TSH-secreting Pituitary Adenoma Research Articles

Resistance to thyroid hormone and nonfunctioning pituitary microadenoma in a 13-year-old boy with THRB mutation.

Resistance to thyroid hormone (RTH) is a rare syndrome characterized by elevated serum free iodothyronines levels and non-suppressed thyroid stimulating hormones (TSH). The most common cause of RTH is heterozygous pathogenic mutations in thyroid hormone receptor β gene (THRB). Because of the similarities in biochemical profiles, differential diagnosis between RTHβ and TSH-secreting pituitary adenoma (TSHoma) is important, and accurate RTHβ diagnosis is essential to prevent inappropriate treatment. A 13-year-old boy was referred to our hospital for a microadenoma and uncontrolled hyperthyroidism despite use of methimazole for more than one year. He suffered from thyrotoxic clinical features and elevated serum T3 and fT4, and normal ranges for TSH and other pituitary hormones were noted. TSH receptor antibody was undetectable, and pituitary MRI revealed a 3mm-sized microadenoma. A TRH stimulation test showed normal TSH response, and the TSH-α-subunit level was not elevated, which is consistent with RTH. The patient was diagnosed with RTHβ and coexistent non-functioning pituitary microadenoma based on identification of a heterozygous mutation, c.1021C>G (p.Leu341Val), in THRB. Methimazole treatment was stopped, and a β-adrenergic blocking agent was started, subsequently thyrotoxic symptoms were relieved. Currently, only one pediatric case diagnosed with RTH and TSHoma has been reported so far, and this case is the first to report a pediatric case of coexistence of RTH and non-functioning pituitary microadenoma. Also, this case shows that inappropriate secretion of thyroid hormones requires careful clinical diagnosis to avoid unnecessary and potentially harmful management.

Clinical characteristics and outcomes of patients with TSH-secreting pituitary adenoma and Graves’ disease - a case report and systematic review

BackgroundCoexistence of TSH-secreting pituitary adenoma (TSHoma) and Graves’ disease (GD) is rare and complicates the management decision.MethodsWe present a case of the co-existence of TSHoma and GD. In addition, we systematically searched articles describing TSHoma and GD in the same patient published until 20th March 2023, using Pubmed, Scopus and Embase.Case presentationA 46-year-old man presented with symptoms of thyrotoxicosis. His thyroid function tests showed serum TSH 3.35 (reference range 0.3–4.2) mIU/L, FT3 19.7 (3.7–6.4) pmol/L, and FT4 68.9 (11-23.3) pmol/L. The serum TSH receptor antibody was 11.5 mIU/L (positive at ≥ 1.75 mIU/L). Pituitary magnetic resonance imaging showed macroadenoma compressing the optic chiasm. The patient underwent trans-sphenoidal resection of pituitary adenoma. Postoperatively, he remained on maintenance carbimazole and octreotide.ResultsFourteen articles comprising 15 patients were identified from the systemic search. A total of 16 patients (including the current case) were included in the systematic review. The mean (± SD) age at diagnosis was 41 ± 13.6 years. The majority were females (75%). The median (IQR) TSH was 1.95 (0.12–5.5) mIU/L, the median (IQR) free T3 was 11.7 (7.6–19.7) pmol/L and the median (IQR) free T4 level was 47.6 (33.3–64.4) pmol/L. Ten (76.9%) patients had positive TSH receptor antibody levels. 84.6% had pituitary macroadenoma. Pituitary surgery was performed in 12 (75%) patients. At the last follow-up, 4 (25%) patients had complete resolution of symptoms after pituitary surgery, 3 (18.7%) were on maintenance treatment with thionamides for GD, 1 (6.25%) on beta-blockers and 1 (6.25%) on somatostatin analog.ConclusionTSHoma and GD can co-exist, and it is essential to identify this rare association as it can significantly impact treatment strategies.

A case report: TSh-oma in patient with Down syndrome

Tsh-oma or Thyrotropinoma is a condition in which there is a pituitary adenoma that secretes TSH in an autonomous fashion, resulting in hyperthyroidism with its clinical aspects and complications. It is a very a rare condition comprising less than 0.1% of pituitary adenomas. The diagnosis and evaluation of Tsh-oma are challenging, as the clinical manifestations and the biochemical profile resemble the thyroid hormone resistance syndromes. Therefore, a high index of suspicion is required. Down syndrome is a chromosomal disease (trisomy 21) manifested in clinical, physical, and developmental impacts on affected persons. It is associated with thyroid autoimmune diseases and thyroid hypoplasia (congenital hypothyroidism) however, to our knowledge, there have been no described cases in the literature where Down syndrome was associated with a TSH-secreting pituitary adenoma. We hereby present a 34-year-old male known to have Down syndrome who was found to have a thyroid disorder (Tsh-oma) different from the known thyroid disorders linked to Down syndrome.

FRI476 Asymptomatic Thyrotropin-secreting Pituitary Microadenoma With Biochemical Secondary Hyperthyroidism: A Diagnostic Conundrum

Abstract Disclosure: G. Al-Naqeeb: None. R. Ghosh: None. P. Veeraraghavan: None. C. Cochran: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Background: Thyrotropin (TSH)-secreting pituitary adenomas (TSHAs) are often macroadenomas (>1 cm), and clinically present with secondary hyperthyroidism (SH), but clinically silent microTSHAs (<1 cm) with only biochemical SH pose a diagnostic challenge. Clinical Case: A 49-year-old, healthy male was referred to our center for evaluation of abnormal thyroid function tests (TFTs). Immunoassay (IA) measurements at an outside hospital had identified elevated free T4 (FT4), and an inappropriately normal TSH, and a pituitary magnetic resonance imaging (MRI) had noted an 8mm x 7mm non-invasive adenoma. The patient denied hyperthyroidism symptoms, medication/herbal supplement intake, radiation exposure, headaches, vision changes, and thyroid/pituitary disorders, or abnormal TFTs in relatives. Physical exam revealed no signs and symptoms of hyperthyroidism. No thyromegaly or cervical lymphadenopathy was felt. IA profile at our institute was consistent with an SH pattern [TSH: 3.32 mIU/L (NL: 0.4 - 4.7); FT4: 3 ng/dL (NL: 0.9 - 1.7); total T4: 14.5 mcg/dL (NL: 4.5 - 11.7); triiodothyronine: 266.6 ng/dL (NL: 80 - 200)], with similar values on repeat measurement. Equilibrium dialysis technique also yielded an elevated FT4 value. TSH-receptor, anti-thyroid peroxidase, and anti-thyroglobulin (Tg) antibody (Ab) titers, serum Tg, and thyroid binding globulin levels were normal. Dilution studies ruled out heterophile Ab interference. Familial dysalbuminemic hyperthyroxinemia was unlikely given the elevated FT4 values. Genetic testing revealed a normal THRB gene, thereby ruling out thyroid hormone resistance. THRA gene was not tested due to absence of behavioral or hearing issues. Markers of hyperthyroidism, including angiotensin converting enzyme, carotene, apolipoproteins, and osteocalcin levels were normal, except for an elevated sex hormone binding globulin of 104 nmol/L (NL: 11 - 78). Biochemical evaluation of other pituitary axes was normal. However, an elevated alpha sub-unit fraction (ASF) was noted on two separate measurements. Sonogram revealed a heterogeneous, hypervascular thyroid. Bone densitometry, echocardiogram, and Holter monitor studies were normal. The combination of biochemical SH, elevated ASF, pituitary adenoma, and exclusion of other etiologies causing SH pattern established the diagnosis of TSHA. An active surveillance approach was implemented. A pituitary MRI done 18 months later showed minimal (2mm in one axis) increase in the adenoma size, and the patient continued to demonstrate biochemical SH but remained asymptomatic. Conclusion: MicroTSHAs can present with asymptomatic SH. In this situation, excluding other biochemical SH etiologies is crucial to prevent unnecessary invasive procedures. But once TSHA diagnosis is established, due to the risk of tumor growth leading to symptomatic SH or mass effects, active surveillance is warranted. Presentation: Friday, June 16, 2023

FRI292 Asymptomatic TSH Secreting Pituitary Macroadenoma

Abstract Disclosure: B. Gautam: None. M.S. Hossain: None. H. liao: None. K. Mandal: None. D.S. Rosenthal: None. S.C. Kumar: None. Introduction: TSH-producing adenoma is a rare disorder accounting for 0.5-2% of all pituitary adenomas with prevalence of 1-2 cases/million, often diagnosed at the stage of invasive macroadenoma hence challenging to manage. Case Presentation: A 36 years old male with no PMH referred to endocrine clinic for the evaluation of insomnia with abnormal thyroid panel for last 4 years. He denied skin or hair changes, diaphoresis, tremor, change in appetite, weight or bowel habits, cold/heat intolerance, palpitations, recent use of biotin or x-ray contrast exposure. Patient denied headache, visual or hearing impairment, galactorrhea, sexual dysfunction, change in facial appearance or size of gloves & shoes. Patient also denied childhood history of developmental delay, learning disability and family history of thyroid disorder. Unremarkable physical exam with normal vitals. Thyroid was normal without palpable nodule. No thyroid bruit. Normal visual field by confrontation. No tremors, gynecomastia or galactorrhea noted. Laboratory results showed normal CBC, CMP, TSH 5.2 (0.55-4.78 uIU/ml) with FT4 2.1 (0.8-1.8 ng/dl), FT3 5.4 (2.3-4.2 pg/ml), FT4 by dialysis 3.1 (0.9-2.2 ng/dl), FT3 by dialysis 433 pg/dl, Thyroglobulin ab <1 (<1 IU/ml), TPO ab 3 (<9 IU/ml), TSI <89 (<140%), TBII <1 (<2 IU/L), HAMA <6 (<74 ng/ml). Normal ACTH 17 (6-50 pg/ml), serum cortisol level 10.5 (5.2-22.4 ug/dl), prolactin 9.2 (2-18 ng/dl), GH 0.1 (<7.1 ng/ml), IGF-1 183 (53-331 ng/ml), LH 4.7 (1.5-9.3 mIU/ml), FSH 5.9 (1.6-8 mIU/ml), free testosterone 120 (35-155 pg/ml) and total testosterone 1100 (250-1100 ng/dl), SHBG 82 (10-50 nmol/L), alpha-subunit 0.8 (0.1-0.5 ng/ml) & alpha/TSH molar ratio 1.5. MRI brain with pituitary protocol showed an expansile round enhancing soft tissue mass filling the sellar cavity measuring 1.5 x 1.5 x 1.3 cm tenting the optic chiasm without cavernous sinus involvement. Patient was diagnosed with TSH secreting pituitary adenoma and referred to Neurosurgery. Patient had successful trans-sphenoidal adenectomy. Post-surgery TFTs: TSH 2.18 (0.55-4.78 uIU/ml), FT4 1.2 (0.8-1.8 ng/dl). Pathology report showed pituitary adenoma, IM stains positive for FSH, GH patchy and TSH (patchy and weak), negative for prolactin and ACTH. Rare tumor cells positive for LH Discussion: Our case highlights the importance of early diagnosis and appropriate treatment of TSH secreting adenoma to prevent complications such as hyperthyroidism, visual field defect and pan-hypopituitarism. Diagnosis in our case was particularly challenging as the patient was completely asymptomatic, therefore emphasize the importance of correlating TSH level with FT4 and early evaluation of central cause in the presence of biochemical evidence suggesting central thyroid disorder. Presentation: Friday, June 16, 2023

FRI555 A Misdiagnosis Of TSH-secreting Adenoma With Thyrotoxicosis In A Patient With Graves’ Disease

Abstract Disclosure: J. Huynh: None. A. Makawi: None. G. Elshimy: None. Introduction: Modern healthcare relies on laboratory and imaging results for accurate diagnosis and medical decision-making. However, the collection and distillation of laboratory results is a multi-step process with the potential for error at each stage. This may result in diagnostic errors. A review of salient cases is one avenue to improving awareness of the risk for failure in the laboratory assessment process. We present one such case of a patient initially referred to neurosurgery for management of a thyroid stimulating hormone (TSH) secreting microadenoma, which is a rare disease and accounts for less than 1% of all pituitary adenomas, with incongruent laboratory presentation including elevation in TSH and free T4. Endocrinology consultation prompted further investigations which led to the diagnosis of Graves’ disease with a concomitant nonfunctional pituitary microadenoma. Case Presentation: This is a case of a 61-year-old white male who presented with 30-lb weight loss, insomnia, palpitations, and diaphoresis. Initial thyroid stimulating hormone (TSH) from outside facility was > 90 mcIU/mL with elevated free T4 of 23.4 pg/mL. MRI of the brain shows a 3x3 mm pituitary microadenoma raising concern for an atypical case of TSH-secreting adenoma. The patient referred to Neurosurgery for evaluation by primary care. Endocrinology was consulted for evaluation prior to any surgical intervention. A large goiter was noted on exam. Clinical presentation was highly concern for Graves’ disease. Repeated labs included undetectable TSH with FT4 of 4.4 pg/mL and free T3 12.9 pg/ml. TPO-ab was elevated at 17.1 IU/mL. TSIg index was low. Ultrasound of the thyroid gland revealed a normal thyroid without nodules. He was diagnosed with Graves’ disease and was initiated on methimazole and propranolol with symptomatic improvement. His pituitary panels continued to show suppressed TSH pre and post treatment with no other significant pituitary abnormalities hence the diagnosis of a concomitant nonfunctional pituitary microadenoma was made. Discussion: Ultimately, the initial TSH-secreting microadenoma has deemed a misdiagnosis and he was subsequently treated appropriately for Graves’ disease with normalization of thyroid functions. Standard of care for any laboratory abnormalities is to assess for reproducibility of the result. In our patient, subsequent in-house and outside assays were unable to demonstrate elevation of both TSH and FT4. Instead, the patient had suppressed TSH with elevated FT4, without evidence of nodules consistent with Graves’ disease. Treatment of Graves’ disease differs greatly from the treatment of TSH-secreting pituitary adenoma, which includes surgical resection, radiotherapy, and/or, a somatostatin analog based on the clinical picture. Correct diagnosis prevented our patients from unnecessary surgical complications and lifelong morbidity. Presentation: Friday, June 16, 2023

Central hyperthyroidism combined with Graves' disease: case series and review of the literature.

Central hyperthyroidism is characterized by elevated free thyroid hormone and unsuppressed thyroid stimulating hormone (TSH) and this laboratory feature includes TSH-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone β (RTHβ). Central hyperthyroidism combined with Graves' disease (GD) has been rarely reported. We describe three patients with TSHoma combined with GD and one patient with GD combined with RTHβ and pituitary adenoma. These three patients with TSHoma combined with GD showed elevated thyroid hormone, while TSH level was normal or elevated, and thyroid stimulating hormone receptor antibodies (TRAb) were positive. After thyrotoxicosis was controlled, they all underwent transsphenoidal surgery (TSS). We also describe a patient with an initial presentation of GD who developed hypothyroidism after anti-hyperthyroidism treatment and TSH was inappropriately significantly increased. His head magnetic resonance imaging (MRI) revealed a pituitary adenoma. Genetic testing confirmed a heterozygous mutation in the thyroid hormone receptor β (THRB) gene c.1148G>A (p.R383H). After levothyroxine (L-T4) and desiccated thyroid tablets treatment, TSH level decreased to normal. These four cases highlight the need to consider the diagnosis of GD combined with central hyperthyroidism when faced with inconsistent thyroid function test results, illuminating the specific diagnostic and therapeutic challenges of coexisting primary and central hyperthyroidism. Finally, we propose clinical management for central hyperthyroidism combined with GD.

A TSH-secreting pituitary adenoma cured from SSA monotherapy alone: Disease free more than three years after stopping treatment

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

Long action somatostatin analogues in patients with TSH-secreted pituitary adenomas: treatment experience

Thyrotoxicosis, which characteristics are increased excitability, emotional lability, tachycardia episodes, increasing of free fractions of tetraiodothyronine (T4) and triiodothyronine (T3) is one of the most common endocrinological syndromes. However, during the interpretation of thyroid status it is very important to take into account the possibility that a patient has TSH-secreting pituitary adenoma. Timely diagnosis of TSH-secreting adenomas plays prominent role in guiding the treatment course since it is associated with an improvement of long-term prognosis and an increase of the patient’s total life expectancy. Needed to underline that in some patients with TSH-secreting adenomas manifestations of the other pituitary hormones hypersecretion (first of all — somatotropin and prolactin) come to the fore, that lead to the development of acromegaly and hyperprolactinemia accordingly. Our work basing on two clinical cases presents main principles of diagnosis and specific clinical manifestations of TSH-secreting pituitary adenomas and demonstrates efficacy of somatostatin analogues in the treatment of this pathology.

TSHOMA: A RARE PITUITARY TUMOR

INTRODUCTION: TSH-secreting pituitary adenomas (TSHoma) or thyrotropinoma are rare pituitary tumors that secrete an abnormal Thyroid Stimulating Hormone (TSH) which constitutes up to 1%–2% of all pituitary adenomas. Patients often remain misdiagnosed for years. This case is reported to emphasize the importance of diagnosing it early and accurately to ensure timely management and relief of symptoms before perpetual damage is done. CASE DESCRIPTION: We report a case of a 29 years old patient from Peshawar, Pakistan who was referred to Endocrine unit Hayatabad Medical Complex Peshawar for the review of his persistently raised TSH despite optimal dosing of thyroxine for 2 years. He was initially diagnosed and treated for hyperthyroidism with Neomercazole and then with radioactive iodine (RAI). Post-RAI he developed Hypothyroidism and was subsequently treated with optimal doses of Thyroxine. Despite optimal doses of thyroxine, TSH remains elevated. Previous thyroid function tests also showed persistently raised T3, T4 and raised TSH. Patient was clinically thyrotoxic. MRI findings reveals macro adenoma and was resected by neurosurgeon and advised Endocrine follow up visit in OPD after surgery. CONCLUSION: TSHoma is highly under diagnosed. It is important to consider the pitfalls in diagnosis where normal or low alpha sub unit levels could lead to dubious differentials. The use of advance technology i.e. functional MRI scans to confirm diagnosis should be carried out early on leading to timely treatment options including radiotherapy and surgery.

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.

An Update on the Pathophysiology and Diagnosis of Inappropriate Secretion of Thyroid-Stimulating Hormone.

Inappropriate secretion of thyroid-stimulating hormone (IST), also known as central hyperthyroidism, is a clinical condition characterized by elevated free thyroxine and triiodothyronine concentrations concurrent with detectable thyroid-stimulating hormone (TSH) concentrations. Similarly, the term syndrome of IST (SITSH) is widely used in Japan to refer to a closely related condition; however, unlike that for IST, an elevated serum free triiodothyronine concentration is not a requisite criterion for SITSH diagnosis. IST or SITSH is an important indicator of resistance to thyroid hormone β (RTHβ) caused by germline mutations in genes encoding thyroid hormone receptor β (TRβ) and TSH-secreting pituitary adenoma. Recent evidence has accumulated for several conditions associated with IST, including RTH without mutations in the TRβ gene (non-TR-RTH), the phenomenon of hysteresis involving the hypothalamus-pituitary-thyroid axis (HPT-axis), methodological interference, and Cushing’s syndrome after surgical resection. However, little information is available on the systematic pathophysiological aspects of IST in previous review articles. This report presents an overview of the recent advances in our understanding of the etiological aspects of IST that are relevant for diagnosis and treatment. Moreover, the report focuses on the potential mechanism of IST caused by hysteresis in the HPT-axis (lagging TSH recovery) in terms of epigenetic regulation.

An Atypical Case of TSH-Secreting Pituitary Adenoma in a Patient Presenting With Low Libido and Insomnia

Background: TSH-secreting pituitary adenoma is an incredibly rare cause of hyperthyroidism. Most patients with TSHomas present with clinical hyperthyroidism, but some patients may have atypical signs. Here we present the case of a patient who had been suffering from low libido and insomnia who was found to have secondary hyperthyroidism from a TSH-secreting pituitary adenoma. Clinical Case: A 47-year-old man presented with complaints of progressive headache, fatigue, depression, insomnia, low libido and erectile dysfunction. After questioning, he noted the presence of intentional tremor for more than 5 years. He denied anxiety, palpitations, heat intolerance, hyper defecation, proximal muscle weakness, local compressive symptoms of the neck and ocular symptoms. Physical exam was notable for fine tremor and mild thyromegaly, but otherwise patient had no evidence of anxiety, exophthalmos, hyperreflexia or diaphoresis. The patient was found to have a normal free testosterone (46 pg/mL, n 30-140 pg/mL) but had an elevated TSH (6.302 IU/mL, n 0.4-5 IU/mL), elevated Free T4 (3.6 ng/dL, n 0.6-1.2 ng/dL) and an elevated T3 (422 ng/dL, n 73-178 ng/dL). Further lab work revealed elevated alpha-subunit (4.4 ng/mL, n <0.5 ng/mL) suggestive of TSH-secreting pituitary adenoma. Prolactin and IGF-1 levels were normal. Patient had an MRI pituitary which showed a 2.3 cm sellar mass abutting the optic chiasm without involvement of the cavernous sinus. Patient proceeded to trans-sphenoidal resection. Post-operatively, TSH had dropped from 6.534 to 0.002 IU/mL (n 0.4-5 IU/mL) and Free T4 had dropped from 3.1 to 0.5 ng/dL (n 0.6-1.2 ng/dL). Interestingly, immunohistochemical staining was negative for TSH but the specimen did show histologic features characteristic of TSH-producing adenoma including extensive stromal fibrosis and nuclear pleomorphism. Patient was seen in clinic post-operatively where he noted a dramatic improvement in his headache and insomnia. He did show signs of hypothyroidism including constipation and weight gain. Patient was started on levothyroxine 75 mcg PO daily. Conclusion: This demonstrates the case of a patient with a TSH-secreting pituitary adenoma who presented with minimal thyrotoxic symptoms despite elevated thyroid hormones. Patients with this condition may present with atypical symptoms, thus requiring clinicians to have a high index of suspicion for this rare tumor.

A Case of TSH-Secreting Pituitary Adenoma With Unusual Positive Staining for SF1

Background: TSH-secreting pituitary adenomas are the rarest functional pituitary tumors. While they are often plurihormonal, SF1 positivity (indicating gonadotroph lineage) is unusual. Here we present the rare case of a patient with TSH-secreting pituitary adenoma with staining positive for TSH, GH, prolactin, SSTR2A, PIT-1, and SF1. Clinical Case: Patient is a 42 year-old male with a history of hypogonadotropic hypogonadism (lost to follow-up), who presented with a 5 day history of nausea and vomiting. Vitals were notable for tachycardia to 108 BPM, with BMI 14.8 kg/m2. On physical exam he had enlarged right hemi-thyroid and exophthalmos. Labs were notable for TSH 12.55 μIU/mL (0.27-4.20), Free T4 >7.77 ng/dL (0.80-1.80), Free T3 29.02 pg/mL (2.57-4.43), 8am cortisol 0.9 μg/dL (6.0-18.4), FSH 0.6 μIU/ml (1.5-12.4), LH 0.8 μIU/mL (1.7-8.6), PRL 8.5 ng/mL (4.0-15.2), total testosterone <5 ng/dL (249-836), and IGF-1 88.9 ng/mL (94.4-223.0). MRI showed large lobulated pituitary mass extending into the suprasellar region with mass effect and thyroid US showed enlarged almost completely cystic right hemi-thyroid. The patient was started on methimazole 30mg BID, prednisone 40mg daily, and cabergoline 0.5mg weekly (he declined octreotide). FT4 and FT3 remained significantly elevated despite escalation of cabergoline to 0.5mg 5 days weekly, so the patient was admitted two months after his initial presentation for plasmapheresis followed by thyroidectomy. His hospital course was complicated by post-op meningitis and DI, both successfully treated. Surgical pathology was notable for patchy expression of TSH with rare cells expressing GH and prolactin, SSTR2A positivity, strong nuclear positivity for PIT-1 with negative T-PIT staining, and unusual positivity for SF1. At follow-up he is clinically euthyroid and stable without use of LT4 or HC therapy. Repeat TSH, FT4, ACTH, cortisol, and testosterone are pending. He declines chemotherapy, radiation, and octreotide. Conclusion: This is a rare case of TSH-producing adenoma demonstrating SF1 positivity in addition to TSH, GH, PRL, and PIT-1 expression, in the absence of excess gonadotroph secretion. When such tumors secrete multiple hormones, this has been used as evidence to support the argument that such tumors arise from a stem cell population(1). However, the implications for our patient remain unclear.

Coexistence of Thyroid Hormone Resistance and Autoimmune Thyroid Disease: Not a Mere Coincidence

Introduction: The coexistence of thyroid hormone resistance and autoimmune thyroiditis was initially thought to be a chance event. In a large cohort study, Barcoff et al. demonstrated an increased likelihood of thyroid autoantibodies in patients with thyroid hormone resistance (RTH). We report a unique case to epitomize the coexistence of these two conditions and discuss the postulated mechanisms.Clinical Case: A 22-year-old woman with a history of Hashimoto’s thyroiditis, attention deficit hyperactivity disorder, and migraine presented to the endocrinology clinic with symptoms of weight loss, fatigue, decreased appetite, and heat intolerance for 4 months. She was diagnosed with Hashimoto’s thyroiditis at age 12 with elevated TSH only and had been on levothyroxine 25 mcg since diagnosis. Physical exam demonstrated a body mass index of 34.14 kg/m2, blood pressure of 138/91 mmHg, pulse of 77 bpm, and an enlarged palpable thyroid gland. Laboratory investigations revealed elevated thyroid peroxidase (TPO) antibody at 234 IU/mL (<9) and thyroglobulin Antibody at 3 IU/mL (<1) with elevated free T4 of 3.76 ng/dL (0.61-1.36), elevated total T4 of 21.58 mcg/dL (6.09-12.23), increased T3 uptake of 51.2% uptake (32-48.4), and upper normal TSH of 3.99 uIU/mL (0.44-5.33). Elevated free T4 was confirmed by the equilibrium dialysis method at 6.2 ng/dL (0.9-2.2) with upper normal TSH at 3.77 uIU/mL. Thyroid ultrasound demonstrated thyromegaly and hypervascularity of the gland. TSH secreting pituitary adenoma was ruled out with a normal alpha subunit of 0.2 ng/ml (0.1-0.6) and molar ratio of the alpha subunit to TSH ratio <1 along with a normal pituitary MRI. She was not taking other medications or supplements. She was diagnosed with thyroid hormone resistance and is undergoing genetic testing to differentiate the THRB genetic mutations from Non-TR-RTH. Her symptoms improved after discontinuing her levothyroxine.Clinical Lesson: Our case highlights the importance of evaluating thyroid disorders properly before starting treatment and illustrates the coexistence of autoimmune thyroiditis with thyroid hormone resistance. Barcoff et al. demonstrated that there was an increased likelihood of thyroid autoantibodies with odds ratio = 2.36 (p = 0.002) in a large patient cohort with RTH, compared to their unaffected first-degree relatives. However, since there was no correlation in increased antibody with increased age and the duration of the disease, the proposed hypothesis did not substantiate chronic TSH stimulation inducing autoimmune response. The proposed mechanism is that the elevated TSH in RTH stimulates the immune system at the TRα level which was demonstrated in murine models with increased activation of thymic function in correlation with TSH level. More research is needed to understand the underlying mechanism of their coexistence.

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.

Successful Multimodal Treatment of a TSH-Secreting Pituitary Adenoma (TSH-oma)

Background: TSH-omas are rare tumors accounting for 0.5-2% of all pituitary adenomas. Due to their indolent nature, most TSH-omas are diagnosed at the stage of invasive macroadenomas. Over the past several decades, the management of TSH-omas has evolved substantially. While surgery remains first-line therapy, somatostatin analogs have emerged as important therapeutic agents as a result of their effectiveness in normalizing thyroid hormone levels in ~95% of patients with severe hyperthyroidism and reducing TSH-oma size in ~50% of patients. Clinical Case: A 52-year-old woman with a history of multinodular goiter was incidentally found to have a 2.2 x 1.8 x 2.1 cm pituitary macroadenoma with suprasellar extension, mass effect on the optic chiasm, and left cavernous sinus involvement when she presented with chest pain, palpitations, headache, and left-sided numbness and weakness. Laboratory results showed high FT4/T4/T3 with inappropriately high TSH, elevated α-subunit, and low cortisol with low-normal ACTH highly suggestive of TSH-oma with concurrent secondary adrenal insufficiency. An ophthalmology exam revealed a left superior temporal defect. The patient was treated with atenolol, prednisone, and octreotide two weeks before surgery with symptomatic improvement and near-normalization of FT4. Following an uncomplicated transsphenoidal resection, FT4 normalized within one week. At her one-month follow-up, both TSH and FT4 were normal, and her secondary adrenal insufficiency had resolved. Her visual field defect also recovered. Laboratory Results: TSH 5.35 (normal range 0.40-4.60 μU/mL), FT4 3.0 (0.8-1.7 ng/dL), T4 18.1 (5.0-12.0 μg/dL), T3 235 (80-200 ng/dL), ACTH 10 (6-50 pg/mL), cortisol 4.5 (5.0-25.0 μg/dL), α-subunit 8.0 (0.1-1.5 ng/mL); after 2 weeks on SQ octreotide 50mg q12h: TSH 1.93 (0.30-4.20 μU/mL), FT4 1.7 (0.6-1.5 ng/dL); 1 month post-op: TSH 1.53 (0.30-4.20 μU/mL), FT4 0.8 (0.6-1.5 ng/dL), ACTH 12 (7.2-63 pg/mL), cortisol 6.9 (4.0-20.0 μg/dL) Conclusion: Since the first reported case of TSH-oma in 1960, the diagnostic and therapeutic management of these rare pituitary adenomas have evolved due to the emergence of ultrasensitive TSH assays, advanced imaging and surgical techniques, and somatostatin analogs. However, to this day, most TSH-omas are still diagnosed at the stage of invasive macroadenomas, when successful surgical resection becomes more difficult. Hence, up to two-thirds of patients may require adjuvant therapy with medication or radiation. As evidenced in our patient, who achieved a near-euthyroid state within just two weeks of starting low dose octreotide, somatostatin analogs are highly effective in controlling hyperthyroidism and have solidified their place in the therapeutic management of TSH-omas. This case highlights the success of a multimodal approach to the treatment of TSH-omas.

An undiagnosed TSH-secreting pituitary macroadenoma found during pregnancy.

SummaryThyroid stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is an uncommon cause of thyrotoxicosis, and is even rarer when found during pregnancy. Our patient presented with thyrotoxicosis accompanied by an inappropriately normal TSH level at 10 weeks of gestation during work-up of surgical termination of pregnancy (STOP). Subsequent investigations performed after STOP confirmed the presence of a TSH-secreting pituitary macroadenoma. She was initially treated with anti-thyroid drugs for biochemical control, followed by trans-sphenoidal surgery after STOP had been performed. Her thyroid function completely normalized after the trans-sphenoidal surgery. Our case illustrated the importance of recognizing the syndrome of inappropriate TSH secretion and highlighted several pregnancy-related aspects in the diagnosis and management of TSHoma during pregnancy.Learning pointsThis case report illustrates the need to raise awareness in recognizing the syndrome of inappropriate TSH secretion.Illustrate the different hormone tests available for reaching the diagnosis of TSH-secreting pituitary adenoma.Highlight the physiological changes in the thyroid status during pregnancy and the importance of using trimester-specific reference ranges for assessment of thyroid function during pregnancy.Describe the challenges in the management of TSH-secreting pituitary adenoma during pregnancy.

SAT-276 Co-Secreting TSH and Growth Hormone Pituitary Adenoma

Introduction: Secreting pituitary adenoma is exceedingly rare. Less than 15 cases having been reported. Its clinical presentation and diagnosis is challenging. We report a case of pituitary macroadenoma, with features of acromegaly and hyperthyroidism. Case report: A 75 years’ old man presented with new onset atrial fibrillation. He had high FT4 with normal TSH. His ultrasound scan of the neck showed a solitary nodule. He had ablation twice and was started on bisoprolol and anticoagulant. He had MRI scan for headaches and this showed a pituitary macroadenoma. He had high IGF-1. His oral glucose tolerance showed failure of GH suppression. His FT4 was persistently high with normal TSH and he had high a subunits. This suggested the diagnosis of TSH and GH secreting pituitary adenoma. Discussion: TSH-secreting pituitary adenomas are rare and not uncommonly, they co-secrete other pituitary hormones including growth hormones. Somatotrophs and lactotrops share common transcription factors with thyrotrophs. TSH-secreting adenomas are benign but 60% of them are locally invasive. TSH-secreting pituitary adenomas typically present with either symptoms of tumor growth like headache or visual field disturbance or symptoms of hyperthyroidism. Thyroid nodules are common in patients with TSHomas. In patients with TSH-secreting pituitary adenomas, majority will need only surgery and radiation. The medical treatment used to normalize TSH and FT4 levels is somatostatin analogs. This is effective in about 90% of patients with TSH secreting pituitary adenomas TSHoma should be differentiated from resistance to thyroid (RTH). The main difference between TSHoma and RTH is the presence of signs and symptoms of hyperthyroidism in patients with TSHoma, absence of a family history, normal thyroid hormone levels in family members, and the presence of an elevated glycoprotein α-subunit in patients with pituitary tumor. Reference: H Adams and D Adams. A case of a co-secreting TSH and growth hormone pituitary adenoma presenting with a thyroid nodule. EDM case reports 2018 Hatem.eid1@nhs.net

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.