The cortisol burden in elderly subjects with metabolic syndrome and its association with low-grade inflammation.

BACKGROUND: Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. AIMS: To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). METHODS: From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). RESULTS: In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) µg/g creatinine/12 h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3 µg/g creatinine/12 h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. DISCUSSION: The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. CONCLUSION: The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

Hypovitaminosis D: comparison between patients with hip fracture and patients with vertebral fractures.

This study analyses the difference in 25OH-vitamin D values between two groups of patients both affected by severe osteoporosis with fragility fractures, but one group has vertebral fractures and the other one has hip fractures. Patients with hip fractures have vitamin D values lower than patients with vertebral fractures. INTRODUCTION: The purpose of this study was to evaluate 25OHD levels in patients with fragility vertebral fractures (VF) and hip fractures (HF) and make a comparison between the groups. METHODS: In the first group were enrolled ambulatory patients with 3 or more moderate to severe VF; in the second group were enrolled patients hospitalized in the Department of Orthogeriatrics undergoing surgery for HF. For all patients, we collected values of 25OHD and PTH. The group of patients with VF was further subdivided into pre-existing VF or recent VF treated within 30 days with vertebroplasty. RESULTS: The sample consists of 180 subjects divided into two groups: 90 with VF and 90 with HF. The average value of 25OHD in the total sample was 13.2 ± 9.6 ng/ml, Vitamin D was significantly lower in the HF group than the VF group (p < 0.001)(VF 18.6 ± 9.7 ng/ml, HF 7.9 ± 5.7 ng/ml). The mean PTH value in the total sample was 67.5 ± 54.9 pg/ml and PTH was significantly higher in the HF group compared to the group with VF (p < 0.001) (VF 55.6 ± 27.2 pg/ml, HF 78.7 ± 70.2 pg/ml). The mean 25OHD value in the recent VF group is 16.0 ± 6.6 ng/ml while in the pre-existing VF group is 19.5 ± 10.4 ng/ml with a statistically significant difference (p < 0.001). CONCLUSIONS: Patients of the same age with severe osteoporosis have a lower 25OHD value when the fracture occur at the hip and is recent, probably this is due to the inflammation caused by fracture and/or surgical intervention.

The management of hip fracture in the older population. Joint position statement by Gruppo Italiano Ortogeriatria (GIOG).

This document is a Joint Position Statement by Gruppo Italiano di OrtoGeriatria (GIOG) supported by Società Italiana di Gerontologia e Geriatria (SIGG), and Associazione Italiana Psicogeriatria (AIP) on management of hip fracture older patients. Orthogeriatric care is at present the best model of care to improve results in older patients after hip fracture. The implementation of orthogeriatric model of care, based on the collaboration between orthopaedic surgeons and geriatricians, must take into account the local availability of resources and facilities and should be integrated into the local context. At the same time the programme must be based on the best available evidences and planned following accepted quality standards that ensure the efficacy of the intervention. The position paper focused on eight quality standards for the management of hip fracture older patients in orthogeriatric model of care. The GIOG promotes the development of a clinic database with the aim of obtaining a qualitative improvement in the management of hip fracture.

Adherence to anti-osteoporotic therapies: role and determinants of "spot therapy".

UNLABELLED: A successful therapy needs high level of adherence consisting in right drug intake in terms of persistence and compliance. Our study suggests adherence is higher if spot (less than 30 days) therapies are excluded; the analysis of spot therapy causes underlines the importance of the interpersonal aspects of medical practice. INTRODUCTION: A successful therapy needs a high level of adherence consisting in right drug intake in terms of persistence and compliance. The aim of this study was to evaluate anti-osteoporotic therapies recorded in general practitioner databases in the area of Rome, which used the same computerized medical record management. The study focused on evaluating therapy adherence, any adherence changes excluding spot therapies (less than 30 days), and any cause of early therapy discontinuation in a subgroup of patients randomly selected. METHODS: Thirty-one databases were evaluated, including a total of 6,390 anti-osteoporotic therapies: 5,853 were prescribed to women and 537 to men. The prescribed drugs were: vitamin D (13 %), calcium (8.7 %), vitamin D + calcium (40.1 %), raloxifene (3.3 %), alendronate (16.4 %), risedronate (7.7 %), clodronate (10.4 %), or other drugs (0.4 %). Spot therapies represented 53.7 % of the total prescriptions. The difference between adherence in the total group (24.64 %) and the group excluding spot therapies (43.38 %) is significant. The main factors influencing low adherence were side effects (27 %), misinformation given by the physician (17 %), insufficient motivation (9 %), difficult intake (9 %), and no perceived benefits (9 %). RESULTS: Our study suggests adherence is high and similar to other chronic diseases if spot therapies are excluded. The analysis of spot therapy causes suggests that an important role is played by the physician and the interpersonal aspects of medical practice, especially at the first prescriptions. CONCLUSIONS: The physician should collaborate with patients in choosing a personalized medical treatment. Reducing spot therapy could be the real goal in order to improve anti-osteoporotic therapy adherence.

Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

A global call to action to improve the care of people with fragility fractures.

The ageing of society is driving an enormous increase in fragility fracture incidence and imposing a massive burden on patients, their families, health systems and societies globally. Disrupting the status quo has therefore become an obligation and a necessity. Initiated by the Fragility Fracture Network (FFN) at a "Presidents' Roundtable" during the 5th FFN Global Congress in 2016 several leading organisations agreed that a global multidisciplinary and multiprofessional collaboration, resulting in a Global Call to Action (CtA), would be the right step forward to improve the care of people presenting with fragility fractures. So far global and regional organisations in geriatrics/internal medicine, orthopaedics, osteoporosis/metabolic bone disease, rehabilitation and rheumatology were contacted as well as national organisations in five highly populated countries (Brazil, China, India, Japan and the United States), resulting in 81societies endorsing the CtA. We call for implementation of a systematic approach to fragility fracture care with the goal of restoring function and preventing subsequent fractures without further delay. There is an urgent need to improve: To address this fragility fracture crisis, the undersigned organisations pledge to intensify their efforts to improve the current management of all fragility fractures, prevent subsequent fractures, and strive to restore functional abilities and quality of life.

Arbuscular mycorrhizae increase the arsenic translocation factor in the As hyperaccumulating fern Pteris vittata L.

Phytoremediation techniques are receiving more attention as decontaminating strategies. Phytoextraction makes use of plants to transfer contaminants from soil to the aboveground biomass. This research is devoted to study the effects of arbuscular mycorrhizae (AM) on growth and As hyperaccumulation in the Chinese brake fern Pteris vittata. We grew for 45 days P. vittata sporophytes, infected or not infected with the AM fungi Glomus mosseae or Gigaspora margarita, in a hydroponic system on quartz sand. As-treated plants were weekly fed with 25 ppm As. The As treatment produced a dramatic increase of As concentration in pinnae and a much lower increase in roots of both mycorrhizal and control plants. Mycorrhization increased pinnae dry weight (DW) (G. margarita = G. mosseae) and leaf area (G. margarita > G. mosseae), strongly reduced root As concentration (G. mosseae > G. margarita), and increased the As translocation factor (G. mosseae > G. margarita). The concentration of phosphorus in pinnae and roots was enhanced by both fungi (G. margarita > G. mosseae). The quantitatively different effects of the two AM fungi on plant growth as well as on As and P distribution in the fern suggest that the As hyperaccumulation in P. vittata can be optimized by a careful choice of the symbiont.

Potent in vivo and in vitro prolactin inhibiting activity of sauvagine, a frog skin peptide.

The effect of sauvagine (SAU), a frog skin peptide, on prolactin (PRL) levels was studied in vivo and in vitro. Subcutaneous administration of SAU (20 micrograms/kg) reduced plasma PRL levels in normal adult male rats and suppressed the suckling-induced rise of PRL in lactating rats even at doses of 1 and 5 micrograms/kg. Perfusion of isolated and dispersed rat pituitary cells in vitro with increasing doses of SAU (from 5 x 10(-10) to 1.7 x 10(-8)M) induced a significant dose-related decrease of PRL secretion in the eluate. These results indicate that SAU is a potent PRL inhibiting factor and that its action is exerted at the pituitary level. If SAU or a SAU-related peptide is present in the mammalian brain, it can be tentatively hypothesized that this peptide plays an important role in the control of PRL secretion.

Inhibitory effect of bromocriptine treatment on luteinizing hormone secretion in polycystic ovary syndrome.

In order to investigate a possible common role of central dopaminergic mechanisms in the release of PRL and LH in patients with the polycystic ovary syndrome (PCO), plasma LH pulsatile profiles and the response to GnRH were studied in a group of 12 PCO patients before and after 3 months of treatment with bromocriptine, 2.5 mg twice daily. They were divided into two groups of six patients according to the occurrence or not of hyperprolactinemia (plasma PRL, 30.3 +/- 2.7 (SE) ng/ml vs. 9.5 +/- 0.8 (SE) ng/ml). Integrated LH secretion significantly decreased in hyperprolactinemic [2537 +/- 371 (SE) vs. 907 +/- 102 mIU/ml X min] as well as in normoprolactinemic (2847 +/- 460 vs. 901 +/- 152 mIU/ml X min) patients, but there was no difference in the response of the two groups. The LH increment after a bolus injection of 100 micrograms GnRH was reduced (P less than 0.01) to the same extent in both groups. These results indicate a dopaminergic component in the control of LH release in PCO patients, independent of the mechanism governing PRL secretion. Since bromocriptine reduced LH secretion, it may be useful for the management of this condition.

MRI in multiple sclerosis during the menstrual cycle: relationship with sex hormone patterns.

We investigated MRI activity in MS during the menstrual cycle in relation to physiologic sex hormone fluctuations. Eight women with relapsing-remitting MS were submitted to serial brain gadolinium-enhanced MRI examinations over a 3-month period in two alternate follicular and luteal phases of the menstrual cycle. The ratio of progesterone/17-beta-estradiol during the luteal phase was significantly associated with both number (r = 0.6, p = 0.03) and volume (r = 0.7, p = 0.009) of enhancing lesions, providing support for a role of these hormones as immunomodulatory factors in MS.

Effect of chronic bromocriptine treatment on psychological profile of patients with PRL-secreting pituitary adenomas.

Hyperprolactinaemic patients are characterized by an altered psychological profile, positively modified by the administration of dopaminergic drugs. This would suggest that the same neurochemical disorder is responsible for both hyperprolactinaemia and abnormal psychological profile in these patients. To identify depression, anxiety, and aggressiveness, nine women affected by prolactin (PRL)-secreting pituitary adenomas were studied before and after 6 and 12 mo of bromocriptine therapy, by the use of different psychometric tests (Mean Minnesota Multiphasic Personality Inventory [MMPI], State-Trait Anxiety Inventory [STAI], and State and Trait Aggressiveness Scale [STAS]). As a group, the patients did not show any depressive, anxious, or aggressive tendencies. Furthermore, no significant modifications were observed during dopaminergic treatment. Patients bearing PRL adenomas seem to be characterized by a dopaminergic background different from that found in functional hyperprolactinaemia. This hypothesis could explain the different psychological configuration and behavior in response to the administration of dopaminergic compounds.

Prolactin release in polycystic ovary.

Ten normoprolactinemic and 10 hyperprolactinemic patients, all with polycystic ovary syndrome (PCO), were subjected to prolactin (PRL) stimulatory tests with thyrotropin-releasing hormone (TRH), 200 microgram intravenously, and haloperidol (a dopamine-blocking agent), 1 mg intramuscularly. The results were compared with those of 8 women with idiopathic hyperprolactinemia and 10 normal female volunteers. Distinctive features of PCO were elevated plasma concentrations of luteinizing hormone, estrone, and testosterone in the presence of normal estradiol, whereas in idiopathic hyperprolactinemia estradiol was reduced. Both groups of patients with PCO exhibited responses to TRH and haloperidol significantly higher than the controls (P less than .001), whereas only the hyperprolactinemic PCO patients reacted with an excessive PRL discharge (P less than .001). As expected, the response to both secretagogue agents was blunted in patients with idiopathic hyperprolactinemia. The present report discusses the possible implication of estrogen and the dopaminergic system in the mechanisms leading to hyperprolactinemia and enhanced PRL release in PCO.

The brain-gut-skin triangle: new peptides.

New data on tachykinins and bombesins are displayed and the present situation of research on the novel amphibian skin peptides sauvagine and dermorphin is illustrated. The potent stimulant effect of sauvagine on ACTH and beta-endorphin release has been confirmed both in vivo and on columns of isolated and dispersed rat pituitary cells, and similarly the potent inhibitory effect on PRL and GH release, both in the rat and man. Particular emphasis is laid on the occurrence of sauvagine-like immunoreactivity in fish urophysis and in amphibian nervous structures, including the retina. It is suggested that the long-searched corticotropin releasing factor and PRL release-inhibiting factor may be a sauvagine-like peptide. Dermorphin, in its turn, has been found to cause, by intracerebroventricular injection, not only analgesia and catalepsy, but also conspicuous EEG and behavioral changes in the rabbit and chick, as well as a sharp reduction in gastric emptying time and gastric acid output in the rat, together with marked stimulation of PRL release.

Sex-related variations in serum nerve growth factor concentration in humans.

A role of nerve growth factor (NGF) in the neuro-endocrine-immune interactions has been recently suggested by the presence of NGF and its receptors in cells of the immune and endocrine systems. The improvement in the comprehension of the role played by NGF in humans is linked to the availability of a sensitive and reliable method to quantify NGF concentrations in body fluids and tissues. As a consequence of different methods used, normal levels of human serum NGF reported in the literature show wide differences. The present results indicate that ELISA appears very sensitive (detection limit 1.4pg/ml) and allows the discrimination of subtle variations of serum NGF concentrations. ELISA performed in serum obtained from men indicated that NGF concentration was 40.8+/-10.8pg/ml, whereas women showed significantly lower levels that were influenced by the menstrual cycle. In particular, the mean value of this neurotrophin during the follicular phase was 8.2+/-1.4pg/ml; the luteal phase, in turn, showed levels up to 14.4+/-2.9pg/ml. The difference of serum NGF concentrations between the follicular and luteal phase in each woman was statistically significant. Differences in NGF concentrations between men and women (in both phases of the menstrual cycles) were also statistically significant. In conclusion, a possible role of sex steroids as modulators of NGF secretion in humans is strongly supported by the present paper. However, mechanisms underlying this phenomenon are still unknown. The evidence indicating physiological sex hormone-related variations in NGF levels would be of interest in view of the possible use of circulating NGF modifications as a laboratory biomarker in different diseases.

Immunohistochemical localization of beta-endorphin in hyperplastic interstitial tissue of the human testis.

The immunohistochemical localization of beta-endorphin in the normal testis (two patients) and in the pathologic testis (two cases of Sertoli Cell Only Syndrome, two cases of Klinefelter Syndrome, two cases of post-orchitis tubular sclero-hialinosis) was investigated. No beta-endorphin immunostaining was detected in the normal testis, while positive beta-endorphin immunostaining has been observed in pathologic tissues. These results indicate that, as in animals, beta-endorphin is present in human Leydig cells and may play a local role in regulating male reproductive function.

Calcified pituitary adenoma associated with severe hyperprolactinemia. Case report.

A patient with a completely calcified chromophobe adenoma is reported. Endocrine evaluation revealed very high prolactin levels. Such extensive calcifications in prolactin-secreting adenomas are extremely rare. The possible pathogenetic mechanisms of this association are discussed.

Effect of r-interferon alpha administration on hypothalamus-pituitary-thyroid axis in chronic hepatitis.

Recent studies pointed out the development of autoimmune thyroid diseases during interferon (IFN) therapy, mainly in patients with positive thyroid autoantibodies (MsAb and TgAb) before treatment. The effects of recombinant human IFN alpha (rhIFNalpha) on thyroid function and thyroid autoantibodies were studied in 12 patients with chronic active hepatitis associated with virus B or C, selected on the basis of negative results for MsAb and TgAb. No significant variation in T3, T4 and TSH levels was observed either after the first administration of rhIFN alpha (3 million IU i.m.) or after three months of therapy (3 million IU i.m. 3 times a week). TSH response to TRH was in the normal range either before or after the therapy. The absence of MsAb and TgAb was confirmed in all the patients at the end of the treatment. These results indicate that no patient developed thyroid disorder during IFN therapy. Nevertheless, since positive MsAb and TgAb have been considered as a risk factor for thyroid diseases, in patients selected for IFN therapy they should be carefully assessed for autoantibodies before undergoing IFN treatment.

Phospholipid liposomes and prolactin secretion: effects on spontaneous and drug-induced hyperprolactinaemia.

Bovine brain phospholipid liposomes (BC-PL) reduce plasma prolactin (PRL) levels in humans after acute administration and counteract the metoclopramide- and sulpiride-induced hyperprolactinaemia. However, BC-PL, like nomifensine, a dopamine (DA) reuptake inhibitor and therefore an indirect dopaminergic compound, does not influence TRH-induced hyperprolactinaemia. Moreover, BC-PL and nomifensine reduce plasma PRL levels in hyperprolactinaemic PCO syndromes but not in PRL secreting pituitary adenomas. The results obtained indicate that BC-PL antagonizes the DA blockade-induced hyperprolactinaemia and that the main site of action of BC-PL seems to be at the hypothalamic level; however a concomitant pituitary effect cannot be ruled out.

Effects of different dopamine agonists and antagonists on post-menopausal hot flushes.

The dopaminergic system seems to be involved in both pulsatile luteinizing hormone (LH) secretion and hot flushes in post-menopausal women. With the aim of further clarifying its role, the effectiveness of dopaminergic and antidopaminergic drugs in the treatment of hot flushes was studied. Self-assessed scores for vasomotor symptoms were evaluated in 5 groups of 15 patients treated for 20 days with one of the following agents: placebo; the dopamine receptor agonist, bromocriptine; the indirect dopaminergic agent, Liposom; the antidopaminergic drug, veralipride or the peripheral antidopaminergic agent, domperidone. All of these treatment regimens were effective in alleviating hot flushes, but the pharmacological agents proved to be more effective than the placebo. A direct dopaminergic action is hypothesized in the case of bromocriptine and Liposom, while the antidopaminergic drugs might act through different indirect mechanisms such as the short-loop feedback exerted by hyperprolactinaemia on tuberoinfundibular dopamine (TIDA) neurons with a secondary dopamine-like activity, or stimulation of the opioid system.