Understanding Progestins: From Basics to Clinical Applicability.

Progestin is a term used to describe a synthetic progestogen. The activity and potency of synthetic progestins are mostly evaluated via parameters associated with their endometrial effects, which are related to their interactions with progesterone, estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. The chemical structure of progestins is the key to understanding their interactions with these receptors and predicting the other effects associated with these drugs. Due to their endometrial effect, progestins are used for different gynecological conditions, such as endometriosis, contraception, hormonal replacement therapy, and artificial reproduction techniques. This review is focused on improving our knowledge of progestins (from their history and biochemical effects related to their chemical structures to clinical applications in gynecological conditions) in order to improve clinical practice.

Silent pituitary plurihormonal adenoma: clinical relevance of immunohistochemical analysis / Adenoma hipofisario silente plurihormonal: relevancia clínica de la inmunohistoquímica

Background: Non-functional pituitary adenomas (NFPAs) present low growth rates; however, some are aggressive and invasive. In 2017 the World Health Organization recognized clinically aggressive adenomas as "high-risk pituitary adenomas". These include the sparsely granulated somatotroph adenoma, the Crooke's cell adenoma, the silent corticotroph adenoma and the plurihormonal Pit-1-positive adenoma (subtype 3). Clinical case: 25-year-old woman who presented oligomenorrhea, increased weight, decreased visual acuity and chronic headache. Biochemical and imaging evaluation showed a NFPA. Transsphenoidal surgery was performed with complete resection of lesion, and during short-term follow-up it was observed recurrence, which is why the patient needed two more interventions. The immunohistochemistry reported: ACTH ++ 90%, prolactin ++ 20%, GH ++ 5%, CKAE1-AE3 +++ 90%, Ki-67 10%. The final diagnosis was plurihormonal adenoma, since the immunohistochemical analysis was positive for more than one pituitary hormone and suggested two distinct cell lineages: Pit-1 and Tpit, both recognized as aggressive adenomas. Conclusions: This case report highlights the significance of a comprehensive immunohistochemical study, which includes transcriptional factors to classify cell lineage, in order to predict aggressiveness and provide personalized treatment.

Introducción: los adenomas hipofisarios no funcionantes (AHNF) presentan una baja tasa de crecimiento; sin embargo, algunos son agresivos e invasivos. En 2017 la Organización Mundial de la Salud denominó los adenomas de comportamiento clínico agresivo como "tumores hipofisarios de alto riesgo", incluyendo los adenomas del somatotropo escasamente granulados, los adenomas de células de Crooke, los silentes de corticotropo y los adenomas plurihormonal Pit-1 positivo (subtipo 3). Caso clínico: mujer de 25 años de edad con oligoamenorrea, aumento de peso, disminución del campo visual y cefalea crónica. La evaluación bioquímica y de imagen correspondió a un AHNF. Se realizó cirugía transesfenoidal con resección completa de la lesión y durante el seguimiento a corto plazo se observó recurrencia tumoral, por lo que ameritó dos intervenciones más. La inmunohistoquímica reportó: ACTH ++ 90%, prolactina ++ 20%, GH ++ 5%, CKAE1-AE3 +++ 90%, Ki-67 10%. El diagnóstico definitivo correspondió a un adenoma plurihormonal, debido a que la inmunohistoquímica fue positiva para la expresión de más de una hormona hipofisaria, con sugerencia de contenido celular con dos linajes distintos, tanto de Pit-1 como de Tpit, ambos reportados como adenomas agresivos. Conclusiones: este caso resalta la importancia de una inmunohistoquímica completa que incluya factores de transcripción que permitan clasificar el linaje celular para predecir agresividad y proporcionar un tratamiento individualizado.

Difficult-to-diagnose diabetes in a patient treated with cyclophosphamide - the contradictory roles of immunosuppressant agents: a case report.

BACKGROUND: Cyclophosphamide may induce autoimmune diabetes through a decrease in suppressor T cells and increase of proinflammatory T helper type 1 response in animal models. In humans, this association is not as clear due to the presence of other risk factors for hyperglycemia, but it could be a precipitant for acute complications. CASE PRESENTATION: A 31-year-old Mestizo-Mexican woman with a history of systemic lupus erythematosus presented with severe diabetic ketoacidosis, shortly after initiating a multi-drug immunosuppressive therapy. She did not meet the diagnostic criteria for type 1 or type 2 diabetes and had no family history of hyperglycemic states. She persisted with hyperglycemia and high insulin requirements until the discontinuation of cyclophosphamide. After this episode, she recovered her endogenous insulin production and the antidiabetic agents were successfully withdrawn. After 1 year of follow up she is still normoglycemic. CONCLUSION: Cyclophosphamide may be an additional risk factor for acute hyperglycemic crisis. Glucose monitoring could be recommended during and after this treatment.