Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The antioxidant defense system in liver tissue in experimental hyperthyroidism and/or in iron supplementation was investigated. Thyroid hormones (T3, T4, TSH), ferritin (marker of iron status), antioxidant status components (glutathione [GSH], glutathione peroxidase [GSH-Px], superoxide dismutase [SOD]), and serum transaminases (GOT and GPT, both of which are known to be released from damaged hepatocytes), were measured. Hyperthyroidism in rats, induced by L-thyroxine administration, significantly raised SOD activity (p < 0.05), but significantly decreased GSH-Px activity and GSH values (p < 0.001) in the liver. In the L-thyroxine administered and iron supplemented (TI) group, GSH and GSH-Px values of liver tissues were significantly lower than those of control rats (p < 0.05). GSH-Px levels of the TI group were higher (p < 0.001), and SOD levels significantly lower (p < 0.001) than those of the L-thyroxine administered group. We conclude that hyperthyroidism induces SOD activity in liver; ferritin levels increase in hyperthyroidism, contributing to the antioxidant defense system; GSH-Px and GSH levels are decreased significantly in hyperthyroidism either due to inactivation due to increased oxidative stress or to insufficient synthesis; iron supple- and GPT analysis); iron decreases the effect of T4. This must be taken into consideration during iron supplementation.
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PMID:Evaluation of antioxidant status in liver tissues: effect of iron supplementation in experimental hyperthyroidism. 1063 95

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

Despite improved hematologic care, multiendocrine dysfunction is a common complication of homozygous transfusion-dependent beta-thalassemia. In this study our goal was to estimate the prevalence of thyroid dysfunction in a large homogenous group of thalassemic patients. Two hundred patients with beta-thalassemia major (100 males and 100 females; mean age, 23.2 +/- 6.7 years; age range 11-43 years), regularly transfused and desferioxamine chelated, were randomly selected from a pool of approximately 800 patients with beta-thalassemia followed in our department. Thyroid function and iron-load status were evaluated by measurements of free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH), and serum ferritin levels. Of the subgroup of patients who proved to have normal thyroid hormone values, 26 (12 males, 14 females; mean age, 23.6 +/- 6.8 years; age range, 15-36 years) were randomly selected and underwent a standard TRH stimulation test. Thyroid dysfunction was defined as follows: overt hypothyroidism: low FT4 and/or FT3, increased TSH levels; subclinical hypothyroidism: normal FT4, FT3, increased TSH levels; exaggerated TSH response: normal FT4, FT3, normal basal TSH, deltaTSH > or = 21 microIU/mL (TSH levels measured prior and 30 minutes after intravenous TRH administration). Normal thyroid hormone values were found in 167 (83.5%) of the 200 patients studied. Eight (4%) of the remaining patients had overt hypothyroidisim, and 25 (12.5%) had subclinical hypothyroidism. Exaggerated TSH response to TRH was revealed in 7 of the 26 patients with normal hormone values tested (26.9%). Antithyroglobulin and anti-thyroid peroxidase (TPO) antibody titers were negative in 191 patients (95.5%). Mean ferritin levels in hypothyroid and euthyroid patients were 2707.66 +/- 1990.5 mg/L and 2902.9 +/- 1997.3 mg/L, respectively, (p = 0.61), indicating no correlation between ferritin levels and thyroid functional status. Mean ferritin levels in the patients who responded normally to TRH stimulation and in those who overresponded, were 2,586 +/- 1791 mg/L and 3,228 +/- 2473 mg/L, respectively (p = 0.46; NS). Thyroid failure is a rather rare endocrine complication in patients with beta-thalassemic from Greece. In our series, no case of central hypothyroidism was observed. No correlation was found between thyroid functional status and ferritin plasma levels. Approximately 1 of 5 beta-thalassemic patients with normal thyroid hormone values showed an exaggerated TSH response to TRH test. It is to be investigated how many of these patients will establish overt or subclinical hypothyroidism in the future.
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PMID:Assessment of thyroid function in two hundred patients with beta-thalassemia major. 1191 84

ABSTRACT : BACKGROUND : The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications. METHODS : Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires. RESULTS : Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 +/- 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected. CONCLUSION : High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions.
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PMID:Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran. 1291 70

Twenty-six consecutive patients who presented with clinically euthyroid multinodular goitre were studied for an overnight fasting serum lipid profile and 24 h Holter monitoring. Mean serum TSH was 0.6 +/- 0.4 vs 2.4 +/- 1.3 mU/l (p < 0.0001) and mean TT3 2.4 +/- 0.4 vs 2.0 +/- 0.5 nmol/l (p = 0.009) in patients vs controls (n = 15) while mean FT4 was not different from controls. Total serum HDL, LDL cholesterol and triglycerides were lower in patients but creatinine, ferritin and SHBG levels did not differ between patients and controls. The 24-hour ambulatory continuous ECG recordings did not demonstrate significant differences in mean, minimal and maximal heart rate between the study and the control group. Nocturnal heart rate, measured between 23.00 and 06.00 hours, also showed no differences between the two groups. Atrial fibrillation was absent in both the study and the control group. Premature atrial and ventricular complexes occurred equally frequently in both groups. Comparison of patients with a serum TSH below 0.4 mU/l (n = 11) and patients with a TSH above 0.4 mU/l revealed no differences. In conclusion, in consecutive patients who present with multinodular goitre, effects were found on the lipid profile, but not on the heart. It is argued that in this type of patients, cardiac effects depend on the degree of subclinical hyperthyroidism.
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PMID:Cardiac and metabolic effects in patients who present with a multinodular goitre. 1470 9

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.
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PMID:Klinefelter's syndrome presenting with leg ulcers. 1536 65

Reduced serum insulin-like growth factor-1 (IGF-1) and hypogonadotrophic hypogonadism are common features of adult beta-thalassemia, and warrant evaluation of the growth hormone (GH)-IGF-1 axis. The aim of this study was to determine GH reserve in beta-thalassemia patients (9 females, 7 males, 15 major, 1 intermedia), age 29.3 +/- 6.9 years, BMI 21.3 +/- 1.9 kg/m2, and in 20 age, sex and BMI-matched healthy controls, using the GH-releasing hormone (GHRH)-arginine test. The associations between peak GH response and hormonal and biochemical indices were evaluated. Using BMI-related cut-off limits for peak GH response in the GHRH-arginine test, 4/16 beta-thalassemia patients had peak GH lower than 11.5 microg/l, the cut-off limit suggested for lean subjects, and were diagnosed as GH deficient (GHD). Using 9 microg/l as the cut-off limit 2/16 patients were GHD. Reduced serum IGF-1 and IGFBP-3 were present in 69% and 19% of the patients, respectively. Peak GH did not correlate with serum IGF-1, TSH, and fT4 levels or gonadal status. Neither peak GH nor IGF-1 correlated with serum ferritin. Our findings suggest that GHD is present in up to a quarter of adult beta-thalassemia patients. The clinical benefits of GH therapy need to be determined. GHD alone does not account for the high prevalence of reduced IGF-1 in adult beta-thalassemia.
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PMID:Growth hormone reserve in adult beta thalassemia patients. 1770 95

Telogen effluvium (TE) is the most common cause of diffuse hair loss in adult females. TE, along with female pattern hair loss (FPHL) and chronic telogen effluvium (CTE), accounts for the majority of diffuse alopecia cases. Abrupt, rapid, generalized shedding of normal club hairs, 2-3 months after a triggering event like parturition, high fever, major surgery, etc. indicates TE, while gradual diffuse hair loss with thinning of central scalp/widening of central parting line/frontotemporal recession indicates FPHL. Excessive, alarming diffuse shedding coming from a normal looking head with plenty of hairs and without an obvious cause is the hallmark of CTE, which is a distinct entity different from TE and FPHL. Apart from complete blood count and routine urine examination, levels of serum ferritin and T3, T4, and TSH should be checked in all cases of diffuse hair loss without a discernable cause, as iron deficiency and thyroid hormone disorders are the two common conditions often associated with diffuse hair loss, and most of the time, there are no apparent clinical features to suggest them. CTE is often confused with FPHL and can be reliably differentiated from it through biopsy which shows a normal histology in CTE and miniaturization with significant reduction of terminal to vellus hair ratio (T:V < 4:1) in FPHL. Repeated assurance, support, and explanation that the condition represents excessive shedding and not the actual loss of hairs, and it does not lead to baldness, are the guiding principles toward management of TE as well as CTE. TE is self limited and resolves in 3-6 months if the trigger is removed or treated, while the prognosis of CTE is less certain and may take 3-10 years for spontaneous resolution. Topical minoxidil 2% with or without antiandrogens, finestride, hair prosthesis, hair cosmetics, and hair surgery are the therapeutically available options for FPHL management.
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PMID:Diffuse hair loss in an adult female: approach to diagnosis and management. 1917 26

A 16-year-old boy with transfusion-dependent thalassemia major presented with tetany, numbness, bone pain, short stature and pubertal delay. His height SDS score=-2.6, BMI=22.4, spleen was palpable 5 cm and liver 7 cm below the costal margins. The cardio-vascular examination was normal. Laboratory investigations showed a hemoglobin level (8 g/dL), hypocalcemia, hyperphosphatemia and elevated alkaline phosphatase (ALP) with serum 25-OH D below 3 ng/ml and a normal magnesium level. Serum parathyroid hormone (PTH) level was lower (21 pg/mL; normal 16-70 pg/mL) than expected for the degree of hypocalcemia. Serum ferritin concentration was 4442 ug/L, insulin-like growth factor I (IGF-I) was 31 microg/L (normal 122- 286 microg/L), free T4 was 13.1 microg/dL, TSH 1.2 mIU/ml. These results revealed a combined vitamin D-parathyroid defect. Peak growth hormone (GH) responses to clonidine and glucagon tests were 7.6 ng/ml and 6.2 ng/ml, respectively. Serum LH and FSH concentrations were below 0.5 U/L and testosterone was below 10 ng/dl. Radiographs revealed osteopenia of the phalanges and long bones and DXA scanning revealed low BMD Z-score of the femoral neck and 4th and 5th lumbar spines. MRI showed evidence of hemosiderin deposition in the pituitary. The patient was started on oral daily calcium carbonate (1500 mg elemental calcium) and vitamin D2 (calciferol) 25,000 IU/day and intensive iron chelation therapy. A low dose of IM testosterone enanthate (1 mg/kg/month) was injected for 6 months. Follow-up after 4, 8 and 12 months revealed normal Ca, PO4, ALP, and 25-OH D concentrations and disappearance of spasms and numbness and increased growth velocity. In conclusion, investigating calcium homeostasis at regular intervals and early management of any abnormality can preclude the occurrence of complications.
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PMID:An adolescent boy with thalassemia major presenting with bone pain, numbness, tetanic contractions and growth and pubertal delay: panhypopituitarism and combined vitamin D and parathyroid defects. 1933 71

The severity of thyroid dysfunction in patients with beta-thalassaemia major is variable in different series. An exaggerated thyrotropin response to thyrotropin-releasing-hormone (TRH) has been found in 1 out of 5 beta-thalassaemia major patients. Because it is not well known how many of these patients will develop overt or subclinical hypothyroidism, we reviewed retrospectively the thyroid status (thyroid hormones, TBG, TG basal and TSH peak after TRH test) of 24 children and adolescents with beta-thalassemia major (mean age 12.1+/-3.9 years) on periodic transfusion therapy, regularly followed in our Centre during the last 20 years. As controls we studied 30 normal subjects aged 13.4+/-2.5 years. In our group of 24 thalassaemics an exaggerated TSH response to TRH test was found in 8 (33.3%), 3 of whom developed subclinical or overt hypothyroidism from 3 to 11 years later. TSH peak values correlated directly with ferritin levels, ALT, and compliance index to chelation therapy. Our data suggest that an exaggerated TSH response to TRH test is frequent in beta-thalassemia major, and may evolve into subclinical or overt hypothyroidism as we found in 37.5% of our patients with sub-biochemical hypothyroidism.
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PMID:Exaggerated TSH response to TRH ("sub-biochemical" hypothyroidism) in prepubertal and adolescent thalassaemic patients with iron overload: prevalence and 20-year natural history. 1933 73


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