Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiratricol has been used to suppress pituitary TSH secretion, with reported attenuation of extrapituitary thyromimetic effects. A randomized, double-blind trial was performed to define precisely the tissue-specific thyromimetic actions of tiratricol. Ten athyreotic patients, treated for thyroid carcinoma, were randomly assigned to receive L-T4 sodium 0.7 micrograms/kg daily and either tiratricol 10 micrograms/kg or placebo twice daily. The daily dose of L-T4 was increased by 25-50 micrograms increments until the TRH-stimulated TSH level was less than 0.1 mU/L. After measurement of biochemical and physiological parameters of thyroid hormone actions, patients crossed treatment groups. Patients required 46% less L-T4 to achieve equivalent TSH suppression when taking tiratricol. Hepatic effects were enhanced by tiratricol administration, with significant increases in sex hormone binding globulin and ferritin concentrations, 14% and 37%, respectively. Levels of serum cholesterol, LDL cholesterol, and apolipoprotein B were reduced by 7%, 10%, and 13%, respectively, during tiratricol therapy. Triglyceride levels also declined, but there were no changes of high density lipoprotein cholesterol or apolipoproteins AI and AII. Resting metabolic rate, body weight, urea nitrogen excretion, and symptoms did not differ between the two treatment regimens. Cardiovascular function, as reflected by mean arterial pressure and pulse wave arrival time, was not different during tiratricol therapy. Skeletal metabolic activity was affected by tiratricol, with marked elevation of osteocalcin without significant change in serum calcium, PTH, and urinary calcium and hydroxyproline excretion. Tiratricol has increased hepatic and skeletal actions of potential therapeutic value, but does not have enhanced thyromimetic activity specific to the pituitary gland.
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PMID:Organ-specific effects of tiratricol: a thyroid hormone analog with hepatic, not pituitary, superagonist effects. 151 83

TSH secretion, with particular regard to the nocturnal surge of the hormone, was evaluated in 15 women (age range, 35-66 yr; mean, 50 yr) with untreated major endogenous depression and 15 healthy women (age range, 32-67 yr; mean, 53 yr) using an ultrasensitive assay. Mean morning (0830 h) TSH values did not differ in the 2 groups (1.3 +/- 02 mU/L in depressives and 1.4 +/- 0.1 mU/L in controls), whereas mean nighttime (2400-0200 h) values were significantly reduced in depressives (1.5 +/- 0.3 vs. 3.1 +/- 0.3 mU/L; P less than 0.0005). At variance with the control group, morning and nighttime TSH values did not differ in the depressives. The nocturnal serum TSH surge was abolished in 14 of 15 depressed patients. The mean peak TSH value after TRH was slightly yet significantly lower in the depressives. Patients with subnormal (less than 0.4 mU/L) TSH values in the morning had a serum TSH increase after TRH less than 2 mU/L in 5 of 6 cases and a lack of the nocturnal TSH surge in 6 of 6. Among the 9 patients with normal TSH values in the morning, the nocturnal serum TSH surge was lost in 8 of 9, whereas the response to TRH was normal in all. The depressives, at variance with other reports, showed significantly lower values of total and free thyroid hormones. Mean serum sex hormone-binding globulin (SHBG) and ferritin were also significantly reduced. In conclusion, major endogenous depression is associated with a major impairment of TSH secretion, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal. In this regard, the loss of the nocturnal serum TSH rise would appear to be a more sensitive indicator of hypothalamus-pituitary-thyroid axis alterations in depressives than the TRH test, which is commonly used in the evaluation of these patients. The lack of the nocturnal TSH surge may be responsible for the reduced thyroid hormone secretion and supports the case for some degree of central hypothyroidism in endogenous depression.
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PMID:Nocturnal serum thyrotropin (TSH) surge and the TSH response to TSH-releasing hormone: dissociated behavior in untreated depressives. 211 39

We studied pituitary-gonadal function in 11 male and 5 female patients, aged 12-30 yr, with severe beta-thalassemia and chronic iron overload. All had normal basal serum cortisol, T4, and PRL concentrations and normal serum cortisol and GH responses to insulin-induced hypoglycemia and TSH responses to TRH. Of the 11 male patients (all over 17 yr of age), only 3 attained full pubertal development and 4 had subnormal serum LH and FSH responses to GnRH. As a group, their mean basal serum testosterone (T) level was low [11.7 +/- 4.9 (+/- SE) nmol/L; normal, 10-40 nmol/L], and 9 of the 11 male patients responded to hCG with a rise in serum T. Two of the 3 female patients over 17 yr of age were prepubertal with undetectable serum estradiol (E2) levels and absent serum LH and FSH responses to GnRH; the other female patient had regular menstrual cycles and normal serum E2 levels and LH and FSH responses to GnRH. Six of the prepubertal patients (4 males and 2 females, aged 17-30 yr) were studied serially for 3 yr after the start of chelation therapy. Despite a fall of median serum ferritin from 11,910 to 1,303 pmol/L, there was no progression of puberty, and their basal and GnRH-stimulated serum LH and FSH and serum T or E2 levels did not change. Three of these patients (1 male and 2 female) then received pulsatile sc GnRH therapy in addition to chelation therapy for 6 months with no improvement. We conclude that chronic iron overload in patients with severe thalassemia leads to variable degrees of hypogonadotropic hypogonadism, which do not respond to chelation therapy given late in the course of the disease. The hypogonadism in most patients was due to pituitary hyporesponsiveness to GnRH.
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PMID:Hypogonadotropic hypogonadism in severe beta-thalassemia: effect of chelation and pulsatile gonadotropin-releasing hormone therapy. 249 34

In a pilot therapeutic trial, four patients with amyotrophic lateral sclerosis (ALS) were treated with long term, continuous infusions of TRH, three intrathecally and one epidurally. They had prompt increases in serum TSH and thyroid hormone concentrations, averaging 120% for TSH, 49% for serum T4, 68% for the serum free T4 index, 49% for serum T3, and 67% for the serum free T3 index. These elevations were statistically significant for all but serum T3 and persisted for the duration of treatment (4-7 months). Mean values during treatment were near the upper limit of normal for each of these hormone measurements. After TRH withdrawal, serum TSH fell transiently below the normal range. A comparison group of four patients with ALS treated by twice weekly intrathecal bolus doses of TRH had no significant changes in serum TSH, T4, or T3. During continuous TRH treatment, the responsiveness of both TSH and PRL to a standard iv TRH stimulation test was blunted, but not abolished. Basal serum PRL was occasionally elevated in the two women during continuous TRH treatment, but was normal in the men, and serum GH was normal in all patients. In the patients receiving continuous TRH treatment, indexes of end-organ effects of thyroid hormone were inconclusive; none had a rise in serum ferritin, one of four had a rise in serum sex hormone-binding globulin, and three had increased creatinuria. These results provide direct evidence in man that chronic TRH administration can cause modest sustained increases in serum TSH and thyroid hormones, though the metabolic consequences of these changes are uncertain, and appears to raise the set-point of the pituitary-thyroid axis, i.e. the serum T4 and T3 concentrations needed for a given degree of suppression of basal TSH secretion.
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PMID:Sustained rises in serum thyrotropin, thyroxine, and triiodothyronine during long term, continuous thyrotropin-releasing hormone treatment in patients with amyotrophic lateral sclerosis. 309 28

Androgenetic alopecia (a.A.) occurs quite frequently. Up to 79% of women suffer at least temporarily from varying degrees of intermittent diffuse hair loss in the centro-parietal and/or fronto-temporal regions. A.A. is caused by an androgen excess acting on the hair follicle for prolonged periods of time in the presence of a genetic predisposition. However, often hyperandrogenemia cannot be demonstrated in such patients. 125 women with clinically typical a.A. were investigated prospectively under standardized conditions. Patient age ranged from 18 to 68 years (mean +/- SD: 34 +/- 11.6). Atypical uterine bleeding such as menorrhagia, hypermenorrhea and polymenorrhea were found in 69 women. The hair loss varied between 50 and 400 hairs per day (124 +/- 125). Additional signs of hyperandrogenism, i.e. seborrhea (n = 83), acne (n = 52) and hirsutism (n = 28), were often observed. Basal levels of total and free testosterone (T and FT), dihydro-T (DHT) DHEA-sulfate (DS), delta 4-androstendione (A), 17 alpha-hydroxy-progesterone (17P), cortisol (F), progesterone (P), 17 beta-estradiol (E2), sex hormone binding globuline (SHBG), prolactin (PRL), thyreoidea-stimulating hormone (TSH), ferritin (Fe), vitamin B12 (B12) and folat (Fo) were determined by RIA. FT was also measured by equilibrium dialyses. Different methods of determining bound and unbound T were used; their diagnostic value is discussed in detail. In addition, a combined ACTH/TRH-stimulation test was performed in all patients. Pathologic changes of one parameter were detectable in 26.4% of patients, while 67.2% revealed deviations of two or more indices. Excluding clinically relevant borderline values, only 6.4% of patients were without any abnormalities. The incidence rate of pathologic parameters was as follows: FT in % = 52%, Fe = 42%, PRL = 34%, E2 = 34%, FT in pg = 29%, DHT = 28%, SHBG = 26%, TSH = 20.8%, DS = 19%, T = 14%, 17P = 11%, Fo = 7%, A = 6%, F = 6%, B12 = 5%. Group and individual case analyses revealed significant correlations between (1) the levels of the various androgens, PRL and TSH and (2) the E2, SHBG and FT values; these, in turn, were correlated to (3) the occurrence of certain bleeding anomalies (amount, duration, interval) and corresponding ferritin deficiency. Therapy was directed at normalizing the disturbed estrogen-androgen-balance. Using low-dose antiandrogens, estrogens, prolactin suppressants, corticoids, iron-II-preparations as well as estrogen-containing hair lotions hair loss was arrested in 74 of 104 treated women, while regrowth of hair was accomplished in 16 patients. 14 women did not respond to therapy.
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PMID:[Hormonal diagnosis in so-called androgenetic alopecia in the female]. 337 87

Endocrine function was evaluated in 20 prepubertal patients with homozygous beta-thalassemia treated with frequent transfusions and long term iron chelation therapy. FSH, LH, PRL, and TSH secretion were evaluated by LRH and TRH testing and L-dopa and ACTH were used to assess GH and adrenocortical reserve. No statistically significant differences were found between FSH, LH, PRL, GH, and cortisol secretion in the patients and in normal subjects. There was a relatively high incidence (35%) of primary thyroid impairment since 1 patient had primary hypothyroidism and 6 others had evidence of subclinical hypothyroidism as manifested by increased TSH responses to TRH. However, no statistically significant correlations were found between either serum ferritin levels, total blood transfusions received, and thyroid function.
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PMID:Endocrine functioning in multitransfused prepubertal patients with homozygous beta-thalassemia. 632 34

Thyroid function was investigated by a TRH test in 24 clinically prepubertal children, 3-15 years old with beta-thalassaemia major; in 7 of them the test was repeated once and in 2 twice at intervals of at least 12 months. Basal T4, T3, TBG and TSH levels and the TSH levels during a TRH test were determined and correlated with age and serum ferritin levels. Basal serum T4, T3 and TBG levels were lower and serum TSH levels were higher during the test and in the basal state in thalassaemia major children than in control children. These results show a compensated sub-clinical primary hypothyroidism. The transversal study did not show any significant correlation between the hormonal parameters studied and chronological age or serum ferritin levels. In contrast, the longitudinal study showed a significant correlation between pituitary-thyroidal axis function and siderosis (positive correlations between the variations of TSH levels as delta, peak, 30 and 45 min values and the variations of serum ferritin levels). The thyroid impairment seems not to be correlated with serum ferritin levels in the transversal study because of the presence of an individual different sensitivity of the gland to the iron overload. The ferritin dependence of this impairment is shown only by longitudinal studies where individual differences in sensitivity of the gland are absent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endocrine involvement in children with beta-thalassaemia major. Transverse and longitudinal studies. I. Pituitary-thyroidal axis function and its correlation with serum ferritin levels. 643 70

We present data of a detailed study of endocrine function in 50 patients (21 males, 29 females) with thalassaemia intermedia, 15-46 years old (mean age 28.7 yr), with raised serum ferritin levels (mean 1540 micrograms/l). Mean haemoglobin concentration was 8.1 g/dl. Half of them had had more than 50 transfusions in their life and had received irregular intramuscular or subcutaneous chelation therapy. Delayed puberty was one of the most frequent (36%) clinical endocrine abnormalities found in our patients. Primary amenorrhea was observed in two patients and secondary amenorrhea in four patients. Two males, aged 19 and 36 years, had hypogonadism. A poor response to GnRH, found in three females and in both males tested, suggested that pituitary dysfunction was wholly or partially responsible for hypogonadism. Gonadal function was normal in all patients studied. Glucose intolerance and primary hypothyroidism were less frequent (24 and 5.7%, respectively) and milder than in thalassaemia major patients. Two patients had low T3 and T4 and normal basal and stimulated response of TSH to TRH. This condition has been found in euthyroid sick syndrome and it is likely that it represents an adaptive response by the body to minimize catabolism when undergoing major stress. As a consequence, we believe that periodic endocrine evaluation should be carried out in subjects with beta-thalassaemia intermedia, particularly in those over 14 years old, in order to detect and to treat endocrine dysfunction.
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PMID:Final height and endocrine function in thalassaemia intermedia. 1009 Nov 74

Resistance to thyroid hormone (RTH) action is due to mutations in the beta-isoform of the thyroid hormone receptor (TR-beta). RTH patients display inappropriate central secretion of TRH from the hypothalamus and of TSH from the anterior pituitary despite elevated levels of thyroid hormone (T4 and T3). RTH mutations cluster in three hot spots in the C-terminal portion of the TR-beta. Most individuals with TR-beta mutations have generalized resistance to thyroid hormone, where most tissues in the body are hyporesponsive to thyroid hormone. The affected individuals are clinically euthyroid or even hypothyroid depending on the severity of the mutation. Whether TR-beta mutations cause a selective form of RTH that only leads to central thyroid hormone resistance is debated. Here, we describe an individual with striking peripheral sensitivity to graded T3 administration. The subject was enrolled in a protocol in which she received three escalating T3 doses over a 13-day period. Indexes of central and peripheral thyroid hormone action were measured at baseline and at each T3 dose. Although the patient's resting pulse rose only 11% in response to T3, her serum ferritin, alanine aminotransferase, aspartate transaminase, and lactate dehydrogenase rose 320%, 117%, 121%, and 30%, respectively. In addition, her serum cholesterol, creatinine phosphokinase, and deep tendon reflex relaxation time fell (25%, 36%, and 36%, respectively). Centrally, the patient was sufficiently resistant to T3 that her serum TSH was not suppressed with 200 microg T3, orally, daily for 4 days. The patient's C-terminal TR exons were sequenced revealing the mutation R383H in a region not otherwise known to harbor TR-beta mutations. Our clinical evaluation presented here represents the most thorough documentation to date of the central thyroid hormone resistance phenotype in an individual with an identified TR-beta mutation.
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PMID:The thyroid hormone receptor-beta gene mutation R383H is associated with isolated central resistance to thyroid hormone. 1048 71

Resistance to thyroid hormone (RTH), a syndrome characterized by variable tissue hyposensitivity to thyroid hormone (TH), is linked to mutations in the thyroid hormone receptor (TR) beta gene. We report a new family with a heretofore unreported mutation, P247L. The proposita, a 31-year-old female, presented with goiter and palpitations. RTH was suspected because of elevated serum free thyroxine (FT4) level with a normal thyrotropin (TSH). Sequencing the TRbeta gene revealed a mutation causing replacement of a proline at position 247 with leucine. Seven family members were heterozygous for the mutation, two of whom also had evidence of autoimmune thyroid disease. The mutant TRbeta had a Ka for triiodothyronine (T3) 30% that of the wild-type TRbeta, approximately a threefold reduction in T3-induced transactivation and a low level dominant negative activity when tested with a positively regulated reporter gene. In vivo sensitivity to TH was evaluated in three affected subjects by measurement of the responses to graded doses of levotriiodothyronine (LT3). Peak TSH responses to TRH were reduced and were not completely suppressed at even the highest dose of LT3, (0.9, 0.2, and 0.2, compared to < 0.01 microU/mL in unaffected controls), confirming pituitary resistance to TH in all three subjects. In contrast, peripheral tissues responded variably to LT3: serum cholesterol decreased in all by 15%-25%, serum creatine kinase decreased by 15% in two subjects and increased 35% in another, but serum ferritin and sex hormone-binding globulin increased in only one of the three affected individuals that were tested. Basal metabolic rate and sleeping pulse did not change in three and two individuals, respectively. Hyporesponsiveness to exogenous TH established the clinical diagnosis of RTH in one member of the family with a mutant TRbeta but normal tests of thyroid function at baseline. Three affected subjects had an axis I diagnosis of major depression but had Wechsler Intelligence Scale for Children, III (WISC-III) full-scale IQs (FSIQs) in the normal range. This novel TRbeta mutation is associated with a realtively mild RTH. Results of responses to LT3 underscore the variable phenotype of RTH.
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PMID:A novel point mutation in cluster 3 of the thyroid hormone receptor beta gene (P247L) causing mild resistance to thyroid hormone. 1064 58


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