Thyrotropin-secreting Pituitary Adenoma Research Articles

A challenging case of a pituitary macroadenoma and toxic thyroid adenoma with inappropriate TSH secretion.

Thyroid-stimulating hormone-secreting pituitary adenomas (TSHomas) are rare, accounting for less than 1% of all pituitary adenomas. We present a case of hyperthyroidism secondary to a likely TSHoma and coexisting functional thyroid adenoma. Laboratory errors and familial abnormalities in thyroid function tests were ruled out, and a diagnosis of the toxic thyroid adenoma was confirmed on a thyroid uptake scan. However, the triiodothyronine suppression test was contraindicated due to the patient's cardiovascular disease, and the thyrotropin-releasing hormone stimulation test, measurement of glycoprotein hormone alpha-subunit, and genetic testing were unavailable. Magnetic resonance imaging of the brain revealed a suprasellar pituitary macroadenoma measuring 40 mm × 20.3 mm × 17 mm. The patient was initiated on carbimazole; however, thyroid stimulating hormone and thyroxine levels remained elevated. The patient declined trans-sphenoidal surgery and was treated with radioactive iodine to manage the toxic thyroid adenoma, leading to reduced thyroxine levels and symptom improvement. Unfortunately, the patient passed away before long-acting somatostatin analogs became available. This case highlights the diagnostic and therapeutic challenges involved in managing thyrotoxicosis with dual etiology. Hyperthyroidism can have multiple etiologies, which can coexist in the same patient. Persistent discordant thyroid function tests warrant further investigation. The gold standard for diagnosis of TSHomas remains immunohistochemical analysis of the tumor tissue.

Thyrotropin Secreting Pituitary Adenoma: A Clinical Case of Postoperative Re-Onset Thyrotoxicosis with Adenoma Recurrence.

Thyrotropin-secreting pituitary adenomas are rare benign tumours. Proper diagnosis can be challenging, requiring TSH autonomous production and differentiation from resistance to thyroid hormone action (RTH).Undetectable TSH levels one week after surgery and/or positive T3 suppression test or no response to TRH stimulation test seem to be the criteria with the best prognostic value post-treatment.Close clinical, biochemical and imaging follow-up is crucial to detect TSHoma recurrence.

The Endoscopic Endonasal Transsphenoidal Approach for Thyrotropin-Secreting Pituitary Adenomas: Single-Center Experience and Clinical Outcomes of 49 Patients

To analyze surgical outcomes and tumor characteristics of 49 patients with thyrotropin-secreting pituitary adenoma, a rare functional pituitary adenoma subtype with challenging surgery, who underwent endoscopic endonasal transsphenoidal surgery. In this single-center study, clinical, radiological, surgical, and endocrinological data of 49 patients diagnosed with thyrotropin-secreting pituitary adenoma were retrospectively reviewed. Mean tumor size was 21.12 mm (6 microadenomas, 41 macroadenomas, 2 giant adenomas). Cavernous sinus invasion was present in 12 (24.48%) patients. Tumor consistency was firm in 23 (46.93%) patients. Plurihormonal secretion characteristics were present in 9 patients (5 growth hormone+ thyrotropin and 4 growth hormone+ prolactin+ thyrotropin). Mean follow-up duration was 51.73 months. Of the cases with firm tumors, 14 patients had a history of antithyroid drug use; there was no statistically significant correlation between the antithyroid medication and the firmness of the tumor. Gross total resection was achieved in 32 (65.30%) cases, near-total resection was achieved in 14 (28.57%) cases, and subtotal resection was achieved in 3 (6.12%) cases. The analysis showed that the negative effect of >2 cm tumor size and cavernous sinus invasion on resection rate was statistically significant (P < 0.001). Although early remission was achieved in 33 (67.34%) patients, 44 (89.79%) patients were in euthyroid state at >3 months' follow-up. Complications were 4 new-onset pituitary deficiencies, 3 cases of permanent diabetes insipidus, 1 thyrotoxic crisis, and 1 cerebrospinal fluid leak. Endoscopic endonasal transsphenoidal surgery is the first-line treatment in thyrotropin-secreting pituitary adenoma and should be performed in a tertiary center. Gross total resection is the goal, and early diagnosis is essential for surgical success.

Abstract 127: Pituitary resistance to thyroid hormone due to a novel mutation in the NCOR2 gene: The first case report

Background: Pituitary resistance to thyroid hormone-β (RTH-β) presents with the symptoms of hyperthyroidism with inappropriate secretion of thyroid stimulating hormone (TSH). Mutation in the coding region of the TR-β gene is not observed in 10% of cases, which are termed as non-TRβ RTH. Till date, the specific contributions of co-repressors and co-activators in pituitary resistance to thyroid hormone remain unknown.Materials and Methods: We present a case of 44-year male with pituitary RTH, showing features suggestive of thyrotoxicosis, atrial fibrillation and goiter. Clinical investigations included estimation of serum FT4, T3, TSH, TRab, TPO antibodies, Tc-thyroid scan, MRI for sella. To understand the genetic cause of the disorder, we undertook the whole genome sequencing (WES) in the proband and family members, which was followed by Sanger's sequencing for confirmation. To validate the possibility of RTH due to the novel gene discovered, we undertook in-vitro functional studies using NCOR2 siRNA.Results: A 44 year old male presented with atrial fibrillation with thyrotoxicosis and elevated serum T4, FT4, and T3, and nonsuppresed TSH levels (serum total T4 24.50 ug/dl, total T3 5.22 nmol/l and TSH 5.50 uIU/ml. On treatment with PTU, he had serum TSH 16.24 uIU/ml, FT4 50 nmol/l, and total T3 6.61 nmol/l. Further clinical workup by 99mTc pertechnetate thyroid scan showed bilateral diffusely increased uptake, negative serum TRAb and TPO antibody. A differential diagnosis of RTH or TSH secreting pituitary adenoma was made. Gadolinium enhanced MRI of sella was normal. We observed loss of inverse correlation of serum T3 and TSH levels, signifying the loss of negative feedback mechanism. WES identified two novel mutations in the NCOR2 gene (p.Ser2304Gly, p.Ala2489Thr) in the proband. Both the mutation (p.Ala2489Thr) were confirmed in the proband and one of his children. Bioinformatics analysis suggested p.Ala2489Thr to be pathogenic. Functional studies in GH3 cell lines using NCOR2 siRNA revealed NCOR2 dependent regulation of TSH levels, further strengthening that NCOR2 mutations could cause RTH.Conclusion: We hereby describe the first case of pituitary RTH due to a novel mutation in the NCOR2 gene in a family with thyrotoxicosis.

Thyreotroop adenoom van de hypofyse: een zeldzame oorzaak van hyperthyreoïdie

TSH-secreting pituitary adenoma: a rare cause of hyperthyroidism Central hyperthyroidism is noted in a 35-year-old man with recurrent panic attacks. Thyroid-stimulating hormone-secreting pituitary adenoma (TSH-secreting adenoma) is found to be the underlying etiology. A pituitary adenomectomy is carried out, with regression of the symptoms and hyperthyroidism. TSH-secreting adenomas are rare and cause hyperthyroidism due to autonomous TSH secretion. In addition to hyperthyroidism, dysfunction of other pituitary axes and neurological problems due to local compression may also be present. Biochemically, TSH adenoma is characterized by elevated levels of thyroid hormones without suppression of the TSH concentration. After analytical interference has been ruled out, additional biochemical and radiological investigations are necessary in the differential diagnosis and to establish diagnostic certainty. Neurosurgical resection is the cornerstone of the treatment, although radiotherapy and somatostatin analogs may also be considered.

ENDOCRINE TUMOURS: Thyrotropin-secreting pituitary adenoma: a structured review of 535 adult cases.

Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare entity, occurring in one per million people. We performed a systematic review of 535 adult cases summarizing the clinical, biochemical, hormonal and radiological characteristics of TSHoma. Furthermore, we discussed the current guidelines for diagnosis and treatment. A structured research was conducted using Pubmed and Web of Science with the following MeSH terms: 'thyrotropin secreting pituitary adenoma' OR 'TSHoma' OR 'thyrotropinoma.' Our analysis included 535 cases originating from 18 case series, 5 cohort studies and 91 case reports. The mean age at diagnosis was 46 years. At presentation, 75% had symptoms of hyperthyroidism, 55.5% presented with a goitre and 24.9% had visual field defects. The median TSH at diagnosis was 5.16 (3.20-7.43) mU/L with a mean FT4 of 41.5 ± 15.3 pmol/L. The majority (76.9%) of the TSHomas were macroadenoma. Plurihormonality was seen in 37.4% of the adenoma with a higher incidence in macroadenoma. Surgical resection of the adenoma was performed in 87.7% of patients of which 33.5% had residual pituitary adenoma. Post-operative treatment with a somatostatin analogue (SSA) led to a stable disease in 81.3% of the cases with residual tumour. We noticed a significant correlation between the diameter of the adenoma and residual pituitary adenoma (r = 0.490, P < 0.001). However, in patients preoperatively treated with an SSA, this correlation was absent. TSHomas are a rare cause of hyperthyroidism and are frequently misdiagnosed. Based on our structured analysis of case series, cohort studies and case reports, we conclude that the majority of TSHomas are macroadenoma being diagnosed in the fifth to sixth decade of life and presenting with symptoms of hyperthyroidism. Plurihormonalitiy is observed in one-third of TSHomas. Treatment consists of neurosurgical resection and SSA in case of surgical failure.

Thyrotropin-secreting pituitary adenomas induce left atrial enlargement with subclinical atrial fibrillation: an echocardiographic study.

Thyrotropin-secreting pituitary adenoma (TSHoma) is rare but occasionally causes cardiovascular complications such as atrial fibrillation (AF) due to hyperthyroidism. Graves' disease (GD) is a common hyperthyroid condition often associated with subclinical AF. Some reports have shown echocardiographic changes in patients with GD. We aimed to evaluate the preoperative cardiac function in patients with TSHomas and compared the results among patients with TSHomas and GD and control subjects. Patients with TSHomas (n = 6) and GD (n = 20) were compared with control subjects with normal cardiac function (n = 20) based on echocardiographic findings. The average age, sex, and proportions of patients with a history of diabetes mellitus and hypertension were equal in each group, and the AF prevalence was matched in patients with TSHomas and GD. The values of left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), left ventricular ejection fraction (LVEF), and left atrial diameter (LAD) were used to assess cardiac function. In echocardiography, LAD showed a significant difference between patients with TSHomas and control subjects (p = 0.026). The mean LAD values were 36.9 ± 7.1, 38.2 ± 8.9, and 28.7 ± 3.9 mm for patients with TSHomas and GD and control subjects, respectively. There were no significant differences in other echocardiographic parameters among the groups. Before treatment, serum thyroid hormone levels (free triiodothyronine and thyroxin) were not significantly different among patients with TSHomas and GD. We found that patients with TSHomas or GD had enlarged LADs. This finding suggests that AF may be more hidden in patients with TSHomas than previously reported.

Two thyrotropin secreting pituitary adenoma cases diagnosed after response to the somatostatin analogue

Two thyrotropin secreting pituitary adenoma cases diagnosed after response to the somatostatin analogue

Two thyrotropin secreting pituitary adenoma cases diagnosed after response to the somatostatin analogue

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Two thyrotropin secreting pituitary adenoma cases diagnosed after response to the somatostatin analogue

Two thyrotropin secreting pituitary adenoma cases diagnosed after response to the somatostatin analogue

Invasive Thyrotropin-secreting pituitary adenoma: A case report

Invasive Thyrotropin-secreting pituitary adenoma: A case report

Growth Hormone (GH) and Thyroid Stimulating Hormone (TSH) Co-Secreting Pituitary Macroadenoma

Background: TSH secreting pituitary adenomas are rare and accounts for 0.5-3% of all pituitary adenomas. Only 20-25% of those adenomas co-secrete other hormones like growth hormone or prolactin. Mixed GH and TSH secreting adenomas present with symptoms from tumor growth and features of both acromegaly and hyperthyroidism. Clinical Case: A 57 years old woman with a past medical history of chronic joint pains and bilateral knee swelling presented to her PCP with complaints of chronic fatigue. Evaluation revealed a normal TSH level and MNG and patient did not have any further work-up. She reported undergoing periodic knee arthrocentesis which gave her only temporary pain relief. Two years later, patient presented with complaints of unintentional weight loss, tremors and palpitations. She also reported enlargement in the size of hands, feet and forehead and no improvement in the knee swelling after multiple arthrocentesis. Lab evaluation revealed high free T4 2.31ng/dl (0.58-1.64), high free T3 6.44pg/ml (2.50-4.30), non-suppressed TSH 1.32mU/L (0.34-5.00), elevated IGF-1 415ng/ml (47-236), GH 7.76ng/ml (0.01-3.61) and prolactin 6.69ng/mL (2.74-26.72). Neck USG showed multiple nodules and 24hr radioactive iodine uptake scan showed increased uptake at 43%. 75gm OGTT showed non-suppression of GH level. MRI of brain showed 1.8 cm pituitary macroadenoma. Patient underwent transsphenoidal pituitary resection in January 2018 and the final pathology showed positive tumor staining for GH and TSH. Following surgery, patient reported improvement in symptoms. Lab work-up from October 2018 showed normal IGF 189 ng/ml (47-236), normal GH 0.35(0.01-3.61), Free T4 0.80(0.58-1.64), Free T3 2.41(2.50-4.30), TSH 0.06(0.34-5.00) and MRI from August 2020 showed no evidence of residual pituitary tumor. Conclusion: This is a rare case of a GH and TSH co-secreting pituitary macroadenoma. This case highlights the importance of considering acromegaly early in the differential diagnosis of patients presenting with chronic musculoskeletal symptoms and to pursue work up for central hyperthyroidism in a hyperthyroid patient presenting with a non-suppressed TSH level.

Thyrotropin-Secreting Pituitary Adenoma Successfully Treated With Cabergoline

Background: Thyrotropin secreting pituitary adenomas (TSH-oma) account for less than 1% of pituitary adenomas and are a rare cause of hyperthyroidism. In this case, we describe the safe use of cabergoline with the subsequent achievement of euthyroid levels and the resolution of symptoms. Clinical Case: A 67-year-old female with a presumed history of hypothyroidism for the last 3 years managed with Armour thyroid was referred for fatigue associated with palpitations, intermittent diarrhea, insomnia, and anxiety. Her TSH was noted to be suppressed at that time, and her Amour thyroid was changed to Levothyroxine 25 mcg daily, which was eventually stopped as her symptoms persisted. Follow-up thyroid function tests (TFTs) showed elevated TSH (8.60 µU/mL, reference range 0.340 - 5.600 µU/mL), and elevated free T3 (10.8 pg/mL, reference range 2.7-4.7 pg/mL) and free T4 (2.0 ng/dL, reference range 0.8-1.5 ng/dL) levels. Further laboratory workup including basal prolactin, LH, FSH, hCG α-subunit, IGF-1, and ACTH levels were within the normal range. Physical examination showed diffuse thyroid enlargement. An I-123 thyroid uptake and scan showed uniform uptake throughout the gland with no focal hyperintense areas. A dedicated pituitary MRI was performed and revealed an 8 mm microadenoma in the posterior left adenohypophysis. The patient wanted to avoid any invasive treatment and refused trans-sphenoidal surgery and medical therapy was chosen. Unfortunately, using a somatostatin analog as part of the standard medical treatment was not an option due to the high cost and lack of insurance coverage. For these reasons, a trial of cabergoline was started to suppress TSH secretion. Atenolol 25 mg daily was added temporarily for the management of her sympathetic symptoms. On periodic follow-up, her symptoms gradually subsided, and TFTs remained within normal limits. Treatment was continued for one year. Conclusion: Clinical manifestations of hyperthyroidism with biochemical evidence of elevated thyroid hormone levels and TSH levels should raise a strong suspicion for central or secondary hyperthyroidism due to TSH secreting pituitary adenoma. Cabergoline might represent an effective alternative form of medical treatment for TSH-oma in certain situations where the first line therapeutic options are refractory, contraindicated, or declined.

TSH, GH, and Prolactin Producing Pituitary Adenoma: An Unusual Case Presentation

Background: Pituitary adenomas are benign and frequent tumors, some of them with tendency to be recurrent or invasive e. several pituitary tumors are positive for secretion of one or more hormones of the same adenohypophysial cell lineage. However, some cases have a subclinical course and are underestimated because they have plurihormonal secretion of different adenohypophyseal cells lineage. Clinical Case: A 38 years old women with chronic headaches, who is in fertility treatment for 12 month ago presents to the clinic with unremarkable physical examination. Her laboratory studies include: Normal campimetry. T3 (triiodothyronine) 2.15 ng/m L (NR:0.8 - 2.0), TSH (thyroid stimulating hormone) 4.4 uU/mL (NR:0.27 - 4.2), T4 (tetraiodothyronine) 13.54 ug/dl, (NR:5.1 - 14.1), Free T4 2.44 ng/d (NR:0.93 - 1.7), Estradiol 60.2 pg/ml, FSH (Follicle stimulating hormone) 4.3 mUI/ml (NR:1,7-12), Cortisol (?8 am) 9.29 ug/dl (NR:4.2 - 38.4), ACTH (Corticotrophin-releasing hormone) 13.1 pg/ml (NR: 0.0 - 46.0), Somatomedin C (IGF-1) 231 .0 ng/ml (NR for age?: 57.0-241.0). Brain MRI with pituitary protocol showed in T1 an isointense lesion and slightly heterogeneous in T2 in the anterior and left aspect of the turkish saddle, of 1 x 1.1 x 1.1 cm of anteroposterior, transverse and cephalocaudal diameter, suggestive of a macroadenoma. The tumor pathology showed, possitive for a pituitary adenoma. Immunohistochemistry results were negative for: ACTH:, positive for GH, TSH: (+++) and for Prolactin:. Her post-operative findings showed a residual pituitary gland without significant findings. Her post operative pituitary axis include: Sodium 139.2 mmol/l (NR”135.0 - 145.0), Chloride 100.8 mmol/l (NR95.0 - 115.0), Potassium 3.71 mmol/l (NR3.5 - 5.1), ACTH 4.1 pg/ml(NR0.0 - 46.0), Cortisol (am) 11.11 ug/dl (NR4.2 - 38.4), Estradiol 106.5 pg/ml, FSH 5.1 mUI/ml, LH (Luteinizing Hormone) 13.53 mIU/ml, Somatomedin C (IGF-1) 134 .0 ng/m, Free T32.4 pg/ml, TSH 0.9 uU/mL Free T4 0.99 ng/dl, and Prolactin 23.4ng/ml. Patient had a satisfactory clinical course after surgery, she maintained normal pituitary function without requirement of hormonal replacement therapy. Conclusion: We present a a prolactin, TSH and GH secreting pituitary adenoma case, which is very unusual. It i is important to make a proper pituitary evaluation, and offer effective treatment to prevent complications

Somatostatin receptor ligands induce TSH deficiency in thyrotropin-secreting pituitary adenoma.

Somatostatin receptor ligands (SRL) are useful to control central hyperthyroidism in patients with thyrotropin-secreting pituitary adenoma (TSH pituitary adenoma). The aim of this study was to describe the frequency of thyrotropin deficiency (TSH deficiency) in patients with TSH pituitary adenoma treated by SRL. Retrospective study. Patients with central hyperthyroidism due to TSH pituitary adenoma treated by short or long-acting SRL were retrospectively included. TSH deficiency was defined by a low FT4 associated with non-elevated TSH concentrations during SRL therapy. We analysed the frequency of TSH deficiency and the characteristics of patients with or without TSH deficiency. Forty-six patients were included. SRL were used as the first-line therapy in 21 of 46 patients (46%). Central hyperthyroidism was controlled in 36 of 46 patients (78%). TSH deficiency appeared in 7 of 46 patients (15%) after a median time of 4 weeks (4-7) and for a median duration of 3 months (2.5-3). The TSH deficiency occurred after one to three injections of long-acting SRL used as first-line therapy in 6/7 cases. There were no differences in terms of clinical and hormonal features, size of adenomas or doses of SRL between patients with or without TSH deficiency. SRL can induce TSH deficiency in patients with central hyperthyroidism due to TSH pituitary adenoma. Thyrotropic function should be assessed before the first three injections of SRL in order to track TSH deficiency and reduce the frequency of injections when control of thyrotoxicosis rather than tumour reduction is the aim of the treatment.

Incidence, mortality, and cardiovascular diseases in pituitary adenoma in Korea: a nationwide population-based study.

Few nationally representative studies have evaluated the epidemiology of PA (pituitary adenoma). This South Korean study evaluated the incidence of different PA subtypes, cardiovascular disease (CVD), and related mortality. This population-based study evaluated 31,898 patients with PA during 2005-2015. The incidence of PA, mortality, and CVD occurrence in PA cases were evaluated during a median follow-up of 5.3years (range: 0-10years). Cox regression analysis was used to evaluate the associations between CVD and mortality. The annual incidences (per 100,000 population) were 3.5 for non-functioning pituitary adenoma (NFPA), 1.6 for prolactinoma (PRL), 0.5 for growth hormone-secreting pituitary adenoma (GH), and 0.2 for adrenocorticotropic or thyroid-stimulating hormone-secreting pituitary adenoma (ACTH + TSH). The standardized mortality ratios were 1.9 for ACTH + TSH, 1.7 for NFPA with hypopituitarism, 1.4 for NFPA without hypopituitarism, 1.3 for GH, and 1.1 for PRL. During 2005-2015, the overall incidence of CVD among PA patients was 6.6% (2106 cases), and the standardized incidence ratios were 4.1 for hemorrhagic stroke, 3.0 for ischemic stroke, and 1.7 for acute myocardial infarction. The standardized incidence ratios for stroke were significantly higher in the ACTH + TSH and NFPA groups, which also had higher risks of CVD-related mortality, relative to the PRL and GH groups. South Korea had a relatively high incidence of NFPA. The incidence of stroke was highest for ACTH + TSH and NFPA, which was directly related to mortality during long-term follow-up. Patients with these types of PA should receive stroke prevention measures to reduce their risk of mortality.

Cosecreting TSH/GH pituitary adenomas-an 8-year experience in a single tertiary center.

Thyrotropin-secreting pituitary adenoma is a rare disorder and was recently classified as an aggressive tumor in the World Health Organization guidelines. The number of available studies on cosecreting thyrotropin/growth hormone pituitary adenoma is especially limited. A single-center retrospective analysis of patients with thyrotropin/growth hormone pituitary adenoma was performed at Peking Union Medical College Hospital, one of the largest pituitary care centers in China, from January 2012 to January 2020. Additionally, data about cosecreting thyrotropin/growth hormone pituitary adenoma were collected and analyzed. The diagnosis, therapy and follow-up were all compared to that of solo-secreting thyrotropin pituitary macroadenoma. Twelve patients (10.81%) were identified with thyrotropin/growth hormone pituitary adenoma at Peking Union Medical College Hospital within 8years, all of which were classified as macroadenoma. Compared with solo-secreting thyrotropin pituitary macroadenoma, thyrotropin/growth hormone pituitary adenoma presented with a higher proportion of cavernous sinus invasion (50%) and had a larger maximum tumor diameter. The patients had a lower surgical complete remission rate and a worse prognosis. Interestingly, they revealed a striking phenomenon of "solo part remission". Thyrotropin/growth hormone pituitary adenoma is rare. Some patients do not present with the typical manifestations; however, the possibility of a cosecretion tumor should not be excluded. A preoperative comprehensive evaluation of anterior pituitary hormones is necessary. Thyrotropin/growth hormone pituitary adenoma revealed a high tendency of invasion, and the prognosis of patients with thyrotropin/growth hormone pituitary adenoma was poor. If necessary, timely postoperative drug administration or radiotherapy should be carried out.

SAT-261 Thyroid Stimulating Hormone-Secreting Pituitary Macroadenoma and Papillary Thyroid Cancer in a 55-Year-Old Male: A Case Report

Background: Thyroid-Stimulating Hormone Secreting Pituitary Adenoma (TSHoma) is a rare Endocrinologic finding occurring in 0.5–3% of all pituitary adenomas, and is even rarer to find it coexisting with differentiated thyroid cancer. Clinical Case: A 55-year-old male consulted last 2012 for palpitations and resting tachycardia. Initial tests revealed an ECG of sinus tachycardia, normal electrolytes and TSH 3.16 uIU/mL (0.27–4.2) and FT4 66 pmol/mL (12–22). He was referred to an Endocrinologist where thyroid ultrasound was done revealing bilaterally enlarged thyroid lobes with diffuse thyroid parenchymal changes, and a thyroid scan consistent with Graves’ Disease. He was started on methimazole and beta-blockers. Persistently elevated FT4 and a non-suppressed TSH prompted work-up for secondary hyperthyroidism. Pituitary MRI revealed a sellar mass measuring 3.4cm x 2.7cm x 2.6cm, noted to be compressing the left side of the optic chiasm and prechiasmatic left optic nerve laterally. The consideration was pituitary macroadenoma. He underwent trans-sphenoidal surgery but operative technique only involved near total excision of the adenoma due to proximity of the mass to the pre-chiasmatic left optic nerve. The tumor was reduced to 2.8cm x 1.6cm x 1.5cm. Histopathologic diagnosis and immuno-histochemical staining revealed pituitary tumor cells reactive to TSH but non-reactive to FSH, LH and GH. He eventually underwent intensity-modulated radiation therapy (IMRT) which reduced the tumor size, but did not obliterate the tumor. His thyroid function tests persistently revealed elevated TSH and FT4 levels. Last January 2019, he manifested with an enlarged anterior neck mass. An ultrasound revealed thyromegaly with multiple nodules, largest at 1.4cm with multiple sub-centimeter nodules, mostly complex and solid in description. He underwent total thyroidectomy. Histopathology results revealed Papillary Thyroid Cancer with no extracapsular or lymphovascular invasion. He was scheduled for radioactive iodine at 100mci a month after. His I-131 whole body scan revealed foci of residual thyroid tissue but without distant mestastases. He is currently on levothyroxine at 225mcg daily therapy and advised annual cranial MRI readings which mostly showed a stable pituitary tumor. Conclusion: This is a case of TSHoma, S/P trans-sphenoidal surgery and intensity modulated radiation therapy with significant tumor residuals that eventually led to the development of Papillary Thyroid Cancer and subsequent total thyroidectomy and radioactive iodine administration. He is now on frequent tumor monitoring and levothyroxine suppression dose.Reference:P. Beck-Peccoz, A. Lania, A. Beckers, K. Chatterjee d, J.-L. Wemeau. 2013 European Thyroid Association Guidelines for the Diagnosis and Treatment of Thyrotropin-Secreting Pituitary Tumors. Eur Thyroid J 2013;2:76–82.

MON-313 Thyrotropin-Secreting Pituitary Tumors: Clinical Features, Diagnostic Criteria and Treatment Outcomes in 28 Patients

Introduction Thyrotropin-secreting pituitary adenoma (TSH-oma) is a rare cause of thyrotoxicosis and represents 0.5-3% of all pituitary adenomas. Given the rarity of the disease and the lack of extensive clinical experience in world practice, the analysis of each case of TSH-secreting pituitary tumors is extremely relevant. Materials and methods: We enrolled consecutive patients with TSH secreting pituitary adenoma. TSH (0,25-3,5 mIU/L), FT4 (9-20 pmol/l) FT3 (2,5-5,5 pmol/l) were measured by Architect i2000SR (Abbott Laboratories, Abbott Park, Illinois, U.S.A). An octreotide test consisted of injecting short-acting somatostatin analogue (SSA) at a dose of 100 μg 3 times a day subcutaneously during 3 days or long-acting SSA 20 mg in 28 days minimum for two months and measuring thyroid profile blood tests before and at the end of the test. MRI was performed on GE Optima MR450w 1.5T. Results: We present 28 case series with TSH-omas followed in our center from 2010 to 2019, the median age - 46 (from 10 to 71 years) with a predominance of a female (21 cases) over a male (7 cases). Clinical manifestations included cardiac arrhythmias (82.1%), neurological changes (60.7%), visual impairment (39.3%), osteoporosis (28.6%), hypopituitarism (7.1%).At first admission, 17 patients had increased TSH, FT3 and FT4; in 7 patients - FT3 and FT4 only, and in 4 - an increase was in one of the hormones; mean value of TSH was 5,04 mIU/L, FT4 - 24,46 pmol/l, FT3 - 8,9 pmol/l. SSBG, CTx, osteocalcin were elevated in 60.9%, 57.9% and 31.6% of cases, respectively. In 88.5% of cases octreotide test led to thyroid hormones normalization. On MRI macroadenomas was registered in 67.9%. In 12 patients, diagnosis was confirmed by immunohistochemical examination. In 12 patients, the diagnosis verification was based on remission after surgical and medical treatment. In the remaining four cases, the diagnosis was made on clinical and laboratory data, however, confirmation was inconceivable due to inefficacy of medical treatment.Remission was achieved in 23 patients: 17 of 21 after neurosurgery (81%), 3 of 7 after primary administration of SSA, and 3 after administration of SSA after surgery (100% remission in cases of combined treatment and 42.9% of monotherapy); 3 out of 5 patients who did not achieve remission were lost for observation. Two patients died: in one case due to the brain herniation and cachexia in active thyrotoxicosis. In second case, the patient developed a mental disorder (catatonia) after the second transphenoidal adenomectomy, which led to death. Conclusion The diagnosis of TSH-oma should be based on all thyroid hormones assessment, since biochemical thyrotoxicosis can manifest itself in various ways. The most effective treatment is transphenoidal adenomectomy. If a neurosurgery is not effective or contraindicative, preoperative preparations SSA can be used.

Immediate postoperative measurement of thyroid-stimulating hormone as an early predictor of remission in thyroid-stimulating hormone-secreting pituitary adenomas.

Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is a rare type of pituitary adenoma; thus, little is known about TSHomas. The purpose of this study was to analyze clinical characteristics and therapeutic outcomes of TSHomas based on a single-center experience. The authors also searched for reliable preoperative and early postoperative factors that could predict long-term endocrinological remission. The clinical, radiological, and pathological characteristics and surgical and endocrinological outcomes of 31 consecutive cases of TSHomas that were surgically treated between 2005 and 2017 were reviewed retrospectively. Preoperative factors were evaluated for their ability to predict long-term remission by comparing remission and nonremission groups. TSH and free thyroxine levels were measured at 2, 6, 12, 18, and 24 hours after surgery to determine whether they could predict long-term remission. Gross-total removal of tumor was achieved in 28 patients (90.3%), and 26 patients (83.9%) achieved endocrinological remission by surgery alone based on long-term endocrinological follow-up (median 50 months, range 32-81 months). The majority of the tumors were solid (21/31, 67.7%), and en bloc resection was possible in 16 patients (51.6%). Larger tumor size and tumor invasion into cavernous sinus and sphenoid sinus were strong predictors of lower rates of endocrinological remission. Immediate postoperative TSH level at 12 hours after surgery was the strongest predictor, with a 0.62 μIU/mL cutoff. Postoperative complications included CSF rhinorrhea in one patient and epistaxis in another patient, who underwent additional surgical treatment for the complications. Tumor size and extent are major prognostic factors for both extent of resection and endocrinological remission. The consistency of TSHomas was more likely to be solid, which makes extracapsular dissection more feasible. Long-term remission of TSHomas could be predicted even during the early postoperative period.