Search Results (6)

Background: Feminizing adrenocortical tumors (FATs) are an exceedingly rare subset of adrenal neoplasms, typically affecting adult men and characterized by an excess of estrogen, suppressed gonadotropins, and gynecomastia. Most FATs are malignant, with a poor prognosis and a high risk of recurrence. Case Presentation: We report the case of a 24-year-old male with bilateral gynecomastia, abdominal mass symptoms, and one year of unexplained infertility. A hormonal evaluation revealed elevated estradiol (90.1 pg/mL) and suppressed ACTH (2.6 pg/mL), with inappropriately normal cortisol levels (12.1 µg/dL). Imaging identified a right adrenal mass. The patient underwent open adrenalectomy, and histopathology confirmed stage II adrenocortical carcinoma (T2NxM0) with autonomous estradiol secretion, negative margins, and a Ki-67 index of 10%. Postoperatively, gonadal function normalized, and infertility resolved at two months. The multidisciplinary tumor board considered but did not initiate adjuvant mitotane, given the completely resected low-stage disease. Conclusions: This case illustrates the rare presentation of feminizing adrenocortical carcinoma with reversible infertility and highlights the importance of early recognition and close surveillance. In addition, our literature review of 12 male cases reported between 2015 and 2025 emphasizes gynecomastia as the hallmark presentation and discusses emerging evidence supporting active surveillance as a potential alternative to adjuvant mitotane in selected low-risk patients. Full article

Ectopic adrenocorticotropic hormone syndrome (EAS) occurs when a tumor develops neuroendocrine differentiation with the secretion of ACTH resulting in hypercortisolism and possibly Cushing’s syndrome (CS). Only 5–10% of CS cases are attributed to EAS; of these, breast tumors comprise less than 1%. Two known variants of breast neuroendocrine tumors include neuroendocrine-differentiated carcinoma and ductal carcinoma with neuroendocrine features. Currently, guidelines for treatment are limited and EAS is associated with significant morbidity and mortality. A 39-year-old female presented with a rapidly enlarging breast mass. Biopsy demonstrated invasive poorly differentiated breast carcinoma with high-grade neuroendocrine features and necrosis. Staging at diagnosis confirmed metastatic disease of the liver and bone. First-line chemotherapy (Cisplatin/Etoposide/Durvalumab) was initiated with evidence of disease progression after four cycles. Given a poor response to therapy, a simple mastectomy was performed for local control and complete pathologic analysis, demonstrating high-grade neuroendocrine carcinoma with large-cell features. Second-line therapy (Adriamycin/Cyclophosphamide) was initiated for three cycles after which the patient required admission for severe and refractory hypokalemia. Workup confirmed elevated ACTH consistent with paraneoplastic EAS and further evidence of disease progression. Third-line therapy (Nab-Paclitaxel) was initiated, and genetic testing was completed, confirming the PIK3 mutation, for which access to Alpelisib therapy was requested. Given symptoms of progressive severe CS with significant liver disease limiting medical therapies, the patient underwent urgent bilateral laparoscopic adrenalectomy after which she was able to be discharged home while awaiting additional systemic therapy. EAS resulting in CS secondary to breast neuroendocrine carcinoma is a rare and challenging diagnosis. Further research is needed to inform treatment guidelines to improve outcomes. While patient survival is dependent upon the underlying disease process, laparoscopic bilateral adrenalectomy is an accepted, definitive treatment option. Full article

Although polycystic ovary syndrome (PCOS) is primarily considered a hyperandrogenic disorder in women characterized by hirsutism, menstrual irregularity, and polycystic ovarian morphology, an endocrinological investigation should be performed to rule out other hyperandrogenic disorders (e.g., virilizing tumors, non-classical congenital adrenal hyperplasia (NCAH), hyperprolactinemia, and Cushing’s syndrome) to make a certain diagnosis. PCOS and androgen excess disorders share clinical features such as findings due to hyperandrogenism, findings of metabolic syndrome, and menstrual abnormalities. The diagnosis of a woman with these symptoms is generally determined based on the patient’s history and rigorous clinical examination. Therefore, distinguishing PCOS from adrenal-originated androgen excess is an indispensable step in diagnosis. In addition to an appropriate medical history and physical examination, the measurement of relevant basal hormone levels and dynamic tests are required. A dexamethasone suppression test is used routinely to make a differential diagnosis between Cushing’s syndrome and PCOS. The most important parameter for differentiating PCOS from NCAH is the measurement of basal and ACTH-stimulated 17-OH progesterone (17-OHP) when required in the early follicular period. It should be kept in mind that rapidly progressive hyperandrogenic manifestations such as hirsutism may be due to an androgen-secreting adrenocortical carcinoma. This review discusses the pathophysiology of androgen excess of both adrenal and ovarian origins; outlines the conditions which lead to androgen excess; and aims to facilitate the differential diagnosis of PCOS from certain adrenal disorders. Full article

Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors. Full article

Adrenocortical carcinoma is a heterogeneous and aggressive cancer that originates from steroidogenic cells within the adrenal cortex. In this study, we have assessed for the preclinical gold standard NCI-H295 in direct comparison with the more recently established MUC-1 and a here newly reported ACC cell line (TVBF-7) the mutational status of important driver genes (TP53, MEN1, PRKAR1A, CTNNB1, APC, ZNRF-3, IGF-2, EGFR, RB1, BRCA1, BRCA2, RET, GNAS and PTEN), Wnt-signaling specificities (CTNNB1 mutation vs. APC mutation vs. wildtype), steroidogenic-(CYP11A1, CYP17A1, HSD3B2, HSD17B4, CYP21A2, CYP11B1, CYP11B2, MC2R, AT1R) and nuclear-receptor-signaling (AR, ER, GCR), varying electrophysiological potentials as well as highly individual hormone secretion profiles (Cortisol, Aldosterone, DHEA, DHEAS, Testosterone, 17-OH Progesterone, among others) which were investigated under basal and stimulated conditions (ACTH, AngII, FSK). Our findings reveal important genetic and pathophysiological characteristics for these three cell lines and reveal the importance of such cell-line panels reflecting differential endocrine functionalities to thereby better reflect clinically well-known ACC patient heterogeneities in preclinical studies. Full article

Background: Many studies show the occurrence of several multiple endocrine neoplasia syndromes caused by different mutations, for example, in MEN1 and RET genes. Nevertheless, there are less common mutations causing multiple endocrine glands tumors. Examples of such mutations are CHEK2 gene mutations, causing breast, kidney, gastric, colorectal, prostate, lung, ovarian, and thyroid cancers. Case description: In 2005, a 30-year-old woman was admitted to the hospital due to uncontrolled hypertension and obesity. Performed tests have shown ACTH (adrenocorticotropic hormone)—independent micronodular adrenal hyperplasia (AIMAH) as a cause. In 2010, the further diagnostic analysis revealed Cushing’s disease caused by ACTH-secreting pituitary microadenoma. Additionally, in 2011, the patient underwent the strumectomy of multinodular struma. Papillary thyroid carcinoma was found in the excised tissue. In 2018, transvaginal ultrasonography revealed a tumor of the right ovary. After a performed hysterectomy with bilateral salpingo-oophorectomy, the histopathology result has shown female adnexal tumors of probable Wolffian origin (FATWO) located in the broad ligament of the uterus. Due to the history of multiglandular diseases, the patient was referred to genetic testing. We found a positive pathogenic mutation in CHEK2-suppressor gene involved in DNA repair, cell cycle arrest, and apoptosis in response to DNA damage. Conclusion: CHEK2 variants may predispose to a range of endocrine glands tumors, including those identified in our patient. Multiple endocrine glands tumors, as in the presented patient, are a serious problem of public health, due to numerous hospitalizations and necessary repeated surgical treatments. Moreover, the association between CHEK2 and ovarian cancer can be a serious problem with reproductive health. Full article