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.

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.

Diagnosis and treatment of TSH-secreting adenomas: review of a longtime experience in a reference center.

PURPOSE: TSH-secreting pituitary adenomas are among the less prevalent pituitary tumors, corresponding to 0.9-1.5% of all pituitary adenomas in surgical series. METHODS: A series of 11 patients with TSH-secreting and cosecreting adenomas diagnosed and treated in the last 25 years in a single center is described. RESULTS: The mean age at diagnosis was 37 years (range 18-80 years; median 23 years); the ratio of male-to-female patients was similar (6M:5F). Only three patients was the correct diagnosis established shortly after the initial medical evaluation. Other four patients were initially diagnosed with other pituitary adenomas (prolactinoma, acromegaly, and non-secreting pituitary tumor) and another four diagnosed with primary hyperthyroidism. There was a mean diagnostic delay of 6.0 years (range 0.5-25 years; median 2 years). Nine patients had macroadenomas and two patients had microadenomas. Seven patients underwent pituitary surgery which controlled the disease in only two (one micro- and one noninvasive macroadenoma). The other treatments were directed to the thyroid gland (surgery or 131I radiotherapy), pituitary radiotherapy, and somatostatin analog. CONCLUSION: In spite of its relatively straightforward diagnosis, which includes clinical/subclinical hyperthyroidism with or without goiter, increased free thyroxine and nonsuppressed TSH levels, and pituitary mass, the diagnosis of TSH-secreting and cosecreting adenomas was frequently unrecognized and thus much delayed. Serum alpha-subunit levels were high in nearly all patients with TSH-secreting adenomas and useful in excluding other conditions in the differential diagnosis. Proper indication and interpretation of simple laboratory tests should be emphasized in medical education to improve diagnostic accuracy.

A case of TSH-secreting pituitary adenoma with cyclic fluctuations in serum TSH levels.

A 29-year-old man was referred to our department due to adrenal insufficiency with the inappropriate secretion of TSH (SITSH). Magnetic resonance imaging revealed a pituitary tumor. A weak TSH response in the TRH test, elevated sex hormone binding globulin (SHBG) levels, and the absence of a family medical history of SITSH or TRß gene mutations supported the diagnosis of TSH-secreting pituitary adenoma (TSHoma). However, complete TSH suppression and a blunted cholesterol response in the T3 suppression test as well as normal glycoprotein α-subunit (α-GSU) levels were not compatible with TSHoma. Since TSH, FT3, and FT4 spontaneously returned to normal ranges after admission, he was discharged. One month after his discharge, thyrotoxicosis with elevated serum TSH levels relapsed. After admission, his serum TSH levels returned to within the normal range. After his discharge from the second admission, his serum TSH levels fluctuated in accordance with serum FT3 and FT4 levels and symptoms, such as palpitations. Ten months after his discharge, he was admitted to our department again due to adrenal insufficiency and thyrotoxicosis with elevated serum TSH levels, suggesting cyclic SITSH. Although resistance to thyroid hormone (RTH) was not completely excluded, the pituitary tumor was removed by transsphenoidal surgery (TSS). A pathological diagnosis confirmed TSHoma. We herein report a case of TSHoma in which serum TSH, FT3, and FT4 levels fluctuated periodically. To the best of our knowledge, this is the first case report of "cyclic TSHoma", which needs to be considered when making a differential diagnosis of SITSH.

Comprehensive evaluation of thyrotropinomas: single-center 20-year experience.

PURPOSE: To present a single-center 20-year experience with operated thyrotropinomas, including prevalence, clinical, biochemical and histological characteristics, and postoperative outcomes. METHODS: Retrospective series of histopathologically-proven thyrotropinomas (1993-2013), divided in two groups: A (active, central hyperthyroidism) and B (silent, no hyperthyroidism). RESULTS: Of 1628 operated pituitary adenomas, 20 were ß-TSH-positive (1.2%). In increments of 5 years, proportion of thyrotropinomas was 1, 1, 0.04 and 1.77% respectively. Median follow-up was 10.4 months (1.2-150). Group A: 6 patients (5 men), age 41 ± 12 years presented with hyperthyroidism (3), pituitary incidentaloma (2) and acromegaly (1). Tumor diameter was 2.1 ± 1.2 cm, FT4 2.68 ± 2.73 ng/dL; TSH 6.50 ± 3.68 µIU/mL. Glycoprotein alpha subunit (GSU) was uniformly elevated. Two patients had biochemical evidence of acromegaly. Tumors were plurihormonal (5 GH-positive); none atypical. Postoperative euthyroidism was achieved in 4 of 6 patients (66%). Group B: 14 patients (7 men), age 47 ± 14 years presented with acromegaly (6), mass effect (4), incidentaloma (3) and galactorrhea (1). Tumor diameter was 2.0 ± 1.0 cm. Free T4 (1.00 ± 0.24 ng/dL) and TSH (2.02 ± 1.65 mIU/L) were lower than in group A (p < 0.01). GSU was elevated in all tested cases. Nine patients had biochemical evidence of acromegaly. Tumors were plurihormonal (12 GH-positive); none atypical. Gross total resection was achieved in 12 of 14 (86%), and 1 (7%) recurred. CONCLUSION: In our series, more thyrotropinomas were operated in recent years. These tumors were often plurihormonal with heterogenous clinical presentation and frequent GH co-secretion. Surgical outcomes were good but long-term follow up is necessary.

[Thyrotropin-producing adenomas and thyrotropic hyperplasia (clinical case reports and the review of the literature)]. / Tireotropinomy i tireotrofnaia giperplaziia (opisanie klinicheskikh sluchaev i obzor literatury).

An increased blood level of the thyroid stimulating hormone (TSH) is usually associated with primary hypothyroidism (PHT) but can also be observed in such rare cases as TSH-secreting pituitary tumor. The article describes four clinical cases of elevated TSH blood levels: 1) TSH-secreting pituitary adenoma with hyperthyroidism; 2) TSH-secreting adenoma with hypothyroidism; 3) hormonally inactive pituitary adenoma combined with primary hypothyroidism; 4) reversible thyrotropic hyperplasia. These clinical situations substantiate the importance of considering different diagnoses in a patient with a pituitary gland tumor associated with an increased TSH blood level.

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

BACKGROUND: Coexistence of TSH-secreting pituitary adenoma (TSHoma) and Graves' disease (GD) is rare and complicates the management decision. METHODS: We 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 PRESENTATION: A 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. RESULTS: Fourteen 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. CONCLUSION: TSHoma and GD can co-exist, and it is essential to identify this rare association as it can significantly impact treatment strategies.

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.

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.

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.

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.

Management of hyperthyroidism in children.

INTRODUCTION: Treatment of hyperthyroidism in children differs according to its etiology; in particular, the optimal therapy of Graves' disease (GD) remains a matter of debate and there is currently no evidence-based therapeutic strategy that is universally adopted in all the countries. Areas covered: The most recent treatment strategies in the different pediatric conditions which may be associated with hyperthyroidism. We searched PubMed and Cochrane (1990 to 2016) in order to identify articles to include in this review using the following terms: Hyperthyroidism, Childhood, Antithyroid drug therapy, Thyroidectomy, Radioactive iodine. Expert commentary: Although pharmacological therapy represents the first-line approach for GD children, we recommend to individualize, as much as possible, the overall therapeutic approach, with no prejudices towards radical therapies, particularly in the cases with frequent relapses. Clinical and laboratory preferential criteria for an individualized therapeutic approach to GD children are given. Treatment procedures for hyperthyroid children without GD are also discussed.

Pituitary tumor management in pregnancy.

The improved management of pituitary adenomas has led to an increasing number of pregnancies in patients harboring pituitary adenomas. Therefore, adequate management of pregnant women with pituitary adenomas is of growing importance. Because pregnancy produces several physiologic changes to the endocrine system, especially to the pituitary gland, endocrinologists must be knowledgeable and skilled to effectively manage pregnant women with pituitary adenomas and to guarantee the wellbeing of the fetus.