Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine function evaluations in 16 patients with beta-thalassemia indicate that hypogonadotropic hypogonadism, hypoparathyroidism, and reduced adrenocorticotropic hormone reserve occur frequently, whereas reduced growth hormone and thyroid reserve are less common manifestations. Hemosiderosis-induced damage of the endocrine glands seems to be the main cause for endocrine dysfunction in the patients studied.
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PMID:Endocrine abnormalities in thalassemia major. 43 75

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

The effect of long-term human chorionic gonadotropin (HCG) therapy on the linear growth and biological growth parameters was studied in six thalassaemic boys aged 14.5-15.5 years old with hypogonadotropic hypogonadism. A significant (P less than 0.001) increase in growth velocity (from 3.3 +/- 0.3 to 7.6 +/- 0.6 cm/year) was found after 6-12 months of therapy, without acceleration of bone age. A striking improvement in pubertal development was observed. The treatment significantly increased growth hormone (GH) response to L-dopa administration (P less than 0.025) as well as sleep GH secretion (P less than 0.025). Serum growth factors, evaluated as thymidine activity during deep sleep, increased (P less than 0.001), but somatomedin C (Sm-C) levels did not. Prior to treatment, baseline and peak values of plasma growth hormone releasing hormone (GH-RH) following L-dopa were low. After HCG therapy, GH-RH response to L-dopa increased significantly (from 9.2 +/- 5.6 to 20.2 +/- 6.2 pg/ml; P less than 0.05), but remained (P less than 0.001) lower than in normal prepubertal children. This study suggests that in thalassaemia major an impaired GH-RH release can be observed, in addition to the described alteration in Sm-C generation.
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PMID:Effect of human chorionic gonadotropin on growth velocity and biological growth parameters in adolescents with thalassaemia major. 249 61

Female patients with beta-thalassaemia major usually suffer from hypogonadotropic hypogonadism associated with amenorrhea, anovulation and infertility, attributed to the deposition of haemosiderin in the pituitary gland as well as in the ovaries. Pregnancies are rare and, with few exceptions, occur mainly in patients with beta-thalassaemia intermedia. Our study presents histopathological evidence that deposition of haemosiderin occurs in the endometrial glandular epithelium of 3 patients with beta-thalassaemia major. This deposition is mainly evident in the apical part of these cells above the nuclei, and should be taken into consideration as a contributing factor to the infertility in these patients by altering endometrial receptivity for implantation. In 2 patients who received effective iron chelating treatment with desferrioxamine the endometrial haemosiderin deposits either disappeared (patient C.R.), or were significantly reduced (patient G.L.).
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PMID:Endometrial glandular haemosiderosis in homozygous beta-thalassaemia. 275 23

The aim of the study was to find endocrinological parameters for the effectiveness of both, s.c. desferrioxamine therapy and a blood transfusion regimen, in 5 girls with homozygous beta-thalassemia treated in this way over 12-18 months. Physiologically, a sleep-dependent rhythm of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion is detectable during early to mid puberty. Girls with homozygous beta-thalassemia develop persistant hypogonadotropic hypogonadism in the course of untreated hypothalamo-pituitary hemosiderosis and do not show this rhythm. All our patients developed a sleep-dependent gonadotropin rhythm, increased estradiol concentrations as well as secondary sex characteristics, including menarche in one girl. The occurence of sleep-dependent gonadotropin rhythms in previously hypogonadotropic girls emphasizes the effectiveness of s.c. desferrioxamine therapy of hypothalamo-pituitary hemosiderosis in combination with a blood transfusion regimen.
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PMID:[Puberty-specific gonadotropin rhythm in girls with homozygous beta-thalassemia during continuous subcutaneous desferrioxamine infusions and a simultaneous blood transfusion regimen]. 640 32

Body iron stores and endocrine functions were determined in eight patients with chronic hemolytic anemia who had received only small amounts of blood and no iron preparations. Four patients had beta-thalassemia intermedia (BTI) and four had sickle-cell thalassemia (SCT). Hemoglobin levels and degrees of hemolysis were similar in both groups of patients. The patients with BTI showed clear evidence of iron overload, whereas there was no evidence of iron accumulation in the patients with SCT. The three patients with BTI who had endocrinologic evaluations showed endocrine dysfunctions. Two patients with SCT had no endocrine abnormalities and the other two probably had some degree of primary hypogonadism. Iron overload in patients with thalassemia probably results from excessive intestinal iron absorption and can damage various parenchymal and endocrine organs, even in the absence of an external source of iron.
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PMID:Iron loading and endocrine functions in nontransfused patients with beta-thalassemia intermedia or sickle-cell thalassemia. 746 43

Patients with beta-thalassemia major often have pubertal delay, the etiology of which has not been fully elucidated. We investigated the pituitary-gonadal response to short-term subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administration (150 ng/kg body weight every 120 min for 7 days) in five young males (aged 13.6-19.0 years) affected by beta-thalassemia major and presenting signs of delayed puberty. Immunoreactive and bioactive gonadotropin levels were determined and their isoform profiles were examined, before and after GnRH treatment, in a pool of samples collected every 15 min for 240 min. Testosterone, androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone and 17 beta-estradiol were measured as markers of gonadal function on days 0, 1, 3, 5 and 7 of treatment. Five patients (aged 16.9-26.8 years) with confirmed diagnosis of idiopathic hypogonadotropic hypogonadism who were starting pulsatile GnRH therapy were also studied in the same protocol. Increased sex steroid levels were observed in both groups as a result of treatment. On day 7, the thalassemic patients had increased bioactive luteinizing hormone (LH) and follide-stimulating hormone (FSH), although immunoreactive LH and FSH were comparable to day 0. Moreover, fewer acidic and more basic immunoreactive and bioactive isoforms were noted in LH profiles on day 7. Similar results were observed in hypogonadal patients, who also had increased immunoreactive LH and FSH values. We suggest that the early stage of delayed puberty in thalassemia might be characterized by a neuroendocrine dysfunction resulting in an impaired hypothalamic GnRH release, which is inadequate for a proper pituitary stimulation. Pulsatile GnRH treatment seems to re-establish partially the correct pituitary-gonadal function.
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PMID:Delayed puberty in males with beta-thalassemia major: pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids. 762 37

In order to clarify whether the damage in gonadotropin secretion due to iron overload in patients with beta-thalassemia is of pituitary or hypothalamic origin, 14 euthyroid patients (8 females and 6 males, age 15-24 years) affected by beta-thalassemia major with hypogonadotropic hypogonadism were studied. Luteinizing-hormone (LH), follicle-stimulating hormone (FSH) and free alpha-subunit (FAS) were measured during LH-releasing hormone (LH-RH) stimulation test, and thyroid-stimulating hormone (TSH), prolactin (PRL) and FAS during thyrotropin-releasing hormone (TRH) stimulation test. During LH-RH stimulation, the mean basal LH, FSH and FAS levels were similar to those found in normal prepubertal children, but the peak values were lower than those found in such children. Also during TRH stimulation, the mean peak values of FAS were lower than those of normal prepubertal children, but the TSH response was normal. The lack of response of gonadotropins and FAS to LH-RH cannot exclude hypothalamic failure; however, the normal response of TSH to TRH, in spite of the poor response of FAS, indicates that the origin of hypogonadotropic hypogonadism is the pituitary damage concerning not only the gonadotroph but also the thyrotroph cells.
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PMID:Impaired response of free alpha-subunits after luteinizing hormone-releasing hormone and thyrotropin-releasing hormone stimulations in beta-thalassemia major. 831 6

Regular blood transfusions in patients with beta-thalassaemia major lead to secondary hemochromatosis in the majority of cases. As a consequence of chronic iron overload, many endocrinopathies may occur. The most frequent endocrine dysfunction is hypogonadotropic hypogonadism, which is mainly responsible for osteopenia in as much as 80% of thalassemic patients. The frequencies of other endocrine disorders (hypothyroidism, diabetes mellitus and hypoparathyroidism) are lower. We investigated 5 female patients aged 22-25 years for endocrine dysfunction and bone density. All presented with hypogonadotropic hypogonadism and amenorrhea (four primary and one secondary). 4 patients showed absent or delayed pubertal development and short stature (below 10th percentile). In all five, hypogonadism is the most relevant cause of osteopenia as demonstrated by osteodensitometry. Endocrine disorders, especially absent pubertal development, should be detected in good time and treated with hormonal replacement. Established osteopenia is treated hormonally and with vitamin D3 and calcium.
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PMID:[Osteopenia in beta-thalassemia major]. 898 99

A retrospective study analyzing etiological, clinical and hormonal aspects in a population of 45 patients (14 males and 31 females) with permanent hypogonadism was performed, the most important findings were: 1) The most common cause of hypogonadism was gonadal failure (60% of all patients). This included-twenty-three females and four males. Eighteen patients had XO, two XY and two more XX gonadal dysgenesis. In the remaining cases, three patients had bilateral agonadism and two had testicular atrophy secondary to radiochemotherapy. 2) Eighteen patients had hypogonadotropic hypogonadism (40% of the cases). Ten were males and eight females. Eleven patients had gonadotropin deficiency associated with other pituitary dysfunctions. Deficiency of GH was found in all cases. TSH in ten, ACTH in nine and ADH in five. An increase in prolactin was observed in seven patients. The etiology of the hypopituitarism was intracranial tumors in five cases, idiopathic in three, perinatal hypoxemia in two and hypoplastic pituitary in one. In the remaining seven cases, isolated gonadotropin deficiency was found. Four cases were idiopathic, two cases had demyelinating diseases and one beta-thalassaemia. 3) Mean levels of testosterone were 4.20 +/- 6.5 (0, 20) pg/ml. Meal levels of estradiol of the total group, gonadal failure patients and those with hypogonadotropic hypogonadism were 8.51 +/- 14.7 (0, 50), 9 +/- 16 (0, 50) and 7.12 +/- 10.98 (0, 29) pg/ml, respectively. 4) Mean basal levels of LH and FSH in patients with gonadal failure were 35.57 +/- 60.66 (5, 320) and 53.19 +/- 53.92 (4, 230) mUi/ml, respectively. In hypogonadotropic hypogonadism patients, mean basal and peak levels of LH were 0.98 +/- 1.24 (0, 5) and 3.45 +/- 3.94 (0, 12) mUi/ml, respectively. Mean basal and peak levels of FSH after LHRH stimulation were 1.43 +/- 1.88 (0, 6) and 3.85 +/- 4.85 (0, 17) mUi/ml, respectively.
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PMID:[Etiological, clinical and hormonal characteristics of a group of patients with permanent hypogonadism]. 929 97


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