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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 58, Num. 3, 2010, pp. 341-342

Neurology India, Vol. 58, No. 3, May-June, 2010, pp. 341-342


Non-functional pituitary adenomas

Section of Neuropathology, Departments of Neurological Sciences and Pathology, Christian Medical College, Vellore - 632 004, India
Correspondence Address: Geeta Chacko, Professor of Pathology, Section of Neuropathology, Departments of Neurological Sciences and Pathology, Christian Medical College, Vellore - 632 004, India,

Date of Acceptance: 31-Jan-2010

Code Number: ni10095

PMID: 20644259
DOI: 10.4103/0028-3886.65528

In this issue of the journal, Rishi et al. present a series of non-functional pituitary adenomas, seen over a 1.5-year period in a single institution. Not surprisingly, the authors demonstrate that a significant proportion of clinically non-functional adenomas show immunohistochemical evidence of hormone production. Their findings are predominantly confirmatory of previously published data and add to the growing literature on the immunoprofile of non-functional adenomas. [1],[2],[3],[4],[5],[6]

The authors' conclusion that diagnosing subtypes such as gonadotroph adenomas will help selecting such patients for adjunctive medical therapies and is thus of clinical relevance, should be viewed with caution, particularly since at the present time there is no targeted medical therapy for this group of tumors. In fact, the ultimate clinical relevance lies not in the detection of null cell adenomas and gonadotroph adenomas, both of which have low rates of invasion, but rather in the detection of some of the aggressive subtypes of clinically non-functional adenomas. These aggressive subtypes include: 1) Silent corticotroph adenomas, subtypes I and II. [3],[7],[8] These tumors are unaccompanied by elevations in ACTH or clinical evidence of Cushing's disease but display immunopositivity for ACTH. They are usually invasive macroadenomas and have a higher potential for apoplexy and recurrence; 2) Acidophil stem cell adenomas. [9] These tumors are usually clinically non-functional, but are often associated with hyperprolactinemia. Immunohistochemically, they demonstrate production of growth hormone and prolactin. These tumors often display oncocytic change and in addition to ultrastructural evidence of growth hormone and prolactin production, contain gigantic mitochondria not seen in any other subtype. The recognition of this neoplasm is important because the lesions are prone to progressive growth and invasive behavior; 3) Silent adenoma, subtype 3. [5] These tumors may show minor immunopositivity for any combination of pituitary hormones, but could also be immunonegative for all and hence are an important differential to consider with null cell adenomas. These tumors are clinically silent or non-functional and are usually seen in the second and third decades in females and at any age in males. Ultrastructural examination shows that these are highly differentiated with resemblance to glycoprotein hormone producing adenomas. A distinctive feature however is the presence of pleomorphic nuclei containing multiple spheridia. They are reported to be highly infiltrative with a rapid growth rate and a high recurrence rate. Although dopamine agonists are found to reduce serum prolactin levels in this tumor, the tumor has been observed to continue to grow despite therapy. [1],[10],[11]

The current World Health Organization (WHO) classification of the pituitary adenomas, formulated in 2004, [1] takes into consideration clinical, biochemical, surgical findings, neuroimaging as well as the histology, immunohistochemistry and ultrastructural features. The present study reiterates the fact that immunohistochemical analysis of pituitary adenomas, once considered a dispensable tool because of cost constraints, needs to be an integral part of every neuropathology core facility.


1.Tumours of the Pituitary. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, editor. World health organization classification of tumours pathology and genetics of tumours of endocrine organs. 1st ed. Lyon: IARC Press; 2004. p. 9-49.  Back to cited text no. 1    
2.Horvath E, Kovacs K, Singer W, Smyth HS, Killinger DW, Erzin C,et al. Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. Cancer 1981;15:47:761-71.  Back to cited text no. 2    
3.Scheithauer BW, Jaap AJ, Horvath E, Kovacs K, Lloyd RV, Meyer FB, et al. Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery. 2000;47:723-9.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Young WF Jr, Scheithauer BW, Kovacs KT, Horvath E, Davis DH, Randall RV. Gonadotroph adenoma of the pituitary gland: a clinicopathologic analysis of 100 cases. Mayo Clin Proc 1996;71:649-56.  Back to cited text no. 4  [PUBMED]  
5.Horvath E, Kovacs K, Smyth HS, Cusimano M, Singer W. Silent adenoma subtype 3 of the pituitary--immunohistochemical and ultrastructural classification: a review of 29 cases. Ultrastruct Pathol 2005;29:511-24.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Kovacs K, Horvath E, Ryan N, Ezrin C. Null cell adenoma of the human pituitary. Virchows Arch A Pathol Anat Histol 1980;387:165-74.  Back to cited text no. 6  [PUBMED]  
7.Webb KM, Laurent JJ, Okonkwo DO, Lopes MB, Vance ML, Laws ER, Jr. Clinical characteristics of silent corticotrophic adenomas and creation of an internet-accessible database to facilitate their multi-institutional study. Neurosurgery 2003;53:1076-84.  Back to cited text no. 7    
8.Bradley KJ, Wass JA, Turner HE. Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumours but do not recur more frequently. Clin Endocrinol (Oxf) 2003;58:59-64.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Horvath E, Kovacs K, Singer W, Ezrin C, Kerenyi NA. Acidophil stem cell adenoma of the human pituitary. Arch Pathol Lab Med 1977;101:594-9.  Back to cited text no. 9  [PUBMED]  
10.Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W. Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic, and ultrastructural stu dy. Am J Pathol 1980;98:617-38.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Horvath E, Kovacs K, Smyth HS, Killinger DW, Scheithauer BW, Randall R, et al. A novel type of pituitary adenoma: morphological features and clinical correlations. J Clin Endocrinol Metab 1988;66:1111-8.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]

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