Decreased adrenergic tone in acromegaly: evidence from direct recording of muscle sympathetic nerve activity.

OBJECTIVE: Sympathovagal imbalance has been shown in acromegaly by indirect measurements of adrenergic tone. Data regarding direct measurement of sympathetic activity are lacking as yet. Aim of this study was to assess the adrenergic tone through direct recording of muscle sympathetic nerve activity (MSNA) in acromegalic patients. DESIGN: Fifteen patients (age 26-66 years, eight women) with newly diagnosed active acromegaly without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy, and 15 healthy subjects matched for age, sex and body mass index were recruited. After evaluating anthropometric and echocardiographic parameters, anterior pituitary function, glucose and lipid metabolism, and measuring plasma leptin, direct recording of sympathetic outflow via the microneurographic technique was performed. RESULTS: For similar anthropometric and metabolic parameters in patients and controls, HOMA index was significantly increased in the former (4·2 ± 2·39 vs 1·6 ± 0·19, P < 0·001). Surprisingly, this finding of insulin resistance was accompanied by a marked sympathetic inhibition (MSNA 18·3 ± 8·10 vs 37·3 ± 6·48 bursts/min, P < 0·0001, respectively in patients and controls). A reduction in plasma leptin (1·6 ± 1·04 vs 6·5 ± 2·01 µg/l, P < 0·0001) was also recorded in the patients. MSNA was positively correlated with leptin (P < 0·0001). CONCLUSIONS: Newly diagnosed acromegalic patients without cardiac hypertrophy display a decreased sympathetic outflow in spite of insulin resistance. This finding might be related to hypoleptinaemia.

Assessment of biochemical control of acromegaly during treatment with somatostatin analogues by oral glucose load and insulin-like growth factor I.

BACKGROUND: The use of oral glucose tolerance test (OGTT) in evaluating biochemical control in acromegalic patients on somatostatin analogues (SSA) has recently been questioned. AIM: To gain further insights into this topic, we analyzed basal and nadir GH levels during OGTT in acromegalic patients on SSA. SUBJECTS AND METHODS: Basal IGF-I and GH values, as well as GH levels along the test, were analyzed in 115 standard OGTT performed in 33 acromegalic patients followed up between 1993 and 2009. All patients were on SSA at the time of the study; 22 of them had previously undergone unsuccessful surgery. No patient had undergone radiotherapy. GH suppression was considered normal when the hormonal value fell to <1 µg/l during OGTT. Diagnostic accuracy was analyzed by receiver operating characteristic (ROC) curves. RESULTS: ROC analysis showed that the GH basal value yielding the best specificity (100%) was 3.9 µg/l. All patients with basal GH>3.9 µg/l displayed lack of GH suppression after OGTT and 80% also displayed high IGF-I. Conversely, patients with basal GH<3.9 µg/l presented a variable biochemical pattern with half of them failing to suppress GH after OGTT and 36.6% displaying high IGF-I levels. CONCLUSIONS: Our results show that baseline GH levels >3.9 µg/l are predictive of absent OGTT-dependent GH suppression; however, 20% of these patients display partial biochemical control (normal IGF-I levels). On the other hand, basal GH values <3.9 µg/l are not predictive of GH suppressibility by glucose and are often discordant with IGF-I levels.

Thyroid nodules in acromegaly: The role of elastography.

INTRODUCTION: Ultrasound elastography (US-E) is a helpful tool for the diagnosis of thyroid cancer. In acromegaly, multinodular goiter is a common occurrence while the prevalence of thyroid cancer is still matter of debate. Our aims were to evaluate thyroid nodules in acromegaly and to assess the accuracy of US-E in providing information on their nature (benign vs. malignant) using cytological analysis as a reference. MATERIALS AND METHODS: US-E was performed in 25 patients with acromegaly (active in 10 cases, medically controlled in 8, and cured by pituitary surgery in 7), each of whom had at least one solid thyroid nodule. A total of 90 nodules were classified according to the elastography scores (ES): ES1 and ES2 for soft nodules, ES3 and ES4 for an elastic lesions. FNAC was performed in 78.6% of the ES 4 lesions and 54.1% of the ES 3 nodules. RESULTS: Fourteen of the 90 nodules (15.5%) displayed an ES of 1, 25 (27.7%) an ES of 2, 37 (41.3%) an ES of 3, and 14 (15.5%) an ES of 4. The prevalence of hard nodules in patients with active acromegaly (68.9%) was greater than that observed in patients with cured (44.4%) or controlled (52.5%) acromegaly. The prevalence of hard nodules in the total series (56.7%) was higher than that reported in nonacromegalic goitrous subjects. All thyroid nodules subjected to FNAC were negative for malignant cells and follicular lesions. DISCUSSION: Acromegaly (particularly active forms) is associated with a high prevalence of stiff thyroid nodules that exceeds that observed in nonacromegalic patients with goiters (33.7%). However, these nodules were never malignant at cytology, and their firmness is probably due to fibrosis. US-E therefore appears to be of limited value for the diagnosis of thyroid cancer in patients with acromegaly.

Somatostatin analogs and gallstones: a retrospective survey on a large series of acromegalic patients.

CONTEXT: Development of gallstones (GS) is reported during the use of somatostatin analogs (SA) that are at present the mainstay for the medical treatment of acromegaly. OBJECTIVE: To review the prevalence and clinical and biochemical correlates of GS in acromegalic patients. DESIGN AND SETTING: Retrospective survey on hospital records in acromegalic patients followed up in the last 20 yr in tertiary referral centers. PATIENTS: Four hundred and fifty-nine patients (272 females). MAIN OUTCOME MEASURES: According to SA use and GS occurrence, patients were divided in 4 groups: 1) treated with SA without GS (SA+GS-), 2) GS developed while on SA (SA+GS+), 3) GS without SA use (SA-GS+), 4) neither GS nor SA (SA-GS-). RESULTS: Patients were unevenly distributed in the 4 groups: 232, 125, 38, 64, respectively, pointing to a prevalence of GS in acromegaly of 8.3% at diagnosis with an additional 35% developing GS during SA. GS occurred after 3 months-18 yr (median 3 yr) of SA treatment, were diagnosed after symptoms in 17.6%, were associated to steatosis, ultrasound biliary dilation, and biochemical cholestasis, in 25.6%, 12.8%, and 4% of patients, respectively. Ursodehoxicolic acid was administered after GS occurrence, causing their dissolution in 39% of patients after 3-48 months (median 12). Cholecystectomy was performed in 16.8%of patients in group 2. At multivariate analysis obesity, dyslipidemia, and SA treatment were independent predictors of GS onset, whereas gender and age were not. CONCLUSIONS: GS are a frequent occurrence in acromegalic patients treated with SA, may occur at any time, but are seldom symptomatic or prompt acute surgery. Obesity and dyslipidemia appear to play a major role in the occurrence of GS in acromegalic patients on SA treatment.