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Context: Amiodarone-induced thyrotoxicosis (AIT) resulting from destructive thyroiditis (type 2) is commonly treated with glucocorticoids, but time needed to restore euthyroidism may be unacceptable for patients with underlying cardiac disorders., Objective: The objective of this prospective study was to identify factors affecting the response to glucocorticoids in a large cohort of patients with type 2 AIT followed prospectively., Setting: This study was conducted at university centers., Patients: Sixty-six untreated patients with type 2 AIT were enrolled in the study., Intervention: All patients were treated with prednisone (initial dose, 0.5 mg/kg.d) as long as needed to restore euthyroidism, defined as cure of AIT., Main Outcome Measure: The main outcome measure was cure time., Results: The median cure time was 30 d (95% confidence interval, 23-37 d). Serum free T4 concentration (picograms per milliliter) and thyroid volume (milliliters per square meter) (and, to a lesser extent, serum free T3 concentration) at diagnosis were the main determinants of response to glucocorticoids, with a cure hazard ratio of 0.97 (95% confidence interval, 0.95-0.99; P = 0.005) and 0.84 (95% confidence interval, 0.77-0.91; P = 0.000) for unit of increment, respectively. AIT was cured in all patients with a complete follow-up; euthyroidism was reached in 30 d or less in 60% of patients but in more than 90 d in 16%. A prompt control of thyrotoxicosis (

Background: Obesity is a clinical feature of patients with Cushing's disease. Peroxisome proliferators-activated receptor (PPAR)gamma is the master regulator of adipogenesis; however, the expression of PPARgamma isoforms in the subcutaneous adipose tissue (SAT) of patients with Cushing's disease is unknown., Aim and Methods: The expression of PPARgamma1 and PPARgamma2 was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence (PPARgamma2 only) in SAT samples of 7 patients with untreated active Cushing's disease (Cushing(UNTR)), 8 with Cushing's disease in remission (Cushing(REM)) after pituitary adenomectomy, 15 normal lean subjects (Control(LEAN)), and 15 obese patients (Control(OBE))., Results: Control(LEAN) had a higher degree of PPARgamma1 than PPARgamma2 (PPARgamma2/PPARgamma1 ratio, 0.55 +/- 0.35). PPARgamma2/PPARgamma1 ratio decreased in Cushing(UNTR) (0.10 +/- 0.043, P < 0.03 vs. Control(LEAN) and Control(OBE)), because of either increased PPARgamma1 or reduced PPARgamma2 expression. PPARgamma2/PPARgamma1 ratio was 0.48 +/- 0.07 in Cushing(REM) patients (P < 0.04 vs. Cushing(UNTR), P < 0.03 vs. Control(OBE)). PPARgamma2/PPARgamma1 ratio was higher in Control(OBE) 0.90 +/- 0.38 than in Control(LEAN) (P < 0.005 vs. Control(LEAN), P < 0.03 vs. Cushing(REM), P < 0.009 vs. Cushing(UNTR)). PPARgamma2/PPARgamma1 ratio was related to serum cortisol levels only in patients with Cushing'disease (r = 0.688, P < 0.02)., Conclusions: Cushing(UNTR) patients had an abnormal expression of PPARgamma isoforms in SAT related to serum cortisol levels. Although further studies are necessary, it is conceivable that variations in the expression of PPARgamma isoforms might have a role in the abnormal adipogenesis of patients with Cushing's disease.

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.

Background: Patients with acromegaly have an increased risk of developing colonic tumours; reduced apoptosis is considered a leading mechanism in tumorigenesis. GH and IGF-1 decrease apoptosis in several cell lines including human colonic adenocarcinoma, but it is unknown whether epithelial cells of colonic mucosa of patients with acromegaly have reduced apoptosis., Aim: The aim of the study was to evaluate the degree of apoptosis in a cross-sectional study, in biopsy samples of colonic mucosa obtained from patients with acromegaly., Patients and Methods: Eleven patients with active, untreated acromegaly (AcroUntr), 16 patients with acromegaly in remission (AcroRem) and 23 controls were enrolled in the study. Samples of colonic mucosa were obtained during colonoscopy; apoptosis was evaluated by either DNA fragmentation or terminal deoxynucleotidyl transferase assay., Results: Apoptotic cells were 60.0 +/- 2.5% in samples of colonic mucosa of controls, 62.0 +/- 3.4% in those from patients with AcroRem (P = ns vs. controls), and 39.0 +/- 4.1% in those from patients with AcroUntr (P < 0.0001 vs. the other groups). Apoptosis was inversely related to serum IGF-I (r = 0.771, P < 0.001) or GH (r = 0.404, P = 0.05) levels and less to the estimated duration of disease (r = 0.384, P = 0.07). PPARgamma is considered to be a tumour suppressor gene the expression of which might be involved in colonic tumorigenesis. The expression of PPARgamma was lower in the colonic mucosa of patients with AcroUntr (2845 +/- 947 transcripts) than in that of controls (35 200 +/- 2450 transcripts) or AcroRem (29 547 +/- 3650 transcripts) (P < 0.005). The recovery of PPARgamma expression was associated with apoptosis in most cells. The lower degree of apoptosis in patients with AcroUntr was associated with a reduced expression of the antiapoptotic Bax protein., Conclusion: In conclusion, patients with AcroUntr have reduced apoptosis in colonic mucosa that is apparently reversed after acromegaly is cured. It is conceivable that reduced apoptosis may represent an early event in colonic tumorigenesis of patients with acromegaly.

Purpose: The aim of this study was to analyze the clinical, audiological, radiological, and genetic features of a group of patients affected with large vestibular aqueduct syndrome., Materials and Methods: Seventeen patients affected with large vestibular aqueduct syndrome (LVAS), diagnosed by means of high-resolution magnetic resonance imaging of the inner ear, with 3-dimensional reconstructions of the labyrinth and by high-resolution spiral computed tomography of the temporal bone, performed only on the oldest patients, have been submitted to a complete audiological evaluation, a thyroid functional and ultrasonographic study, and a molecular study of the PDS gene., Results: The clinical presentation of LVAS was very variable in our group of patients. The enlarged vestibular aqueduct was bilateral in 15 cases and unilateral in 2; it was the only malformation of the labyrinth in 12 patients, whereas it was associated with other inner ear anomalies in the other 5. The hearing loss was very variable in degree (from mild to profound), age at onset, and progression. Moreover, among the 17 patients, 10 were clinically affected by Pendred's syndrome (PS), 3 by distal renal tubular acidosis associated with large vestibular aqueduct, whereas in 3 patients the large vestibular aqueduct was not syndromal. Finally, we identified mutations in the PDS gene in 5 of 10 patients with PS., Conclusions: Our data underscore the frequent role of the large vestibular aqueduct syndrome in the pathogenesis of sensorineural hearing loss and the overall wide variability in its audiological features. It is also highlighted that LVAS is often part of some syndromal diseases, most of which are PS, which is often misdiagnosed because of the varying degree of thyroid symptoms. This study also underscores the possible role of hydro-electrolyte and acid-base endolymphatic fluid disorders in the pathogenesis of enlarged vestibular aqueduct syndrome.

Background: Acromegalic patients have increased left ventricular (LV) mass (M) and impaired diastolic function., Aim: Using ultrasonic cardiac tissue characterization, we evaluated the early changes in cardiac fibrosis (IBS) and intrinsic myocardial contractility (CVI) as well as their reversibility after treatment with somatostatin analogues (SMSA) in patients with acromegaly., Patients and Methods: Twenty-two acromegalic patients with active untreated disease (Acro(UNTR)) underwent conventional Doppler echocardiography and integrated backscattering; 25 healthy subjects (controls) and eight patients with acromegaly in remission after pituitary adenomectomy (Acro(REM)) served as controls., Results: As expected, Acro(UNTR) at baseline had higher LVM than controls or Acro(REM) (P < 0.001); LVM reduced in acromegalic patients after SMSA (P < 0.005 vs. baseline) while LV ejection fraction did not change. LV diastolic function was reduced in all acromegalic patients, either at baseline or after SMSA therapy (E/A ratio, 0.96 +/- 0.3 and 1.1 +/- 0.3, respectively, P < 0.002 vs. controls, 1.6 +/- 0.3). CVI was reduced in Acro(UNTR) (14.3 +/- 5.8%, P < 0.003 vs. controls, 28.7 +/- 7.5%) and greatly improved after SMSA (22.5 +/- 4.5%, P < 0.003 vs. baseline). Cardiac fibrosis was increased in Acro(UNTR) (IBS(MSI), 53.7 +/- 5.3%P < 0.002 vs. controls) and reduced after SMSA (43.7 +/- 4.2%P < 0.002 vs. baseline) albeit not reaching values observed in controls. More importantly, five of 22 (23%) Acro(UNTR) patients had normal LVM, but increased cardiac fibrosis as revealed by back scattering. IBS values and CVI% were related with serum GH and IGF-1 (P < 0.0001) levels, and the estimated duration of disease (P < 0.005)., Conclusions: The present study demonstrated that active acromegalic patients had early impairment of systolic function and increased cardiac fibrosis; increased fibrosis may precede LV hypertrophy; these changes are related to the activity of disease and might improve during treatment with SMSA.

GH has antiapoptotic effects on several cells. However, the antiapoptotic mechanisms of GH on colonic mucosa cells are not completely understood. Peroxisome proliferator activated receptor-gamma (PPARgamma) activation enhances apoptosis, and a link between GH and PPARgamma in the colonic epithelium of acromegalic patients has been suggested. We investigated the effects of GH and of PPARgamma ligands on apoptosis in colonic cancer cell lines. Colonic cells showed specific binding sites for GH, and after exposure to 0.05-50 nm GH, their apoptosis reduced by 45%. The antiapoptotic effect was due to either GH directly or GH-dependent local production of IGF-1. A 55-85% reduction of PPARgamma expression was observed in GH-treated cells, compared with controls (P < 0.05). However, treatment of the cells with 1-50 microm ciglitazone (cig), induced apoptosis and reverted the antiapoptotic effects of GH by increasing the programmed cell death up to 3.5-fold at 30 min and up to 1.7-fold at 24 h. Expression of Bcl-2 and TNF-related apoptosis-induced ligand was not affected by either GH or cig treatment, whereas GH reduced the expression of Bax, which was increased by cig treatment. In addition, GH increased the expression of signal transducer and activator of transcription 5b, which might be involved in the down-regulation of PPARgamma expression. In conclusion, GH may exert a direct antiapoptotic effect on colonic cells, through an increased expression of signal transducer and activator of transcription 5b and a reduction of Bax and PPARgamma. The reduced GH-dependent apoptosis can be overcome by PPARgamma ligands, which might be useful chemopreventive agents in acromegalic patients, who have an increased colonic polyps prevalence.

GH secretion is impaired in most patients with primary hyperparathyroidism (PHP), although the secretion of the other anterior pituitary hormones is unaffected. However, whether restoration of euparathyroidism is associated with reversal of GH deficiency in PHP patients is not known. To address this issue, we studied 30 consecutive patients with PHP due to a single parathyroid adenoma before and after parathyroidectomy. GH secretion was evaluated by peak serum GH after the maximal GHRH + arginine (Arg) stimulation test. A group of 35 age- and sex-matched normal subjects served as controls. Serum IGF-I concentration was below the normal age- corrected values in six of 30 patients before surgery and in four of 30 patients after parathyroidectomy (P = not significant). Mean serum peak GH values after the GHRH + Arg test were 17.5 +/- 2.8 micro g/liter before surgery and 23.8 +/- 2.5 micro g /liter after surgery (P = 0.0008). The GH response to the GHRH + Arg test was reduced in 20 (67%) and normal in 10 (33%) of 30 PHP patients at baseline; after surgery, 22 of 30 (73%) PHP patients had a normal GH response to the GHRH + Arg test, and only eight (27%) had an impaired GH secretion (P < 0.02). In conclusion, this study confirms that GH secretion is impaired in PHP patients and indicates that it is reversed in many patients after parathyroidectomy. Accordingly, GH deficiency in PHP patients must be considered a functional phenomenon for which GH therapy is not recommended.

Objective: To determine whether hypercalcemia per se might be responsible for an impairment in GH secretion., Design: Prospective study., Patients: Six subjects of two unrelated families with familial hypocalciuric hypercalcaemia (FHH), an autosomal dominant disorder due to inactivating mutations in the calcium receptor gene, leading to an increase in serum calcium levels and inappropriately normal serum PTH concentrations. Forty normal subjects, matched for sex and age served as controls., Measurements: Serum GH concentrations were measured after GHRH-Arginine (GHRH-Arg) stimulation test; serum IGF-I, ACTH, cortisol, FT4, FT3, TSH, PRL, LH, FSH levels were measured under basal conditions., Results: All subjects (two male, four female, age range 24-74 years) had increased serum ionized calcium levels (range 1.36-1.56 mmol/l) and five of six patients had normal PTH levels (range for all patients was 14-68 ng/l). Basal serum GH concentrations ranged from 0.1 to 7.0 micro g/l. Mean serum GH secretory peak after GHRH-Arg stimulation test was reduced in five subjects (mean 9.3 +/- 3.6 microg/l, P < 0.006 vs. Controls, mean 67.0 +/- 44.0 microg/l, cut-off, 16.0 microg/l) and normal in one subject (38.7 microg/l). However, serum IGF-I levels were reduced only in two patients (29 and 57 microg/l) and normal in four subjects (range 127-208 microg/l). The basal secretion of the other anterior pituitary hormones was within their normal ranges., Conclusions: The results of the present study support the concept that elevated serum calcium levels impair GH secretion. However, the clinical relevance of GH deficiency in FHH remains to be elucidated.

Acromegalic patients have an increased prevalence of colonic neoplasms and lower peroxisome proliferator-activated receptor gamma (PPARgamma) levels, the latter acting as a tumor suppressor gene. In this study we evaluated the expression of PPARgamma in the biopsy samples of the polyps and outside polyps colonic mucosa from seven patients with active, untreated acromegaly, 11 with cured disease, and 15 controls. Serum GH and IGF-I levels were higher in patients with untreated acromegaly than in those with acromegaly in remission or controls (P = 0.003 and P = 0.002, respectively) The expression of PPARgamma mRNA (mean +/- SE) was 1) mucosa outside polyps, 24,188 +/- 3,254 transcripts in the controls, 22,432 +/- 2,006 transcripts in acromegaly in remission, and 1,952 +/- 342 transcripts in untreated acromegaly (P < 0.0001 vs. controls and acromegaly in remission); and 2) polyps mucosa, 1,554 +/- 236 transcripts in the controls, 1,112 +/- 143 in acromegaly in remission, and 1,570 +/- 251 in untreated acromegaly (P = NS among polyps groups and mucosa outside polyps of untreated acromegaly; P < 0.0001 vs. mucosa outside polyps of controls and acromegaly in remission). Eighty-five percent of the cells in the mucosa outside polyps from controls or acromegaly in remission were positive at immunohistochemistry, at variance with 45% of the cells from polyps mucosa from each group and from those of mucosa outside polyps of untreated acromegaly (P = 0.0002). In conclusion, patients with untreated acromegaly have reduced expression of PPARgamma in the mucosa outside polyps, which might be reversed by curing the disease; conversely, patients with acromegaly in remission have the same low levels of expression of PPARgamma in the polyps mucosa as untreated acromegaly or controls, supporting the concept that reduced expression of PPARgamma might be an early event in colonic tumorigenesis.

Amiodarone-induced thyrotoxicosis (AIT) may occur either in the presence of underlying thyroid disease (type I AIT) or in apparently normal thyroid glands (type II AIT). Type II AIT, a destructive thyroiditis, often favorably responds to glucocorticoids. Iopanoic acid (IopAc) is an iodinated cholecystographic agent that inhibits deiodinase activity and reduces the conversion of T(4) toT(3). It has recently been reported that cholecystographic agents restore euthyroidism in patients with type II AIT. We describe the results of a prospective randomized study conducted in 12 patients with type II AIT treated with either iopanoic acid (group A, n = 6) or glucocorticoids (group B, n = 6). Serum free T(3) levels normalized rapidly in both groups after 7 d, from 0.75 +/- 0.20 ng/dl (11.5 +/- 3.1 pmol/liter) to 0.46 +/- 0.10 ng/d (7.1 +/- 1.7 pmol/liter), P < 0.01, and from 0.58 +/- 0.10 ng/dl (9.0 +/- 1.2 pmol/liter) to 0.34 +/- 0.03 ng/dl (5.2 +/- 0.5 pmol/liter), P < 0.003, in groups A and B, respectively (P = NS). Serum free T(4) levels reduced at 6 months in group B [from 2.70 +/- 0.32 ng/dl (35.1 +/- 4.1 pmol/liter) to 1.0 +/- 0.04 ng/dl (13.4 +/- 0.6 pmol/liter), P < 0.0001] but not in group A (from 2.90 +/- 0.6 ng/dl (38.0 +/- 7.5 pmol/liter) to 2.30 +/- 0.4 ng/dl (35.6 +/- 6.1 pmol/liter, P = 0.39; P = 0.005 group B vs. group A). All patients in both groups became euthyroid and had their amiodarone-induced destructive thyroiditis cured as defined by normalization of both serum free T(4) and free T(3) levels, during both drugs therapy. However, patients in group B were cured more rapidly than patients in group A (43 +/- 34 d vs. 221 +/- 111 d, respectively, P < 0.002). This study shows that, albeit both drugs are effective, glucocorticoids are probably the drug of choice for more rapidly curing type II AIT.

Background: Amiodarone-induced thyrotoxicosis (AIT) may develop either in apparently normal glands (type II AIT) or in the presence of thyroid abnormalities (type I AIT). Sometimes AIT is resistant to conventional treatment. Thyroidectomy was used in patients with AIT, but in patients who are thyrotoxic it may be hazardous. METHODS; Seven patients with AIT (6 type I and 1 type II, 5 men, 2 women, mean age 70 years [range, 60-82 years]) were prepared for total thyroidectomy with a short course of iopanoic acid (1 g/day orally for a mean of 13 days), an oral iodinated cholecystographic agent inhibiting 5'-deiodinase and causing a reduction in the peripheral conversion of thyroxine to triiodothyronine. Mean thyroid volume was 64 mL (range, 10-145 mL)., Results: Mean serum-free triiodothyronine levels decreased from 20 +/- 16.7 pmol/L to 6 +/- 2 pmol/L (P =.0004), whereas serum-free thyroxine values remained unchanged. Euthyroidism was rapidly (7-20 days) restored, allowing an uncomplicated total thyroidectomy in all patients and the ability to continue amiodarone therapy in 6 patients. None had increased surgical bleeding, recurrent nerve palsy, or hypoparathyroidism. No cardiovascular complications occurred., Conclusions: Iopanoic acid is an effective drug allowing rapid control of hyperthyroidism in AIT.

Serum thyroid hormone concentrations increase after radioiodine (RAI) therapy for Graves' disease. This phenomenon has been ascribed to either antithyroid drug withdrawal before RAI therapy or release of preformed thyroid hormones into the bloodstream from the RAI-damaged thyroid. Lithium blocks the release of iodine and thyroid hormones from the thyroid, thus enhancing the effectiveness of RAI therapy. Changes in serum-free thyroxine (FT4) and triiodothyronine (FT3) levels after methimazole (MMI) discontinuation and RAI therapy were evaluated in a prospective, randomized, control study of 36 patients with Graves' disease. After a 3- to 4-month course of MMI, patients were assigned to one of three groups: G1 (RAI alone); G2 (RAI plus lithium for 6 d starting on the day of RAI therapy); or G3 (RAI plus lithium for 19 d starting on the day of MMI withdrawal). G1-G2 patients had an increase in serum FT4 and FT3 levels from 13.5 +/- 6.5 to 19.8 +/- 9.2 pmol/liter and 5.0 +/- 2.0 to 8.0 +/- 4.8 pmol/liter, respectively (P < 0.0001), 2-5 d after MMI withdrawal, but G3 patients showed no changes. In the 30 d after RAI therapy, mean serum FT4 values increased in G1 patients (P = 0.02), peaking at 3-7 d (P < 0.05) but not in G2 and G3 patients. Serum FT3 levels decreased in G1, G2, and G3 (P = 0.03, P = 0.001, P = 0.02, respectively). Hyperthyroidism was cured in 8 of 12 G1 patients, 11 of 12 G2 patients, and 11 of 12 G3 patients (P = 0.31). Control of hyperthyroidism was prompter in G2 (P = 0.08) and G3 (P < 0.05) than in G1 patients. Patients in the three groups received a similar dose of RAI, but the committed radiation to the thyroid was higher in G3 (563 +/- 174 Gray) and G2 (588 +/- 347 Gray) than in G1 (429 +/- 204 Gray) (P < 0.03). In conclusion, the results of the present study demonstrate that: 1) MMI withdrawal is associated with a slight rise in serum thyroid hormone levels; 2) a further increase occurs after RAI therapy; 3) changes in serum thyroid hormone concentrations are prevented by lithium; and 4) the increased effectiveness of RAI therapy in lithium-treated patients is related to the increased RAI retention in the thyroid gland. Accordingly, a short course of lithium therapy can be considered a useful adjunct to RAI therapy to obtain a prompter control of thyrotoxicosis and avoid its transient exacerbation because of MMI withdrawal and RAI administration.

Objective: Acromegaly is characterized by an enlargement of various organs. The aim of the present study was to evaluate whether acromegalic patients have an increased volume of submandibular salivary glands., Design and Subjects: Prospective study on 40 consecutive acromegalic patients (18 male, 22 female; mean age +/- SD, 50 +/- 13 years, range 22-74 years) submitted to submandibular salivary gland ultrasound. Among acromegalic patients, 15 had active and untreated disease (Acro-U), 13 were under long-acting somatostatin analogue therapy (Acro-SA), 12 were in remission after surgery (Acro-R). Two hundred subjects (90 male, 110 female, mean age +/- SD, 50 +/- 11 years, range 23-74 years) matched for age, sex and body mass index served as controls., Measurements: Submandibular salivary gland volume was measured in all acromegalic patients and normal subjects by ultrasound and calculated by the ellipsoid model. Serum GH and IGF-I concentrations were measured in all subjects., Results: Acro-U patients had higher serum IGF-I levels (691 +/- 235 microg/l) than Acro-R (174 +/- 74 microg/l), Acro-SA (436 +/- 239 microg/l) or controls (151 +/- 66 microg/l) (P < 0.0001, P = 0.008, P < 0.0001, respectively). The mean submandibular salivary gland volume was higher in acromegalic patients than in controls: Acro-U 18.1 +/- 3.3 ml, Acro-SA 16.2 +/- 3.3 ml, Acro-R 15.7 +/- 3.0 ml and controls 8.2 +/- 2.4 ml (P < 0.0001). Differences among subgroups of Acro patients were not significant. Enlargement of the submandibular salivary glands was present in 35/40 (87.5%) acromegalic patients. A positive correlation between serum IGF-I (P < 0.0001), GH (P < 0.0001) and submandibular salivary gland volume was found., Conclusions: Acromegalic patients have an increased volume of submandibular salivary glands, independently of the activity of disease.

Objective: To determine whether acromegalic patients have increased thyroidal vascularity and blood flow on colour flow Doppler sonography (CFDS)., Design: Prospective study of consecutive patients., Patients: Twenty-four acromegalic patients (11 men, 13 women, age 49 +/- 9 years); 38 patients with nontoxic goitre (NTG; 12 men, 26 women, age 50 +/- 7 years); 36 normal subjects (controls; 16 men, 20 women, age 46 +/- 9 years). Among acromegalic patients, 10 had active, untreated disease (Acro-U), seven were in remission after surgery (Acro-R), seven had active disease under treatment with somatostatin analogues (SMSa) (Acro-SA) (Sandostatin LAR, 20 mg, every 28 days)., Measurements: CFDS pattern and intrathyroidal peak systolic velocity (PSV) were determined by a colour Doppler system with a 7.5-MHz linear transducer. PSV measurements were made at the level of the intrathyroidal arteries (normal values 3.8 +/- 1.0 cm/s). Thyroid volume was calculated by the ellipsoidal model. Assays included measurements of serum GH, IGF-I, free T4, free T3, TSH, antithyroglobulin (anti-Tg) and antithyroperoxidase (anti-TPO) antibodies, TSH-receptor antibodies (TRAb)., Results: Serum GH (+/- SD) and IGF-I (+/- SD) levels were: Acro-U: GH 26 +/- 31 microg/l, IGF-I 783 +/- 299 microg/l; Acro-SA: GH 15 +/- 25 microg/l, IGF-I 366 +/- 212 microg/l; Acro-R: GH 1.3 +/- 1.0 microg/l, IGF-I 241 +/- 99 microg/l. To convert values for serum GH to mU/l multiply by 2.6; to convert values for serum IGF-I to nmol/l multiply by 0.13075. All controls had CFDS pattern 0 (absent vascularity or minimal spots); among NTG patients, 36 had pattern 0 and two had pattern I (parenchymal blood flow with patchy uneven distribution). Five patients with acromegaly had pattern 0, 12 had pattern I and seven pattern II (mild increase of colour flow Doppler signal with patchy distribution). Among the five acromegalic patients with pattern 0, three were Acro-R and two were Acro-SA. Among patients with pattern I, six were Acro-U, two were Acro-SA and four were Acro-R. Among patients with pattern II, four were Acro-U and three Acro-SA; two patients of the latter group had elevated serum IGF-I under SMSa treatment. Intrathyroidal PSV was 3.8 +/- 1.0 cm/s in controls, 4.0 +/- 1.1 cm/s in NTG, 7.4 +/- 0.8 cm/s in Acro-U, 4.9 +/- 1.3 cm/s in Acro-SA treatment and 4.5 +/- 1.0 in Acro-R. (Acro-U vs. Acro-SA, P = 0.0003; vs. Acro-R, Controls, or NTG, P < 0.0001). PSV values in Acro-SA were higher than those observed in NTG or controls (P = 0.05, P = 0.01, respectively); PSV values in Acro-R did not differ from those in NTG or controls. Intrathyroidal PSV values were correlated with serum IGF-I (r = 0.73, P < 0.0001) and, although less strongly, GH levels (r = 0.54, P = 0.01). Goitre was present in 19 of 24 patients; diffuse in three and nodular in 16. Thyroid function was normal in all subgroups of acromegalic patients. Anti-Tg, anti-TPO antibodies and TRAb were negative in all subjects., Conclusions: Patients with active acromegaly have increased intrathyroidal blood flow (colour flow Doppler sonography pattern II, increased peak systolic velocity values); this was not observed in the large majority of patients under treatment with somatostatin analogues and in any patient in remission. Accordingly, colour flow Doppler sonography and peak systolic velocity measurements may be considered an additional useful peripheral parameter for rapid assessment of the activity of acromegaly.

Unlabelled: Acromegalic patients have an increased prevalence of colonic polyps, due to the elevated serum insulin like growth factor (IGF)-I levels. The mechanisms underlying this process are poorly understood. Peroxisome proliferator activated receptor (PPAR)gamma, a nuclear receptor that regulates adipocyte differentiation, is highly expressed in the human colonic mucosa, where it induces growth inhibition and cell differentiation. In the present study we evaluated the expression of PPARgamma in the bioptic samples of colonic mucosa from 22 patients with acromegaly (Acro) and 13 normal subjects (CONTROLS) matched for age and sex. Among Acro patients, 10 had active, untreated disease (AcroUntr), 6 were in remission after surgery (AcroRem), and 6 had active disease under treatment with somatostatin analogs (AcroSMSa). Serum GH and IGF-I (mean +/- SD) levels were as follows: AcroUntr: GH, 36 +/- 40 microg/l; IGF-I, 769 +/- 298 microg/l; AcroRem: GH, 1.0 +/- 1.3 microg/l; IGF-I, 248 +/- 96 microg/l; AcroSMSa: GH, 7.8 +/- 12 microg/l; IGF-I, 429 +/- 221 microg/l;, Controls: GH, 0.8 +/- 0.7 microg/l; IGF-I, 203 +/- 67 microg/l. In the CONTROLS the level of expression of PPARgamma mRNA was 15230 +/- 891 transcripts. Patients with AcroUntr had 2750 +/- 688 transcripts of PPARgamma. (p < 0.0001) vs. CONTROLS); patients AcroSMSa had 4629 +/- 1286 transcripts of PPARgamma. (p = NS vs AcroUntr, p = 0.0002 vs. CONTROLS); patients with AcroRem had 8261 +/- 2481 transcripts of PPARgamma (p = 0.008 vs. AcroUntr, p = NS vs. AcroSMSa, p = 0.007 vs. CONTROLS). A significant inverse correlation was found between serum IGF-I concentrations and the level of expression of PPARgamma (r = 0.43, p = 0.03). In conclusion, patients with active Acro have a reduced expression of PPARgamma in the colonic mucosa, which appears be related to the increased serum IGF-I levels and might lead to an increased prevalence of colonic polyps.