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)

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

From 1990 to 1991, the Pediatric and Adolescent Endocrine Outpatient Clinic of Arcispedale S. Anna admitted 97 thalassaemia major (TM) patients for endocrine evaluation. Their mean age was 14.2+/-5.7 years (range 5-28 years). Sixty-eight (70%) had normal thyroid function and twenty-one (21.6%) were discharged with a diagnosis of hypothyroidism of different degrees of severity. Thirteen patients out of 21 (61.9%) were females. Twelve patients (57.1%) fulfilled the criteria for subclinical hypothyroidism (SH). Their mean age was 15.7+/-3.5 years (range 9-22 years). A positive direct correlation was observed between the following variables: TSH and serum ferritin, TG and basal TSH, basal TSH and peak levels after TRH stimulation test. In 6 out of 12 TM patients (50%) with SH type a, the basal ejection fraction assessed by MUGA scan was normal; 1 TM patient (8.3%) showed mild abnormality and 5 TM patients (41.6%) showed severe abnormalities. A normal response during exercise (increase in LVEF greater than 5 percentage units) occurred in 10 patients (83.3%). Global or segmental left ventricular dysfunction at rest and during exercise were found in 8 patients (66.6%) and 10 patients (83.3%), respectively. These cardiac abnormalities were more common in TM patients with severe iron overload and poor compliance to DFX treatment (group A: serum ferritin above 2500 ng/ml) compared to TM patients with mild-moderate iron overload (group B: serum ferritin below 2500 ng/ml). In the control group of TM patients (group C) with normal thyroid function the assessment of MUGA scan was normal in all subjects at rest and after exercise. Global or segmental left ventricular dysfunction was observed only during exercise in 50% of TM patients with normal thyroid function (group C). Our patients with SH exhibited three different thyroid function patterns during follow-up: a. 3 (25%) of 12 studied TM patients showed a normalization of serum TSH levels b. 2 patients (16.6%) showed intermittent elevation of serum TSH with normal serum FT4 concentrations c. 3 patients (25%) had a persistent mild elevation of serum TSH concentration (from 6.3 to 7.6 microU/ml) with serum FT4 concentrations within the normal range. Two TM patients (16.6%) were treated with L-thyroxine. The reason for starting therapy was an abnormality of basal LVEF in the presence of mild iron overload (serum ferritin levels 665 ng/ml and 523 ng/ml). One TM patient with persistent SH type a developed a papillary carcinoma, and another, a multinodular goiter. The serum ferritin levels at diagnosis were 4739 ng/ml and 744 ng/ml,respectively. The thyroid function in TM patients from group C remained normal during the follow-up period. Two patients (Group A: patients no. 1 and 2) with severe iron overload and poor compliance to chelation therapy died during the follow-up, due to heart failure and arrhythmia. The time intervals between the first abnormal LVEF value and the development of symptomatic heart failure were 3.8 and 4.3 years. An improvement of LVEF was observed in three TM patients from group A after 24 months of intensive subcutaneous chelation therapy with DFX, and in two patients from Group B after 12-14 months of L-thyroxine replacement therapy in association with regular iron chelation therapy. In those two TM patients the basal LVEF increased from 37% to 45% and from 45% to 49%. In conclusion, although the findings are limited to a small group of TM patients with SH type a, our results show a high prevalence of primary hypothyroidism with the predominance of its mildest form, its stable course over years in most patients, and the presence of cardiac involvement in patients with severe-moderate iron overload. Regular iron chelation therapy should be advised for these patients to prevent thyroid dysfunction and the development of clinically significant myocardial dysfunction. In addition, therapy with L-thyroxine should be considered in iron overloaded TM patients with SH and a poor response to chelation therapy and in patients with SH and mild iron overload.
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PMID:Mild subclinical hypothyroidism in thalassaemia major: prevalence, multigated radionuclide test, clinical and laboratory long-term follow-up study. 1933 74