Endocrine complications of beta-thalassemia major: Primary amenorrhea as a revealing feature of hypogonadotropic hypogonadism

Beta-thalassemia major is a hereditary hemoglobinopathy requiring lifelong blood transfusions, leading to chronic iron overload responsible for multiorgan endocrine complications, of which hypogonadism is the most frequent. We report the case of a 22-year-10-month-old female patient, followed for β-thalassemia major since the age of 3, presenting with primary amenorrhea. Clinical examination revealed late-onset breast development at Tanner stage II and pubic hair at Tanner stageIV. Hormonal workup confirmed isolated hypogonadotropic hypogonadism, with the following results: estradiol<24pg/mL, follicle-stimulating hormone 1.14 uIU/mL (ref: 3.03–8.08), luteinizing hormone 0.2uIU/mL (ref:2.39–6.6), prolactin 9.8ng/ml and serum ferritin at 7288µg/L sixty times above upper limit on deferiprone 500mg, three tablets three times daily. Pituitary MRI demonstrated an age-appropriate gland with T2*-weighted-hypo-intensity consistent with pituitary siderosis, providing objective imaging evidence of iron deposition at the gonadotroph level as the underlying mechanism of central hypogonadism. Bone assessment by bone densitometry revealed osteoporosis at multiple sites. Workup for other iron overload-related endocrinopathies returned within normal limits. The patient was initiated on transdermal-17beta-estradiol at progressively increasing doses starting at0.25mg/day.
The pedagogical originality of this case report lies in the association between primary amenorrhea — reflecting gonadotroph damage early enough to prevent pubertal completion — and pituitary siderosis directly visualized on MRI, offering a didactically valuable illustration of the causal link between chronic iron overload and central hypogonadotropic hypogonadism. This case underscores the importance of systematic and early endocrine screening in transfusion-dependent thalassemia patients, and highlights the need for prompt hormone replacement therapy initiation and optimized iron chelation to prevent irreversible endocrine complications.