The 10:00-11:00 pm urine cortisol/creatinine ratio. An alternative to late-night salivary cortisol for the diagnosis of Cushing's syndrome.

The aim of this study was to investigate interchangeability of two tests to diagnose Cushing's syndrome. We compared 10:00-11:00 PM urinary free cortisol/creatinine ratio (UFC/Cr) with late night 11:00 PM salivary cortisol (LNSC) in normal and obese controls vs. patients with Cushing's syndrome. Mean UFC/Cr did not differ between 69 normal and 62 obese controls (9.9 ± 7.9 vs. 9.7 ± 9.3) whereas 116 Cushing's patients had significantly higher values (277.0 ± 318.0; z: -11.1 and -10.2, respectively; p < 0.001). LNSC was 1.9 ± 1.2 nmol/l in 44 normal and 2.5 ± 1.6 in 45 obese subjects with no differences between them, but was significantly higher in 47 Cushing's patients (24.8 ± 23.3; z: -7.22 and -6.96, respectively, p < 0.001). Comparison of UFC/Cr and LNSC in samples obtained simultaneously showed that UFC/Cr was 12.0 ± 8.7 ng cortisol/mg creatinine in 34 normal, 12.3 ± 8.9 in 40 obese and 319.5 ± 333.4 in 35 CS subjects (p < 0.001 vs. normal and obese), whereas LNSC was 1.8 ± 1.2 nmol/l in normal, 2.6 ± 1.7 in obese and 24.6 ± 17.4 in CS patients (p < 0.001 vs. normal and obese); ROC curves showed comparable high sensitivity and specificity figures for the diagnosis of CS. We concluded that UFC/Cr test is easy to perform, readily available in routine laboratories, has high sensitivity and specificity, and offers a valuable alternative to LNSC in the study of Cushing's syndrome.

Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina.

We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34-78 years, presenting aggressive pituitary tumors. In all the patients tested O(6)-methylguanine-DNA methyltransferase (MGMT) immunoexpression in surgical specimens was absent. Patients received temozolomide 140-320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson's syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing's disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on-until now-incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration.

[Analysis of a pituitary adenoma registry]. / Análisis de un Registro de adenomas pituitarios.

Collection and analysis of data obtained during the clinical treatment of pituitary tumours are of great utility in the decision making process, when facing clinical situations. We report here data on 519 from 670 patients with pituitary adenomas obtained from a computerized registry. Three hundred and forty five were females (66%) and 174 males (34%), aged 14-80. Final diagnosis was acromegaly in 176, Cushing's disease in 153, prolactinoma in 101 and clinically non-functioning adenoma in 89. Mean age at diagnosis was 43.9 ± 13.5 (16-80) for acromegalics, 35.7 ± 12.9 (14-72) for Cushing's, 30.0 ± 13.4 (15-79) for prolactinoma and 52.1 ± 15.2 (17-79), for non-functioning tumours. The setup of an institutional registry on pituitary tumours constitutes a useful tool to analyze clinical experience, optimize the cost/benefit ratio of procedures used for diagnosis and to ameliorate therapeutic strategies, improving patient's care. It greatly contributes to teaching medical students as well as to post-graduate physicians and provides a basis for developing clinical research.

Análisis de un registro de adenomas pituitarios / Analysis of a pituitary adenoma registry

Dada la complejidad que reviste el enfoque diagnóstico y terapéutico de los tumores pituitarios, el registro y análisis de la experiencia clínica acumulada es de gran ayuda en la toma de decisiones. En este trabajo se informan datos clínico-terapéuticos, extraídos de un registro computarizado, sobre 519 de un total de 670 pacientes con adenomas pituitarios. Trescientos cuarenta y cinco fueron mujeres (66%) y 174 varones (34%), de 14 a 80 años de edad. El diagnóstico final fue: acromegalia en 176, enfermedad de Cushing en 153, prolactinoma en 101 y adenoma clínicamente no-funcionante (ANF) en 89. La edad media al momento del diagnóstico de acromegalia fue 43.9 ± 13.5 (16-80), para enfermedad de Cushing 35.7 ± 12.9 (14-72), para prolactinomas 30.0 ± 13.4 (15-79) y para ANF 52.1 ± 15.2 (17-79) años. La creación de un registro institucional de tumores de hipófisis es un instrumento de gran utilidad para el análisis de la experiencia adquirida y constituye una herramienta valiosa para mejorar la estrategia terapéutica, optimizar la relación costo/beneficio y mejorar el cuidado del paciente. Contribuye a la docencia médica, tanto en el pre como en el posgrado y da base a la realización de trabajos de investigación clínica, aportando a la difusión y transferencia de conocimientos.

Collection and analysis of data obtained during the clinical treatment of pituitary tumours are of great utility in the decision making process, when facing clinical situations. We report here data on 519 from 670 patients with pituitary adenomas obtained from a computerized registry. Three hundred and forty five were females (66%) and 174 males (34%), aged 14-80. Final diagnosis was acromegaly in 176, Cushing's disease in 153, prolactinoma in 101 and clinically non-functioning adenoma in 89. Mean age at diagnosis was 43.9 ± 13.5 (16-80) for acromegalics, 35.7 ± 12.9 (14-72) for Cushing's, 30.0 ± 13.4 (15-79) for prolactinoma and 52.1 ± 15.2 (17-79), for non-functioning tumours. The setup of an institutional registry on pituitary tumours constitutes a useful tool to analyze clinical experience, optimize the cost/benefit ratio of procedures used for diagnosis and to ameliorate therapeutic strategies, improving patient's care. It greatly contributes to teaching medical students as well as to post-graduate physicians and provides a basis for developing clinical research.

In what clinical settings should Cushing's syndrome be suspected?

Despite its low frequency, endogenous Cushing's syndrome is not an exceptional clinical entity. A growing number of cases are currently derived to specialized centers suggesting an increasing knowledge of the clinical features of hypercortisolism by specialists of diverse branches of clinical medicine. Clinical signs derive from an exaggeration of the physiological actions of cortisol inducing protein breakdown, hyperglycemia, fat mobilization, dyslipidemia, hydrosaline retention, immunosuppression and increased susceptibility to infection. Despite its low specificity, symptoms such as unexplained development of central obesity, mood changes, fatigue, weakness, myopathy, easy bruisability, red striae, arterial hypertension, diabetes and hyperlipidemia, are suggestive of the diagnosis. From an epidemiological point of view, Cushing's syndrome is to be suspected and consequently searched for among patients with uncontrolled high blood pressure or diabetes mellitus, metabolic syndrome, polycystic ovarian syndrome, osteoporosis, depression or adrenal incidentaloma. True Cushing's syndrome has to be differentiated from pseudo syndromes. Most sensitive physical signs for discriminating Cushing's syndrome from pseudo-Cushing states are the presence of supraclavicular fat pads, myopathy, thin skin and easy bruising. The recognition of the clinical manifestations of Cushing's syndrome and of the sub-populations at risk of contracting the disease should be improved through medical education at the medical school and at postgraduate levels. Clinical detection of Cushing's syndrome must be performed mainly by non-endocrinologists, yet its etiological diagnosis and therapeutic management is to be carried out in highly experienced and specialized centers, to ensure the best results in the treatment of this really challenging endocrine disturbance.