Thyroid-stimulating Hormone-secreting Adenomas Research Articles

Endoscopic Endonasal Resection of a Thyroid-Stimulating Hormone-Secreting Pituitary Adenoma With Invasion of the Medial Wall of the Cavernous Sinus.

Thyroid-stimulating hormone-secreting adenomas (TSH-oma) are exceptionally rare.1 The primary treatment is surgical resection with radiation and pharmacotherapy postoperatively if subtotal resection, especially with cavernous sinus invasion.2 We present the case of a 29-year-old man with TSH-oma with cavernous sinus medial wall invasion. This is the first documented case with selective resection of the cavernous sinus medial wall to achieve a complete resection and biochemical remission in TSH-oma through endoscopic endonasal approach. The patient had elevated TSH and thyroid hormones with symptoms of weight loss, palpitations, excess sweating, and decreased endurance. MRI revealed a 1.3 × 2.1 × 1.2 cm contrast-enhancing sellar mass with rightward pituitary gland displacement without evidence of cavernous sinus invasion (Knosp 2). The patient consented to procedure/publication. No institutional review board approval needed per institution. We performed standard resection of the firm sellar tumor portion and noted that there was tumor invasion into the left cavernous sinus medial wall dura. The bony opening was expanded to expose the anterior wall of the cavernous sinus, which was opened to identify the cavernous internal carotid artery and the medial wall attachments. The thickened medial wall was completely resected. We achieved a complete tumor resection, and the patient's TSH and thyroid hormone dropped to a desired threshold.3 Tumor stained for GATA3 and PIT1, characterizing the TSH-oma.4,5 Understanding cavernous sinus vascular and ligamentous anatomy allows for safe separation of invaded medial wall dura from the cavernous internal carotid artery,6 allowing for a more complete tumor resection, improving surgical cure rates, and sparing the patient from future radiation and pharmacotherapy.

Growth Hormone (GH) and Thyroid Stimulating Hormone (TSH) Co-Secreting Pituitary Macroadenoma

Background: TSH secreting pituitary adenomas are rare and accounts for 0.5-3% of all pituitary adenomas. Only 20-25% of those adenomas co-secrete other hormones like growth hormone or prolactin. Mixed GH and TSH secreting adenomas present with symptoms from tumor growth and features of both acromegaly and hyperthyroidism. Clinical Case: A 57 years old woman with a past medical history of chronic joint pains and bilateral knee swelling presented to her PCP with complaints of chronic fatigue. Evaluation revealed a normal TSH level and MNG and patient did not have any further work-up. She reported undergoing periodic knee arthrocentesis which gave her only temporary pain relief. Two years later, patient presented with complaints of unintentional weight loss, tremors and palpitations. She also reported enlargement in the size of hands, feet and forehead and no improvement in the knee swelling after multiple arthrocentesis. Lab evaluation revealed high free T4 2.31ng/dl (0.58-1.64), high free T3 6.44pg/ml (2.50-4.30), non-suppressed TSH 1.32mU/L (0.34-5.00), elevated IGF-1 415ng/ml (47-236), GH 7.76ng/ml (0.01-3.61) and prolactin 6.69ng/mL (2.74-26.72). Neck USG showed multiple nodules and 24hr radioactive iodine uptake scan showed increased uptake at 43%. 75gm OGTT showed non-suppression of GH level. MRI of brain showed 1.8 cm pituitary macroadenoma. Patient underwent transsphenoidal pituitary resection in January 2018 and the final pathology showed positive tumor staining for GH and TSH. Following surgery, patient reported improvement in symptoms. Lab work-up from October 2018 showed normal IGF 189 ng/ml (47-236), normal GH 0.35(0.01-3.61), Free T4 0.80(0.58-1.64), Free T3 2.41(2.50-4.30), TSH 0.06(0.34-5.00) and MRI from August 2020 showed no evidence of residual pituitary tumor. Conclusion: This is a rare case of a GH and TSH co-secreting pituitary macroadenoma. This case highlights the importance of considering acromegaly early in the differential diagnosis of patients presenting with chronic musculoskeletal symptoms and to pursue work up for central hyperthyroidism in a hyperthyroid patient presenting with a non-suppressed TSH level.

Endoscopic endonasal approach for pituitary adenomas: Results from a multidisciplinary management

BackgroundEndoscopic endonasal approach (EEA) has gained increasing acceptance in the world; however, pituitary adenomas require multidisciplinary management for good outcomes. The aim of this study is to report the results of this management of a consecutive series of patients who underwent a purely endoscopic endonasal approach for pituitary adenomas resection in our hospital and compare them to other series. MethodsA retrospective review of clinical and radiographic records of 80 consecutive patients with pituitary adenomas who were operated on using an EEA between 2011 and 2019 was performed. The patientś clinical, ophthalmologic, endocrinologic and radiographic outcomes were evaluated. Results57% were women and 43% men. The age ranged from 10 to 79 years. 72 tumours (90%) were macroadenomas; in 19 patients (23.75%) the cavernous sinus was invaded. There were 58 non-functioning adenomas and 17 growth hormone secreting, 4 prolactin-secreting, and 1 thyroid-stimulating hormone-secreting adenomas. Gross total resection was achieved in 76.2% of tumours without cavernous sinus invasion. Of the 53 patients presenting with visual loss, 47 (88.6%) improved or normalized. The remission rates with EEA alone were 58% in the GH-secreting adenomas and 75% in the prolactinomas group. Complications included CSF leak in 12.5%, new hormonal deficit in 18.75%, epistaxis in 6.25%, sella hematoma in 3.75% and neuroinfection in 1 patient (1.25%). We did not have mortality. The follow-up was from 6 to 87 months. ConclusionsA multidisciplinary management is required for the adequate treatment of pituitary adenomas. With good surgical training, the EEA is safe and effective around the world. Our results are similar compared with those reported in previous series of microscopic or endoscopic approaches.

Pituitary Adenomas: What Are the Key Features? What Are the Current Treatments? Where Is the Future Taking Us?

Pituitary tumors are a heterogeneous group of lesions (usually benign) and proper understanding of the anatomy, physiology, and pathology of the hypothalamic/pituitary region is essential to make an accurate diagnosis and define the essential treatment options (i.e., surgery, medical therapies, and radiotherapy, alone or in combination). Surgery is the primary treatment for acromegaly, Cushing disease, thyroid-stimulating hormone-secreting adenomas, resistant prolactinomas, and nonfunctioning pituitary adenomas causing mass effect. Medical and radiation therapy are reserved in cases in which surgery is not possible or does not provide a complete cure. In the last decades, tremendous innovations (i.e., targeted drugs and refined surgical tools and techniques) have expanded the treatment strategies for pituitary adenomas. We herein report the current indications for and depiction of the surgical techniques in pituitary surgery, review current medical treatments, and provide a glimpse of future possibilities.

Evaluation and Management of Children with Thyrotoxicosis.

Uncontrolled thyrotoxicosis, especially in early infancy, may cause irreversible damage to the central nervous system as well as profound effects on the function of many organs. Thyrotoxicosis has multiple etiologies and treatment depends on the underlying etiology. An accurate diagnosis is essential so that appropriate treatment can be initiated without undue delay. To review in depth the evaluation, diagnosis, and treatment of children with thyrotoxicosis. A PubMed search was completed in Clinical Queries using the key terms "thyrotoxicosis" and "hyperthyroidism". The search strategy included meta-analysis, randomized controlled trials, clinical trials, observational studies, and reviews. Patents were searched using the key terms "thyrotoxicosis" and "hyperthyroidism" from www.freepatentsonline.com and www.google.com/patents. Graves' disease accounts for approximately 96% of pediatric cases of thyrotoxicosis. Other causes include Hashitoxicosis, toxic adenoma, toxic multinodular goiter, subacute granulomatous thyroiditis, acute suppurative thyroiditis, pituitary thyroid-stimulating hormone-secreting adenoma, pituitary thyroid hormone resistance, iodine-induced thyrotoxicosis, and drug-induced thyrotoxicosis. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. The underlying cause of thyrotoxicosis should be treated if possible. Treatment options for Graves' disease include antithyroid medications, radioiodine therapy, and surgery. Recent patents related to the management of thyrotoxicosis are discussed. Currently, antithyroid medications are considered to be the initial treatment of choice for Graves' disease in the pediatric age group. Radioactive iodine treatment is generally used for children with poor compliance with antithyroid medications, children not in remission after 1 to 2 years of antithyroid medications, and children with a major adverse effect while receiving an antithyroid medication. Total or near-total thyroidectomy should be considered in children younger than 5 years of age who do not respond to or experience a major adverse effect to antithyroid medications. Surgery should also be considered in those with very large goiter, severe ophthalmopathy, pregnancy, persistent hyperthyroidism in spite of treatment with antithyroid medications and radioactive iodine, and personal preference.

Parasellar Extension Grades and Surgical Extent in Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenomas : A Single Surgeon's Consecutive Series with the Aspects of Reliability and Clinical Validity.

ObjectiveThe inter-rater reliability of the modified Knosp's classification was measured before the analysis. The clinical validity of the parasellar extension grading system was evaluated by investigating the extents of resection and complication rates among the grades in the endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenomas.MethodsFrom November 2008 to August 2015, of the 286 patients who underwent EETS by the senior author, 208 were pituitary adenoma cases (146 non-functioning pituitary adenomas, 10 adrenocorticotropic hormone-secreting adenomas, 31 growth hormone-secreting adenomas, 17 prolactin-secreting adenomas, and 4 thyroid-stimulating hormone-secreting adenomas; 23 microadenomas, 174 macroadenomas, and 11 giant adenomas). Two neurosurgeons and a neuroradiologist independently measured the degree of parasellar extension on the preoperative sellar MRI according to the modified Knosp's classification. Inter-rater reliability was statistically assessed by measuring the intraclass correlation coefficient. The extents of resection were evaluated by comparison of the pre- and post-operative MR images; the neurovascular complications were assessed by reviewing the patients' medical records. The extent of resection was measured in each parasellar extension grade; thereafter, their statistical differences were calculated.ResultsThe intraclass correlation coefficient value of reliability across the three raters amounted to 0.862. The gross total removal (GTR) rates achieved in each grade were 70.0, 69.8, 62.9, 21.4, 37.5, and 4.3% in Grades 0, 1, 2, 3A, 3B, and 4, respectively. A significant difference in the extent of resection was observed only between Grades 2 and 3A. In addition, significantly higher complication rates were observed in the groups above Grade 3A.ConclusionAlthough the modified Knosp's classification system appears to be complex, its inter-rater reliability proves to be excellent. Regarding the clinical validity of the parasellar extension grading system, Grades 3A, 3B, and 4 have a negative predictive value for the GTR rate, with higher complication rates.

Endoscopic endonasal transsphenoidal surgery for pituitary adenomas.

The objective of this study was to report the efficacy, safety, and outcomes of endoscopic endonasal transsphenoidal techniques for pituitary adenomas. A retrospective data analysis of 32 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenoma between February 2011 and December 2013 was performed. The patients' demographic data, clinical presentations, radiologic findings, recurrence rates, and complications were analyzed. There were 14 men and 18 women with age ranging from 23 to 74 years (mean age, 48.6 y). Functioning and nonfunctioning tumors were present in 22 (68.8%) and 10 patients (31.2%), respectively. Among the functioning adenomas, 8 patients (25%) had growth hormone-secreting adenomas, 6 patients (18.8%) had prolactinomas, 5 patients (15.6%) had adrenocorticotropic hormone-secreting adenomas, 2 patients (6.2%) had follicle-stimulating hormone/luteinizing hormone-secreting adenomas, and 1 patient (3.1%) had thyroid-stimulating hormone-secreting adenomas. Of the 32 patients, 20 (62.5%) had pituitary macroadenomas and 12 patients (37.5%) had microadenomas. Total-subtotal tumor resection was achieved in 75% and 45% of the microadenomas and macroadenomas, respectively. Radiologically, 60% of the macroadenomas had suprasellar and carvenous sinus extension. Postoperative cerebrospinal fluid leaks occurred in 3 patients. Two patients developed temporary diabetes insipidus. Endoscopic transsphenoidal surgery is an effective and safe treatment for most patients with pituitary adenoma and could be considered the first-choice therapy in these patients.

Endoscopic endonasal transsphenoidal surgery of 1,166 pituitary adenomas.

AimTo report the results of a series of patients undergoing pure endoscopic endonasal pituitary surgery and to evaluate the efficacy and safety of this procedure.Materials and methodsThe data of 1,166 patients that underwent endoscopic endonasal transsphenoidal adenoma removal between December 2006 and June 2013 were retrospectively reviewed. Pre- and postoperative hormonal status (3 months after surgery) were analyzed and compared with the clinical parameters originally presented by the patients. The incidences of tumor removal, hormonal control, and tumor removal complications were retrospectively analyzed.ResultOut of 577 nonfunctioning adenomas, 180 were growth hormone (GH) secreting, 308 prolactin (PRL) secreting, 26 mixed GH/PRL adenomas, 68 adrenocorticotropin secreting, and 7 thyroid-stimulating hormone-secreting adenomas. The gross total removal of pituitary adenomas was achieved in 98 % of microadenomas, 92 % of macroadenomas, and 76 % of giant adenomas. Hormonal control was achieved in 47 (69 %) cases of ACTH adenomas, 119 (66 %) GH adenomas, 262 (85 %) PRL adenomas, and 6 (86 %) TSH adenomas. Postoperative complications were observed in 168 (14.4 %) patients. The most frequent complications were diabetes insipidus (7 %), epistaxis (1.7 %), hyposmia (1.5 %), anterior lobe insufficiency (1.3 %) ,and CSF leaks (0.6 %).ConclusionThe pure endoscopic approach is a safe, efficacious, and minimally invasive technique for the removal of pituitary adenomas. A higher gross total resection rate is vital for non-functional and functional adenomas. For patients with functional adenomas, while hormonal remission is unlikely to be achieved by surgery, the use of adjuvant therapy is advocated to obtain long-term hormonal control.

ANTERIOR CEREBRAL ARTERY AMPUTATION AND SALVAGE REPAIR OF INTERNAL CAROTID ARTERY TEAR

Abstract OBJECTIVE We describe a novel technique used to repair an unanticipated tear of the internal carotid artery (ICA) requiring anterior cerebral artery (ACA) amputation to allow primary repair of the arteriotomy. CLINICAL PRESENTATION A 59-year-old woman underwent an orbitozygomatic craniotomy to treat a large, suprasellar, thyroid-stimulating hormone-secreting adenoma. During resection, an incidental ICA tear occurred opposite the exit of the middle cerebral artery. TECHNIQUE After an ICA tear on the wall opposite the middle cerebral artery occurred, clips were placed on the ICA, middle cerebral artery, and ACA. Primary closure was not feasible without critically stenosing the ICA. The ipsilateral ACA was clipped and amputated just distal to its origin. The relaxation afforded by amputating the ACA allowed primary suture repair of the arteriotomy. A clip was placed on the proximal ACA stump. The distal ACA stump revealed good backflow and was also clipped. CONCLUSION When an arteriotomy of a large intracranial artery cannot be repaired primarily, creative alternatives must be considered. Amputation of a branch artery with sufficient collateral flow is a method to afford adequate relaxation for primary repair of an arteriotomy. This novel method should be considered in the armamentarium of neurosurgeons to minimize the impact of potentially disastrous vascular complications.

Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center

Pituitary tumors are challenging tumors in the sellar region. Surgical approaches to the pituitary have undergone numerous refinements over the last 100 years. The introduction of the endoscope have revolutionized pituitary surgery. The aim of this study is to report the results of a consecutive series of patients undergoing pituitary surgery using a pure endoscopic endonasal approach and to evaluate the efficacy and safety of this procedure. We reviewed the data of 228 consecutive patients who underwent endonasal transsphenoidal adenoma removal over an 10-year period. Pre- and post-operative hormonal status (at least 3 months after surgery) were analyzed and compared with clinical parameters presented by the patients. Tumor removal rate, endocrinological outcomes, and complications were retrospectively assessed in 228 patients with pituitary adenomas who underwent 251 procedures between December 1998 and December 2007. There were 93 nonfunctioning adenomas, 58 growth hormone-secreting, 41 prolactin-secreting, 28 adrenocorticotropin hormone secreting, 7 FSH-LH secreting and 1 thyroid-stimulating hormone-secreting adenomas. Gross total removal was achieved in 79.3% of the cases after a median follow-up of 61.5 months. The remission results for patients with nonfunctioning adenomas was 83% and for functioning adenomas were 76.3% (70.6% for GH hormone-secreting, 85.3% for prolactin hormone-secreting, 71.4% for ACTH hormone-secreting, 85.7% for FSH-LH hormone-secreting and 100% for TSH hormone-secreting), with no recurrence at the time of the last follow-up. Post-operative complications were present in 35 (13.9%) cases. The most frequent complications were temporary and permanent diabetes insipidus (six and two cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (two cases) and CSF leaks (eight cases). There was no death related to the procedure in this series. The endoscopic endonasal approach for resection of pituitary adenomas, provides acceptable results representing a safe alternative procedure to the microscopic approach. This less invasive method, associated with a small number of complications, provides excellent tumor removal rates and represents an important tool for the achievement of good results in the pituitary surgery, mainly for the complete removal of large adenomas.

PURE ENDOSCOPIC ENDONASAL APPROACH FOR PITUITARY ADENOMAS

The aim of this study was to report the results of a consecutive series of patients undergoing pituitary surgery using a pure endoscopic endonasal approach and to evaluate the efficacy and safety of this procedure. We reviewed 200 consecutive patients with pituitary adenoma who underwent purely endoscopic transsphenoidal resection of their lesions. The patients' clinical outcomes, including remission rates, degrees of tumor removal, and complications, were evaluated and compared with a previous microscopic series. There were 111 nonfunctioning adenomas and 34 growth hormone-secreting, 27 adrenocorticotropin hormone-secreting, 25 prolactin-secreting, and 3 thyroid-stimulating hormone-secreting adenomas. The degree of gross total removal for tumors with suprasellar or parasellar extension and without cavernous sinus involvement was 96% and for intrasellar lesions was 98%. After a median follow-up period of 19 months, the remission results for patients with functioning adenomas were 71% for growth hormone-secreting, 81% for adrenocorticotropin hormone-secreting, and 88% for prolactin-secreting adenomas, with no recurrence at the time of the last follow-up. This compares with similar results reported from series using a standard microsurgical approach (growth hormone-secreting adenomas, 67%; adrenocorticotropin hormone-secreting adenomas, 78%; and prolactin-secreting adenomas, 62%). Endoscopic surgery for recurrent or residual nonfunctioning adenomas that had been previously treated using a microscopic approach revealed in the majority of cases a more limited exposure during the initial surgery, frequently with incomplete tumor removal. Complication rates have been low, and the average length of hospital stay was reduced. A purely endoscopic approach for pituitary adenoma treatment is a safe and effective alternative to the traditional microscopic procedure. Although our results reveal excellent tumor-removal rates, comparable remission rates in functioning tumors, and a very low rate of complications, additional studies with longer follow-up periods are required to confirm whether this approach should be considered the preferred procedure for pituitary surgery.

Atrial fibrillation associated with a thyroid stimulating hormone-secreting adenoma of the pituitary gland leading to a presentation of acute cardiac decompensation: A case report

IntroductionHyperthyroidism is a well established cause of atrial fibrillation (AF). Thyroid Stimulating Hormone-secreting pituitary tumours are rare causes of pituitary hyperthyroidism. Whilst pituitary causes of hyperthyroidism are much less common than primary thyroid pathology, establishing a clear aetiology is critical in minimising complications and providing appropriate treatment. Measuring Thyroid Stimulating Hormone (TSH) alone to screen for hyperthyroidism may be insufficient to appropriately evaluate the thyroid status in such cases.Case presentationA 63-year-old Caucasian man, previously fit and well, presented with a five-day history of shortness of breath associated with wheeze and dry cough. He denied symptoms of hyperthyroidism and his family, social and past history were unremarkable. Initial investigation was in keeping with a diagnosis of atrial fibrillation (AF) with fast ventricular response leading to cardiac decompensation.TSH 6.2 (Normal Range = 0.40 – 4.00 mU/L), Free T3 of 12.5 (4.00 – 6.8 pmol/L) and Free T4 51(10–30 pmol/L). Heterophilic antibodies were ruled out. Testosterone was elevated at 43.10 (Normal range: 10.00 – 31.00 nmol/L) with an elevated FSH, 18.1 (1.0–7.0 U/L) and elevated LH, 12.4 (1.0–8.0 U/L). Growth Hormone, IGF-1 and prolactin were normal. MRI showed a 2.4 cm pituitary macroadenoma. Visual field tests showed a right inferotemporal defect.While awaiting neurosurgical removal of the tumour, the patient was commenced on antithyroid medication (carbimazole) and maintained on this until successful trans-sphenoidal excision of the macroadenoma had been performed. AF persisted post-operatively, but was electrically cardioverted subsequently and he remains in sinus rhythm at twelve months follow-up off all treatment.ConclusionThis case reiterates the need to evaluate thyroid function in all patients presenting with atrial fibrillation. TSH-secreting pituitary adenomas must be considered when evaluating the cause of hyperthyroidism. Early diagnosis and treatment of such adenomas is critical in reducing neurological and endocrine complications.

Wirkungen von Strahlentherapie und inhibierenden Medikamenten auf die Hypophyse und ihre Adenome

Radiation therapies of pituitary adenomas induce an increase in fibroses and nuclear pleomorphism. Most growth hormone (GH) secreting pituitary adenomas react to somatostatin analogues by a distinct decrease of GH secretion. In two thirds, levels of IGF-1 can be normalized. Some cases show a shrinkage of adenomas that correlates with fibrosis of the tumor. With these drugs, thyroid stimulating hormone secreting adenomas can also be treated. Prolactin secreting adenomas are mostly treated primarily with dopamine agonists. Up to 90% of cases show a strong decrease in hormone secretion and a distinct shrinkage of the adenomas based on strong decrease in adenoma cell volume. Long-term medication with high doses of glucocorticoids induces Crooke's cells in the anterior pituitary. These are suppressed ACTH cells and characterized by increased numbers of large lysosomes and dense bundles of cytofilaments.

Treatment of Pituitary Tumors: Somatostatin

Somatostatin is an important physiological regulator of neuroendocrine function across multiple biological systems, including the brain and the gastrointestinal tract. In the pituitary gland, somatostatin regulates the secretion of hormones such as growth hormone and thyroid-stimulating hormone in healthy and pathological states. The short half-life of somatostatin makes it unsuitable for clinical use in chronic diseases, which led to the development of long-acting somatostatin analogs for the treatment of acromegaly and thyroid-stimulating hormone-secreting adenomas, which were administered by intermittent injection twice or three times a day. More recently, depot versions have been developed that permit dosing once every month. This review assesses the efficacy of somatostatin analogs in the treatment of pituitary adenomas, including acromegaly, thyroid-stimulating hormone-secreting tumors, non-functioning adenomas, and Cushing's disease.

Immunohistochemical Analysis of RCAS1 in Human Pituitary Adenomas

It has been reported that RCAS1 (receptor-binding cancer antigen expressed on SiSO cells) acts as a ligand for a receptor present on normal peripheral lymphocytes and induces apoptotic cell death. It is expressed in uterine and ovarian carcinomas, especially in invasive cancers. This immunohistochemical study is aimed to elucidate the expression of RCAS1 in human pituitary adenomas in order to clarify its role in their proliferative regulation and invasiveness. Five normal pituitary glands, 50 human pituitary adenomas, and one malignant glioma were subjected to immunohistochemical studies. In normal pituitary glands, immunostaining of RCAS1 and MIB-1 was not found. In malignant glioma, large numbers of cell nuclei were positive for MIB-1 (MIB-1 index: 28%), and RCAS1 was detected both in the cytoplasm and on the membrane of the tumor cells. Expression of RCAS1 was noted in 48% of pituitary adenomas immunohistochemically (60.0% of growth hormone-secreting adenomas, 60.0% of prolactin-secreting adenomas, 42.9% of adrenocorticotrophin-secreting adenomas, 40.0% of thyroid-stimulating hormone-secreting adenomas, 33.3% of nonfunctioning adenomas, and 44.4% of gonadotropin-subunit-positive adenomas). It showed no correlation with tumor type, size, and invasiveness. The statistically significant relationship between RCAS1 and MIB-1 positivity was identified in our study. These results suggest that expression of RCAS1 as well as MIB-1 positivity predict the growth potential of individual pituitary adenomas.

Functional Differentiation and its Regulation in Pituitary Cells.

It has been an interesting problem to understand why specific hormones are produced from specific cells. It is known that in the human anterior pituitary gland, tumors are classified into those of growth hormone (GH), prolactin (PRL). ACTH, thyroid stimulating hormone (TSH), and gonadotrophin secreting adenomas as well as nonfunctioning adenomas. In human pituitary adenomas, GH secreting adenoma is usually plurihormonal, i. e., the adenoma not only produces GH but also PRL and TSH. TSH secreting adenoma is also plurihormonal, and adenoma produces TSH as well as GH and PRL. Thus, it was supposed that common transcriptional factors participate in the functional differentiation of GH, PRL, and TSH. Pit-1 has been proposed to regulate GH, PRL, and TSH cells and the dwarf mutants in mice were produced by Pit-1 gene mutations. Simmons et al. (1990) observed Pit-1 protein expression in GH, PRL, and TSH cells [10], in the adult rat pituitary gland although Pit-1 mRNA expression was observed in all cell types (Fig. 1). Therefore it was anticipated that, in human pituitary tumors, the functional expression in GH and TSH secreting adenomas may be under the regulation of Pit-1 protein. We describe here the overview of transcriptional factors depicted by immunohistochemistry and in situ hybridization.

Treatment of thyroid-stimulating hormone-secreting adenomas with octreotide

From data collected in the literature, the effects of octreotide therapy in 37 patients with thyroid-stimulating hormone (TSH)-secreting adenomas who received short-term (1 to 2 weeks, n = 23) and long-term treatment (3 to 36 months) are reviewed. In 20 of 21 patients studied, short-term administration of octreotide (50 or 100 μg subcutaneously [SC] produced a 25% to 100% (mean ± SD, 55.3% ± 29%) decrease in TSH levels, with the nadir being obtained between the third and sixth hour following injection. After 1 to 2 weeks therapy with 50 to 100 μg twice or three times a day, 21 of 23 patients studied demonstrated a 66% (±30%) decrease in TSH levels and 14 of 16 showed a 64% (±27%) decrease in α-subunit levels. In approximately two thirds of the patients, the response was better than after short-term administration. The effect of octreotide on clinical and biological thyroid status was significant in all patients studied. After 1 week or 1 month of treatment, thyroid hormone levels were reduced in all patients and were normalized in 78%. Response to therapy was similar whether TSH secretion was pure or mixed (growth hormone [GH]-TSH adenomas). Fourteen patients received long-term treatment (3 to 36 months; mean, 12 ± 10) with daily doses ranging from 200 to 1,500 μg. The response was better than or similar to that with short-term treatment. An escape occurred in TSH levels in two patients and in thyroid hormone levels in three patients, leading to an adjustment of dose or frequency of injection. A partial shrinkage of the adenoma was demonstrated by a computerized tomography (CT) scan and/or magnetic resonance imaging (MRI) in six patients, with a 30% to 50% reduction occurring in three of these patients. In conclusion, octreotide may currently be considered the treatment of choice in TSH-secreting adenomas when surgery and/or radiotherapy have been unsuccessful. Octreotide reduced TSH secretion in almost all the patients, leading to normalization of thyroid hormone levels in three quarters; partial tumor shrinkage was observed in one third of the patients on long-term treatment.