PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Pituitary ACTH Hypersecretion”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2006

The discriminatory value of the low-dose dexamethasone suppression test in the investigation of paediatric Cushing's syndrome.

BACKGROUND: Low- and high-dose dexamethasone suppression tests (LDDST, HDDST) are used in the investigation of Cushing's syndrome (CS). In adults with Cushing's disease (CD), cortisol suppression during LDDST predicts suppression during the HDDST. METHODS: We reviewed the results of the LDDST (0.5 mg 6 hourly x 48 h), HDDST (2.0 mg 6 hourly x 48 h) and corticotrophin-releasing hormone (CRH) test in 32 paediatric patients with CS: 24 had CD, 1 ectopic ACTH syndrome, 5 nodular adrenal hyperplasia and 2 adrenocortical tumours. RESULTS: In CD, LDDST suppressed cortisol from 590.7 +/- 168.8 (mean +/- SD) to 333.7 +/- 104.0 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 45.1%; CI (30.8, 59.4%); 16/24 (66%) suppressed >30%; mean suppression 68.1%, CI (58.1, 77.9%)). The HDDST suppressed cortisol from 596.3 +/- 174.5 to 47.1 +/- 94.8 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 93.5%; CI (88.2, 98.8%) with 17/24 (71%) suppressing to <50 nmol/l and 100% to <50% of baseline). In the LDDST, suppression correlated with that during the HDDST (r = +0.45, p < 0.05) with >30% suppression predicting that in the HDDST and hence CD. CRH increased cortisol by +100.3% (CI 62, 138.5%), 22/24 (91.7%) showing a >20% increase. In the other CS pathologies (n = 8) the LDDST induced no significant decrease in cortisol. CONCLUSION: The LDDST was of diagnostic value by discriminating between CD and other CS aetiologies. In our view the HDDST is redundant in the investigation of paediatric CS.

Adolescent↗
PubMed2006

New aspects in the diagnosis and treatment of Cushing disease.

Cushing disease, which is caused by the excessive production of ACTH, is a rare and complex endocrine disorder that still represents a major challenge for the physician in terms of accurate diagnosis and efficient treatment. Diagnosing Cushing syndrome and its etiology is an elaborate procedure and no single test is sensitive and specific enough to provide sufficient accuracy. Therefore, an ordered cascade of tests is necessary recommended by a consensus statement in 2002. The proposed diagnostic algorithm will be summarized in the following section. In the absence of efficient drug therapy, transsphenoidal resection of the pituitary adenoma is the treatment of choice for the reduction of ACTH secretion. However, not all patients can be cured by surgery. In the present article, we examine recent studies that have investigated the therapeutic potential of new generations of drugs for the treatment of Cushing disease such as cabergoline and SOM230. The role of nuclear receptors: retinoic acid receptors and peroxisome proliferator-activated receptor-gamma as new approaches for treating pituitary tumors is also discussed.

Algorithms↗
PubMed2005

The aberrant expression of the gastric inhibitory polypeptide (GIP) receptor in adrenal hyperplasia: does chronic adrenocorticotropin exposure stimulate up-regulation of GIP receptors in Cushing's disease?

CONTEXT: Cortisol secretion is usually under the control of ACTH. However, cortisol secretion occurs in response to gastric inhibitory polypeptide (GIP) in rare cases of food-dependent Cushing's syndrome (CS). OBJECTIVE: We have investigated whether chronic ACTH stimulation or activation of the ACTH signaling pathway might be associated with GIP receptor (GIPR) expression. DESIGN: RT-PCR analysis and primary culture of hyperplastic adrenals. PATIENTS: All patients presented with CS: 20 unilateral adrenal adenomas, five Cushing's disease, one food-dependent CS. RESULTS: RT-PCR revealed GIPR expression in all hyperplastic adrenals studied. No RT-PCR product could be detected in two normal adrenals or 20 hyperfunctioning adrenal adenomas. Primary culture revealed a significant cAMP response to ACTH in all adrenals available for study (EC50, 8.1 x 10(-10) M in normals, 4.7 x 10(-10) M in Cushing's disease, and 4.4 x 10(-10) M in food-dependent disease). However, cultures taken from all four ACTH-dependent and the one food-dependent hyperplastic adrenals studied were also responsive to GIP (EC50 for cAMP, 1.3 x 10(-9) M in Cushing's disease and 4.1 x 10(-10) M in food-dependent disease). Fasting cortisol levels were low in the case of food-dependant Cushing's, rising postprandially as predicted. However, there was no trend toward low fasting or high postprandial cortisol in the other cases, suggesting that the presence of detectable GIPR alone, albeit with definite function in vitro, is not sufficient to cause clinically food-dependent CS. CONCLUSIONS: These data are consistent with the hypothesis that chronic ACTH stimulation or constitutive activation of the ACTH signaling pathway may be associated with aberrant GIPR expression, and suggest one mechanism for the pathogenesis of this phenomenon.

Adrenal Cortex↗
PubMed2005

Quality of life in patients after long-term biochemical cure of Cushing's disease.

To evaluate the long-term impact of cured Cushing's disease on subjective well-being, we assessed quality of life by validated health-related questionnaires in 58 patients cured from Cushing's disease by transsphenoidal surgery (n = 58), some of whom received additional radiotherapy (n = 11) and/or bilateral adrenalectomy (n = 3). The mean duration of remission was 13.4 +/- 6.7 yr (range of 2-25 yr). Patient data were compared with a control group of 98 healthy subjects with the same age and sex distribution and with age-adjusted reference values available from the literature. General perceived well-being, measured by the Nottingham Health Profile and the Short Form, was reduced compared with controls for all subscales (P < 0.001). Patients with Cushing's disease had worse scores on subscales of fatigue Multidimensional Fatigue Index and anxiety and depression (Hospital Anxiety and Depression Scale). Compared with reference values from the literature, quality of life was also reduced in the patients according to all questionnaires and all items, except pain (Short Form), sleep (Nottingham Health Profile), and reduced activity (Multidimensional Fatigue Index). Despite conventional hormone replacement therapy, hypopituitarism was an important independent predictor of reduced quality of life. Patients without hypopituitarism (n = 28) showed reduced scores on physical items but normal scores on mental items compared with controls. In conclusion, despite long-term cure of Cushing's disease, patients experience a considerable decrease in quality of life, with physical and psychosocial impairments, especially in the presence of hypopituitarism.

Adrenalectomy↗
PubMed2005

Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas.

CONTEXT: Cushing's disease as a result of a pituitary macroadenoma is an uncommon cause of Cushing's syndrome, and reports in the published literature are few and of limited size. OBJECTIVE: Our objective was to establish the clinical and biochemical characteristics of macroadenomas associated with Cushing's disease compared with a large cohort of microadenomas and to assess their response to therapy. DESIGN: We conducted a retrospective case-records study for the years 1964-2001. SETTING: The study occurred at a tertiary referral hospital center. PATIENTS: Patients had Cushing's disease presenting with a pituitary macroadenoma, in comparison with a large group of microadenoma patients. INTERVENTIONS: Interventions included therapy with surgery and radiotherapy. MAIN OUTCOME MEASURES: Outcome measures included basal and dynamically responsive plasma ACTH and cortisol levels and response to treatment. RESULTS: We identified 18 patients with Cushing's disease secondary to a macroadenoma; basal 0900 h plasma ACTH was 135.8 +/- 32.5 and 45.0 +/- 4.3 ng/liter (mean +/- SEM), respectively, in macroadenomas and microadenomas (P = 0.013). Mean 0900 h serum cortisol was significantly increased in the macroadenomas (27.5 +/- 3.0 microg/dl, 759.6 +/- 82.6 nmol/liter, vs. 22.6 +/- 0.6 microg/dl, 624.7 +/- 16.4 nmol/liter) (P = 0.021). Testing with high-dose dexamethasone showed less suppression in the macroadenomas (57.6 +/- 8.7% vs. 74.4 +/- 2.1%; P = 0.02) and an attenuated ACTH response to CRH. For all biochemical variables there was considerable overlap between the two groups. Few patients with macroadenomas were cured by surgery. CONCLUSIONS: Pituitary macroadenomas causing Cushing's disease have biochemical features largely distinct from patients harboring microadenomas but represent one end of a continuum.

Adenoma↗
PubMed2005

Sulfur amino acids in Cushing's disease: insight in homocysteine and taurine levels in patients with active and cured disease.

BACKGROUND: Cushing's syndrome is associated with an increased cardiovascular risk. Although a series of cardiovascular risk factors have been identified, sulfur amino acids (SAAs), recently indicated as independent cardiovascular risk factors, have been poorly investigated in patients with Cushing's syndrome. AIM: The aim of this cross-sectional controlled study was to evaluate serum and urinary levels and urinary excretion rate (ER) of SAAs in patients with Cushing's disease (CD) during the active disease and after long-term disease remission. SUBJECTS AND METHODS: Forty patients with CD (20 with active disease and 20 with cured disease for at least 5 yr) and 40 controls entered the study. Serum and urinary concentrations and urinary ER of SAAs, namely methionine, cystine, homocysteine, and taurine, were measured by means of cationic exchange HPLC. Serum folic acid and vitamin B12 levels were also evaluated in patients and controls and correlated to SAA levels. RESULTS: CD patients with active disease had higher serum and urinary concentrations of cystine and homocysteine, and lower serum and higher urinary concentrations and ER of taurine than cured patients and controls. Vitamin B12 levels were significantly decreased in patients with active disease compared with cured patients and controls, whereas folic acid levels were slightly decreased in patients than in controls. In patients with active CD, urinary cortisol concentrations were significantly and inversely correlated to serum taurine and directly correlated to taurine urinary ER, and fasting serum glucose levels were significantly correlated to taurine urinary ER. At the multiple regression analysis, urinary cortisol concentrations were the best predictors of taurine ER. CONCLUSIONS: CD is associated with hyperhomocysteinemia and hypotaurinemia. Glucocorticoid excess, acting directly or indirectly, seems to be the most responsible for this imbalance in SAA levels. The long-term disease remission is accompanied by normalization of SAA levels. Hyperhomocysteinemia and hypotaurinemia might contribute to the increased cardiovascular risk of CD.

Adult↗
PubMed2006

The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas.

CONTEXT: There is no tumor-directed medical therapy available for Cushing's disease. OBJECTIVE: The objective was to determine the in vitro effect of the somatostatin analog pasireotide (SOM230) on cell proliferation in human corticotroph tumors. DESIGN/METHODS: Expression of somatostatin receptors (SSTR 1-5) was determined by quantitative RT-PCR in 13 human corticotroph tumors and by immunohistochemistry (IHC) in 12 of the 13 tumors. SOM230 effects on cell proliferation and ACTH release were evaluated in vitro using primary cultures of six of the 13 human corticotroph adenomas. RESULTS: In our series, we found expression of SSTR subtypes 1, 2, 4, and 5 in human corticotroph tumors by quantitative RT-PCR. All receptor subtypes were detected by IHC, with SSTR subtype 5 having the highest IHC score in 83% (10 of 12) of the cases. Significant suppression of cell proliferation was observed in all tumors cultured (percent suppression range: 10-70%; P = 0.045-0.001). SOM230 inhibited ACTH secretion in five of the six tumors cultured (percent suppression range: 23-56%; P = 0.042-0.001). CONCLUSION: Corticotroph tumors express multiple SSTR subtypes. SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. These in vitro results support the hypothesis that SOM230 may have a role in the medical therapy of corticotroph tumors.

ACTH-Secreting Pituitary Adenoma↗
PubMed2006

Corticotroph tumor progression after adrenalectomy in Cushing's Disease: A reappraisal of Nelson's Syndrome.

CONTEXT: Adrenalectomy is a radical treatment for hypercortisolism in Cushing's disease. However, it may lead to Nelson's syndrome, originally defined by the association of a pituitary macroadenoma and high plasma ACTH concentrations, a much feared complication. OBJECTIVE: The objective of the study was to reconsider Nelson's syndrome by investigating corticotroph tumor progression based on pituitary magnetic resonance imaging scan and search for predictive factors. DESIGN: This was a retrospective cohort study. SETTING: The complete medical records of Cushing's disease patients at Cochin Hospital were studied. PATIENTS: Patients included 53 Cushing's disease patients treated by adrenalectomy between 1991 and 2002, without previous pituitary irradiation. MEASUREMENTS: Clinical data, pituitary magnetic resonance imaging data, and plasma ACTH concentrations for all patients and pituitary gland pathology data for 25 patients were recorded. Corticotroph tumor progression-free survival was studied by Kaplan-Meier, and the influence of recorded parameters was studied by Cox regression. INTERVENTION: There was no intervention. RESULTS: Corticotroph tumor progression ultimately occurred in half the patients, generally within 3 yr after adrenalectomy. A shorter duration of Cushing's disease (adjusted hazard ratio: 0.884/yr), and a high plasma ACTH concentration in the year after adrenalectomy [adjusted hazard ratio per 100 pg/ml (22 pmol/liter): 1.069] were predictive of corticotroph tumor progression. In one case, corticotroph tumor progression was complicated by transitory oculomotor nerve palsy. During follow-up, corticotroph tumor progression was associated with the increase of corresponding ACTH concentrations (odds ratio per 100 pg/ml of ACTH variation: 1.055). CONCLUSION: After adrenalectomy in Cushing's disease, one should no longer wait for the occurrence of Nelson's syndrome: modern imaging allows early detection and management of corticotroph tumor progression.

Adolescent↗
PubMed2006

Hypercortisolism in alcohol dependence and its relation to hippocampal volume loss.

OBJECTIVE: The effects of hypercortisolism on hippocampal volume have not been studied in heavy drinkers. Prior work suggested increased hypothalamic-pituitary-adrenal activity in relation to lowered total hippocampus volume (THV) in heavy-drinking alcohol-dependent (AD) subjects. The present study hypothesized the following: (1) that chronic heavy-drinking subjects would demonstrate significantly higher salivary cortisol concentrations than light-drinking control subjects and (2) that data from the whole sample group would present an inverse relationship between cortisol concentration and THV. METHOD: In carefully selected test and control subject groups matched for age, gender, and ethnicity, we measured salivary cortisol samples at waking, waking + 30 minutes, noon, and 4 PM on the day of magnetic resonance imaging of the brain. We next compared mean cortisol concentrations between groups and assessed the statistical association between cortisol concentration and hippocampus volume measures. RESULTS: Comparison of AD test subjects (n = 8) and non-AD control subjects (n = 8) found significantly higher cortisol concentrations at both morning sampling times (mean [SD] at waking: 0.49 [0.23] vs 0.24 [0.14] microg/dl, p = .012; at waking + 30 minutes: 0.57 [0.37] vs 0.28 [0.11] microg/dl, p = 0.043). Controlling for intracranial volume, there was a significant inverse correlation between waking cortisol concentration and THV (p = .007) in the total sample group (N = 16). However, when analyzed separately, only the control group maintained a strong, inverse association (p = .025). There was no association among the heavy drinking subjects. CONCLUSIONS: These early data in a small sample support the view that chronic heavy drinking results in high salivary cortisol concentrations. What remains unclear is whether hypercortisolism exerts a selectively injurious effect that results in observed hippocampus volume loss. Further research in larger groups using more frequent, monitored sampling must address the following: (1) whether this finding can be replicated and (2) if replicated, whether the lack of an association between low hippocampal volumes and high cortisol levels may indicate an extent of injury beyond which a normal association of the two may be lost.

Adult↗
PubMed2005

The negative association between total ghrelin levels, body mass and insulin secretion is lost in hypercortisolemic patients with Cushing's disease.

OBJECTIVE: Ghrelin exerts a wide spectrum of endocrine and non-endocrine actions. The stomach is the major source of circulating ghrelin levels that are negatively associated with body mass, insulin and glucose levels. The role of glucocorticoids in ghrelin secretion and action is still unclear. DESIGN: In 8 patients with Cushing's disease (CD, BMI 29.8 +/- 1.6 kg/m(2)), 7 normal (NS) and 6 obese subjects (OB, BMI 32.9 +/- 1.1 kg/m(2)) we studied: a) total ghrelin levels (every 15 min over 3 h) and their correlation with BMI, insulin, glucose, homeostatic model assessment (HOMA) index, ACTH and cortisol levels; b) GH, ACTH, cortisol, insulin and glucose responses to acylated ghrelin administration (1.0 mug/kg i.v. at 0 min). RESULTS: CD patients had BMI, insulin and glucose levels as well as HOMA index higher than those in NS (P < 0.05) but similar to those in OB. Despite this, total ghrelin levels in CD were similar to those in NS and both were higher (P < 0.05) than those in OB. No correlation was found among total ghrelin and BMI, insulin, glucose, ACTH and cortisol levels in CD patients. The GH responses to ghrelin in CD and OB were similar and both were lower (P < 0.002) than those in NS. In CD ghrelin induced exaggerated ACTH and cortisol responses clearly higher (P < 0.005) than in OB and NS. Ghrelin administration increased glucose in all groups; insulin levels showed slight decrease that was significant (P < 0.05) in OB only. CONCLUSIONS: Hypercortisolism in humans is associated with impaired ghrelin secretion and action. In fact, total ghrelin secretion in CD is not reduced despite increased BMI, insulin and glucose levels, while the GH and ACTH responses to acylated ghrelin are clearly reduced and enhanced, respectively.

Acylation↗
PubMed2006

Transsphenoidal pituitary surgery via the endoscopic technique: results in 35 consecutive patients with Cushing's disease.

OBJECTIVE AND DESIGN: The endoscopic technique has been recently introduced in the field of transsphenoidal pituitary surgery. This technique allows inspection of sellar, supra- and parasellar structures and removal of the tumor under direct visualization, is minimally traumatic and permits easier reoperations. This is the first report on the results of endoscopic surgery for patients with Cushing's disease. Our aim was to retrospectively analyze the results of pituitary surgery in 35 consecutive patients with Cushing's disease operated in our hospital after the introduction of the endoscopic technique (1998-2004). METHODS: Remission was defined as suppression of plasma cortisol (< or =50 nmol/L) after 1 mg dexamethasone overnight determined in the first 3 months after surgery and disappearance of clinical signs and symptoms of hypercortisolism. The patients were followed for an average of 27 months (range 4 to 81 months, median 20 months). RESULTS: Pituitary MRI showed a macroadenoma in 6 patients, a microadenoma in 17 patients and no adenoma in 12 patients. After the initial surgery 27 patients (77%) were in remission. None of the patients had a relapse during follow-up. In the remaining 8 patients hypercortisolemia persisted after surgery. Three of them had a second endoscopic pituitary surgery resulting in remission in two patients. In one patient a second endoscopic pituitary surgery will soon follow. The remaining four patients were treated with radiotherapy postoperatively. Two of them were at the time of data collection in remission. One patient from the remission group had a serious epistaxis and three patients had cerebrospinal fluid leakage, one requiring an external lumbar drain, shortly after surgery. No complications were recorded in the failure group. Postoperatively 34% of all patients required substitution with levothyroxine, 40% required substitution with glucocorticoids, 17% received estrogens or testosterone and 6% still required desmopressin. CONCLUSIONS: Endoscopic transsphenoidal pituitary surgery resulted in our series of patients with Cushings disease in an excellent postoperative remission rate. A randomized clinical trial, comparing endoscopic and conventional pituitary surgery in patients with Cushings disease, is needed to determine the pros and cons of both techniques.

ACTH-Secreting Pituitary Adenoma↗
PubMed2006

Partial visual recovery from radiation-induced optic neuropathy after hyperbaric oxygen therapy in a patient with Cushing disease.

Here we describe the case of a 41-year-old woman with a history of Cushing disease who had previously undergone unsuccessful neurosurgery, followed by stereotactic radiosurgery. More than 4 years after this treatment, she presented severe visual impairment, which started in the left eye and was documented by neuro-ophthalmic evaluation. Radiological assessment by contrast-enhanced magnetic resonance (MR) imaging initially suggested the diagnosis of glioma of the optic nerve and the patient started corticosteroid treatment (first with prednisone, 80 mg/day, followed by dexamethasone, 8 mg/day). Despite the therapy, vision in the left eye rapidly worsened until light was no longer perceptible; similar symptoms and signs also developed in the right eye, evolving to complete temporal hemianopsia. The clinical evidence was confirmed by the rapid progression of the MR picture, which showed homogeneous enhancement of the chiasm and optic nerves. On the basis of these findings, the original diagnosis of glioma was excluded, and radiation-induced optic neuropathy was diagnosed. As corticosteroids had proved inefficacious, hyperbaric oxygen (HBO) therapy was promptly instituted and vision steadily started to improve. This improvement was documented and confirmed by the progressive recovery of the visual field in the right eye and the changes in the sequential follow-up MR scanning. Optic neuropathy is an infrequent but dramatic complication of radiation therapy. Symptoms develop, on average, 12 months after treatment, and the onset may be acute and characterized by the progressive loss of vision in one or both eyes. HBO has already been used to treat this complication, but its efficacy is still controversial. Here, in addition to describing this particular case, which presented a significantly delayed radiation injury of the optic pathways, we provide a brief literature review and discuss some important points.

Adult↗
PubMed2006

Adipose tissue 11beta-hydroxysteroid dehydrogenase type 1 expression in obesity and Cushing's syndrome.

OBJECTIVE: To evaluate the expression of 11beta-hydrxysteroid dehydrogenase type 1 (11beta-HSD1) in omental adipose tissue of patients with Cushing's syndrome and simple obesity, compared with normal weight controls. DESIGN AND METHODS: We have performed a case-control study and studied omental adipose tissue from a total of 24 subjects (eight obese subjects, ten patients with Cushing's syndrome due to adrenal adenoma, and six normal weight controls). Body mass index, blood pressure, plasma glucose, plasma insulin, plasma cortisol, urinary free cortisol and post dexamethasone plasma cortisol were measured with standard methods. 11beta-HSD1 mRNA and protein expression were evaluated in real-time PCR and western blot analysis respectively. RESULTS: 11beta-HSD1 mRNA was 13-fold higher in obese subjects compared with controls (P=0.001). No differences were found between Cushing's patients and controls. Western blot analysis supported the mRNA expression results. CONCLUSIONS: Our data show the involvement of 11beta-HSD1 enzyme invisceral obesity, which is more evident in severely obese patients than in Cushing's syndrome patients. The lack of increase of 11beta-HSD1 expression in Cushing's syndrome could suggest downregulation of the enzyme as a result of long-term overstimulation.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2007

Gamma knife radiosurgery is a successful adjunctive treatment in Cushing's disease.

OBJECTIVE: Though transsphenoidal surgery remains the first-line treatment of Cushing's disease, recurrence occurs frequently. Conventional radiotherapy and anticortisolic drugs both have adverse effects. Stereotactic radiosurgery needs to be evaluated more precisely. The aim of this study was to determine long-term hormonal effects and tolerance of gamma knife (GK) radiosurgery in Cushing's disease. DESIGN: Forty patients with Cushing's disease treated by GK were prospectively studied over a decade, with a mean follow-up of 54.7 months. Eleven of them were treated with GK as a primary treatment. METHODS: Radiosurgery was performed at the Department of Functional Neurosurgery of Marseille, France, using the Leksell Gamma Unit B and C models. Median margin dose was 29.5 Gy. Patients were considered in remission if they had normalized 24-h free urinary cortisol and suppression of plasma cortisol after low-dose dexamethasone suppression test. RESULTS: Seventeen patients (42.5%) were in remission after a mean of 22 months (range 12-48 months). The two groups did not differ in terms of initial hormonal levels. Target volume was significantly higher in uncured than in remission group (909.8 vs 443 mm(3), P = 0.038). We found a significant difference between patients who were on or off anticortisolic drugs at the time of GK (20 vs 48% patients in remission respectively, P = 0.02). CONCLUSION: With 42% of patients in remission after a median follow-up of 54 months, GK stereotactic radiosurgery, especially as an adjunctive treatment to surgery, may represent an alternative to other therapeutic options in view of their adverse effects.

Adolescent↗
PubMed2005

Surgical management of adrenocorticotropic hormone-secreting macroadenomas: outcome and challenges in patients with Cushing's disease or Nelson's syndrome.

OBJECT: Adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenomas are an uncommon cause of Cushing's disease (CD) and, subsequently, Nelson's syndrome (NS). They have been associated with low postoperative remission rates. The outcome of modern surgical treatment is unclear and thus was assessed in a series of 43 patients, with the goal of improving therapeutic results in patients with ACTH-secreting macroadenomas. METHODS: Thirty-seven patients presented with CD and six with NS. They represented 15% of the patients surgically treated at the authors' institution for ACTH-secreting adenomas. The median patient age was 38 years (range 14-71 years), and the mean duration of follow up was 37 months (range 1-108 months). Remission occurred in 25 (67.6%) of 37 patients with CD, whereas the disease persisted in 12 (32.4%) of 37 patients. After an initial remission, three (12%) of 25 patients demonstrated signs and symptoms indicative of disease recurrence. Among patients with NS, only one (16.6%) displayed remission. Invasion of the dura mater by tumor was histologically demonstrated in 10 patients with CD and in two patients with NS. CONCLUSIONS: Comprehensive management of CD caused by ACTH-secreting macroadenomas through the appropriate use of combination therapy, including surgery, radiotherapy, radiosurgery, and adrenalectomy, can lead to outcomes similar to those for microadenomas. Disease recurrence and persistence rates are higher, often because of the invasiveness associated with macroadenomas. Remission of NS-associated macroadenomas is difficult to achieve. Strategies for the characterization and treatment of invasive macroadenomas are needed.

ACTH-Secreting Pituitary Adenoma↗
PubMed2005

Single-center experience with pediatric Cushing's disease.

OBJECT: Despite ongoing advances in surgical and radiotherapeutic techniques, pediatric Cushing's disease remains a diagnostic and therapeutic challenge. The authors report on the results of a single-center retrospective review of 33 pediatric patients with Cushing's disease, providing details with respect to clinical presentation, diagnostic evaluation, therapeutic course, complications, and outcomes. METHODS: There were 17 female and 16 male patients whose mean age was 13 years (range 5-19 years) in whom a diagnosis of Cushing's disease was based on clinical and biochemical criteria. Typical symptoms included weight gain (91%), prepubertal growth delay (83%), round facies (61%), hirsutism (58%), headache (45%), abdominal striae (42%), acne (33%), amenorrhea (24%), and hypertension (24%). In 67% of the cases, preoperative magnetic resonance images revealed a pituitary lesion and in 82% of the cases the imaging studies effectively predicted lateralization. Inferior petrosal sinus sampling was performed in seven patients (21%), and in all of these cases lateralization was 100% reliable. Fifty-five percent underwent selective adenomectomies and 45% underwent subtotal hypophysectomies. Complications included one case of diabetes insipidus, one of persistent hypocortisolemia necessitating prolonged glucocorticoid replacement therapy, and one minor vascular injury that did not necessitate postoperative management modification or cause sequelae. There were no surgery-related deaths and no cases of postoperative cerebrospinal fluid leakage or meningitis. During a mean follow-up period of 44 months, clinical remission was ultimately achieved in 91% of patients: 76% after transsphenoidal surgery alone and an additional 15% after adjuvant radiosurgery and/or adrenalectomy following surgical failure. Three patients (12%) experienced disease recurrence and underwent a second surgical procedure at 18, 81, and 92 months, respectively; based on clinical and biochemical criteria a second remission was achieved in all. Three patients (9%) remain with persistent disease. CONCLUSIONS: Pediatric Cushing's disease is a rare condition, often requiring a multidisciplinary diagnostic and a multimodal therapeutic approach for successful long-term remission.

Adolescent↗