Circadian rhythm disruption and endocrine-related tumors.

This review delved into the intricate relationship between circadian clocks and physiological processes, emphasizing their critical role in maintaining homeostasis. Orchestrated by interlocked clock genes, the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle, energy metabolism, immune function, and cell proliferation. The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles, while peripheral tissue clocks are influenced by cues such as feeding times. Circadian disruption, linked to modern lifestyle factors like night shift work, correlates with adverse health outcomes, including metabolic syndrome, cardiovascular diseases, infections, and cancer. We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis. Specific associations between circadian disruption and endocrine tumors, spanning breast, ovarian, testicular, prostate, thyroid, pituitary, and adrenal gland cancers, are highlighted. Shift work is associated with increased breast cancer risk, with PER genes influencing tumor progression and drug resistance. CLOCK gene expression correlates with cisplatin resistance in ovarian cancer, while factors like aging and intermittent fasting affect prostate cancer. Our review underscored the intricate interplay between circadian rhythms and cancer, involving the regulation of the cell cycle, DNA repair, metabolism, immune function, and the tumor microenvironment. We advocated for integrating biological timing into clinical considerations for personalized healthcare, proposing that understanding these connections could lead to novel therapeutic approaches. Evidence supports circadian rhythm-focused therapies, particularly chronotherapy, for treating endocrine tumors. Our review called for further research to uncover detailed connections between circadian clocks and cancer, providing essential insights for targeted treatments. We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.

Severe hypocalcemia after denosumab administration in a patient with chronic kidney disease: a case report.

Patients with altered kidney function are at increased risk of hypocalcemia after denosumab administration. There is however a small number of studies and case reports describing hypocalcemia refractory to treatment. We describe a case of severe hypocalcemia, after the administration of three doses of denosumab, in a young patient with lupus nephritis under corticosteroid coverage and osteopenia. However, more studies are needed in order to extract a safe conclusion about the factors that contribute to the development of severe hypocalcemia in this group of patients.

Primary aldosteronism in hypertensive patients: clinical implications and target therapy.

BACKGROUND: The prevalence of primary aldosteronism (PA) in hypertensive patients varies according to diagnostic testing and ascertained normal cut-offs. The aim of this case-control study was to confirm the high prevalence of PA in a large hypertensive population and evaluate the antihypertensive effect of mineralocorticoid receptor antagonists (MRA) treatment. MATERIAL AND METHODS: We investigated 327 hypertensive and 90 matched normotensive subjects with normal adrenal imaging. Serum aldosterone (ALD), active renin (REN) levels and aldosterone/active renin (ALD/REN) ratio were measured before and after a combined sodium chloride, fludrocortisone and dexamethasone suppression test (FDST). Post-FDST values were compared to cut-offs obtained from controls (post-FDST ALD 2·96 ng/dL and post-FDST ALD/REN 0·93 ng/dL/µU/mL). PA patients received MRA treatment. RESULTS: By applying the combination of post-FDST ALD levels and ALD/REN ratio, 28·7% of the hypertensive patients had PA. There was a positive, albeit weak, correlation between systolic (SBP) and diastolic blood pressure (DBP) and ALD levels and/or ALD/REN ratio after the FDST (P < 0·0001). SBP was associated with a post-FDST ALD of 3·24 ng/dL and ALD/REN ratio of 0·90 ng/dL/µU/mL, whereas post-FDST ALD had an inverse association at serum K+ values of less than 3·9 mEq/L. MRA treatment in 69 PA patients, resulted in a significant reduction in the maximum SBP and DBP values (28 ± 15 and 14 ± 7 mmHg, respectively, P < 0·0001). CONCLUSIONS: Using the FDST, an increased prevalence of PA in hypertensives was observed. Α significant blood pressure lowering effect was obtained with MRA treatment, implying that these agents may be beneficial in a significant number of hypertensive patients.