Human immune deficiency virus (HIV) infection and the hypothalamic pituitary adrenal axis.

The hypothalamic pituitary adrenal (HPA) axis is the most common of the endocrine lines/axis' to be affected by HIV infection. There are multiple factors that contribute to this HPA axis dysregulation. Direct invasion of the various organs in the axis can be either by opportunistic infections or infiltrative diseases. The soluble factors or cytokines released during viral infection and the chronic inflammatory state that follows, also contribute to these alterations. The actions of these cytokines released by the immune response can both activate the HPA axis and cause a glucocorticoid resistant state. Further, many of the anti-retroviral and other medications used to treat HIV infection can contribute to HPA axis dysfunction. While the diagnosis and treatment of endocrine dysfunction is the same as in any other patient, management pathways may be quite different. While some may be adaptive responses, life threatening adrenal insufficiency can also be present. It is important the latter be picked up expeditiously and treated promptly to avoid mortality.

Current treatment options for type 2 diabetes mellitus in youth: today's realities and lessons from the TODAY study.

The incidence of type 2 diabetes in children and adolescents has increased over the last 2 decades, paralleled by an increase in obesity over the same time period. Although the value of lifestyle modification in obese youth is unquestioned, scant evidence for optimal treatment of type 2 diabetes in this age group exists. Despite recent therapeutic drug trials, metformin and insulin are the only medicines currently approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes in youth. Because of recently amended pharmaceutical regulations, however, it is likely that more antidiabetic medications soon will be added to the armamentarium of therapeutic options for youth with type 2 diabetes. Additionally, the recently published TODAY study comparing safety and efficacy of three treatment regimens in maintaining glycemic control in youth with type 2 diabetes has shed new light on the problem.

Isolated mild clitoral hypertrophy may reveal 46,XY disorders of sex development in infancy due to 17ßHSD-3 defect confirmed by molecular analysis.

AIMS: 17-ß-Hydroxysteroid dehydrogenase type 3 (17ßHSD-3) is expressed exclusively in the testes where it converts Δ4 androstenedione (Δ4) to testosterone (T). Here, we report a patient with a rare mutation at a critical site in HSD17B3 gene leading to deficiency of 17ß HSD-3 enzyme. METHODS: We describe a 3-year old healthy female of consanguineous Lebanese descent, who presented to the endocrine service with isolated mild clitoromegaly. Adrenocorticotropic hormone (ACTH) and human chorionic gonadotrophin (hCG) stimulation tests were performed. Genes for sex-determining region Y (SRY), steroidogenic factor-1 (SF-1) and 17ßHSD-3 (HSD17B3) were sequenced. RESULTS: The post-hCG stimulation T levels and T/Δ4 ratio was low. Patient had a 46,XY karyotype. Sequence analysis of the HSD17B3 gene revealed a homozygous R80W missense mutation on exon 3. No mutation was found in SRY and SF1 genes. Mullerian structures were not detected on pelvic imaging. CONCLUSIONS: A low T/Δ4 ratio is indicative of 17ßHSD-3 deficiency and associated with isolated clitoromegaly. The R80 site is critical for NADPH binding, thus the mutation at this site leads to 17ßHSD-3 deficiency presenting as 46,XY disorder of sex development.

The clinical and molecular heterogeneity of 17ßHSD-3 enzyme deficiency.

17-ß-Hydroxysteroid dehydrogenase type 3 (17ßHSD-3) deficiency is a rare, but frequently misdiagnosed autosomal recessive cause of 46,XY disorder of sex development (DSD). 17ßHSD-3 enzyme is present almost exclusively in the testes and converts Δ4-androstenedione (Δ4) to testosterone (T). The diagnosis can be easily missed in early childhood as the clinical presentation may be subtle. Any young girl with an inguinal hernia, mild clitoromegaly, single urethral opening or urogenital sinus should raise suspicion. If not diagnosed early, patients present with severe virilization and primary amenorrhea in adolescence and may undergo a change from a female to male gender role. A low T/Δ4 ratio on baseline or hCG (human chorionic gonadotropin)-stimulated testing is suggestive of 17ßHSD-3 deficiency. The diagnosis can be confirmed with molecular genetic studies. This review summarizes the clinical presentations, reported mutations, diagnosis, treatment and clinical course of this disorder. The Arg80 site in exon 3 is the most common location of repeated mutations and can be considered a hot spot in certain Arab populations.