Correlation between Severity of Growth Hormone Deficiency and Thyroid Metabolism and Effects of Long-Term Growth Hormone Treatment on Thyroid Function in Children with Idiopathic Growth Hormone Deficiency.

BACKGROUND/AIM: The significance of changes in thyroid function in children during growth hormone (GH) treatment remains uncertain. We aimed to evaluate the impact of GH replacement on thyroid status in children with idiopathic GH deficiency (GHD). METHODS: Data of 105 GHD children (82 M, 23 F; aged 11.13 years) during a 36-month follow-up were analyzed. At diagnosis the areas under the curve of GH (AUCGH) were calculated during a GH-releasing hormone + arginine (GHRH-Arg) and insulin tolerance test. RESULTS: A significant \u394fT3 (p < 0.001) was documented at 12 months, without any further change at 24 and 36 months and without fT4 and TSH modifications. Grouping patients according to \u394fT3 at 12 months into those with lower (n = 80, 76%) or greater values than the 75th percentile (n = 25, 24%), the latter showed lower AUCGH and GH peak during a GHRH-Arg (p = 0.018 and 0.014, respectively) and insulin tolerance test (p = 0.023 and 0.020, respectively) at diagnosis. In addition, children with lower GH at diagnosis showed a greater \u394fT3 at 12 months (p = 0.030). CONCLUSIONS: In GHD children, GH treatment is associated with a significant increase in fT3 in the first 12 months, more pronounced in patients with more severe GHD, highlighting the strong correlation between severity of GHD and thyroid metabolism

Pasireotide versus pituitary surgery: a retrospective analysis of 12 months of treatment in patients with Cushing's disease

Pituitary surgery represents the first-line treatment for most patients with Cushing\u2019s disease (CD). In the case of surgery failure, additional treatment options are required. Pasireotide has shown favourable results in the first-line treatment of patients with CD, who are not candidates for surgery or in the second-line when surgery has failed. The aim of the current study is to compare the effects of surgery and pasireotide treatment in a cohort of patients with CD, and to evaluate the differences in response rate in terms of hormonal and clinical control, and improvement of metabolic complication

Correlation between adrenal function, growth hormone secretion, and insulin sensitivity in children with idiopathic growth hormone deficiency

Purpose Patients with growth hormone deficiency (GHD) demonstrate an increased cortisol/cortisone ratio which could potentially explain the metabolic features of GHD, while GH treatment (GHT) could increase the cortisol metabolism. Methods In 35 children (27 M, mean age 10.1 years) with idiopathic GHD at baseline and after 12 months of GHT and in 25 controls, in addition to metabolic parameters, we assessed adrenal function by morning serum cortisol, its peak, and its area under the curve (AUCCOR) during insulin tolerance test (ITT). Results A cortisol peak <18 \ub5g/dl was shown in 22 and 31% of GHD children at baseline and after GHT, respectively. At baseline, GHD children had lower fasting glucose (p < 0.001) and ISI-Matsuda (p = 0.042), with concomitant higher Homa-IR (p = 0.006) and morning cortisol (p = 0.012) than controls. Morning cortisol was negatively correlated with GH (p < 0.001), fasting glucose (p < 0.001) and ISI-Matsuda (p < 0.001) and positively with Homa-IR (p = 0.010). Both cortisol peak and AUCCOR were negatively correlated with GH (all p < 0.001) and ISI-Matsuda (p = 0.016 and p = 0.001, respectively). After 12 months of GHT, a significant increase in fasting glucose (p < 0.001), and Homa-IR (p = 0.011) was documented, with a concomitant decrease in morning cortisol (p = 0.002), AUCCOR (p = 0.038), total (p = 0.003) and LDL-cholesterol (p = 0.016). No significant correlations were found among cortisol levels and all parameters were investigated. Conclusions Cortisol levels correlate with GH secretion and with many metabolic parameters in GHD children, while the metabolic effects during GHT are mainly due to GHT per se and less to cortisol reduction

Early Lung Function Abnormalities in Acromegaly.

BACKGROUND: Acromegaly is an insidious disorder caused by a pituitary growth hormone (GH)-secreting adenoma resulting in high circulating levels of GH and insulin-like growth factor I (IGF-I). Respiratory disorders are common complications in acromegaly, and can severely impact on quality of life, eventually affecting mortality. OBJECTIVES: The present study aimed to explore structural and functional lung alterations of acromegalic subjects. METHODS: We enrolled 10 consecutive patients (M/F: 5/5) affected by acromegaly. In all patients, magnetic resonance imaging (MRI) revealed the presence of pituitary tumor. All patients underwent clinical, lung functional, biological, and radiological assessments. Ten healthy age-matched subjects also served as controls. RESULTS: No statistically significant differences in lung function were detected between acromegalic and healthy subjects (p ≥ 0.05 for all analyses). However, the diffusing capacity for CO (TLCO) was significantly lower in the acromegalic group than in healthy subjects (TLCO% predicted: 78.1 ± 16 vs. 90 ± 6 %, respectively, p = 0.04; KCO% predicted: 77 ± 16 vs. 93 ± 5 %, p = 0.02, respectively). None of the lung function parameters correlated with duration of the disease, or with inflammatory marker of the airways. In acromegalics, biological (exhaled NO concentrations) and imaging (total lung volume, TLV, and mean lung density, MLD) evaluations were within normal values. The TLV measured by HRCT was 3540 ± 1555 ml in acromegalics, and the MLD was -711 ± 73 HU. None of the lung functional, radiological, and biological findings correlated with GH or IGF-I levels, and no correlation was found with duration of disease. CONCLUSIONS: In the current study, lung function evaluation allowed to detect early involvement of lung parenchyma, as assessed by TLCO and KCO, even in the absence of parenchymal density alterations of the lung by HRCT. These findings suggest to routinely include the carbon monoxide diffusing capacity in the lung function assessment for an early intervention in acromegaly

Duodenal carcinoma at the ligament of Treitz. A molecular and clinical perspective

Background There is very small occurrence of adenocarcinoma in the small bowel. We present a case of primary duodenal adenocarcinoma and discuss the findings of the case diagnostic modalities, current knowledge on the molecular biology behind small bowel neoplasms and treatment options. Case The patient had a history of iron deficiency anemia and occult bleeding with extensive workup consisting of upper endoscopy, colonoscopy, capsule endoscopy, upper gastrointestinal series with small bowel follow through and push enteroscopy. Due to persistent abdominal pain and iron deficiency anemia the patient underwent push enteroscopy which revealed adenocarcinoma of the duodenum. The patient underwent en-bloc duodenectomy which revealed T3N1M0 adenocarcinoma of the 4th portion of the duodenum. Conclusions Primary duodenal carcinoma, although rare should be considered in the differential diagnosis of occult gastrointestinal bleeding when evaluation of the lower and upper GI tract is unremarkable. We discuss the current evaluation and management of this small bowel neoplasm

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The metabolic outcomes of growth hormone treatment in children are gender specific

OBJECTIVE: To evaluate the impact of gender on the clinical and metabolic parameters in prepubertal growth hormone deficiency (GHD) children at diagnosis and during GH treatment (GHT). DESIGN: The data of 105 prepubertal children (61 males, 44 females, mean age 6.8\u2009\ub1\u20090.7 years) affected by idiopathic GHD were retrospectively evaluated. METHODS: Body height, BMI, waist circumference (WC), IGF-I, HbA1c, lipid profile, fasting and after-OGTT glucose and insulin levels, insulin sensitivity and secretion indices were evaluated at baseline and after 24 months of GHT. RESULTS: At baseline, no significant difference was found in all clinical, hormonal and metabolic parameters between males and females. After 24 months of GHT, both males and females showed a significant increase in height (both P\u2009<\u20090.001), BMI (both P\u2009<\u20090.001), WC (P\u2009<\u20090.001 and P\u2009=\u20090.004, respectively), IGF-I (both P\u2009<\u20090.001), fasting glucose (P\u2009<\u20090.001 and P\u2009=\u20090.001, respectively), fasting insulin (both P\u2009<\u20090.001) and Homa-IR (both P\u2009<\u20090.001), with a concomitant significant decrease in insulin sensitivity index (ISI) (both P\u2009<\u20090.001) and oral disposition index (DIo) (P\u2009=\u20090.001 and P\u2009<\u20090.001, respectively). At 24 months of GHT, females showed significantly higher BMI (P\u2009=\u20090.027), lower ISI (P\u2009<\u20090.001) and DIo (P\u2009<\u20090.001), in concomitance with a significant greater change from baseline to 24 months of BMI (P\u2009=\u20090.013), WC (P\u2009<\u20090.001), ISI (P\u2009=\u20090.002) and DIo (P\u2009=\u20090.072), although the latter does not reach statistical significance. CONCLUSIONS: Twenty-four months of GHT in prepubertal children leads to different metabolic outcomes according to gender, with a greater reduction in insulin sensitivity in females, regardless of auxological and hormonal parameters. Therefore, prepubertal GHD females should probably need a more proper monitoring in clinical practice

Metabolic effects of GH therapy in adults with GH deficiency: a 2 year prospective study

Background Growth hormone deficiency (GHD) in adults is associated with adverse metabolic profile, while data about the metabolic effects of GH treatment are controversial. Aim To evaluate the metabolic influence of GH replacement in GHD. Subjects and Methods Data of 65 patients (35 M, age 54 ± 18 yrs) were analyzed. Before GH therapy and yearly up to 2 years we measured BMI, WC, visceral adiposity index (VAI), IGF-1, lipide profile, HbA1c and basal insulin-secretion (Homa-β) and -sensitivity (Homa-IR) indexes. Results No subject showed overt dysglycemia at baseline and during GH therapy. Hypertriglyceridemia was detected in 36 patients at baseline and in 31 and 20 respectively at 12 and 24 months, while low HDL cholesterol was detected in, respectively, 25, 17 and 8 patients during follow-up. Compared to baseline, WC and VAI significantly decreased after 12 (p<0.001) and 24 months (p<0.001), without changes in BMI. IGF-1 (both p<0.001), total-(both p<0.001), LDL-cholesterol (both p<0.001) and triglycerides ( p=0.84,<0.001 and <0.001, respectively), significantly decreased from baseline to 1 or 2 years, with an increase in HDL (both p<0.001). Insulin, Hba1c, and Homa-IR increased (all p<0.001), while a slight increase in glucose was shown only at 24 months (89.1 ± 13.6 and 92.4 ± 13.9 vs.88.1 ± 14 mg/dl; p=0.85, 0.65 and <0.001, respectively). Homa-β did not significantly change. The favorable changes in lipid profile was more closely related to change of VAI than IGF-1 (data not shown). Conclusions In adults GHD, a slight deterioration of insulin sensitivity, although without overt worsening in glucose metabolism, seems to occur during the first 2 years of GH treatment and it appears well balanced by a significant improvement in body composition (VAI and WC) and lipid profile

Modificazioni di insulino-secrezione, insulino-sensibilit\ue0 e funzione adiposa durante terapia con pasireotide in un gruppo di pazienti con malattia di Cushing

Background: La terapia con pasireotide (PAS) \ue8 efficace nel miglioramento del quadro clinico e biochimico dei soggetti con Malattia di Cushing (MC) da adenoma ipofisario ACTH-secernente, ma una della principali cause di interruzione della stessa \ue8 l\u2019insorgenza di eventi avversi, tra i quali l\u2019iperglicemia \ue8 il pi\uf9 frequente. Obiettivi: Valutare l\u2019effetto della terapia con PAS su metabolismo glucidico, insulino-secrezione e sensibilit\ue0. Metodi: Abbiamo valutato in 8 pazienti con MC recidivata post-chirurgia durante un follow-up terapeutico di 12 mesi, oltre ai parametri clinici ed ormonali, l\u2019insulino-secrezione tramite HOMA\u3b2 e area sotto la curva del C-peptide (AUC2hc-peptide) durante MMTT, l\u2019insulino-sensibilit\ue0 tramite HOMA-IR e clamp euglicemico iperinsulinemico, e una serie di adipocitochine con ruolo metabolico. Risultati: 12 mesi di terapia con PAS determinano riduzione significativa di BMI (p=0.012), circonferenza vita (p=0.011) e colesterolo totale (p=0.017), con contestuale incremento della glicemia a digiuno (p=0.012), dell\u2019AUC della glicemia durante MMTT (p=0.036) e di HbA1c (p=0.027). L\u2019insulino-secrezione \ue8 ridotta, come dimostrato dalla riduzione di HOMA-\u3b2 [72.8 (56.1-221.7) vs.36.3 (29.2-105.6)%; p= 0.036] e AUC2h c-peptide [205.7 (196.4-348.1) vs. 160.9 (149.5-284.5) nmol/l; p = 0.017], senza alcuna modifica nell\u2019insulino-sensibilit\ue0, come dimostrato dagli immodificati valori di HOMA-IR e M-value durante clamp (p=NS). Si osserva inoltre un aumento dei livelli del recettore solubile della leptina (ObR) [(15.4 (7.1-40.5) vs. (23.9 (11.9-51) p=0.028)] e della retinol binding protein 4 (RBP4) [26.4 (18.1-36.5) vs. 41.3 (26.2-63.5); p= 0.017)], con contestuale riduzione del rapporto leptina/ObR [(2.5 (0.25-7.54) vs. 0.66 (0.32-3.82); p=0.017)] e della fatty acid binding protein (FABP) [(82.9 (11.2-137.3) vs. 41.7 (18.6-66.3); p=0.036)]. Conclusioni: PAS determina un peggioramento del metabolismo glucidico dovuto alla significativa riduzione dell\u2019insulino-secrezione, controbilanciato da un miglioramento clinico generale e della funzione adiposa, probabilmente come diretta conseguenza della significativa riduzione ponderale