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)

The increased survival of patients with thalassemia major, made possible by more adequate therapeutic regimens, has emphasized the importance of the endocrine abnormalities often associated with this disease. In twelve thalassemic patients, we evaluated the hypothalamic-pituitary function by measuring plasma levels of anterior pituitary hormones under basal conditions and in the course of provocative tests. An impairment of growth hormone (GH) secretion was demonstrated in a considerable proportion (7/12) of these patients. In some of them failure of GH response to insulin-hypoglycemia and normal hormone rise after growth hormone-releasing hormone indicate a hypothalamic defect. A defective prolactin secretion was observed in the female hypogonadic but not in the male thalassemic patients. This abnormality appears to be dependent on estrogen deficiency rather than on a hypothalamic-pituitary dysfunction. In our series a high prevalence (8/12) of hypogonadism was also noticed. In these cases, the low gonadotropin levels and their unresponsiveness to gonadotropin-releasing hormone are compatible with a hypothalamic and/or pituitary damage. Lastly, the enhanced ACTH responses to the stimuli associated to a reduced cortisol release suggest the existence, in these patients, of a diminished adrenocortical reserve. On the whole, this study has shown several derangements of the hypothalamic-pituitary function in thalassemia. This emphasizes the need for careful endocrine surveillance in this disease.
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PMID:Evaluation of hypothalamic-pituitary function in patients with thalassemia major. 162 77

Thyroid and pituitary function tests using hypothalamic releasing factors were performed in seven patients with thalassaemia and secondary haemosiderosis and in a control group of seven healthy subjects. The TSH level in the thalassaemic patients (18.07 +/- 1.10 microU/ml) was higher than in the controls (1.01 +/- 0.14 microU/ml, P less than 0.001). After TRH administration the TSH values increased less than in controls. Serum thyroxine and FT41 values were lower in the group of patients with thalassaemia (76.7 +/- 7.8 nmol/l and 19.3 +/- 2.2) compared to the controls (116.1 +/- 6.9 nmol/l, P less than 0.005 and 38.6 +/- 3.6, P less than 0.001). The basal prolactin values did not differ significantly between the two groups, but after TRH administration the increment was significantly lower in thalassaemics than in controls (P less than 0.005). The basal LH values were lower in the thalassaemic patients (1.37 +/- 0.24 ng/ml) than in the controls (3.23 +/- 0.50 ng/ml) and did not increase significantly after LHRH administration. The FSH values were also lower in the thalassaemic group (0.46 +/- 0.15 ng/ml) compared to the controls (2.06 +/- 0.08 ng/ml, P less than 0.001), and increased only slightly after LHRH administration. We conclude that in thalassaemia pituitary deficiency exists, mostly of gonadotrophs, but possibly also for the thyrotrophs and the lactotrophs. Latent primary hypothyroidism has also been found in the thalassaemic group. The functional abnormalities found in both endocrine glands are best explained as a consequence of coexisting haemosiderosis.
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PMID:Pituitary and thyroid insufficiency in thalassaemic haemosiderosis. 642 75

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

The objective of this paper was to assess the ability of gonadotropin administration to induce ovarian steroidogenesis, follicle maturation and ovulation in hypogonadal women affected by beta-thalassemia. Thirteen hypogonadal thalassemic women underwent a test with gonadotropin-releasing hormone (GnRH), with estimation of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. They were then administered human menopausal gonadotropin (hMG) for a period ranging from 11 to 15 days with a total dose variable from 3,300 to 4,200 IU. In each patient, the initial dosage of 300 IU daily, adopted for the first 9 days, was modified subsequently according to the ovarian morphology, as shown by serial echographic examinations and by serum estradiol levels. In those patients in whom a dominant follicle was evidenced and the occurrence of pregnancy could be excluded, induction of ovulation was attempted by administration of 10,000 IU of human chorionic gonadotropin (hCG). All patients displayed a reduced LH and FSH rise in response to GnRH. Upon hMG administration, they exhibited echographic evidence of follicular growth with a clear-cut increase of serum estradiol, which peaked between the 9th and the 16th day from the start of treatment. In two out of three patients in whom a dominant follicle developed, ovulation was induced successfully by hCG injection, as shown by the increase of serum progesterone and by the ultrasonographic demonstration of a corpus luteum. This study has shown that, by proper pharmacological stimulation, the steroidogenic function of the gonads and even ovulation can be reinstated in hypogonadal thalassemic women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of follicle maturation and ovulation by gonadotropin administration in women with beta-thalassemia. 780 43

Homozygous transfusion-dependent beta-thalassemia patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload. Short stature, delayed sexual maturation, diabetes mellitus, hypothyroidism, hypoparathyroidism, and metabolic bone disease can and should be diagnosed as early as possible so that the intervention can be fruitful. Primary or secondary amenorrhea is due primarily to pituitary gonadotrope hemosiderosis, as attested by pathology data and the demonstration in vivo of nonstimulable follicle-stimulating hormone and luteinizing hormone release and secretion after the exogenous administration of gonadotropin-releasing hormone or its agonistic analogs. Ovulation can be achieved with the use of exogenous gonadotropins provided that the ovary has no siderosis (as seen in neglected patients) or damage induced by drugs used for bone marrow transplantation. Once pregnancy is achieved, it should be considered high risk and be dealt with or cared for by an expert team to ensure a successful outcome.
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PMID:Reproductive health in patients with beta-thalassemia. 895 76

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

We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 39/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was referred at age of 15 years because of delayed puberty. Complete endocrine evaluation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, 17OHP and ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisotope scanning and gonadal vessels phlebography) did not show internal genitalia and gonads. Karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the Y chromosome. Female genitalia without uterus in a subject with Y chromosome SRY gene, and no detectable testes indicate a condition of male pseudohermaphroditism associated with testicular regression. Low gonadotropin and sex steroid levels are suggestive of combined acquired hypothalamic-pituitary and gonadal impairment, due to iron deposition in both organs. We cannot exclude congenital failure of testosterone synthesis and action in this case, because lack of gonads is an unusual finding in thalassemic hypogonadic subjects.
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PMID:Pituitary deficiency and lack of gonads in an XY pseudohermaphrodite with beta 39/lepore haemoglobinopathy. 1009 Nov 84

To elucidate whether the cause of sexual maturation arrest in thalassaemia is of gonadal or pituitary etiology, 10 males with thalassaemia and delayed puberty and 10 with constitutional delay of growth and pubertal maturation (CSS) were extensively studied. Their spontaneous nocturnal gonadotropin secretion and gonadotropin response to intravenous 100 micrograms gonadotropin-releasing hormone (GnRH) were evaluated. Circulating testosterone concentration and clinical response were evaluated after 3 days, 4 weeks and 6 months of intramuscular administration of human chorionic gonadotropin (HCG) (2500 U/m2/dose). Thalassaemic boys had significantly lower circulating concentrations of testosterone compared to those with constitutional delay of growth and sexual maturation (CSS) at the same pubertal stage. Short- and long-term testosterone response to administrations of HCG was markedly decreased in thalassaemic boys. After 6 months of HCG administration 50 per cent (5/10) of the boys did not show significant testicular enlargement or genital changes. Despite the low circulating concentrations of testosterone, none of the patients had high basal or exaggerated gonadotropin response to gonadotropin releasing hormone (GnRH) stimulation. Luteinizing hormone (LH) peak responses to GnRH were significantly lower as compared to controls. Follicle-stimulating hormone (FSH) peak responses to GnRH did not differ among the two study groups. The mean nocturnal LH and FSH secretion was significantly decreased in all thalassaemic boys as compared to boys with CSS at the same pubertal stage (testicular volume). These data proved that hypogonadotropic hypogonadism is the main cause of delayed/failed puberty in adolescents with thalassaemia major. MRI studies revealed complete empty sella (n = 5), marked diminution of the pituitary size (n = 5), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 8) in thalassaemic patients, denoting a high incidence of structural abnormalities (atrophy) of the pituitary gland. Moreover, in many of the thalassaemic boys, the defective testosterone response to long-term (6 months) HCG therapy denoted significant testicular atrophy and/or failure secondary to siderosis. It appears that testosterone replacement might be superior to HCG therapy in these patients. This therapy should be introduced at the proper time in these hypogonadal patients to induce their sexual development and to support their linear growth spurt and bone mineral accretion.
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PMID:Spontaneous and GnRH-provoked gonadotropin secretion and testosterone response to human chorionic gonadotropin in adolescent boys with thalassaemia major and delayed puberty. 1082 33