Endocrine Abstracts

T3, GH and IGF-1 are essential for skeletal development. GH acts directly on growth plate chondrocytes and also via a local paracrine pathway involving IGF-1, but it is unclear whether T3 stimulates bone formation directly or indirectly. To address this, we determined expression of GH-receptor, IGF-1 and IGF-1 receptor (IGF-1R) by in situ hybridisation and activation of downstream STAT5 and AKT signalling by immunohistochemistry in growth plates from four T3-receptor (TR) muta...

T3, GH and IGF-1 are essential for skeletal development, growth and bone mineralisation. The major growth-promoting actions of GH occur in epiphyseal chondrocytes via direct effects on GH-receptor expressing cells and via a local paracrine pathway involving IGF-1. There is controversy regarding whether T3-actions in bone are direct or occur via regulation of GH secretion and action. We examined this in mice with a mutation (PV) targeted to either T3-receptor (TR) beta or alpha...

Rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome(ODS). Recent days, vasopressin receptor antagonists(VAs) are clinically used for the treatment of congestive heart failure or hyponatremia including SIADH. To date, few cases of ODS caused by VAs have reported; however, it is presumed that the treatment with VAs for severe hyponatremia may be associated with an increased risk of ODS. Therefore, in this study, we investigated whether rapid correct...

Thyroid hormone (T3) is essential for skeletal development and maintenance of bone mineralisation. T3 actions are mediated by two receptors, TRalpha and TRbeta. Mutations in TRbeta cause autosomal dominant resistance to thyroid hormone (RTH) due to dominant negative activity of the mutant receptor. Short stature and abnormal skeletal development are prominent features of RTH, whereas TRalpha mutations have not been described and are postulated to result in no phenotype or to b...

Thyroid hormone (T3) receptor beta (TRbeta) mutations cause resistance to thyroid hormones (RTH), characterised by decreased tissue sensitivity to T3. The TRbetaPV mutation (C-insertion at codon 448 leads to a frameshift of the carboxy-terminal 14 amino acids) was derived from a patient with severe RTH and generates a receptor lacking T3-binding and transactivation activities. Heterozygous mutant mice have a mildly impaired pituitary-thyroid axis; severe RTH and limb shortenin...

Introduction: Surgical treatment of giant GH cell adenomas (>4 cm in maximum diameter; GHomas) has been considered difficult. However, clinical and histological characteristics of these adenomas are still enigmatic. We retrospectively analyzed data of 17 giant GHomas experienced at Toranomon hospital to clarify their characteristics.Methods: These 17 patients, accounting for 3.1% of 549 acromegalic patients undergoing surgery between 2006 and 2011, w...

Background and aims: Excess GH causes insulin resistance resulting in impaired glucose metabolism. Although diabetes mellitus (DM) is common in patients with acromegaly, diabetic ketoacidosis (DKA) is rarely associated with acromegaly. Actually only 11 DKA patients have been anecdotally reported as the first presentation of acromegaly so far. Here we present nine cases of DKA as the first presentation of 860 consecutive patients with acromegaly and their clinical characteristi...