OBJECTIVE: Silent corticotroph adenomas (SCA) are endocrine-inactive pituitary adenomas with positive immunohistochemistry staining for adrenocorticotropic hormone (ACTH). We investigated whether SCA-associated clinical profiles were more aggressive than hormonally negative adenomas (HNA).METHODS: Among 627 patients with pathologically proven endocrine-inactive pituitary adenomas between 2004 and 2013, positive immunohistochemistry revealed 55 SCAs and 411 HNAs. Surgical outcomes and radiological and endocrinological characteristics were compared.RESULTS: Strong female predominance was observed in the SCA group (p<0.001). Cavernous sinus invasion was identified in 22 (40%) SCA patients and 72 (17.6%) HNA patients (p<0.001). There were no differences in ACTH or cortisol levels between the two groups. The incidence of preoperative hypopituitarism and postoperative hormonal outcome did not differ between two groups. Total resection was achieved in 35 patients (63.7%) with SCA and 332 patients (80.8%) with HNA (p=0.007). When tumors were completely removed, recurrence rates were not statistically different between two groups (p=0.60). When complete resection was not achieved, tumors regrew from these remnants in seven patients (35.0%) with SCA and 12 patients (15.2%) with HNA (p=0.05).CONCLUSION: Total surgical resection for SCA is often challenging as these tumors frequently invade a cavernous sinus. Early remnant tumor intervention is justified, because untreated residual pituitary tumors regrow when patients were followed up for a long time. Prophylactic radiotherapy is not warranted for completely resected SCAs as tumor recurrence is uncommon.
ACTH-Secreting Pituitary Adenoma ; Adenoma ; Adrenocorticotropic Hormone ; Cavernous Sinus ; Corticotrophs ; Female ; Humans ; Hydrocortisone ; Hypopituitarism ; Immunohistochemistry ; Incidence ; Pituitary Neoplasms ; Radiotherapy ; Recurrence

The effects of morphine in bringing sleep and an end to pain have been known from the beginning of recorded history. But the existence of endogenous opiates(endorphin) has been demonstrated only in the last decade. Endorphin bind to opiate receptors and exhibit potent opiate-like activity. In the corticotroph cells of the anterior lobe of pitultary, ACTH and beta-endorphin are synthesized simultaneously. There is a hypothalamic releasing factor which causes the secretion both beta-endorphin and ACTH, but ACTH and beta-endorphine are also released simultaneously by stress. Endorphins adversely affect the circulatory status and these effects are reversed by the intravenous injection of the narcotic antagonist, naloxone. The author studied Dirksen's hypothesis that endorphins may be involved in the pathophysiology of hemorrhagic shock. In this experiment, the author divided in the pathophysiology of hemorrhagic shock. In this experiment, the author divided laboratory animals into 3 groups and administered normal saline, salicylate or hyprocortisone, respectively. l. normal saline pretreated group. ll. salicylate pretreated group. lll. hydrocortisone pretreated group. Each group was then divided into 4 subgroups and treated as follows: 1) hypovolemic shock + normal saline. 2) hypovolemic shock + naloxone. 3) hypovolemic shock + hydrocortisone. 4) hypovolemic shock + PGE1. The following results were obtained: 1) MAP was significantly increased after naloxone and PGE1 adminitration in the normal saline pretreated group. 2) MAP was not changed in the salicylate pretreated group. 3) MAP was significantly increased after naloxone and PGE1 administration in the hydrocortisone pretreated group. 4) Pulse pressure was significantly increased after anloxone, hydrocortisone and PGE1 administration in the normal saline and hydrocortisone pretreated groups. From the above experiment, it may be inferred that endorphins and prostaglandin may play a role in the pathophysiology of hypovolemic shock.
Adrenocorticotropic Hormone ; Alprostadil ; Animals ; Animals, Laboratory ; beta-Endorphin ; Blood Pressure ; Corticotrophs ; Endorphins ; Hydrocortisone ; Hypovolemia* ; Injections, Intravenous ; Morphine ; Naloxone* ; Pituitary Hormone-Releasing Hormones ; Rats* ; Receptors, Opioid ; Shock* ; Shock, Hemorrhagic

Isolated ACTH deficiency is an uncommon disorder, which is defined by low cortisol production with low or normal plasma ACTH levels and no other pituitary abnormalities. We report five new cases of this disorder, and summarize the clinical and hormonal features of 8 previously reported cases in Korea plus 5 new cases. 1) The clinical manifestations of isolated ACTH deficiency are variable, non-specific and similar to those seen in adrenocortical insufficiency of any cause, the age of patients ranged from 21 to 66 years old with an average age of 46 years, and the male to female ratio was 10:3. 2) Hyponatremia and hypoglycemia were commmon laboratory findings, so the presence of unexplained hyponatremia or hypoglycemia should always warrant consideration of the diagnosis of isolated ACTH deficiency. 3) 3 of 13 patients accompanied by empty sella suggesting selective destruction of pituitary ACTH producing cells. 4) ACTH response to exogenous CRH or vasopressin was not elicited in all tested cases, suggesting pituitary disorders. 5) Most patients showed dramatic response with oral predinisone. In conclusion, when there are unexplained general weakness, fatigue, weight loss, nausea, vomiting, hypoglycemia, or hyponatremia, isolated ACTH deficiency should be excluded. Immunologic and pathologic studies, and hormonal evolution with glucocorticoid treatment are needed to understand the pathogenesis of isolated ACTH deficiency.
Adrenocorticotropic Hormone ; Aged ; Corticotrophs ; Diagnosis ; Fatigue ; Female ; Humans ; Hydrocortisone ; Hypoglycemia ; Hyponatremia ; Korea* ; Male ; Nausea ; Pituitary Diseases ; Plasma ; Vasopressins ; Vomiting ; Weight Loss

BACKGROUND: Oxytocin (OXT) has been reported to act as a growth regulator in various tumor cells. However, there is a paucity of data on the influence of OXT on cell proliferation of corticotroph adenomas. This study aimed to examine whether OXT affects cell growth in pituitary tumor cell lines (AtT20 and GH3 cells) with a focus on corticotroph adenoma cells. METHODS: Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were conducted with AtT20 cells to confirm the effects of OXT on hormonal activity; flow cytometry was used to assess changes in the cell cycle after OXT treatment. Moreover, the impact of OXT on proliferating cell nuclear antigen (PCNA), nuclear factor κB, and mitogen-activated protein kinase signaling pathway was analyzed by Western blot. RESULTS: OXT treatment of 50 nM changed the gene expression of OXT receptor and pro-opiomelanocortin within a short time. In addition, OXT significantly reduced adrenocorticotropic hormone secretion within 1 hour. S and G2/M populations of AtT20 cells treated with OXT for 24 hours were significantly decreased compared to the control. Furthermore, OXT treatment decreased the protein levels of PCNA and phosphorylated extracellular-signal-regulated kinase (P-ERK) in AtT20 cells. CONCLUSION: Although the cytotoxic effect of OXT in AtT20 cells was not definite, OXT may blunt cell proliferation of corticotroph adenomas by altering the cell cycle or reducing PCNA and P-ERK levels. Further research is required to investigate the role of OXT as a potential therapeutic target in corticotroph adenomas.
ACTH-Secreting Pituitary Adenoma ; Adrenocorticotropic Hormone ; Blotting, Western ; Cell Cycle ; Cell Line ; Cell Proliferation ; Corticotrophs ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Gene Expression ; Oxytocin ; Phosphotransferases ; Pituitary Neoplasms ; Polymerase Chain Reaction ; Pro-Opiomelanocortin ; Proliferating Cell Nuclear Antigen ; Protein Kinases ; Reverse Transcription