Showing papers by "Niki Karavitaki published in 2012"

Etomidate in the management of hypercortisolaemia in Cushing's syndrome: a review.

Abstract: This review addresses the practical usage of intravenous etomidate as a medical therapy in Cushing's syndrome. We reviewed the relevant literature, using search terms 'etomidate', 'Cushing's 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 Cushing's syndrome.

Rathke's cleft cysts.

Abstract: Rathke's cleft cysts (RCCs) are benign, sellar and/or suprasellar lesions originating from the remnants of Rathke's pouch. Although a common finding in routine autopsies (12-33% of normal pituitary glands), symptomatic cases are rare and comprise 5-15% of all surgically resected sellar lesions. Small, asymptomatic RCC do not require surgical intervention, and their natural history is not clear. In series of nonoperated presumed RCCs, 26-94% did not progress during follow-up periods up to 9 years. In symptomatic ones, surgery is indicated, aiming to drain the cyst content and safely remove as much of the capsule as possible. Following surgical intervention, headaches and visual field defects improve or resolve in a significant number of patients (40-100% and 33-100%, respectively) and partial hypopituitarism recovers in 14-50%. Data on relapse rates published in the last 15 years are based on variable follow-up periods and show wide variation (between 0% and 33%). The lowest relapse rates have been described in reports with relatively short mean observation periods (<3 years), whereas in those with longer follow-up the relapse rates increase. Most of the relapses occur within 5-6 years, suggesting that follow-up is required for at least 5 years after surgery. Risk factors for relapse include the presence of squamous metaplasia in the cyst wall, cyst size and the presence of inflammation. Long-term sufficiently powered studies aiming to clarify the natural history of asymptomatic RCCs and of those relapsing postoperatively are required.

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

Abstract: Design: In 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. Setting: The study was conducted at a university hospital. Patients: Thirty-nine sporadic and 10 familial acromegaly patients participated in the study. Intervention: Interventions included preoperative lanreotide treatment and pituitary surgery. Outcome: For 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.

Ipilimumab: A novel immunomodulating therapy causing autoimmune hypophysitis: A case report and review

Abstract: 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.

Prevalence and incidence of pituitary adenomas.

Abstract: Reliable epidemiological data on pituitary adenomas (PAs) are of major importance for estimating the burden on the Health Care System and for designing optimal resource distribution for clinical care and for research activities. Cross-sectional studies from Switzerland, Belgium and the UK have shown that PAs have a prevalence of 78 to 94 cases/100,000 inhabitants (three to five times higher than previously thought). Furthermore, data from Northern Finland show an overall standardized incidence rate of 4 per 100,000 with the incidentally discovered ones demonstrating an increase. The enhanced awareness of pituitary disease and the recent advances in the diagnostic technologies have contributed to the earlier recognition of PAs. Studies from diverse populations and of larger sample size are needed to expand our insight on the epidemiology of PAs.

Mini-review: pheochromocytomas causing the ectopic ACTH syndrome

Abstract: Cushing’s syndrome (CS) is a condition associated with high cortisol levels and affects around 0.7–2.4 cases per million population per year [1, 2, 3]. Approximately 80 % of cases of CS are secondary to excess adrenocorticotrophin (ACTH) secretion, while in around 20 % the primary abnormality lies in the adrenal, most often an adrenal adenoma or carcinoma. Of the ACTH-dependent causes, some 80–90 % are due to a pituitary adenoma—Cushing’s disease—but in a significant proportion the cause is ectopic secretion from a non-pituitary source, the ectopic ACTH syndrome (EAS) [4]. The commonest source of ACTH secretion in these patients is a bronchial carcinoid. However, many other tumors are capable of secreting ACTH, and in most series a small but significant number are secondary to an ACTH-secreting pheochromocytoma. Amalgamating the data from 6 large series of patients with ectopic ACTH, pheochromocytoma was the source of ACTH secretion in 19 out of 363 patients (5.2 %) [5, 6, 7, 8, 9, 10, 11]. In this mini-review, we present a patient presenting to our department with a pheochromocytoma as well as Cushing’s syndrome due to ectopic ACTH secretion by the pheochromocytoma, and we discuss published cases in the world literature to assess its significance. We emphasize the problems in the simultaneous management of these two serious endocrine conditions.

Expression of guanylyl cyclase-B (GC-B/NPR2) receptors in normal human fetal pituitaries and human pituitary adenomas implicates a role for C-type natriuretic peptide.

Abstract: C-type natriuretic peptide (CNP/Nppc) is expressed at high levels in the anterior pituitary of rats and mice and activates guanylyl cyclase B receptors (GC-B/Npr2) to regulate hormone secretion. Mutations in NPR2/Npr2 can cause achondroplasia, GH deficiency, and female infertility, yet the normal expression profile within the anterior pituitary remains to be established in humans. The current study examined the expression profile and transcriptional regulation of NPR2 and GC-B protein in normal human fetal pituitaries, normal adult pituitaries, and human pituitary adenomas using RT-PCR and immunohistochemistry. Transcriptional regulation of human NPR2 promoter constructs was characterized in anterior pituitary cell lines of gonadotroph, somatolactotroph, and corticotroph origin. NPR2 was detected in all human fetal and adult pituitary samples regardless of age or sex, as well as in all adenoma samples examined regardless of tumor origin. GC-B immunoreactivity was variable in normal pituitary, gonadotrophinomas, and somatotrophinomas. Maximal transcriptional regulation of the NPR2 promoter mapped to a region within K214 bp upstream of the start site in all anterior pituitary cell lines examined. Electrophoretic mobility shift assays revealed that this region contains Sp1/Sp3 response elements. These data are the first to show NPR2 expression in normal human fetal and adult pituitaries and adenomatous pituitary tissue and suggest a role for these receptors in both pituitary development and oncogenesis, introducing a new target to manipulate these processes in pituitary adenomas. Endocrine-Related Cancer (2012) 19 497–508

Craniopharyngiomas: An Overview

Abstract: Craniopharyngiomas are rare, mainly sellar/parasellar epithelial tumors diagnosed during childhood or adult life. They may present with a variety of neurological, visual, and hypothalamo-pituitary manifestations. Histologically, they are divided in two main subtypes, adamantinomatous and papillary, but mixed forms have also been reported. Despite their benign histological features, they often show an unpredictable growth pattern, which, combined with the lack of randomized studies, poses significant difficulties in the establishment of an optimal therapeutic protocol. Currently, surgery combined or not with radiotherapy are the most commonly used treatment modalities. Irrespective of the type of primary therapeutic approach, the long-term morbidity (endocrine, visual, hypothalamic, neurobehavioral and cognitive) is substantial compromising quality of life and survival. The identification of clinical and imaging parameters predicting patients with a better prognosis is difficult and central registration of patients may provide correlates between treatments and outcomes.