Diagnosis and Treatment of Pituitary Apoplexy, A True Endocrine Emergency.

Pituitary apoplexy (PA) is a clinical syndrome resulting from a hemorrhagic infarction of the pituitary gland. It is characterized by the sudden onset of visual disturbances, nausea, vomiting, headache and occasionally, signs of meningeal irritation and an altered mental status. The exact pathogenesis of PA remains to be elucidated, although tumor overgrowth of its blood supply remains the most popular theory. Main risk factors for the development of PA include systemic, iatrogenic, and external factors as well as the presence of an underlying pituitary tumor. The diagnostic approach of PA includes both neuroimaging and evaluation of pituitary secretory function. PA is a potentially life-threatening condition which should be managed with hemodynamic stabilization, correction of electrolyte abnormalities and replacement of hormonal deficiencies. PA treatment should be individualized based on the severity of the clinical picture which may vary widely. Treatment options include conservative management with periodic follow-up or neurosurgical intervention, which should be decided by a multidisciplinary team. We conducted a systematic review of the literature to unveil the frequency of PA predisposing factors, clinical and biochemical presentations, management strategies and outcomes.

The molecular biology of sporadic acromegaly.

GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, transcriptomic, proteomic and kynomic landscape of pituitary tumors. Transcriptomic analysis has allowed us to discover specific transcription factors driving the differentiation of pituitary tumors and gene expression patterns. GH-secreting, along with PRL- and TSH-secreting pitNETs are driven by POU1F1; ACTH-secreting tumors are determined by TBX19; and non-functioning tumors, which are predominantly of gonadotrope differentiation are conditioned by NR5A1. Upregulation of certain miRNAs, such as miR-107, is associated with tumor progression, while downregulation of others, like miR-15a and miR-16-1, correlates with tumor size reduction. Additionally, miRNA expression profiles are linked to treatment resistance and clinical outcomes, providing insights into potential therapeutic targets. Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion.

Combining causal and correlative approaches to discover biomarkers of response to paclitaxel.

We recently discovered a putative paclitaxel response predictive biomarker for glioblastoma and breast cancer using the whole genome CRISPR knockout screen. The biomarker candidate was validated in two independent breast cancer patient cohorts that received taxane treatment. To further evaluate the potential application of this biomarker in the clinic for patients with glioblastoma, a prospective validation in cohorts of patients with glioblastoma is essential and will be performed as part of our ongoing phase II clinical trial (NCT04528680). The validation of novel biomarkers of susceptibility to therapy is critical to elucidate the efficacy signal of therapeutic agents. This is especially important in the context of glioblastoma, where therapeutic benefit is variable and unpredictable, leading to negative trials, yet the outcome of subset of patients has outperformed expectations.

Genomics, Transcriptomics, and Epigenetics of Sporadic Pituitary Tumors.

Pituitary tumors (PT) are highly heterogeneous neoplasms, comprising functioning and nonfunctioning lesions. Functioning PT include prolactinomas, causing amenorrhea-galactorrhea in women and sexual dysfunction in men; GH-secreting adenomas causing acromegaly-gigantism; ACTH-secreting corticotrophinomas causing Cushing disease (CD); and the rare TSH-secreting thyrotrophinomas that result in central hyperthyroidism. Nonfunctioning PT do not result in a hormonal hypersecretion syndrome and most of them are of gonadotrope differentiation; other non-functioning PT include null cell adenomas and silent ACTH-, GH- and PRL-adenomas. Less than 5% of PT occur in a familial or syndromic context whereby germline mutations of specific genes account for their molecular pathogenesis. In contrast, the more common sporadic PT do not result from a single molecular abnormality but rather emerge from several oncogenic events that culminate in an increased proliferation of pituitary cells, and in the case of functioning tumors, in a non-regulated hormonal hypersecretion. In recent years, important advances in the understanding of the molecular pathogenesis of PT have been made, including the genomic, transcriptomic, epigenetic, and proteomic characterization of these neoplasms. In this review, we summarize the available molecular information pertaining the oncogenesis of PT.

Langerhans Cell Histiocytosis Presented as Persistent Diaper Dermatitis: A Case Report.

Langerhans cell histiocytosis presents most frequently in pediatric patients with cutaneous manifestations such as erythematous and scaly papules in the trunk or scalp and macerated plaques in intertriginous sites. We present a case of a seven-month-old patient who was brought with complaints of persistent diaper rash. The patient presented with skin fissures in intertriginous areas and pink color papules dispersed widely in the trunk and perineum. The skin biopsy revealed infiltration of abundant histiocytes, eosinophils, lymphocytes, and plasma cells, being CD207, CD1a, and S-100 positive by immunohistochemistry. Due to the diversified presentations of Langerhans cell histiocytosis and its propensity to mimic other dermatological conditions, physicians should have a clinical suspicion of this disease and consider it as a differential diagnosis among common skin diseases in pediatric patients.

Bilateral carotid body tumor case: A novel preoperative management.

Paragangliomas are rare neuroendocrine neoplasms. The most common form of these tumors in head and neck are non-functional carotid body tumors. These neoplasms may present an extensive growth and compromise vital neurovascular structures in the neck, such as carotid vessels. Carotid body tumors usually present clinically as painless neck masses and occur most frequently in adults averaging 45 to 50 years, being the majority of these tumors unilateral and only 5% of all cases bilateral. The main treatment for carotid body paragangliomas is surgical resection, which can be extremely challenging due to tumor hypervascularity and significant blood loss. We present a bilateral carotid body tumor case in a 61-year-old woman who presented due to a pulsatile and painless mass in the right carotid region of the neck of 1-year of evolution. The tumor was found encasing the external carotid artery and classified as Shamblin II. A novel approach for preoperative management was performed, placing a covered graft-stent in the right common and proximal (C1) internal carotid arteries in order to splint and provide structural protection for carotid vessels during surgical resection and temporarily reduce blood flow of the carotid body tumor.

Atypical Cutaneous Leishmaniasis Variant.

Leishmaniasis is a complex group of parasitic infectious diseases caused by intracellular protozoa of the genus Leishmania. It is a zoonosis mainly transmitted by the bite of infected female Phlebotomus or Lutzomyia sandflies. Clinical manifestations of leishmaniasis are diverse and can range from asymptomatic presentations to disseminated systemic disease. Cutaneous leishmaniasis is endemic in more than 80 countries in the world, having a predominance in tropical and subtropical regions. Although the majority of cases follow a classic development, an increasing number of new and rare variants of cutaneous leishmaniasis have been reported. These variants should be suspected as a cause of diverse clinical presentations, especially in endemic regions and travelers, being a diagnostic challenge for physicians. We present a case of atypical cutaneous leishmaniasis found as a single verrucous plaque of eight months of evolution in the left posterior thigh of a 35-year-old man, who presented mild pruritus. The patient reported shrimp farming as his main occupational activity and was living in a rural region surrounded by forest on the Pacific coast of Ecuador. On dermatological examination, a single 4 x 5 cm verrucous plaque with irregular borders and a scaly erythematous violaceous aspect was found. Histopathological analysis revealed the presence of lymphohistiocytic inflammatory infiltrate with plasmocytes and granulomatous inflammation. On the Giemsa stain, intracellular amastigotes (Leishman-Donovan bodies) were observed. The treatment consisted of intramuscular meglumine antimoniate, presenting significant improvement on follow-up.