ALT Addison's disease is characterised by reduced adrenal steroid production. Symptoms can be grouped based on steroid class (glucocorticoid: orange, mineralocorticoid: blue, and adrenal androgen: green). Cortisol deficiency results in loss of negative feedback to the hypothalamic–pituitary–adrenal axis, and a consequent rise in hypothalamic secretion of CRH and secretion of ACTH from the anterior pituitary. Increased melanin production leads to hyperpigmentation. Other features of Addison's disease include reduced quality of life, cognitive deficits, depression, anxiety, and laboratory or biochemical abnormalities. ACTH=adrenocorticotropic hormone. CRH=corticotropin releasing hormone. HRQoL=health-related quality of life. K+=potassium. Na+=sodium. T4=thyroxine. TSH=thyroid-stimulating hormone.
ALT AIP=aryl hydrocarbon receptor-interacting protein. GH=growth hormone. MEN1=multiple endocrine neoplasia type 1. MSA=mammosomatotroph adenomas. MSLA=mixed somatotroph-lactotroph adenomas. PIT-1=pituitary-specific positive transcription factor 1. TSH=thyroid stimulating hormone.
ALT Traditional genotype–phenotype models of Turner syndrome emphasise haploinsufficiency of individual X-linked genes. However, emerging genomic, epigenomic, transcriptomic, proteomic, and metabolomic data suggest that loss of sex-chromosome dosage produces genome-wide regulatory effects. Loss of Xp, PAR1, and X-inactivation escape genes could perturb epigenetic regulators, transcriptional networks, immune pathways, and metabolic signalling. These disturbances propagate across autosomal gene networks and manifest in a tissue-specific manner, contributing to cardiovascular, skeletal, ovarian, metabolic, immune, neurocognitive, and ageing-related features of Turner syndrome. This network model could help explain the limited genotype–phenotype correlation and the marked clinical variability observed even among individuals with 45,X monosomy.
ALT CGM=continuous glucose monitoring. GMI=glucose management indicator.
ALT Colour coding reflects the overall direction of available evidence and does not account for heterogeneity between trials or differences in effect size. Green dot: currently available trials indicate exclusively or predominantly beneficial effects. Yellow dot: currently available trials indicate varying effects (or results are interpretable in varying ways), where evidence does altogether not indicate clear beneficial or clear adverse effects. Red dot: currently available trials indicate exclusively or predominantly adverse effects. Grey dot: currently available trials have not detected an effect on the outcome. White dot: unknown, currently no trials available.
