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Table of Contents    
LETTER TO EDITOR
Year : 2017  |  Volume : 65  |  Issue : 5  |  Page : 1162-1164

Thyrotropic pituitary adenoma with plurihormonal immunoreactivity


Deparment of Neurosurgery, Medical Trust Hospital, Kochi, Kerala, India

Date of Web Publication6-Sep-2017

Correspondence Address:
Tarang K Vora
Department of Neurosurgery, Medical Trust Hospital, Kochi - 682 016, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/neuroindia.NI_577_16

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How to cite this article:
Vora TK, Karunakaran S. Thyrotropic pituitary adenoma with plurihormonal immunoreactivity. Neurol India 2017;65:1162-4

How to cite this URL:
Vora TK, Karunakaran S. Thyrotropic pituitary adenoma with plurihormonal immunoreactivity. Neurol India [serial online] 2017 [cited 2019 Sep 19];65:1162-4. Available from: http://www.neurologyindia.com/text.asp?2017/65/5/1162/214058


Sir,

Since its first reporting in 1960, thyrotropic pituitary adenomas have been considered to be the rarest among pituitary tumors.[1] Famous for their dramatic toxic presentation and a wrong treatment with thyroidectomies in the pre-computed tomography (CT) era, their prevalence has shown a gradual increase. This may be attributed to the availability of advanced neuroimaging and ultrasensitive immunometric hormonal assays. Till date, around 450 cases have been reported in literature.[2]

Most patients are diagnosed late in the 5th or 6th decade of life without any gender predilection. The molecular mechanisms underlying the thyrotropic adenomatous transformation still remain a mystery. Familial occurrence is yet undocumented in these patients. Thus, a multifactorial etiology may be responsible for its origin.

A 64-year old thin built man presented with headaches, tremors, fatigue, palpitations, sweaty hands, weight loss, and intermittent blurred vision, without any evidence of dysthyroid eye disease. He was diagnosed to be having hyperthyroidism an year earlier. Treatment with thyroid peroxidase inhibitors had proven to be futile for him. The underlying pathogenesis responsible for such a resistant and inappropriate thyroid hormone secretion includes a thyroid stimulating hormone (TSH)-secreting pituitary tumor (TSHoma) as well as selective pituitary resistance to thyroid hormone. The presence of compression syndromes and deregulation of other endocrine axes of pituitary point towards the presence of a pituitary neoplasm. In the cases lacking the above picture, biochemical tests measuring the alpha subunit and thyroid releasing hormone (TRH) stimulation (Werner's) test will aid in clinching the diagnosis. Even though it may be tempting to regard magnetic resonance imaging (MRI) as diagnostic, the presence of incidentalomas occurring in 10% of the patients should be kept in mind.[3] Magnetic resonance imaging of our patient revealed a pituitary tumor (3 cm × 2.4 cm × 1.9 cm) encircling the right internal carotid artery (ICA), with a suprasellar extension compressing the optic chiasm. Bitemporal hemianopia was confirmed on Humphreys automated perimetry. Blood tests revealed grossly elevated TSH (52.24 uIU/ml) and mildly elevated prolactin (20.1 ng/ml) levels. Growth hormone (GH), adrenocoticotrophic hormone (ACTH), morning cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone were noted to be within normal limits. The patient did not show any signs of hypercortisolemia, acromegaly, or hyperprolactinemia.

In comparison to other pituitary adenomas, thyrotropic adenomas may be larger, firmer, more invasive, and less amenable to surgical resection. This specially holds true in the older age groups in which patients develop concomitant comorbidities owing to their late presentation for treatment. In nonsurgical patients, somatostatin analogs such as octreotide can achieve euthyroidism and reduction in the size of pituitary mass in approximately 50% patients.[4] Use of dopamine agonists in such cases has yielded a variable response over the years.[5] Surgical adenectomy is, therefore, regarded to be the undisputed first line of treatment. Undetectable TSH levels 1 week after surgery are likely to indicate the performance of a complete adenectomy and has a good prognostic value.[6] Recurrence is rare, though it is more common in these tumors than is seen in other pituitary adenomas, probably owing to the more invasive nature of the former lesions. Further options after surgery in case of residual or recurrent tumors include radiotherapy and somatostatin analogs. Our patient underwent an uncomplicated trans-sphenoidal resection of the firm, invasive pituitary tumor.[7] Some amount of adenomatous tissue encircling the internal carotid artery was left behind and was noted on follow-up MRI [Figure 1].
Figure 1: Preoperative (top row) and postoperative (bottom row) MRI showing a good resolution of the tumor following surgery with minimal residual focus near the right internal carotid artery

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Interestingly, immunostaining of tumor tissue demonstrated a stronger positivity for GH followed by TSH, prolactin, and ACTH [Figure 2]. Approximately 30% of TSHomas are plurihormonal in nature accompanied by deregulation of other endocrine axes. GH and prolactin are the most commonly associated hormones. This may be because somatotroph and lactotroph cells share common transcription factors with thyrotrophs such as Prop-1 and Pit-1. This theory implies that a group of resting poorly differentiated pituitary cells transform, due to environmental influences, into plurihormonal adenomas later in life. In contrast, the rarity of occurrence of mixed TSH adenomas associated with gonadotropic and corticotropic hormones may probably be due to the distant origin of their lineages from thyrotropes.
Figure 2: Histology and immunolabelling of the resected TSHoma cells showing well-differentiated adenomatous cells with dense rounded central nuclei and eosinophilic cytoplasm (top left). Strongly positive immunolabelling to TSH (bottom left), GH (top right), prolactin (middle right) and weakly positive staining for ACTH (bottom right) is present

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In addition, plurihormonality does not always translate into the clinical features of hormonal excess, as other hormones may be biologically silent.[8] As in our case, immunohistochemistry was stronger for GH in comparison to TSH and prolactin, with a mild positivity for ACTH. Lack of a corresponding biochemical and clinical endocrine syndrome of GH, prolactin, and ACTH may be attributed to defective peptide synthesis by the tumor tissue. Retrospectively, we do understand that preoperative dexamethasone suppression test, somatomedin C levels, and oral glucose tolerance test with GH might have aided in diagnosing the subclinical disease of hormonal excess for ACTH and GH in this patient. In addition, elevated prolactin levels in our patient can be explained by the stalk effect; however, strong immunoreactivity for prolactin in the adenomatous tissue usually suggests a tumoral etiology. Similarly, a positive TSH immunostaining without clinical evidence of hyperthyroidism can be found in up to 30% of clinically nonfunctioning pituitary adenomas.[8] It is worth noting that the thyrotoxic presentation is more common in thyrotropic plurihormonal adenomas than in pure TSH secreting adenomas.[9] At a follow up of 18 months, our patient continues to be asymptomatic and euthyriod without any antithyroid medications; there is no increase in the size of the residual tumor [Figure 3].
Figure 3: Biochemical data of the patient

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In conclusion, TSH adenomas have a heterogenous clinical presentation, hormonal profile, and therapeutic response. Increased awareness and more reporting of such cases will lead us to acertain the appropriate etiopathogenesis of this disease.

Acknowledgment

We thank Dr Geeta Verma (SRL Limited, Mumbai), Dr Joseph Katticaran (Medical Trust Hospital, Kochi) for their valuable insight on imunohistochemistry. We are also grateful to our endocrinologist Dr. Jayaprakash (Medical Trust Hospital, Kochi).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Jailer JW, Holub DA. Remission of Graves' disease following radiotherapy of a pituitary neoplasm. Am J Med 1960;28:497-500.  Back to cited text no. 1
[PUBMED]    
2.
Beck-Peccoz P, Lania A, Beckers A, Chatterjee K, Wemeau JL. 2013 European Thyroid Association Guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. Eur Thyroid J 2013;2:76-82.  Back to cited text no. 2
[PUBMED]    
3.
Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: Occult adenomas in the general population. Ann Intern Med 1994;120:817-20.  Back to cited text no. 3
[PUBMED]    
4.
Mannavola D, Persani L, Vannucchi G, Zanardelli M, Fugazzola L, Verga U, et al. Different responses to chronic somatostatin analogues in patients with central hyperthyroidism. Clin Endocrinol 2005;62:176-81.  Back to cited text no. 4
    
5.
Kienitz T, Quinkler M, Strasburger CJ, Ventz M. Long-term management in five cases of TSH-secreting pituitary adenomas: A single center study and review of the literature. Eur J Endocrinol 2007;157:39-46.  Back to cited text no. 5
[PUBMED]    
6.
Losa M, Giovanelli M, Persani L, Mortini P, Faglia G, Beck-Peccoz P. Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 1996;81:3086-90.  Back to cited text no. 6
    
7.
Sharma BS, Sawarkar DP, Suri A. Endoscopic pituitary surgery: Techniques, tips and tricks, nuances, and complication avoidance. Neurol India 2016;64:724-36.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD. Thyrotropin secreting pituitary tumors. Endocrine Rev 1996;17:610-38.  Back to cited text no. 8
    
9.
Bertholon-Grégoire M, Trouillas J, Guigard MP, Loras B, Tourniaire J. Mono- and plurihormonal thyrotropic pituitary adenomas: Pathological, hormonal and clinical studies in 12 patients. Eur J Endocrinol 1999;140:519-27.  Back to cited text no. 9
    


    Figures

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