The aim of this review was to present the metabolism of vitamin D₃, as well as to discuss the role of vitamin D₃ in bone metabolism, temporomandibular joint osteoarthritis (TMJ OA), and autoimmune thyroid diseases (AITD) on the basis of the literature. Vitamin D₃ plays a significant role in human health, as it affects the calcium-phosphate balance and regulates the bone metabolism. Calcitriol impresses the pleiotropic effect on human biology and metabolism. Its modulative function upon the immune system is based on the reduction of Th1 cell activity and increased immunotolerance. Vitamin D₃ deficiency may lead to an imbalance in the relationship between Th1/Th17 and Th2, Th17/Th reg, and is considered by some authors as one of the possible backgrounds of autoimmune thyroid diseases (AITD), e.g., Hashimoto’s thyroiditis or Graves’ disease. Moreover, vitamin D₃, through its direct and indirect influence on bones and joints, may also play an important role in the development and progression of degenerative joint diseases, including temporomandibular joint osteoarthritis. Further randomized, double blind studies are needed to unequivocally confirm the relationship between vitamin D₃ and abovementioned diseases and to answer the question concerning whether vitamin D₃ supplementation may be used in the prevention and/or treatment of either AITD or OA diseases.

Osilodrostat is an oral steroidogenesis inhibitor used in the treatment of hypercortisolism. It works by inhibiting 11-beta-hydroxylase, a key enzyme in cortisol synthesis. As a consequence of drug action, adrenal insufficiency can be observed in about 40% of patients. Although this effect has been accepted as a consequence of therapy, recent reports suggest adrenal insufficiency can persist even after discontinuation of osilodrostat. We present the case of a 74-year-old female patient who developed prolonged adrenal insufficiency after withdrawal of osilodrostat. The patient was diagnosed with ectopic ACTH-dependent Cushing’s syndrome and underwent radiotherapy for a primary lesion located in the anterior mediastinum. During treatment, osilodrostat was introduced (2 to 4 mg/d), and adrenal insufficiency developed within four weeks. Hydrocortisone (intermittently dexamethasone) replacement therapy was initiated, and over time, undetectable morning cortisol levels continued. After de-escalating the osilodrostat dose, the drug was withdrawn 15 months after initiation. Despite being off the drug for 11 months, the patient with adrenal insufficiency (morning serum cortisol: 37.2 nmol/L), still requires hydrocortisone substitution. The underlying mechanism of prolonged adrenal insufficiency after osilodrostat discontinuation remains unclear. It is unknown whether this is due to permanent inhibition of 11-beta-hydroxylase or interference at another step in steroidogenesis. Factors such as treatment duration, dose, or individual sensitivity may play a role, but other mechanisms, such as an adrenolytic effect, should also be considered. We expect an increase of similar cases, which we believe will lead to further research to better understand the mechanisms behind prolonged adrenocortical blockade after osilodrostat discontinuation.