Gonadotropin Insufficiency in Patients with Thalassemia Major*

Abstract

To elucidate whether the cause of sexual maturational arrest in thalassemia major is of hypothalamic or pituitary etiology, three female and two male patients were extensively studied. After the iv administration of 150 micrograms gonadotropin-releasing hormone (GnRH) and 500 micrograms of TRH, all patients demonstrated a minimal LH and no FSH response, with variable PRL and TSH responses. The test was repeated after the patients received 100 micrograms GnRH im daily for 7 days. The LH, FSH, PRL, and TSH responses were similar to those obtained previously. The female patients were then retested twice, after priming with 17 beta-estradiol (2 mg daily for 7 days) and again after treatment with human menopausal gonadotropins. The male patients were treated with hCG and, after testosterone reached normal adult male values, the GnRH-TRH stimulation test was repeated. In both the female and male patients, the pituitary responses remained unchanged. These results demonstrate the presence of primary gonadotropin insufficiency as well as the lack of positive estrogen feedback mechanism in patients with thalassemia major. The site of this abnormality has been demonstrated to be the pituitary gland, since hemosiderosis of the pituitary without hypothalamic involvement has been found at autopsy in one patient.

A Review of Endocrine Disorders in Thalassaemia

“…Multiple gonadal and pituitary-gonadal function studies have confirmed primary gonadal failure due to gonadal iron deposition [27]. Secondary hypogonadism results from iron deposition on gonadotrophic cells of the pituitary gland as shown by poor response of FSH and LH to GnRH stimulation [28][29][30] or a combination of both primary and secondary hypogonadism [31].…”

Correlation of Thyroid Hormone Derangement with Serum Ferritin Level in Children with Beta Thalassaemia Major at a Tertiary Care Hospital of Bangladesh

“…Many endocrine deficiencies were attributed to the deposition of iron in endocrine glands of thalassaemic patients 6 . Endocrine abnormalities includes panhypopituitarism 7 , abnormal secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) 8 , hypogonadism 9 , hypoparathyroidism 10 , elevated serum adrenocorticotropic hormone (ACTH) level with decreased adrenal cortical reserve 11 and diabetes mellitus 12 .…”

The prevalence of endocrinopathies among patients with thalassemia major in the district of Batticaloa, Sri Lanka

“…All our patients had secondary hypogonadism with low basal FSH and LH indicating hypothalamic-pituitary damage. This is likely to be secondary to iron deposition on gonadotrophic cells of the pituitary gland (22)(23)(24). Among patients with thalassaemia major, an impact of the genotype on gonadal function also has been documented (25).…”