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Results for “Pituitary ACTH Hypersecretion”

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At least 145 records · Page 8Linked to original sources
PubMed2007

Patterns of cognitive change over time and relationship to age following successful treatment of Cushing's disease.

Chronically elevated levels of cortisol have been associated with changes in cognitive functioning and brain morphology. Using Cushing's disease as a model to assess the effects of high levels of cortisol on cognitive functioning, 27 patients with Cushing's disease were examined at baseline and three successive follow-up periods up to 18 months after successful surgical treatment. At all follow-up periods, patients were administered cognitive tests as well as measures of plasma and urinary free cortisol. Structural MRIs and a depression measure were taken at baseline and one-year follow-up. Results showed that there is a specific pattern of significant cognitive and morphological improvement following successful treatment. Verbal fluency and recall showed recovery, although brief attention did not. Age of participants was a significant factor as to when recovery of function occurred; younger patients regained and sustained their improvement in cognitive functioning more quickly than older participants. Improvement in verbal recall also was associated with a decrease in cortisol levels as well as an increase in hippocampal formation volume one year after treatment. Overall, these findings suggest that at least some of the deleterious effects of prolonged hypercortisolemia on cognitive functioning are potentially reversible, up to at least 18 months post treatment.

Adolescent↗
PubMed2004

A detailed investigation of hirsutism in a Turkish population: idiopathic hyperandrogenemia as a perplexing issue.

Hirsutism is a common clinical problem in women and the treatment depends on the cause of hirsutism. The study was designed to determine the various causes of hirsutism and their prevalences in a Turkish population. 168 women with hirsutism attending to Endocrinology Outpatient Clinic of Erciyes University Hospital were investigated in detail. Medical history, physical examination, and basal levels of free testosterone (fT), androstenedione, follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone-sulphate (DHEAS), 17 hydroxyprogesterone (17-OHP), 11-deoxycortisol (11-S), thyroid hormones, thyroid stimulating hormone (TSH), and prolactin were determined. ACTH stimulation test was performed for the diagnosis of non-classic congenital adrenal hyperplasia (NCAH). Pelvic/vaginal and adrenal ultrasonographies were performed for the detection of tumors and polycystic ovarian changes. Polycystic ovary syndrome (PCOS) was diagnosed in 96 (57.1 %) patients, idiopathic hirsutism in 27 (16 %), NCAH in 12 (7.1 %), adrenal carcinoma in 3 (1.8 %), and Cushing's disease in 1 (0.6 %) patient. Among patients with NCAH, 11 (91.7 %) patients had 11-beta hydroxylase (11-beta OH) deficiency, and 1 (8.3 %) had 21-hydroxylase deficiency. The etiology of hyperandrogenemia was not clear in 29 (17.4 %) patients and these patients were named as idiopathic hyperandrogenemia. The clinical presentation of 11-beta OH deficiency is indistinguishable from that of other hyperandrogenic states and ACTH stimulation test is the only way to diagnose this entity. Although PCOS is the most common cause of hirsutism, it is notable that nearly one fifth of hirsute women have no apparent cause of hyperandrogenemia.

Adrenal Cortex Neoplasms↗
PubMed2005

Markers of vascular function in hypertension due to Cushing's syndrome.

BACKGROUND: There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arterial hypertension. The aim of the study was to determine some markers of vascular function, including VEGF, active renin and prostaglandin E (2) (PGE (2)) in patients with endocrine hypertension resulting from Cushing's syndrome. MATERIAL AND METHODS: The study comprised 32 patients with active Cushing's syndrome, 22 patients with essential hypertension, and 24 healthy volunteers. RESULTS: VEGF was significantly elevated in the groups of patients compared to controls. VEGF levels in the patients with Cushing's syndrome were significantly higher than in patients with essential hypertension. We did not find significant differences in VEGF levels between patients with Cushing's disease and Cushing's syndrome due to adrenal tumor. Active renin and PGE (2) levels did not differ significantly among groups. CONCLUSION: VEGF levels were significantly elevated in endocrine hypertension due to glucocorticoid excess. Higher VEGF levels were detected in patients with Cushing's syndrome compared to patients with essential hypertension. Based on our results, we could not judge the extent to which this VEGF elevation in the patients with Cushing's syndrome was due to the hypertension itself and/or to the presence of adrenal tumor/hyperplasia.

Adenoma↗
PubMed2013

Evidence for orphan nuclear receptor TR4 in the etiology of Cushing disease.

Cushing disease (CD) is a life-threatening disorder attributed to excess pituitary tumor-derived adrenocorticotrophic hormone (ACTH) and adrenal steroid secretion caused by pituitary tumors. Whereas CD was first described in 1932, the underlying genetic basis driving tumor growth and ACTH secretion remains unsolved. Here, we show that testicular orphan nuclear receptor 4 (TR4, nuclear receptor subfamily 2, group C, member 2) is overexpressed in human corticotroph tumors as well as in human and mouse corticotroph tumor cell lines. Forced overexpression of TR4 in both human and murine tumor cells increased proopiomelanocortin transcription, ACTH secretion, cellular proliferation, and tumor invasion rates in vitro. Conversely, knockdown of TR4 expression reversed all phenotypes. Mechanistically, we show that TR4 transcriptionally activates proopiomelanocortin through binding of a direct repeat 1 response element in the promoter, and that this is enhanced by MAPK-mediated TR4 phosphorylation. In vivo, TR4 overexpression promotes murine corticotroph tumor growth as well as enhances ACTH and corticosterone production, whereas TR4 knockdown decreases circulating ACTH and corticosterone levels in mice harboring ACTH-secreting tumors. Our findings directly link TR4 to the etiology of corticotroph tumors, hormone secretion, and cell growth as well as identify it as a potential target in the treatment of CD.

ACTH-Secreting Pituitary Adenoma↗
PubMed2006

Effect of protracted treatment with rosiglitazone, a PPARgamma agonist, in patients with Cushing's disease.

OBJECTIVE: Cushing's disease, hypercortisolism due to a pituitary ACTH-secreting tumour, is a highly morbid illness as yet without effective medical therapy. Recent studies have demonstrated that peroxisome proliferator-activated receptor gamma (PPARgamma) agonists effectively suppress ACTH secretion in a murine tumoral corticotroph cell line, but the few studies conducted so far in patients with ACTH-secreting pituitary adenomas have yielded variable results. DESIGN: Ten patients with Cushing's disease were treated with 4-16 mg rosiglitazone p.o. daily for 1-8 months (median 3 months) and plasma ACTH and cortisol, urinary free cortisol (UFC), as well as parameters of insulin sensitivity, were recorded. An acute challenge with 8 mg rosiglitazone for 2 days preceded long-term rosiglitazone administration. RESULTS: The acute challenge with rosiglitazone did not significantly modify plasma ACTH and cortisol levels. During protracted treatment with rosiglitazone, four patients showed a persistent reduction in UFC levels (up to 24% of pretreatment values), achieving normalization in three. In the others, UFC as well as plasma ACTH and cortisol decrements were inscribed within wide, random oscillations indicating that disease activity was substantially unchanged. Insulin sensitivity was ameliorated in most patients, without relation to ACTH or cortisol secretion. Untoward effects, such as weight gain, oedema and worsening of ecchymoses, were reported in several patients. CONCLUSIONS: Although effective in a subset of patients, protracted rosiglitazone administration did not consistently restrain ACTH and cortisol secretion in patients with Cushing's disease. Further investigations are needed to fully define the therapeutic potential of PPARgamma agonists in this disorder.

Adrenocorticotropic Hormone↗
PubMed2006

The PPAR-gamma activator rosiglitazone fails to lower plasma ACTH levels in patients with Nelson's syndrome.

BACKGROUND: Peroxisomal proliferator-activated receptors (PPAR)- gamma are expressed abundantly in ACTH-secreting pituitary tumours. The PPAR-gamma activator rosiglitazone has been shown to suppress ACTH secretion in human adrenocorticotroph tumour cells in vitro, and prevent and reduce adrenocorticotroph tumour development in mouse models in vivo. OBJECTIVE: To evaluate the effect of rosiglitazone in patients with persistently elevated plasma ACTH levels postbilateral adrenalectomy for Cushing's disease. PATIENTS: Seven patients were treated with rosiglitazone 8 mg orally per day for 12 weeks. MEASUREMENTS: Plasma ACTH was measured at two hourly intervals from 09:00 h to 17:00 h before and after 6 and 12 weeks of treatment. RESULTS: Plasma ACTH at 09:00 hours immediately before the usual morning hydrocortisone dose was 2599.0 +/- 899.7 ng/l (mean +/- SEM) basally and 1547.6 +/- 515.7 ng/l after 12 weeks of rosiglitazone, whereas levels at 17:00 h were 1433.4 +/- 506.2 ng/l (mean +/- SEM) basally and 1122.3 +/- 460.9 ng/l at 12 weeks (all nonsignificant). CONCLUSION: This study showed no effect of rosiglitazone treatment at maximum approved doses in lowering plasma ACTH levels in patients post bilateral adrenalectomy for Cushing's disease.

Adrenalectomy↗
PubMed2007

Abnormal expression of PPAR gamma isoforms in the subcutaneous adipose tissue of patients with Cushing's disease.

BACKGROUND: Obesity is a clinical feature of patients with Cushing's disease. Peroxisome proliferators-activated receptor (PPAR)gamma is the master regulator of adipogenesis; however, the expression of PPARgamma isoforms in the subcutaneous adipose tissue (SAT) of patients with Cushing's disease is unknown. AIM AND METHODS: The expression of PPARgamma1 and PPARgamma2 was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence (PPARgamma2 only) in SAT samples of 7 patients with untreated active Cushing's disease (Cushing(UNTR)), 8 with Cushing's disease in remission (Cushing(REM)) after pituitary adenomectomy, 15 normal lean subjects (Control(LEAN)), and 15 obese patients (Control(OBE)). RESULTS: Control(LEAN) had a higher degree of PPARgamma1 than PPARgamma2 (PPARgamma2/PPARgamma1 ratio, 0.55 +/- 0.35). PPARgamma2/PPARgamma1 ratio decreased in Cushing(UNTR) (0.10 +/- 0.043, P < 0.03 vs. Control(LEAN) and Control(OBE)), because of either increased PPARgamma1 or reduced PPARgamma2 expression. PPARgamma2/PPARgamma1 ratio was 0.48 +/- 0.07 in Cushing(REM) patients (P < 0.04 vs. Cushing(UNTR), P < 0.03 vs. Control(OBE)). PPARgamma2/PPARgamma1 ratio was higher in Control(OBE) 0.90 +/- 0.38 than in Control(LEAN) (P < 0.005 vs. Control(LEAN), P < 0.03 vs. Cushing(REM), P < 0.009 vs. Cushing(UNTR)). PPARgamma2/PPARgamma1 ratio was related to serum cortisol levels only in patients with Cushing'disease (r = 0.688, P < 0.02). CONCLUSIONS: Cushing(UNTR) patients had an abnormal expression of PPARgamma isoforms in SAT related to serum cortisol levels. Although further studies are necessary, it is conceivable that variations in the expression of PPARgamma isoforms might have a role in the abnormal adipogenesis of patients with Cushing's disease.

Adrenalectomy↗
PubMed2005

The efficacy of linear accelerator radiosurgery in the management of patients with Cushing's disease.

We identified 35 patients who had undergone stereotactic radiosurgery (SRS) for their biochemically proven Cushing's disease in order to assess the efficacy of SRS with regard to control of hypercortisolism, improvement of clinical features and prevention of tumor progression, and subsequent incidence of hypopituitarism. Seventeen (49%) patients achieved control of their cortisol levels following SRS; the mean time to normalization was 7.5 months (range: 1-33). Four (19%) patients experienced recurrent hypercortisolism at a mean time of 35.5 months following therapy (range: 17-64). Control of tumor progression was achieved in 91% patients. Fourteen (40%) patients demonstrated a new pituitary deficiency following SRS. Our results suggest that cortisol levels are normalized more efficiently and with a lower recurrence rate with SRS than with conventional fractionated external beam radiotherapy (EBT). We have confirmed the near 100% tumor control rate reported with SRS. The percentage of patients developing pituitary insufficiency following SRS is less than that of patients having undergone EBT; however, deficits occurred up to 10 years posttreatment. We advocate the use of SRS as the primary therapeutic modality in those patients who are poor surgical candidates, or as the adjunct treatment to microsurgery in eliminating residual tumor cells or disease that is not easily amenable to resection.

Adolescent↗
PubMed2005

Adrenal pathophysiology: lessons from the Carney complex.

The Carney complex (CNC) is a dominantly inherited syndrome responsible mainly for spotty skin pigmentation (lentiginosis), endocrine overactivity, and cardiac myxomas. Adrenocorticotropic hormone independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is a main characteristic of CNC. PPNAD is a very rare cause of Cushing's syndrome due to a primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations nor familial history. One of the putative CNC genes, located on 17q22-24, has been identified as the regulatory subunit R1A of protein kinase A (PRKAR1A). Heterozygous inactivating mutations of PRKAR1A have been reported initially in about 45% of the CNC index cases and could be found in about 80% of the CNC families presenting mainly with Cushing's syndrome. PRKAR1A is a key component of the cyclic AMP signaling pathway that has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene. Interestingly, patients with isolated PPNAD and no familial history of CNC can also present a germline de novo mutation of PRKAR1A. Somatic mutations of PRKAR1A have been found in PPNAD as a mechanism of inactivation of the wild-type allele, in a patient already presenting a germline mutation, and in a subset of sporadic secreting adrenocortical adenomas with clinical, hormonal, and pathological features quite similar to PPNAD. This review will summarize the recent findings on CNC from the perspective of the pathophysiology of adrenal Cushing's syndrome and PPNAD.

Adrenal Cortex Diseases↗