Challenges in the Management of a 7-Year-Old Child with Thyrotropin-Secreting Pituitary Adenoma and the Review of the Literature.

INTRODUCTION: Thyrotropin-producing pituitary adenoma (TSHoma) is a very rare disease, representing less than 1% of the pituitary tumours and presenting with elevated thyroid hormones and normal/high TSH concentrations. CASE PRESENTATION: A 7-year-old boy with nervousness was referred by his psychiatrist for elevated free T4, T3, and TSH levels. Initial evaluation revealed an elevated α-subunit. Pituitary magnetic resonance imaging (MRI) demonstrated a macroadenoma. The patient underwent a trans-sphenoidal tumour resection (TSS) which showed positive immunohistochemical staining for TSH, growth hormone, and prolactin in tumoral tissue. Euthyroidism was achieved for 1 year after TSS, then recurrence of tumour with elevated TSH and thyroid hormone levels necessitated a re-operation with TSS followed by gamma-knife radiosurgery. The euthyroid state was achieved and lasted for 2.5 years this time, but due to the recurrence, medical treatment had been commenced with cabergoline and octreotide. Euthyroidism was maintained for the last 4 years on monthly octreotide treatment. A repeat MRI demonstrated no pituitary mass, but a mass in the sphenoidal sinus had been detected. Removal of this mass by surgery did not achieve euthyroidism. 68Ga-DOTA-TATE positron emission tomography/computed tomography showed residual tissue extending from the pituitary region to the sphenoid sinus. The patient's bone age was advanced by 2 years at diagnosis which became 4 years in 1 year after the diagnosis and remained so throughout follow-up, leading to a final height of -3.3 SDS below his target height at the age of 16 years. CONCLUSION: The diagnosis, treatment, and follow-up of TSHomas are challenging, and short stature due to accelerated bone maturation is a complication of paediatric TSHomas.

Thyrotropin-secreting microadenoma and the importance of a prompt diagnosis: A case report.

Background: The prevalence of thyrotropin-secreting pituitary adenomas, most being macroadenomas, is one to two cases per million inhabitants. Their differential diagnosis may be challenging, especially for microadenomas. Case description: We present the case of a 50-year-old male with progressive neck enlargement, hot sudorific hands, anorexia, diarrhea, and weight loss over the preceding three months. Laboratory evaluation revealed high thyroid hormones, predominantly high free triiodothyronine of 7.74 pg/mL (reference range 2.3-4.2), with a non-suppressed thyroid stimulating hormone (TSH) of 1.73 µIU/mL (reference range 0.55-4.78). A high level of suspicion directed additional evaluation that revealed a high total alpha-subunit of glycoprotein hormones (αGS) and αGS/TSH ratio. Magnetic resonance imaging revealed a six mm pituitary lesion. A microthyrotropinoma was diagnosed, and long-acting octreotide was initiated before surgery for symptomatic control. Endoscopic transnasal transsphenoidal tumor resection was performed months later. The patient was in remission one year after surgery with no pituitary deficits. Conclusions: Reaching an accurate diagnosis on time is crucial for deciding the optimal therapeutic approach and preventing and decreasing the frequency of endocrine and neurological complications. HIPPOKRATIA 2022, 26 (4):157-160.

Syndrome of resistance to thyroid hormone and thyrotropin-secreting pituitary adenoma: Case series study / 中华内分泌代谢杂志

Objective:To outline clinical features in syndrome of resistance to thyroid hormone(RTH) and thyrotropin-secreting pituitary adenoma(TSH adenoma) based on a case series, and to assess the value of octreotide suppression test and high-dose dexamethasone suppression test(HDDST) in differentiating the two diseases.Methods:A total of 22 cases with RTH and TSH adenoma clinically diagnosed in Xiangya Hospital of Central South University from October 2010 to December 2021 were retrieved. The clinical characteristics of the two diseases and results to different tests were analyzed and summarized.Results:(1) The tumors in TSH adenoma patients were larger than those with RTH complicated with pituitary mass, which presented chiasmatic compression on images( P<0.05). (2) In octreotide suppression test, thyrotropin(TSH) inhibition rate in RTH patients was lower than that in TSH adenoma patients( P<0.05). In HDDST, TSH inhibition rate was higher in patients with RTH than in patients with TSH adenoma( P<0.05). (3) The TSH inhibition rate was calculated by receiver operating characteristic(ROC) curve. The sensitivity and specificity of octreotide suppression test were 91.9% and 55.6%, respectively, and the threshold value of TSH inhibition rate was 64.24%. The sensitivity and specificity of HDDST were 54.4% and 89.0%, respectively, and the threshold value of TSH inhibition rate was 65.73%.The combined sensitivity and specificity of the two tests were 77.8% and 90.9%, indicating better diagnostic value( P<0.05). Conclusions:The combination of octreotide suppression test and HDDST is of clinical value in differentiating RTH from TSH adenoma. TSH adenoma is more aggressive than that of pituitary adenoma with RTH.

A 2019 update on TSH-secreting pituitary adenomas.

Thyrotropin-secreting pituitary adenomas (TSH-omas) present with signs and symptoms of hyperthyroidism and they are characterized by elevated serum levels of free thyroid hormones with measurable TSH levels. TSH-omas are very infrequent, accounting for less than 1% of all pituitary adenomas, thus representing a very rare cause of hyperthyroidism. For this reason, data collected on these rare disorders are relatively few, but some new researches shed new light on the etiopathogenesis, the diagnosis and the treatment of such a remarkable disease. Since the same biochemical picture is present in the syndromes of thyroid hormone resistance (RTH), in particular in the form of pituitary RTH, failure in distinguishing these clinical entities may lead to improper patient management. Conversely, early diagnosis and correct treatment of TSH-omas may prevent the occurrence of neurological and endocrinological complications, thus leading to a better rate of cure. In the present short review article, the most relevant recent advances in the pathophysiology of TSH-omas are described.

A comparative study of the clinical features of thyrotropin-secreting pituitary adenomas / 解放军医学杂志

Objective To comparatively analyze the clinical characteristics of thyrotropin-secreting pituitary adenomas (TSH-omas).Methods The clinical features, laboratory variables, imaging and pathological Results were retrospectively compared and analyzed of 26 cases with TSH-omas admitted in Chinese PLA General Hospital from Feb. 2006 to Oct. 2016 and 20 cases with TSH-omas admitted in Shanghai Huashan Hospital from Apr. 2006 to Apr. 2013.Results The female ratio was slightly higher in patients of Chinese PLA General Hospital than in Huashan Hospital [(57.7%(15/26)vs. 45.0%(9/20)], while the mean age was similar [39.5±14.1(18-67 years)vs. 40.0±14.5(17-74 years)]. The most common chief complaint was thyrotoxicosis [73.1%(19/26)vs. 55.0%(11/20)], and mild-to-moderate goiter was the most common symptom. The mean serum TSH levels in Chinese PLA General Hospital and in Huashan Hospital were 5.06(2.97-6.27)mU/L and 6.16(3.76-10.91)mU/L respectively, and patients with normal serum TSH levels were more common in Chinese PLA General Hospital than in Huashan Hospital [57.7%(15/26)vs. 40.0%(8/20)]. Microadenoma was more common in Chinese PLA General Hospital than in Huashan Hospital [34.62%(9/26)vs. 20.0%(4/20)], while macroadenoma was more common in Huashan Hospital than in Chinese PLA General Hospital [20.0%(4/20)vs. 7.7%(2/26)]. Microadenoma was more common in female patients of the both groups [66.7%(6/9)vs. 75.0%(3/4)], while macroadenoma was all found in male patients. Tumor invasion of surrounding tissue and structure was often found in macroadenoma. In terms of octreotide inhibition test, the range of 24h TSH inhibition rate was roughly the same in the two groups (37.4%-91.8% and 46.5%-94.1%, respectively). Mixed adenoma was rare among all the pathologically confirmed cases. In Chinese PLA General Hospitals, TSH immunoreactive negative neoplastic cells were found in 3 of 8 cases, and octreotide scanning showed negative in 2 of 12 cases.Conclusions Patients with TSH-omas in the two hospitals show similarities but also some significant differences in the clinical features. Overall, the domestic patients with TSH-omas are diagnosed without gender difference according to the reports in China. The mean age at diagnosis is significantly younger than that in foreign data. Microadenoma is more common in females, while macroadenoma is more common in males. Serum TSH levels can be normal in patients with TSH-omas. Immunostaining and/or octreotide scanning for TSH can be negative.

One case of a thyrotropin-secreting microadenoma and resistance to thyroid hormone with P453T mutation in TRβgene / 中华内分泌代谢杂志

[Summary] We investigated a 12-year-old girl with elevated serum FT3 , FT4 , and TSH levels. The sequence of thyroid hormone receptorβ( TRβ) exons revealed a CCT→ACT transition mutation at nucleotide 453 site within exon10,whichresultedinthesubstitutionofcytosinetoadenosinein(P453T). Pituitarymagneticresonanceimage 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.

Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases.

OBJECT: The aim of this study was to analyze clinicopathological characteristics and treatment outcomes in a large single-center clinical series of cases of thyrotropin (TSH)-secreting pituitary adenomas. METHODS: The authors retrospectively reviewed clinical, pathological, and treatment characteristics of 90 consecutive cases of TSH-secreting pituitary adenomas treated with transsphenoidal surgery between December 1991 and May 2013. The patient group included 47 females and 43 males (median age 42 years, range 11-74 years). RESULTS: Sixteen tumors (18%) were microadenomas and 74 (82%) were macroadenomas. Microadenomas were significantly more frequent in the more recent half of our case series (12 of 45 cases) (p = 0.0274). Cavernous sinus invasion was confirmed in 21 patients (23%). In 67 cases (74%), the tumors were firm elastic or hard in consistency. Acromegaly and hyperprolactinemia were observed, respectively, in 14 (16%) and 11 (12%) of the 90 cases. Euthyroidism was achieved in 40 (83%) of 48 patients and tumor shrinkage was found in 24 (55%) of 44 patients following preoperative somatostatin analog treatment. Conventional transsphenoidal surgery, extended transsphenoidal surgery, and a simultaneous combined supra- and infrasellar approach were performed in 85, 2, and 3 patients, respectively. Total removal with endocrinological remission was achieved in 76 (84%) of 90 patients, including all 16 (100%) patients with microadenomas, 60 (81%) of the 74 with macroadenomas, and 8 (38%) of the 21 with cavernous sinus invasion. None of these 76 patients experienced tumor recurrence during a median follow-up period of 2.8 years. Stratifying by Knosp grade, total removal with endocrinological remission was achieved in 34 of 36 patients with Knosp Grade 0 tumors, all 24 of those with Grade 1 tumors, 12 of the 14 with Grade 2 tumors, 6 of the 8 with Grade 3 tumors, and none of the 8 with Grade 4 tumors. Cavernous sinus invasion and tumor size were significant independent predictors of surgical outcome. Immunoreactivity for growth hormone, prolactin, or both hormones was present in 32, 9, and 24 patients, respectively. The Ki-67 labeling index was less than 3% in 71 (97%) of 73 tumors for which it was obtained and 3% or more in 2. Postsurgery pituitary dysfunction was found in 15 patients (17%) and delayed hyponatremia was seen in 9. CONCLUSIONS: TSH-secreting adenomas, particularly those in the microadenoma stage, have increased in frequency over the past 5 years. The high surgical success rate achieved in this series is due to relatively early diagnosis and relatively small tumor size. In addition, the surgical strategies used, such as extracapsular removal of hard or solid adenomas, aggressive resction of tumors with cavernous sinus invasion, or extended transsphenoidal surgery or a simultaneous combined approach for large/giant multilobulated adenomas, also may improve remission rate with a minimal incidence of complications.

2013 European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors.

Hyperthyroidism is mainly due to autoimmune thyroid disorders or toxic goiter, and very rarely to the presence of thyrotropin (TSH)-secreting pituitary adenomas (TSHomas). These tumors are characterized by high levels of circulating free thyroid hormones (FT4 and FT3) in the presence of nonsuppressed serum TSH concentrations. Failure to correctly diagnose TSHomas may result in inappropriate thyroid ablation, which results in a significant increase of pituitary tumor mass. The diagnosis is mainly achieved by measuring TSH after T3 suppression and TRH stimulation tests. These dynamic tests, together with pituitary imaging and genetic testing are useful in distinguishing TSHomas from the syndromes of resistance to thyroid hormone action. The treatment of choice is surgery. In cases of surgical failure, somatostatin analogs have been found to be effective in normalizing TSH secretion in more than 90% of patients.

Thyrotropin-secreting pituitary adenomas: report of 5 cases and literature review / 解放军医学杂志

Objective To study the clinical characteristic of the central hyperthyroidism due to thyrotropin-secreting pituitary adenoma. Methods 5 patients with TSH-secreting pituitary adenoma (4 male and 1 female) among 1500 pituitary adenomas were summarize between 1992 and 2006, and clinical characteristics of the 5 patients were analyzed retrospectively. Results 5 patients represented 0.33% of all pituitary adenoma patients were seen during the same period. The mean age of the patients was 39.8 years old, and mean duration 5.84 years. All patients were presented with thyrotoxicosis. 3 patients were previously considered as suffering from primary hyperthyroidism and were treated with anti-thyroid drug for 6 to 16 years, and one of them subsequently underwent hypothyroid operation twice. None of them had visual field defect. Hyperthyroidism was determined in all patients by means of elevated total or free thyroid hormone levels while serum TSH levels varied between 3.94?54.7mU/L. TRH provoked an increase in serum TSH concentration greater than 30 mU/L from the baseline level in one patient, whereas no response was observed in two patients. MRI showed pituitary macroadenomas in four patients, while microadenomas in remaining patient. Four patients underwent transsphenoidal adenomectomy and followed by radio therapy in three patients. This resulted in normalization of all hormone parameters in all patients 1-2 weeks after operation. Conclusion Central hyperthyroidism due to thyrotropin-secreting pituitary adenoma should be considered in patients with elevated thyroid hormone and non-suppressed serum TSH level. Combined treatment (transsphenoidal adenomectomy and radiotherapy) is the choice for thyrotropin-secreting pituitary adenoma.

Piruitray Thyrotropin-Secreting Tumors in Korean / 대한내분비학회지

BACKGROUND: Thyrotropin-secreting pituitary adenoma is an uncommon disease and about 150 cases has been reported in the world literature. In Korea, only seven cases were reported as yet. The authors recently experienced four cases of TSH secreting pituitary tumor and analyzed the clinical characteristics and treatment outcomes of TSH-secreting tumors in Korean. METHODS: We analyzed clinical records of the four cases who had been recently treated at Asan Medical Center and the Korean literature which deals with the previously reported seven cases of TSH-secreting pituitary tumor. RESULTS: The average age at diagnosis was 37 years (ranging from 11 to 55 years). Four were men and seven were women. After the detection of hyperthyroidism, TSH-secreting pituitary adenoma was diagnosed 3.6 years later on the average. Ten patients presented with hyperthyroidism, but one had primary hypothyroidism. Typical features of acromegaly were observed in two patients. Visual disturbance was present in three cases, and galactorrhea was present in one case. Serum TSH concentrations ranged from 1.5 to 42.5uIU/mL showing mildly elevated or unsup-pressed TSH levels despite of elevated serum thyroid hormone concentrations. Among six cases in whom a-subunit level was measured, five showed elevated a-subunit level and a-subunit/TSH molar ratio. Two of 11 cases had microadenoma and the remainder had macroadeno#ma. Immunohisto-cheical studies were done in eight cases and revealed that three were positive for TSH only and five patients were positive for multiple hormones. Eight patients underwent transsphenoidal pituitary surgery and seven (88%) of them were cured. External irradiation or octreotide was used as adjunctive treatment in three cases. After treatment, TSH levels decreased in all six patients studied, hyperthyroidism was eliminated in all eight patients studied and visual disturbance was improved in two patients. CONCLUSION: Clinical characteristics of TSH-secreting pituitary adenoma in Koreans were similar with world literature, but were more common in women, had less visual disturbance and better surgical results. Diagnosis was commonly delayed for several years. TSH-secreting pituitary adenoma may be diagnosed more frequently and earlier with widespread use of sensitive TSH assay and early and proper diagnosis would lead proper treatments with improved outcome.