Pituitary Of Patients Research Articles

Severe Obesity Associated With Pituitary Corticotroph Hyperplasia and Neoplasia

ObjectiveTo investigate the incidence of corticotroph hyperplasia (CH) or lymphocyte infiltration in the pituitary of patients with obesity. MethodsThe pituitary and adrenal glands from 161 adult autopsies performed between 2010 and 2019 at our institution were reviewed. The clinical history, body mass index (BMI), and cause of death were recorded. Routine hematoxylin and eosin staining, reticulin staining, and immunohistochemical staining for adrenocorticotropic hormone, CD3, and CD20 were performed. The results were analyzed using the Fisher and chi-square statistics. Decedents were separated into 4 groups based on BMI (kg/m2): (1) lean (BMI, <25.0), (2) overweight (BMI, 25.0-29.9), (3) obesity class I (BMI, 30.0-34.9), and (4) obesity classes II to III (BMI, >34.9). ResultsCH/neoplasia was identified in 44 of 161 pituitary glands. Four (9.1%) of 53 lean patients had pituitary lesions, whereas 27.3% (12) of overweight, 22.7% (10) of obesity class I, and 40.9% (18) of obesity class II patients had hyperplasia (P < .0001). Small corticotroph tumors were identified in 15 patients; only 1 was a lean patient, and the tumor was associated with the Crooke hyaline change of nontumorous corticotrophs. The presence of CH and neoplasia was associated with adrenal cortical hyperplasia and lipid depletion. Microscopic foci of T and B lymphocytes were identified in the pituitaries of patients in each weight category; no independent association between BMI and lymphocyte inflammation was found. ConclusionOur data indicate an association between CH/neoplasia and obesity. It remains unclear whether obesity is the cause or effect of adrenocorticotropic hormone and cortisol excess.

The functional evaluation of pituitary in patients with a surgical resection of sellar tumours.

IntroductionThe aim of this study was to analyse the incidences of hypopituitarism before and after surgical resection of sellar tumours and to find the factors related to the incidences.Material and methodsFrom January 2009 to December 2011, 191 patients in the Department of Neurosurgery in Xiangya Hospital, who underwent the surgical resection of sellar tumours, were included in this retrospective analysis. Pre- and postoperative pituitary function assessments were performed by the detection of hormone levels. Tumour size and location were analysed by magnetic resonance imaging (MRI).ResultsIn total 152 (79.6%) patients had anterior pituitary hypofunction preoperatively, and 176 (92.1%) patients had anterior pituitary hypofunction postoperatively. The pre- and postoperative adrenal cortex hypofunction incidences were 83 (43.5%) and 103 (53.9%), respectively. Ninety-three (48.7%) patients had thyroid hypofunction preoperatively, and 101 (52.9%) patients had anterior pituitary hypofunction postoperatively. The pre- and postoperative hypogonadism incidences were 131 (68.6%) and 160 (83.8%), respectively. The postoperative incidences of anterior pituitary hypofunction and hypogonadism in patients with craniopharyngioma or pituitary tumours were both significantly higher than the preoperative incidences. Surgery resection methods and tumour sizes were found to be related to the incidence of postoperative hypogonadism.ConclusionsTo sum up, we found that the postoperative incidences of hypopituitarism were higher than the preoperative incidences. Tumour type, surgery resection methods, and tumour sizes were important contributing factors to the incidence of postoperative hypogonadism.

Clinical characteristics of central diabetes insipidus: a retrospective analysis of 230 cases

Objective: To evaluate the clinical characteristics and etiologies of central diabetes insipidus (CDI). Methods: The clinical data of 230 patients with CDI in the Department of Endocrinology of Chinese PLA General Hospital from 2008 June to 2014 December were collected and analyzed retrospectively. Results: The three most common causes of CDI were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. Among all the CDI, the idiopathic CDI accounted for 37.48%. There were significant differences in age onset and gender distribution among the different causes of CDI. The patients with intracranial germ cell tumors [age of onset(19.2±10.2) years] were younger than the other types of CDI. Germ cell tumors patients were more common in male, and lymphocytic hypophysitis patients were more common in female. The most frequent abnormality of anterior pituitary in patients with CDI was growth hormone deficiency, followed by hypogonadism, adrenal insufficiency and hypothyroidism. The dysfunction of thyroid axis and adrenal axis in patients with germ cell tumor was more common than those in patients with idiopathic and lymphocytic hypophysitis. Conclusions: The most common causes of central diabetes insipidus were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. There were differences in age of onset, gender distribution and abnormal production of anterior pituitary hormones among all causes of CDI patients.

MRI features of growth hormone deficiency in children with short stature caused by pituitary lesions.

We verified the advantages of using magnetic resonance imaging (MRI) for improving the diagnostic quality of growth hormone deficiency (GHD) in children with short stature caused by pituitary lesions. Clinical data obtained from 577 GHD patients with short stature caused by pituitary lesions were retrospectively analyzed. There were 354 cases (61.3%) with anterior pituitary dysplasia; 45 cases (7.8%) of pituitary stalk interruption syndrome (PSIS); 15 cases (2.6%) of pituitary hyperplasia due to primary hypothyroidism; 38 cases (6.6%) of Rathke cleft cyst; 68 cases (11.8%) of empty sella syndrome; 16 cases (2.8%) of pituitary invasion from Langerhans cell histiocytosis; 2 cases (0.3%) of sellar regional arachnoid cyst and 39 cases (6.8%) of craniopharyngioma. MRI results showed that the height of anterior pituitary in patients was less than normal. Location, size and signals of posterior pituitary and pituitary stalk were normal in anterior pituitary dysplasia. In all cases pituitary hyperplasia was caused by hypothyroidism. MRI results showed that anterior pituitary was enlarged, and we detected upward apophysis and obvious homogeneous enhancement. There were no pituitary stalk interruption and abnormal signal. We also observed that after hormone replacement therapy the size of pituitary gland was reduced. Anterior pituitary atrophy was observed in Rathke cleft cyst, empty sella syndrome, sellar regional arachnoid cyst and craniopharyngioma. The microstructure of hypophysis and sellar region was studied with MRI. We detected pituitary lesions, and the characteristics of various pituitary diseases of GHD in children with short stature. It was concluded that in children with GHD caused by pituitary lesions, MRI was an excellent method for early diagnosis. This method offers clinical practicability and we believe it can be used for differential diagnosis and to monitor the therapeutic effects.

Comparison of Vasopressin and Oxytocin Expressions in the Hypothalamo-Neurohypophysial System of Patients with Chronic Heart Failure

The hypothalamic nonapeptide vasopressin is a known player in the pathogenesis of chronic heart failure. According to the large body of clinical evidence, vasopressin has an impact on salt and water imbalance, hyponatremia, and subsequent renal insufficiency - the most common and destructive co-morbidity of patients afflicted with chronic heart failure. Despite the well-documented elevated levels of vasopressin in the blood of such patients, its expression in the magnocellular hypothalamic nuclei and transport to the posterior pituitary has not yet been investigated. In addition, the literature almost lacks the information on the contribution of another member of nonapeptide family, oxytocin, in the pathogenesis of this disease. Here we present a postmortem analysis of vasopressin and oxytocin-immunoreactive neurons and their terminals in the posterior pituitary of 8 male patients (53.8+/-9.3 years) who had died from CHF and 9 male controls (54.6+/-11.8 years). In line with previous clinical reports, our study on hypothalami of chronic heart failure patients revealed a significant increase in the relative profile density (+29%) of vasopressin-positive neurons in the hypothalamic supraoptic nucleus. Consistently we found a significant increase in the relative optic density of vasopressin-immunoreactivity in the posterior pituitary (+33%) of these patients. In contrast, the similar analysis applied for oxytocin neurons revealed no statistically significant differences to controls. In conclusion, our study provides the morphological evidence for activation of vasopressin (but not oxytocin) expression and vasopressin transport to the posterior pituitary in patients with chronic heart failure.

Hormonal, pituitary magnetic resonance, LHX4 and HESX1 evaluation in patients with hypopituitarism and ectopic posterior pituitary lobe

LHX4 and HESX1 are important in early stages of pituitary development and their mutations can be associated with an ectopic posterior lobe (EPL) in the pituitary of patients with hypopituitarism. The EPL can be located at the median eminence or at the path of the pituitary stalk. The aim of this study was to analyse LHX4 and HESX1 and characterize the hormonal deficiency profiles, establishing relationships with magnetic resonance imaging (MRI) findings in these patients. Sixty-two patients with hypopituitarism associated with EPL were submitted to evaluation of pituitary function, analysis of MRI with EPL location and molecular analysis of LHX4 and HESX1 using polymerase chain reaction (PCR), digestion with restriction enzyme and automatic sequencing. Forty-two patients had a nonvisualized pituitary stalk (NPS), and 20 a visualized pituitary stalk (VPS). Most patients (95%) with NPS had combined pituitary hormone deficiency (CPHD), with ACTH deficiency in 85%. In patients with VPS, CPHD was found in 50% and ACTH deficiency occurred in only 20%. The frequency of the location of EPL was similar in patients with VPS and NPS: 35% at median eminence and 65% at the path of the stalk. No mutations in LHX4 and HESX1 were identified. Three new polymorphisms in LHX4 were found. ACTH deficiency is frequent in patients with hypopituitarism and NPS (85%), the location of EPL at the median eminence was not predictive of the hormonal profile [isolated GH deficiency (IGHD) or CPHD], and LHX4 and HESX1 genes mutations remain rare causes of hypopituitarism associated with EPL.

Heterozygous Men1 mutant mice develop a range of endocrine tumors mimicking multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by the occurrence of multiple endocrine tumors of the parathyroid, pancreas, and anterior pituitary in patients. To study tumorigenesis related to the MEN1 syndrome, we have generated Men1 knockout mice using the gene targeting approach. Heterozygous Men1 mutant mice developed the same range of major endocrine tumors as is seen in MEN1 patients, affecting the parathyroid, pancreatic islets, pituitary and adrenal glands, as well as the thyroid, and exhibiting multistage tumor progression with metastatic potential. In particular, extrapancreatic gastrinoma, pancreatic glucagonoma, and mixed hormone-producing tumors in islets were observed. In addition, there was a high incidence of gonadal tumors of endocrine origin, i.e. Leydig cell tumors, and ovary sex-cord stromal cell tumors in heterozygous Men1 mutant mice. Hormonal disturbance, such as abnormal PTH and insulin levels, was also observed in these mice. These tumors were associated with loss of heterozygosity of the wild-type Men1 allele, suggesting that menin is involved in suppressing the development of these endocrine tumors. All of these features are reminiscent of MEN1 symptoms in humans and establish heterozygous Men1 mutant mice as a suitable model for this disease.

Glucocorticoid Receptor Expression in Nontumorous Human Pituitaries and Pituitary Adenomas

Glucocorticoids have multiple actions, including a suppressive feedback effect on pituitary corticotrophs via the glucocorticoid receptor (GR). By immunocytochemistry, we studied GR expression in 86 surgically removed various pituitary adenoma types. Ten cases contained nontumorous pituitary fragments, which were suitable for immunocytochemical investigation. In addition, 30 autopsy-obtained pituitaries, 10 of them containing incidental microadenomas, were examined as well. Using a polyclonal GR antibody, the streptavidin-biotin-peroxidase complex method revealed nuclear and/or cytoplasmic GR immunoreactivity in many nontumorous corticotrophs and other adenohypophysial cell types and in S-100 protein immunopositive stellate cells. Cellular localization was confirmed by double immunostaining. Pars intermedia corticotrophs, posterior lobe axons, Herring bodies, and pituicytes as well as several endothelial cells lining the capillaries were also immunopositive. GR immunoreactivity was also demonstrated in many GH, PRL, ACTH, TSH, FSH, LH α-subunit producing adenomas, null cell adenomas, and oncocytomas. The extent and degree of immunostaining varied considerably from case to case. Suppressed corticotrophs showing the Crooke’s hyaline change due to glucocorticoid excess were present in the nontumorous pituitaries of patients with Cushing’s disease and in those treated with pharmacologic doses of glucocorticoids. Many suppressed nontumorous corticotrophs exhibited only weak or no GR immunopositivity, indicating GR downregulation accompanied by cellular injury. Study of autopsy obtained pituitaries for GR yielded inconclusive results indicating that autopsy obtained adenohypophyses are not suitable for the immunocytochemical investigation of GR.

Electron Microscopic investigation of crooke’s change in the pituitaries of patients with hypercorticism

Human pituitary corticotropins have unique morphologic markers: bundles of type-1 filaments, measuring approximately 70 A in width and representing cytokeratin. The extreme ring-like accumulation of type-1 filaments, known as Crooke's hyalinization, signals functional suppression of the corticotropins and occurs in endogenous and exogenous glucocorticoid excess, caused by ACTH-secreting pituitary adenoma, glucocorticoid secreting adrenocortical tumor, ectopic ACTH-syndrome and administration of pharmacologic doses of glucocorticoids. Cells of autonomous corticotroph adenomas usually do not show Crooke's hyalin change. A minority of these tumors, however, retains sensitivity to the negative feed-back effect of elevated blood glucocorticoid levels and display typical Crooke’s change.In the present study pituitary corticotropins in various phases of Crooke's hyalinization were investigated in patients with glucocorticoid excess of various origin, applying histology, immunocytochemistry, count of argyrophilic nucleolar organizer regions (AgNOR), and transmission electron microscopy.

Effects of cyproheptadine, reserpine, and synthetic corticotropin-releasing factor on pituitary glands from patients with Cushing's disease.

Direct effects of cyproheptadine, reserpine, synthetic ovine corticotropin-releasing factor (CRF), dexamethasone, and lysine-8-vasopressin (LVP) on the secretion of immunoreactive ACTH and beta-endorphin from the adenoma and the nonadenomatous tissue of patients with Cushing's disease were examined using a superfusion system. Cyproheptadine and reserpine (10(-9)-10(-7) M of each) suppressed immunoreactive ACTH and beta-endorphin secretion from both tissues. CRF (10(10)-10(7) M) stimulated the secretion of both peptides from the nonadenomatous tissue, but only a high dose of CRF could stimulate the secretion of these peptides from some adenomas. Such CRF-induced secretion was partially suppressed by dexamethasone. LVP (10(-9)-10(-7) M) stimulated peptide secretion from both types of tissue. These results suggest direct inhibitory effects of cyproheptadine and reserpine on the secretion of these peptides from the pituitary of patients with Cushing's disease, a different stimulatory mechanism of LVP from that of CRF in these tissues, and low sensitivity of the adenoma to CRF.

Characterization of Mammotrophs Separated From the Human Pituitary Gland 2

Human pituitary tissues from 27 patients and 7 persons post mortem were dissociated into single cell suspensions. On the average, 23% of the cells were mammotrophs. The concentration of prolactin in these suspensions averaged 3.8 ng/1,000 cells. After cell separation by velocity sedimentation at unit gravity, mammotrophs and other cell types were enriched twofold to threefold. The separated mammotrophs retained structural integrity at light and electron microscopic levels. In eight separation experiments, cells recovered from different gradient regions were assayed for intracellular prolactin levels. In cells from "normal" subjects, 8.5% of the prolactin recovered from the gradient was associated with large mammotrophs, whereas in patients with breast cancer, 28% of the hormone was associated with large mammotrophs. The number of mammotrophs recovered from this gradient region (beyond fraction 6) was doubled in breast cancer (2 expts). These mammotrophs showed areas of hypertrophied Golgi and endoplasmic reticulum. Culture of the separated cells from 1 patients with diabetes and 2 patients with breast cancer for 21 days showed that mammotrophs in the upper gradient fractions (diabetic) secreted seven times more hormone than those in the lower regions, whereas those mammotrophs from patients with breast cancer that fell to the lower gradient regions secreted 15 times more prolactin than did those in the upper regions. These data suggest that pituitaries of patients with breast cancer contain a small pool (10-20%) of hypertrophied mammotrophs that have the potential for significant secretory activity in vitro.

The histological features and human growth hormone content of the pharyngeal pituitary gland in normal and endocrinologically-disturbed patients.

SUMMARYThe pharyngeal pituitary was studied in forty‐seven patients who did not have evidence of endocrine disturbance and in nineteen patients with some evidence of endocrine disorder. Various histological patterns were encountered: the ‘activated’type showed adenohypophyseal differentiation, the ‘inactivated’type showed squamous epithelium or undifferentiated cells and the ‘mixed’type contained elements of the other two types of tissue. The appearance of squamous foci in the pharyngeal pituitary was shown to be an ageing phenomenon. Human growth hormone was detected by immunofluorescence in scattered cells of some glands with adenohypophyseal differentiation. There was no evidence of hyperplasia of HGH‐containing cells in the pharyngeal pituitary in patients with virtually complete sellar pituitary ablation: in anencephaly, basophil cells predominated and HGH‐containing cells were scanty: ‘pregnancy cells’were not identified in the pharyngeal pituitary of a parturient woman.

ULTRASTRUCTURE AND HORMONE DISTRIBUTION OF THE HUMAN CORTICOTROPHIC ANTERIOR PITUITARY CELL UNDER NORMAL CONDITIONS, IN CORTICOTROPHIC ADENOMA AND IN EXOGENOUS HYPERCORTISOLISM

Using improved methods, simultaneous immunohistological and electron microscope studies were done on corticotrophic anterior pituitary adenomas (Nelson's syndrome), pituitaries of patients under exogenous corticosteroid therapy, and normal pituitaries. In consecutive semi-thin and ultra-thin sections immunohistological ACTH-localization could be directly coordinated with the ultrastructural details of the same cell. The ultra-structural characteristics of the corticotrophic anterior pituitary cell could thus be clearly determined for the first time.

Abnormal thyrotropic substance in the pituitaries of patients with Graves' disease.

ABSTRACT The thyrotropic substance in the pituitary glands of 4 patients with Graves' disease was studied and found to be immunologically abnormal. The time response curve in the bioassay for pituitary thyrotropic activity in all patients was normal. The pituitary thyrotropic activity in 3 patients who died in a hyperthyroid state was found to be about the normal average, and failed to be neutralized by antinormal TSH serum in an amount 50–200 times the minimum amount required for neutralization of normal TSH. The activity in the gland of a patient who died in a euthyroid state was within the normal range, and was partially neutralized by anti-TSH serum. Normal human TSH added to the patient's pituitary extract was neutralized by anti-TSH serum. The thyrotropic activity not neutralized with anti-TSH serum in the patients' pituitary glands was extracted by the percolation method of Bates and showed a dose response curve similar to that of normal TSH.

Exophthalmos-producing activity in the serum and in the pituitary of patients with Cushing's syndrome and acromegaly.

ABSTRACT In the serum of 5 exophthalmic patients with Cushing's syndrome and of 2 exophthalmic patients with acromegaly, an elevated titer of EPS was found. Two patients underwent pituitary surgery and 2 were treated by pituitary x-ray irradiation. In all of them the exophthalmogenic activity disappeared from the serum, while the ocular symptoms simultaneously regressed. In one patient, the EPS activity increased and the exophthalmos remained unchanged following total adrenalectomy. In one patient with Cushing's syndrome and in 3 acromegalics who showed no eye signs, serum tests were negative. In pituitary tissue of 2 patients with Cushing's syndrome obtained at operation, an elevated exophthalmogenic activity was found. By control experiments necessary for the evaluation of these findings, it was established that human pituitary glands obtained at autopsy contain an exophthalmos-producing substance.