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      Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

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          Summary

          Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour.

          Learning points

          • While non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare.

          • Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas.

          • GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma.

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          Most cited references10

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          Classical pituitary apoplexy: clinical features, management and outcome.

          The term classical pituitary apoplexy describes a clinical syndrome characterized by sudden headache, vomiting, visual impairment and meningismus caused by the rapid enlargement of a pituitary adenoma usually due to haemorrhagic infarction of the tumour. Most published reports looking at the clinical features and management of pituitary apoplexy have not differentiated between patients with clinical and subclinical apoplexy, the latter diagnosed at surgery. Furthermore, little is reported on the clinical outcome, in particular visual and endocrinological, and the role of radiotherapy. The purpose of this study was to observe not only the clinical presentation but also the possible predisposing events, investigations, management, clinical outcome as well as the role of radiotherapy in patients presenting with classical pituitary apoplexy. In a retrospective analysis 1985-96, the medical records of 21 male and 14 female patients (mean age 49.8 years, range 30-74) with classical pituitary apoplexy were reviewed. This represents all patients seen with this condition over the stated period. In all patients, pre- and post- operative measurements were made of FT4, FT3, TSH, PRL, LH, FSH, cortisol (0900 h), GH, oestradiol (females) and testosterone (males). Pituitary imaging was by computerized tomography (CT) scan, magnetic resonance imaging (MRI) or both. Patients were followed for up to 11 years (mean 6.3 years: range 0.5-11). Headache (97%) was the commonest presenting symptom, followed by nausea (80%) and a reduction of visual fields (71%). Hypertension, defined as a systolic > 160 mmHg and/or a diastolic > 90 mmHg, was seen in 26% of patients. MRI correctly identified pituitary haemorrhage in 88% (n = 7), but CT scanning identified haemorrhage in only 21% (n = 6). By immunostaining criteria, null-cell adenomas were the most common tumour type (61%). Transsphenoidal surgery resulted in improvement in visual acuity in 86%. Complete restoration of visual acuity occurred in all patients operated on within 8 days but only in 46% of patients operated on after this time (9-34 days). Long-term steroid or thyroid hormone replacement was necessary in 58% and 45% of patients, respectively. Of the male patients, 43% required testosterone replacement, and long-term desmopressin therapy was required in 6%. Only two patients (6%) with tumour recurrence after transsphenoidal surgery for the initial apoplectic event, subsequently required radiotherapy. In classical pituitary apoplexy, headache is the commonest presenting symptom and hypertension may be an important predisposing factor. MRI is the imaging method of choice. Transsphenoidal surgery is safe and effective. It is indicated if there are associated abnormalities of visual acuity or visual fields because, when performed within 8 days, it resulted in significantly greater improvement in visual acuity and fields than if surgery was performed after this time. Radiotherapy is not indicated immediately as the risk of tumour recurrence is small, but careful follow-up initially with annual imaging is indicated in this group.
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            Clinical review: Functioning gonadotroph adenomas.

            Functioning gonadotroph adenomas (FGAs) are pituitary tumors secreting biologically active gonadotropins. The published literature includes only small case series or individual case reports. This review summarizes the published data on this rare entity and, based on them, suggests guidance on the follow-up of these patients.
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              Clinicopathological correlations in pituitary adenomas.

              Pituitary adenomas are common neuroendocrine neoplasms arising from adenohypophysial cells. Recent progress in our understanding of pituitary tumorigenesis as well as pathways involved in molecular cytodifferentiation of the adenohypophysis has impacted on the classification of pituitary adenomas. The detailed comprehensive classification of pituitary adenomas is now well recognized to reflect specific clinical features and genetic changes that predict targeted treatments, as well as prognostic information for patients with pituitary adenomas. Therefore, the clinical responsibility of pathologists is not only limited to the distinction of pituitary adenomas from other sellar lesions, but also to provide a comprehensive subtype classification using appropriate ancillary tools. In this article, we highlight an approach to clinical diagnosis and pitfalls in the classification of these common neoplasms. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                edm
                EDM Case Reports
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                8 June 2016
                2016
                : 2016
                : 160021
                Affiliations
                [1 ]Department of Endocrinology , University Hospital Galway, Newcastle, Galway, Ireland
                [2 ]Department of Radiology , University Hospital Galway, Newcastle, Galway, Ireland
                [3 ]School of Medicine , National University of Ireland Galway, Newcastle, Galway, Ireland
                [4 ]Department of Pathology , Beaumont Hospital, Beaumont Road, Dublin 9, Ireland
                Author notes
                Correspondence should be addressed to A Egan; Email: aoife.egan@ 123456gmail.com
                Article
                EDM160021
                10.1530/EDM-16-0021
                4898068
                27284452
                3a0b9a90-8998-4339-a885-fb8382e3bc3c
                © 2016 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 25 April 2016
                : 10 May 2016
                Categories
                Insight into Disease Pathogenesis or Mechanism of Therapy

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