Prevalence of thyroid diseases in patients with acromegaly: results of an Italian multi-center study

Acromegaly is frequently associated with the presence of thyroid disorders, however the exact prevalence is still controversial. An Italian multicenter study was performed on 258 patients with active acromegaly (high levels of IGF-I and lack of suppression of serum GH levels below 2 microg/l after an OGTT). The control group was represented by 150 patients affected by non-functioning and PRL-secreting pituitary adenomas. Two hundred and two out of 258 acromegalic patients (78%) were affected by thyroid disorders with a significantly higher prevalence with respect to the control group (27%, p<0.0001). One hundred and three patients presented (39.9%) non-toxic nodular goiter, 46 (17.8%) non-toxic diffuse goiter, 37 (14.3%) toxic nodular goiter, 1 toxic diffuse goiter (0.4%), 12 (4.6%) Hashimoto's thyroiditis, 3 (1.2%) thyroid cancer. Two patients presented a co-secreting TSH pituitary adenoma. Thirty-six patients had been previously treated for various thyroid abnormalities. Among the 222 acromegalic patients never treated for thyroid disorders thyroid ultrasonography was performed on 194 subjects. Thyroid volume in patients with thyroid abnormalities was 28+/-17.5 ml (median 23) while it was 10.8+/-3.6 ml (median 10) in patients without thyroid disorders (p<0.0001). Thyroid volume was correlated with the estimated duration of acromegaly (r=0.7, p<000.1), but not with age or with serum GH, IGF-I and TSH concentrations. Thyroid volume was higher in acromegalic patients than in the above control population (23.5+/-16.9 ml vs 13.9+/-12.8 ml, p<0.0001). In 62 acromegalic patients 101 fine-needle biopsies of thyroid nodules were performed; 7 nodules were suspicious and the patients were submitted to thyroid surgery: papillary thyroid carcinoma was found in 3 patients. In conclusion, in a large series of acromegalic patients an increased prevalence of thyroid disorders (78%), particularly non-toxic nodular goiter, has been observed. Thyroid volume, evaluated by ultrasonography, was correlated to the estimated duration of acromegaly. Finally, the prevalence of thyroid carcinoma was slightly increased than in the general population.     

Prevalence of colonic polyps is not increased in patients with acromegaly: analysis of 60 patients from India

BACKGROUND: There are conflicting data on the prevalence of colorectal adenomas in patients with acromegaly. It has been suggested that the risk of colorectal adenomas may be dependent on the geographic and ethnic origin of the patients. MATERIALS: Sixty consecutive patients with active acromegaly due to somatotropinoma underwent colonoscopy prior to definitive surgery. They included 35 men and 25 women with a mean (+/- SD) age of 37.4 +/- 13.2 years and a lag time between symptomatology and diagnosis of acromegaly of 64.6 +/- 58.0 months. The control group included 160 patients (88 men, 72 women; mean age, 38.2 +/- 14.0 years) with a diagnosis of irritable bowel syndrome who were also subjected to colonoscopy. None of these patients had previous or family history of colonic neoplasm, bleeding or colonic surgery. RESULTS: Colonoscopic examination was complete to the cecum in 52 patients (88%), and to the splenic flexure in the remaining 12%. In the control group, it was complete to the cecum in 144 patients (90%). Four of the acromegalic patients (6.7%) and five in the control group (3.1%; P=0.24) had hyperplastic polyps. No patient in either of the groups had adenomatous polyps or colonic adenocarcinoma. The group of acromegalic patients with and without polyps did not differ significantly in age, duration of disease, growth hormone levels or glycemic status. The number of skin tags, however, was significantly higher (P=0.04) in the polyp group as compared to those without polyps. CONCLUSION: The present study has failed to demonstrate the high prevalence rate of colonic neoplasia in patients with acromegaly as compared to reports from the Western world.     

Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in the proximal colon.

BACKGROUND & AIMS: Obesity and diabetes mellitus are associated with an increased incidence of proximal colon cancer. Colonic adenoma that has been reported to be associated with elevated serum insulin levels and subsets of hyperplastic polyps might serve as a precursor of colon cancer. In this study, we sought to determine segment-specific associations between serum insulin levels and the prevalence of adenoma and hyperplastic polyps in the proximal and distal colon. METHODS: We studied 343 consecutive patients who underwent colonoscopy in our hospital. All medical information, including fasting serum insulin, was obtained at colonoscopy. We performed multinomial logistic regression models by using the outcome categories of none (reference), proximal-only, distal-only, and both-segment lesions for the presence of adenoma/hyperplastic polyp with serum insulin, age, gender, lifestyle characteristics, and the presence of other types of lesions as predictors. Odds ratios (ORs) and 95% confidence intervals (CIs) are provided for a 5-muU/mL increase in serum insulin. RESULTS: Overall, serum insulin levels were significantly associated with adenoma (OR, 1.5; 95% CI, 1.1-2.0; P = .005) and borderline associated with hyperplastic polyps (OR, 1.3; 95% CI, 1.0-1.7; P = .075). In multinomial logistic regression models, elevated serum insulin levels were significantly associated with proximal-only adenoma (OR, 1.8; 95% CI, 1.2-2.5; P = .002), both-side hyperplastic polyp (OR, 1.7; 95% CI, 1.1-2.5; P = .015), and proximal-only hyperplastic polyp (OR, 1.5; 95% CI, 1.0-2.1; P = .048) and borderline associated with distal-only adenoma (OR, 1.5; 95% CI, 1.0-2.1; P =.059) but not with distal-only hyperplastic polyp. CONCLUSIONS: Serum insulin levels directly correlate with the presence of adenoma and hyperplastic polyps in the proximal colon and might also less strongly correlate with the presence of distal adenoma.     

Identification of acromegalic patients at risk of developing colonic adenomas

BACKGROUND: Acromegaly seems to be associated with an increased prevalence of colonic adenomas, although factors affecting their development and recurrence of the latter are not fully known. SUBJECTS AND METHODS: Seventy-nine patients with active acromegaly were prospectively followed up for 5 yr. Two hundred eighty healthy subjects served as controls. Colonoscopy and assessment of acromegaly activity were performed at 1-yr intervals. Acromegaly was defined as controlled if serum IGF-I levels were within the normal age-adjusted range. RESULTS: Colonic adenomas were found in 26 of 79 acromegalic patients (32.9%) and 60 of 280 controls (21.4%) at baseline (P = 0.035, adjusted for age and sex, odds ratio 1.82, 95% confidence interval, 1.02-3.25). Seven patients had hyperplastic polyps; the remaining 46 acromegalic patients had no detectable lesions at baseline and did not develop adenomas during the study period. Of the 26 patients with colonic adenomas at baseline, 16 (61.5%) had at least one recurrence of colonic adenomas (P < 0.0001 vs. patients without colonic lesions at baseline), and multiple recurrences were more frequent in patients with uncontrolled acromegaly (66.7% vs. 17.6% in patients with controlled acromegaly, P = 0.028). CONCLUSIONS: The first colonoscopy helps to identify acromegalic patients at high risk of developing colonic adenomas. If colonic adenomas are not present initially, it is unlikely that they develop thereafter, independently of metabolic control of acromegaly. Conversely, new lesions are frequent (and often multiple) in patients who already have colonic adenomas at baseline, particularly if acromegalic disease is poorly controlled by treatment.     

Acromegaly and intestinal neoplasms

Acromegalic subjects show increased frequency of neoplastic lesions in the colon and rectum with respect to the general population. Recent prospective studies using colonoscopy have shown a 3 time higher prevalence of intestinal polyps and up to 4 time increased presence of colorectal cancer in acromegaly, independently of sex, age, duration of disease and clinical status of the patients. The polyps are distributed throughout the extension of the large bowel and are often multiple, showing at least two different histologic types: hyperplastic and adenomatous. Sometimes they are associated with intestinal carcinomas. Pancolonoscopy is the procedure of choice for the diagnosis of large bowel neoplasms, even though it may be difficult to complete in these subjects because of the frequent presence of an enlarged and elongated colon. It shows a higher sensitivity and specificity compared to other tests such as the barium enema, fecal occult blood test and serum levels of carcinoembryonic antigen. Therefore, it is recommended to follow up acromegalic patients using pancolonoscopy to obtain early detection of neoplastic lesions in the large bowel.     

Hypertension in acromegaly and in the normal population: prevalence and determinants

BACKGROUND: The GH/IGF-I axis has a relevant role to play in the cardiovascular system but its implication in the pathogenesis of hypertension in the normal population and in acromegaly is not yet clear. PATIENTS AND MEASUREMENTS: The aim of this retrospective and controlled study was to evaluate the prevalence and determinants of hypertension in 200 patients with acromegaly and 200 nonacromegalic subjects, matched for sex, age, body mass index (BMI) and smoking habits. RESULTS: Hypertension was found in 46% of patients and in 25% of controls (P < 0.0001), without any difference between men and women. Family history of hypertension occurred in 30% of hypertensive acromegalic patients and in 62% of hypertensive controls (P < 0.0001). In both groups, hypertensive subjects were older than normotensive subjects. Systolic (SBP) and diastolic blood pressures (DBP) in hypertensive acromegalic patients were lower and higher, respectively, than in hypertensive controls. The risk of hypertension increased with age and was higher in the patients than in the controls [hazard ratio (HR) 1.9; P = 0.0002]. Independent predictors of SBP were age and glucose in the acromegalic population, and BMI, age and glucose levels in the controls. Independent predictors of DBP were age and glucose in the patients, and BMI, age and IGF-I in the controls. CONCLUSIONS: In acromegaly, hypertension is more frequent than in the general population, involves predominantly DBP, and occurs earlier, is not related to gender, and is less frequently related to family history of hypertension and IGF-I levels. IGF-I may have a protective role for DBP in the general population.     

Remission of acromegaly following long-term therapy with cabergoline: report of two cases

Dopamine agonists are effective in some patients with acromegaly and in this condition treatment is considered to be chronic. We describe two acromegalic patients who responded adequately to the long-acting dopamine agonist cabergoline, but surprisingly maintained normal GH and IGF-I levels once therapy was discontinued after 42 and 76 months because of possibly related side effects. A 32-year-old woman with mild acromegaly (IGF-I: 423 μg/l, GH after OGTT: 2.5 μg/l, adenoma 4 mm) was treated with cabergoline as primary therapy and reached safe GH levels (2 μg/l or less) and normal IGF-I levels with 3.5 mg cabergoline weekly. After 42 months of therapy the patient experienced a progressive decrease of libido, which she attributed to the intake of cabergoline. After stopping medication, serum levels of GH and IGF-I remained normal during the following 2.5 years. A 53-year-old man with moderate acromegaly (serum IGF-I: 547 μg/l, GH after OGTT: 5.9 μg/l, adenoma 7 mm) preferred cabergoline as primary therapy. Serum GH levels below 2 μg/l and normal levels of IGF-I were obtained with 3.5 mg cabergoline weekly. When the patient experienced severe stomach pains after 76 months of treatment, cabergoline was held responsible and discontinued. Serum GH and IGF-I did not increase again and stayed at the same level during a follow-up of 5.5 years. These two cases demonstrate that acromegalic patients with a good response to cabergoline may occasionally remain in remission after stopping therapy. This phenomenon has previously only been described in patients with a prolactinoma.     

Secretion of glycoprotein hormone alpha-subunit by pituitary tumors

Serum glycoprotein hormone alpha-subunit levels were determined in 165 patients with pituitary adenomas. Elevated serum alpha-subunit levels were found in 17 patients (acromegaly, 5 of 58; prolactinoma, 6 of 56; nonfunctioning adenoma, 5 of 32; and ACTH-producing adenoma, 1 of 19), most of whom had normal serum TSH and gonadotropin levels. When TRH (0.5 mg) was injected iv in the 6 prolactinoma patients with elevated serum alpha-subunit levels, serum PRL and alpha-subunit levels increased in only 1 patient. Four acromegalic patients with high serum alpha-subunit levels received TRH; serum GH and alpha-subunit increased in 1 patient and did not change in 2, and only serum GH increased in the remaining patient. Oral administration of bromocriptine (5 mg), on the other hand, consistently decreased serum alpha-subunit and PRL levels in 2 patients with prolactinoma and alpha-subunit and GH levels in 1 acromegalic patient. When serum from 3 patients was subjected to Sephadex G-100 gel filtration, immunoreactive alpha-subunit eluted in a single peak, which emerged in fractions corresponding to [125I]TSH alpha. Concanavalin A (Con A) affinity chromatography revealed that the major portion of immunoreactive alpha-subunit was retained to Con A. A pituitary adenoma removed at surgery from a patient with acromegaly was studied in monolayer cell culture. Secretion of both alpha-subunit and GH from cultured adenoma cells was stimulated by TRH and suppressed by dopamine in a dose-dependent manner. Immunohistochemistry of the pituitary adenomas removed from patients with prolactinoma and acromegaly who had high serum alpha-subunit levels demonstrated alpha-subunit-containing cells as well as PRL- or GH-containing cells. These results suggest that elaboration of glycoprotein hormone alpha-subunit occurs without concurrent production of glycoprotein hormones in a substantial number of patients with pituitary adenomas and that alpha-subunit responses to stimuli in such adenomas are generally parallel with those of the concomitantly produced hormones.     

Divergence between growth hormone and insulin-like growth factor-i concentrations in the follow-up of acromegaly

CONTEXT: Divergence between GH and IGF-I values is regularly observed in treated acromegalic patients, and its significance is unclear. OBJECTIVES: The objective of the study was to explore the frequency and identify potential determinants of discordant serum GH and IGF-I concentrations in noncured acromegalic patients. PATIENTS: Two hundred twenty-nine noncured acromegalic patients of the Belgian acromegaly registry (AcroBel) were grouped according to their mean GH level (< or = or > 2 microg/liter) and IGF-I z-score (< or = 2 or > 2). Clinical and metabolic parameters were compared between groups with active disease (high GH and IGF-I; n=81),high GH (with normal IGF-I; n=25), high IGF-I (with normal GH; n=55), and controlled disease (GH and IGF-I normal; n=68). RESULTS: Compared with the high IGF-I group, the high GH group was characterized by younger age (52 vs. 58 yr, P < 0.05), female predominance (72 vs. 36%, P < 0.01), and lower body mass index (25 vs. 31 kg/m(2); P < 0.001), fasting glucose (91 vs. 99 mg/dl; P < 0.05), and glycated hemoglobin levels (5.7 vs. 6.1%; P < 0.01). There was no difference among the groups regarding baseline characteristics of pituitary adenoma, current medical treatment, or symptom score. CONCLUSIONS: Thirty-five percent of noncured acromegalic patients exhibit a discordant GH and IGF-I pattern. The high GH phenotype was found predominantly in younger estrogen-sufficient females, implying a possible role for age, gender, and estrogens in this biochemical divergence. The high IGF-I phenotype was associated with a worse metabolic profile, suggesting that high IGF-I, rather than high GH, is indicative of persistently active disease.     

继发与不继发糖尿病的肢端肥大症型垂体腺瘤患者的临床比较分析

目的：比较分析继发与不继发糖尿病的肢端肥大症型垂体腺瘤患者的临床资料,初步探讨肢端肥大症垂体腺瘤继发糖尿病的可能病理免疫学机制。方法回顾性分析2008年1月至2013年6月济宁医学院附属医院神经外科采用单鼻孔直达蝶窦入路显微手术切除的84例肢端肥大症垂体腺瘤患者的临床资料,运用免疫化学发光法测定术前基础血生长激素（GH）水平,使用多田公式（xyz／2）计算MRI上肿瘤体积,采用免疫组织化学的方法检测肿瘤内分泌激素的表达,采用χ2或t检验比较继发与不继发糖尿病的肢端肥大症垂体腺瘤患者在发病年龄、性别、发病时间、瘤体大小、基础血GH水平以及肿瘤激素免疫反应等方面的差异。结果20例（24％）肢端肥大症垂体腺瘤患者继发糖尿病。继发和不继发糖尿病的肢端肥大症垂体腺瘤患者男女均可发病（χ2＝1.944,P＝0.163）,发病年龄多集中在41～50岁（P＝0.652）,MRI显示瘤体大小均有微腺瘤、大腺瘤、巨大腺瘤,差异均无统计学意义（P＝1.000）;发病时间分别集中在1～5年（55％）、6～10年（45％）,差异有统计学意义（P＝0.004）;术前基础血GH水平分别为（42.83±8.70）ng／ml、（38.91±36.46）ng／ml,差异有统计学意义（t＝5.253,P＝0.031）。继发糖尿病的肢端肥大症垂体腺瘤患者促甲状腺激素（TSH）免疫反应平均光密度值（0.545±0.023）明显高于不继发糖尿病者（0.408±0.019）,差异有统计学意义（t＝5.336,P＝0.001）;TSH免疫反应阳性率（70％）亦明显高于不继发糖尿病的肢端肥大症患者（14％）,差异有统计学意义（χ2＝23.971,P＝0.000）。结论继发与不继发糖尿病的肢端肥大症垂体腺瘤患者在发病年龄、性别、瘤体大小方面无明显差别,但二者在发病时间、术前基础血GH水平及肿瘤病理免疫反应方面存在明显差别,肿?     

Adrenal morpho-functional alterations in patients with acromegaly

Acromegaly is associated with a greater morbidity and higher incidence of tumors, possibly due to the permissive role of elevated GH and IGF-I levels. In the general population, adrenal masses are frequently discovered (prevalence 1-5%) at computed tomography (CT). We evaluated the prevalence of adrenal lesions in patients with acromegaly. We studied 94 acromegalic patients, 54 females (mean age 55.0+/-16.0 yr) and 40 males (mean age 50+/-14 yr) referred to 5 Endocrinology Units between 2001-2003; 49 had active disease and 45 had been treated with surgery and/or were controlled with medical therapy. Abdominal CT showed adrenal lesions in 27 patients; 9 of them had unilateral masses (10%) with benign features (diameter 0.5-3 cm) and 18 had hyperplasia (14 monolateral and 4 bilateral), with no significant differences between patients with active vs controlled disease, and with no correlation between prevalence of masses and duration of disease, GH and IGF-I levels. Hormone study (urinary free cortisol, catecholamines/metanephrines, upright plasma renin activity and aldosterone, morning plasma ACTH and low-dose dexamethasone suppression test) disclosed no major endocrine alterations. During a 1-yr follow-up, the adrenal masses increased in size in 3 cases and 1 patient also developed subclinical Cushing's syndrome. Adrenal lesions seem more frequent in acromegaly than in the general population, but no single factor (GH/IGF-I levels or disease duration) predicts them. The masses appear to be benign and nonhypersecreting, but a longer follow-up is recommended to disclose any changes in their morphofunctional state.     

Predictors of presence, multiplicity, size and dysplasia of colorectal adenomas. A necropsy study in New Zealand.

Three hundred and thirty six forensic necropsy specimens of large bowel were examined in order to identify subject related variables that independently predicted the following adenoma characteristics: presence, size (largest), multiplicity and high grade dysplasia. The variables were age, gender, body mass index, race (European origin versus Maori/Polynesian) and presence of hyperplastic (metaplastic) polyp(s). Subjects included 303 New Zealanders of European origin (M = 185, F = 118) yielding 149 adenomas and 251 hyperplastic polyps and 33 Maori/Polynesians (M = 25, F = 8) yielding five adenomas and one hyperplastic polyp. Independent predictors of adenoma presence as determined by regression analysis were age (p = 0.0001), presence of hyperplastic polyps (p = 0.0001) and male gender (p = 0.05). Models were poor at explaining variation in size, multiplicity, and dysplasia. Larger adenomas occurred more frequently in subjects with multiple adenomas (p = 0.03) and multiple adenomas were probably associated with hyperplastic polyps (p = 0.09) and male gender (p = 0.09) in Europeans. High grade dysplasia was more frequent in women (p = 0.05) and possibly in subjects with hyperplastic polyps (p = 0.2). Body mass index and ethnicity did not predict any adenoma characteristics, but hyperplastic polyp prevalence was influenced by European origin (p = 0.04) and to a lesser extent by body mass index (p = 0.08) as well as presence of adenoma (p = 0.0002) and age ( = 0.005). The association of hyperplastic polyp with presence, multiplicity but not size of adenoma and with a high risk group for colorectal cancer (New Zealanders of European origin) suggests that the hyperplastic polyp serves as a marker for a factor which influences neoplastic evolution at the stages of initiation/transformation but not promotion. Fifty nine per cent of individuals with adenoma(s) did not have hyperplastic polyp(s) emphasising that the last would serve only as a marker of populations and not individuals at high risk of bowel cancer. Low intracolonic butyrate may be the factor linking the expression of the two types of polyp.     

The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients

OBJECTIVE Several in-vitro studies have suggested that the biological actions of IGF-I can be modified by the presence of specific IGF binding proteins. In man, the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term changes in the IGF-l/IGFBP-3 ratio have been described following GH administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated In active acromegaly due to excessive GH secretion. However, the Individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously. METHODS AND MATERIALS We studied this ratio In 198 healthy adults and In 56 acromegalic patients, grouped according to their serum GH levels (group I GH < 2mLU/l II GH 2–10mLU/l; III GH > 10mLU/l). In all subjects a single blood sample was drawn for IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and GH measurements by specific RIAs. In 38 of the patients a 24-hour urinary collection was performed for GH determination. RESULTS In healthy adults serum levels of IGF-I and IGFBP-3 decreased with Increasing age (r =?0.52 and r=?0.34, respectively, P< 0.0001). In addition, the molar IGF-l/IGFBP-3 ratio declined with increasing age (r =?0.44, P – 0.0001). In patients with acromegaly and high serum GH levels (group III), circulating IGF-I was increased 7–97 standard deviations (SDS) and IGFBP-3 was increased 4.20 SOS (P < 0.0001). Serum levels of IGF-II were normal in all three groups (588 ± 240μ/l) whereas IGFBP-1 and IGFBP-2 levels were low and IGFBP-2 levels decreased significantly with increasing serum GH levels (P < 0.0001). The molar IGF-l/IGFBP-3 ratio in the acromegalic patients was significantly higher than in the controls (P < 0.0001) and correlated significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with serum GH levels (r = 0.73, P < 0.0001). CONCLUSION We demonstrated a decreasing molar IGF-l/IGFBP-3 ratio with increasing age in healthy adults and an increased ratio between serum IGF-I and IGFBP-3 levels in acromegalic patients. As IGF-II is normal and IGFBP-1 and IGFBP-2 are inversely correlated to the serum GH levels In the acromegalic patients, we speculate that the molar ratio between IGF-I and IGFBP-3 reflects free (biologically active) IGF-I and Is dependent on GH levels.     

Prevalence of vertebral fractures in men with acromegaly

CONTEXT: Data on osteoporotic fractures in acromegaly are limited. An increased prevalence of radiological vertebral fractures was already observed in postmenopausal women with active acromegaly. It is unknown whether this observation may reflect a more general increased risk of fractures in acromegaly. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at referral centers. PATIENTS AND CONTROL SUBJECTS: Subjects included 40 males with acromegaly (25 patients with controlled disease and 15 patients with active disease) and 31 control males, with age and gonadal status comparable with the patients. INTERVENTIONS: Evaluation of vertebral fractures (quantitative morphometric analysis) and bone mineral density (BMD) at lumbar spine and total hip (dual energy X-ray absorptiometry) was done. MAIN OUTCOME MEASURE: Vertebral fractures were assessed. RESULTS: Although BMD was not significantly different between acromegalic patients and control subjects, the prevalence of vertebral fractures was higher in acromegalic patients as compared with the control subjects (57.5 vs. 22.6%; chi(2): 8.7; P = 0.003). Fractured and nonfractured acromegalic patients showed no significant difference in age and BMD Z-score. However, acromegalic patients with fractures had serum IGF-I values significantly higher and duration of active disease significantly longer with respect to patients without fractures. Moreover, patients with fractures showed significantly longer untreated hypogonadism as compared with patients without fractures. In a multivariate logistic regression analysis, the duration of active acromegaly was the only risk factor significantly correlated with the occurrence of fractures (odds ratio 1.1, confidence interval 1.04-1.6). CONCLUSIONS: This study reports for the first time a high prevalence of osteoporotic vertebral fractures in an unselected acromegalic male population generally considered at low risk of osteoporosis, suggesting that complicated osteoporosis is an important comorbidity of acromegaly.     

Effect of Sandostatin LAR on serum leptin levels in patients with acromegaly

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin LAR on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans. Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin LAR and eight patients underwent transsphenoidal surgery. Serum concentrations of leptin, GH, IGF-1 and insulin were measured before and after treatment. Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2.79 microg/l (2.60) vs. 4.41 microg/l (5.07); median (inter-quartile range); P < 0.01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0.46, P < 0.05) but not in the acromegalic patients before treatment (r = 0.32, ns). In the group of patients treated with Sandostatin LAR, a marked reduction in GH and IGF-1 was achieved by week 8 and GH and IGF-1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2.99 microg/l (2.60) vs. 4.21 microg/l (3.84), P < 0.05]. Leptin levels also significantly increased after transsphenoidal surgery [3.05 microg/l (5.73) vs. 5.19 microg/l (4.93), P < 0.05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin LAR (r = 0.62, P < 0.05) and after surgery (r = 0.81, P < 0.05). Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin LAR or transsphenoidal surgery led to an increase in leptin concentrations.     

Acromegaly associated with type 2 diabetes showing normal IGF-1 levels under poorly controlled glycemia

Acromegaly is caused by excessive secretion of growth hormone (GH), and a resultant persistent elevation of insulin-like growth factor-1 (IGF-1) levels. Diabetes mellitus is accompanied in some acromegalic patients with insulin resistance. We encountered a type-2 diabetic patient who had a poorly controlled glycemic state and was diagnosed as acromegaly with normal IGF-1 levels. The patient showed definite acromegalic features. However, in the first screening test, GH levels were high and IGF-1 levels were inappropriately normal so the results were not close to the diagnosis of acromegaly. After moderate glycemic control, an oral glucose suppression test was performed, showing no suppressed GH response. TRH test revealed paradoxical increases in growth hormone levels and a brain MRI discovered a pituitary adenoma. After several-months insulin treatment, IGF-1 levels were increased to the abnormal state and GH levels were decreased without treatment for acromegaly. Here we report the rare case of acromegaly that presents inappropriately normal IGF-1 levels at the time of diagnosis in uncontrolled type 2 diabetic patient and shows increased IGF-1 levels after glycemic control with insulin therapy. When evaluating acromegaly in type 2 diabetes under poorly controlled glycemia, cautious IGF-1 analysis is needed after sufficient glycemic control.     

Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations

This paper has reviewed current knowledge of clinical, biochemical, and morphological manifestations of extracranial GRH-producing tumors. Excessive GRH release stimulates pituitary somatotrophs causing elevation of blood GH levels and acromegaly. In some patients with GRH-containing tumor, blood GH concentrations are normal and no acromegaly develops. GRH-producing tumors associated with acromegaly are rare. Based on a critical analysis of the literature, 30 tumors are accepted as definitive. They possess unique features: occurrence in young age, female preponderance, foregut derivation, benign biological behavior, small secretory granules, and frequent association with MEN type I syndrome. The pancreas and lung are common primary sites. GRH-containing tumors unassociated with acromegaly include those of gut and thymus, small cell carcinoma of lung, and medullary carcinoma of thyroid. Several tumors are plurihormonal. In contrast to somatotroph adenoma seen in patients with classical acromegaly, the hypophysial lesion represents somatotroph hyperplasia in acromegalic patients with GRH-producing tumor. This finding indicates that GRH not only increases somatotroph secretory activity but causes somatotroph proliferation. Studies of GRH-producing tumors are of fundamental importance in obtaining a deeper insight into endocrine activity of pituitary somatotrophs and the pathogenesis of GH-secreting pituitary adenomas associated with acromegaly; the importance of GRH in the etiology of acromegaly is still unresolved. The relationship between GRH-secreting tumors and MEN type I syndrome is controversial; further studies are required to elucidate whether they represent two distinct entities or whether GRH-producing tumors accompanied by acromegaly are only forme fruste manifestations of MEN type I syndrome.     

Development of acromegaly in patients with prolactinomas

OBJECTIVES: Patients with prolactinomas and patients with acromegaly often have heterogenous adenomas. In this study we have focused on patients with prolactinomas who developed acromegaly and acromegalic patients with hyperprolactinaemia. Our hypothesis is that some patients with hyperprolactinaemia may develop clinical acromegaly. METHODS: We have included patients examined at department M, Odense University Hospital between 1996 and 2001. Seventy-eight patients with prolactinomas, 65 females and 13 males, with a median age (range) of 30 Years (14-74) and 47 Years (20-66), respectively, were included in the study. RESULTS: In females and males the median prolactin (PRL) levels were 90 microg/l (27-4700; normal values (NV) 相似文献   

Acromegaly and colorectal proliferations

Hypersomatotropism causes not only the typical acromegalic symptoms but also very often a splanchnomegaly with participation of the enteron. We performed a colonoscopy in 16 patients with a persistent active acromegaly in spite of full used therapy possibilities. Only in four cases (25%) we could find a polyp. They were distributed on the colon transversum (one), descendens (one) and sigmoideum (two). Three of them (histology: tubular adenoma) had a diameter of less than 5 mm. Only one adenoma had an extent of 3.5 x 3 x 2.5 cm (histology: tubular-villous adenoma). Not any polyp showed signs of malignity. There existed no relations between the coloscopic findings, the degree of activity and the duration of illness. Localisation, histology, frequency and age distribution of the found out polyps of our patients were in the range of real frequency of the occurrence of colorectalic neoplasms. We conclude: Acromegaly is correlated not more than accidentally with colorectalic neoplasms (benign, malignant). Therefore preventive medical examinations of acromegalic patients are not rich in meaning.