Thyrotropin-secreting Adenoma Research Articles

Early identification of postoperative remission for thyrotropin-secreting adenomas.

Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission. We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission. The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff. Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.

Abstract #1411806: A Case of Thyrotropin Secreting Adenoma and Review of Literature

Elevations of TSH, FT4, and FT3 are a feature of secondary hyperthyroidism which could occur in the setting of resistance of thyroid hormone at the pituitary gland, alteration of certain deiodinase enzymes causing lower T3 at the pituitary or a TSH secreting tumor in the pituitary. Other conditions include pregnancy and the use of drugs (amiodarone, heparin). We present a case of secondary hyperthyroidism that was diagnosed with a TSH-secreting adenoma (TSHoma). A 72-year-old male presented with complaints of chest pain. He had a past medical history of primary hyperaldosteronism, occipital lobe ischemic infarct, osteoporosis with low-intensity rib, wrist, and vertebral fractures, coronary artery disease, and had undergone CABG. He was diagnosed with paroxysmal atrial fibrillation and had thyroid function testing which showed a TSH of 7.72μIU/mL (0.42-4.50), FT3 6.2pg/mL (2.0-4.4) and FT4 1.74ng/dL (0.70-1.48). A subsequent CT Head revealed a sellar mass measuring 1.4 cm craniocaudally with abutment of the optic chiasm. Repeat thyroid testing continued to show an elevated TSH, FT3, and FT4. αsubunit glycoprotein was 4.1ng/mL (< 0.5), IGF-1 by LC/MS was 31ng/mL (32-200), prolactin was 46.5ng/mL (4.0-15.2) and SHBG 131.6nmol/L (13.3-89.5). He was managed with methimazole and underwent trans-sphenoidal resection of the tumor. Pathology showed a 3.5 x 1.8 x 0.3 cm mass that on immunoperoxidase stains demonstrated expression of synaptophysin by many of the neoplastic cells. Some expressed GH, few expressed prolactin while rare neoplastic cells expressed TSH. TSHomas are rare pituitary adenomas with a prevalence of 1-2 cases/million. Up to 30% can be associated with hypersecretion of GH, prolactin, LH and FSH. The cells express TRH, somatostatin, and dopamine receptors. Clinical features include headaches, visual field defects, goiter, signs/symptoms of hyperthyroidism, pressure effects of the adenoma, cardiac manifestations (atrial fibrillation, heart failure, pericardial effusion) and vertebral fractures. αsubunit glycoprotein is elevated and an αsubunit to TSH molar ratio >1 can be used with 90% sensitivity to differentiate it from other causes of elevated TSH, FT3 and FT4. Elevations in SHBG are also found in patients. Resistance to the thyroid hormone at the pituitary level can give rise to a similar presentation. Elevated levels of SHBG and αsubunit glycoprotein seen in TSHoma can aid in differentiation. Dynamic testing such as a T3 suppression test with LT3 fails to suppress TSH production in cases of TSHoma. In addition, a TRH stimulation test fails to increase levels of TSH or αsubunit in TSHomas. Due to the presence of somatostatin receptors, TSH reduction starts to occur within hours after the use of somatostatin analogs. Surgical removal is the cornerstone of management and helps achieve normal TSH levels in more than 75% of patients. Pre-operative treatment with octreotide is shown to reduce TSH levels by up to 50% and cause a reduction in size by 20-50%. Undetectable TSH 1-week post-op has good prognostic value and a reduction in TSH on a T3 suppression test has optimal sensitivity and specificity to demonstrate cure.

Clinical characteristics and outcomes of preoperactive short-acting octreotide treatment in patients with thyrotropin-secreting pituitary adenomas

Objective: To explore the clinical characteristics of patients with pituitary thyrotropin-secreting adenoma and evaluate the effect of preoperative short-acting octreotide treatment on hyperthyroidism. Methods: A retrospective analysis was performed in 40 patients with pituitary thyrotropin adenoma diagnosed in Beijing Tiantan Hospital from January 2008 to January 2018. The general data, laboratory examinations and imaging findings were reviewed and analyzed. The clinical effect of preoperative octreotide on hyperthyroidism was evaluated. Results: The age of onset year of the 40 patients (male: female = 24∶16) was (30.5±5.1) years. Among them, 35 patients (87.5%) were with macroadenoma. The most common symptoms were thyroid hypermetabolism syndrome, followed by headache, dizziness, visual field damage and hypogonadism. The thyroid function of 30 patients (75%) recovered to normal within 3-5 days after the octreotide treatment. The total effective rate of the octreotide was 90.0%. The level of free thyroxine (FT4) before treatment in patients with more than 10 times of effective cumulative dose was significantly higher than that in patients with less than 10 doses. Conclusions: Thyroid hypermetabolism syndrome and pituitary occupying effect are the most common clinical manifestations of thyrotropin-secreting adenoma. Preoperative octreotide treatment can effectively control hyperthyroidism. The level of FT4 is a crucial factor affecting the efficacy of octreotide.

Thyrotropin Secreting Adenoma in a Patient with Autoimmune Hypothyroidism: Case Report of a Challenging Diagnosis

Clinical presentation: We describe a case of a 47-year-old woman with a longtime primary autoimmune hypothyroidism with a progressive rising of TSH levels despite increasing of LT4 therapy. LT4 dose was increased up to 2.9 mcg/kg/day causing an excess of circulating fT4 a minor increase of fT3 concentrations without, however, achieving TSH normalization. The patients was asymptomatic and during the long observation period she had two term pregnancies. A withdrawal of thyroid hormone replacement therapy appropriately induced a further increase of TSH levels and a decrease of fT3 and fT4 below the normal range. LT4 therapy was then resumed and, because TSH levels failed to normalize, central hyperthyroidism or thyroid hormone resistance were suspected. Thyroid levels of first grade relatives were normal, and TSH response to TRH was positive, leaving the diagnosis unclear. The magnetic resonance imaging (MRI) of sellar region revealed a pituitary macroadenoma. The remaining pituitary function was normal. The patient underwent transphenoidal surgery (TNS) and histological examination showed positive immunostaining for TSH, and a mild positivity for GH. After surgery, TSH levels quickly fall down and her replacement therapy could finally be optimized.

Thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1: one case report and literature review

Objective To improve the understanding of thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1(MEN1) through analyzing the clinical diagnosis and treatment process, as well as outcomes in one case of this disorder. Methods The clinical manifestations, biochemical and hormone levels, imaging presentations, medical and surgical treatments, and post-operational pathologic findings in the process of diagnosis and treatment of a patient with thyrotropin-secreting adenoma in MEN1 were analyzed. The next generation sequencing followed by Sanger method was used for analyzing MEN1 and related genes. The results were evaluated with online PolyPhen2 and PROVEAN for variation hazard. Results One 19-year old male patient was diagnosed with hyperthyroidism due to thyrotoxicosis and high level of thyroid hormones(THs) with measurable TSH(2.78 mIU/L) and negative thyrotropin receptor antibody(TRAb). Meanwhile, primary hyperparathyroidism was suggested by hypercalcemia, hypophosphatemia, and elevated intact parathyroid hormone(PTH) level, all the parameters were returned to normal after surgical resection of the mass which was below the left thyroid lobe indicated by ultrasound and 99mTc scan. Thyrotoxicosis remained in spite of one year treatment with antithyroid drug, thyrotropinoma was then suspected, and subsequent MRI scan found a macroadenoma at right pituitary. TSH and THs returned to normal 1 month after transsphenoidal removal of the adenoma. As expected, immunohistochemical staining revealed TSH positive. In addition, a pancreatic mass was found by both CT and MRI scan, which was considered as a silent neuroendocrine tumor. Gene analysis revealed a missense mutation of MEN1 as c. 415C>T and p. His139Tyr(H139Y), which was predicted highly hazard. Only five cases of thyrotropinoma in MEN1 were previously reported. Conclusion Thyrotropinoma should be cautiously identified from hyperthyroidism to avoid misdiagnosis and mistreatment, and it should keep in mind that thyrotropinoma may be associated with MEN1 though it would be very rare. Key words: Thyrotropinoma; Multiple endocrine neoplasia type 1; Hyperthyroidism; Hyperparathyroidism; MEN1 gene; Silent pancreatic neuroendocrine tumor

SURG-08. SURGICAL OUTCOMES OF PITUITARY ADENOMAS TREATED WITH TRANSSPHENOIDAL SURGERY: A SINGLE INSTITUTION’S EXPERIENCE

Abstract We retrospectively analyzed surgical outcomes of transsphenoidal surgery for pituitary adenomas. A total of 366 consecutive patients undergoing transsphenoidal surgery for a pituitary adenoma from December 1990 through May 2017 were included in this study. The most common tumor type was nonfunctioning pituitary adenoma (NFPA) (63.7%), followed by prolactin-secreting adenoma (20.5%), growth hormone-secreting adenoma (13.4%), adrenocorticotropin-secreting adenoma (2.2%), and thyrotropin-secreting adenoma (0.2%). This cohort study consisted of 164 male and 202 female patients. The median patients age was 48 years. The median follow-up duration was 63 months. Gross-total resection (GTR) was achieved in 83.7% of patients with a NFPA, 76% of prolactin-secreting adenomas, 71.4% of growth hormone-secreting adenomas, 75% of adrenocorticotropin-secreting adenomas, 100% of thyrotropin-secreting adenomas. There were 326 macroadenomas (69.1%). Surgical outcome was better in patients with microadenomas than in patients with macroadenomas (100% and 77.9%, respectively). Improvement of visual disturbances occurred in 148 (93.7%) of the 158 cases. Hormonal impairment by pituitary adenoma was improved in 105 (87.5%) of the 120 cases. There were 24 (8.2%) cases of recurrence after GTR; 17 patients underwent second surgery, 5 patients received radiotherapy, and the others continued conservative treatment. The median time interval between TSA and recurrence was 56 months. Postoperative cerebrospinal fluid leakage occurred in seven (1.9%) of 366 patients. Transsphenoidal surgery is an effective and safe treatment modality for most patients with pituitary adenoma.

Strengthen multidisciplinary collaboration to enhance the level of diagnosis and treatment of thyrotropin secreting adenoma

Strengthen multidisciplinary collaboration to enhance the level of diagnosis and treatment of thyrotropin secreting adenoma

One case of a thyrotropin-secreting microadenoma and resistance to thyroid hormone with P453T mutation in TRβ gene

We investigated a 12-year-old girl with elevated serum FT3, FT4, and TSH levels. The sequence of thyroid hormone receptor β(TRβ)exons revealed a CCT→ACT transition mutation at nucleotide 453 site within exon 10, which resulted in the substitution of cytosine to adenosinein(P453T). Pituitary magnetic resonance image showed a pituitary micoradenoma. The patient underwent transsphenoidal pituitary adenomectomy. Pathological results exhibited positive TSH-β, GH, prolactin, ACTH, and α-HCG staining for the tumor. This is the first case report with thyroid hormone resistance syndrome and thyrotropin-secreting adenoma. Key words: Thyroid hormone resistance; Thyroid hormone receptor β; Gene mutation; Thyrotropin-secreting pituitary adenoma

Clinical analysis of 2 case of central hyperthroidism due to thyrotropin-secreting adenoma and literature review

垂体促甲状腺素(TSH)分泌瘤引起中枢性甲状腺功能亢进症(甲亢)非常少见,迄今国内报告的总例数共21例[1-5],其治疗与原发性甲亢截然不同,采用原发性甲亢常用的治疗措施,不仅不能使中枢性甲亢得到控制,反而有加重垂体瘤的危险[6]。

Coexisting intracranial tumors with pituitary adenomas: Genetic association or coincidence?

The co-occurrence of two or more brain tumors with different histological features is rare. The authors report three rare cases of intracranial tumors associated with pituitary adenomas. Two of the pituitary tumors were functioning adenomas: a prolactinoma and a thyrotropin secreting adenoma. Two of the associated intracranial neoplasms were gliomas and one was a meningioma. Radiological and clinical examination for syndromal association was negative in all cases. We briefly discuss the presentation and treatment options of these cases and review the 19 previous publications in the literature of pituitary tumors occurring in association with other neoplasms and explore the possible links underlying these co-occurring neoplasms. Our three cases represent 0.86% of all pituitary tumors operated at our institute over a 9-year period.

Octreotide Normalizes Thyroid Function Tests in a Pregnant Woman With a Thyrotropin-Secreting Adenoma

Octreotide Normalizes Thyroid Function Tests in a Pregnant Woman With a Thyrotropin-Secreting Adenoma

Results of Transsphenoidal Surgery in a Large Series of Patients with Pituitary Adenoma

To report the efficacy and safety of microsurgical transsphenoidal surgery in a series of previously untreated patients with pituitary adenoma. One thousand one hundred forty consecutive patients undergoing transsphenoidal resection of a pituitary adenoma at our department from January 1990 through December 2002 were included in our study. Postoperative results were classified uniformly during the period of the study. Patients were considered in remission of disease when strict hormonal and radiological criteria of cure were met. The most frequent tumor type was clinically nonfunctioning adenoma (NFPA) (33.2%), followed by growth hormone-secreting adenoma (28.1%), adrenocorticotropin-secreting adenoma (23.0%), prolactin-secreting adenoma (13.2%), and last, thyrotropin-secreting adenoma (2.5%). The patient population was 59.7% female and 40.3% male. Mean age was 43.0 +/- 0.4 years. There were 788 macroadenomas (69.1%), and in 233 patients (20.4%), the tumor invaded one or both cavernous sinuses. The overall rate of early surgical success was achieved in 504 (66.1%) of the 762 patients with a hormone-active adenoma. Surgical outcome was better in patients with microadenomas than in patients with macroadenomas (78.9% and 55.5%, respectively), whereas tumors invading the cavernous sinus had a poorer outcome (7.4%). In patients with NFPA, no residual adenoma was present in 234 patients (64.8%). Normalization of visual defects occurred in 117 (40.5%) of the 289 patients with visual disturbances and improved in another 148 patients (51.2%). Three patients (0.3%) died as a consequence of surgery. Transsphenoidal surgery is an effective and safe treatment for most patients with pituitary adenoma and could be considered the first-choice therapy in all cases except for prolactinomas responsive to dopamine agonists. Other treatment methods, such as radiotherapy, stereotactic radiosurgery, and medical therapy, play an important role in patients not cured by surgery.

Surgical treatment of thyrotropin-secreting pituitary adenomas

Thyrotropin-secreting pituitary adenomas have been diagnosed more frequently as radiographic techniques and biochemical assays have improved; however, they remain uncommon and are unfamiliar to most neurosurgeons. This report concerns eight patients with hyperthyroidism, inappropriately elevated levels of serum thyrotropin and alpha-subunit, and radiographic evidence of pituitary tumor. All underwent surgery and had pathological confirmation of a thyrotropin-secreting adenoma, and most had been subjected to prior ablation of the thyroid gland. Only one tumor was a microadenoma; the others ranged in size from 1.4 to 12 cm, and invasion of parasellar structures was common. Thyrotropin, triiodothyronine, thyroxine, and alpha-subunit were measured preoperatively and at intervals postoperatively. Coexistent hormonal abnormalities (which occurred in all patients) included acromegaly and hyperprolactinemia and were also monitored. All four patients who had tumors less than 2 cm in diameter remain alive. Complete extirpation of tumor in these patients produced rapid correction of all hormonal abnormalities and resolution of clinical hyperthyroidism. The other four patients had larger invasive tumors: two died soon after surgery, one died of disseminated tumor 8 years after presentation, and one remains alive with residual tumor. Tumors secreting thyroid-stimulating hormone are less easily cured by surgery than are other types of pituitary adenoma because of the large size and invasive features that many attain during the delay to diagnosis; medical therapy can subdue the tumor but not cure it. The experience with these patients establishes the importance of early diagnosis and surgical excision for successful treatment, and demonstrates the utility of modern diagnostic techniques for finding these lesions. As occurs in Nelson's syndrome after adrenalectomy for Cushing's disease, ablation of the target organ may allow the tumor to convert to a more clinically malignant form which is resistant to cure.