Is cholangiocarcinoma another complication of insulin resistance: a report of three cases.

BACKGROUND: Cholangiocarcinoma is the second most common primary liver cancer, and the number of cases of intrahepatic cholangiocarcinoma (ICC) have been steadily increasing worldwide. Although the reasons for this surge are unknown, insulin resistance (IR) could be a risk factor, similar to what has been reported for other cancers. CASE REPORT: We report on 3 cases of ICC arising in subjects sharing IR as an underlying risk factor. Case 1 was an obese and dyslipidemic patient with NAFLD. The second and the third patients were affected by type 2 diabetes. CONCLUSIONS: Evidence for a link between IR and onset of cholangiocarcinoma in our patients rests on three lines of evidence: epidemiological, biological, and exclusion of others risk factors. Studies are needed to confirm our hypothesis that IR is a risk factor for the development of ICC.

Cardiovascular and catecholamine response to clonidine in obese subjects.

OBJECTIVE: To investigate central alpha-2 adrenergic activity, one of the main inhibitory factors affecting norepinephrine secretion, in human obesity. DESIGN: Cardiovascular and catecholamine responses to clonidine (300 micrograms per os) were evaluated in a group of obese subjects. SUBJECTS: 10 obese men (OM) and 14 obese women (OW). MEASUREMENTS: Mean arterial pressure, pulse rate, plasma norepinephrine (NE) and epinephrine (E) before and 120', 130', 140' after clonidine (CL) administration. RESULTS: The mean arterial pressure decreased after CL administration in obese patients (from 92 +/- 12 to 79 +/- 2 mmHg; P < 0.001) with no significant differences between OM and OW. The values of pulse rate were reduced in obese patients after clonidine (60 +/- 1 b/min vs 65 +/- 1 b/min before clonidine; P < 0.01) with no differences between OM and OW. Plasma E was not affected by the administration of clonidine and no sex related differences were found in the basal (OM: 0.23 +/- 0.03 vs OW: 0.15 +/- 0.03 nmol/L; P = NS) and in the post-CL E levels (OM: 0.22 +/- 0.02 vs OW: 0.14 +/- 0.03 nmol/L; P = NS). Basal plasma NE values were not different between OM (1.32 +/- 0.15 nmol/L) and OW (1.03 +/- 0.11 nmol/L; P = NS). Plasma NE decreased after CL in obese patients (from 1.20 +/- 0.10 to 0.59 +/- 0.08 nmol/L; P < 0.001) and a significant difference was found in the post-CL values between OM and OW (0.74 +/- 0.11 vs 0.40 +/- 0.06 nmol/L respectively; P < 0.01). The decrease in plasma NE was strongly correlated with the basal value of NE (r = 0.70; P < 0.001). The sex-related differences in plasma NE responses to clonidine in obese subjects did not differ with those previously observed in control subjects (P = NS). CONCLUSION: The cardiovascular and catecholamine response to CL in obese patients were similar to that previously observed in normal subjects, indicating a normal alpha-2 adrenergic activity. The sex related difference in the NE response to CL, previously reported in normal subjects, was maintained in obese patients.

Hypokalemic thyrotoxic periodic paralysis in a Caucasian male with Graves' disease.

The case of a 34-yr-old Caucasian male with Graves' disease presenting with a flaccid quadriplegia and severe hypokalemia is reported. The weakness was prevalent at the lower extremities and began during nocturnal sleep, after a strenuous physical exertion performed during the day. Correction of hypokalemia promptly reversed the quadriplegia. The occurrence of hypokalemic thyrotoxic periodic paralysis several months after the beginning of thyrotoxic symptoms, and the normal insulin serum levels on admission differentiate this patient from most of the previously reported cases.

Pituitary and ovarian interleukin-1 alpha content changes according to estrous cycle and acute stress exposure.

A complex interaction between the immune and neuroendocrine systems has been established. In particular, cytokines are known to be one of the mediators of the stress response, and modulate hormone secretion by acting in the brain, pituitary and gonads. The aim of the present study is to investigate whether pituitary and ovarian interleukin-1 alpha (IL-1 alpha) content changes according to the estrous cycle. In addition, the possible pituitary and ovarian IL-1 alpha changes in rats exposed to acute (5 min) or chronic intermittent (twice a day for 4 days) cold swimming stress were studied. The IL-1 alpha content of ovarian and pituitary homogenates was measured by a sensitive and specific radioimmunoassay. Immunoreactive IL-1 alpha (irIL-1 alpha) was detectable only in ovaries collected in rats at proestrus and estrus while not in those collected at diestrus I and II. The highest values were found at proestrus. No significant changes were found in ovarian irIL-1 alpha content in rats exposed to acute or chronic intermittent stress in comparison to control rats. In the pituitary, no difference in IL-1 alpha content was found throughout the estrous cycle. Acute stress induced a significant increase in pituitary irIL-1 alpha content only at proestrus (p < 0.01), however, no significant differences were found in comparison to control rats after chronic intermittent stress. The proestrus-related changes of ovarian IL-1 alpha may constitute a hormone-dependent signal within the ovary that is involved in the ovulatory process.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus.

The utilisation of assays for TSH with improved sensitivity has revealed that abnormal TSH results are frequently observed in patients with nonthyroidal illnesses, such as trauma, renal diseases, liver diseases or sepsis. The aim of this study was to investigate the prevalence of abnormal TSH concentrations, using a sensitive immunometric assay, in patients with type 2 (non-insulin-dependent) diabetes mellitus. The study population consisted of 290 type 2 diabetics, 159 females and 131 males aged 40 to 93 years (mean 60.6 +/- 11.9 years), hospitalised because of poor diabetic control or recent-onset diabetes (mean HbA1c value = 9.6 +/- 2.2%). All patients with TSH values outside the normal range (0.45 to 3.66 mlU/l) had FT4 assay and thyroid microsomal autoantibody assay performed on the same specimen of serum. Abnormal TSH concentrations were detected in 91 patients (31.4%). Subclinical hypothyroidism (high TSH, normal FT4) was most common (48.3%), followed by subclinical hyperthyroidism (low TSH, normal FT4) (24.2%) and by definite hypothyroidism (high TSH, low FT4) (23.1%). Definite hyperthyroidism (low TSH, raised FT4) was found in 4 patients (4.4%). None of the patients with low TSH values had increased FT3 concentrations. The prevalence of abnormal thyroid function test results was significantly higher in the female than in the male patients (40.9% vs. 19.8%, p < 0.0005) and in the insulin-treated patients than in those receiving oral hypoglycaemic agents (OHA) (37.3% vs. 23.1%, p < 0.02). Thirty patients with abnormal thyroid function test results (33.0%) had evidence of thyroid autoimmunity (titre of thyroid microsomal autoantibodies > 250 IU/l). Five thyroid microsomal antibody-negative patients had non-autoimmune thyroid diseases, 7 had nonthyroidal illnesses other than diabetes mellitus and 4 were receiving drugs known to affect the hypothalamic-pituitary-thyroid axis. Twenty-seven thyroid microsomal auto-antibody-negative patients with abnormal TSH values (17 with subclinical hypothyroidism and 10 with subclinical hyperthyroidism), who were not receiving drugs known to affect TSH secretion and were free of diseases other than diabetes mellitus, were retested after two months of adequate treatment of diabetes with OHA or insulin. TSH concentrations decreased in all but one patient with initial subclinical hypothyroidism and increased in all patients with initial subclinical hyperthyroidism. These changes were coupled with a significant fall of glycated haemoglobin values. In view of the transient changes in TSH secretion, we suggest that the diagnosis of thyroid dysfunction in type 2 diabetics should be delayed until improvement of the metabolic status.

[Endocrine-metabolic aspects of rarefying osteopathy of patients with cirrhosis]. / Aspetti endocrino metabolici dell'osteopatia rarefacente del cirrotico.

Hepatic diseases and particularly cholestasis are well known to affect bone metabolism and induce osteoporosis. We have studied bone metabolism in normal volunteers and in 20 patients with non alcoholic liver cirrhosis without cholestasis, classified stage "B" according to Child's classification. A reduced bone density as measured by mineralometry was observed in patients as compared to controls. Serum osteocalcin and urinary hydroxyproline levels were consistent with the "low turnover" osteoporosis type of osteopathy. The major determinants of the bony loss seem to be low blood testosterone and the consequent reduced metabolism in cirrhotics.

[Obesity: relationships with the endocrine system]. / Obesità: rapporti con il sistema endocrino.

In this study we have examined the relationship between obesity and endocrine glands. We have underlined that obesity can be a symptom of some endocrine diseases and that, on the other side, only a few number of cases with excessive weight have a true endocrine pathogenesis. The endocrine implications of essential obesity, only detectable with appropriate dynamic tests, are sometimes expression of an altered peripheral metabolism. The more relevant hormonal data that we will examine in details are: increase of insulin plasma levels, altered hypothalamic neuroregulation with consequence on the gonadotropin secretion and values of prolactin, growth hormone and cortisol.

[The growth hormone/somatomedin C system from the first years of life to young adulthood. Physiological aspects and physiopathologic involvement in diabetic syndrome]. / Il sistema growth hormone/somatomedina-C dalle prime età della vita al giovane adulto. Aspetti fisiologici e coinvolgimento fisiopatologico nella sindrome diabetica.

The growth hormone (GH)/somatomedin-C (Sm-C) endocrine system plays a fundamental role in human anabolism. Whereas from a physiological point of view GH conforms to the classic hormone behaviour, Sm-C appears to follow a peripheral and local pattern of action with autocrine or paracrine involvement. The hormonal GH system interacts with the functional pattern of insulin and other hormones, and in addition with entire maturation process. On the basis of several reports, the puberal age seems to represent the first real "maturative-tumultuous" event managed by the operative GH/Sm-C system. It is thus possible to hypothesise that alterations to this system, as found in dysmetabolic diseases (e.g. diabetes), may either be seen as a cause or consequence of the disease process. It can therefore also be supposed that such alterations may interact with the development of the entire organism, above all when they occur during the delicate puberal phase.