Combined therapy of somatostatin analogues and dopamine agonists in the treatment of pituitary tumours

Pituitary tumours express both somatostatin and dopamine receptors. Medical treatment with somatostatin analogues is a cornerstone of GH- and TSH-secreting tumours, while treatment with dopamine agonists is a cornerstone of prolactin-secreting tumours. Dopamine agonists have also demonstrated some efficacy in patients with GH- and TSH-secreting adenomas. Neither ACTH-secreting nor clinically non-functioning tumours have a well-established medical treatment. Nevertheless, some recent results have indicated a potential usefulness of the dopamine agonist cabergoline in patients with pituitary-dependent Cushing's disease. Combination treatment with both somatostatin analogues and dopamine agonists has been poorly investigated. Some studies conducted in small series have documented an additive effect of both drugs in patients with GH-secreting adenomas. Of mention is that none of the studies were randomised and cross-sectional so that the results should be confirmed by other well-designed studies. No data are available in other pituitary tumour histotypes. Preliminary observations in patients with clinically non-functioning adenomas are very promising.     

Growth hormone response to arginine test distinguishes multiple system atrophy from Parkinson's disease and idiopathic late-onset cerebellar ataxia

OBJECTIVE: Multiple system atrophy (MSA) is difficult to distinguish from idiopathic Parkinson's disease (PD) and idiopathic late-onset cerebellar ataxia (ILOCA). This study aimed to evaluate GH response to three different GH stimulation tests in order to establish a reliable test to differentiate these degenerative disorders. DESIGN: Twelve patients with MSA, 10 with PD, eight with ILOCA and 30 healthy controls entered the study. They were submitted to clonidine, arginine, and GH-releasing-hormone (GHRH) + arginine tests in a random manner on three different nonconsecutive days. The peak serum GH response was used as a primary variable for analysis of stimulation tests. By ROC analysis, the optimum cut-off level was considered as the cut-off with the maximal sum of sensitivity and specificity. RESULTS: After clonidine administration, GH peak was significantly lower in patients with MSA than in those with ILOCA (P < 0.05) and in the controls (P < 0.001). At the optimum cut-off level of 5 mU/l, the clonidine test distinguished patients with MSA from those with PD with a sensitivity and specificity of 78%. Moreover, this test distinguished patients with MSA from those with ILOCA with a sensitivity of 100% and a specificity of 75% at a cut-off level of 5 mU/l, and with a sensitivity of 75% and a specificity of 100% at the cut-off level of 7.6 mU/l. After arginine administration, the GH peak was significantly lower in patients with MSA than in those with ILOCA (P = 0.001) and in controls (P < 0.001). At the optimum cut-off level of 5 mU/l, the arginine test distinguished patients with MSA from those with PD with a sensitivity and a specificity of 100%. At a GH peak cut-off value of 3.6 mU/l the arginine test distinguished patients with MSA from those with ILOCA with a sensitivity and specificity of 100%. After GHRH + arginine administration, a significant GH increase was found in all groups of patients and controls. CONCLUSIONS: The GH response to arginine administration is impaired in MSA. Therefore, the arginine test showed the highest diagnostic accuracy to distinguish MSA from both PD and ILOCA, and could be used in the clinical practice of these neurodegenerative diseases.     

Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study

Introduction

Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty.

Differential expression of galectin-3 in medullary thyroid carcinoma and C-cell hyperplasia

OBJECTIVE AND DESIGN: Galectin-3 is a beta-galactoside-binding protein that plays a role in cell adhesion and tumour progression. It was shown recently to diagnose malignant follicular thyroid lesions accurately. The reliability of this marker in the differential diagnosis between medullary thyroid carcinoma and C-cell hyperplasia was studied by immunohistochemistry. PATIENTS: Tissue specimens were obtained from 34 patients belonging to families with medullary thyroid carcinoma who underwent prophylactic thyroidectomy for RET gene mutation and/or abnormally increased plasma calcitonin levels. RESULTS: Galectin-3 was expressed in 23 of 25 cases of medullary thyroid carcinoma and in none of the nine cases of C-cell hyperplasia only, giving a sensitivity of 92% and a specificity of 100% for the diagnosis of carcinoma. A significant association was found between higher galectin-3 expression and occurrence of lymph node metastases (P < 0.05). CONCLUSIONS: Galectin-3 is a reliable diagnostic marker of medullary thyroid carcinoma, and its use may provide relevant information for prognosis and therapy.     

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

     

US-guided percutaneous radiofrequency thermal ablation for the treatment of solid benign hyperfunctioning or compressive thyroid nodules

The aim of the study was to define the effectiveness and safety of ultrasound-guided percutaneous radiofrequency (RF) thermal ablation in the treatment of compressive solid benign thyroid nodules. Thirty-one patients not eligible for surgery or radioiodine (¹³¹I) treatment underwent RF ablation for benign nodules; a total of 33 nodules were treated (2 patients had 2 nodules treated in the same session): 10 cold nodules and 23 hyperfunctioning. Fourteen patients complained of compressive symptoms. Nodule volume, thyroid function and compressive symptoms were evaluated before treatment and at 1, 3 and 6 mo. Ultrasound-guided RF ablation was performed using a Starbust RITA^® needle, with nine expandable prongs; total exposure time was 6 to 10 min at 95° C in one area or more of the nodule. Baseline volume (measured at the time of RF ablation) was 27.7 ± 21.5 mL (mean ± SD), but significantly decreased during follow-up: 19.2 ± 16.2 at 1 mo (–32.7%; p < 0.001), 15.9 ± 14.1 mL at 3 mo (–46.4 %; p < 0.001) and 14.6 ± 12.6 mL at 6 mo (–50.7%; p < 0.001). After treatment, all patients with cold nodules remained euthyroid: five patients with hot nodules normalized thyroid function, and the remaining sixteen showed a partial remission of hyperthyroidism. Besides a sensation of heat and mild swelling of the neck, no major complications were observed. Improvement in compressive symptoms was reported by 13 patients, with a reduction on severity scale from 6.1 ± 1.4 to 2.2 ± 1.9 (p < 0.0001). Radiofrequency was effective and safe in reducing volume by about 50% and compressive symptoms in large benign nodules. Hyperfunction was fully controlled in 24% of patients and partially reduced in the others. (E-mail: mdeandrea@libero.it)     

Construction of a telephone interview to assess the relationship between mood and sleep in adolescence

Telephone interviews have been used extensively as a tool to explore and assess sleep disorders and psychopathological conditions. The aim of this study was to set up and validate a telephone interview aimed at assessing the correlation between mood and sleep variables in adolescents. The study included 16–18 years subjects. A total of approximately 4,000 calls were made; 529 adolescents were finally enrolled. The questionnaire was divided into two parts: the first one focused on affective variables, the second one explored sleep variables. A factorial analysis was carried out to explore the structure of the questionnaire according to two factors: the first, which we labeled “affective factor”, and the second, “quality of sleep”. A positive correlation was found regarding the feeling of wellbeing on awakening. A negative correlation was found between feeling of wellbeing on awakening and daytime drowsiness. In adolescence, increased daytime sleepiness seemed to correlate with worsening mood.     

Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy.

Typing somatostatin receptor expression in neuroendocrine tumors is of relevance to target somatostatin analogue-based diagnostic approach and treatment. The expanding use of immunohistochemistry to detect somatostatin receptors is to date not paralleled by an accurate methodological setting and standardized interpretation of the results. A multicentric study was designed to compare somatostatin receptor immunohistochemical expression with in vivo scintigraphic data and verify its usefulness in the clinical management of neuroendocrine tumors. After methodological setting by testing different somatostatin receptor antibodies, 107 cases of neuroendocrine tumors with available somatostatin receptor scintigraphy data and pathological material were retrospectively analyzed for somatostatin receptor types 2A, 3 and 5 immunohistochemical expression, and compared with scintigraphic images and, whenever available, with the clinical response to somatostatin analogue treatment. Restricting 'positive cases' to the presence of a membrane pattern of staining, an overall somatostatin receptor type 2A immunohistochemistry/somatostatin receptor scintigraphy agreement of 77% (chi2 test P<0.0001) was reached. Lower concordance ratios were detected in preoperative and metastatic tumor samples, possibly as a consequence of somatostatin receptor expression heterogeneity. Pure somatostatin receptor type 2A cytoplasmic staining showed poor correlation with somatostatin receptor scintigraphy (54% concordance rate). The immunohistochemical detection of somatostatin receptor types 3 and 5, which showed almost exclusively a cytoplasmic pattern, did not improve the concordance with scintigraphic data. In a pilot series, somatostatin receptor type 2A immunohistochemistry correlated with clinical response in 75% of cases. In conclusion, we propose a scoring system for somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors correlated with in vivo data, based on the evidence that only membrane (rather that cytoplasmic) staining should be considered for a reliable, standardized and clinically relevant report.     

Multimodal imaging with <Superscript>18</Superscript>F-FDG-PET/CT and <Superscript>111</Superscript>In-Octreotide SPECT in patients with metastatic medullary thyroid carcinoma

Objective

The aim of our study was to determine the role of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) and indium-111 Octreotide single photon emission tomography (¹¹¹In-Octreotide SPECT) in the evaluation of metastatic medullary thyroid carcinoma (MMTC).

Methods

Twenty-five MMTC patients were retrospectively evaluated. All patients had undergone whole-body ¹⁸F-FDG-PET/CT including 20 who had also undergone ¹¹¹In-Octreotide SPECT within a maximum interval of 6 weeks. Diagnostic contrast-enhanced computed tomography (CT) alone or as part of ¹⁸F-FDG-PET/CT examination was performed in all patients.

Results

Contrast-enhanced CT detected a total of 131 lesions including 79 enlarged lymph nodes and 14 bone lesions. ¹⁸F-FDG-PET/CT visualized a total of 92 true positive lesions (SUV_max range 1.1–10.0, mean 4.0 ± 1.7) including 66 lymph nodes, 7 of which were not enlarged on CT, and 8 bone metastases. In the 20 patients studied with both techniques, a total of 64 and 46 true positive lesions were detected by ¹⁸F-FDG-PET/CT and ¹¹¹In-Octreotide SPECT, respectively. In particular, ¹⁸F-FDG uptake was found in 43 lymph nodes and in 7 bone metastases whereas ¹¹¹In-Octreotide uptake was detected in 27 lymph nodes and in 10 bone metastases.

Conclusions

In MMTC patients, ¹⁸F-FDG-PET/CT provides a useful contribution mainly in evaluating lymph node involvement whereas ¹¹¹In-Octreotide SPECT can contribute to the detection and somatostatin receptor characterization especially of bone lesions.