Irfan Vardarli

Subclinical hyperthyroidism: Physical and mental state of patients

SummaryWe investigated whether subclinical hyperthyroidism [subnormal basal thyroid-stimulating hormone (TSH) level, attenuated TSH response to thyrotropin-releasing hormone (TRH) stimulation, peripheral thyroid hormones within normal range] is accompanied by physical and mental changes. Thirty-five subclinically hyperthyroid patients (27 female, 8 male) were compared with 60 overtly hyperthyroid patients (51 female, 9 male) and with 28 euthyroid control patients (18 female, 10 male) with respect to physical symptoms, affective state, short-term memory, ability to concentrate and psychomotor performance. Patients with subclinical hyperthyroidism ranged between the other two groups. The major difference between controls and subclinically hyperthyroid patients was an increase in frequency of nervous symptoms and symptoms due to an increase of metabolic rate and thermal regulation changes. The major differences between subclinically hyperthyroid and overtly hyperthyroid patients were psychomotor impairment and symptoms of increased metabolic rate. Self-ratings of affective state tended to be similar in patients with subclinical and overt hyperthyroidism. The ability to concentrate and short-term memory were not impaired in any group. Symptoms in patients with subclinical hyperthyroidism probably result from central changes which lead to attenuated TSH responses to TRH, or from elevated but still normal thyroxine levels, which possibly enhance the effect of catecholamines.

Mental and physical state in subclinical hyperthyroidism: Investigations in a normal working population

We investigated whether subclinically hyperthyroid individuals selected from a nonpatient working population exhibit similar impairments to those found in studies with patients. Sixteen subclinically hyperthyroid subjects without apparent reason (SH-0) and 15 subclinically hyperthyroid subjects on levothyroxine (SH-T4) were compared with 27 euthyroid controls with respect to signs and symptoms of hyperthyroidism, sleep, depressivity, ability to concentrate, anxiety, and other dimensions of well-being. We found that SH-T4 exhibited significantly higher TT4 levels, TT4/TBG ratios, and more palpitations than controls. Furthermore, they slept less. The SH-0 subjects reported being in a better mood and less touchy than controls. Psychometric results of all groups were within the normal range. A comparison of this study to previous studies reveals that TT4 levels or TT4/TBG ratios may play a crucial role in the development of the predominantly nervous symptoms in subclinical hyperthyroidism. Possible reasons for the discrepancies between results in hospital and nonhospital settings are discussed.

Hypothalamo-hypophysäre Schilddrüsen-Achse, Plasmaproteinkonzentrationen und die hypophysäre Gonaden-Achse im Low-T3-Syndrom nach akutem Myokardinfarkt (AMI)

SummaryIn patients with severely acute diseases, a special relationship of thyroidal hormones with decreased T3 and increased rT3 levels is known, the so-called low T3 syndrome. The aim of this study was to elucidate the involvement of the hypothalamo-pituitary thyroid axis, the pituitary-gonadal axis, the altered hepatic function, the plasma proteins in the low T3 syndrome, and the evaluation of these parameters for prognosis in patients with acute myocardial infarction. Thirty-one patients (29 male, 2 female) with AMI entered the study for the determination of hypothalamo-pituitary thyroid axis and the plasma proteins. Besides routine laboratory determinations, TRH, TSH, T4, T3, rT3, CHE, albumin, total protein, TBG, and estradiol concentrations in plasma were measured daily for 5 days after AMI using immunological and other methods. Twelve male patients with AMI entered the study for the determination of pituitary-gonadal axis; the T3, rT3, estradiol, testosterone, FSH, and LH concentrations in serum were determined using immunological methods. We found that T3 and T4 decreased significantly to a minimum on the first and the second day, respectively, after admission and increased in the course of the observation period. In contrast, rT3 was elevated significantly within the first 2 days and decreased later. TSH and TRH decreased in the first 2 days and increased in the following days. CHE, albumin, and total protein levels significantly showed a minimum on day 4 and TBG significantly showed a minimum on the second day after AMI and increased to day 4. The estradiol and testosterone levels were high on admission and decreased in the following days and increased again in the observation period. FSH decreased in the first 2 days and increased in the following course similar to estradiol and testosterone. Patients who died within 2 weaks after AMI showed a plasma hormonal pattern of hypothyroidism with low TSH levels and hypogonadotropic hypogonadism on the second day, whereas this pattern is persistent in the following days. These results show the involvement of the hypothalamo-pituitary axis in the low T3 syndrome and that characteristics for acute partial insufficiency of the anterior pituitary gland are signs of a bad prognosis. Whether Gn-RH and ACTH also decreased after AMI is unknown. The necessity for substitution is unclear and needs further investigationIn patients with severely acute diseases, a special relationship of thyroidal hormones with decreased T3 and increased rT3 levels is known, the so-called low T3 syndrome. The aim of this study was to elucidate the involvement of the hypothalamo-pituitary thyroid axis, the pituitary-gonadal axis, the altered hepatic function, the plasma proteins in the low T3 syndrome, and the evaluation of these parameters for prognosis in patients with acute myocardial infarction. Thirty-one patients (29 male, 2 female) with AMI entered the study for the determination of hypothalamo-pituitary thyroid axis and the plasma proteins. Besides routine laboratory determinations, TRH, TSH, T4, T3, rT3, CHE, albumin, total protein, TBG, and estradiol concentrations in plasma were measured daily for 5 days after AMI using immunological and other methods. Twelve male patients with AMI entered the study for the determination of pituitary-gonadal axis; the T3, rT3, estradiol, testosterone, FSH, and LH concentrations in serum were determined using immunological methods. We found that T3 and T4 decreased significantly to a minimum on the first and the second day, respectively, after admission and increased in the course of the observation period. In contrast, rT3 was elevated significantly within the first 2 days and decreased later. TSH and TRH decreased in the first 2 days and increased in the following days. CHE, albumin, and total protein levels significantly showed a minimum on day 4 and TBG significantly showed a minimum on the second day after AMI and increased to day 4.(ABSTRACT TRUNCATED AT 250 WORDS)

The Kruppel-like zinc-finger gene ZNF236 is alternatively spliced and excluded as susceptibility gene for diabetic nephropathy

Diabetic nephropathy (DN) is the most common cause of renal failure in the western hemisphere. Epidemiological studies have suggested a genetic susceptibility for DN. Linkage analysis showed evidence for a locus on chromosome 18q22.3-q23 in Turkish families. We report the construction of a transcript map of the target region on chromosome 18q22.3-q23 and analysis of the candidate gene ZNF236. By using recent publications, human genome databases, and a multitude of available protein-predicting programs, we obtained a detailed map of this 4.7-Mb-spanning region. We sequenced ZNF236 in patients with diabetic nephropathy and diabetes without nephropathy, as well as in unaffected controls. We observed multiple splice forms in all individuals but no mutation in any of the patients. It seems improbable, therefore, that ZNF236 is a gene that confers DN susceptibility.

Circadian and pulsatile levels of human thyroid-stimulating hormone (TSH) in various stages of hyperthyroidism

We investigated the influence of various degrees of hyperthyroidism to thyrotropin circadian and pulsatile pattern for 24 h. Furthermore, we investigated the influence of sex and of sleep deprivation on the circadian and pulsatile pattern of TSH in euthyroid female and male volunteers. In euthyroidism the circadian rhythym is well known [1, 3]. With regard to circadian rhythm of TSH in hyperthyroidism only very preliminary data have been described [2]. We observed a total of 10 euthyroid healthy volunteers (age range 23-26 years, 4 men, 6 women); from 5 of them we collected blood from sleep on, and from the rest we collected blood during sleep deprivation tbr 24 h. Furthermore, blood was collected in 4 patients (age range 60-74 years, 3 women, 1 man), 2 presenting latent and 2 manifest hyperthyroidism. Informed consent was obtained from each subject. The subjects were classified into euthyroid and hyperthyroid status according to known biochemical criteria. In M1 subjects blood was collected at 10-min intervals for 24 h from an indwelling cubital vein canule kept patent with a slow infusion of saline. All subjects were hospitalized for the study period; regular hospital meals and only standard activities were allowed during the study period. All premenopausat female sujects were in the luteal phase of the menstrual cycle. TSH was measured using a very sensitive enhanced luminescence method (Amerlite TSH Assay, monoclonal) [7]. Statistical analysis was performed by spectrum analysis [4] and spline techniques [5]. In euthyroid volunteers we found intraindividually three overlapped patterns of TSH, which are different in amplitude and frequency and can be found interindividually, too. The first pattern is equivalent to the circadian rhythm with a nocturnal acrophase. The last pattern is equivalent to the methodic rustle, with a TSIt amplitude of 0.07 gU/ml (TSH mean level 1.2 gU/ml) or 0.02 gU/ml in lower TSH range, and a variable frequency. The second pattern is equivalent to the putsatile secretion with a frequency of 12.0_+ 1.9 pulses/24 h and TSH mean amplitude of 0.19 _+ 0.04 gU/mt. We did not find that the TSH pulsatile pattern depended on sex. During sleep deprivation for 24 h, TSH levels remain on a high plateau for the night period until approximately 8.00 h. Sleep deprivation prevents TSH decrease after the midnight TSH peak. The mean TSH level for 24 h in latent hyperthyroidism (2 = 0.09 gU/ml) is higher than in manifest hyperthyroidism (£=0.015 gU/ml). In both cases the circadian pattern is nonexistent. Whereas the pulsatile secretion in latent hyperthyroidism is existent, in manifest hyperthyroidism the TSH pulses are abolished. In manifest hyperthyroidism depressive symptoms are well known. Until now the latent hyperthyroidism as already defined was not regarded as illness. However, in our own open pilot study latent hyperthyroidism altered psychometric parameters [6], and few clinical symptoms improved after carbimazole treatment. Prospective trials in this respect are ongoing. Our data suggest that the 24 h TSH pattern is dependent on the degree of the hyperthyroidism and that the latent and manifest hyperthyroidism, as defined until now, might be revised and updated as degrees of hyperthyroidism. As proposed we would recommend the following classification of hyperthyroidism: stage I, tosts of circadian TSH rhythm, existence of TSH pulses, normal T3, T4, TBG levels, and little clinical symptoms; stage II, T3 and T4 elevated, TSH as stage I but no pulses existent, little or typical clinical symptoms; and stage III, thyroidal storm with coma (thyrotoxic crisis).

Plasma levels of thyrotropin-releasing-hormone in various splanchnic, renal, suprarenal, and cerebral veins

SummaryEndogenous TRH levels were determined in plasma obtained selectively via percutaneous transhepatic and femoral catheterization. TRH was measured using a very sensitive RIA method. In the pancreatic veins, internal jugular vein, left testicular vein, and other described veins, normal peripheral levels were found. An involvement of the TRH degrading enzyme (TDE) or a rapid intravasal dilution leading to normal peripheral TRH levels in the veins leaving the brain or pancreas, respectively, is discussed.