Authors: Xin Zhao, Jiaquan Zhou, Xiaohong Lyu...

BACKGROUND

Mild autonomous cortisol secretion (MACS) accounts for a significant proportion of adrenal incidentaloma. Current endocrinological screening tests for MACS are complex, particularly in areas with limited medical resources. This study aimed to develop a diagnostic tool based on leukocyte-related parameters to differentiate between MACS and non-functioning adrenal adenoma (NFA).

METHODS

Inthis retrospective case-control study, propensity score-matching was used to select 567 patients from a cohort of 1108 patients (201 MACS, 907 NFA). External validation cohort included 52MACS and 48 NFA from two hospitals, which did not overlap with the modeling cohort patients. Leukocyte-related parameters were evaluated, and the diagnostic efficacy of each parameter was assessed by calculating Youden's J index (J) and the area under the curve (AUC). The study population was divided into training and testing samples using a 10-fold cross-validation method. Machine learning (ML) and classification and regression tree (CART) model were established.

RESULTS

After propensity score matching, 567 patients were enrolled, including 197 MACS and 370 NFA. With the exception of basophil percentage, all other parameters differed significantly between the two groups. Lymphocyte count, lymphocyte percentage, eosinophils count, eosinophils percentage, and basophil percentage were lower in the MACS group compared to the NFA group. Eosinophils percentage demonstrated the highest AUC (0.650), with a sensitivity of 51.3% and specificity of 73.2%. The ML model, based on multiple parameters,exhibited better performance in diagnosing MACS (sensitivity 76%, specificity 77.4%, and AUC 0.818). A clinically usable CART model achieved an AUC of 0.872, with a sensitivity of 95% and a specificity of 75.7%.  In the validation cohort, the prediction accuracy of the ML model and the CART model were 0.784 and 0.798, respectively.

CONCLUSION

TheCART diagnostic model, constructed based on leukocyte-related parameters, could assist clinicians in distinguishing between MACS and NFA.

Topics: Humans; Male; Female; Middle Aged; Hydrocortisone; Retrospective Studies; Adrenal Gland Neoplasms; Case-Control Studies; Leukocytes; Aged; Adult; Diagnosis, Differential; Machine Learning; Adenoma; Adrenocortical Adenoma

PubMed: 39384846
DOI: 10.1038/s41598-024-74452-y

Authors: Ana Silvia Corlan, Anca Maria Cîmpean, Eugen Melnic...

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

Topics: Adenoma; Adenoma, Acidophil; Adenoma, Basophil; Adenoma, Chromophobe; Gene Expression Regulation; Humans; Immunohistochemistry; Pituitary Hormones; Pituitary Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived

PubMed: 30838843
DOI: 10.4081/ejh.2019.3010

Authors: L Symon, J Jakubowski

A consecutive series of 101 pituitary tumours treated in the 10 year period 1968-78 has been examined, giant lesions being excluded. There were 48 female cases and 53 male, women predominating in the ratio of three to two in the age group 40-50 years and men showing a slight predominance in the age group 50-60 years. Most cases presented with visual deterioration which in 22 cases had been present for between one and two years, and in a further 22 for an even longer period, between two and 10 years. All patients underwent subfrontal craniotomy with mainly radical excision of the tumour followed by radiotherapy. The operative mortality was 0.99%. A system of grading of visual field defect has been described and used to compare preoperatively visual loss with postoperative visual recovery. Fifty-six per cent of cases returned to normal vision over the first two years, and a further 37% showed appreciable improvement in visual fields or acuity or both. Six per cent of cases showed no improvement in visual fields, and one patient died of postoperative deep vein thrombosis and pulmonary embolism. The degree of visual improvement has been correlated with the extent of visual defect, length of visual complaint, and size of the tumour. The importance of central and peripheral visual field analysis is emphasised yet again.

Topics: Adenoma, Acidophil; Adenoma, Basophil; Adenoma, Chromophobe; Adult; Aged; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pituitary Neoplasms; Postoperative Complications; Vision Disorders; Visual Acuity; Visual Fields

PubMed: 217970
DOI: 10.1136/jnnp.42.2.123

Authors: H Cushing

Topics: Adenoma, Basophil; Cushing Syndrome; Female; History, 20th Century; Humans; Obesity; Pituitary Neoplasms

PubMed: 16353601
DOI: 10.1002/j.1550-8528.1994.tb00097.x

Authors: H E Macmahon, H G Close, G Hass...

PubMed: 19970135
DOI: No ID Found

Authors: A C CROOKE, H D PURVES, D S RUSSELL...

Topics: Adenoma, Basophil; Basophils; Humans; Neoplasms; Pituitary Gland; Pituitary Neoplasms

PubMed: 13389465
DOI: 10.1177/003591575604901211

Authors: A T Rasmussen, A A Nelson

PubMed: 19970391
DOI: No ID Found

Authors: Julia H Carter, Harry W Carter, James A Deddens...

Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver and the known concentrations of this compound in drinking water, reliable biologically based models to reduce the uncertainty of risk assessment for human exposure to DCA are needed. Development of such models requires identification and quantification of premalignant hepatic lesions, identification of the doses at which these lesions occur, and determination of the likelihood that these lesions will progress to cancer. In this study we determined the dose response of histopathologic changes occurring in the livers of mice exposed to DCA (0.05-3.5 g/L) for 26-100 weeks. Lesions were classified as foci of cellular alteration smaller than one liver lobule (altered hepatic foci; AHF), foci of cellular alteration larger than one liver lobule (large foci of cellular alteration; LFCA), adenomas (ADs), or carcinomas (CAs). Histopathologic analysis of 598 premalignant lesions revealed that (a)) each lesion class had a predominant phenotype; (b)) AHF, LFCA, and AD demonstrated neoplastic progression with time; and (c)) independent of DCA dose and length of exposure effects, some toxic/adaptive changes in non-involved liver were related to this neoplastic progression. A lesion sequence for carcinogenesis in male B6C3F(1) mouse liver has been proposed that will enable development of a biologically based mathematical model for DCA. Because all classes of premalignant lesions and CAs were found at both lower and higher doses, these data are consistent with the conclusion that nongenotoxic mechanisms, such as negative selection, are relevant to DCA carcinogenesis at lower doses where DCA genotoxicity has not been observed.

Topics: Adenoma, Acidophil; Adenoma, Basophil; Adenoma, Liver Cell; Animals; Carcinogenicity Tests; Dichloroacetic Acid; Dose-Response Relationship, Drug; Glycogen; Linear Models; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Necrosis; Rats; Rats, Inbred F344; Water Pollutants

PubMed: 12515679
DOI: 10.1289/ehp.5442

Authors: J Cassar, F H Doyle, P D Lewis...

Eight patients with Nelson's syndrome were treated with a pituitary implant of yttrium-90 or gold-198 four to 16 years after adrenal surgery. All had considerable pigmentation. One already had cranial nerve abnormalities and visual field defects and had had both a craniotomy and deep x-ray treatment. Radiographs showed that the pituitary fossa was abnormal in seven patients. A biopsy performed in six cases showed mucoid (or basophil) adenoma in all. In the four specimens examined ACTH was identified by electron microscopy or immunofluorescence, or both. Patients were followed up after pituitary implantation for three months to 12 years. All showed decreased pigmentation, and six became normal. Four patients regained normal ACTH levels and the other two studied had decreased levels. In no case did new cranial nerve disease or further sellar expansion develop since operation, and two patients showed remodelling of the sella. Complications were temporary leakage of cerebrospinal fluid and diabetes insipidus in one patient and gonadotrophin deficiency in another.

Topics: Adenoma; Adolescent; Adrenalectomy; Adrenocorticotropic Hormone; Adult; Child; Diabetes Insipidus; Female; Gold Radioisotopes; Humans; Male; Middle Aged; Pigmentation Disorders; Pituitary Neoplasms; Radiotherapy Dosage; Yttrium Radioisotopes

PubMed: 182313
DOI: 10.1136/bmj.2.6030.269

Authors: R V Lloyd, L Jin, K Fields...

To study the relationship between null cell adenomas, oncocytomas and gonadotroph adenomas, we analyzed 32 surgically removed formalin-fixed paraffin-embedded pituitary tumors for the expression of pituitary hormone messenger RNAs (mRNAs) by in situ hybridization (ISH). Most tumors were also analyzed for chromogranin A mRNA. To identify the cell type constituting the tumors and to assess hormone content, all tumors were investigated by histology, transmission electron microscopy and immunohistochemistry. Most null cell adenomas (6/11) and gonadotroph adenomas (9/10) expressed the mRNAs for alpha-subunit of glycoprotein hormones whereas only 2/11 oncocytomas expressed alpha-subunit mRNA. FSH beta and/or LH beta mRNA were present in most null cell and gonadotroph adenomas but only in a few oncocytomas. Prolactin (PRL) mRNA was detected in two null cell tumors and in one gonadotroph adenoma, whereas GH and POMC mRNA were present in one null cell adenoma. Chromogranin A mRNA, which codes for the major secretory granule protein, was present in 25/26 tumors including all tumors that were negative for pituitary hormone mRNAs, indicating adequate preservation of specific mRNA transcripts in the paraffin-embedded sections of tumor cells. These results indicate that null cell adenomas and gonadotroph adenomas are closely related neoplasms and that oncocytomas may represent a functionally defective form of null cell adenoma characterized by mitochondrial abundance, which has retained the capacity to synthesize the major secretory granule protein chromogranin A. Although the cytogenesis of null cell adenomas and oncocytomas is not clear, it can be suggested that these two tumor types are derived from a pluripotential precursor cell that is capable of undergoing multidirectional differentiation and synthesizing various hormones, mainly glycoproteins.

Topics: Adenoma; Adenoma, Basophil; Chromogranin A; Chromogranins; Humans; Nucleic Acid Hybridization; Pituitary Hormones; Pituitary Neoplasms; RNA, Messenger

PubMed: 1653518
DOI: No ID Found