Abnormal linear growth in paediatric adrenal diseases: Pathogenesis, prevalence and management.

Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.

Adrenal disorders: Is there Any role for vitamin D?

An emerging branch of research is examining the linkage between Vitamin D and nonskeletal disorders, including endocrine diseases. In this regard, a still little studied aspect concerns the involvement of vitamin D in adrenal gland disorders. Adrenal gland disorders, which might be theoretically affected by vitamin D unbalance, include adrenal insufficiency, Cushing's syndrome, adrenocortical tumors and hyperaldosteronism. In this review, we provide an updated document, which tries to collect and discuss the limited evidence to be found in the literature about the relationship between vitamin D and adrenal disorders. We conclude that there is insufficient evidence proving a causal relationship between vitamin D levels and adrenal disorders. Evidence coming from cross-sectional clinical studies can hardly clarify what comes first between vitamin D unbalance and adrenal disease. On the other hand, longitudinal studies monitoring the levels of vitamin D in patients with adrenal disorders or, conversely, the possible development of adrenal pathologies in subjects affected by impaired vitamin D levels would be able to elucidate this still unclear issue.

Prevalence of hormonal and endocrine dysfunction in patients with lichen planopilaris (LPP): A retrospective data analysis of 168 patients.

BACKGROUND: Studies on the pathophysiology and comorbidities associated with lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are limited. OBJECTIVE: The purpose of this study was to determine the prevalence of androgen excess in the postmenopausal LPP population, in relation to demographics and comorbidities. METHODS: A retrospective data analysis of 413 patients with LPP, FFA, and LPP/FFA seen in the Department of Dermatology at the Cleveland Clinic Foundation in Ohio between 2005 and 2015 was conducted. Of this cohort, 168 patients met the inclusion criteria. RESULTS: Androgen excess was identified in 31.5% (n = 53) of the 168 patients with LPP and all subtypes (P < .001). Androgen deficiency was identified in 32.1% (n = 17) of the 53 patients with FFA (P < .001). The androgen excess group was significantly more likely to present with hirsutism, seborrheic dermatitis, polycystic ovary syndrome, ovarian cysts, or a combination of these (P < .001). LIMITATIONS: This study was limited by being retrospective. CONCLUSION: Our study demonstrated that LPP is associated with androgen excess, and FFA is associated with androgen deficiency.

CT screening for lung cancer: Frequency of enlarged adrenal glands identified in baseline and annual repeat rounds.

OBJECTIVES: To determine the frequency of adrenal enlargement of participants in a CT-screening program for lung cancer and demonstrate the progression during follow-up, separately for baseline and annual repeat rounds. MATERIALS AND METHODS: HIPAA-compliant informed consent was obtained in 4,776 participants. The adrenal gland was defined as enlarged if it measured ≥6 mm at its largest diameter. Logistic regression analyses were performed. RESULTS: At baseline, 202 (4 %) of 4,776 participants had adrenal enlargement. Significant factors were age (OR = 1.4, 95 % CI: 1.2-1.7) and current smoker (OR = 1.8, 95 % CI: 1.3-2.4). Follow-up 7-18 months after baseline for 133 cases with adrenal enlargement <40 mm showed it decreased or was stable in 85 (64 %), and increased by <10 mm in 48 (36 %). Five (0.04 %) cases of adrenal enlargement were newly identified, none increased beyond 40 mm on follow-up. Adrenal enlargement was a significant predictor of a subsequent diagnosis of lung cancer (OR = 2.0, 95 % CI: 1.2-3.4). CONCLUSION: Participants with adrenal enlargement <40 mm identified at baseline and on repeat screening could be reasonably assessed on subsequent annual screening. Adrenal enlargement increased with increasing pack-years of smoking. Adrenal enlargement was an independent predictor of a subsequent diagnosis of lung cancer. KEY POINTS: • Adrenal enlargement was seen in 4 % of participants at baseline screening. • Age and currently smoking were significantly associated with adrenal enlargement. • 0.04 % of participants were newly identified with adrenal enlargement. • Annual follow-up for adrenal enlargement <40 mm was appropriate. • Adrenal enlargement was an independent predictor of a diagnosis of lung cancer.

[Precocious puberty in boys]. / Przedwczesne dojrzewanie plciowe u chlopców.

Precocious puberty in boys is defined as the onset of puberty before the age of 9 years. It is divided into two categories: central precocious puberty, characterized by the premature activation of the hypothalamic-pituitary-gonadal axis, and peripheral precocious puberty presents when premature sexual development is dependent on steroid production regardless of gonadotropin secretion. Although precocious puberty occurs more frequently in girls, in the case of boys it is more often associated with identifiable organic disorders of the central nervous system, adrenal glands or testes. The diagnosis should include detailed anamnesis and clinical examination, measurement of pituitary and sex hormones, assessment of bone age, and imaging of the hypothalamus, pituitary gland, adrenal glands and testes. Indications for treatment are based on the type of precocious puberty and its progression rate, advancement of bone age, predicted adult height and psychological evaluation. The purpose of this article was to discuss the etiopathogenesis of precocious puberty in boys and to provide the approach to its diagnosis, differentiation and treatment.

Outcomes after laparoscopic adrenalectomy.

BACKGROUND: Laparoscopic adrenalectomy (LA) has become the standard of care for many conditions requiring removal of the adrenal gland. Previous studies on outcomes after LA have had limitations. This report describes the 30-day morbidity and mortality rates after LA and analyzes factors affecting operative time, hospital length of stay (LOS), and postoperative morbidity. METHODS: Patients undergoing LA in 2007 and 2008 were identified from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP). Using multivariate analysis of variance (ANOVA) and logistic regression, 52 demographic/comorbidity variables were analyzed to ascertain factors affecting operative time, LOS, and morbidity. RESULTS: The mean age of the 988 patients was 53.5 ± 13.7 years, and 60% of the patients were women. The mean body mass index (BMI) of the patients was 31.8 ± 7.9 kg/m(2). The 30-day morbidity and mortality rates were 6.8% and 0.5%, respectively. The mean and median operative times were 146.7 ± 66.8 min and 134 min, respectively. The mean and median hospital stays were 2.6 ± 3.1 days and 2 days, respectively. Compared with independent status, totally dependent functional status was associated with a 9.5-day increase in LOS (P = 0.0006) and an increased risk for postoperative morbidity (odds ratio [OR], 14.7; 95% confidence interval [CI], 2.4-91.9; P < 0.0001). Peripheral vascular disease (OR, 7.3; 95% CI, 1.7-31.7; P = 0.008) also was associated with increased 30-day morbidity. Neurologic and respiratory comorbidities were associated with increased LOS (P < 0.05). American Society of Anesthesiology (ASA) class 4 patients had a longer operative time than ASA class 1 patients (P = 0.002). CONCLUSIONS: The morbidity and mortality rates after LA are low. Dependent functional status and peripheral vascular disease predispose to postoperative morbidity. Dependent status, higher ASA class, and respiratory and neurologic comorbidities are associated with longer operative time and LOS.

Characterisation of the onset and severity of adrenal and thyroid dysfunction associated with CTLA4-related hypophysitis.

CONTEXT: The use of the CTLA4 inhibitor, ipilimumab, has proven efficacious in the treatment of melanoma, renal carcinoma and non-small cell lung cancer; however, it is associated with frequent immune-related adverse events (irAE). Ipilimumab-induced hypophysitis (IIH) is a well-recognised and not infrequent endocrine irAE. OBJECTIVE: To investigate the timing of onset and severity of adrenal and thyroid hormone dysfunction around the development of IIH in patients treated for melanoma. DESIGN: Aretrospective review of hormone levels in consecutive adult patients treated with ipilimumab (3 mg/kg) for advanced melanoma as monotherapy or in combination with a PD-1 inhibitor. RESULTS: Of 189 patients, 24 (13%; 13 males; 60.5 ± 12.2 years) presented with IIH at a median of 16.1 (range: 6.7-160) weeks after commencing treatment, occurring in 14 (58%) after the fourth infusion. At the presentation of IIH, corticotroph deficiency was characterised by an acute and severe decrease in cortisol levels to ≤83 nmol/L (≤3 µg/dL) in all patients, often only days after a previously recorded normal cortisol level. Free thyroxine (fT4) levels were observed to decline from 12 weeks prior to the onset of cortisol insufficiency, with the recovery of thyroid hormone levels by 12 weeks after the presentation of IIH. A median fall in fT4 level of 20% was observed at a median of 3 weeks (IQR: 1.5-6 weeks) prior to the diagnosis of IIH. CONCLUSION: IIH is characterised by an acute severe decline in cortisol levels to ≤83 nmol/L at presentation. A fall in fT4 can herald the development of ACTH deficiency and can be a valuable early indicator of IIH.

[Spontaneous adrenal hematomas. Retrospective analysis of 20 cases from a tertiary center]. / Hématomes surrénaliens non traumatiques : série rétrospective de 20 cas.

INTRODUCTION: Spontaneous adrenal hemorrhages (AH) are a rare condition with no consensus about their management. METHODS: Patients were identified using the Medicalization of the Information System Program database, imaging software and a call for observations to internists, intensivists and obsetricians working at our institution. Adult patients whose medical records were complete and whose diagnosis was confirmed by medical imaging were included. RESULTS: From 2000 to 2007, 20 patients were identified, including 15 were women. The clinical onset of AH was non-specific. In five cases, AH occurred during pregnancy; four of them were unilateral and right sided. The etiology of the other fifteen (bilateral adrenal hemorrhage in 11) were as follows: antiphospholipid syndrome (n=8), heparin-induced thrombocytopenia (n=4), essential thrombocythemia (n=3), spontaneous AH due to oral anticoagulants (n=1), complication of a surgical act (n=3), and sepsis (n=3). In seven cases, two causes were concomitant. The diagnosis of AH was often confirmed by abdominal CT. An anticoagulant treatment was initiated in 16 cases. Ten of the eleven patients presenting with bilateral adrenal hematomas were treated using a long-term substitute opotherapy. One patient died because of a catastrophic antiphospholipid syndrome. CONCLUSION: The clinical onset of HS is heterogeneous and non-specific. The confirmatory diagnosis is often based on abdominal CT. The search for an underlying acquired thrombophilia is essential and we found in this study etiological data comparable to the main series in the literature. Adrenal insufficiency is most of the time definitive in cases of bilateral involvement.

Adrenal hematoma after nephrectomy.

OBJECTIVE: The objective of our study was to retrospectively define the incidence of adrenal hematoma on CT or MRI after nephrectomy. MATERIALS AND METHODS: Between January 2008 and June 2009, 465 patients underwent nephrectomy at our institution. Of these, patients without both preoperative and postoperative abdominal CT or MR studies within 6 months of surgery (n = 83) and those with documented adrenalectomy at the time of radical nephrectomy (n = 33) were excluded. Thus, 349 patients (292 male, 57 female; mean age, 60.2 years; range, 2-88 years) were included in the study. Preoperative and postoperative CT or MR studies were reviewed by two radiologists in consensus for the presence or absence of adrenal hematoma. Diagnosis of adrenal hematoma was made by imaging findings and follow-up. The incidence of adrenal hematoma was calculated with a 95% CI. RESULTS: Of the 349 patients (partial nephrectomy, n = 232; radical nephrectomy, n = 117), 19 patients developed adrenal hematoma after nephrectomy (partial nephrectomy, n = 12; radical nephrectomy, n = 7) with an incidence of 5.4% (95% CI, 3.1-7.8%). All adrenal hematomas were located on the side of nephrectomy (right adrenal gland, n = 8; left adrenal gland, n = 11). In nine patients, the adrenal hematoma appeared as a round or oval lesion on postoperative imaging with a mean size of 2.6 cm (range, 1.5-4.0 cm). In 10 patients, the adrenal hematoma appeared as diffuse enlargement of the adrenal gland on postoperative imaging with a mean thickness of 1.3 cm (range, 0.6-1.8 cm). CONCLUSION: An adrenal hematoma was identified in 5.4% of patients on CT or MRI after nephrectomy. A new round or oval adrenal mass after nephrectomy should be differentiated from a metastasis.

Growth hormone deficiency due to traumatic brain injury in a patient with X-linked congenital adrenal hypoplasia.

X-linked adrenal hypoplasia congenita (AHC) is characterized by primary adrenal insufficiency and is frequently associated with hypogonadotropic hypogonadism (HH). The production of other pituitary hormones (adrenocorticotropic hormone [ACTH], growth hormone [GH], thyroid-stimulating hormone [TSH], and prolactin [PRL]) is usually normal. Mutations of the DAX-1 gene have been reported in patients with AHC and HH. We present a 13-year-old male patient with AHC caused by a nonsense mutation in the DAX-1 gene who developed GH deficiency following head trauma. He showed signs of adrenal insufficiency at the age of 23 months, and glucocorticoid and mineralocorticoid treatment was started. His parents reported head trauma due to a traffic accident at the age of 21 months. Adrenal computed tomography revealed hypoplasia of the left and agenesis of the right adrenal gland. Decreased growth rate was noted at the age of 12.5 years while receiving hydrocortisone 15 mg/m2/day. His height was 139.9 cm (-1.46 SD), body weight was 54.9 kg, pubic hair was Tanner stage 1, and testis size was 3 ml. His bone age was 7 years. His gonadotropin (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and testosterone levels were prepubertal. The evaluation of GH/insulin-like growth factor-1 (IGF-1) secretion at the age of 13 years revealed GH deficiency. Pituitary magnetic resonance imaging demonstrated a hypoplastic hypophysis (< 2.5 mm) and a normal infundibulum. GH treatment (0.73 IU/kg/week) was started. This paper reports a patient with genetically confirmed AHC demonstrating GH deficiency possibly due to a previous head trauma. Complete pituitary evaluation should be performed in any child who has survived severe traumatic brain injury.

Allelic Variants of ARMC5 in Patients With Adrenal Incidentalomas and in Patients With Cushing's Syndrome Associated With Bilateral Adrenal Nodules.

Objective: Germline ARMC5 mutations are considered to be the main genetic cause of primary macronodular adrenal hyperplasia (PMAH). PMAH is associated with high variability of cortisol secretion caused from subclinical hypercortisolism to overt Cushing's syndrome (CS), in general due to bilateral adrenal nodules and rarely could also be due to non-synchronic unilateral adrenal nodules. The frequency of adrenal incidentalomas (AI) associated with PMAH is unknown. This study evaluated germline allelic variants of ARMC5 in patients with bilateral and unilateral AI and in patients with overt CS associated with bilateral adrenal nodules. Methods: We performed a retrospective multicenter study involving 123 patients with AI (64 bilateral; 59 unilateral). We also analyzed 20 patients with ACTH pituitary independent overt CS associated with bilateral adrenal nodules. All patients underwent germline genotyping analysis of ARMC5; abdominal CT and were classified as normal, possible or autonomous cortisol secretion, according to the low doses of dexamethasone suppression test. Results: We identified only one pathogenic allelic variant among the patients with bilateral AI. We did not identify any pathogenic allelic variants of ARMC5 in patients with unilateral AI. Thirteen out of 20 patients (65%) with overt CS and bilateral adrenal nodules were carriers of pathogenic germline ARMC5 allelic variants, all previously described. The germline ARMC5 mutation was observed in only one patient with bilateral AI; it was associated with autonomous cortisol secretion and showed to be a familial form. Conclusion: The rarity of germline ARMC5 mutations in AI points to other molecular mechanisms involved in this common adrenal disorder and should be investigated. In contrast, patients with overt Cushing's syndrome and bilateral adrenal nodules had the presence of ARMC5 mutations that were with high prevalence and similar to the literature. Therefore, we recommend the genetic analysis of ARMC5 for patients with established Cushing's syndrome and bilateral adrenal nodules rather than patients with unilateral AI.

Adrenal histoplasmosis in immunocompetent individuals a case series from the North-Western part of India, Rajasthan province: An emerging endemic focus.

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum and very few cases reported from North-West India. Adrenal histoplasmosis is an even more uncommon mycotic disease. We describe five immunocompetent men with adrenal histoplasmosis presenting with constitutional symptoms. Four patients had bilateral adrenal involvement, whereas one had unilateral adrenal mass. Three patients had adrenal insufficiency at presentation and the other two developed adrenal insufficiencies during follow-up. All the patients received amphotericin B and itraconazole treatment which led to symptomatic improvement but adrenal insufficiency persisted in all patients at the end of the follow-up.

Open adrenalectomy: A 20-year review of our experience in a developing country.

Introduction: The aim of this study was to present our 20-year experience regarding open adrenalectomy (OA) during laparoscopic era in a developing country Turkey. Materials and Methods: A retrospective and descriptive study of patients with adrenal mass undergoing OA in the surgery department of our hospital, between January 1993 and January 2013, was carried out. All operations were performed by two surgeons. Results: Ninety patients who underwent OA in our clinic were reviewed retrospectively. The mean number of adrenal operations per month during this period was 0.38 ± 0.12. The patient included 35 men (38.8%) and 55 women (61.2%), with a mean age of 46.4 ± 17 years. The mean body mass index was 28.4 ± 5.25, and the mean American Society of Anesthesiologists score was 2.6 ± 0.57. The mean operative time was 88 ± 27 min. The mean maximum diameter of all the lesions was 4.8 ± 1.3 cm (range: 1.2-21 cm). The mean blood loss was 118 ± 23 ml during the operations. Postoperative complications were observed in four patients (5.5%). There was no mortality. The length of hospital stay was 6.2 ± 2.1 days. The most frequent type of the histological type was benign adenoma (48.8%). Conclusion: OA in a developing country is a safe method as an alternative for laparoscopic adrenalectomy which has a difficult learning curve.

RésuméIntroduction: Le but de cette étude est de présenter nos 20 ans dæexpérience de læadrénalectomie ouverte (OA) lors de la laparoscopie dans un pays en développement. Matériaux et méthodes: Une étude rétrospective et descriptive a été prévue dans le service de chirurgie générale de notre hôpital, incluant des patients ayant subi entre janvier 1993 et janvier 2013 une adrénalectomie ouverte pour une masse adrrénalienne. Toutes les opérations ont été effectuées par 2 chirurgiens. Résultats: Quatre-vingt-dix patients qui ont subi une adrénalectomie ouverte dans notre clinique ont été évalués rétrospectivement. Le nombre moyen dæopérations adrénaliennes par mois au cours de cette période était de 0,38 ± 0,12. Læâge moyen des patients était de 46,4 ± 17 ans: 35 (38,8%) étaient des hommes et 55 (61,2%) étaient des femmes. Læindice de masse corporelle (IMC) moyen était de 28,4 ± 5,25 et le score moyen de læAmerican Society of Anesthesiologists (ASA) était de 2,6 ± 0,57. La durée moyenne d'opération était de 88 ± 27 minutes. Le diamètre moyen de toutes les lésions était de 4,8 ± 1,3 cm (entre 1,2 et 21 cm). La quantité moyenne de saignements rencontrés au cours des opérations était de 118 ± 23 ml. Des complications postopératoires ont été observées chez quatre patients (5,5%). La mortalité næa été observée chez aucun des patients. La durée moyenne dæhospitalisation était de 6,2 ± 2,1 jours. Le type histologique le plus courant était læadénome bénin (48,8%). Conclusion: Dans un pays en développement, læadrénalectomie ouverte est une alternative sûre à læadrénalectomie laparoscopique qui a une courbe dæapprentissage difficile.

The Adult Adrenal Cortex Undergoes Rapid Tissue Renewal in a Sex-Specific Manner.

Evolution has resulted in profound differences between males and females that extend to non-reproductive organs and are reflected in the susceptibility and progression of diseases. However, the cellular and molecular basis for these differences remains largely unknown. Here we report that adrenal gland tissue renewal is highly active and sexually dimorphic, with female mice showing a 3-fold higher turnover than males. Moreover, in males, homeostasis relies on proliferation of cells within the steroidogenic zone, but females employ an additional stem and/or progenitor compartment situated in the adrenal capsule. Using lineage tracing, sex reversal models, gonadectomy, and dihydrotestosterone treatments, we further show that sex-specific stem cell activity is driven by male hormones that repress recruitment of Gli1+ stem cells from the capsule and cell proliferation. Taken together, our findings provide a molecular and cellular basis for adrenal sex dimorphism that may contribute to the increased incidence of adrenal diseases in females.

Assessment of neonatal adrenal size using high resolution 2D ultrasound and its correlation with birth demographics and clinical outcomes.

OBJECTIVE: Assessment of adrenal function in a sick neonate remains a challenge in spite of major advances in neonatal care. We used 2D ultrasound of adrenal glands to assess maturity of adrenal glands in extremely preterm infants and sick term and near term infants. STUDY DESIGN: We collected demographics details of 99 mother-infants pairs (24-41 weeks) and obtained 2D ultrasound scans of adrenal glands in first week of life to measure adrenal volume, fetal zone size, and adrenal to kidney ratios. Relationship between adrenal measurements, antenatal factors, and postnatal outcomes were studied. RESULTS: We reported normative adrenal gland volume data during gestation from 80 appropriate for gestational age (AGA) infants. In a binary analysis, adrenal size was significantly related to gender, race, intrauterine growth restriction (IUGR), maternal chorioamnionitis, and maternal hypertension. Linear regression analysis showed that fetal zone is significantly related to not only gestational age but also chorioamnionitis and later development of intraventricular hemorrhage (IVH). Adrenal volume likewise is also related to gestational age, preeclampsia, and IVH. CONCLUSIONS: Antenatal maternal factors and uterine environment affects adrenal growth and development thus postnatal high resolution 2D US scan of adrenal glands can provide useful information to predict outcomes. This information can complement hormone and adrenocorticotrophic hormone (ACTH) stimulation assays.

Familial risks for hospitalization with endocrine diseases.

CONTEXT: Familial clustering of a disease is an indicator of a possible heritable cause. In the era of genome scans, the consideration of data on heritability should be important in the assessment of the likely success of the scans. OBJECT: The objective of the study was to carry out a family study on nonthyroid endocrine diseases to search familial clustering of these diseases beyond the known syndromes. DESIGN AND SETTING: The Swedish Multigeneration Register on 0- to 72-yr-old subjects was linked to the Hospital Discharge Register from years 1964 to 2004. MAIN OUTCOME MEASURE: Standardized incidence ratios were calculated for offspring of affected parents and siblings by comparing with those whose relatives had no hospitalization for nonthyroid endocrine diseases. RESULTS: A total of 11,948 hospitalized cases and 443 familial cases were identified. The familial standardized incidence ratios were increased for parathyroid, pituitary, and adrenal hyperfunctions and hypofunctions, some findings consistent with known syndromes, most clearly that for adrenal cortical hypofunction showing recessive inheritance described for autoimmune polyendocrine syndrome 1. The sibling risks were very high for many diseases, but some of these affecting young individual may be due to bias caused by selective hospitalization. A high sibling risk observed for anterior pituitary hypofunction may represent a yet-unknown recessive syndrome. CONCLUSIONS: To our knowledge this is a first population-based study on nonthyroid endocrine diseases. The results call for further studies to sort out the challengingly high sibling risk for many individual nonthyroid endocrine diseases, whether they are due to bias or possible recessive effects.

Incidentally discovered adrenal masses.

Independently, endocrinology, radiology, and nuclear medicine can not optimally differentiate the etiology of the incidental adrenal mass. Rather, the insight necessary for this task must be contributed by all three disciplines. Incidentally discovered adrenal masses are being detected at an increasing rate. This trend is expected to continue based on the incidence of adrenal masses in autopsy series and the increasing use of high resolution abdominal imaging techniques. CT and MRI are able to definitely characterize only a minority of these lesions (simple cyst, myelolipoma, obvious local malignant invasion). Biochemical screening for hormone excess is essential regardless of a nonsuggestive complete history and physical examination. An argument may be made for not further pursuing nonhypersecreting lesions with the typical features of a benign adenoma on CT scan and an attenuation value of 0 HU or less. Adrenocortical scintigraphy is recommended in all patients with normal biochemical screening tests, especially those with CT attenuation values greater than 0 HU. In this setting, we believe that the functional and anatomical information provided by NP-59 and [75Se]selenomethylnorcholesterol scintigraphy allows one to noninvasively, accurately, and less expensively (Table 9) categorize adrenal masses as benign nonhypersecretory adenomas (the vast majority) vs. a possibly malignant lesion (the minority). In the presence of normal biochemistry, a concordant NP-59 imaging pattern is diagnostic of a nonhypersecretory benign adrenal adenoma and requires no immediate therapeutic intervention. Conversely, patients with discordant patterns of NP-59 scintigraphy have lesions that carry a significant risk for malignancy, and the pursuit of a tissue diagnosis is indicated, usually by means of FNA. Normal adrenocortical tissue on cytological studies in this setting may represent inadvertent sampling of adjacent normal adrenocortical tissues or the presence of a well differentiated adrenocortical carcinoma. In patients with lesions larger than 2 cm in whom NP-59 scintigraphy is nonlateralizing, the possibility of a periadrenal or pseudoadrenal mass is likely and should prompt review, or perhaps even repeat, of high resolution adrenal imaging (occasionally angiography may be helpful). In lesions shown to be 2 cm or less in size with a nonlateralizing NP-59-scan, there is a possibility of a periadrenal or pseudoadrenal mass; however, once this is excluded it must be recognized that benign and malignant lesions, because of the limitations of scintigraphy, cannot always be clearly distinguished by this method when masses are small.(ABSTRACT TRUNCATED AT 400 WORDS)

Safety of inhaled budesonide: clinical manifestations of systemic corticosteroid-related adverse effects.

Inhaled corticosteroid (ICS) therapy is central to the long-term management of asthma and is extensively used in the management of chronic obstructive pulmonary disease (COPD). While administration via inhalation limits systemic exposure compared with oral or injected corticosteroids and, therefore, the risk of systemic corticosteroid-related adverse effects, concerns over the long-term safety of ICS persist. The assessment of the long-term effects of ICS therapy requires considerable research effort over years or even decades. Surrogate markers/predictors for clinical endpoints such as adrenal crisis, reduced final height and fractures have been identified for use in relatively short-term studies. However, the predictive value of such markers remains questionable.Inhaled budesonide has been available since the early 1980s and there is a considerable evidence base investigating the safety of this agent. To assess the long-term safety of inhaled budesonide therapy in terms of the actual incidence of the clinical endpoints adrenal crisis/insufficiency, reduced final height, fractures and pregnancy complications, we undertook a review of the scientific literature. The external databases BIOSIS, Cochrane Central Register of Controlled Trials, Current Contents, EMBASE, International Pharmaceutical Abstracts and MEDLINE were searched, in addition to AstraZeneca's internal product literature database Planet, up to 29 February 2008. Only original articles of epidemiological studies, national surveys, clinical trials and case reports concerning inhaled budesonide were included.Eight surveys of adrenal crisis were found. The only survey with specified criteria for diagnosis involved 2912 paediatricians and endocrinologists and revealed 33 patients with adrenal crisis associated with ICS therapy; only one patient used budesonide (in co-treatment with fluticasone propionate). In addition, 14 case reports of adrenal crisis in budesonide-treated patients were found. In only two of these, budesonide was used at recommended doses and in the absence of interacting medication.Three retrospective studies and one prospective study assessing final height were found. None of them showed any reduced final height in patients receiving inhaled budesonide during childhood or adolescence.Seventeen epidemiological studies investigating the risk of fractures were found. When adjusting for confounding factors, they did not provide any unequivocal data for an increased fracture risk with budesonide. Four prospective placebo-controlled clinical trials of 2-6 years duration with inhaled budesonide in patients with asthma or COPD were found. None of the studies identified any association between inhaled budesonide and increased risk for fractures.Four studies using data from the Swedish birth and health registries showed there was no increased risk for congenital malformations, cardiovascular defects, decreased gestational age, birth weight or birth length among infants born to women using inhaled budesonide during pregnancy compared with the general population. This was confirmed by five observational studies in Australia, Canada, Hungary, Japan and the US. Similarly, one randomized clinical trial comparing pregnancy outcomes among asthma patients receiving inhaled budesonide or placebo did not demonstrate any difference in outcome of pregnancy.In summary, based on 25 years of experience with different doses and in different populations, inhaled budesonide therapy only in very rare cases appears to be associated with an increased risk of adrenal crisis, reduction in final height, increases in the number of fractures or complications during pregnancy.

Outcomes of laparoscopic adrenalectomy. Clinical experience with 68 patients.

The aim of this study was to analyze feasibility and outcomes of laparoscopic adrenalectomy (LA). Pathology, size and bilateral site of lesions were considered. Between December 1998 and May 2007 in our institution a total of 68 patients of mean age of 53 years underwent unilateral (n=57) or bilateral (n=11) LA. Adrenal masses averaged 5.4cm in size (range 1.2-13cm) and 56.7g in weight (range 10-265) including 71 benign and 8 malignant lesions. A total of 79 adrenal glands were resected, 44 right sided and 35 left sided. Removal was complete in 77 cases and partial (sparing adrenalectomy) in 1 patient affected by bilateral pheochomocytoma. Three left adrenalectomies for pheochromocytoma were robot-assisted. The transperitoneal lateral approach was preferred and the posterior retroperitoneal approach was adopted in 5 patients. The mean duration of surgery for each LA was 138+/-90min and 3.8 trocar were used on average (range 3-6). Conversion was needed in 3 cases owing to difficult dissection of large masses. Estimated mean blood loss for each LA was 95+/-30ml and it was greater for bilateral LA. Mortality was nil and morbidity was 5.8%. The average length of hospital stay (LOS) in surgical unit was 4+/-2.4 days (range 2-8). Patients affected by hormone secreting or bilateral lesions, by unilateral or bilateral pheochromocytoma and by bilateral Cushing's disease were transferred to the endocrinological ward so that their overall hospital stay was prolonged to 9+/-2.8 days on average (range 7-17). Mean duration of follow-up of patients was 38 months (range 2-100) and demonstrated acceptable endocrine results. Three primary cortical carcinomas were discovered as chance findings on histologic examination. While long-term results after LA for cortical carcinomas were poor and LA is not recommended in such cases, long-term results after LA for adrenal metastases were encouraging.

The incidental adrenal mass on CT: prevalence of adrenal disease in 1,049 consecutive adrenal masses in patients with no known malignancy.

OBJECTIVE: The purpose of our study was to determine the nature and prevalence of adrenal lesions identified on CT in patients with no known malignancy. MATERIALS AND METHODS: A computer search of abdominal CT reports using the term "adrenal" was performed in 65,231 consecutive patients with examinations performed from January 2000 to December 2003. An adrenal mass was identified in 3,307 (5%) patients. Patients with no known malignancy and no suspicion for a hyperfunctioning adrenal mass were further isolated. Nine hundred seventy-three patients with 1,049 adrenal masses fulfilled the study criteria. The nature of each lesion was determined by histopathology; imaging characterization with CT, MRI, or washout; a minimum of 1 year of stability on follow-up imaging; or clinical follow-up of at least 2 years. RESULTS: One thousand forty-nine adrenal masses were characterized with the following methods: histopathology (n = 12), imaging characterization (n = 909), imaging follow-up (n = 87), and clinical follow-up (n = 41). There were 788 adenomas constituting 75% of all lesions. There were 68 myelolipomas (6%), 47 hematomas (4%), and 13 cysts (1%). Three pheochromocytomas (0.3%) and one cortisol-producing adenoma (0.1%) were found incidentally. One hundred twenty-eight lesions (12%) were presumed to be benign by imaging or clinical stability. No malignant adrenal masses were found, even among the 14 patients who later developed malignancy elsewhere. CONCLUSION: In 973 consecutive patients with an incidental adrenal mass and no history of cancer, no malignant lesions were identified. Adenomas (75%) and myelolipomas (6%) were the most common lesions.