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Biomedical subjects

G Murialdo

Publications and source records attributed to G Murialdo.

At least 19 recordsLinked to original sources

Effects of recombinant human thyrotropin on heart rate variability and blood pressure in patients on l-thyroxine-suppressive therapy for differentiated thyroid carcinoma.

BACKGROUND: Recombinant human thyrotropin (rhTSH) is now currently used for the follow-up of patients with differentiated thyroid carcinoma (DTC) after total thyroid ablation. Side effects after rhTSH could involve the autonomic system and TSH receptors are possibly expressed in the heart and coronary arteries. METHODS: Heart rate variability (HRV), studied by power spectral analysis of low (LF) and high frequency (HF) powers, blood pressure (BP) and their responses to orthostatism were investigated before and 3, 6, 9 days after the first of two administrations of rhTSH on alternate days in 11 patients on chronic l-thyroxine (l-T4) suppressive therapy for DTC and in 31 healthy controls. RESULTS: A transient asymptomatic decrease in systolic and mean BP was observed during the rhTSH test, but rhTSH did not modify sympathovagal control of HRV and the lying to standing responses. Decreased LF power and LF/(LF + HF) and LF/HF ratios in DTC patients versus healthy controls indicated a sympathetic failure ascribed to the TSH-suppressive therapy with l-T4 rather than to direct effects of rhTSH. CONCLUSIONS: These findings allowed us to confirm the cardiovascular safety of rhTSH and the absence of its effects on sympathovagal control of HRV when used in the follow-up of patients with normal heart function after thyroid ablation for DTC.

Adult↗

Pituitary tumor disappearance in a patient with newly diagnosed acromegaly primarily treated with octreotide LAR.

We describe the case of an acromegalic patient primarily treated with octreotide LAR in whom the pituitary tumor disappeared after 18 months of treatment. A 68-yr-old woman, with clinical suspicion of acromegaly, was admitted to our Unit with the ultrasonographical evidence of cardiac hypertrophy, arrhythmias, right branch block and interatrial septum aneurism. She referred hands and feet enlargement since the age of 30 and facial disfigurements since the age of 50. At the age of 45 she underwent surgery for carpal tunnel syndrome and at the age of 61 an euthyroid nodular goiter was diagnosed. Hormonal evaluation showed elevated circulating GH levels (25+/-3.2 ng/ml), not suppressible after oral glucose load, and elevated IGF-I levels (646 ng/ml), whereas the remaining pituitary function was normal. Visual perimetry was normal, whereas magnetic resonance imaging (MRI) showed an intrasellar pituitary adenoma with maximal diameter of 9 mm. In order to improve cardiovascular function before surgery, the patient started octreotide LAR 20 mg every 4 weeks for 3 months. Then based on IGF-I values, the dose was adjusted to 30 mg. After 6 months a second MRI showed significant tumor reduction (>50% of baseline maximal diameter), GH and IGF-I were within the normal range and the patient continued the treatment. After one-year therapy, an improvement of cardiac alterations was recorded and the patient was referred to the neurosurgeon. However, she refused the operation. At 18-month follow-up, MRI showed the complete disappearance of direct and indirect signs of pituitary adenoma. To our knowledge, this is the first case of complete radiological remission of pituitary tumor during octreotide LAR treatment in acromegaly.

Acromegaly↗

Graves' ophthalmopathy and atrophic thyroiditis: a case report.

Graves' ophthalmopathy (GO)--also known as thyroid-associated orbitopathy or ophthalmopathy--usually affects patients with Graves' disease. Antibodies stimulating the TSH receptor are thought to be involved in the pathogenesis of this important and disabling extra-thyroidal manifestation of Graves' disease. Less frequently, GO occurs in subjects who neither have nor have ever shown evidence of thyroid dysfunction ("euthyroid GO"), while the occurrence of GO in patients with autoimmune Hashimoto's thyroiditis is thought to be quite rare and has sporadically been reported. The late and abrupt occurrence of severe GO without hyperthyroidism in an 88-yr-old woman with primary myxedema due to atrophic thyroiditis must be considered as an exceptional event. In this patient, GO was combined with elevated titres of serum auto-antibodies directed against the TSH receptor, while serum levels of anti-thyroglobulin and thyroperoxidase antibodies were within the normal range or only occasionally slightly above the normal values.

Aged↗

Spectral analysis of R-R interval variability by short-term recording in anorexia nervosa.

Subjects with anorexia nervosa (AN) present a number of changes in autonomic system functions, such as thermoregulation, vascular motility, heart rate and rhythm, and blood pressure. We evaluated the changes in the autonomic control of heart rate and blood pressure after postural variation by means of the spectral analysis of R-R interval variability (HRV in 13 female subjects with AN diagnosed on the basis of diagnostic statistical manual (DSM-IV) criteria, a mean age of 25 +/- 5.8 years and a mean body mass index (BMI) of 16.9 +/- 2.6. The controls were 16 healthy female subjects with a mean age of 25 +/- 2.3 years and a normal BMI. The data were statistically evaluated by means of one-way analysis of variance or Student's t test. The high frequency (HF) components of the spectral analysis did not significantly change when passing from clino- to orthostatism in the AN subjects, but there were significant changes in the controls. The changes in the low frequency (LF) components were similar in both groups, but smaller in the AN subjects. However, the difference between the two series was not statistically significant. The variance in the orthostatic R-R intervals recorded in the AN subjects was significantly less than the clinostatic intervals, the intervals recorded in the controls. These results indicate that AN subjects show signs of autonomic dysfunction. The increase in the HF component of the spectral analysis suggests that parasympathetic modulation is abnormally persistent during orthostatism, furthermore, the variability of the R-R intervals indicates that orthosympathetic regulation is also altered in AN.

Adolescent↗

Dementia: a neuroendocrine perspective.

The etiology of Alzheimer's disease (AD) has not been as yet completely defined. Genetic, environmental and neurophysiological aspects should all be taken into account. The disease has also neuroendocrine implications, some of which are discussed in this review. It is known that stress and glucocorticoids may affect neurone survival. On the contrary, some data indicate that DHEA and DHEAS exert a neuroprotective action. In AD, changes in hypothalamic-pituitary-adrenal axis function have been reported. Experimental and clinical evidence indicates that glucocorticoid hypersecretion and DHEAS levels decrement may add to hippocampal dysfunction in aging and in AD. Glucocorticoid and beta-amyloid concur in the mechanism of neurone damage, as well as excitatory amino acids (EAA), Ca++ and reactive oxygen species (ROS). The neuroprotective effects exerted by IGFs are also hindered in aging and even more in AD. Production and biological actions of IGFs are negatively influenced by cortisol hypersecretion and DHEAS decrease in patients with AD.

Aging↗

Relationships between cortisol, dehydroepiandrosterone sulphate and insulin-like growth factor-I system in dementia.

Changes in the hypothalamus-pituitary-adrenal axis (HPAA) function, entailing elevated cortisol circulating titres, occur in aging and in some neurological conditions, such as Alzheimer's disease (AD). Excess cortisol has neurotoxic effects which affect hippocampal neurones. Dehydroepiandrosterone sulphate (DHEAS) has an antiglucocorticoid activity and neuroprotective effects, but its levels decrease with aging. Glucocorticoids influence the production of insulin-like growth factor-I (IGF-I) and modify its systemic and neurotrophic biological activity by inducing changes in IGF-binding proteins (IGFBPs). We looked for relationships between cortisol, DHEAS levels, and IGF-I - IGFBPs system in AD. Cortisol, DHEAS and GH levels at 02:00, 08:00, 14:00, 20:00 h, basal IGF-I, IGFBP-1 and IGFBP-3 levels were determined by RIAs or IRMA in 25 AD patients, aged 58-89 yr, and in 12 age-matched healthy controls. AD subjects had higher cortisol, lower DHEAS levels and increased cortisol/DHEAS ratio (C/Dr) than controls. In AD cases, total IGF-I, IGFBP-3, and IGF-I/IGFBP ratios were significantly lowered, while IGFBP-1 levels were significantly higher than in controls. We found a significant inverse correlation between IGF-I and IGFBP-3 levels vs C/Dr, and between both IGF-I/IGFBPs ratios vs mean cortisol levels. IGFBP-3 correlated directly with DHEAS. Cortisol was directly and IGF-I inversely correlated with cognitive impairment. In AD patients we found that alterations in HPAA function and elevated C/Dr are related to lowered total and free IGF-I levels. These findings and their relationship to cognitive impairment suggest that changes in hormonal set-up might influence the clinical presentation of the disease.

Adrenal Glands↗

Dexamethasone effects on cortisol secretion in Alzheimer's disease: some clinical and hormonal features in suppressor and nonsuppressor patients.

Alterations in the hypothalamic-pituitary-adrenal axis (HPAA) and failure of dexamethasone (DXT) to suppress cortisol secretion occur in Alzheimer's disease (AD). This study was aimed to settle possible differences in some clinical (age, body weight, body mass index, dementia severity) and hormonal parameters in AD patients non-responders to overnight 1 mg-DXT suppression test compared with the responder subjects. ACTH, cortisol and dehydroepiandrosterone sulphate (DHEAS) day-time levels were assessed in 25 AD patients and in 12 age-matched healthy controls before DXT administration. In view of their neuroprotective effects, plasma levels of Insulin-like Growth Factor-I (IGF-I) and of IGF-Binding Proteins (IGFBPs) were also determined. After DXT, 8 AD subjects (32%) showed cortisol levels above the conventional cut-off of 140 nmol/L. No significant differences were found in clinical parameters in suppressor vs nonsuppressor patients. AD subjects showed higher cortisol, cortisol/DHEAS ratios, and lower DHEAS levels in comparison with controls. Both ACTH and cortisol levels were not different in suppressor and nonsuppressor patients, but DHEAS levels were significantly lower in nonsuppressor cases, who also exhibited ACTH and cortisol periodicities more altered than in suppressor and in control subjects. IGF-I and IGFBP-3 levels were lower and those of IGFBP-1 higher in nonsuppressor than in suppressor cases and in healthy controls. IGF-I/IGFBPs system data were correlated with cognitive impairment and adrenal steroid levels in AD patients.

Aged↗

Hippocampal perfusion and pituitary-adrenal axis in Alzheimer's disease.

The hippocampus is involved in Alzheimer's disease (AD) and regulates the hypothalamus-pituitary-adrenal axis (HPAA). Enhanced cortisol secretion has been reported in AD. Increased cortisol levels affect hippocampal neuron survival and potentiate beta-amyloid toxicity. Conversely, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are believed to antagonize noxious glucocorticoid effects and exert a neuroprotective activity. The present study was aimed at investigating possible correlations between hippocampus perfusion - evaluated by SPECT - and HPAA function in AD. Fourteen patients with AD and 12 healthy age-matched controls were studied by (99m)Tc-HMPAO high-resolution brain SPECT. Plasma adrenocorticotropin, cortisol, and DHEAS levels were determined at 2.00, 8.00, 14.00, 20.00 h in all subjects and their mean values were computed. Cortisol/DHEAS ratios (C/Dr) were also calculated. Bilateral impairment of SPECT hippocampal perfusion was observed in AD patients as compared to controls. Mean cortisol levels were significantly increased and DHEAS titers were lowered in patients with AD, as compared with controls. C/Dr was also significantly higher in patients. Using a stepwise procedure for dependent SPECT variables, the variance of hippocampal perfusional data was accounted for by mean basal DHEAS levels. Moreover, hippocampal SPECT data correlated directly with mean DHEAS levels, and inversely with C/Dr. These data show a relationship between hippocampal perfusion and HPAA function in AD. Decreased DHEAS, rather than enhanced cortisol levels, appears to be correlated with changes of hippocampal perfusion in dementia.

Adrenocorticotropic Hormone↗

Relationship between cognitive function, growth hormone and insulin-like growth factor I plasma levels in aged subjects.

Basal growth hormone (GH) and insulin-like growth factor I (IGF-I) as well as GH responses to GH-releasing hormone (GHRH) were studied in 22 subjects (7 females, 15 males), aged between 65 and 86 years. The study was aimed at investigating the possible correlations between the age-dependent GH-IGF-I axis decline and the cognitive function - assessed by the Mini Mental State Examination (MMSE). The relationship between hormonal data, cognition and age, body weight, body mass index (BMI), some nutritional indices (triceps skinfolds, TSF, mid-arm circumference, MAC), and physical activity - quantified by the physical functioning index (PFI)--were also analyzed. GH basal levels were within the normal range, while GH responses to GHRH were blunted in most cases. GH peaks after GHRH were directly correlated with GH basal values. IGF-I serum levels were found to be in the lower part of the reference range for adult subjects or below it. GH responses to GHRH, but not GH and IGF-I basal levels, were inversely correlated with subject age. GH secretion areas after GHRH were inversely correlated with BMI, but no further correlations between GH data and clinical or nutritional parameters were found. MMSE values directly correlated with MAC and PFI values. IGF-I levels were directly correlated with MMSE scores, being lowered in patients with more advanced cognitive deterioration, and with MAC values--the decrease of which is thought to reflect protein caloric malnutrition--but not with body weight, BMI, TSF and PFI. MMSE-related protein caloric malnutrition and decreased physical activity possibly take part in affecting IGF- I function in subjects with mild cognitive impairment and, reciprocally, IGF-I decrement might affect neuronal function.

Aged↗

Menstrual cycle and ovary alterations in women with epilepsy on antiepileptic therapy.

Impaired reproductive function is thought to frequently affect women with epilepsy, mainly when seizures originate in the temporal lobe. In this study, we evaluated menstrual cycle features and assessed ovulation by determining luteal progesterone (Pg) levels in 101 consecutive women with epilepsy (36 with idiopathic generalized epilepsy -IGE; 65 with partial epilepsy -PE), aged between 16 and 50 years, treated with various antiepileptic drugs (AED). PE originated in the temporal lobe (TLE) in 40 subjects, in the frontal lobe in 13, in the parietal lobe in 2, while the origin of focal seizures remained undetermined in 10 patients. In all patients, menstrual and reproductive history, body mass index, hair distribution and hormonal pattern were assessed. Suprapubic ovary ultrasound (US) examination was carried out in 83 patients (28 with IGE, 55 with PE). Three patients with IGE and one with PE were amenorrheic. Oligomenorrhea occurred in 16 patients, polymenorrhea in 2. Changes in menstrual cyclicity were independent from epilepsy type (19.4% in IGE; 23.1% in PE) and from origin of focal discharges (22.5% of patients with TLE; 20.0% with origin in other brain areas). Luteal Pg levels remained below 2 ng/ml in 30 patients independently of epilepsy type. Corpus luteum dysfunction was combined with hyperandrogenism in 15 of these patients. In the other cases different alterations of hypothalamus-pituitary-ovary axis were observed. Valproic acid blunted luteal Pg surge more frequently than other AED. Polycystic ovaries (PCO) were observed in 14 (16.9%) patients (21.0% with IGE: 14.5% with PE). These prevalences are not higher than those reported in the general population. Among PE patients, PCO was found in 1 case with undetermined focal origin and in 7 TLE cases, who also had ovary volume significantly larger than patients with seizures originating from the frontal or parietal lobe. Epileptic women exhibited an increased occurrence of multifollicular ovaries (MFO) found in 12 cases (14.4% vs 5% in the general population). However, no defined hormonal or clinical pictures were associated with this US alteration in most patients. These findings reappraise the impact of ovary alterations in women mainly affected by mild to moderate epilepsy, on differing AED regimens, with the exception of more frequent ovulatory dysfunction and PCO occurrence in patients taking VPA.

Adolescent↗

Sex hormones and pituitary function in male epileptic patients with altered or normal sexuality.

Male epileptic patients frequently complain of sexual dysfunction, particularly impotence and loss of libido. Epilepsy itself, antiepileptic drugs (AEDs), and psychosocial factors are believed to contribute to impaired sexuality. We studied luteinizing hormone (LH) pulsatile secretion, gonadotropin, and prolactin (PRL) responses to LH-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) in 37 adult male epileptic patients receiving AED monotherapy who were seizure-free and had normal EEGs. Sexuality was assessed by psychological interview. Impotence was diagnosed in 8 patients (in 2 combined with loss of sexual desire). The occurrence of hyposexuality (approximately 20%) was independent of epilepsy syndrome or AED. No change in total testosterone (T) level was observed. Free T (fT) and dihydrotestosterone (DHT) levels were lower and sex hormone binding globulin (SHBG) levels were higher in epileptic subjects than in healthy controls, but a statistically significant difference was not observed between hypo- and normosexual patients. In impotent epileptic patients, estradiol (E2) levels were significantly increased as compared with those of patients with preserved sexuality and of healthy controls. The unbalanced relation between androgen and E2 levels was emphasized by decreased T/E2, fT/E2, and DHT/E2 ratios obtained in hyposexual epileptic patients. In this group, LHRH induced blunted LH peaks. No changes were noted in LH pulsatility features. These findings of higher E2 levels and of decreased LH response to LHRH administration in some epileptic patients with impaired sexuality, may suggest they have subclinical hypogonadotropic hypogonadism.

Adult↗

Lowered circannual urinary melatonin concentrations in episodic cluster headache.

The circannual secretion of melatonin in 14 Swedish and 15 Italian patients suffering from episodic cluster headache was compared with 14 Swedish and 15 Italian healthy controls matched for sex and age. Overnight samples of urine were collected once a month from 8 to 14 months and kept at -20 degrees C until analysed with RIA. The melatonin concentrations in nocturnal urine were permanently low in cluster headache and there was no consistent change of the melatonin concentration in relation to cluster periods occurring during the study. There was no definitive circannual or infraannual rhythmicity of melatonin in patients or controls. Multiple analysis of variance with repeated measurements showed a significant effect of disease (p < 0.05), but not of time. Sex, geographical location, age, and smoking also had significant effects (p < 0.001) on the melatonin concentrations. Lower melatonin levels in cluster headache patients than in controls may in part be related to a larger number of smokers in the patient group. The relation between tobacco use and melatonin should be further studied.

Adult↗

Urinary melatonin excretion throughout the ovarian cycle in menstrually related migraine.

Nocturnal urinary melatonin excretion was significantly decreased throughout an ovarian cycle in 12 migraine without aura patients compared to 8 healthy controls. Normal increases in urinary melatonin excretion during the luteal phase was less pronounced in the migraine patients. Melatonin excretion was further decreased during headache. The data indicate impaired pineal function in migraine.

Adult↗

Sex hormones, gonadotropins and prolactin in male epileptic subjects in remission: role of the epileptic syndrome and of antiepileptic drugs.

Sex steroid peripheral pattern, pulsatile luteinizing hormone (LH) secretion, gonadotropin and prolactin responses to LH-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) were studied in 35 male epileptics treated with phenobarbital (PB), carbamazepine (CBZ), or phenytoin (PHT), and in age-matched healthy males. Idiopathic generalized epilepsy (IGE) was diagnosed in 12 cases and partial epilepsy (PE) in 23 cases. Patients were seizure-free and did not show EEG abnormalities at repeated controls in the last 5 years, so that interfering effects of seizures were possibly excluded. The aim of the study was to evaluate both the role of epileptic syndromes and of anti-epileptic drugs on the endocrine function. Changes in sex hormone binding globulin, total and free testosterone, dihydrotestosterone and delta 4-androstenedione were found to be independent of the epileptic syndrome type. The LH response to LHRH was lower in PB-treated PE than in IGE subjects on the same drug regimen. An impairment of LH pulsatility with respect to controls was found in PE but not in IGE patients taking PB. Among antiepileptic drugs, PHT is associated with higher sex hormone binding globulin and estradiol and lower free testosterone and dihydrotestosterone levels. PB and CBZ, but not PHT, blunt the LH response to exogenous LHRH in PE. Prolactin responses to TRH were consistently enhanced in PE subjects treated with CBZ or PHT.

Adult↗

Circadian secretion of melatonin and thyrotropin in hospitalized aged patients.

Alterations in periodical functions are known to occur in aging and may be regarded as markers of the aging process itself. Melatonin and Thyroid Stimulating Hormone (TSH) circadian periodicities were studied in 22 aged subjects and in 13 adult controls. The study of rhythmicity was performed by the Cosinor analysis. Elderly subjects were hospitalized because of various concomitant diseases. Circadian periodicity of both hormones was disrupted in the aged group, and the deterioration of melatonin periodicity was significantly correlated with the decay in cognitive functions, quantified by the Mini Mental State evaluation. Diabetes was also found to affect, though not significantly, melatonin, but not TSH, periodicity. Melatonin and TSH nocturnal peaks were decreased in aged people. TSH oscillation amplitudes were inversely correlated with age. No correlation was found between melatonin and TSH secretory features both in adult and in aged subjects.

Adult↗

Effects of pyridostigmine, corticotropin-releasing hormone and growth hormone-releasing hormone on the pituitary-adrenal axis and on growth hormone secretion in dementia.

Alterations of neuroendocrinological indices determined by the impaired regulating effects of cholinergic neurotransmission have been described in primary dementia. In this study we have evaluated the effects of acetylcholinesterase inhibition by pyridostigmine on growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol secretion and on their responses to GH-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) in 7 patients with primary degenerative dementia and in 8 sex- and age-matched controls. Demented subjects showed higher cortisol basal levels and lower ACTH levels than controls. Pyridostigmine increased the GH response to GHRH in both groups, the effect being significantly enhanced in patients. An increase of ACTH and cortisol levels was found in both groups after pyridostigmine and CRH administration. Pyridostigmine pretreatment significantly increased the ACTH response to CRH in controls but not in patients. The obtained data may indicate that a muscarinic receptor upregulation and an impairment of somatostatinergic function are operative in the regulation of GH secretion in dementia. An underlying hyperactivity of the hypothalamic-pituitary-adrenal axis impairs the responses of ACTH and cortisol to CRH in this disorder.

Adrenocorticotropic Hormone↗

Urine melatonin in alcoholic patients: a marker of alcohol abuse?

Ethanol is known to alter central neurotransmission and endocrine functions. Urine melatonin was studied in 10 male chronic alcoholic patients, before and after two weeks of controlled alcohol abstinence, and in sex and age matched healthy controls. In both groups, 24-hour urines were collected in two fractions corresponding to day- (D) (08:00-20:00) and night- (N) (20:00-08:00) time. Urine melatonin was assayed by RIA after methylene chloride extraction. Twenty-four hour urine melatonin levels were calculated adding up D and N values. In patients during alcohol intake, the 24-hour urine melatonin levels were significantly higher than in controls (p = 0.004, Student's t test). A disruption of the physiological ratio between N and D values was also observed, since the higher melatonin levels occurred in the D fraction. In drinking alcoholics, melatonin D values were significantly higher than the D values found in controls (p less than 0.01, Student's t test) and in the same patients after alcohol withdrawal (p less than 0.05). The N/D ratio approximated 1 during alcohol intake and became larger than 1 after alcohol withdrawal, as in the controls. The melatonin data were correlated with the suppressive effects of dexamethasone (DXT) on cortisol secretion evaluated both during alcohol intake and during abstinence. After alcohol withdrawal, the two (out of 10) patients, who remained unresponsive to the DXT suppression test, showed high D melatonin values and a low N/D ratio. These preliminary data indicate that in chronic alcoholism the pattern of urinary "melatonin- like immunoreactivity" is altered.

Adult↗