ACTA ENDOCRINOLOGICA (BUC)

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.

Context. Metabolic surgery is currently the most efficient treatment for obesity, but concern is raised about the possible long-term nutritional side effects. Bone metabolism is often adversely affected after surgery, but literature data are contradictory. Objective. The aim of this study was to evaluate the evolution of bone mass parameters in the first year after laparoscopic sleeve gastrectomy in relation to anthropometric and body composition parameters and specific hormones of obesity. Design. We conducted a prospective study on 75 patients with obesity that underwent metabolic surgery over a course of 18 months at our center, with a follow-up period of 12 months. Subjects and Methods. All patients underwent a complex preoperative assessment and were required to return for medical follow-up at 6 and 12 months after surgery. Each visit included anthropometric parameters, DEXA and determination of specific hormonal parameters. Results. We noticed a significant improvement in anthropometric and body composition parameters after surgery. The value of adiponectin presented a significant increase after surgery and leptin showed a significant decrease at 6 and 12 months postoperative; ghrelin level decreased postoperative compared to preoperative, but without statistical significance. We observed no reduction in BMD after surgery, but a significant improvement in BMC at 12 months after surgery compared to preoperative. Ghrelin negatively correlated to BMD preoperative. Conclusions. Despite the significant alterations in anthropometric, body composition and hormonal parameters, we found no negative effect on BMD and BMC in our study population.

Context. Parental history of osteoporosis is associated with an increased risk of fracture. However, there are not many data on the mechanism of action. Our objective was to determine if heredity influences fracture rate: independently or through the bone mineral density; to identify also the strongest independent risk factors of osteoporotic fractures among our study population. Methods. We processed data of 541 women outpatients with an average age of 55 years, participating in an osteoporosis screening program. Our results confirm that the presence of family history significantly increases fracture prevalence, (37% vs. 17%, p<0.001, OR 2.853, p=0.001) and decreases BMD scores. Fractures occur at higher (better) T and Z-scores. The risk of having T values in the range of (0- -1) and Z values in (-1--2) is much higher in the positive group. The logistic regression analysis confirms the BMD-independent influence of heredity on fracture risk. Conclusions. Parental history of osteoporosis negatively affects bone density and significantly increases the incidence of fractures. The latter happens also independently of the bone density values. Timely intervention in these easy-to-detect cases may be the most effective prevention of osteoporotic fractures.

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