Gonadotropin-secreting and thyrotropin-secreting pituitary adenomas: A single-center experience

ABSTRACT Objective: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India. Materials and methods: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical (inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas. Results: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, median largest dimension 40 mm, range 33-60 mm) and six TSHomas (median age 34.5 years, four women, two TSHomas cosecreting GH, median largest dimension 42.5 mm, range 13-60 mm). Symptoms of sellar mass effects led to pituitary imaging in most patients with FGA. Patients with TSHomas had symptoms of excess hormone secretion (GH/TSH) or sellar mass effects. The TSHomas that cosecreted GH/FSH were larger than those secreting only TSH. Transsphenoidal resection was the most common first-line therapy but significant residual disease was frequent (3 out of 6 FGAs and 4 out of 5 TSHomas). Conclusion: This is the first and second case series of FGAs and TSHomas, respectively, from India. In this study, TSHomas presented at younger age, were larger and had low surgical cure rates.

Gonadotropin-secreting and thyrotropin-secreting pituitary adenomas: A single-center experience.

Objective: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India. Materials and methods: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical(inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas. Results: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, median largest dimension 40 mm, range 33-60 mm) and six TSHomas (median age 34.5 years, four women, two TSHomas cosecreting GH, median largest dimension 42.5 mm, range 13-60 mm). Symptoms of sellar mass effects led to pituitary imaging in most patients with FGA. Patients with TSHomas had symptoms of excess hormone secretion (GH/TSH) or sellar mass effects. The TSHomas that cosecreted GH/FSH were larger than those secreting only TSH. Transsphenoidal resection was the most common first-line therapy but significant residual disease was frequent (3 out of 6 FGAs and 4 out of 5 TSHomas). Conclusion: This is the first and second case series of FGAs and TSHomas, respectively, from India. In this study, TSHomas presented at younger age, were larger andhad low surgical cure rates.

A reference center study in thyrotropin-secreting pituitary adenomas: clinicopathological, therapeutic and long-term follow-up outcomes.

PURPOSE: This study aims to analyze the clinicopathological features, diagnostic steps, and therapeutic results of TSHomas and to reveal the effective factors on remission. METHODS: The clinical, radiological, and pathological features and surgical and endocrinological results of 41 TSHoma cases followed between 2005 and 2022 were retrospectively analyzed. The factors affecting the surgical cure were investigated by comparing the groups with and without remission. RESULTS: A total of 41 patients (23 male,18 female) were included in the study and the mean age was 42 (31.5-49). Palpitation and headache were the most common complaints. The time from the onset of symptoms to diagnosis was 8 (3-20) months. There were 8 patients with a preoperative clinical and biochemical diagnosis of TSH + GH co-secretion. In the TRH stimulation test, a blunted TSH response was obtained in 18 patients (90.0%). Complete suppression could not be obtained in any of the patients who underwent the T3 suppression test. The median maximum tumor diameter was 19.0 mm (6.8-41). There was microadenoma in 4 (9.8%) patients and macroadenoma in 37 patients (92.8%). Remission was achieved in 31 (75.6%) of 40 patients who underwent endoscopic transsphenoidal surgery (eTSS). The Ki-67 labeling index was 2% (1.00-4.00) in the entire patient group. Preoperative use of antithyroid drugs appears to be significantly associated with surgical cure. CONCLUSION: Diagnosis of TSHoma is still full of challenges and dynamic tests remain important. Recognition and good management of inappropriate TSH secretion states affect subsequent surgical outcomes.

Case report: A rare case of thyrotropin-secreting pituitary macroadenoma with diffuse calcification presenting with hyperthyroidism and literature review.

Background: Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas (TSHomas) are rare and usually present with hyperthyroidism. Calcification in pituitary tumors is an infrequent finding. Herein, we report an extremely rare case of TSHoma with diffuse calcification. Case description: A 43-year-old man was admitted to our department with a complaint of palpitations. An endocrinological examination revealed elevated serum levels of TSH, free triiodothyronine (FT3), and free thyroxin, whereas the physical examination revealed no obvious abnormality. Computerized tomography (CT) showed a sellar mass with diffuse calcification. Contrast-enhanced T1-weighted images revealed a less-enhancing tumor without obvious suprasellar or parasellar expansion. The tumor was completely removed via endoscopic transnasal-sphenoidal surgery. Microscopically, nests of cells were inconspicuous among the diffuse psammoma bodies. Expression of TSH was patchy, and only several TSH-positive cells were observed. Postoperatively, the serum levels of TSH, FT3, and FT4 decreased to their normal range. Follow-up MR images showed no evidence of residual tumor or regrowth after the resection. Conclusions: Herein, we report a rare case of TSHoma with diffuse calcification that presented with hyperthyroidism. A correct and early diagnosis was made according to the European Thyroid Association guidelines. This tumor was completely removed via endoscopic transnasal-transsphenoidal surgery (eTSS), and thyroid function was normalized after the operation.

A patient with an ectopic sphenoid bone TSH secretory adenoma: Case report and review of the literature.

Ectopic thyroid-stimulating hormone (TSH)oma located outside the sella turcica is exceedingly rare and can be associated with significant diagnostic delay. The clinical presentation depends on the anatomical location and size of the ectopic tumor and the degree of thyrotoxicosis. A 71-year-old woman presented with goiter and thyrotoxicosis. Initial investigations revealed elevated free thyroxine (fT4) and tri-iodothyronine (fT3) with inappropriately high-normal TSH. Assay interference was unlikely, pituitary magnetic resonance imaging (MRI) scan was reported as "normal," and germline sequencing was negative for thyroid hormone receptor ß pathogenic variants. One year later, total thyroidectomy for enlarging symptomatic goiter and suspicious nodule revealed multifocal microscopic papillary thyroid carcinoma. Six years later, she presented to an ear, nose, and throat surgeon with nasal congestion, and a sphenoid bone mass was discovered on nasoendoscopy and imaging. Ectopic TSHoma was confirmed on surgical resection, and a review of the initial pituitary MRI scan revealed the mass which had initially been missed. This is the first reported case of an ectopic TSHoma located in the sphenoid bone. Ectopic TSHoma should be considered in patients with inappropriate TSH secretion when more common differentials are excluded including thyroid hormone resistance or pituitary TSHoma.

A Case Report of a Thyrotropin-Secreting Pituitary Macroadenoma.

Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma is a rare case that is characterized by high or inappropriately normal thyrotropin levels along with an increase in thyroid hormones that lead, in most of the patients, to signs and symptoms similar to those of hyperthyroidism problems. Its diagnosis and management are still challenging. A 65-year-old male patient presented to the emergency department for palpitations. He was firstly misdiagnosed due to incomplete lab tests. After a full workup, he was found to have TSH-secreting pituitary adenoma and referred to trans-sphenoidal surgery for macroadenoma excision. Currently, he is maintained on somatostatin analogue and methimazole. This is the second case report of TSHoma in Lebanon with signs and symptoms of thyrotoxicosis. Usually, the clinical features of TSHomas vary between patients which makes the confirmation of diagnosis more difficult. Surgery is still the first line of treatment with the addition of encouraging effects of medical therapy consisting of somatostatin analogues.

A challenging TSH/GH co-secreting pituitary adenoma with concomitant thyroid cancer; a case report and literature review.

BACKGROUND: Thyroid stimulating hormone (TSH) secreting pituitary adenoma (TSHoma) with coexisting thyroid cancer is extremely rare, and proper treatment of both diseases may pose a unique clinical challenge. When TSHoma has plurihormonality, particularly involving the co-secretion of growth hormone (GH), management can be more complicated. Herein, we present a difficult-to-manage case of papillary thyroid cancer with an incurable TSH/GH-secreting pituitary adenoma. CASE PRESENTATION: A 59-year-old man was referred to our hospital due to memory impairment and inappropriate TSH level. Sella magnetic resonance imaging revealed a huge pituitary mass extending to the suprasellar area. Clinical diagnosis of TSH/GH co-secreting pituitary adenoma was made based on elevated free T4, total T3, serum α-subunit, insulin-like growth factor-1 levels and non-suppressible GH levels after oral glucose loading. Rectal cancer and multifocal papillary thyroid microcarcinoma (PTMC) were diagnosed during initial screening for internal malignancy; lower anterior resection was performed and close observation was planned for PTMC. Long-acting octreotide therapy was commenced, which resulted in a dramatic reduction in TSHoma size and facilitated control of hormonal excess. Total thyroidectomy and radioactive iodine (RAI) therapy were needed during follow up due to the growth of PTMC. After the surgery, the pituitary adenoma represented resistance to somatostatin analogue therapy and the tumor size gradually increased despite the addition of dopamine agonist therapy. Furthermore, TSH suppressive therapy with levothyroxine was impossible and an adequate TSH level for RAI therapy was unmountable. Late debulking pituitary surgery was ineffective, and the patient gradually deteriorated and lost to follow up. CONCLUSION: We report the first aggravated case of TSH/GH co-secreting pituitary tumor after total thyroidectomy for concomitant multifocal PTMC. Deferring of thyroid surgery until the TSHoma is well controlled may be the optimal therapeutic strategy in patients with TSHoma and coexistent thyroid cancer; ablative thyroid surgery may result in catastrophic pituitary tumor growth.

Ectopic TSH-secreting Pituitary Adenoma in Nasopharyngeal Region.

Objective: TSH-secreting pituitary adenomas (TSH-omas) are very rare disorders. This report describes the diagnosis and treatment of a thyroid-stimulating hormone-secreting ectopic pituitary adenoma in the nasopharyngeal region. Subjects and Methods: We report a 37-year-old male patient with thyroid-stimulating hormone-secreting ectopic pituitary adenoma in nasopharyngeal region. Results: A patient suffering from sweating, palpitations, dizziness and abnormality in thyroid tests was referred to our clinic. Thyroid function tests showed high basal levels of free thyroxine (FT4), free tri-iodothyronine (FT3), and serum TSH. TRH stimulation test results indicated blunted response. Scintigraphy showed increased radionuclide uptake (iodine-123), and a thyroid ultrasound scan revealed diffuse enlargement of the thyroid gland. A pituitary MRI indicated a normal pituitary. However, MRI showed a mass in the nasopharynx that was confirmed with endoscopy. Endoscopic total endonasal resection was done and the mass was removed. The pathology reported a TSH-secreting pituitary adenoma. Conclusion: In this report, an identified case of thyroid-stimulating hormone-secreting ectopic pituitary adenoma in nasopharyngeal region is reported and it is the only tenth case in the literature indicated in the nasopharyngeal region. Ectopic TSH-omas should be considered during inappropriate secretion of TSH as a candidate cause to enable correct diagnosis and improve the treatment of patients.

A remarkable case of thyrotoxicosis initially caused by graves' disease followed by a probable TSHoma - a case report.

BACKGROUND: Graves' disease is the commonest cause of thyrotoxicosis whilst thyrotropin (TSH)-producing pituitary adenomas (thyrotropinomas, TSHomas) are very rare and account for just 1-2% of all pituitary adenomas. Coexistence of a TSHoma and Graves' disease has been very rarely reported. Here, we report a case of a patient whose initial presentation with primary thyrotoxicosis due to Graves' disease, was subsequently followed by a relapse of thyrotoxicosis due to a probable TSHoma. CASE: A sixty-eight year old woman was referred to our department with classical features of thyrotoxicosis. Initial biochemistry confirmed hyperthyroxinaemia [free thyroxine (fT4) 20.4 pmol/L (reference range 7.0-16.0)] and a suppressed TSH [< 0.02mIU/L (0.50-4.20)]. A technetium pertechnetate uptake scan was consistent with Graves' Disease. She was treated with carbimazole for 18 months and remained clinically and biochemically euthyroid. After stopping carbimazole her fT4 started to rise but TSH remained normal. Laboratory assay interference was excluded. A TRH stimulation test demonstrated a flat TSH response and pituitary MRI revealed a microadenoma. Remaining pituitary hormones were in the normal range other than a slightly raised IGF-1. An 11C-methionine PET/CT scan coregistered with volumetric MRI (Met-PET-MRICR) demonstrated high tracer uptake in the left lateral sella region suggestive of a functioning adenoma. The patient declined surgery and was unable to tolerate cabergoline or octreotide. Thereafter, she has elected to pursue a conservative approach with periodic surveillance. CONCLUSION: This is a very unusual case of thyrotoxicosis caused by two different processes occurring in the same patient. It highlights the importance of considering dual pathology when previously concordant thyroid function tests become discordant. It also highlights a potential role of Met-PET-MRICR in the localisation of functioning pituitary tumours.

Concurrent Graves' Disease and TSH Secreting Pituitary Adenoma Presenting Suppressed Thyrotropin Levels: A Case Report and Review of the Literature.

Background: Thyroid stimulating hormone (TSH) secreting pituitary adenoma (TSHoma) is a rare cause of hyperthyroidism. To date there have been only thirteen cases reporting the coexistence of TSHoma with Graves' disease (GD). The diagnosis and management for such hyperthyroidism due to both etiologies remain challenging. Case Report: A 55-year-old Chinese female presented with signs and symptoms of thyrotoxicosis. Thyroid function tests showed elevated thyroid hormones and mildly suppressed TSH values. Her anti-thyrotropin receptor antibody (TRAb) was positive. Octreotide suppression test successfully decreased her TSH. Magnetic resonance imaging showed a pituitary macroadenoma. She underwent endoscopic trans-sphenoidal resection and surgical pathology confirmed a TSH producing pituitary adenoma. Methimazole was prescribed after surgery and her clinical course was monitored. Conclusions: Here we report a case of a 55-year-old female with TSHoma and Graves' disease whose TSH level was mildly suppressed. This case emphasizes the importance of thoroughly evaluating the thyroid function test during the diagnosis of hyperthyroidism. It also highlights the challenges in the diagnosis and treatment of this rare condition.

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

PURPOSE: 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. METHODS: 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. RESULTS: Twelve patients (10.81%) were identified with thyrotropin/growth hormone pituitary adenoma at Peking Union Medical College Hospital within 8 years, 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". CONCLUSIONS: 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.

Hyperthyroxinemia with a non-suppressed TSH: how to confidently reach a diagnosis in this clinical conundrum.

Disorders of thyroid function are among the commonest referrals to endocrinology. While interpretation of thyroid function testing is usually straightforward, accurate interpretation becomes significantly more challenging when the parameters do not behave as would be expected in normal negative feedback. In such cases, uncertainty regarding further investigation and management arises. An important abnormal pattern encountered in clinical practice is that of high normal or raised free thyroxine (fT4) with inappropriately non-suppressed or elevated thyroid-stimulating hormone (TSH). In this short review using two clinical vignettes, we examine the diagnostic approach in such cases. A diagnostic algorithm is proposed to ensure that a definitive diagnosis is reached in these challenging cases.

A Thyroid-stimulating Hormone (TSH) Producing Adenoma in a Patient with Severe Hypothyroidism: Thyroxine Replacement Reduced the TSH Level and Tumor Size.

We treated an extremely rare thyroid-stimulating hormone (TSH)-producing pituitary adenoma in a 63-year-old woman with severe hypothyroidism due to autoimmune thyroiditis. She was presented with dizziness and fatigue. The blood level of TSH, prolactin, and fT4 was 288.2 µIU/mL, 72.9 ng/mL, and 0.24 ng/dL, respectively. Magnetic resonance imaging demonstrated a large pituitary tumor, 31 mm in height, and a normal pituitary gland. Preoperative thyroxine replacement reduced the TSH level to 2.05 µIU/mL and produced a significant reduction in the tumor volume. Histopathologically, the surgically removed tumor was a TSH-producing pituitary adenoma.

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.

Massive pleural and pericardial effusion due to hypothyroidism in a patient with a surgically treated thyroid-stimulating hormone-producing pituitary adenoma.

Hypothyroidism is relatively rare etiology of serositis with effusion, but massive pleural effusion is very unusual. This is a report of massive pleural effusion in patient taking methimazole after surgical resection of thyroid-stimulating hormone (TSH)-producing pituitary adenoma (TSHoma). The patient was clinically and biochemically hypothyroid and responded well to discontinuation of methimazole and thyroid hormone replacement therapy. When assessing patients with pleural effusion, we should not rely on laboratory test results alone, as a detailed medical history and thorough physical examination could be more useful.

A case of coexistence of TSH/GH-secreting pituitary tumor and papillary thyroid carcinoma: Challenges in pathogenesis and management.

Co-existence of thyrotropin/growth hormone-secreting pituitary adenoma with differentiated thyroid carcinoma is exceedingly rare, with less than 15 cases having been reported. Its clinical presentation and treatment strategy are challenging. We report a case of pituitary macroadenoma, with clinical syndromes of acromegaly and hyperthyroidism, and a thyroid nodule, with cytologically confirmed to be a papillary thyroid carcinoma. Clinical implications, focusing on the strategy for proper management, and possible pathogenesis were discussed.

Surgical treatment and outcome of TSH-producing pituitary adenomas.

BACKGROUND: Thyrotropin-producing adenomas (TSHomas) account for approximately 1-2% of all pituitary tumors. Recently, there has been debate on primary treatment as some studies suggest a high rate of hypopituitarism after transsphenoidal surgery and therefore suggest primary use of somatostatin analogs (SSA) instead. We would like to challenge this assumption by presenting our single-center experience with transsphenoidal surgery for TSHoma. METHODS: Fifteen patients treated consecutively between May 2010 and December 2016 were analyzed for long-term postoperative remission and pituitary function. RESULTS: Data on the development of TSH, fT3 and fT4 were available for 12 of 15 patients (mean follow-up was 18 months, 8 patients >12 months), showing mean TSH levels of 1.289 mU/l (0.02-2.04, SD 0.66), mean fT3 levels of 3.76 pmol/l (0.5-6.16, SD 1.8) and mean fT4 levels of 16.5 pmol/l (11.7-21.9, SD 3.66). Six of those patients were substituted with a mean of 85.4 µg L-thyroxine after a median follow-up of 20.7 months. The other six patients did not receive L-thyroxine at a median follow-up of 15.5 months. One patient with a known tumor remnant on MRI stayed euthyreotic with cabergoline at the timepoint of follow-up 22 months after the operation. Control of the corticotrop axis was also available in 12 of 15 with no patient showing a corticotroph insufficiency in the long term. CONCLUSIONS: We argue that transsphenoidal surgery for TSHoma should be considered as the treatment of choice as remission following surgery is highly probable and postoperative hypopituitarism is very unlikely if patients are referred to centers with high pituitary surgery case loads.

Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report.

BACKGROUND: Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. CASE PRESENTATION: A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. CONCLUSIONS: This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma and Graves' disease.

Thyrotropinoma and multinodular goiter: A diagnostic challenge for hyperthyroidism.

Thyroid disorders are frequently encountered. The diagnosis is straightforward unless clinical or laboratory findings are inconclusive and/or perplexing. Hyperthyroidism due to a thyrotropin-secreting pituitary adenoma rarely occurs and symptoms due to thyroid hormone excess are subtle. The presentation of the disease becomes unusual when co-secretion of other hormones with thyrotropin or concomitant thyroid parenchymal pathology exist. We present the case of a 63-year-old female patient with thyrotropinoma co-secreting growth hormone and multinodular goiter. She developed hyperthyroidism first due to thyrotropinoma and later due to a toxic nodule. Herein, we discuss the diagnostic and therapeutic challenges of hyperthyroidism with atypical presentation.