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DOI: http://dx.doi.org/10.20534/ESR-17-5.6-51-53
Khalimova Zamira Yusufovna, Head of Department of Neuroendocrinology with pituitary surgery, Center for the Scientific and Clinical Study of Endocrinology, Uzbekistan Public Health Ministry E-mail: doctorsh@mail.ru Kholikova Adliya Ommonulaevna, Head of neuroendocrinology department Center for the Scientific and Clinical Study of Endocrinology, Uzbekistan Public Health Ministry Safarova Shokhsanam Masharipovna, Junior researcher
Department of Neuroendocrinology with pituitary surgery, Center for the Scientific and Clinical Study of Endocrinology, Uzbekistan Public Health Ministry Jabbarova GavkharMuzravjonovna, Medical resident Neuroendocrinology department, Center for the Scientific and Clinical Study of Endocrinology, Uzbekistan Public Health Ministry
VALUE OF IGF-1 AND IGFBP-3 LEVELS IN DEFINITION OF THE DISEASE ACTIVITY IN PATIENTS WITH ACROMEGALY
Abstract: Our data showed that IGF-1 level is the sensitive marker of diagnostics of activity of process and efficiency of treatment in patients with newly revealed acromegaly and ones received medicamentous treatment. And for patients undergone surgical removal of somatotropinomas and X-ray therapy, the most sensitive criteria reflecting efficiency of treatment and characterizing presence or absence of residual secreting tumor tissue, is IGFBP-3 level which may be used as an additional biochemical marker for active process.
Keywords: acromegaly, insulin-like growth factor, marker.
IGF-1 and IGFBP-3 are the important markers of growth hormone functions. Detection of their levels in blood plasma is of the paramount diagnostic importance at various forms of GH secretion disorders [1]. There are data that serum IGF-1 levels correlate with average daily values of GH in blood which proves importance of its detection in patients with acromegaly undergoing dispensary monitoring [2]. IGF-1 level remains elevated for a long time in patients "cured" for acromegaly comparing to the healthy ones. Though they have normal basal GH level, average GH level in intervals between its peaks at these patients remains slightly elevated, and correlates with IGF-1 [3].
IGF-1 and IGFBP-3 levels strictly correlate in patients with clinical signs of acromegaly; and for the raised levels of IGFBP-3 typical for acromegaly, there was no data for any of them to be at range of normal levels for healthy people (4). However according to the experience of some authors (5) such cases have take place, and though there were crossings of IGF-1 levels in healthy people and patients with newly diagnosed acromegaly, there is no case for IGFBP-3. Therefore, measurement of IGFBP-3 levels can be useful in estimation of condition of patients with clinical signs of
acromegaly and suspiciously normal levels of IGF-1 and results of the oral glucose tolerance test (4).
Proceeding from the above-stated, the objective of our researches was studying of IGF-1 and IGFBP-3 levels in previously untreated patients and in patients receiving different types of therapy.
Materials and methods. 48 patients with GH secreting pituitary adenomas addressing in RSSPMCE were examined. Middle age was 41±19 years, disease duration — from 1 to 23 years. Patients were divided into four groups on 12 in each one: 1st group — untreated patients (newly revealed) (n/r), 2nd — undergone surgical treatment (ST) (transnasosphenoidal pituitary adenomectomy), 3rd — undergone X-ray therapy (XT) (gamma therapy for hypothalamus-pitu-itary area), and 4th group — receiving medicamentous therapy with dopamine agonists (MT) (parlodel, bromergone, bromocriptin) in a daily dose of 7.5-12.5 mg/day regularly. The control group was made by 12 healthy subjects of the same age. All patient undergone clinic and biochemical tests; basal levels of pituitary and peripheral glands' hormones, IGF-1, and IGFBP-3 levels were studied by RIA method (Immunotech, Chechia); pituitary CT/MRT was performed; daily rhythm of GH secretion was defined.
Section 4. Medical science
Research results.IGF-1 and IGFBP-3 levels of 46 patients were compared with daily average GH levels of healthy control patients (table 1).
The study found out, that GH levels varied over a wide range from 7.4±1.8 mU/l to 71.78±17.7 mU/l, being 37.26±6.7 mU/l on average, which is almost 2 times exceeded the top normal threshold
and is more than 10 times higher than the average daily rhythm of healthy persons. The highest basal GH levels were found to be in patients with newly revealed acromegaly (71.78±17.7 mU/l) and MT group (42.47±12.1 mU/l), and rather low levels of the hormone were in patients undergone XT (13.4±2.2mU/l). Patients undergone ST had normal GH levels (3.4±1.8 mU/l).
Table 1. - Basal GH, IGF-1, and IGFBP-3 levels in blood serum of patients with acromegaly
Groups GH (mU/l) IGF-1 (ng/ml) IGFBP-3 (ng/ml)
Newly revealewd, n= 12 71.78 ± 17.7 1,525 ± 70.31 15,413 ± 1,201.9
MT, n = 12 42.47 ± 12.11 1,451 ± 124.9 19,938.1 ± 1,943.8*
XT, n = 12 13.4 ± 2.2*** 731.5 ± 28.17*** 39,694 ± 10,790.9
ST, n = 12 3.4 ± 1.8*** 202.7 ± 27.4*** 13,287 ± 1,515.1
Total (n = 48) 37.7 ± 6.7 1,011.6 ± 87.5 22,465.5 ± 3,211.1
Control group, n = 12 15-23 107-310 1,531-4,277
P between MT and XT p < 0.001 p < 0.001 p < 0.01
P between MT and ST p < 0.001 p < 0.001 p < 0.01
P between XT and ST p < 0.05 p < 0.001 p < 0.01
Note: *P < 0.05; **P<0.01; ***P < 0.001 - statistical difference in relation to n/r
Interesting data were received regarding IGF-1 and IGFBP-3 levels. IGF-1 level in patients with clinical signs of acromegaly varied from 128 ng/ml to 2,087 ng/ml (1,011.6 ± 87.5 ng/ml on average), which exceeded 2.5 times those variations in healthy subjects. It is necessary to notice, that the clear parallelism in levels of GH and IGF-1 was revealed. With increase of GH level, the level of IGF-1 raised accordingly, and its highest levels were registered in patients with newly revealed acromegaly being 1,525±70.31 ng/ml, and the least levels — 202.7 ± 27.4 ng/ml were revealed in patients undergone ST.
The comparative analysis of IGFBP-3 levels in patients receiving various types of MT found out following interesting data (table 1). Thus, the least IGFBP-3 levels were revealed in patients undergone radical tumour removal (13,287 ± 1,515.1 ng/ml),
and the highest levels were in group of patients undergone XT 39,694 ± 10,790.9 ng/ml. I. e. its levels mismatched with average values of basal levels of GH and IGF-1 in patients undergone XT. It is necessary to notice, that levels of its physiological fluctuations widely vary from 1,531 to 4,277 ng/ml, which makes it complicated to use it in estimation of degree of acromegaly activity as a biochemical marker. So, in our study as well its levels varied from 13,287 to 39,694 ng/ml and were on average 22,465.5 ± 3,211.1 ng/ml. Moreover, patients undergone ST had also elevated IGFBP-3 levels despite normal levels of GH and IGF-1.
Further we studied correlation between basal levels of GH and IGF-1 as a whole and depending on therapy applied. We thus found out high positive correlation r = 0,92 in a whole (fig. 1), but this dependence has grown at the separate analysis.
Figure 1. Correlation between GH and IGF-1 in patients with acromegaly
We revealed the highest correlation coefficient in patients with newly revealed acromegaly (r = 0.9), and ones receiving MT (r = 0.97), which specifies low efficiency of MT using dopa-mine agonists, even in cases of high daily doses administration (7.5-12.5 mg/day). This coefficient was slightly lower in patients after surgery (r = 0.95) and X-ray (r = 0.94) therapy.
According to the literature data, it is known, that IGFBP-3 is the representative of family ofproteins which bind IGF-1 and modulate its action at tissue level [6]. So, IGFBP-3 is the main circulating form of binding proteins and the basic physiological regulator of IGF-1 level which increases its half-time of life and biological activity. In this connection we studied correlation between GH and IGFBP-3 levels (fig. 2).
Figure 2. Correlation between GH and IGFBP-3 levels in patients with acromegaly
At the analysis of correlation between GH and IGFBP-3 by groups, positive correlation in group of ST (r = 0.69) and XT (r = 0.63) was found.
Generalising the received results, it is possible to conclude, that IGF-1 level has strong correlation with GH level in blood, and its detection is informative as well as in untreated and in previously treated patients.
Detection of IGFBP-3 level has an important clinical-diagnostic value; this index may remain high even after process remission, when levels of GH and IGF-1 are within the normal values. Raised serum IGFBP-3 levels specify the presence of residual hypersecretion of GH in patients undergone surgical treatment and ones being in post-X-ray remission. Probably this explains development and progressing of complications of acromegaly even after successful therapy which evidently reflected in normal GH and IGF-1 levels which are basal criteria for any treatment choice in acromegaly. It is known, that in healthy subjects IGF-1 and IGFBP-3 levels clearly reflect condition of GH and have positive correlation [7] with its level, while in patients with acromegaly the given interrelation is not always presented. This results from the fact that the number of factors such as insulin resistance, impaired glucose tolerance, diabetes mellitus and somatic diseases — hepatitis, nephritis, etc. [8] — have
their influence on GH, IGF-1, and IGFBP-3 levels. Therefore in our opinion, IGF-1 and IGFBP-3, as well as GH levels should be estimated only during OGTT which excludes cases of underestimation of activity of acromegaly.
Thus, our data showed that IGF-1 level is the sensitive marker of diagnostics of activity of process and efficiency of treatment in patients with newly revealed acromegaly and ones received medi-camentous treatment. And for patients undergone surgical removal of somatotropinomas and X-ray therapy, the most sensitive criteria reflecting efficiency of treatment and characterizing presence or absence of residual secreting tumor tissue, is IGFBP-3 level which may be used as an additional biochemical marker for active process.
Thus, the most sensitive markers of estimation of acromegaly activity and its progressing with development of various complications, along with indicators of daily rhythm of GH secretion are IGF-1 and IGFBP-3. Carried out survey specify a diagnostic value of serum levels of IGF-1 and IGFBP-3 both in newly revealed, and in patients with acromegaly receiving treatment. Their complex detection is an additional biochemical criterion which allows defining medical-diagnostic strategy in cases of residual GH-activity after surgical treatment and on the background of post-X-ray remission of the disease.
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