Prevalence of Non-autoimmune Hypothyroidism in Steroid Resistant Nephrotic Syndrome in Paediatric Age Group
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH
Authors: Sinha, Seema Rani; Kumari, Rekha; Kumar, Rakesh; Shekhar, Ravi; Prakash, Pritam; Prakash, Prem
Abstract
Introduction: It was observed that approximately 10% of children with Nephrotic Syndrome (NS) are found as Steroid Resistant NS (SRNS). The data on the prevalence of non-autoimmune hypothyroidism among the SRNS in India is limited. Aim: To assess the prevalence of non-autoimmune hypothyroidism in the case of SRNS. Materials and Methods: A case control cross-sectional study was conducted in which 52 cases of SRNS and 52 healthy controls were enrolled. Thyroid profile like serum Thyroid Stimulating Hormone (TSH), Free Triiodothyronine (T3), Free Thyroxine (T4) done in the all cases and controls but anti-Thyroid Peroxidase (TPO), and anti-thyroglobulin antibody test was done in the case and control group with deranged thyroid function test. Low Free T4 (normal: 0.7-2 ng/mL) and elevated serum TSH above the upper limit of the reference range (>4.5 mIU/L) was defined as overt hypothyroidism, whereas elevation in serum TSH with a normal serum FT4 concentration was defined as sub clinical hypothyroidism. MedCalc statistical software Version 19.2.6 was used to do statistical analysis. Results: Prevalence of Non-autoimmune hypothyroidism was 38.46% (20 out of 52), 16 (30.76%) had subclinical and 4 (7.69%) had overt hypothyroidism in case of SRNS in comparison to 1.96% (1 out of 52) in control group. Out of 16 subclinical hypothyroid patients, two cases with grade 1, 12 cases with grade 2, and two cases with grade 3 found. Patients with SRNS had a mean (SD) TSH value of 4.5 +/- 4.7 mlU/L which was significantly higher than control (1.8 +/- 1.1 mlU/L). Serum levels of FT4 were within normal range. Anti-TPO and anti-thyroglobulin titre were in normal range in children with hypothyroidism. Conclusion: The prevalence of non-autoimmune hypothyroidism was high in cases of idiopathic SRNS. So, on the basis of this study estimation of thyroid profile in children with SRNS seems to be the rational approach which will lead to early diagnosis and timely management of hypothyroidism in SRNS.
Thyroid and androgen receptor signaling are antagonized by mu-Crystallin in prostate cancer
INTERNATIONAL JOURNAL OF CANCER
Authors: Aksoy, Osman; Pencik, Jan; Hartenbach, Markus; Moazzami, Ali A.; Schlederer, Michaela; Balber, Theresa; Varady, Adam; Philippe, Cecile; Baltzer, Pascal A.; Mazumder, Bismoy; Whitchurch, Jonathan B.; Roberts, Christopher J.; Haitel, Andrea; Herac, Merima; Susani, Martin; Mitterhauser, Markus; Marculescu, Rodrig; Stangl-Kremser, Judith; Hassler, Melanie R.; Kramer, Gero; Shariat, Shahrokh F.; Turner, Suzanne D.; Tichy, Boris; Oppelt, Jan; Pospisilova, Sarka; Hartenbach, Sabrina; Tangermann, Simone; Egger, Gerda; Neubauer, Heidi A.; Moriggl, Richard; Culig, Zoran; Greiner, Georg; Hoermann, Gregor; Hacker, Marcus; Heery, David M.; Merkel, Olaf; Kenner, Lukas
Abstract
Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3 '-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein mu-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TR alpha/TR beta) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.