Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of "inappropriate secretion of TSH".

An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed.     

Somatotroph Hyperplasia: SUCCESSFUL TREATMENT OF ACROMEGALY BY REMOVAL OF A PANCREATIC ISLET TUMOR SECRETING A GROWTH HORMONE-RELEASING FACTOR

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95+/-9.4 ng/ml; mean+/-SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm(3)) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract.The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified.     

Normal and abnormal regulation of β-MSH in man

The regulation of plasma beta-melanocyte-stimulating hormone (beta-MSH) in man has been studied utilizing a radioimmunoassay previously described (1). In normal subjects plasma beta-MSH values ranged from 20 to 110 pg/ml. Metyrapone increased and dexamethasone decreased plasma beta-MSH levels. Surgical stress stimulated beta-MSH secretion. Plasma beta-MSH levels were elevated in patients with untreated Addison's disease and untreated congenital adrenal hyperplasia, and these levels fell to normal during glucocorticoid therapy. In patients with Cushing's syndrome due to pituitary adrenocorticotropic hormone (ACTH) excess, plasma beta-MSH was slightly elevated before treatment. In those patients who developed pituitary tumors and hyperpigmentation after bilateral adrenalectomy, plasma beta-MSH was greatly elevated. In patients with Cushing's syndrome due to adrenal tumor, plasma beta-MSH was subnormal. In patients with the ectopic ACTH syndrome, the levels of plasma beta-MSH were high. Plasma beta-MSH had a diurnal variation in normal subjects, patients with Addison's disease, and patients with congenital adrenal hyperplasia; but the normal diurnal variation was lost in patients with Cushing's disease. In patients with high plasma beta-MSH, simultaneous determinations of plasma ACTH showed close correlation between the degree of elevation of ACTH and that of beta-MSH. In extracts of tumors from patients with the ectopic ACTH-MSH syndrome the quantities of the two hormones were roughly equivalent. In patients with hyperpigmentation due to a variety of disorders other than pituitary-adrenal abnormalities, plasma beta-MSH was normal. It is concluded that the secretion of beta-MSH is regulated by the same factors that regulate ACTH.     

EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas

Cushing disease is a condition in which the pituitary gland releases excessive adrenocorticotropic hormone (ACTH) as a result of an adenoma arising from the ACTH-secreting cells in the anterior pituitary. ACTH-secreting pituitary adenomas lead to hypercortisolemia and cause significant morbidity and mortality. Pituitary-directed medications are mostly ineffective, and new treatment options are needed. As these tumors express EGFR, we tested whether EGFR might provide a therapeutic target for Cushing disease. Here, we show that in surgically resected human and canine corticotroph cultured tumors, blocking EGFR suppressed expression of proopiomelanocortin (POMC), the ACTH precursor. In mouse corticotroph EGFR transfectants, ACTH secretion was enhanced, and EGF increased Pomc promoter activity, an effect that was dependent on MAPK. Blocking EGFR activity with gefitinib, an EGFR tyrosine kinase inhibitor, attenuated Pomc expression, inhibited corticotroph tumor cell proliferation, and induced apoptosis. As predominantly nuclear EGFR expression was observed in canine and human corticotroph tumors, we preferentially targeted EGFR to mouse corticotroph cell nuclei, which resulted in higher Pomc expression and ACTH secretion, both of which were inhibited by gefitinib. In athymic nude mice, EGFR overexpression enhanced the growth of explanted ACTH-secreting tumors and further elevated serum corticosterone levels. Gefitinib treatment decreased both tumor size and corticosterone levels; it also reversed signs of hypercortisolemia, including elevated glucose levels and excess omental fat. These results indicate that inhibiting EGFR signaling may be a novel strategy for treating Cushing disease.     

Pituitary tumor apoplexy: a review

Pituitary tumor apoplexy is an uncommon syndrome resulting often spontaneously from hemorrhage or infarction of a pre-existing pituitary adenoma. As the primary event involves the adenoma, the syndrome should be referred to as pituitary tumor apoplexy and not as pituitary apoplexy. The sudden increase in sellar contents compresses surrounding structures and portal vessels, resulting in sudden, severe headache, visual disturbances, and impairment in pituitary function. Initial management of patients with pituitary tumor apoplexy includes supportive therapy (intravenous fluids and corticosteroids), following which many patients exhibit clinical improvement. Because those patients can be effectively managed with supportive measures, many who remain clinically and neurologically unstable might benefit from urgent surgical decompression by an experienced neurosurgeon. All patients presenting with this syndrome require long-term follow-up to treat any residual tumor and/or pituitary dysfunction. Close interaction between members of the management team is necessary for optimal patients' outcome.     

Excess corticotropin releasing hormone-binding protein in the hypothalamic-pituitary-adrenal axis in transgenic mice.

Corticotropin-releasing hormone (CRH) is the primary hypothalamic releasing factor that mediates the mammalian stress response. The CRH-binding protein (CRH-BP) is secreted from corticotropes, the pituitary CRH target cells, suggesting that the CRH-BP may modulate hypothalamic-pituitary-adrenal (HPA) axis activity by preventing CRH receptor stimulation. Transgenic mice were generated that constitutively express elevated levels of CRH-BP in the anterior pituitary gland. RNA and protein analyses confirmed the elevation of pituitary CRH-BP. Basal plasma concentrations of corticosterone and adrenocorticotropin hormone (ACTH) are unchanged, and a normal pattern of increased corticosterone and ACTH was observed after restraint stress. However, CRH and vasopressin (AVP) mRNA levels in the transgenic mice are increased by 82 and 35%, respectively, to compensate for the excess CRH-BP, consistent with the idea that CRH-BP levels are important for homeostasis. The transgenic mice exhibit increased activity in standard behavioral tests, and an altered circadian pattern of food intake which may be due to transgene expression in the brain. Alterations in CRH and AVP in response to elevated pituitary CRH-BP clearly demonstrate that regulation of CRH-BP is important in the function of the HPA axis.     

Diagnosis and pathophysiology of Cushing's syndrome

Cushing's syndrome is the consequence of a sustained overproduction of cortisol (hydrocortisone) by the adrenal cortex. This may be due to excessive secretion of cortisol by functioning adrenocortical tumors or to "nontumorous" adrenocortical hyperfunction. The latter may be a result of stimulation of the adrenal cortex by increased release of corticotropin (ACTH) from a small pituitary tumor or from nonpituitary nonadrenal tumor. Carcinoids or carcinomas of the lung or pancreas, and even pheochromocytomas have caused the syndrome of ectopic ACTH production. The problems involved in the diagnosis of Cushing's syndrome are establishing its presence and determining the underlying cause. Treatment is then dependent upon the underlying pathogenetic lesion.     

Ectopic ACTH Production in Carcinoma of the Lung

Immunoreactive ACTH was found in almost all tissue extracts of lung carcinoma from patients without clinical evidence of Cushing's syndrome; i.e. 14 of 15 primary tumors, nine of nine metastatic lymph nodes, and four of four metastatic liver nodules contained immunoreactive ACTH. The incidence of ACTH in extracts of other tumor types was much lower. Comparable normal tissues contained no detectable ACTH. Immunoreactive growth hormone, parathyroid hormone, or gastrin was not found in the same carcinoma tissue. The predominant form of ACTH in the tumor extracts was big ACTH. In pituitary extracts little ACTH predominated.53% of 83 patients with lung carcinoma had afternoon plasma ACTH levels greater than 150 pg/ml; more than 90% of plasmas containing less than 150 pg/ml were obtained from patients who had received radiation therapy or chemotherapy. 31% of 45 patients with chronic obstructive pulmonary disease (COPD), 28% of 25 patients with other severe lung disease, and 6% of 33 controls had elevated values. Big ACTH predominated in the plasma of patients with lung carcinoma or COPD having elevated ACTH levels. Tissue from the lung of a smoking dog with atypical histologic changes contained immunoreactive ACTH, almost exclusively in the big form, while tissue from another smoking dog that was histologically normal contained no ACTH. Thus ACTH may be present even in precancerous lung lesions. These studies suggest that serial plasma ACTH levels may be of value in screening for, and/or management of, patients with carcinoma of the lung.     

Thyroid hormone resistance

General resistance to the action of thyroid hormones is characterized by increased levels of thyroid hormones and normal thyroid hormone binding proteins but clinical euthyroidism. There is a wide clinical spectrum ranging from patients with congenital goitre and signs of subclinical hypothyroidism to subjects with no physical abnormality. In the most affected patients special physical features have been described. Serum thyrotrophin (TSH) and the response to thyrotrophin releasing hormone (TRH) is mostly normal but may fluctuate being at times elevated and even markedly increased values may be encountered. Studies on lymphocytes and fibroblasts indicate that a decreased affinity of thyroid hormones for nuclear receptors, a decreased binding capacity of the receptors or some post-receptor mechanism may be responsible for these changes. Hitherto, six families, comprising 24 patients and seven single cases, have been described. The pedigrees are compatible with dominant inheritance. Selective refractoriness of the pituitary thyrotrophs to thyroid hormones has been described in five patients with hyperthyroidism. Excessive secretion of TSH is the cause of hyperthyroidism. In four of the cases reported TRH caused an exaggerated TSH response and TSH was partially suppressible by additional exogenous thyroid hormone. The response of TSH and the behaviour of the alpha- and beta-subunits of TSH distinguish this syndrome from TSH-induced hyperthyroidism due to pituitary tumours. The underlying mechanisms are unknown.     

The proMMP-2 activation rate in patients with chronic viral liver disease

BACKGROUND: Crush syndrome has been described as extensive muscle damage, leading to acute renal failure. The aim of this study was to evaluate the possible role of nitric oxide, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in crush syndrome. PATIENTS AND METHODS: A total of 17 patients suffering from crush syndrome, 7 patients without crush syndrome and 10 healthy controls were enrolled in the study. Plasma nitrate, TNF-alpha, IL-1 beta levels and biochemical parameters were measured. RESULTS: All patients with crush syndrome demonstrated acute renal failure. Plasma nitrate levels were elevated significantly in the crush syndrome patients compared with patients without crush syndrome (33.5 +/- 20.1 vs. 15.3 +/- 5 micromol/l, p=0.014). There was no significant difference in TNF-alpha and IL-1 beta levels between control and patient groups. CONCLUSION: Increased plasma nitrate levels in the crush syndrome may be related either to the elevated production of NO or the diminished excretion of nitrate or both.     

Elevated levels of immunoglobulin E may indicate steroid resistance or relapse in adult primary nephrotic syndrome, especially in minimal change nephrotic syndrome

Immunoglobulin E (IgE) antibodies may play a role in the development of kidney diseases that are related to hypersensitivity reactions. Patients with idiopathic nephrotic syndrome often exhibit increased serum IgE levels and this may be related to sensitivity to steroid treatment. In the present study, the serum IgE levels in 120 patients with different types of primary nephrotic syndrome (PNS) were analysed and found to be significantly elevated in cases of minimal change nephrotic syndrome (MCNS) compared with membranous nephropathy or membrano-proliferative glomerulonephritis. No difference in serum IgE level was observed between cases of steroid-sensitive nephrotic syndrome (SSNS) or steroid-resistant nephrotic syndrome, although the serum IgE level was significantly elevated in SSNS patients in relapse compared with SSNS patients in remission. In MCNS patients, 73.6% exhibited SSNS regardless of their serum IgE level at diagnosis. It is concluded that elevated levels of IgE may be a feature of steroid resistance or relapse, indicating prognostic significance in adult PNS, particularly in MCNS.     

Thyrotropin-secreting pituitary tumor and Hashimoto's disease: a novel association

A 69-year-old man was referred for elevated thyroid hormone levels. He had no symptoms apart from mild hyperhidrosis and heat intolerance with occasional headaches. Past medical history included a right hemithyroidectomy for a multinodular goiter and Hashimoto's disease. At presentation the patient had a firm, slightly enlarged left thyroid lobe. There were no visual abnormalities, and the rest of the physical findings were unremarkable. Laboratory findings included elevated values of free T4, free T3, total T3, thyrotropin-secreting hormone (TSH), antithyroglobulin, and antimicrosomal antibodies. Normal values were found for cortisol, prolactin, testosterone, follicle-stimulating hormone, luteinizing hormone, alpha-subunit, and thyroid-stimulating immunoglobulin. Thyroid 123I scan showed an increased 5-hour uptake of 23% and a 24-hour uptake of 53% with a diffuse uniform enlargement of the left side. TSH level did not increase after a thyrotropin-releasing hormone stimulation test. Serum sex hormone binding globulin was elevated. Magnetic resonance imaging of the pituitary revealed a pituitary macroadenoma with suprasellar extension to the optic chiasm. Histologic examination of the adenoma after transsphenoidal hypophysectomy showed cells that stained positive for TSH. TSH-secreting pituitary adenomas account for 1% of functioning pituitary tumors and are an exceedingly rare cause of hyperthyroidism. To our knowledge, this is the first report of pituitary tumor inducing hyperthyroidism in the setting of Hashimoto's disease. There is a possibility that TSH elevation related to Hashimoto's disease might have contributed to the development of a TSH-secreting pituitary adenoma.     

经蝶垂体瘤切除术后低钠血症的危险因素分析

目的 探讨经蝶垂体瘤切除术后低钠血症危险因素及预防措施.方法 选择2017年5月至2019年5月医院124例经蝶垂体瘤切除术患者为研究对象,将其中出现低钠血症的22例纳为病例组,未出现低钠血症的102例纳为对照组,收集患者年龄、合并症、术后并发症等病历资料,采用多因素Logistic回归分析调查经蝶垂体瘤切除术后低钠血...     

Primary hypothyroidism and pituitary insufficiency.

A 40-year-old man with primary hypothyroidism and sellar enlargement is described. There was deficiency of all pituitary tropic hormones except TSH which was elevated. TRH stimulation revealed responsiveness of pituitary thyrotropic cells, and thyroxine administration suppressed the elevated TSH. These findings are compatible with either a TSH-producing chromophobe adenoma resulting from primary hypothyroidism or, because of the suppressibility of the TSH secretion, thyrotropic hyperplasia secondary to hypothyroidism maintaining TSH secretion in the face of a non-TSH-secreting pituitary tumor.     

Medical treatment for Cushing's syndrome

Systemic cortisol plays an important role in the metabolism of glucose, lipids and proteins, as well as in the regulation of electrolyte balance. It is well known that the development of the microvascular disease of various organs such as the heart and kidney, in patients with diabetes mellitus, hyperlipidemia and hypertension of which disorders are frequently associated with Cushing's syndrome. Thus, we should treat Cushing's syndrome as soon as possible, since many complications, including cardiovascular diseases and infections, will soon occur when the definite diagnosis is delayed. Adrenalectomy is essential for treatment for Cushing's syndrome even in the patients with pituitary or ectopic ACTH-producing tumor. Some case can not be treated with surgical procedures because of worsened conditions with several complications of infection and diabetes. Then we choose medical treatment. Medical adrenalectomy is achieved by using with mitotane which is usually used for adrenocortical cancer. We commonly treat the patients with Cushing's syndrome due to adrenal tumor and pituitary or ectopic ACTH producing tumor by using metyrapone which mainly inhibits 11-hydroxylase. Metyrapone is also recommended to treat the patients who are not well differentiated Cushing's disease from ectopic ACTH syndrome. We rarely use trilostane which is an inhibitor against 3beta-hydroxysteroid dehydrogenase (3beta-HSD). Replacement therapy with hydrocortisone should be considered if adrenal failure will occur during treatment with those drugs.     

Strongyloides hyperinfection syndrome complicating (ectopic) Cushing syndrome

Strongyloidiasis can present with a wide variety of symptoms and can lead to a potentially fatal hyperinfection. Although any factors that suppress the host defense mechanisms can potentially trigger hyperinfection, prolonged steroid use has been quite well described. A patient with disseminated small cell lung cancer suffered a Strongyloides stercoralis hyperinfection syndrome complicating ectopic adrenocorticotropic hormone (Cushing syndrome). Evaluation revealed lymphopenia, elevated levels of adrenocorticotropic hormone in the setting of elevated cortisol levels, a normal pituitary, and metastatic malignancy. S. stercoralis larval forms were seen in the stool and sputum. At autopsy, S. stercoralis larval forms were seen in the lung along with evidence of metastatic small cell lung carcinoma.     

Adrenal and pituitary emergencies

Although loss of normal pituitary function may be silent and asymptomatic, sudden loss of gland function (pituitary apoplexy) typically results in characteristic presentations. Sheehan's syndrome is the development of hypopituitarism after postpartum hemorrhage or shock. Patients with Sheehan's syndrome may have typical or atypical presentations based on the extent of pituitary gland destruction. Patients with typical symptoms fail to lactate after giving birth; subsequently these patients also develop symptoms and signs of hypopituitarism. Measuring the serum prolactin level after giving thyrotropin-releasing hormone is a reasonable first step in the diagnosis of this condition in patients who fail to lactate after giving birth. The diagnosis of hypopituitarism is delayed for up to 7 years in patients with atypical symptoms. Acute symptomatic failure of the pituitary gland (pituitary apoplexy) commonly occurs in patients who have asymptomatic pituitary tumors. Many patients with pituitary tumors do not have signs of abnormal endocrine gland secretion and have a normal appearance. Most patients have the following signs or symptoms: headache; acute disturbances in visual acuity or visual fields; ophthalmoplegia, and changes in the level of consciousness. The syndrome of pituitary apoplexy usually evolves over hours to days. Subarachnoid hemorrhage and acute bacterial meningitis are the two most important mimics of pituitary apoplexy. Intravenous steroids and prompt neurosurgical consultation are mandatory in cases of pituitary apoplexy since both steroids and surgery can improve vision. Testings for acute or chronic hypopituitarism is challenging in the Emergency Department setting; however, carefully chosen tests will aid in the subsequent early correct diagnosis after initial Emergency Department management.     

Plasma plasminogen activator inhibitor 1, insulin resistance and android obesity

Plasma plasminogen activator inhibitor 1 (PAI-1) levels are elevated in insulin-resistant subjects and are associated with increased cardiovascular risk of atherothrombosis. Strong association between PAI-1 and the metabolic components of the insulin resistance syndrome is found in clinical studies, suggesting that insulin resistance may regulate circulating PAI-1. However, the mechanisms underlying increased PAI-1 levels in such conditions are still poorly understood. Several studies have been carried out specifically in patients with central or android obesity, a major characteristic of the insulin resistance syndrome, and have suggested that visceral adipose tissue may be the major component of the relationship between android obesity and PAI-1. Accordingly, adipose tissue PAI-1 production was found to be elevated in obese human subjects, particularly in visceral adipose tissue. The genetic background for having high PAI-1 levels in several populations have been looked for and its role appeared to be weaker than that of the metabolic condition. High plasma PAI-1 levels are then clearly related to android obesity and insulin resistance, but the mechanisms whereby PAI-1 increases in plasma in these diseases remain to be determined.     

定位诊断困难的支气管类癌致库欣综合征一例及文献复习

  目的  探讨库欣综合征病因为支气管类癌所致异位促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)综合征的定位诊断方法。  方法  报道1例定位诊断困难的49岁女性库欣综合征患者, 收集其临床资料, 对其定位诊断过程和方法进行回顾性分析。  结果  患者曾经被误诊为库欣病并接受经蝶窦垂体手术。库欣综合征的症状在垂体手术后仍持续存在。经过6个月的随访和数周的酮康唑治疗, 胸部CT显示右肺内一个直径约5 mm小结节在9个月内无明显变化。生长抑素受体显像和氟脱氧葡萄糖-正电子发射断层显像(fluorodeoxyglucose-positron emission tomography, FDG-PET)不能确定肺内结节为分泌ACTH的肿瘤。岩下窦静脉取血结果表明病因为异位ACTH综合征。胸腔镜下右肺中叶切除术后, 血ACTH、皮质醇和24 h尿游离皮质醇均降至正常。组织学证实该结节为典型支气管类癌, 免疫组织化学染色示ACTH阳性。  结论  岩下窦静脉取血对于异位分泌ACTH肿瘤的定位诊断非常重要, 对于疑诊异位ACTH综合征的患者应进行岩下窦静脉取血联合不同的影像学诊断技术来定位病灶, 必要时可行探查手术。     

Functional role of estrogen in pituitary tumor pathogenesis

Pituitary hyperplasia and lactotroph replication are induced by estrogen. The product of the pituitary tumor transforming gene (PTTG) exhibits in vitro and in vivo transforming activity and induces basic bFGF secretion, thereby modulating pituitary angiogenesis and tumor formation. We demonstrated previously that pituitary pttg is induced by estrogen and bFGF, the latter being expressed in a concordant fashion with pttg in experimental and human pituitary adenomas. We now elucidate the role of estrogen in paracrine regulation of pituitary tumorigenesis by PTTG. Coincident with the circulating rat estradiol surge and maximal pituitary proliferation, pituitary pttg mRNA, bFGF, and VEGF expression increased approximately threefold during proestrus and estrus. Osmotic mini-pump coinfusion of estrogen and antiestrogen abrogated estrogen-induced pituitary pttg expression in vivo, suppressed serum PRL concentrations by 88%, and attenuated prolactin-secreting pituitary tumor growth by 41% in rats. Antiestrogen treatment of primary human pituitary tumor cultures reduced PTTG expression approximately 65%. Pituitary pttg, bFGF, and VEGF are cyclically expressed during the rat estrus cycle, concordantly with estrogen levels. Because anti-estrogens reduced PTTG expression in human pituitary tumors in vitro and suppressed experimental tumor growth in vivo, concomitantly with reduced PRL secretion, these results indicate a role for selective antiestrogens in treating pituitary tumors.