Management of acromegaly in Latin America: expert panel recommendations

Although there are international guidelines orienting physicians on how to manage patients with acromegaly, such guidelines should be adapted for use in distinct regions of the world. A panel of neuroendocrinologists convened in Mexico City in August of 2007 to discuss specific considerations in Latin America. Of major discussion was the laboratory evaluation of acromegaly, which requires the use of appropriate tests and the adoption of local institutional standards. As a general rule to ensure diagnosis, the patient’s GH level during an oral glucose tolerance test and IGF-1 level should be evaluated. Furthermore, to guide treatment decisions, both GH and IGF-1 assessments are required. The treatment of patients with acromegaly in Latin America is influenced by local issues of cost, availability and expertise of pituitary neurosurgeons, which should dictate therapeutic choices. Such treatment has undergone profound changes because of the introduction of effective medical interventions that may be used after surgical debulking or as first-line medical therapy in selected cases. Surgical resection remains the mainstay of therapy for small pituitary adenomas (microadenomas), potentially resectable macroadenomas and invasive adenomas causing visual defects. Radiotherapy may be indicated in selected cases when no disease control is achieved despite optimal surgical debulking and medical therapy, when there is no access to somatostatin analogues, or when local issues of cost preclude other therapies. Since not all the diagnostic tools and treatment options are available in all Latin American countries, physicians need to adapt their clinical management decisions to the available local resources and therapeutic options

Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28–81 years), male 81%, Child–Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0–9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways

Efficacy and complications of neurosurgical treatment of acromegaly

The aim of the study was to evaluate the frequency of occurrence of pituitary failure following neurosurgery and the efficacy of transsphenoidal tumour resection in acromegalic patients. We retrospectively evaluated 85 patients (60 female and 25 male), of mean age 43.9 ± 13.2 years, treated by transsphenoidal neurosurgery. Macroadenoma and microadenoma of pituitary were found in 66 (77.6%) and 19 (22.4%) of these patients, respectively. Criteria of cure following neurosurgery were: basal GH < 2.5 μg/l, GH at 120 min in OGTT < 1.0 μg/l and serum concentration of IGF-1 within normal ranges for age and sex. After surgery 32 patients (37.6%) were cured and 53 patients (62.4%) required somatostatin analogue treatment. In patients cured by surgery, lower levels of basal GH (P < 0.05), IGF-1 (P < 0.001), GH at 120 min in OGTT and smaller size of pituitary tumour (P < 0.05) were found at diagnosis, as compared to patients in whom surgery was unsuccessful. Significant correlation between basal serum level of GH at diagnosis and size of pituitary tumour was found (P < 0.001). Invasive tumours were found in 45 of 53 (84.9%) patients not cured and in only 8 of 32 (25.0%) patients cured (P < 0.001). Impaired function of pituitary anterior lobe after surgery was observed in 30% and 4% of patients with macro- and microadenoma, respectively (P < 0.05). The efficacy of neurosurgery is affected by concentration of basal serum GH and IGF-1, GH at 120 min in OGTT, tumour size and invasiveness. Hypopituitarism after surgery is more frequent in patients with macroadenoma. Pituitary insufficiency, as a consequence of surgery, was found in 21% of patients with normal pituitary function prior to operation

GH Receptor Antagonist: Mechanism of Action and Clinical Utility

This review focuses on the development of GH receptor antagonist as a novel agent for treatment of acromegaly, its mechanism of action and potential areas of use. A brief overview of acromegaly, its diagnosis and existing medical, surgical and radiotherapy options of treatment is necessary to justify the addition of yet another therapeutic modality to the already vast therapeutic armamentarium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47874/1/11154_2005_Article_5219.pd

Acromegaly

Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The prevalence is estimated at 1:140,000–250,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected). Due to insidious onset and slow progression, acromegaly is often diagnosed four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet), widened thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth-hormone-releasing hormone (GHRH) responsible for pituitary hyperplasia. The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT) and by detection of increased levels of insulin-like growth factor-I (IGF-I). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly. Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain

Determinants of cardiac troponin T elevation in COPD exacerbation – a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Cardiac Troponin T (cTnT) elevation during exacerbations of chronic obstructive pulmonary disease (COPD) is associated with increased mortality the first year after hospital discharge. The factors associated with cTnT elevation in COPD are not known.</p> <p>Methods</p> <p>From our hospital's database, all patients admitted with COPD exacerbation in 2000–03 were identified. 441 had measurement of cTnT performed. Levels of cTnT ≥ 0.04 μg/l were considered elevated. Clinical and historical data were retrieved from patient records, hospital and laboratory databases. Odds ratios for cTnT elevation were calculated using logistic regression.</p> <p>Results</p> <p>120 patients (27%) had elevated cTnT levels. The covariates independently associated with elevated cTnT were increasing neutrophil count, creatinine concentration, heart rate and Cardiac Infarction Injury Score (CIIS), and decreasing hemoglobin concentration. The adjusted odds ratios (95% confidence intervals in parentheses) for cTnT elevation were 1.52 (1.20–1.94) for a 5 × 10⁶/ml increase in neutrophils, 1.21 (1.12–1.32) for a 10 μmol/l increase in creatinine, 0.80 (0.69–0.92) for a 1 mg/dl increase in hemoglobin, 1.24 (1.09–1.42) for a 10 beats/minute increase in heart rate and 1.44 (1.15–1.82) for a 10 point increase in CIIS.</p> <p>Conclusion</p> <p>Multiple factors are associated with cTnT elevation, probably reflecting the wide panorama of comorbid conditions typically seen in COPD. The positive association between neutrophils and cTnT elevation is compatible with the concept that an exaggerated inflammatory response in COPD exacerbation may predispose for myocardial injury.</p

Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas

Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients

Association of Glomerular Filtration Rate with High-Sensitivity Cardiac Troponin T in a Community-Based Population Study in Beijing

BACKGROUND: Reduced renal function is an independent risk factor for cardiovascular disease mortality, and persistently elevated cardiac troponin T (cTnT) is frequently observed in patients with end-stage renal disease. In the general population the relationship between renal function and cTnT levels may not be clear because of the low sensitivity of the assay. In this study, we investigated the level of cTnT using a highly sensitive assay (hs-cTnT) and evaluated the association of estimated glomerular filtration rate (eGFR) with detectable hs-cTnT levels in a community-based population. METHODS: The serum hs-cTnT levels were measured in 1365 community dwelling population aged ≥45 years in Beijing, China. eGFR was determined by the Chinese modifying modification of diet in renal disease (C-MDRD) equation. RESULTS: With the highly sensitive assay, cTnT levels were detectable (≥3pg/mL) in 744 subjects (54.5%). The result showed that eGFR was associated with Log hs-cTnT (r = -0.14, P<0.001). After adjustment for the high predicted Framingham Coronary Heart Disease (CHD) risk (10-year risk >20%) and other prognostic indicators, moderate to severe reduced eGFR was independently associated with detectable hs-cTnT, whereas normal to mildly reduced eGFR was not independently associated with detectable hs-cTnT. In addition, after adjustment for other risk factors, the high predicted Framingham CHD risk was associated with detectable hs-cTnT in the subjects with different quartile levels of eGFR. CONCLUSION: The levels of hs-cTnT are detectable in a community-based Chinese population and low eGFR is associated with detectable hs-cTnT. Moreover, eGFR and high predicted Framingham CHD risk are associated with detectable hs-cTnT in subjects with moderate-to-severe reduced renal function

An examination of multiple factors affecting community structure in an aquatic amphibian community

The potential effects of multiple factors structuring certain larval amphibian communities were studied using a pen experiment in a natural pond. Potential factors (predation and competition from other species) were allowed to act in a stepwise fashion such that their relative importance could be evaluated. Based on a previous study, it was hypothesized that predation by Ambystoma salamander larvae on other larval amphibian species would be the most important factor. Survival of Ambystoma jeffersonianum salamander larvae and Rana sylvatica tadpoles was significantly depressed only by Ambystoma opacum predation. Survival of Ambystoma maculatum salamander larvae was significantly greater in the absence of both A. opacum and A. jeffersonianum predators. The virtual elimination of Hyla chrysoscelis larvae in all treatments also can be largely attributed to Ambystoma predation. Thus, Ambystoma predation was the dominant factor determining larval survival of four amphibian prey species in the experimental communities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47785/1/442_2004_Article_BF00324643.pd

Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: a literature review

Acromegaly is a rare disease with a multifaceted clinical presentation. In 90–95% of patients with acromegaly, the disease is caused by a growth hormone (GH)-secreting pituitary adenoma with elevated GH levels that ultimately induce excessive hepatic secretion of insulin-like growth factor-1 (IGF-1). Somatostatin receptor ligands (SRLs) are considered the standard medical choice for the treatment of acromegaly, and normalization of GH and IGF-1 is attainable with effective therapy. This review aims to summarize the literature relative to SRL dose escalation therapy in patients with acromegaly. A United States National Library of Medicine PubMed search of SRL’s was conducted using the following search terms: ((((LAR) OR ATG) OR octreotide) OR lanreotide Autogel) AND acromegaly. Related articles in non peer-reviewed journals were excluded. The rationale and benefits of SRL dose optimization therapy were investigated with emphasis on describing the clinical recognition, treatment, and management of patients with acromegaly. We found that dose escalation could provide additional biochemical control of acromegaly in patients who are inadequately controlled with conventional starting doses of octreotide LAR and lanreotide Autogel®. Furthermore, patients should routinely have their GH and IGF-1 levels closely monitored and their SRL dose increased or decreased thereafter according to individual response