Abstract
INTRODUCTION
In thalassemia patients transfusion therapy and inappropriately increased iron absorption due to ineffective erythropoiesis cause iron overload, which account for most morbidity in these patients, with involvement of liver, heart and endocrine glands. The most frequent endocrine defect is hypogonadotropic hypogonadism, followed by diabetes mellitus, hypothyroidism and hypoparathyroidism. The hypothalamic-pituitary-adrenal axis is rarely affected, but the identification of asymptomatic patients is crucial, as adrenal insufficiency is a potentially life-threatening condition. Hypoadrenalism can play a dramatic role in stressful situations like acute cardiac failure, sepsis or surgery. A better understanding of emerging complications, including adrenal insufficiency, is essential in the thalassemia population, considering their increased survival and life activities.
We describe three cases of thalassemia major patients regularly monitored at our Rare disease Center. The annual endocrinological follow-up at our Clinic includes the evaluation of basal adrenal function (cortisol and corticotrophin serum levels), with completely normal results in the patients described. In all of them there were no symptoms nor clinical signs of hypoadrenalism, which dramatically emerged only on occasion of acute events and was confirmed by the finding of inappropriately low serum cortisol levels.
CASE REPORT 1. A 52-year-old male was admitted to the Intensive Care Unit for severe sepsis due to bacterial pneumonia and heart failure associated with atrial fibrillation in November 2015. He was regularly transfused every three weeks, on oral iron chelation therapy with deferasirox with no liver nor cardiac iron overload. Conversely, endocrinopathy was present with type 2 diabetes, hypogonadotropic hypogonadism and hypoparathyroidism. Adrenal crisis was suspected because of persistent hypotension despite intensive treatment for septic shock, including intravenous norepinephrine. Intravenous replacement therapy with hydrocortisone rapidly reverted the hypotension.
CASE REPORT 2. A 44-year-old male patient was admitted to the Intensive Care Unit in February 2015 for severe sepsis, hyponatremia, hypoglycemia and mental confusion. He was regularly transfused with two/three units of packed red cells every three weeks, on iron chelation therapy with deferasirox. He had not liver nor heart iron overload, and the only endocrine defect was hypogonadotropic hypogonadism. Hypoadrenalism was suspected as severe hypoglycemia did not respond to continuous ev glucose administration. Glucose blood levels normalized only after hydrocortisone ev.
CASE REPORT 3. A 40-year-old male patient had a right abdominal mass known since 2002, and ascribed to extramedullary erythropoiesis. The mass volume had been progressively increasing up to 19 x 15 x 25 cm³. In 2015 a computed tomography scan of the abdomen showed a huge well circumscribed retroperitoneal mass in the right abdomen, originating from the right adrenal gland, displacing the liver medially and the right kidney caudally and anteriorly; moreover, it compressed the inferior vena cava and displaced the mesenteric vessels. In view of surgery, though adrenal basal function was normal an ACTH test was performed, disclosing adrenal insufficiency. Replacement therapy with hydrocortisone was set to make the patient able to cope with the stressful event. Laparotomy was performed and a 3.5 kg encapsulated tumour attached to the right adrenal gland was removed; histology revealed a giant myelolipoma.
CONCLUSIONS
The three cases presented show that adrenal insufficiency requires early detection, that it may be underdiagnosed and it can present dramatically in acute and even life-threatening conditions. Pituitary-adrenal axis should be screened in asymptomatic thalassemic patients, and once adrenal insufficiency has been identified, it should be treated to prevent potentially lethal consequences. Currently, our patients are asymptomatic on chronic oral replacement therapy with cortisone acetate. Increased awareness of the risks of hypoadrenocorticism in patients with iron overload is needed, because symptoms are usually not clinically evident and often neglected because of their mildness, especially in non-stressful situations.
Disclosures
Cappellini: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genzyme-Sanofi: Membership on an entity's Board of Directors or advisory committees.
Hypogonadotropic hypogonadism presenting with arhinia: a case report