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Long-Term Biochemical Status and Disease-Related Morbidity in 53 Postoperative Patients with Acromegaly

Service of Endocrinology (O.S., C.B.) and Service of Neurosurgery (J.H.), Centre Hospitalier de l’Université de Montreal, Notre-Dame Hospital, University of Montreal, Montreal, H2L 4M1 Canada

Address all correspondence and requests for reprints to: Dr. Omar Serri, M.D., Ph.D., Metabolic Unit, Centre Hospitalier de l’Université de Montreal, Notre-Dame Hospital, 1560 Sherbrooke East, Montreal (Quebec), Canada H2L 4M1. E-mail: omar.serri{at}umontreal.ca.

	Abstract

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Assessment of postoperative disease activity of acromegaly is a major challenge. The consensus criteria for cure, which are glucose-suppressed GH less than 1 µg/liter and normal IGF-I levels, might be discrepant, and their respective relationship to acromegaly-related morbidity is not well known. The aims of our study were: firstly, to correlate plasma IGF-I with plasma glucose-suppressed GH concentrations; and secondly, to correlate each of these biochemical parameters with morbidity [impaired glucose tolerance (IGT), diabetes, and hypertension] in postoperative patients with acromegaly. Fifty-three patients with long-term follow-up (mean, 12.7 yr; range, 1–30 yr) after transsphenoidal surgery for acromegaly and 20 healthy subjects matched for age, sex, and body mass index were evaluated for plasma glucose [by 75-g oral glucose tolerance test (OGTT)], GH (by immunoradiometric assay), plasma IGF-I (by immunoradiometric assay), and blood pressure (BP) measurements. Remission was defined by a normal IGF-I. We identified 34 acromegalics in remission and 19 with active disease. There was no statistical difference between all three groups for age, sex, BMI, and for fasting and 2-h post-OGTT plasma glucose. The time elapsed since surgery was similar in both groups of acromegalics. The OGTT-GH nadir was less than 1 µg/liter in 31 patients in remission (91.2%) and in nine patients with active disease (47.4%). Prevalence of IGT was lower in acromegalics in remission (14.7%) in comparison with patients with active disease (47.4%; P = 0.01). Plasma IGF-I and GH nadir cut-off of 0.25 µg/liter were strong predictors of abnormal glucose tolerance (odds ratio, 13.6; confidence interval, 2.5–73.7; P = 0.003). GH nadir cut-off of 1 µg/liter and basal GH of 2.5 µg/liter failed to predict abnormal glucose tolerance. There was no statistical difference for prevalence of hypertension and systolic BP values, but diastolic BP was significantly lower in patients in remission than in those with active disease (P < 0.05). Our observations indicate that the validity of the GH threshold of 1 µg/liter post OGTT might be inadequate as a criterion of biochemical remission of acromegaly and as a marker of associated comorbidities. However, normalized IGF-I concentrations and a lower GH cut-off value less than 0.25 µg/liter are strongly associated with a lower prevalence of IGT and lower diastolic BP in long-term postoperative acromegaly.

	Introduction

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OVER THE YEARS, the criteria for biochemical cure and consequently the biochemical goals of therapy in acromegaly have changed with the availability of reliable IGF-I assays and more sensitive GH assays. Along with the measurement of IGF-I, oral glucose tolerance test (OGTT) is the recommended test to assess a biochemical cure of acromegaly (1). With this test, cure was previously defined as a suppression of GH to less than 2 µg/liter, as measured by a polyclonal RIA (2). However, with this cut-off of 2 µg/liter, glucose-suppressed GH values in healthy subjects overlapped with those in patients with active acromegaly. Therefore, a consensus statement in the year 2000 by Giustina et al. (3) established that using all current commercial assays normally should suppress GH to less than 1 µg/liter after oral glucose ingestion. However, the validity of this new cut-off value of 1 µg/liter as a criterion of biochemical cure could be questioned in light of the results of a study by Freda et al. (4) of a cohort of postoperative patients with acromegaly. In that study, nadir GH values less than 1 µg/liter were found in up to 50% of patients with active disease (defined by elevated serum IGF-I).

The validity of a criterion of biochemical cure should be related to long-term morbidity and mortality. A normal postoperative IGF-I value restores life expectancy to normal (5, 6). A mean postoperative random GH value less than 2.5 µg/liter has also been related to a normalized life expectancy in acromegalic patients (7, 8). There are no data correlating the post-OGTT GH nadir less than 1 µg/liter or postoperative IGF-I to acromegaly-related morbidity such as glucose intolerance, diabetes, or arterial hypertension. Therefore, the aims of our study were, firstly, to correlate plasma IGF-I with plasma glucose-suppressed GH concentrations and, secondly, to correlate these biochemical parameters with morbidity [impaired glucose tolerance (IGT), diabetes, and hypertension] in postoperative patients with acromegaly.

	Subjects and Methods

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Patient population

We studied 53 patients with acromegaly who underwent transsphenoidal surgery by the same neurosurgeon (J.H.) between 1970 and 2000. Subjects were selected for their availability and willingness to participate in the study. (Most of the patients were referred to us for this study by endocrinologists from our hospital and some by regional endocrinologists). All patients were studied at least 1 yr after surgery with a mean period from surgery to evaluation of 12.7 ± 1.5 yr (range, 1–30 yr). All patients had pathological confirmation of a GH-secreting adenoma. Patients with hypopituitarism were excluded.

Five patients had received radiation therapy postoperatively (three in the group in remission and two in the group with active acromegaly). Twenty healthy subjects with no family history of diabetes, matched with the patients for age, gender, and body mass index (BMI), also were studied.

Study procedures

The protocol was approved by the Ethics Committee of Notre-Dame Hospital. Written informed consent was obtained from all patients and healthy subjects. Patients were asked about family history of diabetes (considered positive if the patient had at least one first-degree relative who was diagnosed with diabetes after age 30), about personal history of hypertension and use of antihypertensives, and about use of any medications, including hormonal replacement. Three patients were treated with somatostatin analogs and were studied after an 8-wk period of withdrawal.

After an overnight fast, all patients had an OGTT. Blood was sampled twice at baseline (at -15 min and at 0 min), and then at 60, 90, and 120 min after a 75-g oral glucose ingestion. One baseline blood sample was assayed for IGF-I, and blood samples at all time points were assayed for glucose and GH. Classification of subjects was made according to the American Diabetes Association criteria approved by the World Health Organization (WHO) (9, 10): subjects with 2-h plasma glucose level less than 7.8 mmol/liter were classified as normoglycemic, those with 7.8–11.0 mmol/liter were classified as having IGT, and those with more than 11.1 mmol/liter were classified as having diabetes. Blood pressure (BP) was measured with a standard mercury sphygmomanometer at -15 min and 0 min in a relaxed position after a more than 5-min period of rest. The average of the two measurements is given.

Assays

GH. GH was measured by immunoradiometric assay (IRMA) using a kit from Nichols Institute Diagnostics (San Juan Capistrano, CA). This assay used anti-human-GH mouse monoclonal antibodies. The standards were calibrated to the National Institutes of Health reference: NIAMDD-hGH-RP-1. The assay sensitivity was 0.02 µg/liter. The interassay coefficients of variation in our laboratory were 13.3% for mean GH of 2.3 µg/liter and 8.1% for mean GH of 7 µg/liter.

IGF-I. IGF-I was measured by IRMA using a kit from Nichols Institute Diagnostics. Recombinant human IGF-I was used for the standards and labeled with ¹²⁵I for the tracer. The antiserum for IGF-I showed no cross-reactivity with IGF-II, proinsulin or insulin. The standard was calibrated against WHO First International Reference Reagent, IGF-I 87/518. The assay sensitivity was 6 µg/liter. The interassay coefficients of variation were, in our laboratory, 11.3% for mean IGF-I of 88 µg/liter and 7.8% for mean IGF-I of 244 µg/liter. The normal ranges for this assay are as follows: ages 19–39 yr, 122–400 µg/liter; ages 40–54 yr, 75–306 µg/liter; and ages 55 yr and older, 48–225 µg/liter.

Statistical analysis

Mean values for age, BMI, time since surgery, fasting glucose, 2-h postload plasma glucose, basal GH, nadir GH, IGF-I, systolic BP, and diastolic BP were calculated for each group of subjects and were expressed ± SE. Nadir GH was defined as the lowest value at any time after oral glucose ingestion. All variables were compared for significant difference between groups by ANOVA with post hoc testing using Tukey’s multiple comparison test. When values were not normally distributed, Kruskal-Wallis statistics were made using Dunn’s multiple comparison test. The difference between groups of acromegalics for the prevalence of diabetes and IGT was evaluated using the ² test. Multivariate analysis was used to determine the correlations among IGF-I, basal GH, nadir GH, systolic BP, diastolic BP, fasting plasma glucose, plasma glucose 2-h post-OGTT, age, and BMI. The relationship of variables (age, sex, BMI, basal GH, glucose-suppressed GH, and IGF-I) transformed into categorical data to the prevalence of abnormal glucose tolerance was evaluated using logistic regression analysis to obtain odd ratios. All data analysis was performed using the SPSS computer program (SPSS, Inc., Chicago, IL).

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patients were separated into two groups: 34 had an IGF-I normal for their age (22 males and 12 females) and were considered in remission; 19 had a high IGF-I (14 males and 5 females) and were considered to have active acromegaly.

Clinical and biochemical characteristics of both groups of acromegalic patients and healthy subjects are shown in Table 1. Age, gender, BMI, plasma fasting, glucose, plasma 2-h post-OGTT glucose, and systolic BP were not significantly different in all three groups. Time elapsed since surgery and prevalence of hypertension were not significantly different between the two groups of acromegalics. A history of treated hypertension was found in 11 patients in remission (32%) and in five patients with active acromegaly (26%). Diastolic BP was significantly lower (P < 0.05) in patients in remission (70 ± 1 mm Hg) than in patients with active disease (77 ± 2 mm Hg) but not different from that in healthy subjects (73 ± 1.8 mm Hg).

Basal GH measurements were not significantly different in all three groups. Plasma IGF-I and glucose-suppressed GH concentrations were significantly lower in patients in remission (163 ± 11 and 0.25 ± 0.07 µg/liter) than in patients with active disease (425 ± 38 and 1.2 ± 0.3 µg/liter) (P < 0.001) but not different from those of healthy subjects (137 ± 8 and 0.04 ± 0.00 µg/liter) (Table 2). GH nadir was less than 1 µg/liter in 31 patients in remission (91.2%) and in nine patients with active disease (47.4%).

When all acromegalics were considered together, IGF-I levels were correlated significantly with basal GH (r = 0.49; P = 0.000), nadir GH (r = 0.73; P = 0.000), and diastolic BP (r = 0.28; P = 0.042) and were inversely correlated with age (r = -0.31; P = 0.02). IGF-I levels were not correlated with BMI, with systolic BP, or with fasting and 2-h glucose values.

Glucose tolerance

The OGTT revealed abnormalities of glucose tolerance consisting of either IGT (n = 5) or diabetes mellitus (n = 2) in acromegalics in remission. IGT was observed in nine patients and diabetes was observed in two patients in the group of acromegalics with active disease. Thus, the prevalence of either IGT or combined IGT and diabetes was significantly increased in patients with active disease (47.4 and 57.9%, respectively) vs. patients in remission (14.7 and 20.6%, respectively) (² = 6.7; P = 0.01, and ² = 7.6; P = 0.006). A positive family history for diabetes was noted in four patients with acromegaly in remission and in three patients with active disease. The odds ratio for prevalence of abnormalities of glucose tolerance with elevated IGF-I was 13.6 (95% confidence interval, 2.5–73.7; P = 0.003) and was of 1.1 for each additional year of age (95% confidence interval, 1.03–1.2; P = 0.008). GH nadir less than 1 µg/liter and basal GH less than 2.5 µg/liter were not predictors of abnormal glucose tolerance. However, GH nadir less than 0.25 µg/liter was significantly associated with reduced prevalence of abnormal glucose tolerance (² = 5.85; P = 0.016).

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
In the present study, we first confirmed a previous observation by Freda et al. (4) that a glucose-suppressed cut-off GH value of 1 µg/liter fails to identify a significant proportion of postoperative acromegalic patients with active disease defined by elevated IGF-I. In their study of 60 postoperative patients, Freda et al. (4) found that GH was suppressed to less than 1 µg/liter in 11 of 22 patients (50%) with active disease. Dimaraki et al. (11) also reported 16 patients with newly diagnosed acromegaly in whom GH and IGF-I levels were discrepant. All had an elevated IGF-I, but GH was suppressed to less than 1 µg/liter during OGTT in eight patients. We found, similarly to these two studies, that nadir GH post OGTT was less than 1 µg/liter in 9 of 19 patients (47.4%) with elevated plasma IGF-I levels. The highest nadir GH value in our control group was 0.15 µg/liter, and, in the patients with active disease, GH was suppressed as low as 0.25 µg/liter. Using a GH nadir cut-off value of 0.25 µg/liter to define remission or disease activity, we obtained a 94.7% sensitivity and 85.2% specificity. Freda et al. (4) found that the lowest GH nadir (measured by IRMA) in their patients with elevated IGF-I was 0.33 µg/liter. Using 0.4 µg/liter as a cut-off value in our series yields an 84.2% sensitivity and 88.9% specificity. Taken together, these results indicate that the post-OGTT GH nadir of 1 µg/liter is inappropriately high for the assessment of postoperative acromegaly activity and that there is a need to revise the diagnostic criteria proposed in the consensus statement on acromegaly by Giustina et al. (3). Our results are in agreement with a recommendation by Trainer (12), published in an editorial in JCEM, that if both the GH is less than 0.3 µg/liter and the IGF-I is normal, then active acromegaly is excluded.

The novel observation in our study was that postoperative acromegalic patients with biochemically active disease (elevated IGF-I) had increased prevalence of IGT in comparison with patients in remission (normal IGF-I). There are no data in the literature correlating the means of biochemical parameters of disease activity (IGF-I and GH nadir post OGTT) in postoperative patients to morbidity of acromegaly. We have chosen to correlate these parameters with IGT, diabetes, and hypertension because of their major impact on mortality of acromegaly. Average life expectancy in patients with acromegaly is reduced by approximately 10 yr, and cardiovascular disease is the principal cause of premature death (7, 8, 13, 14, 15). IGT in itself is a condition known to carry its own risk of eventual cardiovascular disease as well as the propensity to develop type 2 diabetes (16).

Elevated IGF-I was a very strong predictor of the presence of abnormal glucose tolerance in our acromegalic patients (odds ratio, 13.6; P = 0.003). The GH cut-off of 1 µg/liter was again inadequate to predict abnormal glucose tolerance. The only other significant predictor was age (odds ratio of 1.1 per additional year of age). However, when the GH nadir cut-off of 0.25 µg/liter was used, we found that it was a significant predictor of abnormal glucose tolerance (P = 0.016). Using 0.4 µg/liter as a cut-off value, patients in our series with a GH nadir less than 0.4 µg/liter also had a lower incidence of abnormal glucose tolerance, although less significantly (P = 0.055) than with the cut-off of 0.25 µg/liter. Excess GH concentrations are associated with insulin resistance in a large majority of patients with acromegaly before treatment, with IGT occurring in approximately 40% and diabetes mellitus in 10–25% (17). With any treatment modality, blood glucose levels fall toward normal, but glucose tolerance does not always become normal (18). The high prevalence of IGT in our patients with elevated IGF-I is comparable to these figures in acromegalic patients before any therapy.

Arterial hypertension is commonly observed in acromegaly, occurring in approximately one third of the patients, and represents an additional risk factor for cardiovascular disease (19, 20, 21). In our study, the prevalence of treated hypertension was 30% in all acromegalics, with prevalences not significantly different in the two groups of patients in remission and those with active disease. However, the measurement of BP on the morning of the OGTT has shown that the mean diastolic BP was significantly higher in patients with active disease than in those in remission or in healthy subjects.

In conclusion, this study in postoperative patients with acromegaly provides further evidence that the validity of GH cut-off of 1 µg/liter post OGTT may be inadequate as a criterion of biochemical remission of acromegaly and as a marker of associated comorbidities. However, normalized IGF-I concentrations and a lower GH cut-off value less than 0.25 µg/liter are strongly associated with a lower prevalence of IGT and lower diastolic BP in long-term postoperative acromegaly. Because the number of patients with abnormal glucose tolerance is small in our series, studies with a larger cohort of patients may be needed to confirm the prevalence of diabetes and comorbidities in patients with elevated IGF-I. The improvements in glucose tolerance and BP profile should contribute to reducing the cardiovascular risk in these patients.

	Acknowledgments

	Footnotes

 
Abbreviations: BMI, Body mass index; BP, blood pressure; IGT, impaired glucose tolerance; IRMA, immunoradiometric assay; OGTT, oral glucose tolerance test.

Received May 27, 2003.

Accepted October 16, 2003.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Melmed S, Casanueva FF, Cavagnini F, Chanson P, Frohman L, Grossman A, Ho K, Kleinberg D, Lamberts S, Laws E, Lombardi G, Vance ML, Von Werder K, Wass J, Giustina A 2002 Guidelines for acromegaly management. J Clin Endocrinol Metab 87:4054–4058[Free Full Text]
2. 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]
3. 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]
4. 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]
5. Swearingen B, Barker 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]
6. Beauregard C, Truong U, Hardy J 2003 Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly. Clin Endocrinol (Oxf) 58:86–91[CrossRef][Medline]
7. 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
8. Orme SM, McNally RJQ, Cartwright RA, Belchetz PE 1998 Mortality and cancer incidence in acromegaly: a retrospective cohort study. J Clin Endocrinol Metab 83:2730–2734[Abstract/Free Full Text]
9. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 1997 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183–1197[Medline]
10. Alberti KGMM, Zimmet PZ 1998 Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553[CrossRef][Medline]
11. Dimaraki EV, Jaffe CA, De Mott-Friberg R, Chandler WF, Barkan A 2002 Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab 87:3537–3542[Abstract/Free Full Text]
12. Trainer PJ 2002 Editorial: acromegaly–consensus, what consensus? J Clin Endocrinol Metab 87:3534–3536[Free Full Text]
13. Wright AD, Hill DM, Lowy C, Fraser TR 1970 Mortality in acromegaly. Q J Med 34:1–16
14. Bengtsson BA, Eden S, Ernest I, Oden A, Sjögren B 1988 Epidemiology and long-term survival in acromegaly. Acta Med Scan 223:327–335[Medline]
15. Rajasoorya C, Holdaway IM, Wrightson P, Scott DJ, Ibbertson HK 1994 Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf) 41:95–102[Medline]
16. Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A 1999 Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. Diabetes Care 22:920–924[Abstract]
17. Duncan E, Wass JAH 1999 Investigation protocol: acromegaly and its investigation. Clin Endocrinol (Oxf) 50:285–293[CrossRef][Medline]
18. Wass JAH, Cudworth AG, Bottazzo GF, Woodrow JC, Besser GM 1980 An assessment of glucose intolerance in acromegaly and its response to medical treatment. Clin Endocrinol (Oxf) 12:53–59[Medline]
19. Ezzat S, Forster MJ, Berchtold P, Redelmeier DA, Boerlin V, Harris AG 1994 Acromegaly: clinical and biochemical features in 500 patients. Medicine 73:233–240[Medline]
20. Colao A, Baldelli R, Marzullo P, Ferretti E, Ferone D, Gargiulo P, Petretta M, Tamburrano G, Lombardi G, Liuzzi A 2000 Systemic hypertension and impaired glucose tolerance are independently correlated to the severity of the acromegalic cardiomyopathy. J Clin Endocrinol Metab 85:193–199[Abstract/Free Full Text]
21. Jaffrain-Rea ML, Moroni C, Baldelli R, Battista C, Maffei P, Terzolo M 2001 Relationship between blood pressure and glucose tolerance in acromegaly. Clin Endocrinol (Oxf) 54:189–195[CrossRef][Medline]

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This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Serri, O. Articles by Hardy, J. Search for Related Content PubMed PubMed Citation Articles by Serri, O. Articles by Hardy, J.