Clinical characteristics of functioning gonadotroph adenoma in women presenting with ovarian hyperstimulation: Audit of UK pituitary centres.

OBJECTIVE: Functioning gonadotroph adenomas (FGAs) are rare pituitary tumours stimulating ovarian function with potential life-threatening consequences in women. However, a lack of aggregated clinical experience of FGAs impairs management in affected women. The aim of this study is to present the clinical course of FGA-induced ovarian hyperstimulation syndrome (OHSS) cases as identified by some of the largest UK pituitary endocrine tertiary centres with a view to increasing awareness and improving diagnosis and management of women with FGA. DESIGN: A retrospective observational study; audit of eight UK regional pituitary centres for cases of FGAs. SETTING: Specialist neuroendocrine centres in the United Kingdom. PATIENTS AND MEASUREMENTS: Women diagnosed with FGA-induced OHSS. Description of their clinical course. RESULTS: Seven cases of FGA were identified in women, all causing OHSS. Mean age was 33.4 years at diagnosis. Abdominal pain, irregular periods, headache, and visual disturbances were reported at presentation by 100%, 71%, 57% and 43% of women, respectively. Three of seven women underwent ovarian surgery before FGA diagnosis. Six women underwent transsphenoidal surgery (TSS) with incomplete tumour resection in five of those, but all showed improvement or resolution in symptoms and biochemistry postoperatively. CONCLUSION: FGA is a rare cause of spontaneous OHSS. TSS improves clinical and biochemical features of ovarian hyperstimulation in FGAs. Improved awareness of FGA will prevent inappropriate emergency ovarian surgery.

Cardiovascular health and mortality in Cushing's disease.

Exposure to cortisol excess in Cushing's disease (CD) results in increased cardiovascular morbidity and reduces survival, with cardiovascular disease being a leading cause of death. At diagnosis, a significant number of patients have adverse cardiovascular profiles (e.g., obesity, diabetes or impaired glucose tolerance, dyslipidemia, hypertension, cardiac abnormalities and vascular disease). Remission of hypercortisolemia reduces but does not completely eliminate the cardiovascular complications; hazard ratios for myocardial infarction and stroke are high during long-term monitoring, highlighting the long-lasting effects of hypercortisolism and the importance of the timely diagnosis and successful management of this condition. Data on mortality of patients in remission are not consistent but in a multicenter study, an increased all-cause and circulatory mortality in patients with CD in remission for at least 10 years has been demonstrated. Cardiovascular morbidity requires particular focus and effective management during the care of patients with CD, from their presentation until long-term follow up.

Central diabetes insipidus (vasopressin deficiency) after surgery for pituitary tumours: a systematic review and meta-analysis.

OBJECTIVE: Central diabetes insipidus or vasopressin deficiency (AVP-D) is the most frequent water balance disorder after transsphenoidal surgery (TSS) with variable prevalence amongst studies. We aimed to determine rates of newly developed transient or permanent AVP-D in patients with pituitary tumours treated with TSS. DESIGN AND METHODS: We performed systematic review of Medline, Embase, and Cochrane Library between January 1, 2000 and January 31, 2021 for studies reporting on outcomes for pituitary adenoma, craniopharyngioma, and Rathke's cleft cyst (RCC) after TSS and providing definition of post-operative AVP-D. We pooled the results as proportions with 95% confidence intervals (CIs) using Freeman-Tukey transformation random effects meta-analysis. RESULTS: From 11 694 studies, 51 were included. Rates of transient or permanent AVP-D were: 17% (95% CI, 13-21) and 3% (95% CI, 2-5) in total group, 16% (95% CI, 12-21) and 2% (95% CI, 2-3) in pituitary adenomas, 31% (95% CI, 24-39) and 30% (95% CI, 22-39) in craniopharyngiomas, and 35% (95% CI, 16-57) and 14% (95% CI, 6-23) in RCCs, respectively. Based on diagnostic criteria, rates of transient or permanent AVP-D were: For hypotonic polyuria, 14% (95% CI, 8-22) and 3% (95% CI, 1-4), for hypotonic polyuria and hypernatraemia, 21% (95% CI, 13-29) and 5% (95% CI, 2-11), and for desmopressin administration, 22% (95% CI, 15-29) and 9% (95% CI, 0-30), respectively. CONCLUSIONS: Following TSS, a small proportion of patients with pituitary adenoma have permanent AVP-D (2%), but prevalence reaches 30% in ones with craniopharyngioma and 14% in those with RCC. Diagnostic criteria for post-operative AVP-D remain variable affecting reported rates of this condition.

The diagnosis and management of Cushing's syndrome in pregnancy.

Endogenous Cushing's syndrome (CS) is rarely encountered during pregnancy. Clinical and biochemical changes in healthy pregnancy overlap with those seen in pregnancy complicated by CS; the diagnosis is therefore challenging and can be delayed. During normal gestation, adrenocorticotrophic hormone, corticotrophin-releasing hormone, cortisol, and urinary free cortisol levels rise. Dexamethasone administration fails to fully suppress cortisol in pregnant women without CS. Localisation may be hindered by non-suppressed adrenocorticotrophic hormone levels in a large proportion of those with adrenal CS; smaller corticotroph adenomas may go undetected as a result of a lack of contrast administration or the presence of pituitary hyperplasia; and inferior petrosal sinus sampling is not recommended given the risk of radiation and thrombosis. Yet, diagnosis is essential; active disease is associated with multiple insults to both maternal and foetal health, and those cured may normalise the risk of maternal-foetal complications. The published literature consists mostly of case reports or small case series affected by publication bias, heterogeneous definitions of maternal or foetal outcomes or lack of detail on severity of hypercortisolism. Consequently, conclusive recommendations, or a standardised management approach for all, cannot be made. Management is highly individualised: the decision for surgery, medical control of hypercortisolism or adoption of a conservative approach is dependent on the timing of diagnosis (respective to stage of gestation), the ability to localise the tumour, severity of CS, pre-existing maternal comorbidity, and, ultimately, patient choice. Close communication is a necessity with the patient placed at the centre of all decisions, with risks, benefits, and uncertainties around any investigation and management carefully discussed. Care should be delivered by an experienced, multidisciplinary team, with the resources and expertise available to manage such a rare and challenging condition during pregnancy.

A quality improvement project reducing adverse events and improving adherence to guidelines surrounding VRIII usage.

Variable rate intravenous insulin infusions (VRIII) are frequently used in hospitals and incorrect use can lead to electrolyte imbalance, hypoglycaemia and adverse outcomes. The Joint British Diabetes Societies (JDBS) published guidelines in 2014 and recommended the use of a balanced fluid as substrate. There was no published data to demonstrate the superiority of this fluid in reducing adverse events. This quality improvement project aimed to review the existing practice at our Trust in accordance with JDBS guidelines. We predicted introducing this fluid would reduce adverse events and demonstrating this was a prerequisite condition from our Trust Medicines Management Committee to approve its long-term availability. We carried out an audit of our practice in 2015, at which time the JBDS recommended fluid (0.45% sodium chloride/5% dextrose with 0.15% potassium chloride) was not available in our Trust. Our VRIII guideline was re-written with recommendation for use of the balanced fluid, after procurement from pharmacy. Our primary areas for improvement as highlighted from the 2015 audit were correct substrate prescription and rate reduction of hypokalaemia (potassium <3.5 mmol/L) and hypoglycaemia (glucose <4 mmol/L) during VRIII use. Analysis of the pre-intervention (December 2016) and post-intervention (September-November 2017) data showed a significant increase in correct fluid use; 11% pre-intervention to 76% post-intervention (χ2, p<0.0001). The number of hypoglycaemic events per VRIII reduced from 0.73 (±1.78) to 0.28 (±0.84) (p<0.05) peri-intervention. Similarly, the number of hypokalaemic events per VRIII reduced from 0.15 (±0.54) pre-intervention to 0.05 (±0.25) post-intervention. There was also a significant reduction in number of VRIII episodes associated with a hyponatraemia event from 26% at baseline to 12% post-intervention (p<0.01). Some of these marked improvements were not sustained at 1-year post follow-up. We reduced adverse outcomes with a substantial net-cost saving during this period, through implementation of new and accessible guidelines, trust-wide education programmes and posters to raise awareness.

Rathke's Cleft Cyst Abscess with a Very Unusual Course.

Infected Rathke's cleft cysts (RCC) are extremely rare with only a few published cases. We report the case of a 31-year-old man who presented with headaches, visual disturbance, and hypopituitarism secondary to an infected RCC with extension of abscesses along the optic tract. Magnetic resonance imaging showed ring enhancing cystic lesions within an expanded sella with suprasellar and intraparenchymal extension. The radiological appearance suggested a high-grade optic glioma, but an endoscopic transsphenoidal biopsy revealed frank pus in the pituitary fossa, which subsequently grew Staphylococcus aureus . Pathological examination of the cyst wall showed an inflamed RCC. Following a prolonged course of intravenous antibiotics, the infection resolved and vision improved. RCC abscesses are rare and the intracranial extension of the infection in our case makes it unique.