An observational study of self-reported sedentary behaviour in people with chronic obstructive pulmonary disease and bronchiectasis.

BACKGROUND: Few studies have examined sedentary behaviour in chronic respiratory disease. The limited evidence suggests that increased levels of sedentary behaviour are associated with increased mortality. OBJECTIVES: This study aimed to compare the level of self-reported sedentary behaviour in people with chronic obstructive pulmonary disease (COPD) and bronchiectasis as well as to identify associations between sedentary time with functional performance measures and health-related quality of life in the chronic respiratory disease group. METHODS: An observational study design was used. Participants completed the Sedentary Behaviour Questionnaire from which average sedentary time (hours/day) was determined. Functional performance was measured using the six-minute walk test, the four-metre gait speed test and the five sit-to-stand test. Health-related quality of life was measured using the St George's Respiratory Questionnaire. Sedentary time was compared between groups using an unpaired t-test. Univariate analysis explored relationships amongst variables. RESULTS: The convenience sample consisted of 103 people with COPD [52% male; mean±SD age: 73±9 years, FEV1% predicted: 56±23] and 33 people with bronchiectasis [52% male; 74±8 years, FEV1% predicted: 69±25]. Average self-reported sedentary time in COPD was 7.6±2.7 hours/day and in bronchiectasis was 8.0±4.1 hours/day, with no between-group difference (-0.4, 95% CI -1.7, 0.8). No associations were found between sedentary time and any functional performance outcome or with health-related quality of life. CONCLUSION: There was no difference in the high sedentary time between people with COPD and bronchiectasis. Sedentary behaviour was not associated with functional performance or disease-related health-related quality of life in people with chronic respiratory disease.

Cytoplasmic expression of SSTR2 and 5 by immunohistochemistry and by RT/PCR is not associated with the pharmacological response to octreotide.

OBJECTIVE: To evaluate expression of somatostatin receptor subtypes 2 and 5 (SSTR 2 and 5) by RT/PCR and immunohistochemistry (IHC) in GH-secreting adenomas, seeking correlations with response to octreotide. METHODS: SSTR2 and 5 expression was tested by IHC (n=37), RT/PCR (n=36) or both (n=13) in GH-secreting adenomas from 60 patients with acromegaly who had undergone pituitary surgery; 36 had been treated preoperatively with octreotide LAR for 3-6 months, and were categorized as responders (achievement of GH <2.5ng/mL and a normal age-adjusted IGF-1), partial responders (GH and IGF-1 reduction >50% and >30%, respectively) or non-responders. IHC was performed on a tissue microarray using specific antibodies directed to the carboxyl terminus of SSTR2 and 5. RESULTS: SSTR5 was the predominantly expressed receptor subtype by both IHC and RT/PCR in all tumors tested, regardless of whether they came from octreotide-naïve, octreotide-responsive, or octreotide-resistant patients. Immunostaining was concentrated in the cytoplasm. Neither SSTR2 nor SSTR5 expression correlated with baseline or post-octreotide GH or IGF-1 levels or tumor volume by either method. The agreement rate between RT/PCR and IHC was 77% in all 13 adenomas in which both methods were used. CONCLUSION: Expression of these receptors does not guarantee an adequate response to somatostatin analogs; other functional aspects of this interaction, such as receptor homo- and heterodimerization, and the resulting signaling cascade, probably play a role in determining whether a patient will respond or not to these agents.

[Macroprolactinemia identification in patients with hyperprolactinemia]. / Identificación de macroprolactinemia en pacientes con hiperprolactinemia.

BACKGROUND: Macroprolactinemia is defined as hyperprolactinemia with predominance of the big-big prolactine isoform. Its frequency has not been clearly established due to technical difficulties to identify it. This method used to detect it is gel filtration chromatography, an expensive and complicated procedure that could not be used routinely. OBJECTIVE: To validate the PEG precipitation technique, to identify the presence of macroprolactinemia and to correlate it with the clinical characteristics in a group of pre-selected patients with elevated serum PRL levels from different causes. PATIENTS AND METHOD: There were studied 14 patients non pre-selected with high PRL serum levels. Prolactine levels were determined with commercial immunometric quimioluminescence essays. All the essays were duplicated, and healthy patients serum (without hyperprolactinemia) were used. Technique consists on mixing 250 microL of serum with the same volume of polyethylene glycol. Later it was centrifugated at 3000 rpm during 30 minutes at 4 degrees C. Prolactine level was measured in supernatant. RESULTS: Within patients 7 to 14 macroprolactinemia was ruled out and confirmed truth hyperprolactinemia, some times slight and nontumoral, some times mild, and some times due to prolactin-producer hypophysial macroadenomas. CONCLUSIONS: Polyethylene glycol precipitation technique is reliable to detect macroprolactinemia.

Ectopic ACTH-secreting syndrome: a single center experience report with a high prevalence of occult tumor.

BACKGROUND: Differentiation between the two forms of ACTH-dependent Cushing's syndrome is a challenging task. Although the majority of these cases will be diagnosed as Cushing's disease secondary to an ACTH-secreting pituitary adenoma, 10-15% result from the ectopic ACTH secretion syndrome (EAS), which is usually due to neuroendocrine tumors. In the present study we report our experience with EAS in eight patients evaluated and treated during the past 10 years. METHODS: Our experience in the evaluation and management of EAS was retrospectively reviewed. The latter included a standard biochemical assessment (urinary free cortisol, low- and high-dose dexamethasone suppression tests), petrosal sinus sampling when indicated and imaging techniques such as pituitary MRI, total body CT and somatostatin receptor scintigraphy. RESULTS: The ectopic nature of the ACTH hypersecretion was confirmed with inferior petrosal sinus samplings in all cases. CT scanning localized a putative tumor in 6/8 patients, whereas octreotide scintigraphy was positive in only five. In all cases, the source was traced to the lungs. However, upon performing thoracotomy, a documented ACTH-secreting bronchial carcinoid tumor was found in only four patients. Thus, 4/8 patients with EAS remained "occult." All of these patients underwent adrenalectomy for hypercortisolism control. CONCLUSIONS: EAS is a rare cause of ACTH-dependent Cushing's syndrome. Truly "occult" tumors were frequent and these patients need to be under close surveillance for the detection of neuroendocrine tumors.

Biochemical evaluation of disease activity after pituitary surgery in acromegaly: a critical analysis of patients who spontaneously change disease status.

BACKGROUND: The definition of biochemical cure in acromegaly involves both the normalization of IGF-1 and a glucose-suppressed GH level of < 1 ng/ml. These criteria were reached by several consensus meetings, although no evidence-based recommendations as to the optimal time to perform biochemical evaluations were made, nor was the fact that several patients may change biochemically upon long-term follow-up taken into consideration. OBJECTIVES: To identify and characterize biochemical changes in the follow-up of acromegaly. PATIENTS AND METHODS: One hundred and twenty-six acromegalic patients seen at a referral centre were followed prospectively (6-108 months) with regard to glucose-suppressed GH levels and IGF-1 concentrations. RESULTS: Eighty-nine patients did not change biochemical status, whereas in 37 (29.3%), one or more changes were identified, mostly during the first year. When glucose-suppressed GH values were discordant with the IGF-1 results, the likelihood of biochemical status modification was significantly greater than when such results were concordant [concordant 19.4%, discordant 57.6%, odds ratio (OR) = 5.6, 95% confidence interval (CI) = 2.3-13.3, P = 0.0001]. Among the changing patients, four out of the nine subjects initially considered as cured remained so at the last follow-up, whereas five became discordant; of the nine initially categorized as active, only three kept such a status at the last evaluation, whereas five became GH discordant and one achieved full biochemical criteria of cure; of 17 initially GH-discordant patients, seven remained so upon the last evaluation, whereas six became concordantly active and four concordantly cured. CONCLUSION: A significant proportion of acromegalic patients change biochemical status upon long-term follow-up after surgery. Most of these changes occur within the first postoperative year and are more likely to take place if the initial GH postglucose and IGF-1 levels are discordant.

GSPalpha mutations in Mexican patients with acromegaly: potential impact on long term prognosis.

OBJECTIVE: The frequency of activating mutations of the GSPalpha gene as the etiology of GH-secreting pituitary adenomas has been the subject of important ethnogenetic variability. Whereas up to 40% of Caucasian patients with acromegaly have tumors which harbor these somatic mutations, their prevalence among Asian populations is much lower. The correlation between the presence of these mutations and the clinical and biological behavior of these tumors has also been a matter of controversy. In the present study, we investigated the prevalence of GSPalpha mutations in GH-secreting tumors obtained from a genetically homogenous population of Mexican patients with acromegaly. We also sought to establish whether or not the presence of these mutations correlates in any way with the clinical or biochemical characteristics of the disease. STUDY DESIGN AND METHODS: Fifty eight GH-secreting pituitary adenomas were examined for the presence of point mutations in either codon 201 or 227 of the GSPalpha gene, using PCR and direct sequencing of DNA extracted from either fresh or paraffin-embedded tissues. Patients were prospectively followed clinically and biochemically for up to nine years after pituitary surgery. RESULTS: Heterozygous point mutations in exon 8 (codon 201) were found in 11 patients (19%), and no molecular alterations were evident in exon 9. The frequency and severity of the different clinical features of acromegaly did not differ between patients with and without GSPalpha mutations. Patients with and without mutations had pre-operative GH and IGF-I elevations of similar magnitude, and although microadenomas appeared to be more frequent among patients with GSPalpha mutations, this did not reach statistical significance. Upon short-term follow-up, biochemical cure (normal age- and gender-adjusted IGF-I and post-glucose GH below 1 ng/mL) was similarly achieved in both groups. After 3-9 years of post-operative follow up however, a significantly greater proportion of patients with the mutation achieved a "safe" basal GH value (100% vs 33%, p=0.001) as well a lower nadir post-glucose GH (0.53+/-0.5 vs 2.9+/-6.2 ng/mL, p=0.04) although the rate of IGF-1 normalization did not differ between the 2 groups. CONCLUSIONS: Our results show that the prevalence of GSPalpha mutations in Mexican patients with acromegaly is intermediate between that found in Asian and Caucasian populations. In this well-defined genetic population the presence of codon 201 mutations appeared to be associated with a greater probability of achieving a "safe" GH value upon long-term follow-up.

Clinical-biochemical correlations in acromegaly at diagnosis and the real prevalence of biochemically discordant disease.

OBJECTIVE: To analyze clinical-biochemical correlations in newly diagnosed acromegaly, focusing in particular on patients with discrepant parameters. DESIGN: Retrospective study. METHODS: Data from 164 patients with acromegaly seen between 1995 and 2003. Patients were reviewed for the presence of headaches, arthralgias, hypertension, menstrual abnormalities, impotence, glucose intolerance or diabetes. Biochemical evaluation consisted of age- and gender-adjusted IGF-I levels and glucose-suppressed GH. RESULTS: Magnetic resonance imaging (MRI) revealed macroadenoma in 127 patients and microadenoma in 37. Patients with macroadenomas were younger than those with microadenomas and the disease was more frequent in females. Excluding acral enlargement, which was present in all the patients, the most commonly reported complaints were headaches (66%) and arthralgias (52%). Hypertension was present in 37% of patients, whereas the prevalence of glucose intolerance and diabetes was 27 and 32%, respectively. Hyperprolactinemia was present in 20% of patients with microadenomas and in 40% of patients with macroadenomas. Hypogonadism was demonstrated in more than half of the patients and was not related to tumor size or prolactin level. Of all the clinical and metabolic abnormalities of acromegaly, only the presence of diabetes correlated with both basal and nadir post-glucose GH levels. Only 4 patients (2.4%) had glucose-suppressed GH values of <1 ng/ml in the presence of clinical evidence of acromegaly, an elevated IGF-I level and a pituitary adenoma on MRI. CONCLUSIONS: Clinical features of acromegaly correlate poorly with indices of biochemical activity. The prevalence of biochemically discordant acromegaly is considerably lower than recently reported.