Selcuk Dagdelen

Influence of type 2 diabetes mellitus on bone mineral density response to bisphosphonates in late postmenopausal osteoporosis

Bisphosphonates are effective agents for postmenopausal osteoporosis, but their efficacy in patients with type 2 diabetes mellitus (DM) is not known. The investigators evaluated bone mineral density (BMD) response to alendronate in women with concurrent late postmenopausal osteoporosis and type 2 DM. In a retrospective, matched case-control study, 26 late postmenopausal osteoporotic women with type 2 DM (age, 67.6±7.3 y; type 2 DM duration, 12.8±6.8 y; duration of menopause, 10.9±7.4 y; time on alendronate: 4.8±2.3 y; body mass index [BMI], 31.4±6.3 kg/m2) were matched with 26 controls according to age, BMI, duration of menopause, and alendronate treatment received. All subjects were given alendronate 10 mg/d or 70 mg/wk, along with sufficient vitamin D (≥400 IU) and calcium (≥1 g/d) intake, for 4.8 y. Response to alendronate therapy was determined by assessment of mean percent change in BMD of total hip, femoral neck, forearm, and lateral spine. The presence of type 2 DM resulted in no difference in spinal BMD response to alendronate therapy. In contrast, BMD in the total hip (mean percent change in BMD, −5.6% vs +1.4%;P=.096), femoral neck (−8.1 % vs +1.1 %;P=.015), and forearm (−3.6% vs +12.7%;P=.013) fell progressively from baseline in subjects with type 2 DM who were taking alendronate for 4.8 y, compared with controls. Elderly, postmenopausal, osteoporotic obese women with type 2 DM are resistant to long-term bisphosphonates, especially in regions of the hip, femoral neck, and forearm compared with the spine. The efficacy of bone resorption inhibitors in patients with type 2 DM, especially in comparison with anabolic agents, should be considered in additional studies.

Peroxisome Proliferator-Activated Receptor-γ

Insulin resistance and obesity is a common health problem in the industrialized world. As a result of the availability of high-calorie food and a reduction in energy expenditure, maladaptive metabolic processes may interfere with the action of insulin and increase susceptibility for the development of atherosclerotic cardiovascular diseases. With the advent of peroxisome proliferator-activated receptors (PPARs), the mechanisms of this maladaptation and its relationship to insulin resistance syndrome components have become less obscure, promising new therapeutic approaches for this common problem. In this review we first focus on the molecular structure and cellular mechanisms of action of these receptors and then discuss how PPAR-γ, a PPAR isoform, provides a link between adiposity, insulin resistance, and atherosclerosis.

Endocrine involvement in systemic amyloidosis.

OBJECTIVE To present an overview of the published data on endocrine involvement and endocrine dysfunction in patients with systemic amyloidosis. METHODS We conducted a review of the medical literature using MEDLINE data sources, including clinical trials, in vitro studies, and case reports on pituitary, thyroid, parathyroid, pancreatic, adrenal, and gonadal involvement in systemic amyloidosis. RESULTS Reports of endocrine involvement in systemic amyloidosis seem to consist primarily of small-samplesize clinical trials or case reports, probably because of the rarity of the disease itself. Systemic amyloidosis mainly involves and causes functional impairment in the thyroid and testes in the endocrine system. Evaluation of adrenal function necessitates special consideration because amyloid infiltration of the adrenal glands resulting in failure may be a life-threatening condition. Amyloid deposition commonly seen in the pituitary gland and the pancreas of patients with Alzheimer disease and type 2 diabetes mellitus, respectively, is generally classified as local amyloidosis and should not be confused with systemic involvement. Additionally, detection of amyloid deposition in the thyroid and testes may have a diagnostic role in patients with suspected systemic or renal amyloidosis. CONCLUSION Published data suggest that systemic amyloidosis frequently involves the endocrine system, and endocrine dysfunction seems to be not as rare as previously thought. A rapidly growing goiter or symptoms and signs of adrenal or gonadal dysfunction should raise suspicion of amyloid infiltration. Involvement of pituitary, parathyroid, and pancreatic sites in systemic amyloidosis still remains to be clarified. Further studies with larger sample sizes are needed for complete characterization of the effect of systemic amyloidosis on the endocrine system.

Humoral Hypercalcemia of Benignancy Secondary to Parathyroid Hormone-Related Protein Secreting Uterine Leiomyoma

A 48-year-old women admitted with polyuria and polydipsia. She was found to be hypercalcemic despite suppressed parathormone (iPTH) levels. Subsequently checked parathormone related-protein (PTHrP) level was 2.5 pmol/L (expected normal level <1.3 pmol/L). An extensive workup for a malignancy revealed no abnormality, except for an uterine leiomyoma, 7.1 cm in size. Total abdominal hysterectomy and salpingo-oophorectomy were performed. After the surgical removal of uterine leiomyoma, serum calcium (9.3 mg/dL), iPTH (29.4 pg/mL), and PTHrP (<1.3 pmol/L) levels were normalized. The diagnosis of humoral hypercalcemia of benignancy secondary to PTHrP was confirmed. One month later, her calcium and iPTH levels were normal and 1 year later still remain within the normal ranges. Our case indicates that PTHrP associated hypercalcemia does not solely result from a malignant tumor. Benign tumors like uterine leiomyoma might also cause humoral hypercalcemia.

Amyloid goiter and hypopituitarism in a patient with systemic amyloidosis

Systemic amyloidosis may infiltrate the thyroid or other endocrine glands but rarely causes endocrine dysfunction. We describe a 45 years old female patient with diffusely enlarged goiter and hypopituitarism secondary to amyloid infiltration of the thyroid gland and possibly pituitary gland, respectively. She was on chronic haemodialysis for 3 years due to systemic amyloidosis. While she was being prepared for thyroidectomy, adrenal failure developed. Her anterior pituitary hormone levels were low and magnetic resonance imaging of the hypophysis showed low signal intensity in right part of the adenohypophysis. She improved with corticosteroid replacement therapy and underwent subtotal thyroidectomy without any complication. Histopathologically, amyloid deposition was demonstrated in the thyroid gland. To our knowledge, this is the first case with amyloid goiter and hypopituitarism secondary to systemic amyloidosis. Amyloid infiltration should be considered in a systemic amyloidosis patient presenting with rapidly enlarged thyroid gland and signs of hypopituitarism.

Leptomeningeal infiltration of malignant mesothelioma.

Mesothelioma is a disease mostly involving the pleura, peritoneum, and pericardium. Hematogenously disseminated metastases involving the liver, adrenal glands, kidneys, and contralateral lung have been documented in some patients, but central nervous system (CNS) involvement, especially as leptomeningeal infiltration, is very rare. A 44-yr-old mesothelioma patient admitted to hospital with convulsions and diffuse leptomeningeal infiltration was shown with magnetic resonance imaging. She had a positive history for environmental asbestos exposure. Pleural and axillary lymph node biopsies were consistent with mesothelioma. Diffuse leptomeningeal infiltration is the only constant radiological finding reported as a diagnostic criteria for CNS involvement and histopathological confirmation is usually possible only at autopsy, so clinical and radiological diagnosis is essential after exclusion of other possible causes.

Hemorrhage into a thyroid nodule as a cause of thyrotoxicosis.

OBJECTIVE To describe a case of thyrotoxicosis after nontraumatic hemorrhage into the thyroid gland during anticoagulant therapy. METHODS We report the details of the initial presentation, subsequent course, and outcome in a patient with a nontraumatic thyroid hematoma and thyrotoxicosis. RESULTS In a 63-year-old woman, an acute painful neck mass developed during follow-up while she was receiving low-molecular-weight heparin therapy for deep vein thrombosis. Ultrasound study and magnetic resonance imaging revealed a massive intrathyroidal hematoma. This finding was followed by an increase in serum free thyroxine and free triiodothyronine levels and a decrease in the level of serum thyroid-stimulating hormone (thyrotropin). Anticoagulant therapy was discontinued. The clinical course of the thyrotoxicosis was self-limited, and no antithyroid therapy was necessary. The serum thyroid hormone levels decreased into normal ranges as the hematoma underwent subtotal shrinkage. CONCLUSION Endocrine glands are highly vascularized tissues, but nontraumatic hematomas into these organs are extremely rare conditions. Nevertheless, physicians should be aware of the potential occurrence of such a situation, as emphasized in the current case report.

Serum Adiponectin Levels and Changes in Glucose Metabolism before and after Treatment for Thyroid Dysfunction

OBJECTIVE Adiponectin is an adipokine which is known to decrease in individuals associated with obesity and insulin resistance. In this study, we aimed to investigate the serum adiponectin levels and glucose metabolism in patients with thyroid dysfunction before and after treatment. METHODS Newly diagnosed overt hypothyroid (n=20) and thyrotoxic (n=23) patients and healthy controls (n=20) with a body mass index of <30 kg/m(2) were evaluated prospectively. Patients with a known state of insulin resistance, including prediabetes and overt diabetes, and individuals with chronic diseases were excluded. Thyroid function and fasting plasma glucose (FPG), insulin, homeostatic model assessment (HOMA) insulin resistance (HOMA-IR) and HOMA-beta cell function (HOMA-beta), lipid and adiponectin levels were investigated in the basal state and after the restoration of euthyroidism. RESULTS The basal fasting FPG levels were lower in the hypothyroid patients than the control subjects (p=0.02) and similar between the thyrotoxic patients and control subjects (p=0.127). The basal HOMA-beta levels were higher in the patients with hypothyroidism than in those with thyrotoxicosis (p=0.015). Following the restoration of euthyroidism, the FPG levels significantly increased in the hypothyroid patients (p=0.002) and decreased in the thyrotoxic (p=0.001) patients. The basal plasma adiponectin levels were 14.55±8.4 mcg/mL, 13.79±9.13 mcg/mL and 11.68±6.0 mcg/mL in the hypothyroid and thyrotoxic patients and healthy controls, respectively (p=0.503). The adiponectin levels decreased significantly in the patients with hypothyroidism (p=0.047), whereas they did not change in the patients with thyrotoxicosis (p=0.770) after achieving euthyroidism. CONCLUSION In this study, following the restoration of euthyroidism, the FPG levels increased in the hypothyroidism patients and decreased in the thyrotoxicosis patients, despite the lack of changes in the HOMA-IR and HOMA-beta levels. Meanwhile, the hypothyroid, thyrotoxic and euthyroid subjects had similar basal adiponectin levels, and a significant decrease in the adiponectin levels was observed after treatment for hypothyroidism, despite the absence of changes after treatment for thyrotoxicosis, indicating the need for further studies with a larger sample size.

Functional and structural evaluation of hearing in acromegaly.

Context  The impact of acromegaly on the auditory system remains unknown.

Genetic Alterations in Differentiated Thyroid Cancer Patients with Acromegaly.

AIM Acromegaly is associated with increased thyroid cancer risk. We aimed to analyze the frequency of point mutations of BRAF and RAS genes, and RET/PTC, PAX8/PPARγ gene rearrangements in patients with acromegaly having differentiated thyroid cancers (DTC) and their relation with clinical and histological features. MATERIALS AND METHODS 14 acromegalic patients (8 male, 6 female) with DTC were included. BRAF V600E and NRAS codon 61 point mutations, RET/PTC1, RET/PTC3, and PAX8/PPARγ gene rearrangements were analyzed in thyroidectomy specimens. We selected 14 non-acromegalic patients with DTC as a control group. RESULTS 2 patients (14.3%) were detected to have positive BRAF V600E and 3 patients (21.4%) were detected to have NRAS codon 61 mutation. NRAS codon 61 was the most frequent genetic alteration. Patients with positive mutation had aggressive histologic features more frequently than patients without mutations. Comparison of the acromegalic and non-acromegalic patients with DTC revealed that BRAF V600E mutation was more frequent in non-acromegalic patients with DTC (14.2% vs. 64.3%, p=0.02). RET/PTC 1/ 3, PAX8/PPARγ gene rearrangements were not detected in any patient. None of the patients including the patients with positive point mutations had recurrence, and local and/or distant metastasis. CONCLUSION NRAS codon 61 is the most frequent genetic alteration in this acromegaly series with DTC. Since acromegalic patients have lower prevalance of BRAF V600E mutation, BRAF V600E mutation may not be a causative factor in development of DTC in acromegaly. Despite the relation of BRAF V600E and NRAS codon 61 mutations with aggresive histopathologic features, their impact on tumor prognosis remains to be defined in acromegaly in further studies.