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Pituitary metastases are rare. Until now, few cases have been reported; about 50% of pituitary metastases originate from breast or lung cancers. We describe the clinical case of a primary colon carcinoma first presenting with a pituitary metastasis. A 76-year-old woman, with no history of malignancy, presented with headache, dizziness, and diplopia, at the Emergency Department. The neurologic examination was remarkable for complete left ophthalmoplegia with sensitivity deficit on the left side of the face. Radiologic investigations documented a voluminous sellar and suprasellar lesion, with extension in the left cavernous sinus and temporal lobe. Pituitary hormone levels were suggestive of anterior hypopituitarism and mild hyperprolactinemia. Subtotal surgical removal of the lesion was achieved through a trans-sphenoidal endoscopic endonasal approach. The histological examination disclosed a metastasis of gastrointestinal adenocarcinoma. A subsequent colonoscopy identified right colon cancer. A contrasted total-body computerized tomography ruled out other metastases. Postsurgical MRI showed a stable parasellar residual tumor. Conventional radiotherapy was scheduled. This case underlines the importance of considering pituitary metastases in the differential diagnosis of aggressive pituitary lesions, which should be managed in a pituitary tumor center of excellence through a multidisciplinary approach, for the complexity in diagnosis and therapeutic management of this rare condition. [ABSTRACT FROM AUTHOR]

Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report the first acromegaly patient carrying a RET pathogenic variant: c.2410G>A (rs79658334), p.Val804Met. Alongside the fact that the patient's father and daughter carried the same variant, we investigated the clinical significance of this variant in the context of somatotropinomas and other endocrine tumors, reviewing the RET mutations' oncogenic mechanisms. The aim was to search for new targets to precisely manage and treat acromegaly. Our case describes a new phenotype associated with the RET pathogenic variant, represented by aggressive acromegaly, and suggests consideration for RET mutation screening if NGS for well-established PitNET-associated gene mutations renders negative. [ABSTRACT FROM AUTHOR]

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs. [ABSTRACT FROM AUTHOR]

BAC: kground: Macular oedema tends to be a more rapid complication of diabetic retinopathy and represents the major cause of blindness. Among subjects with type 2 diabetes mellitus, it can be found in 15% of those who use insulin and 4% of those who do not. Use of thiazolidinediones (glitazones) has recently been associated with some cases of macular oedema. METHODS: We recalled 102 diabetic subjects treated with rosiglitazone to our diabetes centre in order to evaluate a possible association of this drug with macular oedema. Of these 102 subjects, we evaluated all 76 who provided written informed consent to participate in the analysis. All of these underwent a battery of four diagnostic tests: (1) visual acuity, (2) Amsler visual field test, (3) Ishihara colour recognition test, and (4) retinal fundus photography. All retinal photographs were examined by two experienced ophthalmologists. RESULTS: The most noticeable result was that most subjects (80%) had satisfactory visual acuity. The Ishihara test chart showed that three subjects were colour blind, but this abnormality was already known. On the Amsler test, one subject had a positive result consisting of visual distortion of a series of straight lines. In the retinal photos, two expert ophthalmologists independently identified one case of ‘paramacular oedema’ in a subject with diabetes of long duration with a proliferative retinopathy. The patient developed bilateral macular oedema during treatment with rosiglitazone 8 mg/day. The patient had been diagnosed with diabetes at the age of 45 years and after a period of 6 years taking oral antihyperglycaemic agents had been switched to insulin, up to four injections per day (total 60–70 IU/day), for the next 15 years. In 2000 a routine examination demonstrated the presence of sustained hypertension and the patient was started on an ACE inhibitor. A computerized test for autonomic neuropathy demonstrated abnormal deep breathing and lying-to-standing responses. Treatment with rosiglitazone was interrupted and the subject underwent a series of retinal photocoagulations for proliferative retinopathy. Two months after rosiglitazone therapy had been discontinued, the visual acuity of the patient reversed to baseline values. CONCLUSION: The study shows that rosiglitazone was not linked to formation of macular oedema, with the exception of one case of bilateral and clinically reversible paramacular oedema, where rosiglitazone was given in co-administration with a long-term insulin treatment regimen in a subject with pre-existing diabetic retinopathy. This patient had a long duration of diabetes and had also been hypertensive since 2000. [ABSTRACT FROM AUTHOR]

Background: Despite conflicting results, considerable evidence suggests the association between single nucleotide polymorphisms in MTHFR, XRCC1 and OGG1 genes and, risk of developing breast cancer. Here a case-control study is reported, including 135 breat cancer patients and 112 healthy women, all representative of Northern Sardinian population.Methods: Polymerase chain reaction/restriction fragment length polymorphism method was used to determine the genotypes of five polymorphisms: MTHFR C677T (rs1801133) and A1298C (rs1801131), XRCC1 Arg194Trp (rs1799782) and Arg399Gln (rs25487) and OGG1 Ser326Cys (rs1052133). Allelic, genotypic and haplotype association analyses with disease risk and clinicopathological parameters were performed.Results: A nominally significant association with breast cancer risk was observed for MTHFR C677T polymorphism heterozygous genotype in the codominant model (OR: 0.57, 95% CI: 0.32-1.00, p = 0.049) and for Cys/Cys genotype of the OGG1 Ser326Cys polymorphism in the recessive model (OR: 0.23, 95% CI: 0.05-1.11, p = 0.0465). No significant differences were found at genotype-level for A1298C polymorphism of the MTHFR gene and Arg194Trp and Arg399Gln of the XRCC1 gene. Furthermore, the OGG1 and XRCC1 rs25487 polymorphisms were nominally associated with PgR, Her2 status and with sporadic breast cancer, respectively.Conclusions: Based on genetic characteristics of individuals included in this study, results suggest that MTHFR CT and OGG1 Cys/Cys genotypes have a protective effect that may have an influence on breast cancer risk in a representative Northern Sardinian population. [ABSTRACT FROM AUTHOR]