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00019616-200409000-00008ReviewThe EndocrinologistThe Endocrinologist© 2004 Lippincott Williams & Wilkins, Inc.14September 2004 p 277-287AcromegalyDiagnostic PitfallsCME Review Article #27Freda, Pamela U. MDAssistant Professor of Clinical Medicine, Department of Medicine, Columbia College of Physicians and Surgeons, New York, New York.The author has disclosed that she has no significant relationships with or financial interests in any commercial company that pertains to this educational activity.Reprints: Pamela U. Freda, MD, Department of Medicine, Columbia College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032. E-mail: [email protected] Editor’s Note:This article is the 27th of 36 that will be published in 2004 for which a total of up to 36 Category 1 CME credits can be earned. Instructions for how credits can be earned precede the CME Examination at the back of this issue.AbstractAn initial clinical suspicion of acromegaly has traditionally been the necessary first step toward making the diagnosis. However, because of the typically insidious nature of the clinical syndrome, acromegaly is usually underrecognized with a long delay from disease onset to diagnosis. Some patients present with few or none of the typical clinical manifestations. Therefore, the first pitfall to avoid in diagnosing acromegaly is to dismiss the diagnosis in a patient without obvious clinical signs or symptoms. Improvements in biochemical testing are now available that may help lead to the detection of this disease in its earlier stages. Biochemical testing consists of evaluation of both the degree of growth hormone (GH) suppression after oral glucose administration (OGTT) and levels of the GH-dependent peptide, insulin-like growth factor I (IGF-I). Potential pitfalls in the biochemical assessment of acromegaly can arise from misinterpretation of the results of GH testing, which can result from failure to recognize that older GH criteria for diagnosis are no longer applicable to interpretation of GH levels measured with modern sensitive and specific GH assays. Suppression of GH to less than 1.0 μg/L during an oral glucose tolerance test (OGTT) may help exclude acromegaly when GH is measured with some current commercially available assays, but with the use of highly sensitive assays, a fall of GH to less than 1.0 μg/L during an OGTT does not necessarily exclude the disease. Failure of GH to suppress, however, may occur in some healthy subjects, in particular young healthy women and adolescents. Clinical settings other than acromegaly can also be associated with failure of normal GH suppression such as chronic renal insufficiency, liver failure, active hepatitis, hyperthyroidism, diabetes mellitus, anorexia nervosa, and other forms of malnutrition. An essential part of the biochemical diagnosis of acromegaly is also documentation of an elevated serum IGF-I level. When measured properly and compared with a well-characterized, age-adjusted normative database, elevation of the serum IGF-I level is a sensitive and specific indicator for the presence of acromegaly. Interpretation of IGF-I levels must consider important regulators of IGF-I production such as nutritional status and age that significantly influence serum levels of IGF-I. Chronic and critical illness, including liver disease, renal failure, diabetes mellitus, and thyroid disease, may also alter serum IGF-I levels. An increased IGF-I is almost always specific for acromegaly, but in 2 important instances, pregnancy and adolescence, IGF-I may be increased without acromegaly. Greater awareness of limitations of current GH and IGF-I assays as well as interpretation of GH testing in conjunction with serum IGF-I levels and within the clinical context of the patient being assessed will help to avoid these potential pitfalls to the diagnostic assessment of acromegaly.Learning ObjectivesDescribe the presenting clinical features of acromegaly, the course of the illness, and coexisting conditions.Explain the diagnostic value of determining the degree of growth hormone (GH) suppression after an oral glucose tolerance test, and how the advent of highly sensitive GH assays have altered diagnostic criteria.Appraise the rationale for estimating serum levels of insulin-line growth factor I, and their value and limitations as a marker of acromegaly.The etiology of acromegaly in almost all patients is a growth hormone (GH)-secreting pituitary tumor. Although the disease is rare with a reported incidence of 3 to 4 per million and a prevalence of 50 to 70 per million,1 it is likely underrecognized and thus underdiagnosed. Acromegaly has no gender predilection and most patients are diagnosed in the fourth to sixth decades of life.2,3 Early diagnosis and prompt initiation of therapy are essential to prevent the development of the irreversible physical changes, numerous morbidities, and increased mortality rate that are associated with inadequately treated acromegaly. Recent data have demonstrated that normalizing the hormonal excesses of the disease can prolong these patients’ survival.4–6 These studies have also provided a clear rationale for the need to refine our diagnostic criteria for acromegaly. Our goal for the diagnosis of acromegaly should be early recognition of the disease based both on a heightened clinical suspicion as well as on rigorously scrutinized biochemical testing.Chronic hypersecretion of GH and the resultant persistent elevation in levels of insulin-like growth factor-I (IGF-I) are the hallmark biochemical features of acromegaly. The widespread availability of improved IGF-I assays and the development of increasingly sensitive and specific GH assays has improved recognition of early disease, greatly facilitated the evaluation, and has led to the tightening of the diagnostic criteria for acromegaly. However, although modern biochemical methods have greatly increased the accuracy of our biochemical assessment, they have also led to the awareness of important pitfalls in the biochemical assessment that need to be taken into consideration. Some of these pitfalls could be encountered with the use of traditional methods of GH testing, whereas others have been revealed by the use of newer methodologies. This review summarizes our current understanding of the optimal biochemical assessment of acromegaly and describes potential pitfalls to this assessment.CLINICAL PRESENTATION OF ACROMEGALYThe first step toward making the diagnosis of acromegaly is considering it and suspecting the disease on clinical grounds is typically required for this. Thus, in patients with characteristic clinical features, the diagnosis may be obvious, but in many others, acromegaly may not be thought of because the clinical manifestations are in their more subtle earlier stages and because of the disease’s rarity. Most patients come to medical attention only after years of often unrecognized signs and symptoms. Not infrequently, patients are diagnosed only after a new physician or dentist noticed signs of the disease or it was found incidentally on testing done for other reasons.2,3 As a result of the insidious nature of this clinical syndrome, there is a delay from the development of the disease or the first noticed symptoms averaging from 5 to 9 years.2,3 Thus, most patients have advanced disease and marked clinical manifestations by the time of diagnosis.The clinical manifestations of acromegaly can result from the effects of hormone excess (ie, chronic exposure to high levels of GH and IGF-I) and/or those secondary to tumor mass effect. These manifestations vary considerably between patients for reasons that are not completely known, but factors such as the age at disease onset, its duration, the patient’s genetic susceptibility to diabetes mellitus or hypertension, and tumor size and rate of growth may play a role in determining these differences. Patients’ most common presenting complaints are changes in facial appearance (typically a coarsening of the features), enlargement of the hands and feet, soft tissue swelling, headache, and hyperhidrosis.7,8 Other clinical manifestations include menstrual dysfunction, hypertension, diabetes mellitus, visual impairment, osteoarthritis, carpal tunnel syndrome, hyperprolactinemia, and sleep apnea.2,9,10 Many of these signs and symptoms are not specific for the diagnosis of acromegaly, explaining in part why the disease can go unrecognized for years. Many patients with acromegaly also have cardiovascular disease, a major cause of the excess mortality of acromegaly.8 Although coexistent hypertension and diabetes mellitus are likely to be important factors in their heart disease, some patients may have a distinct cardiomyopathy of acromegaly.8,11 Some patients, by virtue of the fact that most tumors are large at diagnosis, have signs and symptoms resulting from compression by the tumor mass in addition to headache such as visual field deficits or hypopituitarism.12Although the classic clinical presentation of acromegaly is clearly the most likely, some patients present with none or few of these manifestations. Therefore, one of the first pitfalls to avoid in diagnosing acromegaly is to dismiss the diagnosis in a patient without obvious clinical signs or symptoms. Not all patients have acral and facial changes that are most often the clinical tip off to the diagnosis. For example, at our center we have seen a few patients without any such changes, who presented for evaluation of osteoporosis that was subsequently found to be the result of secondary hypogonadism, which led to the diagnosis of acromegaly.13 We have also diagnosed mild acromegaly in some patients with no clinical features of acromegaly but whose pituitary tumor is found on an imaging study of the head that was done for an unrelated reason. Thus, a simple biochemical workup for acromegaly, in particular a serum IGF-I level, is warranted in anyone presenting with a pituitary tumor. A heightened awareness, on the part of physicians, to the more subtle signs and symptoms of acromegaly is needed so that an early diagnosis can be made.BIOCHEMICAL ASSESSMENT AND POTENTIAL PITFALLSGrowth HormoneGrowth Hormone AssaysMisinterpretation of GH measurements is a major potential pitfall in the biochemical assessment of acromegaly. The fact that GH assays have changed yet diagnostic criteria have not necessarily kept pace with these changes is generally the cause of this misinterpretation. An understanding of how GH assays have evolved is needed to avoid these pitfalls. Classic GH criteria for diagnosing acromegaly and important epidemiologic data, which have been traditionally used as a guide for therapeutic decisions, were derived largely from GH measurements made by polyclonal radioimmunoassays (RIA).14 However, most current commercially available GH assays are now more sensitive and specific 2-site chemiluminescence or immunoradiometric assays. Comparison of GH levels measured in traditional versus contemporary GH assays has shown as expected that GH levels measured by the latter are significantly less than those measured by the former.15,16 For example, in 1 set of paired samples, GH levels of less than 2.5 μg/L measured by polyclonal RIA were generally less than 0.5 μg/L by an IRMA, and nadir levels during a OGTT were approximately 4-fold less with the IRMA.15,16 However, conversion factors between assays could not be established because of substantial intersubject variation in the ratios of the 2 types of GH measurements. Other studies have also shown marked variability among GH assays. Thus, interpreting GH levels measured with modern sensitive and specific GH assays based on criteria derived with traditional GH assays is a potential pitfall in the diagnosis of acromegaly.Interpretation of GH measurements is further complicated because modern GH assays also vary with respect to many characteristics such as antibody specificity, reference preparations, and assay design.17–21 For example, some GH assays use 2 monoclonal antibodies and others a combination of monoclonal and polyclonal antibodies that may recognize only 22K or variable percentages of 20K and 22K GH.20 The GH standards used in recent studies in patients with acromegaly have also varied from the recombinant human GH 22K specific reference preparation WHO 88/624 to WHO standard 80/505, which contains both 20K and 22K GH22–24 to polyclonal GH standards obtained from other sources such as the NIH and National Hormone and Pituitary Program.25,26 Thus, the GH assays with which normal ranges for GH measurements were constructed and to assess patients for acromegaly differ. As a result, normative data characterized with 1 assay may not be reliable when used with others. With the general use of a new recombinant human GH reference preparation, 98 /574, interassay comparisons should be improved,27 but until more standardization of GH assay methodology is in place,28 published diagnostic GH criteria for acromegaly need to be viewed with current GH assay limitations in mind and can only serve as a general guide.Oral Glucose Tolerance TestingThe cornerstone of the biochemical evaluation of acromegaly has traditionally been assessment of GH suppression after oral glucose (OGTT).29–31 The diagnostic use of the OGTT stems from the fact that an acute rise of plasma glucose suppresses GH secretion from the pituitary in healthy people, whereas impaired GH suppression after glucose ingestion is a well-known characteristic of patients with active acromegaly.26,32 Many patients with active acromegaly may also have a paradoxic rise in GH after the OGTT, but this rise does not provide added diagnostic value to that of failure of suppression. After an overnight fast, blood samples are taken before and then 60, 90, and 120 minutes after ingestion of a 100-g glucose drink. In many centers, 75 g of glucose is used, but the merits of this versus 100 g glucose have not been studied. The nadir GH achieved during the OGTT is then compared with a specific cutoff and if above this diagnosing or if below excluding acromegaly.An assessment of OGTT levels cannot be done without an understanding of what constitutes a normal glucose-suppressed GH. Reassessment of diagnostic criteria for acromegaly developed in parallel with the realization that traditional GH assays lacked the sensitivity required to detect the extent of GH suppression that occurs in healthy subjects. With newer assays, GH levels have been shown to suppress to less than 1.0 μg/L in healthy subjects.22 If the data from 3 recent studies are examined together, nadir GH levels after oral glucose were <0.2 μg/L in all healthy adults except some young women22,25,33 (Fig. 1). Other measures of GH secretion are higher in women, and some data also suggest that young women in particular have higher nadir GH levels after oral glucose than other healthy subjects.34–39 Chapman and colleagues demonstrated higher nadir GH levels after oral glucose in young healthy females; GH levels suppressed to <0.72 μg/L in young healthy women versus <0.065 μg/L in young healthy men.22 Of the 6 young women in this study, 2 had nadir GH levels of 0.36 μg/L and 0.72 μg/L and all other men and women had nadir GH values ≤0.14 μg/L. We have found that nadir GH levels were 0.19 and 0.18 μg/L in 2 young women on oral contraceptives, whereas nadir levels were less than 0,14 μg/L in all other 46 healthy subjects.33 In another study, Costa and colleagues found that nadir GH levels were highest in women between the ages of 28 and 33; 3 women had nadir values of 0.2 μg/L and 1 of 0.7 μg/L, whereas all other healthy subjects had nadir GH levels less than 0.2 μg/L.25 However, it is unclear if such gender differences could be reliably distinguished with current commercial GH assays that lack the sensitivity of those used in these research studies. Nevertheless, it needs to be considered that as more sensitive and specific GH assays are in clinical use, a higher nadir GH cutoff may be necessary for young women. In addition, nadir GH levels overlap in young women with the range seen in some patients with active acromegaly as discussed subsequently. Timing of testing within the menstrual cycle, variable estrogen milieu, and use of oral contraceptives also likely are important in determining the extent of GH suppression in women. These potential sources of variability could potentially contribute to failure of “normal” GH suppression in healthy young women without acromegaly. This potential pitfall to the diagnostic assessment of young women can in part be avoided if OGTT-suppressed GH levels are examined in conjunction with serum IGF-I levels and within the clinical context of the patient being evaluated.JOURNAL/endst/04.03/00019616-200409000-00008/figure1-8/v/2021-02-17T201744Z/r/image-tiff Nadir growth hormone (GH) levels after oral glucose as measured with a highly sensitive GH immumoradiometric assay in healthy subjects. Data are from references 15, 22, and 24.As the expectations for GH suppression with modern assays in healthy subjects have been revised, so too have those OGTT criteria for establishing or excluding the diagnosis of acromegaly. The interpretation of current OGTT results must consider that GH cutoffs for diagnosing or excluding acromegaly have changed. A nadir GH level <2.0 μg/L during a OGTT was considered to exclude acromegaly, and nadir GH levels above this cutoff were thought to be consistent with the diagnosis when GH was measured with a polyclonal RIA.40 Most newly diagnosed patients with acromegaly will have nadir GH levels >2 μg/L with use of any GH assay. However, the use of more sensitive and specific GH assays, especially in conjunction with IGF-I measurements, has shown that acromegaly can be diagnosed with GH levels much lower than previously thought. In addition, the cutoff of 2 μg/L was found to lack specificity because the values obtained in healthy subjects overlapped with those in patients with active acromegaly and those in remission.15 More recently, a failure of GH to fall after glucose to <1.0 μg/L was proposed as the diagnostic criterion for use with more specific 2-site assays such as immunoradiometric assays.41 Some data support the cutoff of 1 μg/L,25 but other data have found that this cutoff is too high when GH is measured with highly sensitive immumoradiometric (IRMA) or chemiluminescence assays, erroneously misclassifying some patients as not having active acromegaly. Recent data have shown that nadir GH levels after oral glucose in some newly diagnosed patients can be substantially less than 1.0 μg/L24 (Fig. 2). Dimaraki and colleagues found that 8 of 16 patients with newly diagnosed acromegaly who were recognized by elevated IGF-I levels had a nadir GH after oral glucose of less than 1 μg/L. In our cohort of newly diagnosed patients, we have also identified patients with elevated IGF-I levels and nadir values less than 1 μg/L and as low as 0.42 μg/L who went on to surgically documented GH-producing pituitary tumors.13 Thus, the diagnosis of acromegaly cannot be excluded with suppression below this cutoff when GH is measured with contemporary assays.JOURNAL/endst/04.03/00019616-200409000-00008/figure2-8/v/2021-02-17T201744Z/r/image-tiff Nadir growth hormone (GH) levels after oral glucose as measured with highly sensitive GH assays in patients with newly diagnosed acromegaly from references 13 and 24.In postoperative patients, a nadir GH cutoff of 1 μg/L has also been proposed to best distinguish active disease from remission.41 Some studies have found the cutoff of 1.0 μg/L to provide good separation of active disease from remission using high or normal IGF-I levels to distinguish these 2 groups25,26,90 Other data with highly sensitive and specific GH assays has have shown that this OGTT cutoff is too high and will miss some patients with persistent active disease and elevated IGF-I levels who may have nadir GH levels as low as 0.33 μg/L15,33 Overall, with 1 particular IRMA GH assay, a GH cutoff of 0.3 μg/L best separated patients with active acromegaly, newly diagnosed and postoperative patients, from patients with acromegaly in remission and healthy subjects.15 However, these data can only serve as a guide for evaluation of nadir GH levels in patients with acromegaly evaluated with other GH assays.The need to factor in age and body mass index (BMI) into criteria for glucose-suppressed GH levels has also been examined. Although the age-related decline in many parameters of GH secretion is well characterized,42,43 a need for age-adjusted standards for GH suppression testing has not been clearly demonstrated. In 1 group of healthy subjects, nadir GH levels and age were not correlated,33 but others have shown some negative relationship between nadir GH levels and increasing age with these levels being higher in younger (<40 years.) versus older (≥40 years.) women, but nadir values in men showed no such age-related decline.25,44 Results of the investigation of the relationship between BMI and GH suppression has also varied. We found no correlation between BMI and nadir GH values in our healthy subjects or patients with acromegaly, but another study suggests some negative relationship between nadir GH and BMI.44 Although additional studies are warranted, insufficient data are currently available to recommend standards for nadir GH values based on age or BMI.Pitfalls in the interpretation of glucose-suppressed GH levels can also occur in other clinical settings associated with abnormal GH suppression, including chronic renal insufficiency, liver failure, active hepatitis, hyperthyroidism, diabetes mellitus, anorexia nervosa, and other forms of malnutrition45–47(Table 1). In these clinical settings, however, IGF-I levels should be either normal or low, so elevation in IGF-I level along with persistently high GH levels despite the coexistence of these conditions would support the diagnosis of acromegaly. Diabetes mellitus, common in acromegaly, is particularly important to consider because it alone can be associated with higher GH levels that do not suppress normally after an OGTT.48,49 Thus, the OGTT may not be a reliable diagnostic test in a patient with acromegaly and coexistent diabetes mellitus. Overall, in most cases, diagnosing acromegaly with coexistent diabetes is not difficult because IGF-I will be elevated and GH obviously high.JOURNAL/endst/04.03/00019616-200409000-00008/table1-8/v/2021-02-17T201744Z/r/image-tiff Conditions Associated With an Abnormal Growth Hormone Suppression After Oral GlucoseIn addition, failure of GH to suppress into the designated “normal” range can occur in some healthy individuals, in particular young healthy women as discussed here and in some adolescents.50,51 In 1 study in adolescents, GH failed to suppress to <1 μg/L in 30% of 126 children with tall stature but with normal IGF-I levels and without acromegaly.51 GH criteria being developed in adults cannot necessarily be applied to the evaluation of adolescents, but insufficient data are available to recommend OGTT criteria to use in patients less than 20 years old with highly sensitive and specific GH assays.Interpretation of other types of assessments of GH secretion are also subject to pitfalls, especially with use of modern assays. One such test is the assessment of mean GH levels, often used to diagnose acromegaly and to assess disease status. Mean GH levels, in general, correlate with serum IGF-I level52 as well as with nadir GH during an OGTT.53 The validity of mean GH levels as a marker of disease status in acromegaly is also supported by data demonstrating normalization of mortality associated with these levels <2.5 μg/L.14,54,55 These data were derived with polyclonal GH RIAs, and it is currently unknown how to translate this epidemiologically validated criterion to GH levels measured with modern assays. In some centers, taking the mean of 5 serial GH samples collected over an approximately 10-hour period (day series or curve) is the usual and preferred method for assessing GH secretion.45,45,56 A recent series found a high rate of discrepancies between IGF-I levels and mean GH levels on a day series above and below a cutoff of 2.5 μg/L.55 Although these discrepancies could be interpreted to mean that IGF-I levels are a less reliable marker of disease, other evidence also supports the opposite conclusion. Mean GH levels may be less representative of overall GH secretion than serum IGF-I levels.55 With use of sensitive GH assays, in particular in patients with mild GH excess, it has been shown that mean 24-hour GH levels can overlap in patients with active acromegaly and healthy control subjects.24,57–59 In 1 series, mean 24-hour GH values were less than 2.5 μg/L in 12 of 16 of patients with active acromegaly, overlapping with those in healthy controls.24 Despite similar mean GH levels, patients with acromegaly, who have elevated trough GH concentrations, produce higher IGF-I levels than healthy subjects, who have normal pulsatile GH secretion.59 Thus, we need to use caution when interpreting mean GH measurements, especially with modern highly sensitive and specific GH assays. In addition, in the United States, these measurements are not practical for routine disease surveillance in clinical practice and we do not currently have data with which to define an appropriate cutoff for mean GH measurements measured with modern GH assays.Use of random GH levels to diagnose or exclude acromegaly is also subject to pitfalls. Use of either a cutoff for random GH above which acromegaly is diagnosed or one below which acromegaly is excluded could lead to potentially misleading conclusions. Although persistently high random GH levels are found in many patients with newly diagnosed acromegaly, these are frequently between 2 and 10 μg/L and can overlap with the range of pulsatile GH secretion in healthy subjects.40,45 Basal GH levels can also be elevated in poorly controlled diabetes mellitus, renal failure, malnutrition as well as in the setting of stress or during exercise and sleep,43 further reducing the specificity of a value above a given level for acromegaly. Therefore, any sufficiently high cutoff for random GH levels would fail to diagnose many patients with active acromegaly.Exclusion of acromegaly based on a designated “low” random GH level is also a potential pitfall. Random GH levels in some patients with active acromegaly are considerably lower than was recognized in the past, sharing with the range of GH levels thought only to be found in healthy subjects.24,33 Although at one time, a random GH level <5 μg/L was thought to be inconsistent with acromegaly, it is now known that GH levels in patients with active acromegaly can be found to fall within the “normal” ranges of many commercial GH assays.15,52,57,60 Further evaluation has shown that with the use of highly sensitive and specific GH assays, some patients with newly diagnosed acromegaly may have random GH levels <1.0 μg/L.13,24 A random GH <0.4 μg/L along with a normal IGF-I level41 was recently suggested as a criterion for exclusion of acromegaly. In 1 study, a random or basal GH level of less than <0.3 μg/L along with a normal IGF-I excluded active acromegaly,33 but the reproducibility of this cutoff with other GH assays is unknown. Although most newly diagnosed patients will not have spontaneous GH levels <0.4 μg/L, some may. Also, because of the overlap of random GH levels in healthy subjects and patients with acromegaly, designation of a diagnostic criterion for random GH for use with highly sensitive assays would be unreliable.Insulin-Like Growth Factor-IThe peptide IGF-I has a crucial role in the regulation of cell growth and differentiation.61 IGF-I is synthesized predominantly in the liver62 and circulates bound in a 150-kDa ternary complex to 2 GH-regulated carrier proteins, IGFBP-3 and acid-labile subunit (ALS). These proteins also serve an important purpose in IGF-I regulation. Binding of IGF-I to IGFBP-3 and ALS extends the half-life of IGF-I to approximately 12 to 15 hours in circulation,62,63 and results in serum concentrations of IGF-I that are relatively stable over a 24-hour period in healthy humans.64 A very small percentage, less than 1%, of IGF-I circulates in a free form, unbound to these carrier proteins.65GH is a major regulator of IGF-I production and IGF-I in turn mediates the majority of the growth-promoting and anabolic actions of GH.62,63 Serum IGF-I concentrations have been found to be proportional to the degree of GH hypersecretion reaching a plateau when 24-hour mean GH levels are above approximately 20 μg/L.66 IGF-I levels correlate with suppressed GH levels obtained after oral glucose administration.33,53 IGF-I levels also reflect clinical disease activity in patients with acromegaly, correlating with clinical markers of GH action such as heel-pad thickness and fasting and 1-hour postprandial glucose concentration.67This relationship between GH secretion and IGF-I production makes IGF-I levels an accurate and useful biochemical marker for acromegaly. IGF-I levels are above and separate from those of healthy subjects.57,68–71 Thus, IGF-I elevation can be used to identify patients with acromegaly. Data in support of the usefulness of IGF-I measurements in following disease status also comes from studies demonstrating that IGF-I levels return to normal with effective medical therapy with somatostatin analogs72 or the GH receptor antagonist, pegvisomant.73,74 Normalization of IGF-I level also generally reflects normalization of 24-hour GH-secretory patterns after successful surgery.57,58,66,75 Persistent IGF-I elevation in the face of treatment signifies persistent GH hypersecretion.76The use of IGF-I levels as a marker of disease has also been supported by the emergence of data demonstrating that IGF-I normalization is associated with improvement in clinical symptoms, morbidities, and the excess mortality in acromegaly. For example, most data would predict that IGF-I normalization is followed by improved clinical parameters such as symptom scores or blood glucose and insulin response to OGTT.67,70,73,77–82 Also, cardiovascular disease in acromegaly is improved as IGF-I is normalized with somatostatin analog therapy.83,84 Three studies have also now demonstrated that the approximately 3-fold excess mortality found in those patients with persistent IGF-I elevation is returned to that expected for the general population in the subgroups of patients whose IGF-I is normalized.4–6IGF-I elevation has proven to be not only a specific, but also a sensitive marker for GH excess. Because along with the clinical availability of IGF-I measurements has been the development of increasingly sensitive GH assays, elevation of IGF-I has revealed GH excess at progressively lower GH levels.52,67,82,85,86 Recently, IGF-I elevation in conjunction with highly sensitive GH measurements has revealed mild GH hypersecretion at GH levels once considered to be “normal.”15,24Despite the great merit of measuring serum IGF-I levels, failure to consider factors other than acromegaly that can alter these levels is a potential pitfall to their use (Table 2). A first important consideration is the reliability of the serum IGF-I level itself. Not all IGF-I assays are comparable in quality, reproducibility, and reliability.87 This stems in part from different assay methodology. IGF-I must be removed from its binding proteins by an extraction process or equivalent blocking procedure,87 but not all assays accomplish this process well. Other assay characteristics are also variable. In addition, considerable variability in the reported normal range exists among assays. Because of this variability, switching between different assays in the care of a patient is obviously problematic. An effort should be made to have IGF-I levels measured with a high-quality assay for which normative data is well characterized and broken down by age. Future data will hopefully lead to better standardization of IGF-I assays.88JOURNAL/endst/04.03/00019616-200409000-00008/table2-8/v/2021-02-17T201744Z/r/image-tiff Pitfalls in the Interpretation of IGF-I LevelsAlthough elevation of IGF-I is very specific for acromegaly, in 2 clinical settings IGF-I may be increased in the absence of acromegaly. In the latter half of pregnancy, IGF-I levels can be elevated as a result of placental lactogen stimulation and are thus not a reliable marker for acromegaly in pregnancy.64 IGF-I levels can also be unreliable for the diagnosis of acromegaly during the peak of IGF-I production in adolescence when these levels can be elevated above the “normal” range in some adolescents without acromegaly.Interpretation of IGF-I levels in the assessment of acromegaly also needs to take into account physiological and pathophysiological processes that can alter these levels, nutritional status, age, and gender.89 Fasting, of just a few days’ duration, can reduce IGF-I levels by as much as 50% in healthy subjects.64,90,91 Thus, IGF-I levels can be lowered in malnutrition from a number of causes, including protein calorie malnutrition, which occur in AIDS, inflammatory bowel disease, celiac disease, and anorexia as well as in starvation.64 In patients with acromegaly, nutritional status could thus potentially impact on serum IGF-I levels. For example, in 1 report, the serum IGF-I level was reduced into the normal range in 1 patient with active acromegaly with a coexistent protein losing enteropathy.92 Despite the important role of nutritional status in regulation of circulating IGF-I levels, standardization by nutritional status is not practical.93Chronic and critical illness, including liver disease, renal failure, diabetes mellitus, and thyroid disease, may alter serum IGF-I levels.64 Because the liver is the predominant source of circulating IGF-I, serum IGF-I levels are lowered in the setting of liver disease.94 In chronic renal failure, total IGF-I is usually normal,95 but it may be low96 and free IGF-I may be low, which may explain the apparent peripheral GH resistance and increased GH levels that are found in renal failure.97,98 In hypothyroidism, serum IGF-I may be somewhat lowered and they may be raised in hyperthyroidism but return to baseline with treatment of the thyroid abnormality.64,99 Some decrease in IGF-I levels can also occur in patients with poorly controlled insulin-dependent diabetes mellitus,91,100 but this decrease should not be enough to normalize the IGF-I level in a newly diagnosed patient or other patients with active acromegaly.91,100Circulating levels of IGF-I are also dependent to a great extent on age. IGF-I levels rise during childhood, peak in the second stage of puberty, then decline during adulthood, most steeply from the ages of 20 to 30, and then more gradually throughout the remainder of adulthood.64,93,101–103 Thus, a well-characterized, age-adjusted normative database is key to accurate analysis of serum IGF-I levels.The relationship between gender and serum IGF-I levels has also been investigated. The interaction between GH secretion and IGF-I production do differ in men and women. Women secrete more GH, and if GH-deficient require larger doses of GH replacement,36 to produce similar IGF-I levels suggesting that women have some degree of resistance to GH-stimulated IGF-I production.38,104 This may be the result of the effect of hepatic estrogen milieu on IGF-I production because IGF-I levels are lowered in postmenopausal women on oral, but not on transdermal, estrogen replacement therapy.105,106 Despite these gender differences, there has not been a consensus on the need for gender distinct normal ranges for serum IGF-I across all age groups with some data showing no gender difference in normal IGF-I ranges in adults,101,103 whereas other data have found IGF-I levels to be lower107 or higher44 in men than women throughout all or some102 adult age ranges. Each IGF-I assay needs to be evaluated for the need for gender specific ranges.In acromegaly, by virtue of the same GH/IGF-I relationship seen in healthy subjects, for comparable IGF-I levels, GH levels are somewhat higher in women.33,108 IGF-I levels in patients with acromegaly can be lowered with oral estrogen administration raising the possibility that estrogen use in women could modify the disease status designation or mask active acromegaly based on IGF-I measurements alone.64,109,110 By contrast, androgen status and androgen administration do not appear to influence serum IGF-I levels.64Although there is considerable evidence that serum IGF-I is an excellent and accurate marker of GH secretion, there is the potential possibility that subtle abnormalities of GH secretion may not be detected with IGF-I levels alone. For example, in our series, we have found some patients who are in apparent remission with normal IGF-I levels but who have subtle abnormalities of GH suppression that precede the development of disease recurrence.111 Others have also questioned the validity of relying on IGF-I alone to assess disease status in acromegaly. For example, in 1 recent study serum GH levels, and not IGF-I, predicted excess mortality in acromegaly.112 Because further studies into this issue are still needed, combined assessment of GH and IGF-I levels for follow up of patients with acromegaly seems warranted.Other Diagnostic TestsMeasurement of IGFBP-3, the principal IGF-I-binding protein, has been used as a diagnostic test for acromegaly. IGFBP-3 levels are elevated in most patients with acromegaly, but in general do not provide greater separation than IGF-I of patients with acromegaly from healthy subjects. Also, IGFBP-3 levels are lowered in liver disease and in states of poor nutrition. In some patients in whom other testing results are equivocal, IGFBP-3 levels may be helpful, but in most cases do not provide an advantage to measurements of IGF-I and GH suppression.16 A number of hormonal stimulation tests have also been used to diagnose acromegaly. The most commonly used of these is TRH testing. Some patients with acromegaly have paradoxic GH responses to TRH. This response, however, is unpredictable making TRH testing not specific or sensitive enough for the diagnosis acromegaly. Overall, use of other tests is more problematic and does not provide an advantage to measurement of GH or IGF-I for the diagnosis of acromegaly.Acromegaly Without a Clear Pituitary Tumor on Magnetic Resonance ImagingA pituitary magnetic resonance image (MRI) is an essential part of the diagnostic workup of acromegaly. Almost all patients with acromegaly at diagnosis have a visible pituitary tumor. In fact, most studies have shown that approximately 75% of tumors have been found to be macroadenomas or over 1 cm in size at diagnosis.12 With increasingly sensitive biochemical testing, however, we may see an increasing number of patients with small tumors at diagnosis. A patient presenting with acromegaly without an obvious tumor is rare and should prompt an evaluation for a possible origin of acromegaly outside the pituitary gland. In very rare patients with acromegaly, an ectopic GH-secreting adenoma40 or other malignancy113 is the source of GH excess. Also rarely, acromegaly can result from ectopic GHRH production from a pancreatic islet cell tumor,114 bronchial carcinoid tumor, or hypothalamic gangliocytoma.115 Measurement of serum GHRH levels and other imaging studies should be done to pursue the unlikely but possible diagnoses of ectopic GH or GHRH secretion in patients without a discrete pituitary tumor on MRI. If this evaluation is unrevealing, medical therapy may be warranted while continued surveillance and investigation for the source of GH excess are undertaken.CONCLUSIONSDiagnosing acromegaly requires proof of GH excess based on failure of normal GH suppression after oral glucose and elevation of levels of IGF-I. Both IGF-I and GH evaluations provide valuable and complimentary information in the assessment of acromegaly. Appropriately, biochemical evaluation will be directed in most instances toward patients with the characteristic clinical setting, but this can also be undertaken in patients with only subtle clinical manifestations. Despite the fact that substantial improvements have been made to the methods of biochemical testing for acromegaly, pitfalls to the assessment of this disease still exist. To some extent, these pitfalls can be avoided by recognizing clinical settings that can distort the serum levels of IGF-I or lead to failure of normal GH suppression after oral glucose. Limitations of current GH and IGF-I assays and how criteria have changed with these new assays also need to be recognized. With the availability of modern biochemical techniques and awareness of potential pitfalls in the diagnosis of acromegaly, it should now be possible to accurately detect acromegaly in its earlier stages.ACKNOWLEDGMENTSThis work was supported by NIH grant R01 DK 064720.REFERENCES1.Alexander L, Appleton D, Hall R, et al. Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol (Oxf). 1980;12:71–79.[Context Link][CrossRef][Medline Link]2.Nabarro JD. Acromegaly. Clin Endocrinol (Oxf). 1987;26:481–512.[Context Link][CrossRef][Medline Link]3.Ezzat S, Forster MJ, Berchtold P, et al. Acromegaly. Clinical and biochemical features in 500 patients. Medicine (Baltimore). 1994;73:233–240.[Context Link][Full Text][CrossRef][Medline Link]4.Swearingen B, Barker FG II, Katznelson L, et al. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab. 1998;83:3419–3426.[Context Link][CrossRef][Medline Link]5.Beauregard C, Truong U, Hardy J, et al. Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly. Clin Endocrinol (Oxf). 2003;58:86–91.[Context Link][Full Text][CrossRef][Medline Link]6.Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab. 2004;89:667–674.[Context Link][Full Text][CrossRef][Medline Link]7.Freda PU. Advances in the diagnosis of acromegaly. Endocrinologist. 2000;10:237–244.[Context Link][CrossRef][Medline Link]8.Molitch ME. Clinical manifestations of acromegaly. Endocrinol Metab Clin North Am. 1992;21:597–614.[Context Link][CrossRef][Medline Link]9.Grunstein RR, Ho KK, Sullivan CE. Effect of octreotide, a somatostatin analog, on sleep apnea in patients with acromegaly. Ann Intern Med. 1994;121:478–483.[Context Link][Full Text][CrossRef][Medline Link]10.Kaltsas GA, Mukherjee JJ, Jenkins PJ, et al. Menstrual irregularity in women with acromegaly. J Clin Endocrinol Metab. 1999;84:2731–2735.[Context Link][Full Text][CrossRef][Medline Link]11.Lopez-Velasco R, Escobar-Morreale HF, Vega B, et al. Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension? J Clin Endocrinol Metab. 1997;82:1047–1053.[Context Link][CrossRef][Medline Link]12.Freda PU, Wardlaw SL, Post KD. Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg. 1998;89:353–358.[Context Link][CrossRef][Medline Link]13.Freda PU, Reyes CM, Nuruzzaman AT, et al. Basal and glucose-suppressed GH levels less than 1 μg/L in newly diagnosed acromegaly. Pituitary. 2003;6:175–180.[Context Link][Full Text][CrossRef][Medline Link]14.Bates AS, Vanthoff W, Jones JM, et al. Does treatment of acromegaly affect life expectancy. Metab Clin Exp. 1995;44:1–5.[Context Link][CrossRef][Medline Link]15.Freda PU, Post KD, Powell JS, et al. Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab. 1998;83:3808–3816.[Context Link][CrossRef][Medline Link]16.Freda PU. Current concepts in the biochemical assessment of the patient with acromegaly. Growth Horm IGF Res. 2003;13:171–184.[Context Link][CrossRef][Medline Link]17.Celniker AC, Chen AB, Wert RM Jr, et al. Variability in the quantitation of circulating growth hormone using commercial immunoassays. J Clin Endocrinol Metab. 1989;68:469–476.[Context Link][CrossRef][Medline Link]18.Levin PA, Chalew SA, Martin L, et al. Comparison of assays for growth hormone using monoclonal or polyclonal antibodies for diagnosis of growth disorders. J Lab Clin Med. 1987;109:85–88.[Context Link][Medline Link]19.Reiter EO, Morris AH, MacGillivray MH, et al. Variable estimates of serum growth hormone concentrations by different radioassay systems. J Clin Endocrinol Metab. 1988;66:68–71.[Context Link][CrossRef][Medline Link]20.Ebdrup L, Fisker S, Sorensen HH, et al. Variety in growth hormone determinations due to use of different immunoassays and to the interference of growth hormone-binding protein. Horm Res. 1999;1(suppl):20–26.[Context Link][CrossRef][Medline Link]21.Seth J, Ellis A, Al-Sadie R. Serum growth hormone measurements in clinical practice: an audit of performance from the UK National External Quality Assessment scheme. Horm Res. 1999;1(suppl):13–19.[Context Link][CrossRef][Medline Link]22.Chapman IM, Hartman ML, Straume M, et al. Enhanced sensitivity growth hormone (GH) chemiluminescence assay reveals lower postglucose nadir GH concentrations in men than women. J Clin Endocrinol Metab. 1994;78:1312–1319.[Context Link][CrossRef][Medline Link]23.De Marinis L, Mancini A, Bianchi A, et al. Preoperative growth hormone response to thyrotropin-releasing hormone and oral glucose tolerance test in acromegaly: a retrospective evaluation of 50 patients. Metabolism. 2002;51:616–621.[Context Link][CrossRef][Medline Link]24.Dimaraki EV, Jaffe CA, DeMott-Friberg R, et al. Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab. 2002;87:3537–3542.[Context Link][Full Text][CrossRef][Medline Link]25.Costa AC, Rossi A, Martinelli CE Jr, et al. Assessment of disease activity in treated acromegalic patients using a sensitive GH Assay: Should we achieve strict normal GH levels for a biochemical cure? J Clin Endocrinol Metab. 2002;87:3142–3147.[Context Link][Full Text][CrossRef][Medline Link]26.Hattori N, Shimatsu A, Kato Y, et al. Growth hormone responses to oral glucose loading measured by highly sensitive enzyme immunoassay in normal subjects and patients with glucose intolerance and acromegaly. J Clin Endocrinol Metab. 1990;70:771–776.[Context Link][CrossRef][Medline Link]27.Bristow AF. International standards for growth hormone. Horm Res. 1999;1(suppl):7–12.[Context Link][CrossRef][Medline Link]28.Ranke MB, Orskov H, Bristow AF, et al. Consensus on how to measure growth hormone in serum. Horm Res. 1999;1(suppl):27–29.[Context Link][Medline Link]29.Melmed S, Jackson I, Kleinberg D, et al. Current treatment guidelines for acromegaly. J Clin Endocrinol Metab. 1998;83:2646–2652.[Context Link][CrossRef][Medline Link]30.Camacho-Hubner C. Assessment of growth hormone status in acromegaly: what biochemical markers to measure and how? Growth Horm IGF Res. 2000;10(suppl B):S125–129.[Context Link]31.Jaffe CA, Barkan AL. Acromegaly. Recognition and treatment. Drugs. 1994;47:425–445.[Context Link][Full Text][CrossRef][Medline Link]32.Earll JM, Sparks LL, Forsham PH. Glucose suppression of serum growth hormone in the diagnosis of acromegaly. JAMA. 1967;201:628–630.[Context Link][CrossRef][Medline Link]33.Freda PU, Landman RE, Sundeen RE, et al. Gender and age in the biochemical assessment of cure of acromegaly. Pituitary. 2001;4:163–171.[Context Link][Full Text][CrossRef][Medline Link]34.Frantz AG, Rabkin MT. Effects of estrogen and sex difference on secretion of human growth hormone. J Clin Endocrinol Metab. 1965;25:1470–1480.[Context Link][CrossRef][Medline Link]35.Engstrom BE, Karlsson FA, Wide L. Gender differences in diurnal growth hormone and epinephrine values in young adults during ambulation. Clin Chem. 1999;45:1235–1239.[Context Link][Full Text][CrossRef][Medline Link]36.van den Berg G, Veldhuis JD, Frolich M, et al. An amplitude-specific divergence in the pulsatile mode of growth hormone (GH) secretion underlies the gender difference in mean GH concentrations in men and premenopausal women. J Clin Endocrinol Metab. 1996;81:2460–2467.[Context Link][CrossRef][Medline Link]37.Tonshoff B, Blum WF, Mehls O. Derangements of the somatotropic hormone axis in chronic renal failure. Kidney Int Suppl. 1997;58:S106–113.[Context Link][Medline Link]38.Ho KY, Evans WS, Blizzard RM, et al. Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J Clin Endocrinol Metab. 1987;64:51–58.[Context Link][CrossRef][Medline Link]39.Pincus SM, Gevers EF, Robinson IC, et al. Females secrete growth hormone with more process irregularity than males in both humans and rats. Am J Physiol. 1996;270:E107–115.[Context Link][CrossRef][Medline Link]40.Chang-DeMoranville BM, Jackson IM. Diagnosis and endocrine testing in acromegaly. Endocrinol Metab Clin North Am. 1992;21:649–668.[Context Link][CrossRef][Medline Link]41.Giustina A, Barkan A, Casanueva FF, et al. Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab. 2000;85:526–529.[Context Link][Full Text][CrossRef][Medline Link]42.Zadik Z, Chalew SA, McCarter RJ Jr, et al. The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab. 1985;60:513–516.[Context Link][CrossRef][Medline Link]43.Hartman ML, Veldhuis JD, Thorner MO. Normal control of growth hormone secretion. Horm Res. 1993;40:37–47.[Context Link][CrossRef][Medline Link]44.Vierhapper H, Heinze G, Gessl A, et al. Use of the oral glucose tolerance test to define remission in acromegaly. Metabolism. 2003;52:181–185.[Context Link][CrossRef][Medline Link]45.Duncan E, Wass JA. Investigation protocol: acromegaly and its investigation. Clin Endocrinol (Oxf). 1999;50:285–293.[Context Link][Full Text][CrossRef][Medline Link]46.Vinik A, Pimstone B, Buchanan-Lee B. Impairment of hyperglycemic induced growth hormone suppression in hyperthyroidism. J Clin Endocrinol Metab. 1968;28:1534–1538.[Context Link]47.Becker MD, Cook GC, Wright AD. Paradoxical elevation of growth hormone in active chronic hepatitis. Lancet. 1969;2:1035–1039.[Context Link]48.Kayath MJ, Russo EM, Dib SA, et al. Do impaired glucose tolerance and diabetes mellitus interfere with the interpretation of the growth hormone response to the oral glucose tolerance test? Braz J Med Biol Res. 1992;25:449–455.[Context Link]49.Grecu EO, Walter RM Jr, Gold EM. Paradoxical release of growth hormone during oral glucose tolerance test in patients with abnormal glucose tolerance. Metabolism. 1983;32:134–137.[Context Link]50.Pieters GF, Smals AG, Kloppenborg PW. Defective suppression of growth hormone after oral glucose loading in adolescence. J Clin Endocrinol Metab. 1980;51:265–270.[Context Link][CrossRef][Medline Link]51.Holl RW, Bucher P, Sorgo W, et al. Suppression of growth hormone by oral glucose in the evaluation of tall stature. Horm Res. 1999;51:20–24.[Context Link][CrossRef][Medline Link]52.Bates AS, Evans AJ, Jones P, et al. Assessment of GH status in acromegaly using serum growth hormone, serum insulin-like growth factor-1 and urinary growth hormone excretion. Clin Endocrinol (Oxf). 1995;42:417–423.[Context Link][CrossRef][Medline Link]53.Dobrashian RD, O’Halloran DJ, Hunt A, et al. Relationships between insulin-like growth factor-1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly. Clin Endocrinol (Oxf). 1993;38:589–593.[Context Link][CrossRef][Medline Link]54.Rajasoorya C, Holdaway IM, Wrightson P, et al. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf). 1994;41:95–102.[Context Link][CrossRef][Medline Link]55.Kaltsas GA, Isidori AM, Florakis D, et al. Predictors of the outcome of surgical treatment in acromegaly and the value of the mean growth hormone day curve in assessing postoperative disease activity. J Clin Endocrinol Metab. 2001;86:1645–1652.[Context Link][Full Text][CrossRef][Medline Link]56.Peacey SR, Shalet SM. Insulin-like growth factor 1 measurement in diagnosis and management of acromegaly. Ann Clin Biochem. 2001;38:297–303.[Context Link][CrossRef][Medline Link]57.Ho KY, Weissberger AJ. Characterization of 24-hour growth hormone secretion in acromegaly: implications for diagnosis and therapy. Clin Endocrinol (Oxf). 1994;41:75–83.[Context Link][CrossRef][Medline Link]58.Hartman ML, Veldhuis JD, Vance ML, et al. Somatotropin pulse frequency and basal concentrations are increased in acromegaly and are reduced by successful therapy. J Clin Endocrinol Metab. 1990;70:1375–1384.[Context Link][CrossRef][Medline Link]59.Peacey SR, Toogood AA, Veldhuis JD, et al. The relationship between 24-hour growth hormone secretion and insulin-like growth factor I in patients with successfully treated acromegaly: impact of surgery or radiotherapy. J Clin Endocrinol Metab. 2001;86:259–266.[Context Link][Full Text][CrossRef][Medline Link]60.Parfitt VJ, Flanagan D, Wood P, et al. Outpatient assessment of residual growth hormone secretion in treated acromegaly with overnight urinary growth hormone excretion, random serum growth hormone and insulin like growth factor-1. Clin Endocrinol (Oxf). 1998;49:647–652.[Context Link][Full Text][CrossRef][Medline Link]61.Clemmons DR, Underwood LE. Nutritional regulation of IGF-I and IGF binding proteins. Annu Rev Nutr. 1991;11:393–412.[Context Link][CrossRef][Medline Link]62.Thissen JP, Ketelslegers JM, Underwood LE. Nutritional regulation of the insulin-like growth factors. Endocr Rev. 1994;15:80–101.[Context Link][CrossRef][Medline Link]63.Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16:3–34.[Context Link][CrossRef][Medline Link]64.Clemmons DR, Van Wyk JJ. Factors controlling blood concentration of somatomedin C. Clin Endocrinol Metab. 1984;13:113–143.[Context Link][CrossRef][Medline Link]65.Frystyk J, Ivarsen P, Stoving RK, et al. Determination of free insulin-like growth factor-I in human serum: comparison of ultrafiltration and direct immunoradiometric assay. Growth Horm IGF Res. 2001;11:117–127.[Context Link][CrossRef][Medline Link]66.Barkan AL, Beitins IZ, Kelch RP. Plasma insulin-like growth factor-I/somatomedin-C in acromegaly: correlation with the degree of growth hormone hypersecretion. J Clin Endocrinol Metab. 1988;67:69–73.[Context Link][CrossRef][Medline Link]67.Clemmons DR, Van Wyk JJ, Ridgway EC, et al. Evaluation of acromegaly by radioimmunoassay of somatomedin-C. N Engl J Med 1979;301:1138–1142.[Context Link][CrossRef][Medline Link]68.de Herder WW, van der Lely AJ, Janssen JA, et al. IGFBP-3 is a poor parameter for assessment of clinical activity in acromegaly. Clin Endocrinol (Oxf). 1995;43:501–505.[Context Link][CrossRef][Medline Link]69.Kim HJ, Kwon SH, Kim SW, et al. Diagnostic value of serum IGF-I and IGFBP-3 in growth hormone disorders in adults. Horm Res. 2001;56:117–123.[Context Link][CrossRef][Medline Link]70.Roelfsema F, Frolich M, Van Dulken H. Somatomedin-C levels in treated and untreated patients with acromegaly. Clin Endocrinol (Oxf). 1987;26:137–144.[Context Link]71.van der Lely AJ, de Herder WW, Janssen JA, et al. Acromegaly: the significance of serum total and free IGF-I and IGF-binding protein-3 in diagnosis. J Endocrinol. 1997;155(suppl 1):S9–13; discussion S15-16.[Context Link]72.Lamberts SW, Uitterlinden P, Schuijff PC, et al. Therapy of acromegaly with Sandostatin: the predictive value of an acute test, the value of serum somatomedin-C measurements in dose adjustment and the definition of a biochemical ’cure’. Clin Endocrinol (Oxf). 1988;29:411–420.[Context Link][CrossRef][Medline Link]73.Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. 2000;342:1171–1177.[Context Link][Full Text][CrossRef][Medline Link]74.van der Lely AJ, Hutson RK, Trainer PJ, et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet. 2001;358:1754–1759.[Context Link][CrossRef][Medline Link]75.Jaquet P, Guibout M, Jaquet C, et al. Circadian regulation of growth hormone secretion after treatment in acromegaly. J Clin Endocrinol Metab. 1980;50:322–328.[Context Link]76.Barreca A, Ciccarelli E, Minuto F, et al. Insulin-like growth factor I and daily growth hormone profile in the assessment of active acromegaly. Acta Endocrinol (Copenh). 1989;120:629–635.[Context Link]77.Rieu M, Girard F, Bricaire H, et al. The importance of insulin-like growth factor (somatomedin) measurements in the diagnosis and surveillance of acromegaly. J Clin Endocrinol Metab. 1982;55:147–153.[Context Link][CrossRef][Medline Link]78.Wass JA, Clemmons DR, Underwood LE, et al. Changes in circulating somatomedin-C levels in bromocriptine-treated acromegaly. Clin Endocrinol (Oxf). 1982;17:369–377.[Context Link]79.Jasper H, Pennisi P, Vitale M, et al. Evaluation of disease activity by IGF-I and IGF binding protein-3 (IGFBP3) in acromegaly patients distributed according to a clinical score. J Endocrinol Invest. 1999;22:29–34.[Context Link][CrossRef][Medline Link]80.Paramo C, Andrade O MA, Fluiters E, et al. Comparative study of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) level and IGF-I/IGFBP-3 ratio measurements and their relationship with an index of clinical activity in the management of patients with acromegaly. Metabolism. 1997;46:494–498.[Context Link][CrossRef][Medline Link]81.Arafah BM, Rosenzweig JL, Fenstermaker R, et al. Value of growth hormone dynamics and somatomedin C (insulin-like growth factor I) levels in predicting the long-term benefit after transsphenoidal surgery for acromegaly. J Lab Clin Med. 1987;109:346–354.[Context Link][Medline Link]82.Lindholm J, Giwercman B, Giwercman A, et al. Investigation of the criteria for assessing the outcome of treatment in acromegaly. Clin Endocrinol (Oxf). 1987;27:553–562.[Context Link][CrossRef][Medline Link]83.Colao A, Marzullo P, Ferone D, et al. Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly. J Clin Endocrinol Metab. 2000;85:3132–3140.[Context Link][Full Text][CrossRef][Medline Link]84.Colao A, Cuocolo A, Marzullo P, et al. Is the acromegalic cardiomyopathy reversible? Effect of 5-year normalization of growth hormone and insulin-like growth factor I levels on cardiac performance. J Clin Endocrinol Metab. 2001;86:1551–1557.[Context Link][Full Text][CrossRef][Medline Link]85.Knappe G, Hesse V, Jahreis G, et al. Somatomedin-C in active and successfully treated acromegaly. Exp Clin Endocrinol. 1988;91:2–6.[Context Link]86.Brockmeier SJ, Buchfelder M, Adams EF, et al. Acromegaly with ’normal’ serum growth hormone levels. Clinical features, diagnosis and results of transsphenoidal microsurgery. Horm Metab Res. 1992;24:392–400.[Context Link][CrossRef][Medline Link]87.Clemmons DR. Commercial assays available for insulin-like growth factor I and their use in diagnosing growth hormone deficiency. Horm Res. 2001;2(suppl):73–79.[Context Link][Medline Link]88.Melmed S. Confusion in clinical laboratory GH and IGF-I reports. Pituitary. 1999;2:171–172.[Context Link][Full Text][CrossRef][Medline Link]89.LeRoith D, Clemmons D, Nissley P, et al. NIH conference. Insulin-like growth factors in health and disease. Ann Intern Med. 1992;116:854–862.[Context Link][CrossRef][Medline Link]90.Merimee TJ, Zapf J, Froesch ER. Insulin-like growth factors in the fed and fasted states. J Clin Endocrinol Metab. 1982;55:999–1002.[Context Link][CrossRef][Medline Link]91.Hall K, Hilding A, Thoren M. Determinants of circulating insulin-like growth factor-I. J Endocrinol Invest 1999;22:48–57.[Context Link][Medline Link]92.Gama R, Labib M, Teale JD, et al. Acromegaly with a misleading normal plasma insulin-like growth factor 1. Ann Clin Biochem. 1989;26:102–103.[Context Link][CrossRef][Medline Link]93.Strasburger CJ, Bidlingmaier M, Wu Z, et al. Normal values of insulin-like growth factor I and their clinical utility in adults. Horm Res. 2001;2(suppl):100–105.[Context Link][Medline Link]94.Schalch DS, Kalayoglu M, Pirsch JD, et al. Serum insulin-like growth factors and their binding proteins in patients with hepatic failure and after liver transplantation. Metabolism. 1998;47:200–206.[Context Link][CrossRef][Medline Link]95.Feld S, Hirschberg R. Growth hormone, the insulin-like growth factor system, and the kidney. Endocr Rev. 1996;17:423–480.[Context Link][CrossRef][Medline Link]96.Goldberg AC, Trivedi B, Delmez JA, et al. Uremia reduces serum insulin-like growth factor I, increases insulin-like growth factor II, and modifies their serum protein binding. J Clin Endocrinol Metab. 1982;55:1040–1045.[Context Link][CrossRef][Medline Link]97.Frystyk J, Ivarsen P, Skjaerbaek C, et al. Serum-free insulin-like growth factor I correlates with clearance in patients with chronic renal failure. Kidney Int. 1999;56:2076–2084.[Context Link][Full Text][CrossRef][Medline Link]98.Wong NA, Ahlquist JA, Camacho-Hubner C, et al. Acromegaly or chronic renal failure: a diagnostic dilemma. Clin Endocrinol (Oxf). 1997;46:221–226.[Context Link][Full Text][CrossRef][Medline Link]99.Miell JP, Taylor AM, Zini M, et al. Effects of hypothyroidism and hyperthyroidism on insulin-like growth factors (IGFs) and growth hormone- and IGF-binding proteins. J Clin Endocrinol Metab. 1993;76:950–955.[Context Link][CrossRef][Medline Link]100.Herlihy OM, Perros P. Elevated serum growth hormone in a patient with type 1 diabetes: a diagnostic dilemma. Diabetes Metab Res Rev. 2000;16:211–216.[Context Link][CrossRef][Medline Link]101.Hilding A, Hall K, Wivall-Helleryd IL, et al. Serum levels of insulin-like growth factor I in 152 patients with growth hormone deficiency, aged 19–82 years, in relation to those in healthy subjects. J Clin Endocrinol Metab. 1999;84:2013–2019.[Context Link][Full Text][CrossRef][Medline Link]102.Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, et al. Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clin Endocrinol (Oxf). 1994;41:351–357.[Context Link][CrossRef][Medline Link]103.Ghigo E, Aimaretti G, Gianotti L, et al. New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol. 1996;134:352–356.[Context Link][CrossRef][Medline Link]104.Dall R, Longobardi S, Ehrnborg C, et al. The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men. GH-2000 Study Group. J Clin Endocrinol Metab. 2000;85:4193–4200.[Context Link][Full Text][CrossRef][Medline Link]105.Weissberger AJ, Ho KK, Lazarus L. Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women. J Clin Endocrinol Metab. 1991;72:374–381.[Context Link][CrossRef][Medline Link]106.Cardim HJ, Lopes CM, Giannella-Neto D, et al. The insulin-like growth factor-I system and hormone replacement therapy. Fertil Steril. 2001;75:282–287.[Context Link][CrossRef][Medline Link]107.Gomez JM, Maravall FJ, Gomez N, et al. Interactions between serum leptin, the insulin-like growth factor-I system, and sex, age, anthropometric and body composition variables in a healthy population randomly selected. Clin Endocrinol (Oxf). 2003;58:213–219.[Context Link][Full Text][CrossRef][Medline Link]108.Parkinson C, Ryder WD, Trainer PJ. The relationship between serum GH and serum IGF-I in acromegaly is gender-specific. J Clin Endocrinol Metab. 2001;86:5240–5244.[Context Link][Full Text][CrossRef][Medline Link]109.Clemmons DR, Underwood LE, Ridgway EC, et al. Estradiol treatment of acromegaly. Reduction of immunoreactive somatomedin-C and improvement in metabolic status. Am J Med. 1980;69:571–575.[Context Link][CrossRef][Medline Link]110.Cozzi R, Barausse M, Lodrini S, et al. Estroprogestinic pill normalizes IGF-I levels in acromegalic women. J Endocrinol Invest. 2003;26:347–352.[Context Link][CrossRef][Medline Link]111.Freda PU, Nuruzzaman AT, Reyes CM, et al. Significance of ’abnormal’ nadir growth hormone levels after oral glucose in postoperative patients with acromegaly in remission with normal insulin-like growth factor-I levels. J Clin Endocrinol Metab. 2004;89:495–500.[Context Link][Full Text][CrossRef][Medline Link]112.Ayuk J, Clayton RN, Holder G, et al. Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab. 2004;89:1613–1617.[Context Link][Full Text][CrossRef][Medline Link]113.Melmed S, Ezrin C, Kovacs K, et al. Acromegaly due to secretion of growth hormone by an ectopic pancreatic islet-cell tumor. N Engl J Med. 1985;312:9–17.[Context Link][CrossRef][Medline Link]114.Thorner MO, Perryman RL, Cronin MJ, et al. Somatotroph hyperplasia. Successful treatment of acromegaly by removal of a pancreatic islet tumor secreting a growth hormone-releasing factor. J Clin Invest. 1982;70:965–977.[Context Link][CrossRef][Medline Link]115.Sano T, Asa SL, Kovacs K. Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations. 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