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Summary Objective Left ventricular (LV) hypertrophy and myocardial fibrosis are considered the main pathological features of acromegalic cardiomyopathy. The aim of the study was to evaluate the proportion of LV hypertrophy and the presence of fibrosis in acromegalic cardiomyopathy in vivo using cardiac magnetic resonance (CMR). Design and patients Fourteen consecutive patients (eight women, mean age 46 ± 10 years) with untreated active acromegaly were submitted to two-dimensional (2D) colour Doppler and integrated backscatter (IBS) echocardiography and CMR. Measurements LV volume, mass and wall thickness and myocardial tissue characterization (IBS and CMR). Results On echocardiography: mean LV mass (LVM) and LVM index (LVMi) were 209 ± 48 g and 110 ± 24 g/m2, respectively; hypertrophy was revealed in five patients (36%); abnormal diastolic function [evaluated by isovolumic relaxation time (IVRT) or early (E) to late or atrial (A) peak velocities (E/A ratio)] was found in four patients (29%). Systolic function evaluated by measuring LV ejection fraction (LVEF) was normal (mean 72 ± 12%) in all patients. Six patients (43%) had increased IBS (mean 57·4 ± 6·2%). On CMR: mean LVM and LVMi were 151 ± 17 g and 76 ± 9 g/m2, respectively; 10 patients (72%) had LV hypertrophy. Contrastographic delayed hyperenhancement was absent in all patients; on the contrary, mild enhancement was revealed in one patient. Systolic function was normal in all patients (LVEF 67 ± 11%). LVMi was not related to serum IGF-1 concentrations or the estimated duration of disease. Conclusions CMR is considered to be the gold standard for evaluating cardiac hypertrophy, fibrosis and systolic function. Using CMR, 72% patients with untreated active acromegaly had LV hypertrophy, which was only detected in 36% patients by echocardiography. However, cardiac fibrosis was absent in all patients irrespective of the estimated duration of disease. Although a very small increase in collagen content (as suggested by increased cardiac reflectivity at IBS), not detectable by CMR, could not be ruled out, it is unlikely that it would significantly affect cardiac function.

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.

Summary 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 µg/l, IGF-I 783 ± 299 µg/l; Acro-SA: GH 15 ± 25 µg/l, IGF-I 366 ± 212 µg/l; Acro-R: GH 1·3 ± 1·0 µg/l, IGF-I 241 ± 99 µg/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

OBJECTIVE Pendred's syndrome is an autosomal recessive disorder characterized by goitre, sensorineural deafness and iodide organification defect. It is one of the most frequent causes of congenital deafness, accounting for about 10% of hereditary hearing loss. It is caused by mutations in the pendrin (PDS) gene, a 21 exon gene located on chromosome 7. The aim of this study was to examine an Italian family affected with Pendred's syndrome at the molecular level. PATIENTS Thirteen subjects belonging to a family from Southern Italy were evaluated for the clinical and genetic features of Pendred's syndrome. MEASUREMENTS Exons 2–21 of the PDS gene were amplified from peripheral leucocytes by the polymerase chain reaction; mutation analysis was performed by single strand conformation polymorphism, direct sequencing and restriction analysis. RESULTS The index patient had the classical triad of the syndrome and harboured two mutations in the PDS gene in the form of compound heterozygosity. He was found to be heterozygous for a cytosine to adenosine mutation at nucleotide 1523 in exon 13 and for a IVS 1001 + 1G → A mutation. The former is a novel mutation which results in a change of 508 threonine to asparagine in the putative eleventh transmembrane domain. The latter mutation in the donor splice site has already been described in other patients and is thought to lead to aberrant splicing and premature protein truncation. Three subjects who were heterozygous for one mutation had normal phenotypes. Two subjects had sensorineural deafness and were heterozygous for a single mutation. Goitre was found only in patients with Pendred's syndrome and was absent in all other individuals, albeit residing in an iodine-deficient area. CONCLUSIONS We have identified a novel mutation in the pendrin gene causing Pendred's syndrome, and confirm that molecular analysis is a useful tool for a definitive diagnosis. This is particularly relevant in cases such as in the subjects of our family in which the clinical features might be misleading and other genetics factors might be responsible for deafness.

Summary 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 µg/l. Mean serum GH secretory peak after GHRH-Arg stimulation test was reduced in five subjects (mean 9·3 ± 3·6 µg/l, P

A total of 116 patients on lithium treatment were followed up for 2 years to determine the course and the clinical relevance of thyroid abnormalities. Elevated thyroid-stimulating hormone (TSH) concentrations were transitory in most patients, except those with serum antithyroid antibodies. The patients who initially had microsomal antibodies remained positive, with an increase in titre in two-thirds of cases. Three young patients of both sexes developed thyroid autoimmunity early in the treatment. The risk of developing hypothyroidism was higher in women, especially in the presence of antibodies. TSH concentrations were significantly lower when carbamazepine was combined with lithium.

Thyroid function was evaluated in 150 Sardinian outpatients at different stages of lithium treatment. A visible and/or palpable goitre was found in 51% of patients, and there was no apparent correlation with the duration of treatment. No cases of symptomatic hypothyroidism were observed, but subclinical hypothyroidism was present in 19% of patients. The prevalence of specific antithyroid antibodies was positively correlated with age and duration of lithium treatment, and was higher in women. Subclinical hypothyroidism was observed in 53% of antibody-positive lithium-treated patients. Carbamazepine in combination with lithium was associated with significantly lower levels of total T4 and T3 than with lithium alone, and the ratios between total and free hormones were also decreased.

Summary Context Two main forms of amiodarone-induced thyrotoxicosis (AIT) exist. Type 1 AIT is a form of iodine-induced hyperthyroidism. Its management is complex and includes thionamides, potassium perchlorate and, occasionally, thyroidectomy. Type 2 AIT is a destructive thyroiditis, responds to glucocorticoids, and usually does not require further thyroid treatment once euthyroidism has been restored. Objective To assess retrospectively the prevalence and relative proportion of type 1 and type 2 AIT over a 27-year period at a tertiary referral centre in Italy. Patients Consecutive AIT patients (n = 215) seen at the department of endocrinology of the University of Pisa between 1980 and 2006. Results Type 1 AIT constituted the most frequent AIT form (60%) during the first years covered by this study. The annual mean number of type 1 AIT patients was 3·6 at the beginning of the study period, and 2·5 during the later years. In contrast, the mean annual number of new cases of type 2 AIT progressively increased from 2·4 to 12·5. Likewise, the proportion of type 2 AIT increased in a significant linear manner (P

An ultrasensitive immunoradiometric assay (IRMA) using two monoclonal anti-TSH antibodies has been used for TSH measurements in basal conditions and after TRH stimulation. The results have been compared with those obtained by conventional radioimmunoassay (RIA). The IRMA method had very high sensitivity (0.07 microU/ml). Detectable serum TSH concentrations were found in all normal subjects by IRMA, but in only 76% by RIA. No overlap was observed with the results obtained by IRMA in untreated overtly hyperthyroid patients, in whom serum TSH was below the limit of detection. The relationship between basal and TRH-stimulated serum TSH concentrations by IRMA and RIA was evaluated in 176 subjects including normals and patients with untreated and treated hyperthyroidism, functioning thyroid adenoma, nontoxic goitre and patients on L-thyroxine therapy. A normal TSH response to TRH was observed in virtually all patients with detectable basal serum TSH by both methods. When patients with undetectable basal serum TSH levels were considered, all but one (98%) had no TSH response to TRH by IRMA. On the contrary using RIA, an absent response was found only in 47% of subjects, a blunted responses in 10% and a normal response in 42%. These data indicate that basal serum TSH measurements by IRMA allows a complete discrimination of normal from hyperthyroid patients and can avoid the need for TRH stimulation tests.