Niki Karavitaki

Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK).

Backgroundu2002 Pituitary adenomas (PAs) are associated with increased morbidity and mortality. The optimal delivery of services and the provision of care for patients with PAs require distribution of the resources proportionate to the impact of these conditions on the community. Currently, the resource allocation for PAs in the health care system is lacking a reliable and an up‐to‐date epidemiological background that would reflect the recent advances in the diagnostic technologies, leading to the earlier recognition of these tumours.

Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up.

Backgroundu2002 Craniopharyngiomas account for 2–5% of all primary intracranial tumours. Despite their benign histological appearance, they are often associated with an unfavourable prognosis and their optimal treatment remains controversial.

Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma

Backgroundu2002 The differentiation of a pituitary non‐functioning macroadenoma from a macroprolactinoma is important for planning appropriate therapy. Serum PRL levels have been suggested as a useful diagnostic indicator. However, values between 2500 and 8000 mU/l are a grey area and are currently associated with diagnostic uncertainty.

What is the natural history of nonoperated nonfunctioning pituitary adenomas

Backgroundu2002 Series of patients systematically investigating the outcome of clinically nonfunctioning pituitary adenomas (NFAs) not treated by surgery or radiotherapy during long follow‐up periods are limited. Most reports involve the follow‐up of selected cases of incidentally found lesions, rendering their results unreliable on the assessment of the pros and cons of a ‘watch and wait’ policy.

MECHANISMS IN ENDOCRINOLOGY: Ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review

Ipilimumab (Yervoy; Medarex and Bristol-Myers Squibb) is a human MAB against cytotoxic T-lymphocyte antigen 4, which enhances co-stimulation of cytotoxic T-lymphocytes, resulting in their proliferation and an anti-tumour response. It is licensed for the treatment of unresectable or metastatic malignant melanoma, while multiple clinical trials using this medication in the treatment of other malignancies are ongoing. As a clinical response to ipilimumab results from immunostimulation, predictably it generates autoimmunity as well, causing immune-related adverse events in the majority of patients. Of those, endocrinopathies are frequently seen, and in particular, autoimmune lymphocytic hypophysitis with anterior panhypopituitarism has been reported a number of times in North America. We present a case of a male referred to our department with manifestations of anterior panhypopituitarism after his third dose of ipilimumab for metastatic malignant melanoma, and we discuss the management of his case in the light of previous reports. We also review the published literature on the presenting symptoms, time to presentation, investigations, imaging, treatment and follow-up of ipilimumab-induced autoimmune lymphocytic hypophysitis.

Valvular heart disease and the use of cabergoline for the treatment of prolactinoma

Objectiveu2002 The use of high doses of the ergot‐derived dopamine agonist cabergoline (> 3 mg/day), especially with cumulative doses > 4000 mg, has been associated with an increase in cardiac valvular thickening and significant (moderate to severe) regurgitation. Whether lower doses commonly used in the treatment of prolactinomas (0·25–3 mg/week) are also associated with significant valvulopathy is controversial. The mitral valve tenting area, a subclinical index of leaflet stiffening, has also been correlated with the cumulative dose of cabergoline and severity of valvular regurgitation.

Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway.

CONTEXTnSomatotroph adenomas harboring aryl hydrocarbon receptor interacting protein (AIP) mutations respond less well to somatostatin analogs, suggesting that the effects of somatostatin analogs may be mediated by AIP.nnnOBJECTIVEnThe objective of the investigation was to study the involvement of AIP in the mechanism of effect of somatostatin analogs.nnnDESIGNnIn the human study, a 16-wk somatostatin analog pretreatment compared with no pretreatment. In the in vitro cell line study, the effect of somatostatin analog treatment or small interfering RNA (siRNA)/plasmid transfection were studied.nnnSETTINGnThe study was conducted at a university hospital.nnnPATIENTSnThirty-nine sporadic and 10 familial acromegaly patients participated in the study.nnnINTERVENTIONnInterventions included preoperative lanreotide treatment and pituitary surgery.nnnOUTCOMEnFor the human study, GH and IGF-I levels, AIP, and somatostatin receptor staining were measured. For the cell line, AIP and ZAC1 (zinc finger regulator of apoptosis and cell cycle arrest) expression, metabolic activity, and clone formation were measured.nnnRESULTSnLanreotide pretreatment reduced GH and IGF-I levels and tumor volume (all P < 0.0001). AIP immunostaining was stronger in the lanreotide-pretreated group vs. the surgery-only group (P < 0.001). After lanreotide pretreatment, the AIP score correlated to IGF-I changes in females (R = 0.68, P < 0.05). Somatostatin receptor staining was not reduced in samples with AIP mutations. In GH3 cells, 1 nm octreotide increased AIP mRNA and protein (both P < 0.01) and ZAC1 mRNA expression (P < 0.05). Overexpression of wild-type (but not mutant) AIP increased ZAC1 mRNA expression, whereas AIP siRNA knockdown reduced ZAC1 mRNA (both P < 0.05). The siRNA-mediated knockdown of AIP led to an increased metabolic activity and clonogenic ability of GH3 cells compared with cells transfected with a nontargeting control (both P < 0.001).nnnCONCLUSIONnThese results suggest that AIP may play a role in the mechanism of action of somatostatin analogs via ZAC1 in sporadic somatotroph tumors and may explain their lack of effectiveness in patients with AIP mutations.

THERAPY IN ENDOCRINE DISEASE: Etomidate in the management of hypercortisolaemia in Cushing's syndrome: a review

This review addresses the practical usage of intravenous etomidate as a medical therapy in Cushings syndrome. We reviewed the relevant literature, using search terms etomidate, Cushings syndrome, adrenocortical hyperfunction, drug therapy and hypercortisolaemia in a series of public databases. There is a paucity of large randomised controlled trials, and data on its use rely only on small series, case study reports and international consensus guideline recommendations. Based on these, etomidate is an effective parenteral medication for the management of endogenous hypercortisolaemia, particularly in cases with significant biochemical disturbance, sepsis and other serious complications such as severe psychosis, as well as in preoperative instability. We suggest treatment protocols for the safe and effective use of etomidate in Cushings syndrome.

GH replacement does not increase the risk of recurrence in patients with craniopharyngioma

Backgroundu2002 A significant number of patients with craniopharyngioma are GH deficient. The safety of GH replacement in these subjects has not been established.

Surgical debulking of pituitary macroadenomas causing acromegaly improves control by lanreotide

Backgroundu2002 Macroadenomas causing acromegaly are cured surgically in only around 50% of patients. Primary medical treatment with somatostatin analogues has been suggested to be a means of treating patients with a potentially poor surgical outcome. Previous retrospective studies have also suggested that surgical debulking of pituitary tumours causing acromegaly improves control by somatostatin analogues. No prospective study using lanreotide has been carried out thus far to assess whether this is the case.