Central diabetes insipidus: A rare complication of IVH in a very low birth weight preterm infant.

A 710 g male infant was born at a referring hospital at a gestational age of 23 weeks and 2 days via vaginal delivery and was transferred to our facility at 14 days of age. His delivery was complicated by the breech presentation with difficult head extraction. The infant's initial course was significant for respiratory distress syndrome, grade III-IV intraventricular hemorrhage (IVH), acute kidney injury, and large PDA. On the day of life 29, a gradual increase in serum sodium level refractory to increasing total fluid volume was noted. The combination of persistent hypernatremia (150-160 mmol/l), polyuria (8.4 ml/kg/hr), high plasma osmolality (323 mosm/kg), hyposthenuria (75 mosm/kg) and an undetectable serum ADH (<0.8 pg/ml) confirmed the diagnosis of central diabetes insipidus (CDI). Serum sodium and urine output decreased and urine osmolality increased after subcutaneous DDAVP administration.CDI is an uncommon cause of hypernatremia in the neonatal period. The diagnosis can be difficult as excessive urine output and high serum sodium can often be attributed to high insensible water loss in the extremely premature newborn. CDI in our patient was thought to be due to grade III-IV IVH complicated by post-hemorrhagic hydrocephalus.In conclusion, the diagnosis of central DI should be considered as a complication of severe IVH in the extremely premature neonate who demonstrates persistent hypernatremia, polyuria, decreased urine osmolality, and increased plasma osmolality. Serum ADH levels can be helpful in confirming the central origin of DI and subcutaneous desmopressin can be an effective treatment in the preterm infant.

Roles of type VI collagen and decorin in human mesenchymal stem cell biophysics during chondrogenic differentiation.

Human mesenchymal stem cells (hMSCs) induced towards chondrogenesis develop a pericellular matrix (PCM), rich in type VI collagen (ColVI) and proteoglycans such as decorin (DCN). Individual PCM protein functions still need to be elucidated to fully understand the mechanobiological role of this matrix. In this study we identified ColVI and DCN as important contributors in the mechanical function of the PCM and as biochemical modulators during chondrogenesis through targeted knockdown using shRNA lentiviral vectors. Gene expression, western blotting, immunofluorescence and cell deformation analysis were examined at 7, 14 and 28 days post chondrogenic induction. ColVI and DCN knockdown each affected gene expression of acan, bgn, and sox9 during chondrogenesis. ColVI was found to be of central importance in resisting applied strains, while DCN knockdown had strain dependent effects on deformation. We demonstrate that by using genetic engineering to control the biophysical microenvironment created by differentiating cells, it may be possible to guide cellular mechanotransduction.

Sub-biochemical hypothyroidism: an exaggerated thyroid stimulating hormone response to thyrotrophin releasing hormone.

BACKGROUND: The availability of sensitive and specific assays for evaluation of the thyroid axis has allowed definition of thyroid disorders at subclinical stage. This has almost obviated the use of thyrothrophin releasing hormone (TRH) study. We describe here a group of patients with minimal signs of hypothyroidism having normal thyroid function tests (T3, T4, thyroid stimulating hormone (TSH)) and have shown exaggerated TSH response to TRH. MATERIAL AND METHODS: Total 82 subjects were studied. Of these, 11 were age and sex matched controls, and 71 were patients. In all subjects TSH and other thyroid assays (T3, T4, FT4) were done by immunoradiometric assay (IRMA), and radioimmunoassay (RIA) respectively. Thyroid antibody was carried out by haemagglutination method. Results were compared to age and sex related normal ranges. To further investigate the status of thyroid axis, TRH study was carried out using standard protocol. RESULTS: Based on TRH study patients were grouped in three categories. Group 1 included 29 patients whose TSH response to TRH was normal. Group 2 included 20 patients with normal baseline TSH and exaggerated TSH response to TRH and Group 3 included 18 patients with baseline TSH in the range of 5 to 10 mu IU/ml and exaggerated TSH response to TRH. There was a significant difference to total T3 between group 1 and 3 (p < 0.05) but mean values were within normal limits. While no significant difference was observed in total T4 between controls and patient's group. Serum TSH values were high in group 3 as compared to controls and Group 1 and 2 (p < 0.0001). For Free T4 no statistical significance was observed between Group 1, 2 and 3. Thyroid antibodies were positive in 22.7% of patients in Group 2 and 33.33% in Group 3. CONCLUSION: We conclude from the present study that even with sensitive TSH assays TRH study still has a role to mark the early stage of hypothyroidism. Those with a normal or upper normal TSH with exaggerated response to TRH are termed as sub-biochemical hypothyroidism and can be considered for thyroid replacement therapy.

A newer avenue for evaluation of thyroid dysfunction.

Attempt has been made to rationalise the biochemical assessment of patients suspected to have thyroid dysfunction by introduction of a new rapid and supersensitive immunoradiometric assay (IRMA) for TSH. 294 patients were subjected to thyroid investigation viz; tT3, tT4 and TSH (IRMA). Of these, 51 (17.34%) were hypothyroid, 22 (7.48%) were hyperthyroid and 221 (75.1%) were euthyroid. The ratio of thyroid disorder in male to female was 1:3.38. In all patients with hyperthyroidism TSH (IRMA) was 0.05 to undetectable and it was more than 4.5 ulu/ml in hypothyroid patients. TSH (IRMA) was low in one euthyroid patient a 0.34% incidence of false negativity. In 2 patients with subclinical hyperthyroidism TSH (IRMA) was low while tT3 and tT4 were normal. TSH (IRMA) therefore may obviate the need for more time consuming and expensive TRH test and simplify the approach to thyroid function tests in patients suspected to have masked or overt hyperthyroidism.