SAT-268 Thyrotropin Secreting Pituitary Adenoma Initially Misdiagnosed as Primary Hyperthyroidism in a Taiwanese Man

Background:TSH (Thyrotropin) secreting pituitary adenoma (TSHoma) account for less than 1% of all causes of hyperthyroidism and 1% of all functioning pituitary tumors. Definite diagnosis and treatment of TSHoma are clinical challenges in practice. Here we report laboratory data, imaging findings, endocrine dynamic test, and treatment outcomes in a 50-year-old Taiwanese man with pituitary plurihormonal adenoma secreting TSH and LH. Clinical case:The patient was initially diagnosed as goiter with primary hyperthyroidism and DM while medical check-up by primary care physician in 2014. He had no significant hyperthyroidism symptoms and signs except goiter and mild palpitation. He received propylthiouracil and Metformin. Two years later, he visited to Endocrinologist’s clinic for poor glycemic control. Central hyperthyroidism was diagnosed due to measurable TSH level in the presence of increased serum thyroid hormone level. Moreover sella MRI revealed left sided pituitary lesion. He was referred to Taipei Veteran General Hospital for further management. There was no family history of thyroid disease. Physical examination was not remarkable except diffuse grade 3 goiter and tachycardia (HR 100~115 bpm). Follow up laboratory data showed TSH 4.89; range 0.4~4.0 uIU/ml, free T4: 3.05; range 0.9~1.8 ng/dl, T4: 16.02; range 4.50~12.50 μg/dl, T3: 249; range 58~159 ng/dl, free T3: 8.0; range 2.3~4.3 pg/ml. Two times of TRH stimulation test showed blunted TSH response. Normal limit of thyroid autoantibodies level were found. Thyroid sonography revealed heterogenous echogenicity with increased size and vascularity of both lobes. I-131 uptake was homogenous uptake (94%). Other pituitary hormones level were within normal limit except mild elevation of testosterone 12.69 ng/ml. Sella MRI with contrast showed macroadenoma (size 10x10x7.6 mm) at left pituitary gland. Taken together, he was diagnosed as central hyperthyroidism related to left sided pituitary macroadenoma. Surgery was performed after one year of definite diagnosis due to personal reason. TSH level returned to normal ranges (0.799 uIU/ml) in 1st post operative day. Histologically, the pituitary mass was compatible with plurihormonal adenoma and immunohistochemistry showed positivity for TSH (4+) and LH (3+). Post operative condition was well. Antithyroid agent was discontinued after operation. His blood glucose became well controlled after operation. Clinical lessons:A biochemical hallmark of TSHoma is an escape of TSH from the feedback loop that is detectable TSH levels in the presence of increased serum thyroid hormone level. Diagnosis of TSHoma was frequently unrecognized and thus much delayed despite its relatively straightforward. Physician should keep in mind that the importance interpretation of simple laboratory tests to avoid delay diagnosis and unnecessary treatments.

Plurihormonal Pit-1 lineage adenoma presenting as meningitis with recurrence after somatostatin analogue

Summary A 21 year-old woman was found to have a pituitary macroadenoma following an episode of haemophilus meningitis. Biochemical TSH and GH excess was noted, although with no clear clinical correlates. She was treated with a somatostatin analogue (SSA), which restored the euthyroid state and controlled GH hypersecretion, but she re-presented with a further episode of cerebrospinal fluid (CSF) leak and recurrent meningitis. Histology following transsphenoidal adenomectomy revealed a Pit-1 lineage plurihormonal adenoma expressing GH, TSH and PRL. Such plurihormonal pituitary tumours are uncommon and even more unusual to present with spontaneous bacterial meningitis. The second episode of CSF leak and meningitis appears to have been due to SSA therapy-induced tumour shrinkage, which is not a well-described phenomenon in the literature for this type of tumour. Learning points: Pit-1 lineage GH/TSH/PRL-expressing plurihormonal pituitary adenomas are uncommon. Moreover, this case is unique as the patient first presented with bacterial meningitis. Inmunohistochemical plurihormonality of pituitary adenomas does not necessarily correlate with biochemical and clinical features of hormonal hypersecretion. Given that plurihormonal Pit-1 lineage adenomas may behave more aggressively than classical pituitary adenomas, accurate pathological characterization of these tumours has an increasing prognostic relevance. Although unusual, a CSF leak and meningitis may be precipitated by SSA therapy of a pituitary macroadenoma via tumour shrinkage.

Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data

Objective: The aim of this study was to examine pituitary adenomas in a series of postmortem pituitaries by use of modern technologies of immunostaining, to classify the adenomas according to the current WHO classification and to analyse the possible associations to the available clinical data. Methods: In this study, pituitaries of 3048 autopsy cases obtained from autopsy series of the years 1991–2004 were examined. Results: A total of 334 pituitary adenomas were found in 316 pituitaries. One hundred and thirty-two sparsely granulated prolactin cell adenomas (39.5%), 75 null cell adenomas (22.5%) and 31 oncocytomas were diagnosed. Forty-six ACTH cell adenomas (13.8%, 27 densely granulated, 19 sparsely granulated) and one adenoma composed of Crooke’s cells were detected. Twenty-two gonadotroph cell adenomas (6.6%), seven GH cell adenomas (four sparsely granulated, three densely granulated), one mixed GH cell–PRL cell adenoma, two TSH cell adenomas, five plurihormonal adenoma type I, four plurihormonal adenoma type II and two α-subunit-only adenomas were seen. Six adenomas remained unclassified because the tissue was not contained in all sections for immunohistochemistry. Seventeen pituitaries included multiple tumours. The overall tumour size ranged from 0.1 to 20 mm in diameter. Among 76 adenomas (22.7%), which had a tumour size of ≥ 3 mm, only three tumours were macroadenomas corresponding to a tumour size of more than 10 mm. The evaluation of the available clinical data showed 99 cases of hypertension, 65 cases of diabetes mellitus, six patients with hyperthyroidism and four with hypothyroidism. No symptoms of adenohypophyseal hormone hypersecretion were reported. The statistical correlations to clinical data were discussed. Conclusions: Adenomas in postmortem pituitaries differ from those in surgical series in proportion of adenoma types and biological behaviour.