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1.
Pituitary ; 25(6): 831-841, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35922724

RESUMEN

INTRODUCTION: Acromegaly is a chronic disease with systemic complications. Disease onset is insidious and consequently typically burdened by diagnostic delay. A longer diagnostic delay induces more frequently cardiovascular, respiratory, metabolic, neuropsychiatric and musculoskeletal comorbidities. No data are available on the effect of diagnostic delay on skeletal fragility. We aimed to evaluate the effect of diagnostic delay on the frequency of incident and prevalent of vertebral fractures (i-VFs and p-VFs) in a large cohort of acromegaly patients. PATIENTS AND METHODS: A longitudinal, retrospective and multicenter study was conducted on 172 acromegaly patients. RESULTS: Median diagnostic delay and duration of follow-up were respectively 10 years (IQR: 6) and 10 years (IQR: 8). P-VFs were observed in 18.6% and i-VFs occurred in 34.3% of patients. The median estimated diagnostic delay was longer in patients with i-VFs (median: 11 years, IQR: 3), in comparison to those without i-VFs (median: 8 years, IQR: 7; p = 0.02). Age at acromegaly diagnosis and at last follow-up were higher in patients with i-VFs, with respect to those without i-VFs. The age at acromegaly diagnosis was positively associated with the diagnostic delay (p < 0.001, r = 0.216). A longer history of active acromegaly was associated with a high frequency of i-VFs (p = 0.03). The logistic regression confirmed that patients with a diagnostic delay > 10 years had 1.5-folds increased risk of developing i-VFs (OR: 1.5; 95%CI: 1.1-2; p = 0.017). CONCLUSION: Our data showed that the diagnostic delay in acromegaly has a significant impact on VF risk, further supporting the clinical relevance of an early acromegaly diagnosis.


Asunto(s)
Acromegalia , Humanos , Acromegalia/complicaciones , Estudios de Seguimiento , Diagnóstico Tardío , Densidad Ósea , Estudios Retrospectivos
2.
Artículo en Inglés | MEDLINE | ID: mdl-38963295

RESUMEN

The review explores the 2022 update to the World Health Organization (WHO) classification of pituitary adenomas, now referred to as pituitary neuroendocrine tumors (PitNETs), and his possible impact on the clinical management of PitNET patients. The review highlights the differences and the evolution from the 2017 to 2022 version, with the current classification considering the lineage of the tumor cells, cell type, hormones produced, and other auxiliary characteristics for a comprehensive histological classification. The revision in terminology reflects a broader perspective on neuroendocrine neoplasia. The new approach based on transcription factors, hormone expression and other biomarkers has allowed a major revision of the nomenclature and a more accurate classification of pituitary adenomas. Furthermore, in some cases this approach is also assuming a prognostic value, useful in clinical practice. However, despite this elaborate classification and stratification, the review points out the lack of a robust grading or staging system and suggests the need for further research and validation of diagnostic methods. Despite these limitations, the revised classification presents a significant step towards understanding and managing PitNETs patients.

3.
J Pers Med ; 13(8)2023 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-37623461

RESUMEN

Hypophysitis, a rare inflammatory disorder of the pituitary gland, has seen an uptick in reported cases in recent years. Our objective is to summarize the most recent research on the etiopathogenesis, molecular mechanisms, and genetics of both primary and secondary hypophysitis. Primary autoimmune hypophysitis (PAH): During the acute phase of the disease, the pituitary gland in enlarged due to the infiltration of T and B lymphocytes. The chronic phase is characterized by progressive and irreversible pituitary atrophy. APA may play a role in the management, diagnosis, and prognosis of PAH. Specific autoantibodies such as anti-GH, anti-PIT-1, and anti-T-PIT have been found in patients with hypophysitis and hypopituitarism. A recent study suggested that a mechanism of escaping clonal deletion and mounting an immune response against self antigens can explain the unusual nature of the immune response observed in PAH patients. A cytokine array shows the presence of gamma-interferon and interleukin-17. Patients carrying mutations in the PIT1 or PROP1 genes may present PAH. Individuals carrying the HLA DQ8 haplotype are four times more likely to develop PAH. Immune checkpoint inhibitors induce hypophysitis (IIHs): IIHs is an increasingly frequent toxicity of in patients on treatment with inhibitors targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). ICIs inhibit the CTLA-4 pathway, leading to overactivation of T lymphocytes. The binding of PD-1/PD-L1 suppresses the activity of T cells, promotes the conversion of T-helpers into T-regulatory cells, and activates pro-survival signaling pathways in cancer cells. Cytokines play a crucial role in IIHs. B-cell infiltration has been observed in IIHs, suggesting that antibody-mediated pituitary injury may contribute. Genetic polymorphisms of CTLA-4 and PD-1 genes can increase the risk of IIHs. HLA alleles may also be involved in the onset of IIHs; this HLA association presents a possible alternative mechanistic hypothesis. IIHs may also be linked to a paraneoplastic syndrome triggered by ectopic expression of pituitary specific antigens. SARS-CoV-2-related hypophysitis: Recently, the literature has reported occurrences of hypophysitis associated with the SARS-CoV-2 virus; long COVID-19 may also present as infundibulo-neuro-hypophysitis. The virus enters the central nervous system because of its distinct interaction with angiotensin-converting enzyme receptors via spike proteins binding the capillary endothelium, and it directly damages the pituitary cells. The effect of SARS-CoV-2 can occur indirectly through inflammation and the release of cytokines. The exact mechanism remains ambiguous. The available data on endocrine complications associated with the SARS-CoV-2 vaccine are scant. Nonetheless, isolated cases of hypophysitis have been documented. Treatment of hypophysitis: Glucocorticoids are the cornerstone in managing primary hypophysitis, given their targeted action on inflammation. A better understanding of the etiopathogenesis and molecular mechanism of hypophysitis can lead to more effective and personalized treatment strategies.

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