Unexpected Clinical Course During Treatment of a TSH-Secreting Pituitary Adenoma

ObjectiveTo report the rare occurrence of a patient with thyrotropinoma that transitioned into a secretory thyro-somatotroph adenoma during medical treatment with somatostatin analogue.MethodsWe report the case of a patient with a thyrotroph pituitary adenoma who developed de novo evidence of growth hormone cosecretion following one year of successful medical treatment.ResultsA 78-year-old woman was diagnosed with a thyroid stimulating hormone (TSH) secreting pituitary macroadenoma (TSHoma) based on classical clinical and biochemical features. There was no clinical or biochemical evidence of growth hormone (GH) cosecretion. She declined surgical resection and was treated with primary medical therapy, octreotide long acting repeatable (LAR), to which she had an antitumor and antisecretory response; however, following 12 months of successful medical treatment she developed de novo hypersecretion of growth hormone despite involution of the tumor mass. TSH-secreting pituitary adenomas may rarely become plurihormonal during apparently successful medical treatment. This may represent an unusual form of secondary resistance to somatostatin analogue or the rarer phenomenon of tumor transformation into a secretory thyro-somatotroph adenoma.ConclusionThe unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with TSH secreting pituitary adenomas. (Endocr. Pract. 2013;19:e88-e91)     

Tsh-Staining Pituitary Adenomas: Rare,Silent, and Plurihoromonal

Objective: To characterize a single referral center experience with thyroid-stimulating hormone (TSH)-staining adenomas.Methods: A retrospective chart review was conducted on histopathologic-proven TSH-staining adenomas resected between 2000–2015 at a single center. Tumors were classified as functional (hormonally active) or silent (hormonally inactive). Categorical variables were summarized using counts (n) and percentages; continuous variables were summarized using medians and ranges.Results: From the 1,065 pituitary adenomas operated, 32 (3.0%) showed diffuse staining for TSH. Median (range) age of patients was 49 years (20 to 77 years), and 21 (66%) were male. Tumor diameter was 20 mm (2 to 37 mm), with 7 (22%) microadenomas and 25 (78%) macroadenomas. Functional tumors (n = 5, 16%) had median diameter of 10 mm (5 to 21 mm) (2 microadenomas). At diagnosis, median (range) TSH was 4.3 μU/mL (1.2 to 6.9 μU/mL), and free thyroxine (FT4) was 2.4 ng/dL (2.1 to 3.4 ng/dL). Three tumors stained for TSH alone, and 2 tumors costained with growth hormone (GH). No cavernous sinus invasion was seen, and 3 (60%) were considered cured after surgery. Silent tumors (n = 27, 84%) had median diameter of 20 mm (2 to 37 mm), with 5 (19%) microadenomas and 22 (81%) macroadenomas. Median (range) TSH was 1.2 μU/mL (0.48 to 4.6 μU/mL), and FT4 was 1.2 ng/dL (0.6 to 1.6). Only 2 (7.4%) tumors stained for TSH alone; the rest were plurihormonal, with GH being the most common. Cavernous sinus invasion was seen in 7 (27%) of the tumors, and 17 (63%) were considered surgically cured.Conclusion: In our series, 22% of TSH-staining adenomas were microadenomas, and 84% were silent. Most TSH-staining adenomas were plurihormonal, particularly costaining with GH.Abbreviations: αSU = alpha-subunit; ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone; FT3 = free triiodothyronine; FT4 = free thyroxine; GH = growth hormone; LH = luteinizing hormone; MRI = magnetic resonance imaging; PRL = prolactin; T4 = thyroxine; TSH = thyroid-stimulating hormone     

UPDATE ON THE CLINICOPATHOLOGY OF PITUITARY ADENOMAS

Objective: Pituitary adenomas are the third most common central nervous system tumors and arise from the anterior pituitary within the pituitary fossa.Methods: Literature review and discussion.Results: The signs and symptoms of patients with pituitary adenomas vary from ‘mass effects’ caused by a large adenoma to features secondary to excess pituitary hormones produced by the functioning pituitary adenoma. Detailed histopathologic assessment, based on novel classifications and the latest World Health Organization guidelines, helps to categorize pituitary adenomas into different subtypes and identify features that, in some cases, help to predict their behavior. Most of the pituitary tumors occur sporadically without known genetic predisposition, but in a significant minority of cases, somatic mutations can be identified in the GNAS and USP8 genes. A small proportion of the cases have germline genetic defects or embryonic mutations leading to mosaicism. Genes with germ-line mutations predisposing to pituitary adenomas include AIP, GPR101, MEN1, CDKN1B, PRKAR1A, PRKAR2A, DICER1, NF1, and SDHx, whereas more recently, CABLES1 has also been implicated.Conclusion: Understanding the pathogenesis of pituitary adenomas will allow clinicians to correlate the pathologic and genetic features with clinical data, helping decisions on the best management of these tumors.Abbreviations: ACTH = adrenocorticotropic hormone; AIP = aryl hydrocarbon receptor-interacting protein; αSU = alpha-subunit; EGFR = epithelial growth factor receptor; ER = estrogen receptor; FSH = follicle-stimulating hormone; GH = growth hormone; GHRH = growth hormone–releasing hormone; IGF-1 = insulin-like growth factor 1; LH = luteinizing hormone; MEN1 = multiple endocrine neoplasia 1; MRI = magnetic resonance imaging; NFPA = nonfunctioning pituitary adenoma; PRL = prolactin; TSH = thyroid-stimulating hormone; USP8 = ubiquitin-specific peptidase 8; WHO = World Health Organization     

Development of Thyroid Storm After Surgical Resection of A Thyrotropin-Secreting Pituitary Adenoma

ObjectiveTo describe a patient with a thyrotropinsecreting pituitary adenoma in whom postoperative thyroid storm developed.MethodsWe present a case report with details of the initial presentation, laboratory evaluation, surgical and pathologic findings, and subsequent course in a patient with a thyrotropin (thyroid-stimulating hormone or TSH)- secreting adenoma and postoperative thyroid storm.ResultsAn 18-year-old male patient presented with severe headaches and was found to have a large suprasellar tumor and a mildly elevated level of TSH. Thyroid storm developed immediately after surgical resection of the pituitary mass. Results of laboratory evaluation undertaken preoperatively became available after the patient had undergone the surgical procedure and revealed thyroid hormone levels 2 to 3 times the upper limit of normal. Propylthiouracil and β-adrenergic blocking agents controlled the postoperative thyrotoxicosis and were subsequently discontinued as his TSH and thyroid hormone levels normalized.ConclusionThis case demonstrates the rare case of a TSH-secreting adenoma in a young patient, which was complicated by the development of postoperative thyroid storm. In addition, this case emphasizes the importance of preoperative pituitary hormonal evaluation and treatment of hormonal abnormalities in all patients presenting with sellar or suprasellar tumors. (Endocr Pract. 2008;14:732- 737)     

Thyrotropin-Secreting Adenoma in a Patient with Primary Hypothyroidism

ObjectiveTo describe a patient who developed a thyrotropin (TSH)-Secreting adenoma in the setting of primary hypothyroidism.MethodsWe report the clinical, laboratory, and radiologic findings of a patient with a history of primary hypothyroidism who presented with headache, a bitemporal visual field deficit, and elevated TSH despite long-term levothyroxine therapy. We discuss the diagnostic challenges of this case and review the relevant literature.ResultsA54-year-old woman with a history of primary hypothyroidism presented with a 3-year history of headache and a week of worsening vision. Imaging revealed a heterogeneous sellar mass elevating the optic chiasm. Her serum TSH was 46.5 mIU/L and free thyroxine concentration was 0.1 ng/dL. The differential diagnosis included pituitary hyperplasia and a TSH-secreting adenoma in a patient with primary hypothyroidism. The pathologic characteristics of the tumor were consistent with the latter.ConclusionIn a patient with an elevated TSH concentration and a previous diagnosis of hypothyroidism, it is important to consider other entities besides medication noncompliance. TSH-secreting adenomas can also cause elevated levels of TSH. (Endocr Pract. 2011;17: e135-e139)     

Localization of Carboxyl Ester Lipase in Human Pituitary Gland and Pituitary Adenomas

Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells. (J Histochem Cytochem 58:881–889, 2010)     

Evaluation of Cardiovascular Risk With Arterial Stiffness in Patients With Nonfunctioning Pituitary Adenoma

Objective: Nonfunctioning pituitary adenoma (NFPA) accounts for 30% of all pituitary adenomas, and its incidence has been increasing compared to previous years. Increased risk of cardiovascular effects shown in recent studies is noteworthy in patients with NFPA diagnosis, but the number of studies on the subject is limited. In this study, we aimed to assess possible cardiovascular effects and risk via arterial stiffness measurements in patients diagnosed with NFPA.Methods: We performed arterial stiffness measurements for 30 patients diagnosed with NFPA and 30 healthy volunteers and compared the results to explore the relationship between arterial stiffness parameters, hormone levels, and adenoma size.Results: Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), central SBP, central DBP, augmentation index corrected for a heart rate of 75 beats per minute (AIx@75), and pulse wave velocity (PWV) values of the patients with NFPA diagnosis were significantly higher than the control group. PWV was found to have a significant and negative correlation with growth hormone and insulin-like growth factor 1 (IGF-1). A significant and positive correlation was found between adenoma median short-axis length and PWV. IGF-1 was found to have a significant and negative correlation with adenoma median long- and short-axis length. In multivariate linear regression analysis, we found that IGF-1 was an independent predictor of PWV.Conclusion: Both arterial stiffness parameters such as AIx@75 and PWV and peripheral SBP, DBP, and MBP values were found to be high in NFPA patients with no cardiovascular risk factors. Our findings suggest increased cardiovascular effect and risk in patients with NFPA diagnosis, and therefore, we recommend that patients are monitored closely in this respect.Abbreviations: ACTH = adrenocorticotropic hormone; AIx@75 = augmentation index corrected for a heart rate of 75 beats per minute; BMI = body mass index; CVD = cardiovascular disease; DBP = diastolic blood pressure; FSH = follicle-stimulating hormone; GH = growth hormone; HT = hypertension; IGF-1 = insulin-like growth factor 1; LH = luteinizing hormone; MBP = mean blood pressure; MRI = magnetic resonance imaging; NFPA = nonfunctioning pituitary adenoma; PP = pulse pressure; PWA = pulse wave analysis; PWV = pulse wave velocity; SBP = systolic blood pressure; TSH = thyroid-stimulating hormone     

Immunohistochemical examination of pituitary adenomas. Comparison to clinical and endocrinological findings

A comparison was made with the data of 62 cases of pituitary adenoma, evaluated pre- and postoperatively, including as well the results of immunohistochemical hormone examination (also for calcitonin). Prolactin was found in 18 of the 21 adenomas carrying the preoperative diagnosis of prolactinoma, whereas cells containing other hormones (growth hormone, LH, FSH, TSH, ACTH, beta-endorphin), were only occasionally present. The growth hormone was strongly positive in the adenoma tissue in 16 of the 17 cases of acromegaly. 5 of these adenomas were accompanied by a marked hyperprolactinemia and also contained many prolactin cells. 6 of the 19 adenomas diagnosed as being 'inactive' contained hormone-positive cells, but only a very small number of cells. ACTH was found in 3 of the 4 pituitary adenomas of patients with Cushing's disease. 2 of these were also positive for beta-endorphin. The tissue of 1 gonadotrophic adenoma (with elevated FSH in serum) gave positive results with an anti-LH antiserum. Calcitonin was not found in any adenoma. The preoperative serum prolactin levels did not quantitatively correlate with the percentage of prolactin-positive cells.     

垂体腺瘤的临床与病理观察(附22例报告)

目的探讨垂体腺瘤(pituitary adenoma)的临床与病理特点。方法回顾性分析22例垂体腺瘤患者的临床资料。结果内分泌检查结果:22例垂体腺瘤患者中,催乳激素(PRL)值升高者8例;促性腺激素(GnH)水平改变者8例;生长激素(GH)升高者1例;出现Cushing综合症者2例;激素水平正常者3例。免疫组化结果:22例垂体腺瘤患者中8例PRL阳性;7例卵泡刺激素(FSH)/黄体生成素(LH)阳性;1例GH阳性;1例GH/PRL阳性;1例FSH/PRL阳性;无功能者4例。结论应用病理和内分泌功能分类相结合的方法,对垂体腺瘤进行分类,具有十分重要的实际应用价值。     

Proliferating cell nuclear antigen (PCNA) expression in pituitary adenomas: relationship to the endocrine phenotype of adenoma

The expression of proliferating cell nuclear antigen (PCNA) correlates to cell proliferation and for this reason it is commonly considered as one of proliferation markers. Since proliferation rate is an important factor determining the tumor aggressiveness, the evaluation of PCNA index (the percentage of PCNA-immunopositive nuclei in the investigated tumor sample) is suggested as useful in predicting pituitary adenoma outcome. Seventy three unselected, surgically removed pituitary adenomas were immunostained with antibodies against the pituitary hormones or their subunits and against the proliferating cell nuclear antigen (PCNA). The highest PCNA index was found in ACTH-immunopositive tumors without the manifestation of the Cushing's disease ("silent" corticotropinomas). This value was significantly different in comparison to other adenoma subtypes including corticotropinomas manifesting themselves by Cushing's disease. The lowest PCNA index was noticed in monohormonal GH-secreting tumors. The adenomas which express more than one hormone (plurihormonal adenomas) seem to have a higher PCNA indices than monohormonal ones; the difference was significant in the case of mono- and plurihormonal prolactinomas. The recurrent tumors presented a higher mean PCNA index as compared to the primary tumors, although the difference was significant only in the case of prolactinomas. These findings suggest that the proliferative potential of pituitary adenomas is related to the tumor recurrence and hormone expression.     

Suppressibility of Parathyroid Hormone in Primary Hyperparathyroidism

ObjectiveTo describe an unusual case of pathologically confirmed primary hyperparathyroidism in a patient presenting with severe hypercalcemia and an undetectable parathyroid hormone (PTH) level.MethodsWe present a detailed case report and outline the serial laboratory findings. In addition, the possible causes of low serum PTH levels in the setting of primary hyperparathyroidism are discussed.ResultsA 16-year-old female patient presented with severe epigastric pain, found to be attributable to acute pancreatitis. At hospital admission, her serum calcium concentration was high (14.0 mg/dL); the patient also had a normal serum phosphorus level of 3.6 mg/dL and an undetectable PTH level (< 0.2 pmol/L). An evaluation for non-PTH-mediated causes of hypercalcemia revealed a partially suppressed thyroid-stimulating hormone concentration and a below normal 1,25-dihydroxyvitamin D level, consistent with her suppressed PTH. One week after the patient was dismissed from the hospital, repeated laboratory studies showed a serum calcium value of 11.1 mg/dL, a serum phosphorus level of 2.8 mg/dL, and an elevated PTH concentration of 11.0 pmol/L, consistent with primary hyperparathyroidism. A repeated 1,25-dihy-droxyvitamin D measurement was elevated. A parathyroid scan showed a parathyroid adenoma in the left lower neck area, and she subsequently underwent successful surgical resection of a pathologically confirmed parathyroid adenoma.ConclusionThis case demonstrates that the serum PTH level can be suppressed in patients with primary hyperparathyroidism. Moreover, it emphasizes the need for careful evaluation of the clinical context in which the PTH measurement is determined. Consideration should be given to repeating measurement of PTH and serum calcium levels when the initial laboratory evaluation of hypercalcemia is unclear because dynamic changes in calcium metabolism may occur in the presence of secondary contributing factors. (Endocr Pract. 2007;13:785-789)     

Osteogenic Sarcoma of the Sella After Radiation Treatment of a Pituitary Adenoma

ObjectiveTo report an uncommon case of osteogenic sarcoma of the sella turcica after radiation treatment of a pituitary adenoma.MethodsWe present the clinical history, physical findings, laboratory data, imaging studies, and pathologic findings in a patient found to have osteogenic sarcoma of the sella after radiation therapy for a nonfunctioning pituitary adenoma.ResultsSix years after transsphenoidal resection and postoperative fractionated radiation therapy for a nonfunctioning pituitary adenoma that extended to the cavernous sinus, a 45-year-old man presented with a sinus infection, diplopia, and ophthalmoplegia of the right eye. A computed tomographic scan of the head showed a mass in the sella with involvement of the optic chiasm and right cavernous sinus. Transsphenoidal resection and debulking of the tumor revealed an osteogenic sarcoma. The patient was discharged from the hospital with residual diplopia and ophthalmoplegia. He was treated with levothyroxine, testosterone, and hydrocortisone. Six weeks later, the patient was readmitted after he was found unresponsive, and computed tomographic scans disclosed a massive cerebrovascular accident. He died a few days later.ConclusionOsteogenic sarcoma is a rare, late complication of radiation treatment of pituitary adenoma. Although radiotherapy remains an effective adjunctive treatment in patients with pituitary adenomas, particularly those with residual or recurrent tumor, potential complications must be acknowledged. (Endocr Pract. 2004;10: 335-338)     

Endoscopic Ultrasound-Guided Fine-Needle Aspiration With Aspirate Assay to Diagnose Suspected Mediastinal Parathyroid Adenomas

ObjectiveTo describe our experience with mediastinal parathyroid adenomas diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) and measurement of parathyroid hormone.MethodsWe describe the clinical and pathologic findings and diagnostic techniques used in 2 study patients.ResultsPatient 1 was a 54-year-old man with persistently elevated serum calcium and parathyroid hormone concentrations despite removal of a right inferior parathyroid adenoma. An echoendoscope was used to identify the lesion and to perform FNA. The parathyroid hormone concentration measured in the aspirated material was 1800 pg/mL. Pathologic examination of the resected specimen revealed a 29.7-g parathyroid adenoma. Patient 2 was an 86-year-old woman with recurrent hyperparathyroidism. A linear array echoendoscope was used to perform FNA of the lesion in her mediastinum. The parathyroid hormone concentration measured in the aspirated specimen was 6905 pg/mL.ConclusionsPreoperative localization of recurrent or persistent hyperparathyroidism is often difficult. EUSFNA allows evaluation of masses, such as those found in the mediastinum, that are poorly evaluated by other imaging modalities. This technique may be a useful adjunct in diagnosing mediastinal parathyroid adenomas. (Endocr Pract. 2010;16:437-440)     

Substantial Shrinkage of Adenomas Cosecreting Growth Hormone and Prolactin with use of Cabergoline Therapy

ObjectiveTo present 2 cases of patients with acromegaly and severe hyperprolactinemia whose primary therapy with cabergoline resulted in hormonal normalization and a considerable reduction in the size of their somatotroph macroadenomas.MethodsWe summarize the clinical presentation and the pertinent laboratory findings in 2 patients with acromegaly, as well as their clinical response to the therapy with cabergoline. A review of the literature regarding the use of cabergoline in acromegaly is also presented.ResultsA 48-year-old man (case 1) and a 26-year-old woman (case 2) were found to have acromegaly associated with very high levels of serum prolactin (2,700 and 5,250 ng/mL, respectively). These patients received first-line therapy with cabergoline that resulted not only in clinical improvement and normalization of growth hormone, prolactin, and insulin-like growth factor-I levels but also in a substantial reduction in the size of their somatotroph macroadenomas. By 6 months after the patients began to take cabergoline, tumor shrinkage of 94% (in case 1) and of 70% (in case 2) was demonstrated by magnetic resonance imaging.ConclusionOur findings demonstrate that cabergoline should be considered for medical treatment of adenomas cosecreting growth hormone and prolactin, even in the presence of large tumors with appreciable suprasellar extension, because substantial tumor shrinkage is possible with this therapy. (Endocr Pract. 2007;13:396-402)     

Silent Thyroiditis,Isolated Corticotropin Deficiency,and Alopecia Universalis in a Patient With Ulcerative Colitis and Elevated Levels of Plasma Factor VIII: An Unusual Case of Autoimmune Polyglandular Syndrome Type 3

ObjectiveTo describe an unusual case of autoimmune polyglandular syndrome (APS) type 3 and provide a brief review of the literature.MethodsWe present the clinical course and laboratory data of a patient with silent thyroiditis, isolated corticotropin (adrenocorticotropic hormone or ACTH) deficiency, alopecia universalis, and ulcerative colitis with an associated hypercoagulable state. The related literature is also reviewed briefly.ResultsA 43-year-old man who had a history of ulcerative colitis with an associated hypercoagulable state and alopecia universalis was referred to the endocrinology department for evaluation of fatigue and a mildly elevated level of thyrotropin (thyroid-stimulating hormone or TSH). He previously had mildly increased TSH levels, for which low-dose levothyroxine therapy had been prescribed. During use of this therapy, a suppressed TSH level developed, necessitating discontinuation of thyroid hormone therapy; a subsequent increase in TSH value was followed by a spontaneous return to euthyroidism. An ACTH stimulation test revealed adrenal insufficiency. His ACTH level was low, 21-hydroxylase antibodies were not present, and further testing demonstrated otherwise intact pituitary function. Magnetic resonance imaging of his pituitary gland showed normal findings. Treatment with hydrocortisone promptly decreased his fatigue. He was found to have an elevated factor VIII level as the cause of his hypercoagulable state. The patient continues to feel well with use of hydrocortisone therapy and has normal thyroid function.ConclusionThis patient’s components of APS type 3 have not been previously reported; thus, the complex nature of the APS variants is supported. (Endocr Pract. 2009;15:138-142)     

Hyperthyroidism and Hyperprolactinemia: Is There any Association?

Objective: To compare the serum prolactin level in hyperthyroid and normal control females. Hyperthyroidism is a common disease. Although a direct association has been demonstrated between hypothyroidism and increased prolactin levels, this association has not been established for hyperthyroidism.Methods: Cross-sectional study in cases and control groups. Control subjects were chosen from those participating in the Kerman Coronary Artery Disease Risk Factors study. To select the cases, all women referred to the laboratories of Kerman with a thyroid-stimulating hormone (TSH) level ≤0.5 mIU/L who met the inclusion criteria were entered in the study. A total of 231 women aged 15 to 50 years were enrolled. The case group included 71 hyperthyroid women, and the control group included 160 women with normal thyroid function matched by age.Results: The mean (SD) serum level of prolactin was 16.56 (0.97) ng/mL (95% confidence interval [CI], 15.41 ng/mL to 15.71 ng/mL) in the controls and 23.07 (1.49) ng/mL (95% CI, 22.7 ng/mL to 23.4 ng/mL) in the case subjects. Hyperprolactinemia was more common in the hyperthyroid group (16.5 [0.97] ng/mL versus 23.07 [1.49] ng/mL; P<.001). The prolactin level decreased with age. Hyperthyroidism and estradiol increased the prolactin level. After adjusting for age and estradiol, hyperthyroidism increased the serum prolactin level (P<.001).Conclusion: The results of this study revealed that hyperprolactinemia is more frequent in hyperthyroid females. Serum prolactin level can be increased in hyperthyroidism.Abbreviations:PRL = prolactinT4 = thyroxineTRH = thyrotropin-releasing hormoneTSH = thyroid-stimulating hormone     

A plurihormonal TSH-producing pituitary tumor of monoclonal origin in a patient with hypothyroidism

OBJECTIVE: A clinicopathological and clonal study of a pituitary tumor was made in a 26-year-old woman with chronic thyroiditis to differentiate TSH-producing adenoma from TSH hyperplasia. METHODS: Tumor specimens were subjected to histopathological study and clonal analysis (HUMARA). RESULTS: Immunohistochemical examination disclosed TSH-beta, PRL, GH, ACTH, FSH-beta, LH-beta, and alpha-subunit production in the adenoma cells. These heterogeneous phenotypes are characteristic of both thyrotroph hyperplasia and plurihormonal TSH-producing adenoma. However, the HUMARA method demonstrated monoclonality of the tumor cells. CONCLUSION: Monoclonality of the tumor cells proved that the pituitary tumor was plurihormonal TSH-producing adenoma, not TSH hyperplasia.     

Ectopic Acromegaly due to A Pancreatic Neuroendocrine Tumor Producing Growth Hormone-Releasing Hormone

ObjectiveTo present a case of acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion from a pancreatic neuroendocrine tumor in the context of multiple endocrine neoplasia type 1 (MEN 1).MethodsWe describe the clinical, imaging, and pathologic findings of the study patient.ResultsA 46 year old woman presented with clinical and biochemical findings diagnostic of acromegaly. Magnetic resonance imaging showed a 1.2-cm sellar mass. Following resection of the macroadenoma, serum insulinlike growth factor 1 (IGF-1) and growth hormone (GH) levels remained unchanged. Pathologic examination revealed adenomatous changes, including a nonsecretory focus and a prolactin immunopositive area (GH stain negative in both). Octreotide long-acting release was ineffective. Search for an ectopic tumor included normal octreoscan and abdominal computed tomography. GHRH was greater than 1000 pg/mL. Repeated abdominal computed tomography documented a 6.2-cm mass in the tail and body of the pancreas. Distal pancreatectomy revealed a pancreatic neuroendocrine tumor that stained positive for GHRH. Postoperatively, serum GHRH and IGF-1 normalized. Re-evaluation of the initial pituitary pathologic specimen revealed additional somatotroph hyperplasia of the adjacent, normal pituitary gland. Primary hyperparathyroidism was diagnosed, and multigland parathyroid hyperplasia was noted at surgery. Genetic testing was positive for a mutation in the MEN1 gene.ConclusionThis patient’s acromegaly was resistant to somatostatin analogue therapy, reflecting the negative octreoscan imaging. In addition, this case is novel because the patient presented with pituitary adenomatous changes, which were presumably associated with MEN 1 and/or possibly the elevated GHRH levels. (Endocr Pract. 2011; 17:79-84)     

Endocrine Dysfunction and Follow-Up Outcomes in Patients With Pituitary Abscess

Objective: Endocrine dysfunction caused by pituitary abscess (PA) and its outcomes have not been fully studied. This study aims to investigate endocrine dysfunction and outcomes in patients with PA.Methods: Eight patients (3 males and 5 females) with PA were identified for collecting clinical, hormone, and therapeutic data before and after long-term follow-up lasting 12 to 116 months (median, 25 months) since the first hospitalization, which was regarded as the baseline time. All patients' pituitary and respective target gland functions were evaluated. Six patients had acute onset (less than 1 month), and the other 2 patients had chronic onset (more than 6 months). Five patients underwent surgical therapy, and the other 3 patients underwent conservative therapy. The factors associated with endocrine outcome were analyzed as well.Results: At baseline, the release of 91.7% (22 of 24 total) of pituitary tropic hormones was impaired, but 59.1% (13 of 22) had normalized by the last follow-up. Male gender, acute onset mode, and normal baseline prolactin level seemed to be the factors that favored tropic hormone normalization, whereas surgical operation was not. Two patients received provocative test suggesting decreased reserves of both somatotrophin and prolactin or only somatotrophin. Only 1 patient suffered from permanent diabetes insipidus.Conclusion: The production of almost all pituitary tropic hormones was impaired with PA in the present study, but production of nearly 60% percent of the hormones normalized during follow-up of >1 year. A chronic abscess state may be the most important factor associated with permanent hormone deficiency.Abbreviations: ACTH = adrenocorticotropic hormone GnH = gonadotrophin MRI = magnetic resonance imaging PA = pituitary abscess TSH = thyroid-stimulating hormone