Hip fracture, pre-fracture status.

IntroductionKetoconazole has long been the first-line medical therapy for controlling hypercortisolism secondary to either pituitary or adrenal pathology. However, it is largely unavailable in most countries. As a result, we have turned to fluconazole as a viable alternative in view of its favourable safety profile.Case PresentationA 50-year-old lady developed recurrent Cushing’s disease after being in remission following transsphenoidal surgery (TSS) for a left pituitary microadenoma 16 years ago. The repeat MRI showed a right pituitary microadenoma (1.7 mm × 1.3 mm) for which she underwent a second TSS. However, she continued to have persistent hypercortisolism despite repeated MRIs showing absence of tumour recurrence. She refused bilateral adrenalectomy and external radiotherapy. Ketoconazole was commenced at 200 mg twice daily for disease control but this was hindered by intolerable side effects including pruritus and skin exfoliation. In the meantime, she suffered a right hypertensive basal ganglia hemorrhage. Treatment was subsequently switched to cabergoline and the dose titrated to 0.5 mg daily. Fluconazole 400 mg daily was later added to control the persistent disease. Her clinical and biochemical parameters improved markedly three months after the addition of fluconazole. No adverse event was reported. Her disease has remained stable for the last 15 months up until the time of the recent clinic review.ConclusionsThis case demonstrates the long-term efficacy of fluconazole in tandem with cabergoline for the control of recurrent Cushing’s disease.

Introduction: Candida organisms are opportunistic fungal pathogens that have become a major cause of nosocomial infections worldwide. We investigated the clinical characteristics and outcomes of hospitalized patients with candidaemia caused by Candida albicans and non-albicans Candida spp at HUSM. Materials and Methods: We retrospectively evaluated all hospitalized patients with candidaemia from January 2010 till December 2014 based on inpatient hospital records and laboratory data. Results: A total of 134 patients with candidaemia were enrolled. Candida albicans and non-albicans Candida spp were responsible for 20% (27/134) and 80% (107/134) of candidaemia cases, respectively. Hospitalized patients with diabetes mellitus, surgical conditions, or concomitant septicaemia and those who received instrumentations such as CVC or CBD, and those admitted under medical settings were prone to develop candidaemia caused by either C. albicans or non-albicans Candida spp. All isolates were susceptible to Fluconazole except for C. krusei isolates. All-cause mortality within 30 days post diagnosis of candidaemia was 59%. Factors associated with mortality were solid tumor (p =0.014), surgical illness (p=0.128), central venous catheterization (p= 0.096) and leucocytosis (p=0.116). Only solid tumor was an independent contributory factor for mortality among patients with C. albicans candidaemia in the multivariate analyses (OR 5.09, 95% CI 1.38,18.74, p=0.014). Conclusions: The patients’ clinical characteristics were fairly comparable between Candida albicans and non-albicans candidaemia. The changing epidemiology of candidaemia at this centre was in fact alarming. The outcome associated with candidaemia was poor.

Oestrogen (17β-oestradiol or E2) is a crucial regulator of the synthesis and secretion of pituitary reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL). In this review, we summarise the role of oestrogen receptors in non-functioning pituitary neuroendocrine tumors (NF-Pitnets), focusing on the immunoexpression and gonadotroph cell proliferation and apoptosis. Gonadotroph tumors are the most common subtype of NF-Pitnets. Two major oestrogen receptor (ER) isoforms expressed in the pituitary are oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ). Overall, oestrogen actions are mostly exerted through the ERα isoform on the pituitary. The G protein-coupled oestrogen receptor (GPER) located at the plasma membrane may contribute to non-genomic effects of oestrogen. Nuclear immunoreactivity for ERα and ERβ were highest among gonadotroph and null cell tumors. Silent corticotroph tumors are the least immunoreactive for both receptors. A significantly elevated ERα expression was observed in macroadenomas compared to microadenomas. ERα and ERβ may act in opposite directions to regulate the Slug-E-cadherin pathway and to affect invasiveness of NF-Pitnets. In the cellular pathway, ERs regulate oestrogen induced proliferation and differentiation and impact several signalling pathways including the MAPK and PI3K/Akt pathway. Oestrogen was the first-discovered inducer of pituitary tumor transforming gene 1 (PTTG1) that was abundantly expressed in NF-Pitnets. ERα can be a potential biomarker for predicting tumor size and invasiveness as well as therapeutic target for NF-Pitnets. SERMs or antiestrogen may represent as an alternative choice for the treatment of NF-Pitnets.