Unusual Long Survival with a Giant Invasive Pheochromocytoma of an Incompatible Patient

Pheochromocytomas (PHEOs) are rare neuroendocrine tumors and about 2-13% of PHEOs are malignant. Predicting malignancy in PHEO cases with invasion but without metastasis is still controversial in the literature. This study presents an unusual long survival with a giant invasive PHEO in an incompatible patient and a review of the literature. In 1989, a 23-year-old female patient was operated for a giant adrenal mass with a pathological final diagnosis of PHEO. Information to the patient's family was provided about the short life span of the patient in the postoperative period because the tumor could not be totally resected. The patient started using regular antihypertensive drugs only after 1994. In 1994, 3700 mBq 131-I-metaiodobenzylguanidine (MIBG) treatment was given. Since then, no specific treatment was administered for PHEO due to patient incompatibility. She was diagnosed with type 2 diabetes mellitus at the age of 40 years and had a cerebrovascular accident due to hypertension at the age of 42. New abdominal computed tomography (CT) showed a right-sided 75 x 37 mm irregular and heterogeneous mass lesion extending inferiorly from the diaphragmatic crus level located in the right adrenal locus compatible with local recurrence. There was no I-123-MIBG uptake. She refused to have advanced workup and further treatment options. Malignant PHEOs reduce overall survival as a consequence of excessive catecholamine release, large tumor burden, and malignancy-related complications. Currently, the treatment of a malignant PHEO still has difficulties for both patients and doctors. Main treatment options for malignant PHEOs are primarily surgical excision. The effect of radionuclide therapy on survival time still remains to be determined. Efforts should be made to identify clinical, biochemical, and pathological criteria for malignancy and to develop new therapies in these patients with malignancy. The clinical course of malignant PHEOs is remarkably variable. Disease-specific survival rate changes from 58 to 88.1% at five years in the literature. Recent discoveries have enhanced new options for treatment, from radionuclide therapy and targeted molecular therapy to immunotherapy. A multidisciplinary approach is needed to individualize treatment in patients with malignant and invasive PHEO

Metformin: Hype or Hope for Cancer

Current studies show that especially pancreatic, liver, endometrial, colorectal, bladder and breast cancer incidences are increased by the presence of type 2 diabetes mellitus (T2DM). Possible links between T2DM and cancer include hyperinsulinemia, dysregulation of adipocytokines and hyperglycemia as well as shared confounding risk factors. There is evidence emerging from experimental and clinical studies that metformin can play a crucial anti-cancereous role. Since 2005, multiple studies showed the association between metformin and the reduction of risk in cancers of pancreas, colorectal, stomach, liver, breast and esophagus in diabetes cases. It was also claimed to improve survival in some cancers. Metformin is an insulin sensitizer and mainly acts through inhibiting hepatic gluconeogenesis by activating LKB1/AMP-activated protein kinase (AMPK). Metformin was found to have anti-cancerous and anti-metastatic effects mainly through activating AMPK dependent and independent signaling; inhibiting mTOR, MAPK, HER2, NF-kappa B, IGF signaling pathways and with its possible immuno-modulatory effects. Further studies are needed to evaluate the potential of metformin as adjuvant therapy for cancer especially in non-diabetic patients

Metformin Decreases Thyroid Volume and Nodule Size in Subjects with Insulin Resistance: A Preliminary Study

Objective: The aim of this study was to investigate the effects of metformin on thyroid volume and nodule size. Subjects and Methods: Prospective data were gathered on 100 newly diagnosed subjects with insulin resistance (68 female, 32 male) between August 2008 and May 2010. Each subject followed a standard diet and exercise program, and received 1,700 mg/day of metformin therapy for 6 months. The height, weight, waist circumference (WC) and thyroid hormone levels of each subject were measured. Additionally, the dimensions of the thyroid lobes and maximum diameter of each thyroid nodule were determined by ultrasonography. BMI and thyroid volumes were also calculated. Insulin resistance was estimated by homeostasis model assessment. All these parameters were measured at the beginning and at the end of the treatment period. Results: BMI and WC decreased significantly after metformin therapy (34.5 +/- 5.1 vs. 32.7 +/- 4.8, p < 0.0001, and 106.3 +/- 11.8 vs. 101.8 +/- 19.0 cm, p = 0.008, respectively). Insulin resistance also decreased after metformin therapy (4.5 +/- 1.9 vs. 2.9 +/- 1.7, p < 0.0001). The mean thyroid volume (22.5 +/- 11.2 vs. 20.3 +/- 10.4 ml, p < 0.0001) and mean thyroid nodule size (12.9 +/- 7.6 vs. 11.7 +/- 7.2 mm, p < 0.0001) also decreased after treatment. Conclusion: In subjects with insulin resistance, metformin therapy significantly decreased thyroid volume and nodule size. (C) 2015 S. Karger AG, Base

Do Statins Affect Thyroid Volume and Nodule Size in Patients with Hyperlipidemia in a Region with Mild-to-Moderate Iodine Deficiency? A Prospective Study

Objective: The objective of this study was to assess the anti-proliferative pleiotropic effects of statins on thyroid function, volume, and nodularity. Subjects and Methods: One hundred and six hyperlipidemic patients were included in this prospective study. The 69 patients in the statin groups received atorvastatin (16 received 10 mg and 18 received 20 mg) or rosuvastatin (20 received 10 mg and 15 received 20 mg). The 37 patients in the control group, assessed as not requiring drugs, made only lifestyle changes. Upon admission and after 6 months, all patients were evaluated by ultrasonography as well as for lipid variables (total cholesterol, high-and low-density lipoprotein cholesterol, and triglycerides) and thyroid function and structure. Results: After 6 months, no differences in thyroid function, thyroid volume, the number of thyroid nodules, or nodule size were observed in the statin and control groups. In a subgroup analysis, total thyroid volume had decreased more in patients receiving 20 mg of rosuvastatin than that in the control group (p < 0.05). Maximum nodule size had decreased more in those receiving 10 mg of rosuvastatin (p < 0.05). Conclusions: Our results suggest an association between rosuvastatin treatment and smaller thyroid volume and maximum nodule diameter; this could be attributable to the antiproliferative effects of statin therapy on the thyroid. (C) 2018 The Author(s) Published by S. Karger AG, Base

Thyroid volume in patients with glucose metabolism disorders

Objective: Thyroid volume and the prevalence of thyroid nodules are higher in patients with insulin resistance. A relationship between thyroid volume and glucose metabolism disorders (GMD) has not as yet been clarified. The present retrospective study aimed to investigate the association between GMD and thyroid volume. Subjects and methods: We investigated the data of 2,630 patients who were evaluated for thyroid biopsy in our hospital. The study population included 602 patients with GMD, 554 patients with diabetes mellitus (DM) and 1,474 patients with normal glucose metabolism as a control group. We obtained the levels of serum thyroid stimulating hormone (TSH) and the thyroid volumes of those patients retrospectively. Results: The median ages for the control group, GMD group and DM group were 55 (15-91) years, 60 (27-97) years, and 65 (27-91) years respectively and there was a statistically significant difference between the groups with regard to age and gender (p < 0.001). Levels of TSH were similar in all groups. The median total thyroid volumes for patients with DM and GMD were significantly higher than that of the control group [22.5 (3-202) mL, 20.2 (4-190) mL, and 19.2 (3-168) mL respectively, p <= 0.001 for all parameters]. Also the median total thyroid volume for patients with DM was significantly higher than that of the GMD group (p < 0.001). According to the correlation analysis, thyroid volume was significantly correlated with age (r = 0.92, p < 0.001) and TSH (r = 0.435, p < 0.001). Age, gender, TSH levels, GMD and DM diagnosis were independently correlated with thyroid volume. Conclusion: The thyroid gland is one of the target tissues of metabolic disorders. We reported a positive correlation between GMD/type 2 DM and thyroid volume. Further controlled, prospective, randomized studies on this subject are required to gain more information

Diabetes Mellitus is Frequent, But Retinopathy is Rare in Acromegaly: A Cross-sectional Study

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The roles of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in diabetic retinopathy (DR) are well recognized, but the prevalence and pathogenesis of retinopathy in acromegaly are not fully understood. We established the frequency and severity of glucose intolerance and retinopathy—and the relationship between them—in patients with acromegaly.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;All patients with acromegaly under the care of the Department of Endocrinology, Baskent University Hospital were enrolled. Fundoscopy was carried out by two experienced ophthalmologists. Acromegaly disease state was evaluated by basal GH and IGF-1 measurements, and an oral glucose tolerance test (OGTT) when appropriate. Glucose tolerance states were assessed by means of fasting and postprandial plasma glucose concentrations, glycohemoglobin measurement and an OGTT when appropriate. The relationships between retinopathy, acromegaly disease activity and glucose tolerance states were examined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The cohort comprised 49 patients with acromegaly (24 women), with a median disease duration of 25 months (range 1–420 months). Thirty-three had active disease, with median concentrations of GH of 5.54 ng/ml (0.72–172 ng/ml) and IGF-1 of 541.5 ng/ml (203–1,985 ng/ml). The prevalence of diabetes mellitus (DM) was 30.6% (n =15; 10 patients had active acromegaly, five of whom had uncontrolled DM). Two patients had retinopathy (4.1%); both had active acromegaly and uncontrolled DM at the time of examination.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The prevalence of DM was twice that of a reference population, but that of DR was lower than expected. Our findings suggest that disease activity in acromegaly might not contribute to retinopathy.&lt;/p&gt