ACTA ENDOCRINOLOGICA (BUC)

Background and aims. Increased fat accumulation associated to increased cardiometabolic risk factors is a prominent feature of type 2 diabetes. In type 1 diabetes, increased fat accumulation is not prevalent and its metabolic impact has not been fully evaluated. We aimed to evaluate differences in body composition, clinical and metabolic\r\nprofile in type 1 and type 2 diabetes patients with varying degrees of adiposity.\r\nMaterials and methods. Clinical, biochemical and body composition data (using a bioelectric impedance analyzer) from 96 type 1 and 253 type 2 adult diabetes patients have\r\nbeen collected.\r\nResults. In type 1 patients estimated visceral fat area (eVFA) increased significantly (84.3?27.9 vs. 103.0?27.9 vs. 128.1?29.1 cm2, p=0.006, 0.003, and <0.001) while BMI, body fat mass (BFM) did not differ across age tertiles. Between normal weight (BMI<25 kg/m2) and overweight (BMI>25 kg/m2) type 1 patients there were no significant differences either in triglycerides (128.7?135.6 vs. 92.8?50.6 mg/dl, p=0.1), HDL-cholesterol (53.6?15.9 vs.\r\n52.3?13.7 mg/dl, p=0.6) and uric acid levels (3.4?2.0 vs. 2.9?1.2 mg/dl, p=0.2), or in hypertension (39.5% vs. 40.0%, p=0.7) and nonalcoholic hepatosteatosis (NASH) (10.0% vs.\r\n10.5%, p=0.6) prevalences. In type 2 patients, BMI (32.3?5.9 vs. 29.5?5.1 vs. 27.9?5.0 kg/m2, p=0.001, p=0.04, p<0.001) and BFM (34.5?12.7 vs. 29.6?10.2 vs. 27.1?10.8 kg, p=0.007, p=0.11, p <0.001) decreased, while eVFA did not differ across age tertiles, suggesting that older age increases central fat distribution. Compared to normal weight, overweight type 2 diabetes patients had greater triglycerides (218.8?303.4 vs. 110.9?44.9 mg/dl, p=0.01), uric acid (4.5?2.4 vs. 3.3?1.4 mg/dl, p=0.01), and lower HDL-cholesterol (43.9?12.9 vs. 54.1?15.4 mg/dl, p<0.001) serum levels, and higher prevalences of hypertension (71.8% vs. 39.4%, p=0.005) and NASH (59.1% vs. 25.0%, p=0.005).\r\nConclusion. Visceral fat accumulation is associated with older age in both types of diabetes, but only in type 2 diabetes is associated with cardiometabolic anomalies.

We report a case of anaplastic thyroid carcinoma mimicking acute thyroiditis with skin necrosis. A 82 years woman, with no significant previous medical disorders, was admitted with a few weeks history of a painful rapidly enlarging neck mass associated with hoarseness, dysphagia to solids, dyspnea and a general state deterioration. Physical exam was significant for a left-anterior lateral neck tumor of about 7 cm. The mass was tender, firm, nonpulsatile and nonfluctuant; it was fixed to the underlying cervical tissues. Antero-cervical skin tissues were swollen, hyperemic, presenting necrosis with penetrating tendency, severe neck pain and tenderness, associated with fever, suggesting an acute thyroiditis. The thyroid function was normal (TSH = 0.81 mUI/L, TT3 = 62 ng/dL, TT4= 8.77 ug/dL) as well as antithyroid peroxidase antibody (0.5 UI/mL), while thyreoglobulin was high (384 ng/mL). Thyroid scintigram revealed a cold nodule. Thyroid ultrasound revealed a giant left thyroid mass with necrosis, lymph nodes involvement and displacement of trachea. Fine needle aspiration confirmed the clinical suspicion features of anaplastic thyroid cancer: mitoses, anisocytosis and marked anisokaryosis with enlarged nuclei. Computed tomography confirmed a voluminous mass involving the thyroid, with calcifications, necrosis with multiple latero-cervical lymph nodes, compressing right carotid artery and internal jugular vein; it was detected also a pulmonary metastasis (right medium pulmonary lobe). The patient was diagnosed on having a thyroid carcinoma of the anaplastic type, TNM stage IVc. Surgery was performed through cervical approach without sternotomy, by total thyroidectomy and resection of proximal cervical structures involved by the tumor mass. After surgery, the patient was started on levothyroxine 100 &#956;g/ day and scheduled for cervical radiotherapy, but the tumor relapsed in several weeks. Local disease can be controlled with radiotherapy either alone or in combination with chemotherapy.

Context. Primary hyperparathyroidism related hypercalcemic crisis (PHHC) is a condition that may result in fetal course. So, the early diagnosis and treatment of these patients are important Objective. This study aimed to investigate the clinical features for hypercalcemic crisis (HC) by comparing the groups with and without primary hyperparathyroidism related calcemic crisis. Design. All patients operated with primary hyperparathyroidism (PH) diagnosis in a single clinic between March 2015 and March 2020 were included in this retrospective study. Subjects and Methods. 119 patients included the study.Patients with serum calcium (Ca) level > 14 mg/dl were regarded as HC and the patients were divided into two groups as HC and non-HC. These two groups were compared for demographic data, preoperative biochemical parameters, preoperative localization studies, histopathological assessment and postoperative results. Results. Serum Parathormone (PTH), Ca, Alkaline phosphatase (ALP) and creatinine values among preoperative biochemical parameters were higher in the HC group than the non-HC (p<0.005). The hyper-functional parathyroid size of the patients in the HC group was also bigger compared to non-HC (p<0.05). No difference was observed in the demographic and histopathological data, preoperative localization studies and postoperative results of the two groups (p>0.05). Conclusions. PH is usually an elective operation and PHCC treatment should be relatively more urgent as it can be mortal. Higher HC occurrence possibility should be considered in PH patients with high serum PTH, ALP and creatinine values and large tumor diameters and those patients should be prioritized for treatment.

Context. Diabetes mellitus is the most frequent chronic complication in pregnancy and continues to contribute to increased perinatal morbidity and mortality in newborns. Macrosomia, respiratory distress syndrome, metabolic and electrolytic disturbances, and increased rates of congenital structural defects are well-known neonatal complications associated with maternal diabetes, even if well-controlled. Case report. A macrosomic infant born from an insulin-dependent mother, with uncontrolled diabetes and lack of adequate prenatal care, prenatally diagnosed with hydrocephaly showed a complicated postnatal course. Initial respiratory distress syndrome and transient hypoglycemia, rapidly corrected under treatment, were followed by persistent hypocalcemia and hyperphosphatemia due to hypoparathyroidism and evolving hydrocephaly. Ventriculoperitoneal shunting was followed by resolution of hypocalcemia, but seizures associated with schizencephaly and recurrent respiratory tract infections, aggravated by spondylocostal dysplasia, concurred to infant’s demise at the age of 5 months. Conclusions. The reported case is rare due to multiple aspects: persistent hypoparathyroidism, uncommon association of schizencephaly, and even rarely association with spondylocostal dysplasia, all these conditions requiring a multidisciplinary therapeutic approach. Also, the reported case is evocative for challenges associated with infants born from diabetic mothers.

Context. Accumulating data supports the key role of disrupted amino acids (AAs) metabolism in diabetes. Conflicting data regarding the relevance of serum AAs in diabetes and hypertension suggest that their relationship needs further investigation. Objective. To investigate serum AAs as biomarkers of increased BP variability evaluated during 24-hour ambulatory BP monitoring in the presence of type 2 diabetes. Design. Cross-sectional. Subjects and Methods. We analyzed serum AAs using targeted metabolomics (ultrahigh-performance liquid chromatography/mass spectrometry) in patients with type 2 diabetes (n=80). BP variability was assessed using 24-hour ambulatory BP monitoring. Participants were divided into two groups based on the 24-hour diastolic BP variability median value. Results. Aspartic acid, isoleucine, leucine, and phenylalanine were significantly lower, while glutamine was significantly higher in the group with higher diastolic BP variability (p-value <0.05 and variable importance in the projection >1). Corresponding pathways identified as disrupted in patients with diabetes and a higher 24-hour diastolic BP variability were phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and alanine, aspartate, and glutamate metabolism (pathway impact value >0). Conclusions. We identified specific changes in serum AAs and target AAs pathways in relation to increased 24-hour diastolic BP variability in patients with type 2 diabetes.

Background. Idiopathic hypoparathyroidism is a rarely seen disease which progresses with the hypocalcaemia, hyperphosphatemia and low level of parathyroid hormones. The main symptoms such as leg cramps and generalized muscle weakness result from neuromuscular irritability due to hypocalcaemia, and skeletal abnormalities as well as ectopic calcifications are among the well known features. Case Report. A 32 year-old male patient was referred to our clinic with four years of progressive inflammatory low back and hip pain, prolonged morning stiffness. Upon physical examination limited movements and posture resembling that seen in patients with ankylosing spondylitis (AS) were observed. In laboratory investigation revealed hypocalcaemia (4.6 mg/dL), hyperphosphatemia (7.0 mg/dL) and hypoparathyroidism (7.2 pg/mL). Serum C reactive protein and erythrocyte sedimentation rate were normal. The direct graphic and sacroiliac magnetic resonance image were identified sacroiliitis. A rise in bone density in dual-energy x-ray absorptiometry was recorded. According to the Modified New York criteria, AS includes the whole diagnostic criterias completely. Conclusion. Idiopathic hypoparathyroidism, when undiagnosed for a long period, may result in extreme calcification of soft and bony tissues. The vertebral calcification may be so intense that it may result in an AS like clinical picture. Therefore, idiopathic hypoparathyroidism should also be considered in the differential diagnosis of AS .

The stress driven cortisol dynamics of the Hippocampal-Hypothalamic-(Anterior) Pituitary-Adrenal (HHPA) axis with its negative feedback loops from the adrenals to pituitary and hypothalamus, in particular relation with hippocampus, have been the focus of the last few years boom of papers\r\nusing various distinctive mathematical models, simulations, stability analyses and optimal control of these models. These many quantitative approaches led to discovering unknown connections between cortisol feedback loop dysfunctions and stress disorders (post-traumatic stress\r\ndisorder (PTSD), depression, chronic fatigue syndrome (CFS)), adrenal suppression and atrophy, Alzheimer (AD)\r\nand hypocampal cognitive dysfunctions (memory loss) leading to new drug treatment strategies. We assemble here together and unify these results, including our own early work, in order to create an integrative mathematical system theory framework for HHPA & HPA and stress driven cortisol dynamics in which various clinical disorders appear as various quantifiable negative feedback loop dysfunctions and drug therapies correcting these disorders appear as feedback model based treatments: a neuroendocrine system theory for cortisol ?feedback pathology? and its existing and future possible ?feedback therapies?.

The gastrointestinal (GI) motility, which is important for the digestion and absorption, may be altered in obesity. The aim of this review is to present the GI motility changes occurring in obesity, as well as their underlying mechanisms. We have conducted a systematic review of the published literature concerning GI motility and obesity and have described recent published data on the changes throughout the entire GI tract. Most recent discoveries include evidence supporting the increase of gastroesophageal reflux disease in obesity and inhibition of gastric motility. Intestinal transit of the distal small bowel generally slows down, ensuring enough time for digestion and absorption. Constipation is more frequent in obese patients than in those with a normal weight. The gut-brain axis plays an important role in the pathophysiology of GI motility disorders in obesity. This bidirectional communication is achieved by way of neurons, hormones, metabolites derived from intestinal microbiota and cytokines. The molecular mechanisms of GI motility changes in obesity are complex. Current data offer a starting point for further research needed to clarify the association of obesity with GI motility disorders.

Objective. Ectopic parathyroid adenoma is an uncommon cause of primary hyperparathyroidism. Apart from the usually described sites of ectopic parathyroid adenoma, anecdotal case reports of undescended parathyroid adenoma along the carotid artery have been described. Methods. We report a rare case of a 4 cm large parathyroid adenoma within the carotid sheath. Results. A 27-year-old lady presented with severe bony pains, history of height loss, fracture of left shaft femur following trivial trauma and renal calculi. On evaluation she had hypercalcemia with elevated iPTH suggestive of primary hyperparathyroidism. Ultrasound of neck and 99mTc sestamibi SPECT/CT incorrectly localised the lesion as right inferior parathyroid adenoma leading to a failed initial surgery. Later CECT of the neck identified adenoma posterior to right common carotid artery which was confirmed on repeat surgery and the patient was cured. Conclusion. Ectopic parathyroid adenomas are both difficult to localise and are a common cause of failed initial parathyroid surgery. Surgeons should exercise caution while removing a visually normal parathyroid gland. In case of any discordance with the pre-operative localization, a meticulous systematic dissection using the conventional approach should be performed and the possibility of an undescended gland in the carotid sheath should be considered.