Endocrine Abstracts

Loss of function of succinate dehydrogenase (SDH), caused by mutations in each of the 4 subunits – SDHA/B/C and D – is associated with development of phaeochromocytomas and paragangliomas (PPGLs). The mutations lead to loss of enzymatic activity and subsequent accumulation of the oncometabolite succinate, a driver of tumourigenesis. It is well established but poorly understood why mutations in SDHB are associated with more aggressi...

75% of patients presenting with a phaeochromocytoma (PCC) or paraganglioma (PGL) have no relevant family history, but a germline pathogenic variant is identified in 30–40%. In our genetic endocrine clinic, over 80% of patients with malignant PCC or PGL have SDHA/SDHB/SDHC/SDHD/MAX or FH pathogenic variants identified, confirming high heritability in severe disease.We describe a series of seven patients from fiv...

75% of patients presenting with a phaeochromocytoma (PCC) or paraganglioma (PGL) have no relevant family history, but a germline pathogenic variant is identified in 30–40%. In our genetic endocrine clinic, over 80% of patients with malignant PCC or PGL have SDHA/SDHB/SDHC/SDHD/MAX or FH pathogenic variants identified, confirming high heritability in severe disease.We describe a series of seven patients from fiv...

Case history: An 18 year old male student presented to the dentist with an eight week history of left-sided facial pain and swelling. He was subsequently referred to the maxillofacial team. His only previous medical encounter was for a traumatic right humerus fracture following a roller-skating injury. He took no regular medication. His father died of an unknown malignant process several years previous and family history was otherwise unremarkable. On questioning, the patient ...

Introduction: Glioblastoma, an aggressive intracranial tumour usually is a solitary lesion and not commonly located in the sella turcica. Panhypopituitarism due to multicentric glioblastoma can present with a challenging clinical picture masking or delaying the underlying diagnosis. Case presentation: 58 year old female presented with marked behavioural change, reduced appetite, nausea, polyuria & increased thirst over 4-6 weeks precipitating into an...

ARMC5 mutations are associated with PBMAH risks, but the ARMC5 action mechanism remains unknown. We discovered that ARMC5 was part of a novel ubiquitin ligase (E3) specific for RPB1, the largest Pol II subunit. ARMC5 deletion significantly reduced RPB1 ubiquitination and increased RPB1 accumulation. Surprisingly, the degradation of not only RPB1 but all the 12 subunits of Pol II was compromised in the absence of ARMC5, suggesting that this E3 acts on RPB1 and molecules in its ...

Tumour localisation in Cushing’s disease (CD) can be challenging; most are microadenomas and 50% are <5 mm in diameter. They are, therefore, often difficult to detect by conventional MRI. Volumetric MRI (3D-SGE, spoiled-gradient echo 3D sequence) is a high spatial resolution scanning technique which uses very thin slices (1 mm). Theoretically, this increases the probability of finding small pituitary lesions when compared to conventional (spin-echo, SE) MRI techniques...

A 30-year-old female presented to her general practitioner with a three-month history of fatigue, visual disturbance, polydipsia and dizziness. She was treated for iron deficiency anaemia, but re-presented two-months later with new-onset headache and worsening visual disturbance. Previously, she had childhood leukaemia, treated in Brazil with no cranial irradiation. On examination there was left eye loss of light/dark perception and right temporal vision loss. She was referred...

Liquid Chromatography tandem mass spectrometry (LC–MS/MS) is gold-standard for androgen analysis in biological fluids, superseding immunoassays in specificity, particularly at low concentrations. While LC–MS/MS is well established for analysis of testosterone (T) and androstenedione (A4), 5α-dihydrotestosterone (DHT) presents greater analytical challenges. DHT circulates at low nanomolar concentrations in men and lower in women, ionising inefficiently. Thus, eve...

Cysteine cathepsins are endo-lysosomal proteases that play crucial roles in thyroid physiology. However, in thyroid cancer, cathepsin B is overexpressed and secreted into the extracellular space, thus promoting migratory phenotypes of thyroid carcinoma cells through excessive extracellular matrix degradation. In addition, we have shown that N-terminally truncated forms of cathepsins B and V which lack the signal peptide and parts of the pro-peptide are localized to the nuclei ...