Endocrine Abstracts

Disorders of thyroid hormone action are classified broadly, to encompass conditions with defective cellular uptake, metabolism or nuclear action of thyroid hormones. We describe recent insights into two rare disorders of thyroid hormone action. Impaired conversion of T4 to T3 enables recognition of a multisystem disorder due to mutations in SECISBP2 – a factor directing synthesis of 25 different human, selenocysteine-containing proteins that...

The actions of thyroid hormones (TH) are mediated by receptors (TRα1, TRβ1, TRβ2), encoded by separate genes (THRA, THRB), with differing tissue distribution. TRβ2 mediates negative feedback within the hypothalamic-pituitary axis, with TRβ1 being expressed in the liver & kidney; TRα1 predominates in the myocardium and skeletal muscle.Resistance to Thyroid Hormone, usually due to heterozygous TRβ mutations (...

Disorders of thyroid hormone action are classified broadly, to encompass conditions with defective cellular uptake, metabolism or nuclear action of thyroid hormones. Mutations in SECISBP2 cause a multisystem disorder of defective selenoprotein synthesis, with features due to tissue-specific selenoprotein deficiencies (e.g. male infertility, muscular dystrophy), raised cellular reactive oxygen species due to lack of antioxidant selenoenzymes (e.g. photosensitivity, increased ad...

A 24-year-old, Bengali female presented to her GP with fatigue. Blood tests demonstrated she was pregnant and had elevated thyroid hormones (Free T4 50.4 pmol/l, NR 10.5-24.5; Free T3 19.9 pmol/l, NR 3.1-6.8) with an inappropriately normal TSH (4.04 mU/l, NR 0.27-4.2), prompting referral to our endocrine unit. Her TFTs were repeated on a different platform which excluded assay interference. She reported a 5-year history of a goitre, associated with symptoms of hyperthyroidism ...

TSHoma is rare, with an incidence of 1 per million, and <1% of all pituitary tumours. We reported a case involving a 49-year-old female who was first referred to our endocrine unit in 2006 with excessive lethargy and abnormal TFT’s. She was thought to have thyroid hormone resistance for several years until 2015 when she reported having persistent symptoms and further investigation suggested an alternative diagnosis.Results: Ft4=41.6 pmol/l, TSH=...

Background: Antithyroid drugs include thioimidazoles (carbimazole, methimazole) and propylthiouracil. Carbimazole is most commonly used in the UK. A fixed drug eruption is the drug-induced cutaneous reaction which occurs at the same site after each exposure to that agent. It is uncommon with anti-thyroid medications. Here we report this rare presentation. A 40-year-old Chinese lady who was diagnosed with Graves’ disease was initially treated with carbimazole, and then wit...

Resistance to thyroid hormone due to a mutation in thyroid hormone receptor alpha (RTHα) is a syndrome whose features include delayed growth and neurocognitive development. Macrophages, which derive from circulating monocytes and have recently been recognized as important thyroid hormone target cells, are innate immune cells that are capable of adopting a wide range of phenotypes. Assuming the right phenotype in the right setting is crucial as macrophage dysfunction has b...

Mutations in THRA, a ligand-inducible transcription factor, cause Resistance to Thyroid Hormone α (RTHα). RTHα manifests with features of hypothyroidism (skeletal dysplasia and growth retardation, neurocognitive impairment, low metabolic rate, reduced intestinal transit) reflecting hormone resistance in TRα-expressing tissues, but associated paradoxically with near-normal circulating TH levels. The lack of clear-cut, abnormal thyroid function tests...

Background: Immune checkpoint (CTLA-4, PD-1) inhibitors are increasingly used to treat cancers including advanced melanoma. Although endocrine immune related adverse events (IRAEs) are now well reported, the frequency and type of thyroid and pituitary dysfunction reported varies considerably, with hypophysitis after CTLA-4 inhibitors reported in 2–16%, and thyroid dysfunction after PD-1 inhibitors in 2–39%. In addition, recove...

Background: Immune checkpoint (CTLA-4, PD-1) inhibitors are increasingly used to treat cancers including advanced melanoma. Although endocrine immune related adverse events (IRAEs) are now well reported, the frequency and type of thyroid and pituitary dysfunction reported varies considerably, with hypophysitis after CTLA-4 inhibitors reported in 2–16%, and thyroid dysfunction after PD-1 inhibitors in 2–39%. In addition, recove...