recognized. Healthcare professionals should more commonly consider acromegaly, which can lead to earlier diagnosis and better treatment outcome.
PMCID: PMC2866138  PMID: 19473180
Acromegaly; pituitary tumor; growth hormone; insulin-like growth factor 1
7.  Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: a literature review 
Pituitary  2010;14-14(2):184-193.
Acromegaly is a rare disease with a multifaceted clinical presentation. In 90–95% of patients with acromegaly, the disease is caused by a growth hormone (GH)-secreting pituitary adenoma with elevated GH levels that ultimately induce excessive hepatic secretion of insulin-like growth factor-1 (IGF-1). Somatostatin receptor ligands (SRLs) are considered the standard medical choice for the treatment of acromegaly, and normalization of GH and IGF-1 is attainable with effective therapy. This review aims to summarize the literature relative to SRL dose escalation therapy in patients with acromegaly. A United States National Library of Medicine PubMed search of SRL’s was conducted using the following search terms: ((((LAR) OR ATG) OR octreotide) OR lanreotide Autogel) AND acromegaly. Related articles in non peer-reviewed journals were excluded. The rationale and benefits of SRL dose optimization therapy were investigated with emphasis on describing the clinical recognition, treatment, and management of patients with acromegaly. We found that dose escalation could provide additional biochemical control of acromegaly in patients who are inadequately controlled with conventional starting doses of octreotide LAR and lanreotide Autogel®. Furthermore, patients should routinely have their GH and IGF-1 levels closely monitored and their SRL dose increased or decreased thereafter according to individual response.
PMCID: PMC3094533  PMID: 21161602
Octreotide LAR; Lanreotide Autogel®; Dose optimization; Acromegaly
8.  Management of acromegaly in Latin America: expert panel recommendations 
Pituitary  2009;13(2):168-175.
Although there are international guidelines orienting physicians on how to manage patients with acromegaly, such guidelines should be adapted for use in distinct regions of the world. A panel of neuroendocrinologists convened in Mexico City in August of 2007 to discuss specific considerations in Latin America. Of major discussion was the laboratory evaluation of acromegaly, which requires the use of appropriate tests and the adoption of local institutional standards. As a general rule to ensure diagnosis, the patient’s GH level during an oral glucose tolerance test and IGF-1 level should be evaluated. Furthermore, to guide treatment decisions, both GH and IGF-1 assessments are required. The treatment of patients with acromegaly in Latin America is influenced by local issues of cost, availability and expertise of pituitary neurosurgeons, which should dictate therapeutic choices. Such treatment has undergone profound changes because of the introduction of effective medical interventions that may be used after surgical debulking or as first-line medical therapy in selected cases. Surgical resection remains the mainstay of therapy for small pituitary adenomas (microadenomas), potentially resectable macroadenomas and invasive adenomas causing visual defects. Radiotherapy may be indicated in selected cases when no disease control is achieved despite optimal surgical debulking and medical therapy, when there is no access to somatostatin analogues, or when local issues of cost preclude other therapies. Since not all the diagnostic tools and treatment options are available in all Latin American countries, physicians need to adapt their clinical management decisions to the available local resources and therapeutic options.
PMCID: PMC2855858  PMID: 19882249
Acromegaly; Growth hormone; Insulin-like growth factor 1; Latin America; Octreotide; Radiotherapy; Somatostatin receptors; Surgery
9.  Acromegaly pathogenesis and treatment 
The Journal of Clinical Investigation  2009;119(11):3189-3202.
Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly — a disorder of disproportionate skeletal, tissue, and organ growth. High GH and IGF1 levels lead to comorbidities including arthritis, facial changes, prognathism, and glucose intolerance. If the condition is untreated, enhanced mortality due to cardiovascular, cerebrovascular, and pulmonary dysfunction is associated with a 30% decrease in life span. This Review discusses acromegaly pathogenesis and management options. The latter include surgery, radiation, and use of novel medications. Somatostatin receptor (SSTR) ligands inhibit GH release, control tumor growth, and attenuate peripheral GH action, while GH receptor antagonists block GH action and effectively lower IGF1 levels. Novel peptides, including SSTR ligands, exhibiting polyreceptor subtype affinities and chimeric dopaminergic-somatostatinergic properties are currently in clinical trials. Effective control of GH and IGF1 hypersecretion and ablation or stabilization of the pituitary tumor mass lead to improved comorbidities and lowering of mortality rates for this hormonal disorder.
PMCID: PMC2769196  PMID: 19884662
10.  Acromegaly: the disease, its impact on patients, and managing the burden of long-term treatment 
Acromegaly is a rare disease most often caused by the prolonged secretion of excess growth hormone from a pituitary adenoma. The disease is associated with multiple significant comorbidities and increased mortality. The delay to diagnosis is often long. This may be because of low disease awareness among health care professionals, the insidious onset of differentiating features, and because patients are likely to present with complaints typical of other conditions more frequently seen in primary care. Early identification of acromegaly facilitates prompt treatment initiation and may minimize the permanent effects of excess growth hormone. The primary treatment for many patients will be pituitary surgery, although not all patients will be eligible for surgery or achieve a surgical cure. If biochemical control is not achieved following surgery, other treatment options include medical therapy and radiation therapy. Improved biochemical control may only alleviate rather than reverse the associated comorbidities. Thus, lifelong monitoring of patient health is needed, with particular attention to the management of cardiovascular risk factors. It is additionally important to consider the impact of both disease and treatment on patients’ quality of life and minimize that impact where possible, but particularly for chronic therapies. For the majority of patients, chronic therapy is likely to include somatostatin analog injections. In some circumstances, it may be possible to extend the dosing interval of the analog once good biochemical control is achieved. Additional convenience may be gained from the possibility of self-/partner administration of treatment or administration of treatment by a health care professional at home. Overall, it is clear that the care of patients with acromegaly requires a highly coordinated approach involving numerous specialties (eg, endocrinology, surgery, cardiology). Further, patients’ needs must be at the core of management and every effort must be made to improve health care experiences and minimize treatment burdens.
PMCID: PMC3555549  PMID: 23359786
acromegaly; diagnosis; treatment; quality of life; convenience
11.  Radiation techniques for acromegaly 
Radiotherapy (RT) remains an effective treatment in patients with acromegaly refractory to medical and/or surgical interventions, with durable tumor control and biochemical remission; however, there are still concerns about delayed biochemical effect and potential late toxicity of radiation treatment, especially high rates of hypopituitarism. Stereotactic radiotherapy has been developed as a more accurate technique of irradiation with more precise tumour localization and consequently a reduction in the volume of normal tissue, particularly the brain, irradiated to high radiation doses. Radiation can be delivered in a single fraction by stereotactic radiosurgery (SRS) or as fractionated stereotactic radiotherapy (FSRT) in which smaller doses are delivered over 5-6 weeks in 25-30 treatments. A review of the recent literature suggests that pituitary irradiation is an effective treatment for acromegaly. Stereotactic techniques for GH-secreting pituitary tumors are discussed with the aim to define the efficacy and potential adverse effects of each of these techniques.
PMCID: PMC3275813  PMID: 22136376
acromegaly; fractionated stereotactic radiotherapy; radiosurgery; toxicity; GH-secreting pituitary tumors
12.  Limited effects of growth hormone replacement in patients with GH deficiency during long-term cure of acromegaly 
Pituitary  2009;12(4):339-346.
The aim of this study was to assess the effects of replacement with recombinant human growth hormone (rhGH) in patients with GH deficiency (GHD) after treatment of acromegaly. Intervention study. Sixteen patients (8 men, age 56 years), treated for acromegaly by surgery and radiotherapy, with an insufficient GH response to insulin-induced hypoglycaemia, were treated with 1 year of rhGH replacement. Study parameters were assessed at baseline and after 1 year of rhGH replacement. Study parameters were cardiac function, body composition, bone mineral density (BMD), fasting lipids, glucose, bone turnover markers, and Quality of Life (QoL). During rhGH replacement IGF-I concentrations increased from −0.4 ± 0.7 to 1.0 ± 1.5 SD (P = 0.001), with a mean daily dose of 0.2 ± 0.1 mg in men and 0.3 ± 0.2 mg in women. Nonetheless, rhGH replacement did not alter cardiac function, lipid and glucose concentrations, body composition or QoL. Bone turnover markers (PINP and β crosslaps) levels increased (P = 0.005 and P = 0.021, respectively), paralleled by a small, but significant decrease in BMD of the hip. The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study.
PMCID: PMC2764055  PMID: 19521779
Growth hormone deficiency; Growth hormone replacement; Acromegaly
13.  Characteristics of Acromegaly in Korea with a Literature Review 
Endocrinology and Metabolism  2013;28(3):164-168.
Acromegaly is a slowly progressive disease caused by excessive growth hormone (GH), which is related to a GH secreting pituitary tumor in most cases. Herein, we describe the epidemiology, clinical characteristics, and treatment of acromegaly in Korea with a literature review. The average annual incidence of acromegaly in Korea was 3.9 cases per million people, which was within the range of previous Western studies. The primary treatment for acromegaly was also transsphenoidal adenomectomy, which accounted for 90.4% of patients whose primary therapeutic options were known. The overall surgical remission rates were 89%, 87%, 64%, 70%, and 50% for modified Hardy classification I, II, IIIA, IIIB, and IV, respectively. An updated and larger study regarding the treatment outcome of medical/radiotherapy in Korean acromegalic patients is needed.
PMCID: PMC3811698  PMID: 24396674
Acromegaly; Growth hormone; Pituitary neoplasms
14.  Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas 
Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4–6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits.
PMCID: PMC3888346  PMID: 24421637
GH-secreting pituitary adenoma; somatostatin analogs; lanreotide ATG; octreotide LAR; growth hormone; insulin-like growth factor 1
15.  Modern treatment of acromegaly 
Postgraduate Medical Journal  2003;79(930):189-194.
Acromegaly is an endocrine disorder characterised by increased morbidity and mortality. It is usually caused by a growth hormone secreting pituitary adenoma and is manifested by a variety of clinical features. Surgery is usually the treatment of choice, however over the last few years, several new methods of treatment have been developed. A recent consensus on the targets for treatment has led to multiple studies being conducted to assess the efficacy of the currently available options. This review examines the evidence for and against these treatments.
PMCID: PMC1742666  PMID: 12743333
16.  Clinical, quality of life, and economic value of acromegaly disease control 
Pituitary  2011;14(3):284-294.
Although acromegaly is a rare disease, the clinical, economic and health-related quality of life (HRQoL) burden is considerable due to the broad spectrum of comorbidities as well as the need for lifelong management. We performed a comprehensive literature review of the past 12 years (1998–2010) to determine the benefit of disease control (defined as a growth hormone [GH] concentration <2.5 μg/l and insulin-like growth factor [IGF]-1 normal for age) on clinical, HRQoL, and economic outcomes. Increased GH and IGF-1 levels and low frequency of somatostatin analogue use directly predicted increased mortality risk. Clinical outcome measures that may improve with disease control include joint articular cartilage thickness, vertebral fractures, left ventricular function, exercise capacity and endurance, lipid profile, and obstructive apnea events. Some evidence suggests an association between controlled disease and improved HRQoL. Total direct treatment costs were higher for patients with uncontrolled compared to controlled disease. Costs incurred for management of comorbidities, and indirect cost could further add to treatment costs. Optimizing disease control in patients with acromegaly appears to improve outcomes. Future studies need to evaluate clinical outcomes, as well as HRQoL and comprehensive economic outcomes achieved with controlled disease.
PMCID: PMC3146976  PMID: 21597975
Acromegaly; Somatostatin analogues; Octreotide; Lanreotide; Quality of life; Morbidity; Mortality
17.  Osteoarticular Changes in Acromegaly 
Acromegaly is caused by hypersecretion of growth hormone (GH) and consequently of insulin-like growth factor-I (IGF-1) due to pituitary tumor. Other causes, such as increased growth-hormone releasing hormone (GHRH) production, ectopic GHRH production, and ectopic GH secretion, are rare. Growth hormone and IGF-1 play a role in the regulation of bone metabolism, but accurate effect of growth hormone excess on bone is not fully explained. The issue of osteoarticular manifestations is still very actual, due to development of complications in the majority of patients with acromegaly. Traditionally, acromegaly is considered as a cause of secondary osteoporosis. Nowadays, it is discussed if BMD as predictor of osteoporotic fractures in acromegalic patient is decreased or even normal. Thus, bone quality remains to be more important in assessment of fracture risk. GH excess leads to increased bone turnover, defined by changes of bone markers. The articular manifestations are frequent clinical complications and may be present as the earliest symptom in a significant proportion of acromegalic patients. Articular manifestations are the main causes of morbidity and immobility of these patients, and they are persistent even after successful treatment. Quick recognition of osteoarticular changes and aiming the therapy lead to decrease in complication number.
PMCID: PMC3447355  PMID: 23008710
18.  Reduction of elevated IGF-1 levels in coincident amyotrophic lateral sclerosis and acromegaly 
We report a patient presenting with ALS in whom acromegaly was later confirmed. Insulin-like growth factor-1 (IGF-1) has been tried in the treatment of ALS and despite equivocal results from clinical trials, efforts have continued to try to harness the significant positive effects on motor neuron growth observed in vitro and in survival of mouse models of the disease. One subsequent study has reported an association between higher circulating serum IGF-1 levels and longer disease duration in ALS patients. Concern therefore arose in our case that treatment of the acromegaly with a somatostatin analogue might adversely affect the natural course of his ALS through lowering of potentially beneficial IGF-1 levels. Through clinical observation and prognostic modelling we suggest that this concern was unfounded. The potential interaction of these two rarely coincident disorders in our patient is discussed.
PMCID: PMC3182544  PMID: 19634028
Survival; prognostic; epidemiology
19.  The Coexistence of an Intrasellar Adenoma, Lymphocytic Hypophysitis, and Primary Pituitary Lymphoma in a Patient with Acromegaly 
Case Reports in Endocrinology  2011;2011:941738.
The concomitant presence of three histopathologically different entities in the pituitary gland is a rare occurrence. Most publications identify at least two distinct pathologies, mainly, a pituitary adenoma coexisting with a second intrasellar lesion. We present a case of a 71-year-old female referred for evaluation and treatment of acromegaly. Questioning revealed she was experiencing facial palsy, visual disturbances, and syncopal spells for several weeks. When laboratory evaluation showed elevated somatomedin (IGF-I) levels and an oral glucose tolerance test failed to demonstrate any suppression of her growth hormone (GH) values, an MRI of the pituitary revealed a sellar mass. A presumptive diagnosis of pituitary adenoma was established. The patient underwent transsphenoidal resection of the sellar mass, which proved to be a large B-cell lymphoma (Stage I-E) associated with areas of adenoma and lymphocytic hypophysitis.
PMCID: PMC3420670  PMID: 22937293
20.  Clinical and radiological evidence of the recurrence of reversible pegvisomant-related lipohypertrophy at the new site of injection in two women with acromegaly: a case series 
Pegvisomant-related lipohypertrophy may revert when changing the site of injection, but the lipohypertrophy may recur at the new site of injection. The strength of evidence, however, is weak and comes from information obtained from physical examination only.
Case presentation
We studied two Caucasian women with acromegaly, aged 51 and 71 years, with pegvisomant-related lipohypertrophy. Our two patients were evaluated at baseline, when the site of pegvisomant injection was the periumbilical abdominal region, and then four months after switching the injection site from the abdomen to both thighs. Both physical examination and radiological studies (magnetic resonance imaging and dual energy X-ray absorptiometry) demonstrated that the abdominal lipohypertrophy progressively reverted in both patients after switching the site of injection to the thighs. However, lipohypertrophy reappeared at the new site of injection. The radiological outcome confirmed the reversibility of pegvisomant-related lipohypertrophy and strengthened the body of evidence on this issue.
In clinical practice, physical examination of the injection site or sites leads to an early detection of lipohypertrophy during pegvisomant treatment. Radiological procedures may be of help to confirm subcutaneous fat changes and for a precise monitoring of fat redistribution. Patients should get appropriate information about lipohypertrophy before starting pegvisomant treatment since the rotation of the site of injection may prevent lipohypertrophy.
PMCID: PMC3398337  PMID: 22233881
21.  Therapeutic options in the management of acromegaly: focus on lanreotide Autogel® 
Biologics : Targets & Therapy  2008;2(3):463-479.
In acromegaly, expert surgery is curative in only about 60% of patients. Postoperative radiation therapy is associated with a high incidence of hypopituitarism and its effect on growth hormone (GH) production is slow, so that adjuvant medical treatment becomes of importance in the management of many patients.
To delineate the role of lanreotide in the treatment of acromegaly.
Search of Medline, Embase, and Web of Science databases for clinical studies of lanreotide in acromegaly.
Treatment with lanreotide slow release and lanreotide Autogel® normalized GH and insulin-like growth factor-I (IGF-I) concentrations in about 50% of patients. The efficacy of 120 mg lanreotide Autogel® on GH and IGF-I levels was comparable with that of 20 mg octreotide LAR. There were no differences in improvement of cardiac function, decrease in pancreatic β-cell function, or occurrence of side effects, including cholelithiasis, between octreotide LAR and lanreotide Autogel®. When postoperative treatment with somatostatin analogs does not result in normalization of serum IGF-I and GH levels after noncurative surgery, pegvisomant alone or in combination with somatostatin analogs can control these levels in a substantial number of patients.
PMCID: PMC2721386  PMID: 19707377
acromegaly; lanreotide; somatostatin analog; growth hormone; pegvisomant
22.  Comparison of octreotide LAR and lanreotide autogel as post-operative medical treatment in acromegaly 
Pituitary  2011;15(3):398-404.
Long-acting somatostatin analogs are frequently used as adjuvant treatment of acromegaly patients after noncurative surgery. This sudy aims to compare the efficacy of octreotide long-acting release (OCT) and lanreotide Autogel (LAN) in acromegaly patients. Sixty-eight patients not cured by transsphenoidal endoscopic or microscopic pituitary surgery between 2003 and 2009 were retrospectively analyzed (25 men; 43 women; mean age 41.1 ± 10.9 years [range 18–65 years]). The patients were assigned randomly to OCT (n = 36) and LAN (n = 32) groups. Evaluations included insulin-like growth factor I (IGF-I) and growth hormone (GH) after oral glucose tolerance test (OGTT) 3, 6, 12 and 18 months after starting medical treatment; pituitary magnetic resonance imaging was performed before treatment and after 3 and 12 months. Patients achieving IGF-I levels within the age and gender normal range and GH level <1 μg/l following OGTT were considered a ‘biochemical cure’. Mean IGF-I and GH values and tumor volumes (cm3) in the LAN and OCT groups were similar in the post-operative period before initiation of medical treatment. A statistically significant decrease in GH and IGF-I levels was obtained for both treatment groups at each follow-up visit compared to the previous value. Tumor shrinkage after 12 months of treatment was statistically significant in both groups but the percentage tumor shrinkage (28.5% vs. 34.9%, P = 0.166) and rate of patients achieving biochemical cure (63.9 and 78.1%, P = 0.454) were similar between OCT and LAN groups, respectively. OCT and LAN treatment options have similar efficacy for ensuring biochemical cure and tumor shrinkage in acromegaly patients who had noncurative surgery.
PMCID: PMC3443341  PMID: 21863263
Acromegaly; Somatostatin analogs; Octreotide; Lanreotide
23.  Risk of neoplasms in acromegaly 
Contemporary Oncology  2012;16(2):111-117.
Acromegaly is a chronic disease caused by the excessive secretion of growth hormone (GH), and as a result, of insulin-like growth factor-1 (IGF-1). Untreated, the condition reduces the patients’ life expectancy and leads to a series of complications, among which an increased risk of carcinogenesis is considered most important. This paper is an analysis of the publications on the issue of the formation of neoplasms, both malignant and benign, in acromegalic patients. Although the influence of acromegaly on carcinogenesis remains controversial, a number of studies indicate that the frequency of developing tumors in this patient group is higher. Moreover, numerous publications particularly stress the increased risk of developing neoplasms in patients who had been untreated for a long period of time and show elevated levels of GH and IGF-1. Consequently, a quick diagnosis and the implementation of effective treatment play a key role in the management of this disease.
PMCID: PMC3687397  PMID: 23788865
neoplasms; cancer; acromegaly; epidemiology
24.  Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas 
Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients.
First-line treatment of prolactinomas is pharmacotherapy with dopamine agonists; recent reports of cardiac valve abnormalities associated with this class of medication in Parkinson's disease has prompted study in hyperprolactinemic populations. Patients with resistance to dopamine agonists may require other treatment.
First-line treatment of Cushing's disease is pituitary surgery by a surgeon with experience in this condition. Current medical options for Cushing's disease block adrenal cortisol production, but do not treat the underlying disease. Pituitary-directed medical therapies are now being explored. In several small studies, the dopamine agonist cabergoline normalized urinary free cortisol in some patients. The multi-receptor targeted somatostatin analogue pasireotide (SOM230) shows promise as a pituitary-directed medical therapy in Cushing's disease; further studies will determine its efficacy and safety. Radiation therapy, with medical adrenal blockade while awaiting the effects of radiation, and bilateral adrenalectomy remain standard treatment options for patients not cured with pituitary surgery.
In patients with acromegaly, surgery remains the first-line treatment option when the tumor is likely to be completely resected, or for debulking, especially when the tumor is compressing neurovisual structures. Primary therapy with somatostatin analogues has been used in some patients with large extrasellar tumors not amenable to surgical cure, patients at high surgical risk and patients who decline surgery. Pegvisomant is indicated in patients who have not responded to surgery and other medical therapy, although there are regional differences in when it is prescribed.
In conclusion, the treatment of patients with pituitary adenomas requires a multidisciplinary approach. Dopamine agonists are an effective first-line medical therapy in most patients with a prolactinoma, and somatostatin analogues can be used as first-line therapy in selected patients with acromegaly. Current medical therapies for Cushing's disease primarily focus on adrenal blockade of cortisol production, although pasireotide and cabergoline show promise as pituitary-directed medical therapy for Cushing's disease; further long-term evaluation of efficacy and safety is important.
PMCID: PMC2887860  PMID: 20478050
25.  Aggressive tumors and difficult choices in acromegaly 
Pituitary  2013;17:24-29.
The current article looks at some of the factors associated with pituitary adenomas displaying unusually aggressive biological and clinical behaviour in patients with acromegaly.
This was a retrospective, narrative review of previously published evidence chosen at the authors’ discretion and presented from the perspective of a Latin American case study.
Findings and Conclusions
Although most pituitary tumors in acromegalic patients are benign and non-aggressive many can behave more aggressively, compromising local surrounding structures. These lesions tend to respond poorly to somatostatin analogs, have a higher risk of recurrence after surgery and, thus, a worse prognosis. Patients with more aggressive tumors constitute a particular challenge, as they often require several therapeutic approaches and may be difficult to manage, especially when options are restricted due to limited resources.
PMCID: PMC3906541  PMID: 24293348
Acromegaly; GH; IGF-1; Aggressive tumors; Somatostatin analogs; Dopamine agonists

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