Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome.

OBJECTIVE: Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. PATIENTS AND METHODS: 150 patients, aged ≥65 years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200 ng/dl. RESULTS: Hypogonadism was found in 80 patients (53.3 %). Serum gonadotropin concentrations were elevated in 43.7 % of these patients, whereas 41.3 % of hypogonadic patients showed normal and 15 % low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. CONCLUSION: Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Impact of aromatic residues on the intrinsic disorder and transitional behaviour of model IDPs.

Understanding the interplay between order and disorder in intrinsically disorder proteins (IDPs), and its impact on the properties and features of materials manufactured from them, is a major challenge in the design of protein-based synthetic polymers intended for advanced functions. In this paper an elastin-like diblock co-recombinamer amphiphile (Phe-ELR) based on a hydrophobic block containing five phenylalanine (Phe) residues proximal to the carboxyl function of a glutamic acid (Glu) residue upon folding, and with Glu as the guest residue in the hydrophilic part, was engineered and its assembly behaviour compared with another amphiphilic ELR used as control. Phe-ELR was tailored in order to clarify the impact of the presence of aromatic residues in the amino acid sequence, which even in early studies by Urry's group already demonstrated a certain out-of-trend behaviour compared with other apolar amino acids, especially non-aromatic ones, on ELR behaviour. The combination of several experimental techniques indicates strong molecular interactions associated with the Phe residue, thus resulting in limited reversible character of the temperature-induced transitions during sequential thermal cycles, a lower than expected transition enthalpy, and clear differences in its supramolecular assembly with respect to the control ELR. A distinctive pre-aggregated state for the Phe-ELR under any condition of pH and temperature is found. Eventually, this state gives rise to Phe-core micelles or a solid jelly-like material, depending on the concentration, pH and presence of salts. In conclusion, it appears that the presence of aromatic residues and their ability to promote strong inter- and intramolecular interactions at any temperature and pH causes a complete modification of the order-disorder interplay present in other, non-aromatic ELRs. These molecular events have a profound impact on the physical properties of the resulting polymer when compared with other ELRs. This work helps to shed light on the limits that govern intrinsic disorder in ELRs beyond its inverse temperature transition.

Severe hyperthyroidism: aetiology, clinical features and treatment outcome.

BACKGROUND: Severe hyperthyroidism (SH) is a serious medical disorder that can compromise life. There have not been systematic studies in which SH has been evaluated in detail. Here, our aims were: (1) to analyse both clinical and analytical features and outcome in patients with SH and (2) to compare these data with those found in more usual forms of hyperthyroidism. Patients and methods All patients diagnosed of SH (free thyroxine, FT4 > 100 pmol/l, NR: 11-23) seen in our endocrinology clinic in the last 15 years were studied and compared with a sample of patients with mild (mH; FT4, 23-50 pmol/l) and moderate (MH; FT4, 51-100 pmol/l) hyperthyroidism. Aetiology, clinical analytical and imaging data at diagnosis, therapeutic response and outcome were registered. Results A total of 107 patients with overt hyperthyroidism (81 females, mean age +/- SD 46.9 +/- 16.1 years) were evaluated. We studied a historic group with SH (n = 21; 14 females, 40.9 +/- 17.2 years) and, as a comparator group, we analyszed the data of 86 hyperthyroid patients (67 females, 48.4 +/- 15.5.6 years, NS) comparable in age and gender. The comparator group was classified in MH (n = 37, 26 females, 47.2 +/- 16.6 years) and mH (n = 49, 41 females, 49.4 +/- 14.8 years). In comparison with mH group, SH patients were significantly (P < 0.05) younger and showed a greater proportion of first episode of thyroid hyperfunction (P < 0.05). Graves' disease was the main aetiology in the three groups, but patients with SH showed the highest titre of TSH-receptor antibodies (TRAb) (P < 0.001). Heart rate and size of goitre were higher in SH group than in mH and MH groups (P < 0.01). Atrial fibrillation was more frequently reported in SH group than in MH and mH groups (15.8%vs. 5.4% and 0%, respectively, P < 0.05). RESULTS: from logistic regression analysis showed that younger age [OR 0.958 (95% CI, 0.923-0.995), P = 0.026], presence of asthenia [OR 4.35 (1.48-12.78), P = 0.008] and higher heart rate [OR 1.03 (1.01-1.06), P = 0.013] were independent clinical variables associated to SH. SH patients showed similar biochemical parameters in comparison with mH group, except for increased serum aspartate aminotransferase (AST) (P < 0.01) and calcium (P < 0.05) levels, and decreased serum cholesterol (P < 0.05) and albumin (P < 0.05) concentrations. Logistic regression analysis showed that only AST [OR 1.07 (1.02-1.11), P = 0.005] was an independent biochemical variable associated to SH. No differences in the type of therapy, cure rate and time in achieving cure were found in SH subjects in relation to patients with milder forms of hyperthyroidism. FT4 was the only independent predictor of cure [OR 0.98 (CI 95%, 0.97-0.99), P < 0.05]. CONCLUSIONS: Graves' disease is the most common aetiology in patients with SH. This type of hyperthyroidism is usually de novo and is accompanied by more clinical signs, symptoms, and analytical derangements, as well as higher titres of TRAb at diagnosis than milder forms of hyperthyroidism. The present data are not able to show differences in treatment modality, time to achieve cure, and remission rate among patients with mild, moderate and severe hyperthyroidism.

Serum thyrotropin concentration is an early marker of normalization of low triiodothyronine syndrome in aged hospitalized patients after discharge.

OBJECTIVES: To assess short-term spontaneous evolution of alterations in thyroid function tests in aged hospitalized patients after discharge. METHODS: A group of 146 patients (mean age±SD 85.9±6.2 yr) was studied. Serum concentrations of TSH, free T4 (FT4), and free T3 (FT3) were evaluated in every patient both after admission and 1 month after discharge. RESULTS: At entry, both serum TSH [median (interquartile range), 2.19mU/l (0.89-2.31)] and FT4 (mean±SD, 16.7±3.4 pmol/l) concentrations were into the normal range, whereas serum FT3 concentrations were low (3.3±0.7 pmol/l). After discharge TSH and FT4 concentrations remained normal and FT3 low. However, both serum TSH [2.53 mU/l (1.24-3.33); p<0.01] and FT3 (3.7±1.0 pmol/l; p<0.001) concentrations significantly increased. Most patients (no.=124, 84.9%) showed the euthyroid sick syndrome (ESS). After discharge, ESS diminished to 76 (52.1%) subjects. Patients who normalized thyroid function tests showed significantly lower TSH values at entry compared with those who persisted with altered thyroid function tests [1.27 mU/l (0.69-1.89) vs 1.69mU/l (0.96-2.91), p<0.05]. Logistic regression analysis showed that serum levels of TSH at admission was the only variable negatively related to normalization of thyroid function [odds ratio 0.730; confidence interval 95%, 0.567-0.940; p=0.01). CONCLUSIONS: About 35%of aged patients hospitalized for acute illness spontaneously normalize their thyroid function tests 1 month after discharge, mainly due to the correction of ESS. Serum TSH levels at admission seem to be the only variable negatively related to normalization of thyroid function at this time.

Self-assembly in elastin-like recombinamers: a mechanism to mimic natural complexity.

The topic of self-assembled structures based on elastin-like recombinamers (ELRs, i.e., elastin-like polymers recombinantly bio-produced) has released a noticeable amount of references in the last few years. Most of them are intended for biomedical applications. In this review, a complete revision of the bibliography is carried out. Initially, the self-assembly (SA) concept is considered from a general point of view, and then ELRs are described and characterized based on their intrinsic disorder. A classification of the different self-assembled ELR-based structures is proposed based on their morphologies, paying special attention to their tentative modeling. The impact of the mechanism of SA on these biomaterials is analyzed. Finally, the implications of ELR SA in biological systems are considered.

Natural course of hypogonadism diagnosed during hospitalization in aged male patients.

Our aim was to assess short-term natural course of hypogonadism diagnosed during hospitalization for acute disease in aged male patients after discharge. A group of 43 hypogonadal males, aged 86.7±5.7 year, was studied. Serum concentrations of testosterone (T) and gonadotropins (follicle-stimulating hormone, FSH, and luteinizing hormone, LH) were measured in every patient both at admission and one month after discharge. Mean serum T at entry was 115.4±48.0 ng/dl. Hypogonadism was hyper-, hypo-, and normogonadotropic in 20 (46.5%), 20 (46.5%), and 3 (7.0%) patients, respectively. One month after discharge serum T concentrations increased significantly (230.9±135.6 ng/dl, p<0.001). At this point, more than half of the patients (n=27, 62.8%) showed normal serum T concentrations. Both gonadotropins, FSH (p<0.001), and LH (p=0.04) also increased one month after discharge. Approximately, half of the patients (13, 48.1%) who normalized serum T concentrations also showed normal serum gonadotropin concentrations. Patients who normalized their serum T concentrations one month after discharge showed significantly higher baseline values of T (134.7±33.9 ng/dl) than those who persisted with hypogonadism (n=16, 32.7%; 82.8±51.6 ng/dl, p<0.001). Lastly, serum T was the only independent predictor for achieving eugonadal status (OR 1.030; CI 95%, 1.010-1.050; p<0.001). In conclusion, about 63% of aged patients hospitalized for acute illness with hypogonadism discovered during hospitalization spontaneously normalize their serum T concentrations one month after discharge. Serum gonadotropin concentrations also increased after discharge. Serum T levels at admission was an independent predictor for the normalization of serum T concentrations.

Hypogonadism and Mortality in Aged Hospitalized Male Patients: A 5-Year Prospective Observational Study.

OBJECTIVE: To investigate the relationship between hypogonadism and mortality in aged hospitalized male patients. DESIGN: A 5-year prospective observational study was conducted. Gonadal function was assessed at hospital admission and mortality was registered in the follow-up period. PATIENTS AND METHODS: We studied all patients≥65 years admitted for any reason during 2010 and 2011. Serum T concentrations were quantified in all patients. Hypogonadism was defined by the presence of serum T levels<200 ng/dl. Number of deaths and all-cause and cardiovascular (CV) mortality were registered until December 31(st), 2014. RESULTS: During the study 150 patients were admitted and 103 (68.7%) of them died during follow-up. Hypogonadism was positively associated with mortality (P=0.036). The percentage of hypogonadal patients was significantly (P=0.02) higher in the group of patients who died in hospital compared with those who died after hospital discharge and those who survived. CV disease was the main cause of death in 52 patients (50.5%). Kaplan-Meier analysis showed a median survival time for all-cause mortality of 2.0 (0-16.5) months and 21.0 (5.0-33.2) months for patients with and without hypogonadism, respectively (P<0.001). Similar findings were found when analyzing mortality due to CV disease (P=0.009). Hypogonadism was a strong independent predictor for all-cause (adjusted multivariate analysis, HR 3.35; 1.55-7.23, P=0.002) and CV mortality (HR 2.14; 1.18-3.86, P=0.012). CONCLUSIONS: Hypogonadism discovered during hospitalization is associated with in-hospital and long-term mortality in elderly male patients and predicts both all-cause mortality and CV mortality in this population.