Pegvisomant treatment in gigantism caused by a growth hormone-secreting giant pituitary adenoma.

BACKGROUND: Gigantism is rare with the majority of cases caused by a growth hormone (GH)-secreting pituitary adenoma. Treatment options for GH-secreting pituitary adenomas have been widened with the availability of long-acting dopamine agonists, depot preparations of somatostatin analogues, and recently the GH receptor antagonist pegvisomant. CASE REPORT: A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance. CONCLUSION: Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment.     

Unsuspected meningioma in a patient with pituitary gigantism. Case report with autopsy findings

A unique example of a clinically unsuspected large parasellar meningioma is described in a 36-yr-old pituitary giant who had been treated initially with conventional irradiation, subsequently by surgical excision of an acidophil adenoma, and ultimately with medroxyprogesterone acetate (MPA) prior to his demise. The patient died of increased intracranial pressure resulting from a combined mass effect of the meningioma and recurrent tumor. The relationship between radiation and the development of the meningioma is discussed, as well as the fine ultrastructure of a highly functioning acidophil adenoma.     

Gonadotropin-producing pituitary adenoma in a man with long-standing primary hypogonadism

Pituitary adenomas that secrete gonadotropins are generally believed to arise spontaneously rather than as a response to chronic primary gonadal failure. However, two women who were found to have gonadotroph adenomas several years after ovarian ablation have been reported. We describe a middle-aged man who developed bitemporal hemianopia and was found to have a large pituitary tumor 35 yr after castration. He had never received any replacement therapy. The tumor was considered to be a primary gonadotroph adenoma, rather than secondary gonadotroph hyperplasia, on the basis of its secretory capabilities, its reticulin patterns, and its specific immunostaining for human FSH beta, human LH beta, and alpha-subunit. Furthermore, the tumor did not decrease appreciably in size after 12 months of testosterone treatment, although plasma gonadotropin levels decreased. Unless the association of primary gonadal failure with a gonadotroph adenoma was coincidental, it suggests that some human gonadotroph adenomas may be secondary to failure of the gonads.     

Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.     

Gallbladder villous adenoma in a patient with acromegaly： A case report

Villous adenomas are benign epithelial lesions with malignant potential that can occur in any part of the gastrointestinal tract. We present a case of a middle age woman with acromegaly who was investigated for nonspecifi c gastrointestinal complaints. Ultrasonography and subsequent endosonography diagnosed a large (4.5 cm), hyperechoic, sessile polyp with numerous pedicles. An open cholecystectomy was performed and revealed a villous adenoma with several foci of carcinoma in situ. Detailed investigations showed no other tumors of the gastrointestinal tract. After fi ve years of follow-up, the patient reports no complaints, and the results of laboratory testing and imaging studies are within the normal range.     

Liver cell adenoma with malignant transformation： A case report

A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography. She had taken oral contraceptives for only one month at the age of thirty. Physical examination revealed no abnormalities, and laboratory data, including hepatic function tests, were within the normal range, with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-II (3,502 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass measuring 10 X 10 cm in the left posterior segment of the liver. Because hepatocellular carcinoma could not be completely excluded, this mass was resected. The tumor consisted of sheets of uniform cells with clear cytoplasm, perinuclear eosinophilic granules and round nuclei. These histological findings were consistent with liver cell adenoma. Background hepatic tissue appeared normal. After resection of the tumor, serum PIVKA-II fell to within the normal range. An area of hepatocellular carcinoma (HCC) with a mid-trabecular pattern was immunohistochemically found, which was positive for PIVKA-II. Sinusoidal endothelial cells were CD34-positive, containing scattered PIVKA-II positive cells. This tumor was therefore finally diagnosed as liver cell adenoma with focal malignant transformation to HCC.     

Double adenoma of the pituitary: a somatotroph adenoma colliding with a gonadotroph adenoma

Pituitary collision tumors are rare. They may create difficult diagnostic problems and their histogenesis is not clear. We report here an unusual case of a somatotroph adenoma colliding with a gonadotroph adenoma.The 64-year-old man had clinical acromegaly. His blood growth hormone level was elevated and magnetic resonance imaging demonstrated a pituitary tumor. The surgically removed sellar mass was investigated by histology, immunocytochemistry and electron microscopy. Morphologic study revealed a collision tumor; one was a somatotroph adenoma, the other a gonadotroph adenoma. Authors call attention to the difficulties in clinical, imaging and pathological diagnosis. Detailed morphologic studies are needed to establish the presence of two distinct tumors composed of two different cell types.     

Hyperthyroidism due to a thyroid-stimulating hormone (TSH)-secreting pituitary adenoma associated with functional hyperprolactinaemia. A case report

This paper reports the case of a 31-year-old woman with hyperthyroidism, increased TSH and thyroid hormone levels, evidence of a pituitary adenoma, hyperprolactinaemia, amenorrhoea, and galactorrhoea. Following trans-sphenoidal pituitary adenomectomy, mild hyperthyroidism and increased TSH and alpha subunit levels persisted, whereas hyperprolactinaemia, amenorrhoea, and galactorrhoea disappeared. Serum TSH levels were not affected by administration of TRH, metochlopramide, domperidone, l-dopa or somatostatin. Serum TSH chromatography showed a normal pattern. Following a second trans-sphenoidal pituitary adenomectomy and radiotherapy, hyperthyroidism disappeared, and the TSH and alpha subunit levels returned to normal. Light microscopy showed no specific TSH immunostaining although electron microscopy revealed numerous secretory granules alined along the plasma membrane. The post-operative follow-up confirmed the presence of a TSH-secreting pituitary adenoma associated to functional hyperprolactinaemia.     

Myocardial infarction with Moyamoya disease and pituitary gigantism in a young female patient.

Myocardial infarction is very rare in young female patients with systemic vascular disorders. Moyamoya disease is a cerebrovascular disease associated with an abnormal vascular network. This report presents a 19-year-old female patient who suffered from chest pain and exertional dyspnea for 2 months prior to admission. She had a history of Moyamoya disease and pituitary gigantism since childhood. Her ejection fraction on echocardiogram was 20% and a perfusion defect with partial reversibility in the anterior wall was demonstrated on stress single photon emission computed tomography (SPECT). Diagnostic coronary angiogram revealed critical stenosis in the middle left anterior descending artery, which was treated by coronary stenting. Her subjective symptoms were relieved and the perfusion defect seen on SPECT decreased after coronary intervention.     

Prolactin-secreting pituitary adenomas. Association with multiple endocrine neoplasia, type I

In the course of follow-up of two patients who presented with prolactin-secreting pituitary adenomas, we encountered an unemphasized sequel: the evolution of multiple extrapituitary neoplasms of endocrine-gland origin. Tumors were either present concurrently or evolved sequentially. The pedigree of one family was affected in an autosomal dominant manner with tumors of the pituitary, parathyroid glands and pancreatic islet cells, documenting with the most extensive kindred to date the association of prolactinoma with multiple endocrine neoplasia I.These cases, in conjunction with ultrastructural histopathology of three other multiple endocrine neoplasia I prolactinomas, and review of the literature, delineate the following considerations: (1) a prolactin-secreting pituitary adenoma may be the first manifestation of multiple endocrine neoplasia I, with concurrent or sequential tumor evolution; (2) the occurrence of endocrine tumors in these families is sporadic or conforms to a heritable pattern of autosomal dominance; (3) the ultrastructural morphology of prolactinomas in multiple endocrine neoplasia I cannot be used a priori to identify patients at risk for multiple endocrine neoplasia I from those with randomly occurring, isolated prolactinomas; (4) thus, we recommend serum calcium determinations and a detailed family history with inventory of endocrine systems in all patients with prolactinoma; (5) in identified families with the multiple endocrine neoplasia I syndrome, serum prolactin concentrations should be determined; and (6) the cost effectiveness of extensive biochemical screening for multiple endocrine neoplasia I in patients with prolactinoma without an incriminating family history will require further clarification.     

Prolactin-secreting pituitary adenomas: prolactin dynamics before and after transsphenoidal surgery.

Twenty women with hyperprolactinaemia secondary to a pituitary adenoma were studied before and after selective transsphenoidal removal of the tumour. Pre-operatively, thyrotrophin-releasing hormone (TRH) (200 micrograms iv) and metoclopramide (MCP) (10 mg po) did not produce a positive PRL response in the tumour patients. By contrast, 14 post-partum lactating women, who were used as controls, exhibited a positive response to MCP administration. Methergoline (4 mg po) was shown to decrease serum PRL levels in 8 normal subjects, in 6 puerperal women, and 9 of 10 tumour patients. Bromoergocriptine (CB-154, 2.5 mg po) decreased serum PRL levels in 10 tumour patients. Following transsphenoidal removal of the adenoma serum PRL levels were reduced in all patients, and returned to normal in 14 patients. Prognostics for completely normalizing PRL secretion after transsphenoidal surgery is bettery when initial serum PRL levels are below 200 ng/ml. After surgery all hyperprolactinaemic patients failed to show a positive PRL response to TRH and MCP. Nine normoprolactinaemic patients had a positive response to both stimuli while 3 patients failed to show a positive response immediately following surgery. Long-term studies, however, showed that a positive PRL response was obtained in all patients tested 8-14 months after treatment. A positive PRL response to methergoline and bromocriptine was observed post-operatively in the patients tested regardless of their basal PRL level. Data from this study indicate that surgically proven PRL-secreting adenomas are invariably associated with negative PRL responses to TRH and MCP. The normalization of the prolactin regulation after surgery points toward the intrapituitary localization of the lesion associated with PRL-secreting adenomas.     

Thyroid-stimulating hormone (thyrotropin)-secretion pituitary adenoma in an 8-year-old boy: case report

In this report, an extremely rare case of pediatric thyrotropin-secreting pituitary macroadenoma (TSHoma) is described. An 8-year-old boy, complaining of unsteady gait, was suspected of endocrinopathy because of emaciation and muscle weakness of the legs. Endocrinological work-up established a diagnosis of hyperthyroidism due to syndrome of inappropriate secretion of TSH. Magnetic resonance imaging showed a pituitary macroadenoma with suprasellar and sphenoidal extension without cavernous sinus invasion. He underwent an endoscopic endonasal transsphenoidal adenomectory due to the diagnosis of TSHoma. The adenoma was soft and it was totally removed. Histopathological staining confirmed diagnosis of TSHoma. Postoperative evaluation revealed a subnormal level of TSH (from 13–21 to 0.03 micro U/ml), normalization of alpha-subunit (from 10.0 to 0.09 ng/ml), and as a result, hypothyroidism. The boy left the hospital with oral levothyroxine that continued until 12 months of discharge. The present 8-year-old case is the youngest case to the best of our knowledge based on a bibliographical search. Reasons for endocrinological remission following adenomectomy are (1) correct diagnosis without delay: lack of cavernous sinus invasion, (2) soft and non-fibrous adenoma tissue, and (3) endoscopic technique with wide vision and illumination: safe even for a 8-year-old child. Early recognition/detection and pituitary-conserving adenomectomy can cure TSHoma and avoid long-term medical therapy and/or irradiation, which contribute to the best interests of patients with TSHoma.     

Tubulovillous adenoma of anal canal： A case report

Tumors arising from the anal canal are usually of epithelial origin and are mostly squamous cell carcinoma or basal cell carcinoma. We present a case of benign anal adenomas arising from the anus, an extremely rare diagnosis. A 78-year-old white man presented with rectal bleeding of several months duration. Examination revealed a 4 cm friable mass attached to the anus by a stalk. At surgery, the mass was grasped with a Babcock forceps and was resected using electrocautery. Microscopic examination revealed a tubulovillus adenoma with no areas of high grade dysplasia or malignant transformation. The squamocolumnar junction was visible at the edges of the lesion confirming the anal origin of the tumor. We believe the tubulovillus adenoma arose from either an anal gland or its duct that opens into the anus. Although seen rarely, it is important to recognize and treat these tumors at an early stage because of their potential to transform into adenocarcinoma.