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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-1371
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The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 2 523-527
Copyright © 2009 by The Endocrine Society

The Utility of Oral Glucose Tolerance Testing for Diagnosis and Assessment of Treatment Outcomes in 166 Patients with Acromegaly

John D. Carmichael, Vivien S. Bonert, James M. Mirocha and Shlomo Melmed

Departments of Medicine (J.D.C., V.S.B., S.M.), and Biostatistics (J.M.M.), Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048

Address all correspondence and requests for reprints to: Shlomo Melmed, M.D., Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 2015, Los Angeles, California 90048. E-mail: melmeds{at}cshs.org.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: GH suppression after oral glucose load [oral glucose tolerance test (OGTT)] and normal age- and gender-matched IGF-I levels reflect biochemical control of acromegaly. The OGTT is the gold standard for determining control of GH secretion at diagnosis and after surgical treatment, but the usefulness of performing an OGTT in patients treated with medical therapy has not been determined.

Objective: Our objective was to assess relationships between basal GH levels (basal GH), GH responses to OGTT [GH nadir (GHn)], and IGF-I levels.

Design: This was a retrospective electronic database review.

Setting: This study was performed at a tertiary outpatient pituitary center.

Patients: A total of 166 patients with acromegaly (79 females, 87 males) were included in the study. Four categories of testing were performed: diagnosis, postoperative assessment without medication, testing during somatostatin analog (SA) therapy, and testing during dopamine agonist (DA) therapy.

Main Outcome Measures: Basal serum GH and IGF-I levels and GH levels 2 h after 75 g OGTT were measured.

Results: A total of 482 simultaneous OGTT and IGF-I measurements were observed from 1985–2008. Discordant results of oral glucose tolerance testing (GHn and IGF-I) were observed 33, 48, and 18% in postoperative assessment without medication, SA, and DA categories, respectively. In the SA category, 42% of tests were discordant with normal IGF-I and nonsuppressed GHn. In contrast, 4% of tests were discordant with normal IGF-I and nonsuppressed GH in those treated with DA. No significant differences in discordance were observed when basal GH was used.

Conclusions: Both basal and GHn levels are highly discordant with IGF-I levels during medical therapy with SAs. The OGTT is not useful in assessing biochemical control in these subjects.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
Acromegaly is a rare disease caused by excess GH secretion, most commonly by a pituitary adenoma (1). The disease is characterized by failure to suppress GH levels in response to an oral glucose load [oral glucose tolerance test (OGTT)], and elevated serum IGF-I levels. Acromegaly is associated with enhanced morbidity and mortality if left untreated (2). Surgery is usually the first-line therapy, but many patients are treated with primary medical therapy, adjuvant medical therapy, or radiation. Success of these interventions is measured by biochemical control, symptomatic improvement, and preservation of normal pituitary function, with the overall goal of improving disease-related morbidity and mortality.

The optimal method for assessing the integrity of GH secretion during or after treatment has not been determined. Measuring GH levels is reflective of the neurosecretory dysfunction characteristic of GH-cell adenomas (1), whereas measuring IGF-I levels provides a surrogate marker of peripheral GH bioactivity (3). There is controversy surrounding the use of generalized cutoff points for GH levels when various methods of measuring GH are used (4). The diagnosis of acromegaly is made with observing an elevated IGF-I level as matched for age and gender, and failure to suppress GH in response to an OGTT to a level of less than 1 µg/liter (5). However, it has become increasingly apparent that a lower cutoff point is required with the use of newer, highly sensitive immunometric assays (6). Combined with IGF-I measurement, the OGTT is also recommended to assess the outcome of surgical therapy, with a GH cutoff measurement of less than 0.4 µg/liter, signifying biochemical control using immunometric assays (7). Nevertheless, GH nadir (GHn) levels in response to an OGTT have not been related to normalizing mortality in acromegaly. In contrast, achieving normal IGF-I levels and basal GH levels less than 2.5 µg/liter have been associated with reduced morbidity and mortality, and have, thus, been recommended as target values for therapeutic efficacy (2, 8, 9, 10, 11).

Few studies have reported results of GH levels measured after an OGTT during medical therapy (12, 13, 14). The utility of an OGTT for monitoring therapeutic responses in these subjects has not been determined. To assess the utility of performing an OGTT after surgical resection of a somatotroph tumor, and during medical therapy of the disorder, we examined relationships between basal and post-OGTT GHn levels, and IGF-I levels in 166 subjects with acromegaly. This is the first report analyzing the efficacy of the OGTT to determine disease control in subjects receiving medical therapy for acromegaly.


   Subjects and Methods
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 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects were selected from a computerized pituitary tumor research registry for which patients have provided informed consent (15). The Cedars-Sinai Pituitary Tumor Research Registry comprises tertiary and quaternary referrals, and as of February 2008, includes data for 861 patients with pituitary disease, 272 of whom have acromegaly. All patients with acromegaly had confirmation of diagnosis with either elevated IGF-I or nonsuppressed GH in response to an OGTT or both. Records were reviewed for a diagnosis of acromegaly and the presence of simultaneous results of an OGTT and IGF-I testing. Only subjects with simultaneous IGF-I and OGTT measurements were included for analysis. A total of 166 patients with acromegaly (87 males, 79 females) were assessed by 482 simultaneous OGTT and IGF-I measurements from 1985–2008. Of these patients, 144 were treated with surgery, including 24 treated with multiple surgical interventions. Assessment of tumor size at presentation showed 125 macroadenomas, 19 microadenomas, and 12 unknown. There were 29 subjects treated with radiation therapy (13 females/16 males). A total of 35 patients (19 males/16 females) were treated with primary medical therapy, including 13 treated with preoperative medication. There were 57 patients who received medication postoperatively [32 females/25 males; 47% dopamine agonists (DAs), 89% somatostatin analogs (SAs), 26% combined therapy].

Indications for an OGTT were classified as follows: Diagnosis (Dx) (71 patients, 71 paired OGTT and IGF-I levels); postoperative assessment without medication (POP-NM) (104 patients, 241 paired OGTT and IGF-I levels); testing during SA therapy (47 patients, 120 paired OGTT and IGF-I levels; five subjects, 13 paired OGTT during combined SA/DA therapy); and testing during DA therapy (16 patients, 50 paired OGTT and IGF-I levels). Test results, and not individual patients, were used as the unit of analysis.

Assays

Multiple GH and IGF-I assays were used during the period of assessments. Assays that were used by us include: GH and IGF-I assays at Nichols Institute Reference Laboratories (San Juan Capistrano, CA) from 1986–1994; Esoterix Inc. (Calabasas, CA) from 1994–2005; the Nichols Advantage assay at Nichols Institute/Quest Diagnostics (San Juan Capistrano, CA) from 2005–2006; and the DPC Immulite 2000 assay (Diagnostic Products Corp., Los Angeles, CA) at Quest Diagnostics from 2006-present. All GH and IGF-I assays are two-site RIAs, and each was standardized against World Health Organization international standard preparations, with changes in reference preparations made over the years. The data presented here, retrieved from a registry database, were derived from several laboratories.

Definitions

Basal GH values (GH0) were considered safe at less than 2.5 µg/liter (8). GHn levels were considered controlled at less than 2 µg/liter for patients tested before 1998, and less than 1 µg/liter for those tested thereafter to account for changes in sensitivity of GH assays used, and to reflect contemporary criteria for cure (5, 16). Because several IGF-I assays were used over the years, IGF-I was expressed as a SD score to adjust for the different assays and normal ranges. GH0 results were obtained in the fasting state in 98% of tests. Discordance was defined as disagreement among IGF-I, GH0, and GHn test results, elevated or normal, based on the aforementioned criteria.

Statistics

Statistical analysis was performed using SPSS version 15.0 (SPSS, Inc., Chicago, IL). Bivariate correlations were performed using Spearman rank order correlation. Within each indicated category of oral glucose tolerance testing, the presence or absence of normal GH0, GHn, and IGF-I were established using criteria outlined previously. Differences in percent discordance of GH0, GHn, and IGF-I between each test category were compared using Fisher’s exact test. Within each category, percent discordance between paired IGF-I and GH0 results, and paired IGF-I and GHn results were compared using McNemar’s test. A two-tailed P value of less than 0.05 was considered statistically significant.


   Results
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 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Results of oral glucose tolerance testing are depicted in Table 1Go. Testing was performed on 71 occasions for diagnostic purposes, on 241 occasions for postoperative assessment of disease control without medications, 120 times in subjects receiving SAs, 89 times postoperatively, and 31 times for assessment of primary medical therapy efficacy. Testing was performed 50 times in subjects receiving DA therapy, 33 times postoperatively, and 17 times to assess effectiveness of primary medical therapy. Mean basal GH (GH0), GH response to a glucose load (GHn), and change in GH levels in response to the glucose load ({Delta}GH) are listed in Table 1Go for each group.


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  		TABLE 1. GH and IGF-I results for the test groups

 
Using standard criteria, the percentage of tests in each category indicating disease control as determined by GH0, GHn, and IGF-I, is listed in Table 1Go. All diagnostic testing confirmed the diagnosis of acromegaly by OGTT and IGF-I criteria. Using IGF-I criteria solely, control was achieved in 56% of tests by surgery alone, 57% by treatment with SA, and 16% of tests in subjects receiving DA. In subjects receiving DA therapy, disease control was achieved in 34% as determined by GH0 criteria and in 26% by GHn criteria. Disease control was achieved in 37% by GH0 criteria and 21% of tests by GHn criteria in those receiving SA therapy.

Discordant values between IGF-I and both GH0 and GHn results were observed in the POP-NM, SA, and DA testing categories (Table 2Go). Discordance between paired IGF-I and GHn was not statistically different than the discordance observed between paired IGF-I and GH0 in any testing category (all P = not significant). The greatest discordance was observed in subjects receiving SA therapy (48% for GHn, 45% for GH0). Results of postoperative GHn and GH0 assessments without medications were discordant with IGF-I in 32% of both measurements. In subjects receiving DA therapy, IGF-I results were discordant with GHn results in 18 and in 22% for GH0. The discordance observed in the SA group was significantly higher than the POP-NM (P = 0.03) and DA groups (P < 0.001).


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  		TABLE 2. Discordance and correlations between GH measurements and IGF-I measurements

 
Subjects treated with SAs showed a predominant discordance with high GHn and normal IGF-I results in 42%, compared with 6% with high IGF-I and normal GH levels (Fig. 1Go). Few subjects receiving DAs were controlled, and the predominant discordance was with high IGF-I and normal GHn (14%). Postoperative assessments without medication were discordant with high GHn in 24% compared with 8% with high IGF-I levels.


Figure 1
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  		FIG. 1. Subcategories of concordance and discordance between GHn and IGF-I in the three test groups. The predominant discordance in subjects receiving SAs was normal IGF-I with nonsuppressed GH. A, Postoperative, no medications (n = 241). B, SAs (n = 120). C, DAs (n = 50).

 
GH0 correlated with GHn in all test categories (all P < 0.001). IGF-I significantly correlated with both GHn and GH0 (Table 2Go). Strongest relationships were observed between GHn and IGF-I in postoperative subjects not receiving medications (r = 0.56) and postoperative subjects treated with DAs (r = 0.75). Correlations were weaker for Dx (r = 0.37) and for SA treatment (r = 0.44). Correlations were similar when comparing GH0 and IGF-I except for Dx (r = 0.45), SA treatment (r = 0.36), and for postoperative DA treatment (r = 0.59).


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Measuring GH levels within 2 h of an oral glucose load (OGTT) is a well-established method for diagnosing acromegaly (17, 18). In contrast to control individuals, patients with acromegaly who harbor GH-producing tumors fail to suppress GH secretion in response to an oral glucose load. In the appropriate clinical context, an elevated IGF-I level alone can be diagnostic of acromegaly, and the GH measurement during an OGTT corroborates the diagnosis. There have been reports of patients diagnosed with acromegaly with normal IGF-I levels as well as patients exhibiting normal GH levels after an OGTT (6, 19, 20, 21). Moreover, discordant results of GH and IGF-I measurements after surgical treatment have been well documented (22, 23, 24, 25, 26). Although reports suggest that elevated GH levels despite normal IGF-I levels are associated with a higher rate of disease recurrence (23), further study is required to define the implications of discordant circulating biochemical disease markers reported here.

This study reports a high degree of discordance between both GHn and GH0 values and IGF-I levels in patients treated with SAs. The predominant discordance was with high GH and normal IGF-I levels. The implications of this observation are that subjects with controlled disease (as defined by measuring IGF-I) may be persistently secreting excess GH despite medical therapy. Direct suppression of GH dependent IGF-I induction by peripheral somatostatin action on rat hepatocytes has been demonstrated, which may account for discordant values of IGF-I and GH (27). Alternatively, these results may denote a disturbance in the normal physiological response of the GH axis to oral glucose imparted by medical therapy, and that the lack of suppression is reflective of an artifact of treatment. Supporting the former explanation is the observation that basal GH results are no better in concurring with IGF-I results than the postglucose GHn, even when a level of 2.5 µg/liter is used as a modest cutoff for basal levels. Others have reported the discordance between GH and IGF-I levels in patients with acromegaly during SA therapy, but not using the OGTT (28, 29). The finding of elevated GH and normal IGF-I during SA therapy is in contrast to the predominance of discordance with elevated IGF-I and suppressed GH in subjects receiving DA.

The results presented here were retrieved from a registry database, including results from several laboratories. Methods for both the measurement of GH and IGF-I have changed over the period of this study. We chose standardized cutoff points for defining normal GH that were derived from published guidelines describing the care and management of patients with acromegaly (5, 16). These publications attempted to establish cutoff points that could be applied to the multiple clinically available assays; however, it is accepted that these cutoffs were largely arbitrary, and not assay specific. Recent studies have demonstrated the variation from these accepted cutoff points using sensitive immunoradiometric assays, emphasizing the imprecision of these generalized cutoff points (22, 30, 31). Furthermore, questions remain as to which biochemical marker of disease activity is most relevant to predicting long-term morbidity and mortality (2, 8, 9, 10, 11).

In all groups, IGF-I levels correlated significantly with measures of both basal and nadir GH levels. These results corroborate studies demonstrating a log-linear relationship between the two hormones (32). Although these measurements of GH secretion may correlate, this observation does not translate into concordance between measures of GH and IGF-I when arbitrary, internationally accepted cutoff points are used. For both GH and IGF-I, there is a high degree of variability both within assays and between assays (33, 34). There is no consensus on assay standards, antibodies used, and "normal" population values (30). Therefore, assay-specific cutoff points should be used to define disease activity until uniformity of IGF-I and GH assays is established. Cutoff points should be established with reference values for gender, age, and body mass index because these factors have influenced the GHn after a glucose load (31, 35).

The current state of biochemical assessment of disease activity in acromegaly is fraught with uncertainty. Measurements of key hormone markers are subject to unacceptable variability, methods of assessment are not uniform, and treatment goals have been based on historical data derived from earlier generation assays. Discordant biochemical results are observed in many patients postoperatively, regardless of the method of GH assessment used. The OGTT exhibits a high degree of discordance when performed to assess medical therapy outcomes. Therefore, it is unclear whether to rely on the IGF-I or the GH measurement. The results indicate that the use of the OGTT provides no advantage for assessment of disease status in patients being treated with SAs, compared with measuring basal GH levels.


   Footnotes
 
Disclosure Statement: The authors have nothing to disclose.

First Published Online November 25, 2008

Abbreviations: DA, Dopamine agonist; Dx, diagnosis; GHn, GH nadir; GH0, basal GH, OGTT, oral glucose tolerance test; POP-NM, postoperative assessment without medication; SA, somatostatin analog.

Received June 27, 2008.

Accepted November 17, 2008.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Melmed S 2006 Medical progress: acromegaly. N Engl J Med 355:2558–2573[Free Full Text]
  2. Bates AS, Van't Hoff W, Jones JM, Clayton RN 1993 An audit of outcome of treatment in acromegaly. Q J Med 86:293–299[Medline]
  3. Sata A, Ho KK 2007 Growth hormone measurements in the diagnosis and monitoring of acromegaly. Pituitary 10:165–172[CrossRef][Medline]
  4. Bidlingmaier M, Strasburger CJ 2007 Growth hormone assays: current methodologies and their limitations. Pituitary 10:115–119[CrossRef][Medline]
  5. Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S 2000 Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 85:526–529[Abstract/Free Full Text]
  6. Freda PU, Reyes CM, Nuruzzaman AT, Sundeen RE, Bruce JN 2003 Basal and glucose-suppressed GH levels less than 1 microg/L in newly diagnosed acromegaly. Pituitary 6:175–180[CrossRef][Medline]
  7. Melmed S, Casanueva F, Cavagnini F, Chanson P, Frohman LA, Gaillard R, Ghigo E, Ho K, Jaquet P, Kleinberg D, Lamberts S, Laws E, Lombardi G, Sheppard MC, Thorner M, Vance ML, Wass JA, Giustina A 2005 Consensus statement: medical management of acromegaly. Eur J Endocrinol 153:737–740[Abstract/Free Full Text]
  8. Orme SM, McNally RJ, Cartwright RA, Belchetz PE 1998 Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab 83:2730–2734[Abstract/Free Full Text]
  9. Swearingen B, Barker 2nd FG, Katznelson L, Biller BM, Grinspoon S, Klibanski A, Moayeri N, Black PM, Zervas NT 1998 Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 83:3419–3426[Abstract/Free Full Text]
  10. Holdaway IM, Rajasoorya RC, Gamble GD 2004 Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89:667–674[Abstract/Free Full Text]
  11. Biermasz NR, Dekker FW, Pereira AM, van Thiel SW, Schutte PJ, van Dulken H, Romijn JA, Roelfsema F 2004 Determinants of survival in treated acromegaly in a single center: predictive value of serial insulin-like growth factor I measurements. J Clin Endocrinol Metab 89:2789–2796[Abstract/Free Full Text]
  12. Kendall-Taylor P, Miller M, Gebbie J, Turner S, al-Maskari M 2000 Long-acting octreotide LAR compared with lanreotide SR in the treatment of acromegaly. Pituitary 3:61–65[CrossRef][Medline]
  13. Diez JJ, Iglesias P, Gomez-Pan A 2001 Growth hormone responses to oral glucose and intravenous thyrotropin-releasing hormone in acromegalic patients treated by slow-release lanreotide. J Endocrinol Invest 24:303–309[Medline]
  14. Yetkin DO, Boysan SN, Tiryakioglu O, Yalin AS, Kadioglu P 2007 Forty month follow-up of persistent and difficultly controlled acromegalic patients treated with depot long acting somatostatin analog octreotide. Endocr J 54:459–464[CrossRef][Medline]
  15. Drange MR, Fram NR, Herman-Bonert V, Melmed S 2000 Pituitary tumor registry: a novel clinical resource. J Clin Endocrinol Metab 85:168–174[Abstract/Free Full Text]
  16. Melmed S, Jackson I, Kleinberg D, Klibanski A 1998 Current treatment guidelines for acromegaly. J Clin Endocrinol Metab 83:2646–2652[Abstract/Free Full Text]
  17. Roth J, Glick SM, Yalow RS, Berson SA 1964 The influence of blood glucose on the plasma concentration of growth hormone. Diabetes 13:355–361[Medline]
  18. Earll JM, Sparks LL, Forsham PH 1967 Glucose suppression of serum growth hormone in the diagnosis of acromegaly. JAMA 201:628–630[Abstract/Free Full Text]
  19. Dimaraki EV, Jaffe CA, DeMott-Friberg R, Chandler WF, Barkan AL 2002 Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab 87:3537–3542[Abstract/Free Full Text]
  20. Lim DJ, Kwon HS, Cho JH, Kim SH, Choi YH, Yoon KH, Cha BY, Lee KW, Son HY, Kang SK 2007 Acromegaly associated with type 2 diabetes showing normal IGF-1 levels under poorly controlled glycemia. Endocr J 54:537–541[CrossRef][Medline]
  21. Mercado M, Espinosa de los Monteros AL, Sosa E, Cheng S, Mendoza V, Hernandez I, Sandoval C, Guinto G, Molina M 2004 Clinical-biochemical correlations in acromegaly at diagnosis and the real prevalence of biochemically discordant disease. Horm Res 62:293–299[CrossRef][Medline]
  22. Freda PU, Post KD, Powell JS, Wardlaw SL 1998 Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab 83:3808–3816[Abstract/Free Full Text]
  23. Freda PU, Nuruzzaman AT, Reyes CM, Sundeen RE, Post KD 2004 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 89:495–500[Abstract/Free Full Text]
  24. Alexopoulou O, Bex M, Abs R, T'Sjoen G, Velkeniers B, Maiter D 2008 Divergence between growth hormone and insulin-like growth factor-I concentrations in the follow-up of acromegaly. J Clin Endocrinol Metab 93:1324–1330[Abstract/Free Full Text]
  25. Espinosa-de-los-Monteros AL, Mercado M, Sosa E, Lizama O, Guinto G, Lopez-Felix B, Garcia O, Hernandez I, Ovalle A, Mendoza V 2002 Changing patterns of insulin-like growth factor-I and glucose-suppressed growth hormone levels after pituitary surgery in patients with acromegaly. J Neurosurg 97:287–292[Medline]
  26. Vierhapper H, Heinze G, Gessl A, Exner M, Bieglmayr C 2003 Use of the oral glucose tolerance test to define remission in acromegaly. Metabolism 52:181–185[CrossRef][Medline]
  27. Murray RD, Kim K, Ren SG, Chelly M, Umehara Y, Melmed S 2004 Central and peripheral actions of somatostatin on the growth hormone-IGF-I axis. J Clin Invest 114:349–356[CrossRef][Medline]
  28. Machado EO, Taboada GF, Neto LV, Haute FR, Correa LL, Balarini GA, Shrank Y, Goulart M, Gadelha MR 2008 Prevalence of discordant GH and IGF-I levels in acromegalics at diagnosis, after surgical treatment and during treatment with octreotide LAR. Growth Horm IGF Res 18:389–393[CrossRef][Medline]
  29. Cozzi R, Attanasio R, Grottoli S, Pagani G, Loli P, Gasco V, Pedroncelli AM, Montini M, Ghigo E 2004 Treatment of acromegaly with SS analogues: should GH and IGF-I target levels be lowered to assert a tight control of the disease? J Endocrinol Invest 27:1040–1047[Medline]
  30. Gullu S, Keles H, Delibasi T, Tonyukuk V, Kamel N, Erdogan G 2004 Remission criteria for the follow-up of patients with acromegaly. Eur J Endocrinol 150:465–471[Abstract]
  31. Arafat AM, Mohlig M, Weickert MO, Perschel FH, Purschwitz J, Spranger J, Strasburger CJ, Schofl C, Pfeiffer AF 2008 Growth hormone response during oral glucose tolerance test: the impact of assay method on the estimation of reference values in patients with acromegaly and in healthy controls, and the role of gender, age, and body mass index. J Clin Endocrinol Metab 93:1254–1262[Abstract/Free Full Text]
  32. Barkan AL, Beitins IZ, Kelch RP 1988 Plasma insulin-like growth factor-I/somatomedin-C in acromegaly: correlation with the degree of growth hormone hypersecretion. J Clin Endocrinol Metab 67:69–73[Abstract/Free Full Text]
  33. Strasburger CJ, Bidlingmaier M 2005 How robust are laboratory measures of growth hormone status? Horm Res 64(Suppl 2):1–5
  34. Pokrajac A, Wark G, Ellis AR, Wear J, Wieringa GE, Trainer PJ 2007 Variation in GH and IGF-I assays limits the applicability of international consensus criteria to local practice. Clin Endocrinol (Oxf) 67:65–70[CrossRef][Medline]
  35. Colao A, Pivonello R, Cavallo LM, Gaccione M, Auriemma RS, Esposito F, Cappabianca P, Lombardi G 2006 Age changes the diagnostic accuracy of mean profile and nadir growth hormone levels after oral glucose in postoperative patients with acromegaly. Clin Endocrinol (Oxf) 65:250–256[CrossRef][Medline]



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S. Melmed, A. Colao, A. Barkan, M. Molitch, A. B. Grossman, D. Kleinberg, D. Clemmons, P. Chanson, E. Laws, J. Schlechte, et al.
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