Hormones and depression in the advanced age.

INTRODUCTION: In older people, depression and mental disability are more frequently present than in younger subjects. It is found that depressionis a risk factor for dementia, just as dementia is a risk factor for depression. In turn, both disturbances are known to be influenced by hormones. The present study aimed to see whether the hormonal changes in subjects over 75 years old correlate with the symptoms of depression measured using the Geriatric Depression Scale (GDS). MATERIAL AND METHODS: In a group of patients aged over 75 years, concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, testosterone, dehydroepiandrosterone sulphate (DHEAs), and cortisol were measured in serum with the use of chemiluminescence. The symptoms of depression were estimated by GDS, and the mental functions were assessed by the Mini-Mental State Examination (MMSE). The correlations between the obtained results were estimated by Spearman's test. RESULTS AND CONCLUSIONS: A significant correlation between GDS and MMSE scores was observed in the investigated patients. Some statistically significant correlations concerning cortisol and testosterone with GDS were observed in women, but not in men. On the other hand, no significant correlations between concentrations of FSH, LH, DHEAs, and oestradiol with GDS were noticed. Our data support the role of cortisol (possibly secreted during chronic stress) in the risk of depression. The gender difference in the mechanism of depression and stress in older age could be also hypothesized.

Serum testosterone level correlates with left ventricular hypertrophy in older women.

Introduction: Sex hormones may play an important role in age-related cardiac remodeling. However, their impact on cardiac structure and function in females of advanced age still remains unclear. The aim of this study is to evaluate the relationship between sex hormones level and echocardiographic parameters in older women with concomitant cardiovascular diseases. Materials and Methods: The study group included 52 community-dwelling women with mean age 79.5 ± 2.8 years, consecutive patients of an outpatient geriatric clinic. In all the subjects, a transthoracic echocardiogram was performed and serum testosterone, estradiol, follicle-stimulating hormone, luteinising hormone, dehydroepiandrosterone sulphate, and cortisol levels were determined. Results: Testosterone level correlated positively with interventricular septum diastolic dimension (IVSd) (rS=0.293, p<0.05), left ventricular mass index (rS=0.285, p<0.05), E/E' ratio (rS=0.301, p<0.05), and negatively with E' (rS=-0.301, p<0.05). Estradiol level showed a positive correlation with the posterior wall dimension (rS=0.28, p<0.05). Besides, no significant correlations between clinical or echocardiographic parameters and other hormones were observed. Female subjects with diagnosed left ventricular hypertrophy (LVH) (n=34) were characterized by a significantly higher rate of hypertension (p=0.011), higher waist-to-height ratio (p=0.009), higher testosterone level (0.82 vs. 0.48 nmol/L, p=0.024), higher testosterone/estradiol ratio (16.4 vs. 9.9, p=0.021), and received more anti-hypertensive drugs (p=0.030). In a multiple stepwise logistic regression, the best determinants of LVH were the presence of hypertension (OR=6.51; 95% CI 1.62-26.1), and testosterone level (OR= 6.6; 95% CI 1.19-36.6). Conclusions: Higher serum testosterone levels may contribute to pathological cardiac remodeling, especially in hypertensive women. Estradiol, gonadotropins, DHEAS, and cortisol were not related to echocardiographic parameters.

Endocrine and metabolic aspects of COVID-19.

The paper presents the theoretical considerations on the role of endocrine and metabolic alterations accompanying COVID-19 infection. These alterations may be presumed on the basis of the following two observations. Firstly, the virus SARS-CoV-2 responsible for the COVID-19 infection uses an important renin-angiotensin system (RAS) element - angiotensin-converting enzyme 2 (ACE2) - as a receptor protein for entry into target cells and, in consequence, disturbs the function of the main (circulating) renin-angiotensin-aldosterone system (RAAS) and of the local renin-angiotensin system localized in different tissues and organs. The binding of SARS-CoV-2 to ACE2 leads to the downregulation of this enzyme and, in the aftermath, to the excess of angiotensin II and aldosterone. Thus, in the later stage of COVID-19 infection, the beneficial effects of ACEI and ARB could be presumed. It is hypothesized that the local RAS dysregulation in the adipose tissue is the main cause of the negative role of obesity as a risk factor of severe outcome of the COVID-19 infection. Secondly, the outcome of COVID-19 strongly depends on the age of the patient. Age-related hormonal deficiencies, especially those of melatonin and dehydroepiandrosterone, may contribute to morbidity/mortality in older people. The usefulness of melatonin and angiotensin converting enzyme inhibitors/angiotensin receptor 1 blockers (the latter only in later phases of the infection) as adjuvant drugs is probable but needs thorough clinical trials.

Gonadotropins at Advanced Age - Perhaps They Are Not So Bad? Correlations Between Gonadotropins and Sarcopenia Indicators in Older Adults.

Many hormones fluctuate during the aging process. It has been suggested that gonadotropins, which increase with age, contribute to the occurrence of many diseases and syndromes in older life, such as cardiovascular diseases, obesity, frailty syndrome and osteoporosis. This study aims to assess the relationship between circulating gonadotropins and other hormones potentially contributing to age-related functional decline and sarcopenia indicators in 39 male and 61 female community-dwelling seniors, mean age 80 years. According to the definition developed by the second European Working Group on Sarcopenia in Older People (EWGSOP2), the following indicators of the sarcopenia were assessed: bioimpedance-measured body composition, gait speed, handgrip strength, timed up and go test (TUG), chair stand test, Short Physical Performance Battery (SPPB). Blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, dehydroepiandrosterone sulphate (DHEAS) and cortisol were also measured. In the men, FSH and partially LH correlated positively with muscle mass percentage, gait speed, handgrip strength and SPPB, and negatively with percent body fat. Additionally, testosterone and DHEAS correlated negatively with the percentage of fat mass in men. Whereas in the women, FSH and LH were mainly negatively associated with body mass and adipose tissue measures. Cortisol did not show any relationship with the examined indicators. The study shows that the indicators of sarcopenia are strongly associated with levels of gonadotropins, sex hormones and DHEAS, especially in older men. The obtained results, after being confirmed in a larger group, may modify prevention and treatment strategies of sarcopenia.

Possible role of gonadotropin excess in age-related diseases - return to the old hypothesis in the light of current data.

The paper presents the evaluation of a hypothesis assuming that the elevated levels of gonadotropins which occur physiologically in older persons are involved by their direct extra-gonadal action in the pathogenesis of age-related disorders. The data on the possibilities of the direct action of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and their possible deleterious effects in the brain, bone, cardiovascular system and cancer in older persons are reviewed. A proposal of a new approach to the hormonal prevention treatment of age-related disorders (suppression of gonadotropins by means of gonadotropin releasing hormone analogs) is discussed.

Immunohistochemical detection of prolactin in clinically non-functioning pituitary adenomas.

INTRODUCTION: Approximately one third of pituitary adenomas are manifested neither by specific symptoms of hormone overproduction nor by elevated blood levels of pituitary hormones. However, these tumours, diagnosed before surgical intervention as clinically non-functioning pituitary adenomas (CNFPAs) express in majority different pituitary hormones, as can be revealed by means of immunohistochemical examination. One of the pituitary hormones which may be expressed in CNFPAs is prolactin (PRL) but the clinical and pathological data on this condition are very scarce. MATERIAL AND METHODS: Sixty two pituitary adenomas, diagnosed before surgery as CNFPAs, were immunoassayed with antibodies against PRL, growth hormone (GH), luteinizing hormone (LH), follicle stimulating hormone (FSH), thyrotropin (TSH), alpha subunit (alpha-SU), corticotropin (ACTH) and dopamine receptor type 2. In a proportion of the patients the presurgical concentrations of insulin-like growth factor 1 (IGF-1) were estimated by means of enzyme-amplified chemiluminescence assay. RESULTS: Twenty-three (37.1%) of the examined CNFPAs presented the positive immunoreaction with anti-PRL antibody. Most cases concerned women. Only in two cases (one woman and one man), PRL was the unique hormone expressed in the tumour. In the remaining adenomas PRL immunopositivity was accompanied by GH expression - 17, LH or free bLH - 13, FSH - 2, free a subunit - 4 or by ACTH - 5 tumours. Seven (30.43%) of them were recurrent in comparison with 12.8% PRL-immunonegative recurrent CNFPAs. Dopamine receptors were positively immunostained in all the investigated PRL-immunopositive and all PRL-immunonegative adenomas. CONCLUSIONS: Our data confirm the observations that monohormonal silent prolactinomas are very rare but frequently silent PRL often co-expressed with GH or LH. Although in the whole population of patients with CNFPAs both sexes are equally represented, in the case of silent prolactinomas the female sex is prevalent. The observation of the higher rate of recurrent tumours within PRL-immunopositive adenomas versus PRL-immunonegative CNFPAs has to be confirmed on the larger material.

Are physical and mental abilities of older people related to gonadotropins and steroid hormones levels?

BACKGROUND: Aging is characterized by deep alterations of hormone secretion. In majority, hormone secretion, except gonadotropins, undergoes a pronounced decrease which is thought to contribute to the progression of aging. The recent data indicate that gonadotropin excess may also by itself influence the aging process. The aim of the present study was to investigate the relations between gonadotropins and steroid hormones with physical and mental abilities of older people. MATERIAL AND METHODS: In a group of patients aged over 75 years, concentrations of FSH, LH, estradiol, testosterone, DHEAs and cortisol were measured. The mental ability was estimated by MMSE and CDT and the physical ability by TUG and SPPB tests. RESULTS AND CONCLUSIONS: The positive correlation between SPPB scores and FSH and the negative correlations of SPPB with LH/FSH ratio were observed in men. The correlation of TUG scores and estradiol levels was also noted in men. The positive correlation between CDT scores and FSH in women and the negative correlation between CDT and LH/FSH ratio in men were found. The correlation between the results of CDT and cortisol levels in men was also observed. Thus, we did not confirm the simple deleterious effect of gonadotropins on cognitive abilities. FSH and LH seem exert different (antagonistic?) effects on cognitive functions, but this hypothesis needs further studies.

Gonadotropins and steroid hormones in older people: their mutual connections and relations to body mass indices.

INTRODUCTION: Aging in mammals, including man, is accompanied by deep changes in hormone secretion. In the majority of cases, hormone secretion (mostly of gonadal steroids and adrenocortical hormone dehydroepiandrosterone - DHEA) undergoes pronounced decrease. This decrease is thought to contribute to the progression of aging. In contrast, the secretion of gonadotropins is sharply increased in older adults, as a result of gonadal deficiency. Recent data indicate that gonadotropin excess may also, by itself, influence the aging process. The aim of the present study was to investigate the mutual relation between steroid hormones and gonadotropins and their effect on body mass indices in older people. MATERIAL AND METHODS: In a group of 100 patients (61 women and 39 men) aged over 75 years, blood serum concentrations of folliclestimulating hormone (FSH), luteinising hormone (LH), oestradiol (E2), testosterone, dehydroepiandrosterone sulphate (DHEAs), and cortisol were measured. All the patients were measured for the following: body weight (kg), body mass index (BMI) (kg/m²), and waist-to-height ratio (WtHR). The differences of the numerical data were evaluated by Student's t-test and the correlations between them by means of Pearson's test. RESULTS AND CONCLUSIONS: The most interesting finding of this study was to show that FSH and LH are negatively correlated with body mass and indices such as BMI and WtHR in older women. Because in older women the mediation of ovary is unlikely, we conclude that gonadotropins may influence the body mass by their direct extra-gonadal action.

Expression of α-Klotho protein in human thyroid cancers - an immunohistochemical study.

INTRODUCTION: The α-Klotho protein was discovered as a gene controlling the process of aging, but further studies indicated that it also plays the role of a tumour suppressor. Although numerous studies were performed on the role of the α-Klotho gene and protein in neoplasia, the data on α-Klotho protein expression in thyroid cancers are very scarce. Our study presents the immunohistochemical investigation of α-Klotho expression in benign and malignant thyroid tumours. MATERIAL AND METHODS: The material included samples of benign (nodular hyperplasia, follicular adenoma), differentiated (follicular and papillary) cancers and aggressive thyroid cancers of low differentiation grade. The samples were immunostained using two different monoclonal anti-α-Klotho antibodies. RESULTS: From the two antibodies used in this study, one (EPR6856) reacted probably with the soluble form of Klotho and immunostained mostly the colloid filling thyroid follicles and intravascular or extravascular serum deposits. The other (A-9 antibody) immunostained the follicular epithelium in benign thyroid lesions as well as the epithelial tumoural cells in differentiated thyroid (follicular and papillary cancers). In the thyroid cancers of high malignancy, the immunostaining with A-9 anti-α-Klotho antibody was (except in one case) negative or very weak. CONCLUSION: Our results indicate that lowered expression of a- Klotho is involved in the process of thyroid neoplasia.

Blood serum concentrations of gonadotropins and α-subunit in patients with gonadotropinomas in relation to the immunoreactivity of pituitary adenoma.

INTRODUCTION: Although active gonadotropin-secreting pituitary adenomas are considered very rare, the vast majority of pituitary tumours diagnosed as "non-functioning" express gonadotropins or their free ß or α subunits. However, systemic investigations comparing the serum concentrations of follitropin (FSH), lutropin (LH), and α-subunit (αSU) before surgery with the immunoreactivity of the respective substances in the excised tumours are still lacking. MATERIAL AND METHODS: Immunostaining of FSH, LH, and αSU was compared in 43 surgically removed gonadotropin - expressing pitu-itary adenomas with serum concentrations of the above-mentioned substances before surgery in the same patients. RESULTS: The serum concentrations of FSH were elevated (> 11.6 mU/mL) in 8/12 (66.7%) cases of FSH-positive adenomas. By contrast, in FSH-negative tumours the elevation of FSH is absent. Moreover, only 1/25 (4%) patients with LH-positive adenoma had the elevated serum concentration of LH (51.5 mU/mL). The overproduction of LH was not observed in adenomas expressing free ß LH or in LH-negative tumours. In patients with αSU-positive adenomas elevated serum levels of αSU were observed in 3/15 (20%) cases. No αSU elevations were observed in patients with αSU-negative adenomas. The mean serum FSH, LH, and αSU concentrations were higher in patients with FSH, LH, and/or αSU immunopositive tumours in comparison with immunonegative. However, the differences are not statistically significant. CONCLUSIONS: Although "silent" gonadotropinomas constitute a frequent subtype of pituitary adenomas, the "active" subtype (i.e. manifesting by gonadotropin excess) are rare (approx. 4% of all pituitary adenomas). Gonadotropinomas are difficult to diagnose before surgery. The measurement of gonadotropins including αSU is needed but often not sufficient for presurgical diagnosis.

"Silent" thyrotropin (TSH) expression in acromegaly and clinically non-functioning pituitary adenomas.

INTRODUCTION: The pituitary adenomas secreting thyrotropin (TSH) are considered the rarest type of hormonally active pituitary tumour. In spite of that, many cases are described in the literature. On the other hand, the observations of the co-expression of TSH with other pituitary hormones (mostly with growth hormone [GH]) and "silent" expression of TSH in clinically non-functioning pituitary adenomas (CNFPA) are rather scarce. MATERIAL AND METHODS: Among 93 examined pituitary adenomas, 22 of them were diagnosed as active acromegaly and 71 as clinically non-functioning pituitary adenomas (CNFPA). All of them were immunostained with antibodies against pituitary hormones, including the anti-TSH antibody. TSH-immunopositive adenomas are immunostained also to detect somatostatin receptor subtypes (SSTR 1-5). RESULTS: TSH immunopositivity was found in 4.2% of CNFPA (3/71 tumours) and in 13.6% (3/22) cases of somatotropinomas manifesting as active acromegaly. All of the examined TSH-immunopositive adenomas expressed SSTR subtypes except SSTR4. The symptoms of hyperthyroidism were not observed in any of the acromegalic patients co-expressing TSH with GH. CONCLUSIONS: Our data confirm the relative rarity of TSH expression or co-expression of TSH in pituitary tumours. In most cases TSH is co-expressed with GH in patients with acromegaly and is not accompanied by hyperthyroidism. The "silent" expression of TSH may occur also, although rarely in CNFPA. The strong expression of SSTR in TSH-immunopositive CNFPA ("silent thyrotropinoma") indicates the possibility of the treatment of these tumours with somatostatin analogues. (Endokrynol Pol 2016; 67 (5): 515-518).

Serotonin and melatonin secretion in postmenopausal women with eating disorders.

INTRODUCTION: Postmenopausal women manifest emotional disorders associated with an increase in appetite. The aim of the study was to assess the serotonin and melatonin secretion and metabolism in postmenopausal women in relation to eating disorders. MATERIAL AND METHODS: Sixty postmenopausal women and 30 women without hormonal disturbances were enrolled into the study and divided into three groups: group I (control) - women without menstrual disorders, group II - postmenopausal women without appetite disorders and change in body weight, and group III - postmenopausal women with increased appetite and weight gain. Serum melatonin, serotonin, urinary 6-sulfatoxymelatonin (aMT6s), and 5-hydroxyindoleacetic acid (5-HIAA) excretion were measured. RESULTS: Serum serotonin and melatonin levels in groups II and III were lower compared to group I. Urinary 5-HIAA and aMT6s excretion was lower in overweight women. In group III the correlation between the serum level of serotonin, melatonin, and BMI was negative; a high statistical significance was found between BMI and urinary aMT6s excretion. CONCLUSIONS: Melatonin supplementation and use of drugs modulating the serotonin homeostasis together with female hormones have a beneficial effect in complex treatment of disorders of eating in postmenopausal women. (Endokrynol Pol 2016; 67 (3): 299-304).

Ultrafiltration - an alternative method to polyethylene glycol precipitation for macroprolactin detection.

INTRODUCTION: The aim of the study was to evaluate two methods of macroprolactin (MaPRL) detection - precipitation with polyethylene glycol (PEG) and ultrafiltration and to compare these techniques with "gold standard" - gel filtration chromatography (GFC). MATERIAL AND METHODS: The study was conducted on 245 patients - 45 with organic and 200 with functional hyperprolactinaemia. In all the subjects MaPRL was detected by precipitation with PEG and ultrafiltration. Additionally, gel filtration chromatography was performed in some of the serum samples. RESULTS: Macroprolactinaemia was detected in 27 patients - 8 with prolactinoma and 19 with functional hyperprolactinaemia. Assessing positive and negative results for MaPRL, we observed high diagnostic agreement (95.9%) and positive correlation (r = 0.506, p < 0.001) between the methods. The results of precipitation and ultrafiltration positive for MaPRL were concordant in 63%. The dominance of MaPRL detected with precipitation and/or ultrafiltration was confirmed by GFC in 76% of cases (all patients with functional hyperprolactinaemia). Among 6 examined patients with prolactinoma, GFC showed four false-positive results - 1 case of precipitation and 3 cases of ultrafiltration. CONCLUSIONS: Efficacy of MaPRL detection with precipitation and ultrafiltration is comparable especially in cases of functional hyperprolactinaemia. In patients with prolactinoma, precipitation seems to be a more efficient separation method.

Expression of follicle stimulating hormone receptors (FSHR) in thyroid tumours - a marker of malignancy?

BACKGROUND: In normal conditions FSHR are expressed in granulosa cells of the ovary and Sertoli cells of the testis. They can be expressed also in gonadal tumours. However, recently the expression of FSHR was found in tumoral cells and intra-tumoral blood vessels of many other tumours, including thyroid tumours. Aim of this study was to see whether the expression of FSHR can be useful in the differentiation of benign and malignant thyroid lesions. METHODS: 44 samples of surgically excised thyroids were immunostained with anti- FSHR antibody raised against 1-190 amino acid sequence from the human FSHR. RESULTS: Non-neoplastic thyroid follicles (i.e. the follicles situated outside the tumour) do not show the immunostaining for FSHR. The same concerns the majority of follicular adenomas. In contrast, 87.5% of follicular cancers, the same percentage of papillary cancers and all the examined undifferentiated cancers showed the FSHR immunopositivity of tumoral cells. A tendency towards the higher frequency of FSHR - positive blood vessels also concerns malignant thyroid tumours. CONCLUSIONS: The ectopic FSHR immunostaining seems to be useful to differentiate malignant from benign lesions, especially follicular cancers from follicular adenomas. However, the further studies on larger material are needed.

Ectopic expression of follicle-stimulating hormone receptors in thyroid tumors.

INTRODUCTION: In normal conditions follicle-stimulating hormone receptors (FSHR) are expressed in the ovary and the testis. They can also be expressed in gonadal tumors. However, recently we have found FSHR immunostaining in pituitary adenomas, adrenal tumors and neuroendocrine tumors (carcinoids). The aim of this study was to determine whether the same occurs in thyroid tumors. MATERIAL AND METHODS: Thirty-six samples of surgically excised thyroids were examined. Follicle-stimulating hormone receptors immunostaining was performed on paraffin sections using the rabbit anti-human FSHR polyclonal antibody raised against a 1-190 amino acid sequence from the human FSHR (sc-13935, Santa Cruz). RESULTS: Normal thyroid follicles do not show immunopositivity for FSHR. The same concerns the majority of benign lesions, diagnosed as hyperplasia nodularis or thyroid adenomas. However, positive FSHR immunostaining in some follicles was observed. In all but one thyroid cancer (15 papillary, 10 follicular cancers and one case of anaplastic thyroid cancer) 10-100% of tumor cells exhibit positive FSHR immunostaining. In about 40% of samples FSHR immunoreactivity can be observed also in the endothelia of intrathyroidal blood vessels. This immunopositivity was more frequent in the samples of thyroid cancers (13/27) than in benign lesions (2/9). CONCLUSIONS: Ectopic positive FSHR immunostaining is also present in thyroid cancers, and, to a lesser degree, in benign lesions but not in the normal thyroid epithelium.

Overexpression of prothymosin alpha is related to pituitary adenoma recurrence but not to adenoma invasiveness and proliferation.

INTRODUCTION: Prothymosin alpha (ProTα) is a peptide initially considered as a thymic hormone, but further studies have shown its wide distribution in different tissues and organs. It has a prevalent nuclear localisation and is thought to be involved in the control of proliferation and apoptosis. In earlier studies, the overexpression of ProTα was found in several human tumours, including pituitary adenomas. The present study deals with the relations of ProTα to the pituitary adenoma hormonal phenotype, proliferation, recurrence and invasiveness. MATERIAL AND METHODS: Sixty two pituitary adenomas were included in the study. The invasiveness of the tumours was estimated before surgery by means of magnetic resonance imaging. The paraffin sections of the tumours were immunostained with an antibody against the C-terminal fragment (101-109) of ProTα and with anti-Ki-67 antibody. The hormonal phenotype of the investigated pituitary adenomas had been established previously by means of immunostaining with antibodies to pituitary hormones (GH, PRL, FSH, LH, TSH, ACTH and α-subunit). RESULTS: Strong immunostaining with anti-ProTα antibody occurred in the subpopulation of cell nuclei and the walls of intratumoural blood vessels. ProTα index is higher in clinically non-functioning pituitary adenomas (CNFPA) compared to any type of functioning adenomas. There was no difference in the percentage of ProTα- positive cell nuclei in non-invasive vs. invasive adenomas, but it was significantly more frequent in recurrent than in primary tumours. Moreover, the decrease of ProTα index was found in somatotroph tumours treated with somatostatin analogues vs. untreated ones. The percentage of ProTα nuclei did not correlate with Ki-67 index. CONCLUSIONS: The overexpression of nuclear ProTα in pituitary adenomas is related to tumour recurrence, but not to proliferation or invasiveness.

Expression of follicle stimulating hormone receptors in pituitary adenomas - a marker of tumour aggressiveness?

INTRODUCTION: In our earlier study, we found that pituitary adenomas, like other human tumours, express ectopically follicle stimulating hormone receptors (FSHR) in intratumoural blood vessels endothelia and/or tumoural cells. The aim of the present paper was to provide more detailed data on FSHR expression in different subtypes of pituitary adenomas and to evaluate its possible role as a prognostic and/ or predictive biomarker in these tumours. MATERIAL AND METHODS: Forty two pituitary adenomas, surgically removed, were immunostained with antibodies against the pituitary hormones, antigen Ki-67 and 1-190 fragment of FSHR. RESULTS: The positive FSHR immunostaining was found in blood vessels endothelia of 88% of adenomas and in tumoural cells of 40% adenomas. In tumoural cells, the incidence of at least moderate FSHR immunostaining is significantly higher in invasive tumours (68%) compared to non-invasive (12%) ones, and higher (albeit not statistically significantly) in invasive-proliferating adenomas (Ki-67 > 3%, grade 2b) compared to invasive but non-proliferating (Ki-67 < 3%, grade 2a) ones. CONCLUSIONS: The present study confirms that pituitary adenomas ectopically express FSHR in intratumoural blood vessels endothelia and tumoural cells. Moreover, the expression in tumoural cells is prevalent in invasive and proliferating adenomas vs. non-invasive and non-proliferating tumours.

Immunohistochemical detection of follicle stimulating hormone receptor (FSHR) in neuroendocrine tumours.

INTRODUCTION: Follicle stimulating hormone receptors (FSHR) are well known to be expressed in gonads and in gonadal tumours. Recently,their incidence has also been revealed in endocrine non-gonadal tumours such as adrenal and pituitary tumours. Moreover, FSHR immunostaininghas also been reported in endothelium of intra- and peritumoral blood vessels of a large series of cancers. The presentpaper reports on the incidence of FSHR in both tumoral cells and some intratumoral blood vessels of neuroendocrine tumours (NETs). MATERIAL AND METHODS: Sixteen NETs samples were taken from 14 patients. The tumour samples were immunostained using the antibodyraised against 1-190 amino acid sequence from the human FSH-R and anti-Ki67 antibody. RESULTS: In all the samples examined, the majority of tumoral cells were immunostained with anti-FSHR antibody. Positive immunostainingconcerned also the intratumoral blood vessels endothelia in a half of the examined samples. Immunopositive blood vessels were foundmore often in tumours with higher Ki-67 index. CONCLUSION: FSHR expressed in NETs, if they are functional, may mediate the signals which can enhance further tumour growth.

Influence of melatonin on symptoms of irritable bowel syndrome in postmenopausal women.

INTRODUCTION: Melatonin (MEL) exerts beneficial effects on the gut partly by myorelaxative properties upon the smooth muscle. Its secretion decreases with age, particularly in postmenopausal women. This study was aimed at evaluating the effect of MEL on the symptoms of irritable bowel syndrome (IBS) in this group of patients. MATERIAL AND METHODS: The investigations were carried out in 80 postmenopausal women, aged 48-65 years, divided into two equal groups, diagnosed according to Rome Criteria III: i.e. patients with IBS with constipation predominant (IBS-C), and patients with IBS with diarrhoea predominant (IBS-D). The control group (C) included healthy women aged 46-65 years. In all subjects, 6-sulfatoxymelatonin (6-HMS) concentration urine was measured using ELISA assay. Patients in both groups over the course of six months were given melatonin (at a dose of 3 mg fasting and 5 mg at bedtime) or a placebo (double blind trial). Disease activity was evaluated after two, four and six months, using a ten-point scale to assess the main somatic symptoms: visceral pain, abdominal bloating, etc. RESULTS: The amounts of 6-HMS urine excretion (µg/24 h) were: C 11.4 ± 3.0, IBS-C 10.2 ± 3.2, IBS-D 14.0 ± 6.3 (p 〈 0.05). Correlation between values of symptoms score and contrary excretion of 6-HMS: IBS-C r = -0.714, IBS-D r = 0.409. After six months in the IBS-C group, the intensity of visceral pain and abdominal bloating had decreased in 70% of patients (p 〈 0.01) and constipation in 50% of patients (p 〈 0.05). Beneficial changes in the IBS-D group were noted in 45% of patients, but this was not better compared to the placebo. CONCLUSIONS: Melatonin can be used as part of the treatment of IBS, particularly in patients with constipation-predominant IBS.

Serotonin and melatonin secretion and metabolism in patients with liver cirrhosis.

INTRODUCTION: Hepatic encephalopathy is one of the symptoms of liver failure. The exact causes of encephalopathy are complex and still unclear. Apart from elevated blood ammonia levels, the role of numerous other factors is being considered. OBJECTIVES: The aim of the study was to determine the serum level of serotonin and melatonin and the urinary excretion of their metabolites (5-hydroxyindoleacetic acid [5-HIAA] and 6-sulfatoxymelatonin [6-HMS]) in patients with various stages of liver cirrhosis. PATIENTS AND METHODS: The study comprised 75 patients with alcohol-induced liver cirrhosis and 25 healthy subjects (control group). Based on the Child-Pugh classification, 3 groups of 25 patients each were distinguished - group A, B, and C with grade A, B, and C of liver failure, respectively. Blood samples were drawn at fasting at 9 a.m., and 24-hour urine collection was performed. Immunoenzymatic assays were used to determine serum melatonin and serotonin levels as well as urine 5-HIAA and 6-HMS concentrations. RESULTS: Serum serotonin levels were 159.8 ± 23.1 ng/ml in controls, 179.3 ± 21.1 ng/ml in group A (P >0.05), 143.2 ± 22.8 ng/ml in group B (P >0.05), and 114.5 ± 37.6 ng/ml in group C (P <0.01). Serum melatonin levels were 10.6 ± 1.7 in controls, 31.2 ± 9.8 pg/ml in group A (P <0.01), 49.8 ± 12.2 pg/ml in group B (P <0.001), and 94.8 ± 22.6 pg/ml in group C (P <0.001). Urinary 5-HIAA excretion was 5.9 ± 2.1 mg/24 h in controls, 5.9 ± 1.9 mg/24 h in group A (P >0.05), 4.8 ± 1.2 mg/24 h in group B (P >0.05), and 4.6 ± 1.4 mg/24 h in group C (P <0.05). Urinary 6-HMS excretion was 26.6 ± 15.1 µg/24 h in controls, 23.2 ± 7.9 µg/24 h in group A (P >0.05), 18.3 ± 10.6 µg/24 h in group B (P >0.05), and 6.5 ± 3.6 µg/24 h in group C (P <0.001). CONCLUSIONS: Disturbances in serotonin and melatonin homeostasis observed in patients with liver cirrhosis may be associated with advanced encopaholopathy.