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At least 127 records · Page 7Linked to original sources
PubMed2005

Undetectable inferior petrosal sinus levels of PTH-related peptide (PTHrP) in patients with ACTH-dependent Cushing's disease.

PTH-related peptide (PTHrP), a member of the PTH family, is widely expressed in foetal and adult tissues, and it has been found in benign and malignant tumors, including GH and PRL-secreting adenomas. Conflicting data are reported in literature on serum PTHrP concentrations in patients with Cushing's disease. The aim of the present study was to further evaluate peripheral and inferior petrosal sinus (IPS) serum PTHrP concentrations before and after CRH, in a group of consecutive patients with ACTH-dependent Cushing's disease. Nine patients with active ACTH-dependent Cushing's disease (8 women and 1 man, age +/- SD 41 +/- 13 yr) were submitted to peripheral and IPS sampling under fluoroscopic control before and after iv administration of CRH. All patients were subsequently submitted to transsphenoidal surgery and an ACTH-secreting microadenoma was found in all cases. In all patients, serum IPS and peripheral ACTH measurement were in keeping with the diagnosis of ACTH-dependent Cushing's disease. Serum PTHrP concentrations before and after CRH stimulation were below the sensitivity limit of the assay in all samples, and no gradient between IPS and peripheral sampling was observed. Our data, combined with others reported in literature, indicate that PTHrP release by ACTH-secreting tumors is not a common occurrence. Therefore, we conclude that IPS and peripheral PTHrP are of little clinical usefulness.

Adrenocorticotropic Hormone↗
PubMed2006

Linear growth and body mass index in pediatric patients with Cushing's disease or simple obesity.

BACKGROUND: Increasing prevalence of childhood obesity has resulted in an accelerating rate of referrals of overweight patients to pediatric clinics for exclusion of endocrine or metabolic etiologies. The exclusion of Cushing's disease (CD) requires complex and potentially invasive investigations. OBJECTIVE: To evaluate the sensitivity of accurate measurements of height, weight and body mass index (BMI) in discriminating between simple obesity and CD. METHODS AND PATIENTS: Height, weight and BMI were measured at diagnosis in 25 patients with CD; 14 males, 11 females, mean age 12.9 yr (6.4-17.8) and 41 patients with simple obesity (SO), defined as BMI >2.0 SD; 20 males, 21 females, mean age 9.4 yr (3.5-15.6). RESULTS: Mean (+/-SE) BMI SDS in the CD patients was 2.41+/-0.5 and in the SO patients 3.71+/-1.3. Height SDS in the CD patients was -1.88+/-0.24 and in the SO patients 1.18+/-0.19 (p<0.05). The mean (+/-SE) BMI SDS to height SDS ratio was significantly decreased in the CD compared with the SO patients; -1.81+/-0.54 vs +0.90+/-1.17 (p<0.0001). CONCLUSIONS: Simple, accurate measurement of height and BMI SDS values provides a quick, and sensitive diagnostic discriminator in pediatric patients with CD or SO, thus potentially avoiding complex investigations.

Adolescent↗
PubMed2006

A patient with recurrent hypercortisolism after removal of an ACTH-secreting pituitary adenoma due to an adrenal macronodule.

A 41-yr-old female was referred for signs and symptoms of Cushing's syndrome. Cortisol was not suppressed by 1 mg dexamethasone (0.41 micromol/l). Midnight cortisol and ACTH were 0.44 micromol/l and 18 pmol/l, respectively. Urinary cortisol excretion was 250 nmol/24 h (normal between 30 and 150 nmol/24 h). A magnetic resonance imaging (MRI) revealed a pituitary lesion of 7 mm. ACTH and cortisol levels were unaltered by administration of human CRH and high-dose dexamethasone. Inferior sinus petrosus sampling showed CRH-stimulated ACTH levels of 128.4 (left sinus) vs a peripheral level of 19.2 pmol/l, indicating Cushing's disease. After 4 months of pre-treatment with metyrapone and dexamethasone, endoscopic transsphenoidal resection of an ACTH-positive pituitary adenoma was performed. ACTH levels decreased to 2.6 pmol/l and fasting cortisol was 0.35 micromol/l. Despite clinical regression of Cushing's syndrome and normalization of urinary cortisol, cortisol was not suppressed by 1 mg dexamethasone (0.30 micromol/l). Ten months post-operatively, signs and symptoms of Cushing's syndrome reoccurred. A high dose dexamethasone test according to Liddle resulted in undetectable ACTH, but no suppression of cortisol levels, pointing towards adrenal-dependent Cushing's syndrome. Computed tomography (CT)-scanning showed a left-sided adrenal macronodule. Laparoscopic left adrenalectomy revealed a cortical macronodule (3.5 cm) surrounded by micronodular hyperplasia. Fasting cortisol had decreased to 0.02 micromol/l. Glucocorticoid suppletion was started and tapered over 12 months. Symptoms and signs of hypercortisolism gradually disappeared. This case illustrates, that longstanding ACTH stimulation by a pituitary adenoma can induce unilateral macronodular adrenal hyperplasia with autonomous cortisol production.

ACTH-Secreting Pituitary Adenoma↗
PubMed2006

A case of ACTH-independent bilateral macronodular adrenal hyperplasia and severe congestive heart failure.

Cortisol secretion in ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH) can be regulated by aberrant adrenal receptors. We describe a patient with Cushing's syndrome (CS) due to AIMAH and concomitant Class IV congestive heart failure (CHF). Clinical testing for the presence of aberrant receptors revealed a pronounced serum cortisol (257%) and aldosterone response (212%) to the administration of ACTH and a partial serum cortisol (35%) and aldosterone (106%) response to upright posture. This suggested the possible presence of aberrant hormone receptors for ACTH [melanocortin 2 receptor (MC2-R)], vasopressin, catecholamines or angiotensin II (AT-II) on the patient's adrenal glands. Adrenal tissue from the patient demonstrated an eight-fold increased expression of MC2-R compared to normal adrenal tissue. This increased expression was consistent with the increase in cortisol and aldosterone seen in response to exogenous ACTH. We propose that the severe CHF resulted in activation of the renin-angiotensin system, with an increased production of AT-II. The elevated circulating levels of AT-II may have led to increased expression of MC2-R on the patient's adrenal glands and increased responsiveness to ACTH. This unusual case of CS may elucidate a heretofore unknown mechanism for the development of AIMAH.

Adrenal Glands↗
PubMed2007

Posterior retroperitoneoscopic adrenalectomy: a comparison between the initial experience in the invention phase and introductory phase of the new surgical technique.

BACKGROUND: Today, the posterior retroperitoneoscopic technique has become a standard procedure in adrenal surgery. The procedure allows direct access to the adrenal glands, but it seems to be difficult because of the uncommon anatomic view. This study compares the learning period of the new procedure of "posterior retroperitoneoscopic adrenalectomy" in the primary invention phase and the secondary introductory phase in a different hospital 10 years later. MATERIALS AND METHODS: The analysis included 100 posterior retroperitoneoscopic adrenalectomies (PRA) and involved 50 procedures in each center. Group A consisted of 44 patients (14 males, 30 females; age: 48.7 +/- 14.5 years) undergoing surgery between 07/1994 and 8/1996 (24 right, 26 left; 8 Cushing adenomas, 14 Conn adenomas, 11 pheochromocytomas, 7 nonfunctioning adrenocortical adenomas, 10 ACTH-dependent adrenal hyperplasias). Group B consisted of 50 patients (12 males, 38 females; mean age 59.3 +/- 10.7 years) operated between 01/2004 and 01/2006 (28 right, 22 left tumors; 5 Cushing adenomas, 12 Conn adenomas, 4 pheochromocytomas, 29 nonfunctioning adrenocortical adenomas). All PRAs were performed with the patient in the prone position with 3-4 trocars placed caudally in the region of the 11th and 12th ribs. In group A, the surgical team developed the technique of PRA themselves. Before their first PRA, the surgical team of group B was introduced to the technique by the group A surgeons and afterwards were supervised continuously. RESULTS: No serious intraoperative or postoperative complication occurred in either group. Group A experienced 7 conversions to open surgery, whereas group B had one conversion and one early reoperation due to bleeding (P = 0.03; chi(2)-test). The mean operative time was 117 +/- 41 minutes versus 83 +/- 35 minutes (group A and B respectively; P < 0.001; t-test). Estimated blood loss was similar in the two groups (47.2 +/- 46.2 ml versus 54 +/- 16.3 ml, group A versus B, respectively; P = 0.36; t-test). CONCLUSIONS: The study demonstrates the feasibility, safety, and reproducibility of the new surgical method of PRA both when it is employed in the early phase of invention, as well as when performed by surgeon-learners. After comprehensive training, the operative time and conversion rate are dramatically reduced, allowing for a short learning period.

Adrenal Cortex Neoplasms↗
PubMed2006

Atypical carcinoid tumor of the thymus with ectopic ACTH production developed during the course of etanercept treatment--case report.

Ever since the introduction of anti-tumor necrosis factor (TNF) agents, concerns have been raised regarding their potential for developing malignancy. We report the development of thymic atypical carcinoid tumor 9 months after the initiation of etanercept therapy in a patient having refractory spondylarthritis. This case indicates the need for following large cohorts of patients receiving anti-TNF agents to address the long-term effect of these agents on malignancies.

Adult↗
PubMed2004

Recurrence of Cushing's disease preceded by the reappearance of ACTH and cortisol responses to desmopressin test.

At present no single test is considered of absolute value in identifying patients successfully operated for Cushing's disease who are at risk for recurrence. The present report describes the first two patients in whom ACTH/cortisol abnormal responses to desmopressin disappeared after cure and then clearly reappeared during long-term follow-up several months before the clinical and hormonal features of hypercortisolism became manifest. The case histories of 2 young women are reported. The diagnosis of Cushing's disease was made on the basis of clinical features and standard hormonal criteria. Both patients, showing abnormal ACTH/cortisol rises after desmopressin test, underwent pituitary adenomectomy by transsphenoidal surgery and after operation plasma ACTH and serum cortisol levels were 0.2 and 0.4 pmol/l and 56 and 32 nmol/l, respectively. During the follow-up both patients underwent desmopressin (10 microg iv), ovine CRH (1 microg/kg iv) and 1 mg dexamethasone tests at 1, 6, 12, 24 months after surgery. In these two cases the ACTH/cortisol response to desmopressin normalized following pituitary adenomectomy, concomitantly with the normalization of all the other clinical and hormonal parameters. Subsequently abnormal rises after the synthetic AVP analogue administration appeared: paradoxical ACTH/cortisol increments after desmopressin occurred 24 and 6 months before any other hormonal or clinical sign of recurrence of hypercortisolism. As desmopressin may be able to stimulate ACTH/cortisol release in Cushing's disease, but not in normal subjects, we suggest that it can have a role in early identifying successfully operated Cushing's patients at risk for recurrence.

Adolescent↗
PubMed2006

Cushing's disease.

Cushing's disease, i.e., pituitary ACTH-secreting adenoma causing excess glucocorticoid secretion, is a rare disease with significant mortality and morbidity. Timely diagnosis and appropriate treatment can alter the course of the disease and are therefore mandatory. First step of the diagnostic work-up is the endogenous glucocorticoid excess by measurement of urinary free cortisol, cortisol circadian rhythmicity or suppression by low doses of dexamethasone. In patients with equivocal results, second line tests, such as the dexamethasone-suppressed CRH test and desmopressin stimulation, usually enable the diagnosis to be confirmed. Measurement of plasma ACTH then allows the distinction between ACTH-dependent (e.g., pituitary or extrapituitary neuroendocrine tumors) and ACTH-independent causes (e.g., adrenal tumors). The last step in the diagnostic algorithm is often the most fraught with problems as the distinction between Cushing's disease and ectopic ACTH secretion relies on judicious interpretation of several diagnostic procedures. Positive responses to stimulation with CRH and inhibition by high doses of dexamethasone, if concurrent, enable a pituitary origin to be established whereas conflicting results call for inferior petrosal sinus sampling, the latter to be performed in experienced centres only. Visualisation of the tumor at pituitary imaging is helpful but not required for the diagnosis, as microadenomas often remain undectected by MRI and/or CT scan and, on the other hand, visualisation of a non-secreting incidentaloma may be misleading. Surgical removal of the pituitary tumor is the optimal treatment choice and should be attempted in every patient. Surgical failures as well as relapses can be treated by radiotherapy, medical therapy or, if necessary, bilateral adrenalectomy. Finally, patients cured of Cushing's disease require long-term monitoring given the risk of relapse and clinical burden of associated ailments.

ACTH Syndrome, Ectopic↗
PubMed2006

Specificity assessment of immunoassay kits for determination of urinary free cortisol concentrations.

BACKGROUND: In immunoassay kits for determination of urinary free cortisol (UFC) concentrations, the results vary markedly from kit to kit, so we compared in this study the reaction specificity among 4 commercially available immunoassay kits to determine the applicability of these assays in routine determination of UFC concentrations. METHOD: Using 4 commercially available kits, cross-reaction was investigated. In addition, urine samples were fractionated by HPLC to investigate endogenous immunoreactive cortisol responses. HPLC fractions were subjected to gas chromatography-mass spectrometry (GCMS) to identify substances causing inter-kit assay discrepancies. RESULTS: Among the 4 kits, cortisol Kit "TFB" (Immunotech; IOT-RIA method) showed the lowest cross-reaction (2.5%) for prednisolone. Furthermore, on HPLC, 87.8% of the reaction of the entire fraction was seen in the fractions corresponding to the elution position of standard cortisol with the IOT-RIA method; this was the highest percentage among the 4 kits. GCMS revealed that the substance that showed a cross-reaction with the other 3 kits was 5alpha-tetrahydrocortisol (5alpha-THF) glucuronide. CONCLUSIONS: The IOT-RIA method was found to be the most specific for UFC. The other 3 commercially available kits showed cross-reaction with a conjugate of 5alpha-THF, found to be one of the causes of inter-kit assay discrepancies.

Adult↗
PubMed2005

Adrenal corticosteroid biosynthesis, metabolism, and action.

Adrenal corticosteroids are essential for life, and an appreciation of the mechanisms underpinning their synthesis, secretion, and mode of action in normal physiology is essential if the physician is to diagnose and treat patients who have Cushing's syndromes effectively. In each case, there have been clinically significant advances in the knowledge base over recent years, notably in the understanding of steroidogenesis, cortisol action, and metabolism. This article describes corticosteroid biosynthesis, metabolism, and action.

Adrenal Cortex↗
PubMed2005

The metabolic syndrome and cardiovascular risk in Cushing's syndrome.

Cushing's syndrome (CS) is characterized by a series of systemic complications that increase cardiovascular risk and cause severe atherosclerotic damage that develops in parallel with an acquired metabolic syndrome. Short-term remission from hypercortisolism improves metabolic and vascular damages, but long-term remission from CS seems to be associated with similar or worse metabolic and vascular damage, probably because of persistent abdominal obesity or insulin resistance years after normalization of cortisol secretion. Study results suggest that an increased cardiovascular risk also may persist in patients who undergo treatment with exogenous glucocorticoids after therapy withdrawal. Considering the many patients subjected to corticosteroid treatment, this could be of great clinical relevance and should be investigated thoroughly.

Cardiovascular Diseases↗
PubMed2005

Osteoporosis associated with excess glucocorticoids.

Excess glucocorticoids, whether endogenous or exogenous, can cause osteoporosis and fractures. Even low doses of oral glucocorticoids and mild endogenous hypercortisolism may be associated with bone loss. Patients treated with glucocorticoids, however, often are not evaluated and treated for this problem. Patients on chronic glucocorticoids or initiating these drugs should have their bone density measured and appropriate laboratory studies. They should be treated with adequate calcium and vitamin D, and antiresorptive therapy (particularly bisphosphonates) should be considered.

Glucocorticoids↗
PubMed2005

Glucocorticoid resistance and hypersensitivity.

This article emphasizes the disorders caused by mutations and polymorphisms of the alpha form of the glucocorticoid receptor. These disorders usually present with increased circulating cortisol concentrations and must be distinguished from Cushing's syndrome, because the therapies are markedly different. The other disorders present with clinical features limited to a specific organ system. Although they illustrate important physiologic and pathophysiologic principles, they usually are not confused with Cushing's syndrome.

Adrenocortical Hyperfunction↗
PubMed2026

Cushing's disease and autoimmune thyroid disorders in women: Impacts on fertility, pregnancy, and menopause.

Cushing's disease (CD) and autoimmune thyroid diseases (AITDs) are two distinct but interconnected endocrinopathies affecting predominantly women. A primary cause of CD is excess adrenocorticotropic hormone (ACTH) secretion, which leads to hypercortisolism and profound hormonal and immune changes. As with AITDs, Hashimoto's thyroiditis and Graves' disease are caused by a loss of immune tolerance and frequently coexist with female reproductive dysfunction. Emerging evidence suggests that chronic hypercortisolism in CD suppresses immunity as well as alters hypothalamic-pituitary-thyroid (HPT) axis activity, which may mask or exacerbate thyroid autoimmunity after disease remission. Coexisting CD and AITD has significant effects on women's reproductive health, pregnancy outcomes, and menopausal transitions, as thyroid and adrenal hormones play a crucial role in regulating ovulatory cycles, placental development, bone formation, and cardiovascular health. In this review, shared pathophysiological pathways are explored, clinical and therapeutic challenges are highlighted, and integrated management strategies are discussed. To improve early diagnosis, tailor treatment approaches, and guide future endocrine research, it is essential to understand the compounded risks of dual endocrinopathy.

Humans↗
PubMed2006

Open versus laparoscopic simultaneous bilateral adrenalectomy.

OBJECTIVES: To compare our experience with synchronous bilateral adrenalectomy using laparoscopic and open techniques. Laparoscopic adrenalectomy has become the reference standard for management of benign unilateral adrenal pathologic findings. METHODS: This was a nonrandomized retrospective chart review of 12 known patients who underwent simultaneous bilateral adrenalectomy, comparing five laparoscopic and seven open procedures. One urologic surgeon performed all laparoscopic cases, and one general surgeon performed all open procedures. RESULTS: All patients had Cushing's disease or syndrome. The average patient age was 47.4 years (range 24 to 71) and 42.4 years (range 19 to 70), with an average body mass index of 38.2 kg/m2 and 36.0 kg/m2 for the laparoscopic and open groups, respectively. The operating time was on average 60 minutes longer for the laparoscopic group. No open conversions were necessary. The median blood loss (100 versus 500 mL, P < 0.01) and hematocrit drop (8.5% versus 12.6%, P = 0.05) were lower for the laparoscopic group. The transfusion rates and hospital stay trended lower in the laparoscopic group (20% versus 57% and 3 versus 8.5 days, respectively). Specimen weights for both the right and left glands trended larger for the laparoscopic group. The complication rates were similar between groups at 60% for the laparoscopic versus 71% for the open groups. CONCLUSIONS: Simultaneous laparoscopic bilateral adrenalectomy is safe and effective. Compared with the open approach, it resulted in decreased blood loss, lower transfusion rate, and a trend toward a shorter hospital stay, although the operating time was longer. The laparoscopic approach should be the treatment of choice for bilateral adrenalectomy.

Adrenalectomy↗
PubMed2006

[Use of cabergoline in persisting Cushing's disease].

Cabergoline is a dopaminergic agonist with demonstrated efficiency of for the treatment of prolactin-secreting pituitary tumors. It has also been reported effective for patients with hypercortisolism uncontrolled by conventional therapies. We describe the use of cabergoline in three patients with Cushing's disease, one of them presenting a silent ACTH-secreting pituitary tumor. Those patients underwent surgery and only one has been treated with radiation therapy. However persisting hypercortisolism motivated the use of cabergoline. We describe a decrease or a normalization in hypercortisolism; for one of the subjects, tumor growth seemed to be stopped. While cabergoline can induce a suppression of cortisol secretion or a corticotroph tumor shrinkage, the sites of action remain unclear.

Adrenocortical Hyperfunction↗