Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 4178  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
  » Next article
  » Previous article 
  » Table of Contents
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (56 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

  In this Article
 »  Abstract
 »  Introduction
 »  Case report
 »  Discussion
 »  Acknowledgement
 »  References

 Article Access Statistics
    PDF Downloaded102    
    Comments [Add]    
    Cited by others 2    

Recommend this journal

Year : 2000  |  Volume : 48  |  Issue : 4  |  Page : 374-7

Clinically and biochemically silent thyrotroph adenoma with oncocytic change.

Departments of Pathology and Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Correspondence Address:
Departments of Pathology and Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

  »  Abstract

A case of clinically and biochemically silent pituitary tumour with ultrastructural and immunohistochemical evidence of thyroid stimulating hormone secretion is presented. Significance of recognition of such silent tumours is discussed.

How to cite this article:
Banerjee A K, Sharma B S, Kak V K. Clinically and biochemically silent thyrotroph adenoma with oncocytic change. Neurol India 2000;48:374

How to cite this URL:
Banerjee A K, Sharma B S, Kak V K. Clinically and biochemically silent thyrotroph adenoma with oncocytic change. Neurol India [serial online] 2000 [cited 2023 Nov 29];48:374. Available from:

   »   Introduction Top

Thyrotroph adenomas are the rarest of the secretory pituitary tumours, accounting for less than 1% of cases.[1],[2],[3] Most of these adenomas occur in patients with longstanding hypothyroidism and are accompanied by hyperthyroidism when the thyroid gland is capable of hormone secretion.[1],[2],[3],[4],[5] The recognition of thyrotroph adenoma is important because of its aggressive behaviour and for follow-up evaluation.[6],[7],[8],[9] It is, therefore, particularly relevant to recognize hormonally silent tumours. We report a case of pituitary chromophobe adenoma in an euthyroid patient, which on immunohistochemical and ultrastructural study turned out to be a highly differentiated thyrotroph adenoma with oncocytic change.

   »   Case report Top

A 46 year old female was admitted with the history of headache and progressive visual deterioration of 6 months duration. She had 5 healthy children and was 4 years postmenopausal. There were no clinical features of endocrine dysfunction except for galactorrhoea. She had bilateral primary optic atrophy. Visual acuity was 6/9 in the right eye and only perception of light in the left. Visual fields could be charted only on the right side, which revealed a temporal field defect. Skull X-rays showed sellar enlargement, measuring 110 cm2. Serum cortisol and thyroid stimulating hormone (TSH) levels were normal. Serum prolactin was elevated to 1498 nmol/L (normal 78-600). CT scan showed an enhancing sellar mass with suprasellar extension. Other routine laboratory investigations were normal. Total intracapsular removal of a firm vascular tumour from the sellar and suprasellar region through a right frontal craniotomy was followed by 45 Gy irradiation over a period of 3 weeks. Follow-up one year after surgery revealed absence of headache and galactorrhoea and improvement of visual acuity. CT scan showed no recurrence of the tumour.
Multiple fragments of the excised tissue showed an adenoma consisting of ovoid or spindle shaped cells, arranged in solid nests supported by thin fibrovascular septa [Figure. 1]. The cytoplasm was either clear or granular. Few fine periodic acid Schiff (PAS) positive granules were observed in these cells, but most of these stained greyish on orange-fuchsin-green (OFG) stain. Avidin-biotin-peroxidase complex technique revealed the presence of TSH in the cytoplasm of several adenoma cells. Immunostaining for growth hormone and prolactin was negative. Electron microscopy of tissue, primarily fixed in glutaraldehyde and post fixed in osmic acid, showed closely apposed, moderate sized, elongated adenoma cells, often with angular outlines [Figure. 2]. Focal marked nuclear pleomorphism was present. There were moderate number of rough endoplasmic reticulum and prominent Golgi complexes with developing secretory granules. These granules, measuring 150-200 nm, were distributed unevenly in the cytoplasm [Figure. 3]. These were scanty within the nuclear pole and more numerous within cytoplasmic processes and close to plasma membrane. A substantial number of adenoma cells exhibited advanced oncocytic change.

   »   Discussion Top

Approximately 30% of pituitary adenomas are clinically non-functioning.[10] Clinically, nonfunctioning adenomas usually come to medical attention when they become large enough to cause neurological symptoms, especially visual impair-ment.[11],[12] Visual deterioration, a typical feature of large non-functioning tumours,[11] was the main clinical presentation in the present case. These adenomas represent a heterogenous group morphologically, and the incidence of different tumour types varies depending on the patient's age.[7] These silent, non-secreting or quiescent, pituitary adenomas produce no clinical or biochemical evidence of adenohypophysial hormone production except for low grade hyperprolactinaemia.[9],[10],[11],[12] Lactotroph hyperplasia may result from excess TRH which stimulates lactotrophs with resultant hyperprolactinaemia or from reduced hypothalamic dopamine thereby facilitating prolactin secretion.[4] Low grade hyperprolactinaemia was probably due to the 'stalk section' effect since prolactin was not detected in the tumour on immunostaining and electron microscopy.
Any kind of pituitary adenoma may be clinically nonfunctioning but gonadotroph and thyrotroph adenomas are more likely to be non-functioning.[13] 45% of clinically non-functioning pituitary adenomas are thyrotroph adenomas.[14],[7] Incidence of null-cell adenomas and oncocytomas, which are known to be the most common types of non-secreting pituitary adenomas in patients over 40 years of age, is relatively low in younger patients and this trend is more obvious in patients younger than 30 years of age.[7] Approximately half of silent pituitary adenomas show some degree of oncocytic change. Holck and Laursen[10] used the term 'oncocytoma' in cases with marked oncocytic change whereas Kovacs and Horvath[1] reserved the term for cases showing increased mitochondrial content in practically every tumour cell. Focal adenohypophysial hormone positivity in scattered tumour cells in oncocytoma may reflect the cell type from which the tumour is derived.[1],[2] In the present case, it is possible that the tumour arose from thyrotrophs but partially lost its marker and hormone producing potential due to dedifferentiation, neoplastic transformation or subsequent cellular proliferation.[1] Alternatively, it is likely that the tumour arose from undifferentiated precursor cell that aims to mature into thyrotroph cell line. Oncocyte, a variant of null cell, represents a nonfunctional or inactive rest cell but with preserved functional potential.
Pituitary adenomas secreting TSH in association with abnormal thyroid function have been well described.[13],[15],[16] Calcification in such lesions (pituitary stone) can occur.[3] Thyrotropin secreting pituitary tumours may be found in two opposite clinical situations : the hyperthyroidism secondary to thyrotroph adenoma, also called central hyperthyroidism, and the longstanding primary hypothyroidism which can be accompanied by a compensatory pituitary enlargement.[13],[16] The present case, although functionally silent, showed morphological features of a highly differentiated thyrotroph adenoma with oncocytic change. A small percentage of apparently non-functioning adenomas contain immunoreactive hormone and the majority of these are uncombined biologically inactive alpha or beta subunit alone or both.[11] Several explanations for the failure of correlation between clinical features, serum hormone levels and immunoreactive hormone content have been proposed for such cases.[2],[17] Waldhausl et al[18] reported 6 fractions of tumour TSH with marked difference in the immunoreactivity and bioactivity of plasma and tumour TSH. The present case with, its ultrastructural features of highly differentiated secretorily active TSH adenoma without clinical or biochemical evidence of hypersecretion suggests either a defective release or an abnormal production with preserved immunoreactivity but without bioactivity or inactivation by anti-hormones.
The primary treatment of non-functioning pituitary adenomas is surgery, radiation and pharmacological agents.[12] Early diagnosis and proper treatment of TSH secreting pituitary adenomas prevent signs and symptoms of mechanical compression of adjacent structures by expanding tumour mass (visual field defects, headaches and hypopituitarisms).[13] Characterisation of non-functioning pituitary tumours, according to the predominant cell type, on ultrastructural and immunohistochemical basis, may permit one to make predictions on their biological behaviour, prognosis and responsiveness to therapy.[3] Importance of careful morphological study of clinically non-functioning pituitary adenomas (especially younger patients) by immunohistochemical and electron microscopic examination is useful in assessing prognosis and deciding on the appropriate treatment.[7] SMS 201-995 produces visual improvement and may be a valuable therapeutic agent in the management of thyrotroph adenomas with or without hyperthyroidism.[19],[20] This may provide a basis for treatment of apparently non-functioning adenomas, particularly at recurrence.

   »   Acknowledgement Top

The authors wish to thank Prof. K. Kovacs, Department of Pathology, St. Michael's Hospital, Toronto, Canada, for his help in the investigation of this case.


  »   References Top

1.Kovacs K, Horvath E : Morphology of adenohypophysial cells and pituitary adenomas. In : The pituitary gland, Imura H, ed. Raven Press, New York. 1985; 25-55.   Back to cited text no. 1    
2.Kovacs K, Horvath E : Pathology of pituitary tumours. Endocrinol Metab Clin North Am1987; 16 : 529-551.   Back to cited text no. 2    
3.Webster J, Peters JR, John R et al : Pituitary stone : two cases of densely calcified thyrotrophin-secreting pituitary adenomas. Clin Endocrinol 1994; 40 : 137-143.   Back to cited text no. 3    
4.Pioro EP, Scheithauer BW, Laws ER Jr et al : Combined thyrotroph and lactrotroph cell hyperplasia simulating prolactin secreting pituitary adenoma in longstanding primary hypothyroidism. Surg Neurol 1988; 29 : 218-226.   Back to cited text no. 4    
5.Ghannam NN, Hammami M, Muttair Z et al : Primary hypothyroidism -associated TSH-secreting pituitary adenoma / hyperplasia presenting as a bleeding nasal mass and extremely elevated TSH level. J Endocrinol Invest1999; 22 : 419-423.   Back to cited text no. 5    
6.Comi RJ, Gestindheit N, Murray L et al : Response of thyrotropin secreting pituitary adenomas to a long acting somatostatin analogue. N Engl J Med 1987; 317 : 12-17.   Back to cited text no. 6    
7.Yamada S, Kovacs K, Horvath E et al : Morphological study of clinically non-secreting pituitary adenomas in patients under 40 years of age. J Neurosurg 1991; 75 : 902-905.   Back to cited text no. 7    
8.Shomali ME, Katzuelson L : Medical therapy for gonadotroph and thyrotroph tumours. Endocrinol Metab Clin North Am 1999; 28 : 223-240.   Back to cited text no. 8    
9.Brucker-Davis F, Oldfield EH, Skarulis MC et al : Thyrotropinsecreting pituitary tumours : diagnostic criteria, thyroid hormone sensitivity, and treatment outcome in 25 patients followed at the national Institute of health. J Endocrinol Metab 1999; 84 : 476-486.   Back to cited text no. 9    
10.Holck S, Laursen H : Silent pituitary adenomas. An ultrastructural study. Acta Pathol Microbiol Immunol Scand 1986; 94 : 13-20.   Back to cited text no. 10    
11.Black PML, Hsu DW, Klibanski A et al : Hormone production in clinically non-functioning pituitary adenomas. J Neurosurg 1987; 66 : 244-250.   Back to cited text no. 11    
12.Snyder PJ : Clinically non-functioning pituitary adenomas. Endocrinol Metab Clin North Am 1993; 22 : 163-175.   Back to cited text no. 12    
13.Beck-Peccoz P, Persani L, Asteria C et al : Thyrotropinsecreting pituitary tumours in hyper and hypothyroidism. Acta Med Autriaca 1996; 23 : 41-46.   Back to cited text no. 13    
14.Sano T, Yamada S : Histologic and immunohistochemical study of clinically non-functioning pituitary adenomas : special reference to gonadotropin-positive adenomas. Pathol Int 1994; 44 : 697-703.   Back to cited text no. 14    
15.Girod C, Trouillas J, Claustrat B : The human thyrotropic adenoma : Pathological diagnosis in five cases and critical review of the literature. Semin Diag Pathol 1986; 3 : 58.   Back to cited text no. 15    
16.Ozbey N, Sariyildiz E, Yilmaz L et al : Primary hypothyroidism with hyperprolactinaemia and pituitary enlargement mimicking a pituitary macroadenoma. Int J Clin Pract 1997; 51 : 409-411.   Back to cited text no. 16    
17.Roy S : Ultrastructure of pituitary adenomas with particular reference to chromophobe adenoma. In : Progress in Neuropathology (ed) Zimmerman HM. Raven Press, New York. 1983; 223-259.   Back to cited text no. 17    
18.Waldhausl W, Bratusch-Marrain P, Nowotny P et al : Secondary hyperthyroidism due to thyrotropin hypersecretion: study of pituitary tumour morphology and thyrotropin chemistry and release. J Clin Endocrinol Metab 1979; 49 : 879-887.   Back to cited text no. 18    
19.Guillansseau PJ, Chanson PH, Timsit J et al : Visual improvement with SMS 201-995 in a patient with a thyrotropin secreting pituitary adenoma. N Engl J Med 1987; 317 : 53-54.   Back to cited text no. 19    
20.Wemeau JL, Dewailly D, Leroy R et al : Long term treatment with the somatostatin analog SMS 201-995 in a patient with a thyrotropin and growth hormone secreting pituitary adenoma. J Clin Endocri Metab 1988; 66 : 636-639.   Back to cited text no. 20    


Print this article  Email this article
Previous article Next article
Online since 20th March '04
Published by Wolters Kluwer - Medknow