Physiological and pathophysiological role of somatostatin receptors in the human thymus

During the first half of the previous century, the evidence that the endocrine and nervous systems integrate and regnlate different functions in the human body coincided with the new findings supporting the concept that immune mechanisms may be influenced by these systems as well. In the past decades, many studies were carried out to understand the molecular and cellular basis of interactions between the immune system and neuroendocrine activities. TIle interactions between the inunune, endocrine and nervous systems are very complex. Although the accumulated information is enormous, many reciprocal interactions are poorly understood, several mechanisms are still difficult to interpret, and in some cases the results are even contradictory. Nevertheless, increasing numbers of researchers and many laboratories are nowadays focused on understanding how hormones, neuropeptides, neurotransmitters and specific products of inunWle cells exert their regulatory functions and act in integrating such different systems

Managing Cushing's disease: the state of the art.

Cushing's disease is a rare chronic disease caused by a pituitary adenoma, which leads to excess secretion of adrenocorticotropic hormone (ACTH). The over-production of ACTH leads to hyperstimulation of the adrenal glands and a chronic excess of cortisol, resulting in the signs and symptoms of a severe clinical state (Cushing's syndrome) that leads to significant morbidity, negative impacts on the patient's quality of life, and, if untreated, increased mortality. The management of patients with Cushing's disease is complicated by the heterogeneity of the condition, with signs and symptoms that overlap with those of other diseases, and high subclinical incidence rates. Controversies surrounding the tests used for screening and identifying patients with Cushing's disease add to the challenge of patient management. Surgical intervention to remove the adenoma is the first-line treatment for patients with Cushing's disease, but medical therapies are useful in patients who relapse or are unsuitable for surgery. The recent introduction of pasireotide, the first pituitary-directed medical therapy, expands the number of treatment options available for patients with Cushing's disease. This state-of-the-art review aims to provide an overview of the most recent scientific research and clinical information regarding Cushing's disease. Continuing research into improving the diagnosis and treatment of Cushing's disease will help to optimize patient management

Adult GH deficiency - the value of IGF-I estimation

In patients with growth hormone (GH) deficiency (GHD) the diagnostic value of IGF-I levels has been recently revisited. A normal IGF-I value does not exclude GHD, because its secretion is complex and depends by several factors other than GH, such as age, nutritional status, obesity, as well as catabolic illness. Due to the complexity and costs of GH stimulation tests, several authors have analyzed the predictive and diagnostic value of the concentration of plasma IGF-I in patients suspected for GHD. The evaluation of IGF-I is also determinant to individualized dose-titration strategies, able to avoid the common adult side effects of substitutive therapy with recombinant GH. Current recommendations in clinical practice for GH replacement therapy, in GHD adults, agree on GH dosing regimens to be individualized independently of body weight using IGF-I levels as a biomarker of the treatment. For these reasons, in a clinical setting, appropriate normative values in different age groups in a large healthy population must be established in single laboratories, while, considering the relatively small sex difference, a different reference range for sex seems not necessary. This review discusses the more recent debated issues in the literature on the role of IGF-I, as well as other IGF system components, in the management of adult patients with GHD

The primary role of radiological imaging in the diagnosis of rare musculoskeletal diseases. Emphasis on ultrasound

Objective: In July 2017 a multidisciplinary clinical Center specialized in rare diseases was activated. A rare disease can involve the musculoskeletal system. A multimodality musculoskeletal imaging approach allows for a rapid diagnosis. The purpose of this study was to assess when musculoskeletal radiology, ultrasound in particular, plays a primary role in the diagnostic path of a rare disease. Methods and materials: The Center included a list of 621 main rare diseases. Pathologies in which radiology has a primary diagnostic role were extracted from the list. From September 2017 to January 2018 all conditions involving the musculoskeletal system, including the peripheral nervous system, were systematically evaluated by one radiologist. The second radiologist, an official consultant of the Center, verified the list for consistency. Descriptive analysis was performed. Results: A total of 101/621 (16%) rare diseases can be diagnosed for the first time in the diagnostic path of the patient with medical imaging. A total of 36/101 (36%) rare diseases involve the musculoskeletal system. A total of 14/36 (39%) are pediatric diseases, 10/36 (28%) are adult age diseases, while 12/36 (33%) diseases affect all ages. A total of 23/36 (64%) of the selected rare diseases could be diagnosed with MRI, 19/36 (53%) with CT, 23/36 (64%) with X-ray, 9/36 (25%) with an US, and 1/36 (3%) with PET. Conclusions: Musculoskeletal imaging could be important for a non-invasive diagnosis in up to 36/101 (36%) rare diseases, as well as for outcome prediction, especially in pediatrics. Musculoskeletal imaging plays a crucial role in the diagnosis of rare diseases and could strongly influence the clinical pathway. Ultrasound is crucial in up to 25% of patients with rare diseases affecting the musculoskeletal system

Metabolic and cardiovascular risk in patients with a history of differentiated thyroid carcinoma: A case-controlled cohort study

Hyperthyroidism seems to increase metabolic and cardiovascular risk, while the effects of sub-clinical hyperthyroidism are controversial. We evaluated metabolic and cardiovascular parameters in differentiated thyroid carcinoma (DTC) patients with suppressed thyrotropin (TSH) due to levo-thyroxine (L-T4) therapy. We studied DTC patients and, as a control group, patients with a history of surgery for non-malignant thyroid pathology. Significantly higher insulin and lower HDL-cholesterol levels were recorded in DTC subjects. In both groups, insulin levels were significantly related with body mass index (BMI) but not with age or L-T4 dosage. In DTC patients, a significant negative correlation was seen between HDL-cholesterol and BMI or L-T4 dosage. In both groups, intima-media thickness (IMT) correlated positively with age, BMI, glucose levels and systolic blood pressure. In DTC patients, increased IMT was significantly correlated with glycated hemoglobin (HbA1c), cholesterol and triglycerides. In DTC patients, C-reactive protein correlated positively with insulin, insulin resistance, triglycerides and systolic blood pressure, and negatively with HDL-cholesterol. In both DTC and control subjects, fibrinogen correlated positively with age, BMI, increased IMT, HbA1c and systolic blood pressure. In DTC subjects, plasma fibrinogen concentrations correlated positively with insulin resistance, cholesterol and LDL-cholesterol, and negatively with TSH levels. Our data confirm that the favorable evolution of DTC can be impaired by a high incidence of abnormal metabolic and cardiovascular data that are, at least in part, related to L-T4 therapy. These findings underline the need for adequate L-T4 titration

Biological and Biochemical Basis of the Differential Efficacy of First and Second Generation Somatostatin Receptor Ligands in Neuroendocrine Neoplasms

Endogenous somatostatin shows anti-secretory effects in both physiological and pathological settings, as well as inhibitory activity on cell growth. Since somatostatin is not suitable for clinical practice, researchers developed synthetic somatostatin receptor ligands (SRLs) to overcome this limitation. Currently, SRLs represent pivotal tools in the treatment algorithm of neuroendocrine tumors (NETs). Octreotide and lanreotide are the first-generation SRLs developed and show a preferential binding affinity to somatostatin receptor (SST) subtype 2, while pasireotide, which is a second-generation SRL, has high affinity for multiple SSTs (SST5 > SST2 > SST3 > SST1). A number of studies demonstrated that first-generation and second-generation SRLs show distinct functional properties, besides the mere receptor affinity. Therefore, the aim of the present review is to critically review the current evidence on the biological effects of SRLs in pituitary adenomas and neuroendocrine tumors, by mainly focusing on the differences between first-generation and second-generation ligands

Physiological and pathophysiological role of somatostatin receptors in the human thymus

This is a review summarizing the physiological and pathophysiological role of somatostatin receptors in the human thymus

Long-term outcome of low-activity radioiodine administration preceded by adjuvant recombinant human TSH pretreatment in elderly subjects with multinodular goiter

<p>Abstract</p> <p>Background</p> <p>Large multinodular goiter (MNG) in elderly people is a common finding which can require intervention. The long-term effect of radioiodine therapy on thyroid volume (TV) and function after recombinant human (rh) TSH pre-treatment was evaluated.</p> <p>Methods</p> <p>After baseline evaluation, 40 subjects over 60 years old with a large MNG were treated with ¹³¹I up to the activity of 600 MBq. Nineteen patients were pretreated with rhTSH (0.1 mg on 2 consecutive days; group 1) while 21 subjects underwent treatment without rhTSH pretreatment (group 2). TV was monitored every 6–12 months by ultrasonography. The median follow-up period was 36 months.</p> <p>Results</p> <p>At the baseline, the groups matched in terms of TV, 24-h radioiodine uptake (RAIU), urinary iodine and neck complaints. The number of subjects pretreated with anti-thyroid drugs was significantly (P = 0.01) greater in group 2 than in group 1; TSH was more suppressed (P = 0.003) and f-T3 was more elevated (P = 0.005) in group 2 than in group 1 patients. RhTSH increased 24-h RAIU in group 1 up to the baseline level observed in group 2. The ¹³¹I activity administered was similar in both groups. Adverse events were slight and similar in both groups. A permanent post-radioiodine toxic condition was reported only in 2 patients in group 2. After radioiodine therapy, hypothyroidism was observed in significantly more group 1 patients than group 2 patients (P = 0.002). While TV was reduced in both groups, the percentage TV reduction recorded at the last examination was significantly higher (P = 0.03) in group 1 than in group 2. MNG-related complaints were significantly reduced in both group 1 (P = 0.0001 vs baseline) and group 2 (P = 0.001) patients.</p> <p>Conclusion</p> <p>Low radioiodine activities after pretreatment with low-dosage rhTSH are able to reduce TV and improve MNG-related symptoms in elderly subjects.</p

Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response

Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI

Treatment of Type 2 Diabetes in Subjects with Obesity: What is the Best Approach?

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