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Double pituitary adenomas with distinct histological features and immunophenotypes
  1. C Shimizu1,
  2. T Koike1,
  3. Y Sawamura2
  1. 1Division of Clinical Endocrinology and Metabolism, Department of Medicine II, Hokkaido University Graduate School of Medicine
  2. 2Department of Neurosurgery, Hokkaido University Graduate School of Medicine
  1. Correspondence to:
 Dr C Shimizu
 Department of Medicine II, Hokkaido University Graduate School of Medicine, N-15 W-7, Kita-ku, Sapporo 060-8638, Japan;

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We present a case of double pituitary adenomas with distinct pathological features. A 59 year old Japanese woman was referred to Hokkaido University Hospital for endocrinological examination of acromegaly. The patient showed typical acromegalic features. Growth hormone (GH) and insulin-like growth factor 1 were 17.1 ng/ml and 1620 ng/ml, respectively. Other pituitary hormones including thyroid stimulating hormone (TSH), prolactin, gonadotropins, and adrenocorticotropic hormone (ACTH) were within normal ranges. GH was not suppressed in the 75 g oral glucose tolerance test. Although the response of TSH was normal, GH showed a paradoxical rise to 200 μg with thyrotropin releasing hormone administration. On imaging analysis, double low intensity regions separated by a normal pituitary were identified (fig 1). Based on the diagnosis of acromegaly, transsphenoidal pituitary adenomectomy was done. Each tumour showed distinct histological and immunohistochemical features; the left adenoma consisted of relatively small cells with hyperchromatic nuclei immunoreactive for TSH. In contrast, the tumour cells of the right tumour were acidophilic and cytoplasm rich with an intense immunoreactivity for GH (fig 2). Other pituitary hormones including luteinising hormone, follicle stimulating hormone, prolactin, and ACTH were immunohistochemically negative for both adenomas.

The incidence of double or multiple pituitary adenomas is approximately 1% of autopsy pituitaries1 and 0.4% to 1.3% of a surgically resected series.23 In the present case, one adenoma was endocrinologically active but the other inactive regardless of being immunohistochemically positive for TSH. The independent production of distinct pituitary hormones from each adenoma has been reported,2 so one should take into consideration doing an intensive preoperative imaging analysis if one hopes to accomplish complete remission of endocrinopathy.

Figure 1

(A) Coronal T1 weighted MR image revealing a suprasellar extension on the right side of the pituitary complex. (B) Gadolinium enhanced coronal T1 weighted MR image indicating two hypointense lesions, clearly separated by a well enhanced normal pituitary.

Figure 2

(A) Hematoxylin eosin staining showing relatively small cells in the adenoma left. A rosette like pattern with spindle shaped cells is evident (arrowheads). (B) The right sided tumour was composed of strongly acidophilic, more cellular, adenomatous cells with a diffuse pattern of cell growth. (C) Immunohistochemistry revealing immunoreactivity for thyroid stimulating hormone in the adenoma on the left. (D) Immunohistochemistry revealing immunoreactivity for growth hormone in the other on the right.


This work was supported in part by a Grant-in-Aid for Research on Specific Diseases “Hypothalamo-Pituitary Dysfunction” from the Ministry of Health, Labour and Welfare, Japan.


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