Adrenal Insufficiency in Patients with Beta Thalassemia: A Meta-Analysis.

Background and Objectives: Adrenal insufficiency (AI) can be a significant concern in patients with transfusion-dependent homozygous beta thalassemia (bThal) due to the chronic disease burden and frequent blood transfusions that these patients require. The prevalence of AI in this population remains unclear, with studies often lacking control groups for comparison. This meta-analysis aimed to estimate the proportion of patients with transfusion-dependent bThal who exhibit evidence of AI. Materials and Methods: A systematic review following PRISMA guidelines identified 19 studies for analysis. Results: Despite the variability in the diagnostic methods used to ascertain AI, the meta-analysis revealed that approximately one-third of patients had evidence of AI, with the prevalence rising to 50% in studies focused on adults with bThal. Conclusions: These findings suggest an increased risk of AI in patients with bThal compared to the general population. Clinicians should consider tailored management strategies, including glucocorticoid coverage during surgical procedures, to mitigate the risk of adrenal crises in this vulnerable patient group. Further research is needed to optimize adrenal surveillance and management in patients with bThal.

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.

Effects of teriparatide retreatment in a patient with ß-thalassemia major.

BACKGROUND: Bone disease is a frequent complication of ß-thalassemia major (ß-ΤΜ) and its etiology is multifactorial. Marrow expansion, chronic hypoxia, endocrine complications, and iron overload caused chiefly by chronic transfusion treatment are significant factors affecting skeletal health. Bone disease is prevalent even among patients on regular transfusions and adequate iron chelation. The life expectancy of patients with ß-thalassemia has increased during the past decade and so, nowadays, patients with thalassemia-associated bone disease (TBD) often require long-term management. There are limited data concerning their pharmacologic treatment. Bisphosphonates represent the most widely studied agents in such patients and there are no published studies about the effects of anabolic treatment. Retreatment with teriparatide has only occasionally been studied in patients with osteoporosis. CASE REPORT: We present a male adult patient with ß-ΤΜ with a history of low bone mass and multiple vertebral fractures, who required sequential treatment for his longstanding bone disease. He had exhibited considerable, albeit delayed, response to a course of teriparatide treatment for 18 months but subsequently, and while on alendronate, sustained an insufficiency fracture at the left ischiopubic ramus. A second trial of teriparatide treatment resulted in further remarkable increase in total hip and femoral neck bone mineral density. We present the patient's response to sequential treatment during an 8-year follow-up. CONCLUSION: Teriparatide could represent an alternative treatment for adults with TBD especially when long-term, sequential treatment is needed. Although there are limited data concerning retreatment, in selected cases, this might be considered.

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.

The Role of Somatostatin Analogues in the Control of Diarrhea and Flushing as Markers of Carcinoid Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Somatostatin analogues (SSAs) are the cornerstone of treatment for carcinoid syndrome (CS)-related symptoms. The aim of this systematic review and meta-analysis is to evaluate the percentage of patients achieving partial (PR) or complete response (CR) with the use of long-acting SSAs in patients with CS. METHODS: A systematic electronic literature search was conducted in PubMed, Cochrane, and Scopus to identify eligible studies. Any clinical trials reporting data on the efficacy of SSAs to alleviate symptoms in adult patients were considered as potentially eligible. RESULTS: A total of 17 studies reported extractable outcomes (PR/CR) for quantitative synthesis. The pooled percentage of patients with PR/CR for diarrhea was estimated to be 0.67 (95% confidence interval (CI): 0.52-0.79, I2 = 83%). Subgroup analyses of specific drugs provided no evidence of a differential response. With regards to flushing, the pooled percentage of patients with PR/CR was estimated to be 0.68 (95% CI: 0.52-0.81, I2 = 86%). Similarly, no evidence of a significant differential response in flushing control was documented. CONCLUSIONS: We estimate there is a 67-68% overall reduction in symptoms of CS associated with SSA treatment. However, significant heterogeneity was detected, possibly revealing differences in the disease course, in management and in outcome definition.

Circadian rhythm disruption in cancer biology.

Circadian rhythms show universally a 24-h oscillation pattern in metabolic, physiological and behavioral functions of almost all species. This pattern is due to a fundamental adaptation to the rotation of Earth around its own axis. Molecular mechanisms of generation of circadian rhythms organize a biochemical network in suprachiasmatic nucleus and peripheral tissues, building cell autonomous clock pacemakers. Rhythmicity is observed in transcriptional expression of a wide range of clock-controlled genes that regulate a variety of normal cell functions, such as cell division and proliferation. Desynchrony of this rhythmicity seems to be implicated in several pathologic conditions, including tumorigenesis and progression of cancer. In 2007, the International Agency for Research on Cancer (IARC) categorized "shiftwork that involves circadian disruption [as] probably carcinogenic to humans" (Group 2A in the IARC classification system of carcinogenic potency of an agentagent) (Painting, Firefighting, and Shiftwork; IARC; 2007). This review discusses the potential relation between disruptions of normal circadian rhythms with genetic driving machinery of cancer. Elucidation of the role of clockwork disruption, such as exposure to light at night and sleep disruption, in cancer biology could be important in developing new targeted anticancer therapies, optimizing individualized chronotherapy and modifying lighting environment in workplaces or homes.

Obesity and bone metabolism.

The interaction between obesity and bone metabolism is complex. The effects of fat on the skeleton are mediated by both mechanical and biochemical factors. Though obesity is characterized by higher bone mineral density, studies conducted on bone microarchitecture have produced conflicting results. The majority of studies indicate that obesity has a positive effect on skeletal strength, even though most likely the effects are site-dependent and, in fact, obese individuals might be at risk of certain types of fractures. Mechanical loading and higher lean mass are associated with improved outcomes, whereas systemic inflammation, observed especially with abdominal obesity, may exert negative effects. Weight loss interventions likely lead to bone loss over time. Pharmacological treatment options seem to be safe in terms of skeletal health; however, the skeletal effects of bariatric surgery are dependent on the type of surgical procedure. Malabsorptive procedures are associated with higher short-term adverse effects on bone health. In this narrative review, we discuss the effects of obesity and weight loss interventions on skeletal health.

The role of biphosphonates in the management of thalassemia-induced osteoporosis: a systematic review and meta-analysis.

Thalassemia Major (TM) is a clinical entity with a high prevalence of low bone mass. The aim of the present study was to perform a meta-analysis of all available data on the role of bisphosphonates (BPs) in the therapy of thalassemia major-induced osteoporosis. The PRISMA recommendations for reporting systematic reviews and meta-analyses were used to guide the present study. We searched PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 31, 2017 for articles related to thalassemia and BPs. To meta-analytically synthesize the primary endpoint, we used the standardized mean difference (SMD) after Hedges's g transformation under the scenario of a random effects model. Heterogeneity across studies was examined using the I2 statistic. Nine randomized controlled trials (RCTs) containing original data were included in this review. Three studies were performed in Italy, one in Australia, three in Greece, one in Cyprus, and one in China. The BPs investigated included zoledronate, alendronate, pamidronate, clodronate, and neridronate. Zoledronate and alendronate showed a tendency to perform best as compared to neridronate and the placebo effect with respect to femoral neck, lumbar spine, total hip, and total body in terms of bone mass density (g/cm2). BPs and in particular, zolendronate, were quite effective in the treatment of osteoporosis. These findings suggested that bisphosphonates are still a front-line treatment of osteoporosis in TM. However, to draw more meaningful and significant conclusions for the use and efficacy of BP in TM, larger and more complete RCTs should be conducted.

Adrenal malignant melanoma masquerading as a pheochromocytoma in a patient with a history of a multifocal papillary and medullary thyroid carcinoma.

OBJECTIVE: Adrenal masses usually represent benign and nonfunctional adrenal adenomas; however, primary or metastatic malignancy should also be considered. Discovery of an adrenal mass needs further evaluation in order to exclude malignancy and hormonal secretion. We present a rare case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. CASE REPORT: A 61-year-old male farmer was referred for evaluation of a mass in the right supraclavicular region and a left adrenal lesion. The patient had a history of a multifocal papillary and medullary thyroid carcinoma. Laboratory tests revealed increased 24hour urinary dopamine and also increased serum calcitonin and neuron specific enolase. A pathology report of the resected right supraclavicular mass and left adrenal showed a malignant melanoma. CONCLUSION: This is a case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. Although this case is very rare and there are rigid diagnostic criteria for the diagnosis of primary adrenal melanoma, it underlines the fact that the differential diagnosis of a dopamine secreting adrenal mass should include primary or metastatic malignant melanoma in order to determine the best diagnostic approach for the patient and select the most appropriate surgical management.

The role of KISS1/KISS1R system in tumor growth and invasion of differentiated thyroid cancer.

BACKGROUND/AIM: KISS1 protein and KISS1 receptor form a system that mainly promotes suppression of metastasis in various forms of cancer. We studied the relationship between KISS1/KISS1R expression and tumor progression in differentiated thyroid cancer (DTC). MATERIALS AND METHODS: Thirty-three patients diagnosed with DTC were included in the study. Immunohistochemical cytoplasmic expression was evaluated for KISS1 and cytoplasmic/membranous expression for KISS1R in thyroid cancer tissues. RESULTS: KISS1 expression was significantly higher in tumors with extrathyroidal invasion and advanced stage. KISS1R expression showed a statistically significant, moderate negative correlation with tumor size. CONCLUSION: Increased expression of KISS1 is possibly acquired to prevent further tumor invasiveness and formation of local or distant metastasis. It appears that malignant cells in DTC express increased levels of KISS1 as the tumor invades extrathyroidal tissues. Decreased expression of KISS1R seems to attenuate signaling of the KISS1/KISS1R system, possibly leading to tumor growth.