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      Pituitary hyperplasia: case series and literature review of an under-recognised and heterogeneous condition


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          Pituitary hyperplasia (PH) occurs in heterogeneous settings and remains under-recognised. Increased awareness of this condition and its natural history should circumvent unnecessary trans-sphenoidal surgery. We performed an observational case series of patients referred to a single endocrinologist over a 3-year period. Four young women were identified with PH manifesting as diffuse, symmetrical pituitary enlargement near or touching the optic apparatus on MRI. The first woman presented with primary hypothyroidism and likely had thyrotroph hyperplasia given prompt resolution with thyroxine. The second and third women were diagnosed with pathological gonadotroph hyperplasia due to primary gonadal insufficiency, with histopathological confirmation including gonadal-deficiency cells in the third case where surgery could have been avoided. The fourth woman likely had idiopathic PH, though she had concomitant polycystic ovary syndrome which is a debated cause of PH. Patients suspected of PH should undergo comprehensive hormonal, radiological and sometimes ophthalmological evaluation. This is best conducted by a specialised multidisciplinary team with preference for treatment of underlying conditions and close monitoring over surgical intervention.

          Learning points

          • Normal pituitary dimensions are influenced by age and gender with the greatest pituitary heights seen in young adults and perimenopausal women.

          • Pituitary enlargement may be seen in the settings of pregnancy, end-organ insufficiency with loss of negative feedback, and excess trophic hormone from the hypothalamus or neuroendocrine tumours.

          • PH may be caused or exacerbated by medications including oestrogen, GNRH analogues and antipsychotics.

          • Management involves identification of cases of idiopathic PH suitable for simple surveillance and reversal of pathological or iatrogenic causes where they exist.

          • Surgery should be avoided in PH as it rarely progresses.

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          Most cited references27

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          Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience.

          Transsexuals receive cross-sex hormone treatment. Its short-term use appears reasonably safe. Little is known about its long-term use. This report offers some perspectives. The setting was a university hospital serving as the national referral center for The Netherlands (16 million people). From the start of the gender clinic in 1975 up to 2006, 2236 male-to-female and 876 female-to-male transsexuals have received cross-sex hormone treatment. In principle, subjects are followed up lifelong. Male-to-female transsexuals receive treatment with the antiandrogen cyproterone acetate 100 mg/d plus estrogens (previously 100 microg ethinyl estradiol, now 2-4 mg oral estradiol valerate/d or 100 microg transdermal estradiol/d). Female-to-male transsexuals receive parenteral testosterone esters 250 mg/2 wk. After 18-36 months, surgical sex reassignment including gonadectomy follows, inducing a profound hypogonadal state. Outcome measures included morbidity and mortality data and data assessing risks of osteoporosis and cardiovascular disease. Mortality was not higher than in a comparison group. Regarding morbidity, with ethinyl estradiol, there was a 6-8% incidence of venous thrombosis, which is no longer the case with use of other types of estrogens. Continuous use of cross-sex hormones is required to prevent osteoporosis. Androgen deprivation plus an estrogen milieu in male-to-female transsexuals has a larger deleterious effect on cardiovascular risk factors than inducing an androgenic milieu in female-to-male transsexuals, but there is so far no elevated cardiovascular morbidity/mortality. Low numbers of endocrine-related cancers have been observed in male-to-female transsexuals. Cross-sex hormone treatment of transsexuals seems acceptably safe over the short and medium term, but solid clinical data are lacking.
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            Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients.

            Patients affected by the multiple endocrine neoplasia type I syndrome (MEN1) display a high incidence of pituitary adenomas, though it is still unknown whether these pituitary tumors have specific pathologic features that would distinguish them from sporadic pituitary adenomas. Pituitary tissue specimens of 77 MEN1 patients from the GTE (Groupe d'étude des Tumeurs Endocrines) register were compared with unselected 2509 non-MEN1 sporadic pituitary tumors and also to a control subgroup of 296 cases, where 1 MEN1 tumor was matched with 4 sporadic tumors of the same hormonal immunoprofile. Sex, age, size, and invasiveness of tumors, and menin gene mutations were documented. Histologic analysis took into account 33 items, including immunocytochemical data, the proliferative marker Ki-67, and an examination of the juxtatumoral pituitary. MEN1 tumors were significantly larger and more often invasive by histology. MEN1 patients with large pituitary tumors (grade IV) were younger than non-MEN1 patients. MEN1 tumors had no other characteristic histologic features and no predominance of any one hormone producing subtype. However, plurihormonal adenomas versus monohormonal and nonimmunoreactive adenomas were more frequent in MEN1 tumors (39%) than in the control non-MEN1 group (P = 0.001). Especially, the growth hormone and prolactin plurihormonality with unusual association with follicle-stimulating hormone, luteinizing hormone, or adrenocorticotropic hormone was more frequent in MEN1 tumors. In addition, multiple adenomas were significantly more frequent (4% vs. 0.1%; P < 0.0001), especially prolactin-adrenocorticotropic hormone. Somatotroph hyperplasia, with or without a microadenoma was found in only 3 MEN1 patients, with growth hormone-releasing hormone hypersecretion by a pancreatic tumor in 2 of them. All types of mutation were observed, including frameshifts, nonsenses, missenses, and 1 case of germline MEN1 encompassing large deletion, strongly suggesting the absence of any phenotype-genotype correlation.
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              Size and shape of the pituitary gland during pregnancy and post partum: measurement with MR imaging.

              Cranial magnetic resonance (MR) imaging was performed in 38 pregnant and postpartum women and 30 nonpregnant age-matched control subjects to establish standards for pituitary gland size and shape during this period. Gland height and infundibulum width were measured on midline T1-weighted sagittal images. Gland convexity or concavity was graded qualitatively. Throughout pregnancy, gland height increased linearly by approximately 0.08 mm/wk. No gland exceeded 10 mm in height during pregnancy. Increases in gland convexity also correlated with progression of pregnancy. The largest glands were seen in the immediate postpartum period; during this period, five of 12 glands measured 10.0-11.8 mm. Beyond the first week post partum, glands rapidly returned to normal size, apparently regardless of the status of breast-feeding. The mean diameter of the infundibulum was 2.2 mm (range, 0.8-4.0 mm). The pituitary gland enlarges throughout pregnancy but should probably not exceed 10 mm during most of this period. Size of up to 12 mm may be acceptable immediately post partum.

                Author and article information

                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM Case Reports
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                1 June 2015
                : 2015
                : 150017
                [1 ]Department of Endocrinology , St Vincent's Hospital , Sydney, New South Wales, Australia
                [2 ]Hormones and Cancer Group , Garvan Institute of Medical Research , 384 Victoria Street, Sydney, New South Wales, 2010, Australia
                [3 ]Department of Anatomical Pathology , St Vincent's Hospital , Sydney, New South Wales, Australia
                Author notes
                Correspondence should be addressed to S M C De Sousa Email: s.desousa@ 123456garvan.org.au
                © 2015 The authors

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

                : 12 February 2015
                : 6 May 2015
                Unique/Unexpected Symptoms or Presentations of a Disease


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