D Niculescu

Carol Davila University of Medicine and Pharmacy, Bucharest, Bucuresti, Romania

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Publications (10)4.22 Total impact

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    ABSTRACT: In normal subjects growth hormone (GH) and insulin-like growth factor-I (IGF-I) have opposing effects on glucose metabolism. Active acromegaly is associated with insulin resistance (IR) and glucose intolerance although both GH and IGF-I are elevated. Our objective was to compare whether GH or IGF-I correlates more closely with IR and glucose intolerance in acromegaly. Basal serum IGF-I and GH, glucose and insulin during an oral glucose tolerance test were measured in 70 normoglycemic and 44 hyperglycemic acromegalic patients (21 impaired fasting glucose, 11 impaired glucose tolerance and 12 diabetes mellitus) according to American Diabetes Association criteria. 55 patients were assessed before any treatment for acromegaly and 59 after surgery and/or radiotherapy (15 patients had normal IGF-I after treatment). Patients treated with somatostatin analogs, GH-receptor antagonists or antidiabetic drugs were excluded. IR was assessed by various basal and stimulated indices. Homeostatic Model Assessment 2-Insulin Resistance (HOMA2-IR) index correlated more closely with IGF-I (r = 0.65, p < 0.0001) than nadir (r = 0.23, p = 0.008) or random GH (r = 0.26, p = 0.002). HOMA2-IR correlated better with IGF-I than nadir or random GH also in normoglycemic (n = 70; r = 0.74, p < 0.0001 vs. r = 0.36, p = 0.001 vs. r = 0.39, p < 0.001) and hyperglycemic patients (n = 44; r = 0.54, p = 0.0002 vs. r = 0.09, p = 0.4 vs. r = 0.14, p = 0.26). In multivariate logistic regression analysis IGF-I but not GH was a significant risk factor for glucose intolerance after adjusting for age, sex, weight and acromegaly duration (OR = 1.56, p = 0.01). In acromegaly IGF-I correlates more closely than GH with IR. IGF-I levels but not GH are associated with glucose intolerance.
    Pituitary 05/2013; 16(2)(16(2)):168-74.. · 2.67 Impact Factor
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    ABSTRACT: In acromegalic patients growth hormone (GH) excess induces insulin resistance (IR) but whether this is sufficient for pre-diabetes to occur is a matter of debate. Aim. To assess the relative role of IR and insulin secretion in the pre-diabetes of acromegaly. Methods. 126 patients with acromegaly (79 women, 47 men) were included. Plasma glucose, GH and insulin levels were measured basal and 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT). Basal and stimulated IR was assessed by homeostasis model assessment (HOMA), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI) derived from OGTT (OGTTISI) respectively. Basal and stimulated insulin secretion was assessed using HOMA-B% index and insulinogenic index (IGI), respectively. The local Ethic Committee approved the study. Results. There were 51 subjects with pre-diabetes and 75 subjects with normal glucose tolerance (NGT). Pre-diabetes group had a significantly higher HOMA-IR index (4.8±3.3 vs 2.5±1.6, p<0.001) and nadir GH in OGTT (9.4 (4.3, 22.2) vs. 4.8 (2.2, 14.5) ng/mL, p=0.02) than NGT group. HOMA-IR did not correlate with nadir GH serum level in pre-diabetes group (r =0.22, p=0.12) but correlated significantly in NGT group (r= 0.5, p<0.001). In contrast, the pre-diabetes group had a lower HOMA-B% index than NGT group (165.4±15.7 vs 228.5±29, p<0.001). HOMA-B% did not correlate with nadir GH in both groups. Unadjusted IGI did not differ between the two groups (0.40±0.07 vs. 0.48±0.05, p=0.34) but became statistically significant after adjusting for both basal IR (HOMA-IR) (0.31±0.06 vs. 0.54±0.05, p=0.01) and stimulated IR (OGTTISI) (0.30±0.06 vs. 0.54±0.05, p=0.005). There were no significant differences between pre-diabetes and NGT groups regarding age, duration of acromegaly and sex. Conclusions. Our data suggest that reduced basal and stimulated insulin secretion express the failure of β-cells adaptation to increased GH-induced-insulin resistance and is the pathogenic mechanism of pre-diabetes in acromegaly.
    Acta Endocrinologica. 01/2010; VI:4021-3198718.
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    ABSTRACT: In acromegalic patients growth hormone (GH) excess induces insulin resistance but whether this is sufficient, in the face of normal insulin secretion, for pre-diabetes (impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)) to occur is a matter of debate. Aim: To assess the relative role of insulin resistance and insulin secretion in the pre-diabetes of acromegaly. Methods: One hundred and twenty-four patients with acromegaly (78 women, 46 men, mean age 50±11 years) addmited to our department were included in the study. Plasma glucose, GH and insulin levels were measured basal and 30, 60 and 120 min during a 75 g oral glucose tolerance test (OGTT). Insulin resistance was assessed by HOMA-IR index (fasting plasma glucose (FPG) (mg/dl)*fasting plasma insulin (FPI) (mU/l)/22.5*18). Basal and stimulated insulin secretion was assessed using HOMA-B% index (FPI (mU/l)*20)/(FPG (mg/dl)/18–3.5)) and insulinogenic index (IGI) (Δ insulin(30′–0′) (mU/l)*100/glucose(30′) (mg/dl) respectively. The local Ethic Committee approved the study. Results: According to ADA criteria, there were 49 subjects with pre-diabetes (30 IFG, 11 IGT and 8 combined glucose intolerance). Seventy-five subjects had normal glucose tolerance (NGT). There were no significant differences between pre-diabetes group and NGT group regarding age (53±13 vs 48.7±11 years, P=NS), sex (53 vs 69.3% women, P=NS) and nadir GH in OGTT (18±17 vs 12.3±17 ng/ml, P=NS). The pre-diabetes group had a significantly higher HOMA-IR index (4.6±3.1 vs 2.6±2.1, P<0.001) and lower HOMA-B% index (159±108 vs 236±257, P=0.02) than NGT group. IGI did not differ between the two groups (39±48 vs 48±43, P=NS) but IGI/HOMA-IR was signifficantly lower in pre-diabetes group (9.7±8 vs 24.5±26, P<0.001). Nadir serum GH correlated with HOMA-IR index (r=0.35, P<0.001) but not with HOMA-B% or IGI. Conclusions: Our data suggest that reduced basal and stimulated insulin secretion, reflecting the failure of β-cells adaptation to increased, GH-induced insulin resistance, leads to pre-diabetes in acromegaly.
    European Congress of Endocrinology 2009, Istanbul, Turkey,25 April 2009 - 29 April 2009; 04/2009
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    ABSTRACT: Background. Advances in imaging techniques have led to increasing discovery of adrenal and pituitary "incidentalomas", tumors with normal endocrine function and no compression mass effects. We evaluated the age at diagnosis (AD) in patients with benign non-functioning adrenal incidentalomas, as compared to pituitary non-functioning tumors, in a series of patients from a national center of endocrinology. Methods. From 2,123 consecutive patients with adrenal and pituitary tumors hospitalized between 1977 -2009, 2,069 patients were analysed. The study groups included: group A -137 patients with adrenal incidentalomas (AI), group B -534 patients with pituitary incidentalomas (PI). Control groups included 1,398 patients: group C1 147 patients with adrenal carcinomas or benign hormone-secreting adrenal tumors, and group C2, 1,251 patients with pituitary secreting adenomas or large non-functioning pituitary macroadenomas (NFA). Imaging was done by computed tomography and/or magnetic resonance after 1981 and by skull X-ray or pneumoencephalography before 1981. Results. Mean age AD is more advanced in patients with AI (53 ± 11.9 years, range 21 -78 yr) than in patients with PI (36.8 ± 13.1 years, range 10 -81 yr), p < 0.01. AD was higher in AI than in patients with secreting adrenal tumors, but similar in patients with adrenal malignancy. There is an age-related increase in the proportion of AI among patients with adrenal tumors, and of NFA, but not of PI, among patients with pituitary tumors. In patients aged over 65 years, 74% of patients with adrenal tumors have AI, while only 18% of patients with pituitary tumors have PI and 42% have NFA. AD in NFA (49.3 ± 13.1 yr, range 12 -79 yr) was more advanced than in PI (p < 0.01). AD does not correlate with tumor size. Tumor growth occurred in 24% of AI (follow-up 3.0 ± 2.8 yr) and only in 0.7% of PI, p<0.01 (follow-up 3.1 ± 2.5 yr). Conclusions. Adrenal non-functioning benign tumors show a clear association with ageing, in contrast with pituitary incidentalomas. It seems unlikely that most pituitary incidentalomas in young patients become large NFA, whose development seems to be also age-related. It is tempting to suggest that pituitary tumorigenesis starts earlier than adrenal tumorigenesis.
    Acta Endocrinologica (Buc). 01/2009;
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    ABSTRACT: A 51 years old woman, diagnosed 23 years ago with acromegaly and non-insulin dependent diabetes mellitus, who denied radical treatment and took bromocriptine 2.5 -7.5 mg/day sporadically and oral antidiabetic drugs, presented with chronic headaches, acromegalic features, bilateral temporal hemianopia, hypertension, hyperglycemia. Her pituitary function was normal (random serum growth hormone 2.5 -2.8 ng/mL). The skull X-ray showed an enlarged sella turcica, with blurred multiple contour and an "egg-shell" calcification boarding the interior sellar floor. Cranial CT scan revealed a 1.7/0.7 cm intrasellar macrocalcification with a low-density core, lying on most of the sellar floor. In addition there were partial empty sella, asymmetrical optic chiasm, multiple cerebral, vascular and pineal microcalcifications, but no visible pituitary or tumor mass. Apoplexy within a previous large pituitary growth hormone-secreting tumor, followed by resorption and peripheral calcification, may have produced this rare case of pituitary stone associated with remission of acromegaly and sequelar visual field defect.
    Acta Endocrinologica-bucharest - ACTA ENDOCRINOL-BUCHAREST. 01/2008; 4(2).
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    ABSTRACT: Insulin resistance (IR) can be induced by high amounts of growth hormone (GH). To set up, in acromegaly without diabetes mellitus, a correlation between the disease activity in GH-secreting adenoma (AA) - assessed by minimum GH serum level during an oral glucose tolerance test (OGTT) - and severity of insulin resistance (IR), assessed by HOMA-IR index. 75 out of 88 consecutive patients with acromegaly hospitalized in our department were included in this study. 13 patients proved to have diabetes mellitus and were excluded. Serum glucose, GH and insulin levels were measured by immunoradiometricassay basal and at 30, 60 and 120 minutes after a 75 g OGTT in 88 patients with active or cured acromegaly. IR was assessed using HOMA-IR index (Homa-IR=basal serum glucose (mg/dl) x basal serum insulin (mU/L)/22.5 x 18). A value over 2.5 was considered indicating IR. Out of 75 patients without diabetes mellitus, 36 subjects (48%) were presenting with IR (34 with active disease, 2 cured). We found a significant positive correlation (r=0.56, p<0.001) between AA and HOMA-IR. The GH minimal level corresponding to the intersection of the exponential regression curve with the HOMA-IR level of 2.5 was 8.8 ng/mL, a cut-off point indicating IR with 82% specificity and 78% sensitivity. The odds ratio for developing IR becomes significant at a minimum GH level during OGTT of 2 ng/mL (odds ratio 7.6, 95% confidence interval 2-29). The severity of IR revealed by acromegaly correlates with GH production. A GH serum level higher than 2 ng/mL during OGTT indicates an increased risk for developing IR. This cut-off level of GH can be used as one of criteria of cured disease, regarding the lack of metabolic effects.
    Experimental and Clinical Endocrinology & Diabetes 05/2007; 115(5):308-16. · 1.56 Impact Factor
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    ABSTRACT: Glucose intolerance (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] or diabetes mellitus) due to insulin resistance is a frequent complication of acromegaly due to excessive growth hormone (GH) production. Long-acting somatostatin analogs are known to reduce the GH and IGF-1 serum levels, and to inhibit at the same time the pancreas insulin release. The effect upon acromegalic patients who express IFG before therapy is controversial. We here present two male patients, 66 and 36 years old, with active acromegaly and IFG who were submitted to a treatment with long-acting somatostatin analog lanreotide. After being diagnosed with active acromegaly with high nadir serum GH levels along oral glucose tolerance test (OGTT), i.e. 149 ng/mL and 43 ng/mL respectively, the patients underwent complex therapy (surgery and radiotherapy) which reduced the GH serum levels (20.7 ng/mL and 3.5 ng/mL respectively) without curing the disease. The patients developed IFG with fasting serum glucose levels of 113 mg/dL and 101 mg/dL, respectively. The treatment with the long-acting somatostatin analog lanreotide (30 mg i.m., every two weeks) decreased the GH serum levels close to normal limits (1.5 ng/mL and 1.6, ng/mL respectively). The treatment with lanreotide normalised the fasting serum glucose levels (91 mg/dL and 81 mg/dL, respectively) together with a reduction of serum insulin levels from 14.2 mU/mL to 8.7 mU/mL and from 25.4 mU/mL to 11.5 mU/mL, respectively (HOMA decreased form 3.96 to 1.97 and 6.33 to 2.3, respectively). We discuss the mechanisms by which lanreotide can improve glucose tolerance in patients with active acromegaly despite lowering the serum insulin levels through a direct effect on insulin secretion.
    Acta Endocrinologica (Buc). 01/2007;
  • Acta Endocrinologica (Buc). 01/2006; 2(2):246.
  • XIII Balkan Congress of Endocrinology; 09/2005
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    Acta Endocrinologica-Bucharest. 01/2005; 1(1).