A Multicenter Cohort Study in Patients With Primary Empty Sella: Hormonal and Neuroradiological Features Over a Long Follow-Up.

Objective: primary empty sella (PES) represents a frequent finding, but data on hormonal alterations are heterogeneous, and its natural history is still unclear. Our aim was to evaluate the pituitary function of patients with PES over a long follow-up. Design: multicenter retrospective cohort study enrolling patients referred between 1984-2020 to five Pituitary Units, with neuroradiological confirmed PES and a complete hormonal assessment. Methods: we analyzed hormonal (including basal and dynamic evaluations), clinical and neuroradiological data collected at diagnosis and at the last visit (at least 6 months of follow-up). Results: we recruited 402 patients (females=63%, mean age=51.5 ± 16 years) with PES (partial, total, undefined in 66%, 13% and 21%, respectively). Hypopituitarism was present in 40.5% (hypogonadism=20.4%, hypoadrenalism=14.7%, growth hormone deficiency=14.7%, hypothyroidism=10.2%, diabetes insipidus=1.5%; multiple deficiencies=11.4%) and hypeprolactinemia in 6.5%. Interestingly, hormonal alterations were diagnosed in 29% of incidental PES. Hypopituitarism was associated with male sex (p=0.02), suspected endocrinopathy (p<0.001), traumatic brain injury (p=0.003) and not with age, BMI, number of pregnancies and neuroradiological grade. A longitudinal assessment was possible in 166/402 (median follow-up=58 months). In 5/166 (3%), new deficiencies occurred, whereas 14/166 (8.4%) showed a hormonal recovery. A progression from partial to total PES, which was found in 6/98 patients assessed with a second imaging, was the only parameter significantly related to the hormonal deterioration (p=0.006). Conclusions: this is the largest cohort of patients with PES reported. Hypopituitarism is frequent (40%) but hormonal deterioration seems uncommon (3%). Patients need to be carefully evaluated at diagnosis, even if PES is incidentally discovered.

Psychological complications in patients with acromegaly: relationships with sex, arthropathy, and quality of life.

PURPOSE: Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients' quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL. METHODS: One hundred and seventy-one acromegalic patients (95 women and 76 men, aged 20-85 years) among those recruited in a cross-sectional Italian multicentric study were investigated. Each patient filled in three validated questionnaires: AcroQoL, WOMAC (measuring articular pain, stiffness and functionality), and AIMS (evaluating articular symptoms and depression). RESULTS: A very high (up to 28%) depression rate was detected in acromegalic subjects. Two patients showing pathological AIMS depression scores, committed suicide during the three years observational period. In our population poor psychological status was significantly associated with female sex. Furthermore, a significant strong correlation was found between AIMS depression score and WOMAC score. Both depression and arthropathy-related motor disability turned out to independently contribute with similar strength to the impairment of QoL. CONCLUSIONS: We report a high prevalence of depression in acromegaly, which is associated with female sex and arthropathy. Both depression and arthropathy strongly and independently contribute to the impaired QoL of patients. Our study shows that assessment and monitoring of psychological status is mandatory in acromegaly, also suggesting an inexpensive tool for this assessment.

Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy.

BACKGROUND: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19. METHODS: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization. RESULTS: Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ - 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count. CONCLUSION: In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.

Clinical benefits of sex steroids given as a priming prior to GH provocative test or as a growth-promoting therapy in peripubertal growth delays: Results of a retrospective study among ENDO-ERN centres.

OBJECTIVES: Sex steroids, administered as a priming before GH stimulation tests (GHST) to differentiate between growth hormone deficiency (GHD) and constitutional delay of growth and puberty (CDGP) or as growth-promoting therapy using low-dose sex steroids (LDSS) in CDGP, are much debated. We aimed to compare auxological outcomes of CDGP or GHD children undergoing primed or unprimed GHST and to evaluate LDSS treatment in CDGP. DESIGN: Retrospective study among three paediatric University Hospitals in Italy and UK. METHODS: 184 children (72 females) aged 12.4 ± 2.08 years underwent primed (/P+ ) or unprimed (/P- ) GHST and were followed up until final height (FH). CDGP patients were untreated (CDG P- ) or received LDSS (CDGP+ ). The cohort included 34 CDG P- /P+ , 12 CDGP+ /P+ , 51 GHD/P+ , 29 CDG P- /P- , 2 CDGP+ /P- and 56 GHD/P- . FH standard deviation score (SDS), Δ SDS FH-target height (TH) and degree of success (-1 ≤ Δ SDS FH-SDS TH ≤ +1) were outcomes of interest. RESULTS: GHD/P+ had better FH-SDS (-0.87 vs -1.49; P = .023) and ΔSDS FH-TH (-0.35 vs -0.77; P = .002) than CDGP- /P+ . Overall, GHD/P+ showed the highest degree of success (90%, P = .006). Regardless of priming, both rhGH and LDSS improved degree of success compared to no treatment (89% and 86% vs 63%, P = .0009). GHD/P+ showed a trend towards a higher proportion of permanent GHD compared to GHD/P- (30.43% vs 15.09%; P = .067). CONCLUSION: In peripubertal children, priming before GHST improves diagnostic accuracy of GHST for idiopathic GHD. LDSS treatment improves auxological outcomes in CDGP.

Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests.

INTRODUCTION: The COVID-19 pandemic caused an increased mortality in nursing homes due to its quick spread and the age-related high lethality. RESULTS: We observed a two-month mortality of 40%, compared to 6.4% in the previous year. This increase was seen in both COVID-19 positive (43%) and negative (24%) residents, but 8 patients among those testing negative on the swab, tested positive on serological tests. Increased mortality was associated with male gender, older age, no previous vitamin D supplementation and worse "activities of daily living (ADL)" scores, such as Barthel index, Tinetti scale and S.OS.I.A. CONCLUSION: Our data confirms a higher geriatric mortality due to COVID-19. Negative residents also had higher mortality, which we suspect is secondary to preanalytical error and a low sensitivity of the swab test in poorly compliant subjects. Male gender, older age and low scores on ADL scales (probably due to immobility) are risk factors for COVID-19 related mortality. Finally, mortality was inversely associated with vitamin D supplementation. DESIGN: In this observational study, we described the two-month mortality among the 157 residents (age 60-100) of a nursing home after Sars-CoV-2 spreading, reporting the factors associated with the outcome. We also compared the diagnostic tests for Sars-CoV-2.

Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH).

OBJECTIVE: Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. DESIGN: Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. METHODS: We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). RESULTS: 90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann's syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH. CONCLUSIONS: Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.

Acromegaly is associated with increased cancer risk: a survey in Italy.

It is debated if acromegalic patients have an increased risk to develop malignancies. The aim of the present study was to assess the standardized incidence ratios (SIRs) of different types of cancer in acromegaly on a large series of acromegalic patients managed in the somatostatin analogs era. It was evaluated the incidence of cancer in an Italian nationwide multicenter cohort study of 1512 acromegalic patients, 624 men and 888 women, mean age at diagnosis 45 ± 13 years, followed up for a mean of 10 years (12573 person-years) in respect to the general Italian population. Cancer was diagnosed in 124 patients, 72 women and 52 men. The SIRs for all cancers was significantly increased compared to the general Italian population (expected: 88, SIR 1.41; 95% CI, 1.18-1.68, P < 0.001). In the whole series, we found a significantly increased incidence of colorectal cancer (SIR 1.67; 95% CI, 1.07-2.58, P = 0.022), kidney cancer (SIR 2.87; 95% CI, 1.55-5.34, P < 0.001) and thyroid cancer (SIR 3.99; 95% CI, 2.32-6.87, P < 0.001). The exclusion of 11 cancers occurring before diagnosis of acromegaly (all in women) did not change remarkably the study outcome. In multivariate analysis, the factors significantly associated with an increased risk of malignancy were age and family history of cancer, with a non-significant trend for the estimated duration of acromegaly before diagnosis. In conclusion, we found evidence that acromegaly in Italy is associated with a moderate increase in cancer risk.

25 Hydroxyvitamin D Deficiency and Its Relationship to Autoimmune Thyroid Disease in the Elderly.

BACKGROUND: Low 25(OH) vitamin D levels have been associated with several autoimmune diseases and recently with autoimmune thyroiditis (AT). The aim of the study was to investigate the association of AT with low 25(OH) vitamin D levels in the elderly. METHODS: One hundred sixty-eight elderly subjects (mean age: 81.6 ± 9.4 years) were enrolled. Serum levels of 25(OH) vitamin D, anti-thyroid peroxidase (TPO-Ab), anti-thyroglobulin (TG-Ab) antibodies, free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were measured. RESULTS: The prevalence of AT was significantly higher in subjects with vitamin D deficiency (25(OH) vitamin D < 20 ng/mL) when compared with subjects with normal 25(OH) vitamin D (25(OH) vitamin D ≥ 20 ng/mL) levels (28% vs. 8%, respectively, p = 0.002). Patients with AT and vitamin D deficiency had a comparable hormonal profile compared to patients with AT and vitamin D sufficiency in terms of TSH (p = 0.39), FT3 (p = 0.30), FT4 (p = 0.31), TG-Ab (0.44) and TPO-Ab (0.35). Interestingly, a significant correlation between 25(OH) vitamin D and TPO-Ab (r = -0.27, p = 0.03) and FT3 (r = 0.35, p = 0.006) has been found in subjects with AT while no correlation was found between 25(OH) vitamin D levels and TG-Ab (r = -0.15, p = 0.25), TSH (r = -0.014, p = 0.09) and FT4 (r = 0.13, p = 0.32). CONCLUSIONS: These findings suggest that vitamin D deficiency was significantly associated with AT in the elderly. Therefore, the screening for AT should be suggested in subjects with vitamin D deficiency.

Differential patterns of regional neuroadrenergic cardiovascular drive in acromegalic disease.

It has been shown that acromegaly is characterized by an autonomic imbalance and by marked sympathoinhibition. However, there is no information available as to whether adrenergic inhibition is confined to selected vascular districts or, rather, is generalized. We examined 17 newly diagnosed active acromegalic patients without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy and 14 healthy subjects matched for age, sex and body mass index. For each subject, we collected information regarding anthropometric parameters and echocardiography, and collected plasma samples to investigate anterior pituitary function, glucose and lipid metabolism and plasma leptin levels. Beat-to-beat mean arterial pressure, heart rate and efferent post-ganglionic muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively; determined by microneurography) were measured. Both MSNA and SSNA were recorded in a randomized sequence over two 30 min periods. Measurements also included evaluation of SSNA responses to emotional stimulus. In addition to significant reductions in plasma leptin levels, acromegalic patients had markedly decreased MSNA compared with the healthy controls. There were no significant differences in SSNA between the two groups, either under basal conditions or in responses to arousal stimuli. There was a significant and direct correlation between MSNA and plasma leptin levels, but not between plasma leptin and SSNA. These data provide the first evidence that the sympathetic inhibition characterizing the early phase of acromegaly is not generalized to the entire cardiovascular system.

Low circulating IGF-I bioactivity is associated with human longevity: findings in centenarians' offspring.

UNLABELLED: Centenarians' offspring represent a suitable model to study age-dependent variables (e.g. IGF-I) potentially involved in the modulation of the lifespan. The aim of the present study was to investigate the role of the IGF-I in human longevity. We evaluated circulating IGF-I bioactivity measured by an innovative IGF-I Kinase Receptor Activation (KIRA) Assay, total IGF-I, IGFBP-3, total IGF-II, insulin, glucose, HOMA2-B% and HOMA2-S% in 192 centenarians' offspring and 80 offspring-controls of which both parents died relatively young. Both groups were well-matched for age, gender and BMI with the centenarians' offspring. IGF-I bioactivity (p〈0.01), total IGF-I (p〈0.01) and the IGF-I/IGFBP-3 molar ratio (p〈0.001) were significantly lower in centenarians' offspring compared to offspring matched-controls. Serum insulin, glucose, HOMA2-B% and HOMA2-S% values were similar between both groups. In centenarians' offspring IGF-I bioactivity was inversely associated to insulin sensitivity. IN CONCLUSION: 1) centenarians' offspring had relatively lower circulating IGF-I bioactivity compared to offspring matched-controls; 2) IGF-I bioactivity in centenarians' offspring was inversely related to insulin sensitivity. These data support a role of the IGF-I/insulin system in the modulation of human aging process.

Von Willebrand factor and fibrinolytic parameters during the desmopressin test in patients with Cushing's disease.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Desmopressin is a known haemostatic agent and is also being used, albeit at lower doses, during the diagnostic work-up of Cushing's syndrome, a condition characterized by excess cortisol concentrations and frequent thromboembolic events. No study has yet evaluated whether administration of desmopressin for diagnostic purposes induces significant, adverse changes in endothelial cell markers in these patients. WHAT THIS STUDY ADDS: Administration of desmopressin to patients with Cushing's disease induces changes in endothelial cell markers comparable with those observed in obese and normal weight subjects. It follows, that desmopressin testing does not induce disease-specific untoward changes in coagulatory markers in patients with endogenous hypercortisolism and its use in this context appears safe. AIMS: Desmopressin, a vasopressin analogue, is used for various clinical purposes, including haemostasis and, in recent times, the diagnostic work-up of patients with Cushing's syndrome, a condition associated with a known prothrombotic profile. We decided to evaluate whether and to what extent a diagnostic dose of desmopressin induces significant changes in endothelial parameters in patients with Cushing's disease (CD) and obese and normal weight controls. METHODS: Twelve patients with CD, 10 obese and five normal weight controls were studied. Von Willebrand antigen (VWF:Ag), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured at baseline and up to 4 h after 10 µg desmopressin i.v. RESULTS: Desmopressin 10 µg transiently increased VWF:Ag and t-PA and decreased PAI-1 in all subjects. The magnitude of the VWF:Ag and t-PA increases after desmopressin was comparable in the three groups (VWF:Ag peak-to-basal ratio 1.9 ± 0.17, 1.5 ± 0.11 and 1.8 ± 0.13 and t-PA peak-to-basal ratio 1.6 ± 0.18, 1.6 ± 0.20 and 1.8 ± 0.24 for CD, obese and controls, respectively, all NS). The PAI-1 decrease observed in patients with CD was comparable with obese (0.7 ± 0.07 and 0.6 ± 0.09, NS) and controls (0.7 ± 0.07 vs. 0.4 ± 0.09, P= 0.08). CONCLUSIONS: Administration of desmopressin to patients with CD for diagnostic purposes induces a transitory increase in VWF:Ag counterbalanced by a decrease in PAI-1 and increase in t-PA. The magnitude of these changes is largely comparable with that observed in obese and normal weight controls. Our data show that testing with desmopressin does not induce disease-specific changes in endothelial markers in patients with CD.

The diagnosis of GH deficiency in obese patients: a reappraisal with GHRH plus arginine testing after pharmacological blockade of lipolysis.

BACKGROUND: The diagnosis of GH deficiency (GHD) in obese patients is complicated by the reduced GH secretion associated with overweight. A GH response to GHRH+arginine lower than 4.2 microg/l is currently considered indicative of GHD in obesity. The aim of the study was to investigate the effect of acute pharmacological blockade of lipolysis on the GH response to GHRH+arginine in obese patients. PATIENTS AND METHODS: Two groups of patients were studied: 12 obese patients with proven GHD and 14 patients with essential obesity. On separate occasions, two tests were carried out in each patient: GHRH+arginine and GHRH+arginine preceded by acipimox. RESULTS: The mean GH peak after GHRH+arginine was significantly lower in hypopituitary patients than in subjects with essential obesity. Acipimox significantly increased the mean GH response in patients with essential obesity, but not in hypopituitary subjects. All hypopituitary patients and 7/14 patients with essential obesity displayed GH peaks lower than 4.2 microg/l after GHRH+arginine: the GH response to the test increased after acipimox pretreatment in five of these seven essentially obese subjects. After acipimox administration, free fatty acids (FFAs) significantly fell in both groups with comparable mean absolute decreases. All IGF1 values were normal in both groups of subjects. CONCLUSIONS: Our study has demonstrated that the acipimox-induced acute reduction of circulating FFA levels increases mean somatotropin response to GHRH+arginine in patients with essential obesity, whereas it has no effect in hypopituitary subjects. The current criterion for the diagnosis of GHD in obese patients may be misleading. Indeed, subjects affected by third degree obesity, like most of our patients, may be erroneously classified as really GH-deficient and started on an expensive unjustified treatment. It appears therefore that the current criteria for the diagnosis of GHD in obesity should be reconsidered in the light of further studies also taking into account different body mass index groups.

Elastosonographic evaluation of thyroid nodules in acromegaly.

OBJECTIVE: Ultrasound-elastography (US-E) appears to be a helpful tool for the diagnosis of thyroid cancer. In acromegaly, the prevalence of thyroid cancer is still debated. The aims of this study were to evaluate thyroid nodules in acromegaly and to establish the accuracy of US-E in providing information on their nature, using cytological analysis as a reference. SUBJECTS AND METHODS: US-E was applied to 90 nodules detected in 25 acromegalic patients and to 94 nodules found in 31 non-acromegalic goitrous subjects. The lesions were classified according to the elasticity scores (ES) as soft (ES 1-2) or hard (ES 3-4). Fine needle aspiration cytology could be performed in 60.8% of hard nodules in acromegalics and in 86.7% of hard nodules in controls. RESULTS: The prevalence of hard nodules was significantly higher in the whole group of acromegalic patients than in controls (56.8 vs 16.0%, P<0.0001). The prevalence of hard nodules in patients with active acromegaly (68.9%) was greater, though not to a statistically significant extent, than that observed in cured (44.4%) and controlled (52.5%) patients. Cytology revealed malignancy or suspect malignancy in four of the nodules of non-acromegalic subjects and in none of the nodules of acromegalic patients. CONCLUSIONS: This study has demonstrated a high prevalence of stiff thyroid nodules in acromegaly, greater than that found in non-acromegalic goitrous subjects. In acromegalics, hard nodules appeared not to be malignant on cytopathological examination and are probably of fibrous nature. Thus, US-E appears to be of limited value for the diagnosis of thyroid cancer in acromegaly.

Specificity of first-line tests for the diagnosis of Cushing's syndrome: assessment in a large series.

CONTEXT: The diagnosis of Cushing's syndrome requires highly sensitive screening tests. Therefore, diagnostic cutoffs have been lowered to maximize sensitivity and identify all patients. However, few studies have investigated the impact of these refinements on the specificity of first-line tests. OBJECTIVE: The aim of the study was the assessment of the specificity of three widely used screening tests in a large series of Cushing's syndrome suspects referred to our endocrine service. PATIENTS: We retrospectively reviewed the results of urinary free cortisol (UFC), 1-mg dexamethasone suppression test [overnight suppression test (OST)], and serum cortisol at midnight in 3,461, 357, and 864 patients, respectively, with clinical features suggestive of Cushing's syndrome but in whom this diagnosis was subsequently excluded. RESULTS: UFC and OST at the 5-microg/dl cutoff exhibited the highest specificities [91% (95% confidence intervals [CI] 90.2-92.1%) and 97% (95% CI 96.3-98.5%), respectively]. Conversely, midnight serum cortisol yielded 87% (95% CI 84.3-91.1%) specificity only with the 7.5-microg/dl cutoff, whereas the 1.8-microg/dl threshold resulted in an unacceptably high proportion of false positives at only 20% specificity (95% CI 16.0-24.4%). Gender and age may lead to misleading results in all three screening tests. CONCLUSIONS: Specificity of tests for Cushing's syndrome varies considerably, with OST and UFC presenting the best performances, and circadian rhythm appearing heavily impaired by lowering of diagnostic cutoffs. Indeed, the vast majority of individuals in our series presented midnight serum cortisol values greater than 1.8 microg/dl; thus, caution has to be exercised when this criterion is used to exclude Cushing's syndrome.

Effects of treatment with somatostatin analogues on QT interval duration in acromegalic patients.

OBJECTIVE: Cardiovascular disease is a major contributor to the increased mortality of acromegalic patients. Prolongation of the QT interval is considered an established risk factor for potentially fatal cardiac arrhythmias, an event frequently observed in acromegaly. Changes in ventricular repolarization have been observed with the use of octreotide, one of the somatostatin analogues (SSA) currently used for the medical treatment of this disease. Furthermore, octreotide is listed among the drugs able to prolong the QT interval. Thus, we elected to study the effects of long-term SSA administration on QT duration and left ventricular mass (LVM) in a group of acromegalic patients. DESIGN AND PATIENTS: In a retrospective study, 30 acromegalic patients (19 women and 11 men, aged 25-77 years) were studied under basal conditions; 24 of them (15 women and nine men, aged 25-77 years) were studied again after 3-63 months of treatment (median 18 months) with SSA. Twenty-four healthy volunteers served as controls. MEASUREMENTS: Patients and controls underwent electrocardiographic (ECG) analysis, and QT interval duration corrected for heart rate (QTc) was established according to the Bazett formula. In 17 of the SSA-treated patients, M- and B-mode echocardiography for the assessment of LVM index (LVMi) was performed. RESULTS: Baseline QTc was significantly longer in patients than in controls. SSA administration was followed by a significant decrease in QTc, which reached a mean value similar to that measured in the controls. In particular, treatment with SSA normalized QTc in three out of the six patients with abnormally elevated values at baseline. After treatment, a significant reduction in heart rate was recorded, while LVMi displayed a slight but not significant decrease. CONCLUSIONS: Acromegalic patients frequently display an abnormally prolonged QT interval, a known risk factor for potentially fatal arrhythmias. Treatment of these patients with SSA is able to improve and even normalize this alteration, probably contributing to the beneficial effects of these drugs on cardiac rhythm in this endocrine disorder. The inclusion of octreotide in the list of drugs that may increase QTc should be reconsidered as regards its indication in acromegaly.