Prediabetes Increases the Risk of Frailty in Older Adults With Prefrail Hypertension: Beneficial Effects of Metformin.

BACKGROUND: Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals. METHODS: We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months. RESULTS: We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001). CONCLUSIONS: Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.

Fifteen Years of Iodine Prophylaxis in Italy: Results of a Nationwide Surveillance (Period 2015-2019).

CONTEXT: In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking. OBJECTIVE: The aim of this study was to evaluate efficiency, effectiveness, and possible adverse effects (increased occurrence of thyroid autoimmunity and hyperthyroidism) of the Italian iodine prophylaxis program. METHODS: From 2015 to 2019, a nationwide survey was performed. The use of iodized salt was evaluated in a sample of 164 593 adults and in 998 school canteens. A sample of 4233 schoolchildren (aged 11-13 years) was recruited to assess urinary iodine concentration, prevalence of goiter, and thyroid hypoechogenicity on ultrasound, with the latter being an indirect indicator of thyroid autoimmunity. Neonatal TSH values of 197 677 infants screened in regions representative of Northern, Central, and Southern Italy were analyzed to investigate the percentage of TSH values >5.0 mIU/L. Data on methimazole prescriptions were analyzed as indirect indicators of new cases of hyperthyroidism. RESULTS: The prevalence of the use of iodized salt was 71.5% in adult population and 78% in school canteens. A median urinary iodine concentration of 124 µg/L, a prevalence of goiter of 2.2%, and a prevalence of thyroid hypoechogenicity of 5.7% were observed in schoolchildren. The percentage of neonatal TSH values >5.0 mIU/L resulted still higher (5.1%) than the World Health Organization threshold of 3.0%, whereas the prescriptions of methimazole showed a reduction of 13.5%. CONCLUSION: Fifteen years of iodine prophylaxis have led to iodine sufficiency in Italy, although there still is concern about iodine nutritional status during pregnancy.

A versatile approach to evaluate the occurrence of microfibers in mussels Mytilus galloprovincialis.

Microplastics of fibrous shape are esteemed to be the most abundant micro-debris form present in the environment. Despite the occurrence of microfibers in fish may pose a risk to human health, the literature is scarce regarding studies on the contamination in commercial marine fish mostly due to methodological issues. In this study, a versatile approach, able to discriminate among natural and synthetic microfibers according to the evaluation of specific morphological features, is proposed in farmed mussels (Mytilus galloprovincialis). The approach was useful to determine that microfibers were present in 74% of mussel samples, with a mean number of 14.57 microfibers/individual, corresponding to 3.13 microfibers/g w.w. A negative correlation between the size of analysed mussels and the amount of microfibers/g w.w. was detected, showing that smaller specimens contained more microfibers than the larger ones. This work paves the way to further studies aimed to adequately assess the risk that microfibers may pose to marine biota, also considering the commercial value as seafood items of many species of the Mytilus genus and the potential implication for human exposure.

Lactobacilli Infection Case Reports in the Last Three Years and Safety Implications.

Lactobacilli constitute the dominant microbiota in many fermented foods and comprise widely used probiotics. However, these bacteria cause rare infections mostly in diabetic and immunocompromised subjects in presence of risk factors such as prosthetic hearth valves and dental procedures or caries. The scope of this survey was re-assessing the pathogenic potential of lactobacilli based on the infection case reports published in the last three years. In 2019, 2020, and 2021, total of 17, 15, and 16 cases, respectively, including endocarditis, bacteremia, and other infections, were reported. These annual numbers are higher than those observed previously. Lacticaseibacillus rhamnosus (13 cases), comprising strain GG (ATCC 53103) with established applications in healthcare, L. paracasei (7 cases), Lactobacillus acidophilus (5 cases), L. jensenii (5 cases), Lactiplantibacillus plantarum (3 cases), L. paraplantarum, L. delbrueckii subsp. delbrueckii, L. gasseri, L. paragasseri, Limosilactobacillus fermentum, and L. reuteri (1 case each) were involved. Virulence characterization of two strains that caused infections, a derivative of L. rhamnosus GG and L. paracasei LP10266, indicated that increased biofilm-forming capacity favors pathogenicity and it is determined by variable genetic traits. This survey highlights that the strains of lactobacilli that cause infections are little characterized genetically. Instead, to avoid that these bacteria become a hazard, genetic stability should be periodically re-evaluated by whole genome sequencing (WGS) to ensure that only non-pathogenic variants are administered to vulnerable individuals.

Extraction and identification of microplastics from mussels: Method development and preliminary results.

Microplastics (MPs) are an emerging threat to marine ecosystems. One of the primary environmental risks is their bioavailability for aquatic organisms. Some fish and bivalves are of particular interest because their feeding strategies expose them to particles present in the water column. The aim of the study was to assess an extraction method in order to isolate and quantify MPs from fish gastrointestinal tract (n.8) and muscle (n.4), and bivalves (n.8) samples. The accuracy of the method was assessed through the calculation of the recovery percentage in samples spiked with a known number of MPs using microscopic observation. Successively, the extraction was preliminarily applied on n.20 mussels collected from mariculture plants of the Tyrrhenian and the Adriatic Sea. The results of the digestion protocol showed an average extraction yield of 80% in fish gastrointestinal tracts, 90% in fish muscle samples, and 95% in mussels. Preliminary analysis carried out on farmed mussels showed an average abundance of 3.8 items/individual, and 0.5 items/g of tissue, among those black, was the most represented color.

Iron Support in Erythropoietin Treatment in Myelodysplastic Syndrome Patients Affected by Low-Risk Refractory Anaemia: Real-Life Evidence from an Italian Setting.

Refractory anaemia (RA) among myelodysplastic syndrome (MDS) is associated with a partial functional iron deficit and may require transfusions. In low-risk lymphoma and solid tumour patients, iron support improves erythropoietin (EPO) cost-effectiveness in treating anaemia. The aim of this study is to see if oral sucrosomial iron support improves the cost-effectiveness of EPO treatment in MDS patients affected by low-risk RA. We treated patients with EPO only or with EPO plus oral sucrosomial iron or intravenous (i.v.) iron. The need for transfusions was lowest in the group taking oral iron (p = 0.016) or not receiving supplementation at all (p = 0.022). We compared costs of EPO with i.v. ferric gluconate or oral sucrosomial iron supplementation or no iron supplementation. The oral iron group had fewer side effects, fewer patient medical visits in the out-patient setting, and fewer transfusions; this led to higher savings on direct hospital costs and indirect patient costs (lost days at work) and translated into a 50% abatement of overall expenditures. EPO treatment-related expenditures in MDS-RA patients were lowest with oral sucrosomial iron supplementation (Sideral®), with a longer interval between EPO administration in maintenance treatment, quicker hemoglobin recovery, lower ferritin increase and fewer blood transfusions.

Thyroid dysfunction following a kelp-containing marketed diet.

Complementary medications and herbal medicine for weight loss have become very popular. We report a case of thyroid dysfunction following the ingestion of a kelp-containing marketed diet in a 45-year-old woman with no previous thyroid disease. Signs of hyperthyroidism occurred shortly after a kelp-containing diet. Hyperthyroidism lasted 2 months and was followed by an overt hypothyroidism. The thyroid scintiscan exhibited an extremely low uptake and colour-Doppler ultrasonography revealed multiple small areas of pulsatile flow. After 3 months of levothyroxine substitutive therapy, normal thyroid function was recovered after levothyroxine discontinuation. This clinical history is compatible with a case of iodine-induced thyrotoxicosis followed by prolonged block of the sodium-iodide symporter activity as a consequence of excessive iodine consumption from kelp. Consumers of marketed diets containing kelp or other iodine-rich ingredients should be advised of the risk to develop a thyroid dysfunction also in the absence of underlying thyroid disease.

A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency.

Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management.

Effect of cabergoline on metabolism in prolactinomas.

INTRODUCTION: Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas. PATIENTS AND METHODS: 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria. RESULTS: Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after the 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 µg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations the lipid profile significantly improved compared to baseline. Fasting insulin and homeostatic model assessment of insulin resistance significantly decreased after 1 year of CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months (p = 0.000). The visceral adiposity index significantly decreased after the 60-month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p = 0.022). CONCLUSIONS: CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB.

B-flow twinkling sign in preoperative evaluation of cervical lymph nodes in patients with papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) is the most common histologic type of differentiated thyroid cancer. The first site of metastasis is the cervical lymph nodes (LNs). The ultrasonography (US) is the best diagnostic method for the detection of cervical metastatic LNs. We use a new technique, B-flow imaging (BFI), recently used for evaluation of thyroid nodules, to estimate the presence of BFI twinkling signs (BFI-TS), within metastatic LNs in patients with PTC. Two hundred and fifty-two patients with known PTC were examined for preoperative evaluation with conventional US and BFI. Only 83 with at least one metastatic LN were included. All patients included underwent surgery; the final diagnosis was based on the results of histology. The following LN characteristics were evaluated: shape, abnormal echogenicity, absent hilum, calcifications, cystic appearance, peripheral vascularization, and BFI-TS. A total of 604 LNs were analyzed. Of these, 298 were metastatic, according to histopathology. The BFI-TS showed high values of specificity (99.7%) and sensitivity (80.9%). The combination of each conventional US sign with the BF-TS increases the specificity. Our findings suggest that BFI can be helpful in the selection of suspicious neck LNs that should be examined at cytologic examination for accurate preoperative staging and individual therapy selection.

Safety of long-term treatment with cabergoline on cardiac valve disease in patients with prolactinomas.

OBJECTIVE: Cabergoline (CAB) has been found to be associated with increased risk of cardiac valve regurgitation in Parkinson's disease, whereas several retrospective analyses failed to detect a similar relation in hyperprolactinemic patients. The current study aimed at investigating cardiac valve disease before and after 24 and 60 months of continuous treatment with CAB only in patients with hyperprolactinemia. SUBJECTS AND METHODS: Forty patients (11 men and 29 women, aged 38.7 ± 12.5 years) newly diagnosed with hyperprolactinemia entered the study. Cumulative CAB dose ranged from 12 to 588 mg (median 48 mg) at 24 months and 48-1260 mg (median 149 mg) at 60 months. All patients underwent a complete trans-thoracic echocardiographic examination. Valve regurgitation was assessed according to the American Society of Echocardiography. RESULTS: At baseline, the prevalence of trace mitral, aortic, pulmonic, and tricuspid regurgitations was 20, 2.5, 10, and 40% respectively, with no patient showing clinically relevant valvulopathy. After 24 months, no change in the prevalence of trace mitral (P=0.78) and pulmonic (P=0.89) regurgitations and of mild aortic (P=0.89) and tricuspid (P=0.89) regurgitations was found when compared with baseline. After 60 months, the prevalence of trace tricuspid regurgitation was only slightly increased when compared with that after 24 months (37.5%; P=0.82), but none of the patients developed significant valvulopathy. No correlation was found between cumulative dose and prevalence or grade of valve regurgitation at both evaluations. Prolactin levels normalized in all patients but one. CONCLUSION: CAB does not increase the risk of significant cardiac valve regurgitation in prolactinomas after the first 5 years of treatment.

Results of a single-center observational 10-year survey study on recurrence of hyperprolactinemia after pregnancy and lactation.

CONTEXT: The current survey study investigated the recurrence rate of hyperprolactinemia after cabergoline (CAB)-induced pregnancy and after lactation as well as safety of CAB exposure during early gestation. PATIENTS AND METHODS: From 1997-2008, 143 pregnancies were recorded in 91 patients with hyperprolactinemia (age 30.4 ± 4.7 yr, 76 microadenomas, 10 macroadenomas, and five nontumoral hyperprolactinemia). CAB therapy was discontinued within wk 6 of gestation in all. Pregnancies were monitored until delivery or termination, during and after lactation, twice yearly up to 60 months. The incidence of abortions, premature delivery, and fetal malformations was also analyzed. RESULTS: Pregnancies resulted in 13 (9.1%) spontaneous abortions and 126 (88.1%) live births. No neonatal malformations and/or abnormalities were recorded. In 29 of 91 patients (three with macroadenomas), treatment with CAB had to be restarted within 6 months after lactation because of hyperprolactinemia recurrence, whereas in 68% of cases, no additional therapy was required up to 60 months. No tumor mass enlargement was observed. All patients but three were breastfeeding, 35 (38.5%) for less than 2 months and 56 (61.5%) for 2-6 months. Three months after cessation of lactation and 60 months after pregnancy, no difference in prolactin levels was found between patients nursing for less than 2 months and 2-6 months. CONCLUSIONS: Fetal exposure to CAB at conception does not induce any increased risk of miscarriage or malformations. Pregnancy is associated with normalization of prolactin levels in 68% of patients. Breastfeeding does not increase the recurrence rate of hyperprolactinemia.

Usefulness of salivary cortisol in the diagnosis of hypercortisolism: comparison with serum and urinary cortisol.

OBJECTIVE: Several tests have been proposed to diagnose patients with Cushing's syndrome (CS). The aims of the study were: i) to evaluate the performance of salivary cortisol (SC) in hypercortisolism and ii) to compare SC with serum cortisol (SeC) and urinary cortisol. DESIGN AND PATIENTS: This was a diagnostic study. Twenty-seven patients with untreated Cushing's disease (CD untr), 21 women consuming oral contraceptive pill (OCP), 18 pregnant women, and 89 healthy subjects (controls) were enrolled. METHODS: SC and SeC at baseline and after the low-dose dexamethasone suppression test (LDDST) and urinary free cortisol (UFC) were measured. RESULTS: Midnight SC had a sensitivity of 100% in the CD untr group and a specificity of 97.7% in the controls. Specificity remained high (95.2%) in women taking OCP, while in pregnant women, it decreased to 83.3%. SC after the LDDST showed a sensitivity of 96.3% in the CD untr group; specificity was 97.7% in the controls and 90.5% in OCP women. Midnight SeC had a sensitivity of 100% in the CD untr group. SeC after the LDDST had a sensitivity of 100% in the CD untr group while specificity was 97.7% in the controls and 61.9% in women taking OCP. For UFC, sensitivity was 92.6% in the CD untr group while specificity was 97.7% in the controls and 100% in the OCP group. CONCLUSIONS: SC is a reliable parameter for the diagnosis of severe hypercortisolism, with high sensitivity and specificity. In women during pregnancy or taking OCP, the measurement of SC, identifying the free fraction, could be helpful to exclude CS.

Image-guided robotic radiosurgery (CyberKnife) for pancreatic insulinoma: is laparoscopy becoming old?

Insulinomas constitute about 25% of endocrine pancreatic tumors. Laparoscopic surgery is the treatment of choice. However, pancreas-related complications rate is very high, even in experienced hands, ranging up to 37%. Alternative procedures such as embolization with trisacryl have not been accepted by the surgical community. Image-guided robotic radiosurgery or stereotactic radiosurgery (CyberKnife) is a minimally invasive procedure delivering large doses of ionizing radiation to a well-defined target. CyberKnife radiosurgery is successfully used in brain cancer, lung cancer, prostate cancer, liver metastases, kidney cancer, and pancreatic cancer. The authors present the first case to their knowledge of a benign functioning insulinoma successfully treated by a CyberKnife technique with a 3-year follow-up.

FDG/PET uptake in asymptomatic multilobar Chlamydia pneumoniae pneumonia.

BACKGROUND: FDG-PET is a diagnostic imaging procedure effective in staging primary and recurrent cancer. False-positive uptake already has been described in both inflammatory and infectious respiratory diseases, although no reports associate Chlamydia pneumoniae infection to FDG uptake. CASE REPORT: An incidental diagnosis of asymptomatic multilobar pneumonia during screening for thyroid malignancy is reported. Three areas of pulmonary consolidation strongly positive on PET/CT scan, mimicking pulmonary malignancy were identified. Both radiologic features and serum IgM antibodies for Chlamydia pneumoniae suggested the diagnosis of an unusual presentation of a Chlamydia pneumoniae respiratory infection. Specific antibiotic therapy induced a complete resolution of the areas of pulmonary consolidation. CONCLUSIONS: This case suggests that positive PET is not an absolute indicator for malignancy. Chlamydia pneumoniae respiratory infections can exhibit positive uptake on FDG-PET.

Reduced colonic apoptosis in mice overexpressing bovine growth hormone occurs through changes in several kinase pathways.

OBJECTIVE: Growth hormone (GH) has antiapoptotic effects in several cell lines, including human colonic adenocarcinoma cells. In addition, it has been reported that patients with acromegaly have reduced apoptosis in colonic mucosa. The aim of the study was to investigate colonic apoptosis and underlying molecular mechanisms in transgenic mice overexpressing bovine GH (Acro) aged 3 months (young) or 9 months (elder). DESIGN AND METHODS: Apoptosis in colonic epithelial cells was evaluated by TUNEL and Annexin V; expression of pro- and anti-apoptotic proteins was assessed by Western blot. GH action was blocked treating Acro with a selective GH receptor antagonist. RESULTS: Young and elder Acro had lower colonic apoptosis [driven by GH through p38, p44/42 and PI3 kinase pathways], than littermate controls; changes were abolished by treating Acro with a selective GH receptor antagonist. The effects of GH were consistent with an anti-apoptotic phenotype (reduced cytosolic cytochrome-c, Bad and Bax and increased Bcl-2, and Bcl-XL level) leading to lower activation of caspase-9 and caspase-3. Changes in apoptotic proteins reversed after treatment with a GH receptor antagonist, suggesting a direct effect of GH. In addition, antiapoptotic phenotype of Acro had a protective role against doxorubicin-induced apoptosis. CONCLUSIONS: Our results suggest that GH leads to increased and reduced levels of anti- and pro-apoptotic proteins, respectively, lowering apoptosis in either young or elder transgenic animals through activation of several kinase pathways.

Serum pituitary antibodies in normal pregnancy and in patients with postpartum thyroiditis: a nested case-control study.

OBJECTIVES: The aim of this study was to evaluate antipituitary antibody (APA) prevalence in a series of patients with postpartum thyroiditis (PPT) during pregnancy and in the postpartum. DESIGN: We conducted a nested case-control study on consecutive PPT and normal pregnant women at the Centre for Endocrine and Diabetes Sciences in Cardiff and at the Department of Endocrinology in Pisa. METHODS: We enrolled 30 women with PPT: 17 were hypothyroid (Hypo), 7 with hyperthyroidism (Hyper) and 6 with a transient hyperthyroidism followed by hypothyroidism (Biphasic). Twenty-one healthy pregnant women served as controls. APA (measured using indirect immunofluorescence), free thyroxine, free triiodothyronine, TSH, antithyroid autoantibodies, and thyroid ultrasound were performed during pregnancy and postpartum. The stored sera have been sent to Pisa, where serum APA, IGF1, and cortisol were measured. RESULTS: APA were found in 8 out of the 30 PPT patients (26.7%) and in one normal pregnancy (4.7%, P=0.063). Three out of the seventeen Hypo with PPT (17.6%), three out of the seven Hyper PPT (42.8%), and two out of the six Biphasic PPT (33.3%) were positive for APA. APA prevalence was not significantly different in the PPT subgroups (P=0.453). With one exception, APA all increased in the postpartum period (87.5%, P<0.016). Basal serum IGF1 and cortisol were in the normal range with the exception of two patients with positive APA who presented low serum IGF1 levels (36 and 45 ng/ml). CONCLUSIONS: APA are frequently present in the postpartum period in patients affected by PPT. Further studies are necessary to evaluate whether APA in PPT patients are associated with pituitary function impairment.

Transgenic mice overexpressing growth hormone (GH) have reduced or increased cardiac apoptosis through activation of multiple GH-dependent or -independent cell death pathways.

GH has antiapoptotic effects in cardiac or noncardiac cell lines; however, increased apoptosis has been found in myocardial samples of patients with acromegaly. The aim of this study was to investigate cardiac apoptosis and underlying molecular mechanisms in transgenic mice overexpressing bovine GH [acromegalic mice (Acro)] aged 3 or 9 months. Cardiomyocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase assay and annexin V; expression of pro- or antiapoptotic proteins was assessed by Western blot. Specificity of GH action was confirmed using a selective GH receptor antagonist. Apoptosis was lower in 3-month-old Acro than in controls; reduction was abolished by a GH receptor antagonist. The effects of GH were consistent with an antiapoptotic phenotype (increased Bcl2 and Bcl-XL and reduced Bad and cytochrome c levels, leading to lower activation of caspase-9 and caspase-3). In contrast, apoptosis was higher in 9-month-old Acro than in littermate controls; in addition, a GH receptor antagonist was without effect; the proapoptotic phenotype consisted in increased Bad, cytochrome c, caspase-9, and caspase-3. GH reduced apoptosis through p38 and p44/42 kinase pathways at young ages, whereas phosphatidylinositol-3-kinase was silent; on the contrary, the effects of GH on p38 and p44/42 kinase pathways were overcome by GH-independent stimuli in 9-month-old Acro. In addition, the antiapoptotic effect of GH was still present at this age as shown by phosphatidylinositol-3-kinase/Akt pathway activation. In conclusion, chronic GH excess reduced apoptosis at a young age, whereas its antiapoptotic action was overwhelmed in older animals by GH-independent mechanisms, leading to increased cell death.

Cardiac expression of adenine nucleotide translocase-1 in transgenic mice overexpressing bovine GH.

Heart hypertrophy is a common finding of acromegaly, a syndrome due to GH excess. Impairment of adenine nucleotide translocase-1 (ANT-1) gene, the main mitochondrial ADP/ATP exchanger, leads to cardiac hypertrophy. The aim of the study was to evaluate cardiac expression and the functional role of ANT-1 in 1- to 12-month-old transgenic mice overexpressing bovine GH (acromegalic mice, Acro) and littermate controls (wild-type mice, Wt). GH specificity of protein degree variation was assessed treating Acro with pegvisomant, a GH receptor competitor. Tissue levels of ANT-1, NF-kappaB, ATP, and lactic acid were evaluated by western blot, bioluminescence, and Fourier transform infrared spectroscopy respectively. The degree of ANT-1 expression was higher in 1-month-old Acro than in Wt (47+/-5% OD vs 33+/-4% OD, P<0 01). On the contrary, ANT-1 expression was lower in 3- to 12-month-old Acro than in Wt (P<0 03). Changes in ANT-1 expression were associated with consistent changes of cellular ATP content, increasing at 1 month (P<0 05) and reducing thereafter in Acro when compared with Wt (P<0 04). Treatment with pegvisomant abolished ANT-1 and ATP changes observed in 1- and 3-month-old Acro, thus supporting a GH-dependent mechanism. Reduced ATP generation in hypertrophied hearts of older Acro was associated with increased lactic acid levels suggesting that part of energy was due to glycolysis. Variations in ANT-1 expression were linked to GH through changes in NF-kappaB, the levels of which changed accordingly. In conclusion, 1-month-old acromegalic mice had increased ANT-1 expression and higher degree of ATP production. Long-standing disease was associated with a consistent reduction of ANT-1 and ATP tissue levels, which became GH-independent in older animals. This study demonstrated a direct effect of GH on key proteins involved in energy metabolism of acromegalic hearts.

Thyroid color flow Doppler sonography: an adjunctive tool for differentiating patients with inappropriate thyrotropin (TSH) secretion due to TSH-secreting pituitary adenoma or resistance to thyroid hormone.

BACKGROUND: Thyrotropin (TSH)-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone (RTH) are two forms of inappropriate TSH secretion. Thyroid blood flow is largely TSH dependent. OBJECTIVE: To assess whether thyroid blood flow may help to differentiate TSHoma and RTH. DESIGN: Intrathyroidal color flow Doppler sonography (CFDS) pattern and peak systolic velocity (PSV) were assessed at baseline and during T(3) suppression test on eight consecutive patients with TSHoma and 10 with RTH. MAIN OUTCOME: All controls had CFDS pattern 0. Three RTH patients had pattern I and seven had pattern II. Two TSHoma patients had pattern I, five had pattern II, and one had pattern III. PSV at baseline was 3.8 +/- 1.3 cm/s in controls, 8.8 +/- 2.5 cm/s in RTH, 11.1 +/- 2.7 cm/s in TSHoma (p < 0.0003 vs. controls, p = 0.087 RTH vs. TSHoma). After T3 suppression test, PSV values were lower in RTH than in TSHoma (4.6 +/- 1.8 vs. 7.7 +/- 2.6 cm/s, p = 0.008). PSV values and CFDS pattern normalized in nine and eight RTH patients, respectively, after T(3) suppression test; conversely, only one TSHoma patient had a normalization of PSV values, and none had a normalization of CFDS pattern (p < 0.003 vs. RTH). CONCLUSIONS: Both RTH and TSHoma have increased CFDS pattern and PSV values; however, after T(3) both parameters normalized in most patients with RTH but not in those with TSHoma. Accordingly, CFDS pattern and PSV are adjunctive tools to differentiate these two forms of inappropriate TSH secretion.