A Low Dose Adrenocorticotropin Test (1 μg ACTH) for the Evaluation of Adrenal Function in Children with ß-Thalassemia Receiving Hypertransfusion with Suboptimal Iron-chelating Therapy

Jaruratanasirikul, Somchit; Tanchotikul, Santi; Wongcharnchailert, Malai; Laosombat, Vichai; Sangsupavanich, Pasuree; Leetanaporn, Kalaya

doi:10.1515/jpem.2007.20.11.1183

Cited by 17 publications

(17 citation statements)

References 4 publications

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“…This is relatively high compared with other studies 1,2,4,5,22 , but may be due to a relatively conservative peak cortisol cut-off used (18 μg/dL), as well as a somewhat small study cohort. There have been various proposed cut-off levels to define adrenal insufficiency using the GST in non-thalassemia major populations.…”

Section: Discussionmentioning

confidence: 67%

A Significant Proportion of Thalassemia Major Patients Have Adrenal Insufficiency Detectable on Provocative Testing

Huang

Mittelman

Coates

et al. 2015

Journal of Pediatric Hematology/Oncology

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Advances in chelation therapy and noninvasive monitoring of iron overload have resulted in substantial improvements in the survival of transfusion dependent patients with thalassemia major. Myocardial decompensation and sepsis remain the major causes of death. While endocrine abnormalities are a well-recognized problem in these iron-overloaded patients, adrenal insufficiency and its consequences are under-appreciated by the hematology community. The aims of this study were to determine the prevalence of adrenal insufficiency in thalassemia major subjects, to identify risk factors for adrenal insufficiency, and to localize the origin of the adrenal insufficiency within the hypothalamic-pituitary-adrenal axis. Eighteen subjects with thalassemia major (18.9 ± 9.3 years old, 7 female) were tested for adrenal insufficiency using a glucagon stimulation test (GST). Those found to have adrenal insufficiency (stimulated cortisol < 18 μg/dL) subsequently underwent an ovine corticotrophin-releasing hormone (oCRH) stimulation test to define the physiological basis for the adrenal insufficiency. The prevalence of adrenal insufficiency was 61%, with an increased prevalence in males over females (92% vs. 29%, p=0.049). Ten of 11 subjects who failed the GST subsequently demonstrated normal ACTH and cortisol responses to oCRH, indicating a possible hypothalamic origin to their adrenal insufficiency.

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Section: Discussionmentioning

confidence: 67%

A Significant Proportion of Thalassemia Major Patients Have Adrenal Insufficiency Detectable on Provocative Testing

Huang

Mittelman

Coates

et al. 2015

Journal of Pediatric Hematology/Oncology

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“…Among the endocrine dysfunctions, hypogonadism, growth retardation and bone demineralization are the most frequent in thalassaemia. As for the pituitary-adrenal axis, previous studies have reported a variable prevalence of impaired function, ranging from 0 to 45.8% depending on the degree of iron overload, but also on the tests used for diagnosis (2)(3)(4)(5)(6)(7). Furthermore, the majority of studies addressing this issue have been performed in children or young adults.…”

Section: Introductionmentioning

confidence: 99%

The pituitary–adrenal axis in adult thalassaemic patients

Scacchi

Danesi

Cattaneo

et al. 2010

European Journal of Endocrinology

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Objective: We previously described in young thalassaemic patients an altered cortisol and ACTH responsiveness suggesting an impaired adrenocortical reserve. Owing to iron overload, a worsening of adrenal function should be expected in adult patients. Design: In 124 adults with b-thalassaemia, urinary free cortisol (UFC) and plasma ACTH levels were determined and compared with those measured in 150 controls. In 45 patients, cortisol was measured in response to: i) tetracosactide 1 mg as an i.v. bolus (low-dose test, LDT) and ii) tetracosactide 250 mg infused i.v. over 8 h (high-dose test, HDT). Results: UFC and serum cortisol were within the reference range in all patients. Conversely, basal plasma ACTH values were above the upper limit of the normal range in 19 patients. There were no statistically significant differences in the mean values of UFC, basal serum cortisol and plasma ACTH between patients and controls. A subnormal cortisol response to the LDT was registered in 18 out of 56 patients. Three of these patients also displayed a subnormal response to the HDT, together with elevated baseline plasma ACTH levels. In the LDT, a positive correlation was found between basal and peak cortisol values (P!0.0001). The latter were negatively correlated with basal ACTH values in both LDT (P!0.0001) and HDT (P!0.0001). Conclusions: Adult thalassaemic patients often present a subtle impairment of adrenocortical function. This may become clinically relevant in case of major stressful events. Thus, we recommend an assessment of adrenocortical function in all adult thalassaemic patients.

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“…Primary myocardial dysfunction can be caused by hypoparathyroidism [168][169][170] and hypothyroidism, 171,172 and these conditions may exacerbate iron cardiomyopathy. Decreased adrenal reserve is also common in TM, [173][174][175][176][177][178] and patients in HF should be treated as though they have adrenal insufficiency until proven otherwise. Hypogonadotrophic hypogonadism is the most common endocrinopathy observed in TM, 1,179 and low sex steroids may exacerbate HF symptoms.…”

Section: Endocrine Metabolic and Infectious Comorbiditiesmentioning

confidence: 99%

“…Give hydrocortisone on the presumption of inadequate adrenal response to stress. 175 10. Check thyroid, liver, and renal function and calcium, magnesium, vitamin D, carnitine, and other metabolic parameters and correct these when necessary.…”

Section: Management Of Acute Decompensated Hf In Tmmentioning

confidence: 99%

Cardiovascular Function and Treatment in β-Thalassemia Major

Pennell¹,

Udelson²,

Arai³

et al. 2013

Circulation

332

172

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This aim of this statement is to report an expert consensus on the diagnosis and treatment of cardiac dysfunction in β-thalassemia major (TM). This consensus statement does not cover other hemoglobinopathies, including thalassemia intermedia and sickle cell anemia, in which a different spectrum of cardiovascular complications is typical. There are considerable uncertainties in this field, with a few randomized controlled trials relating to treatment of chronic myocardial siderosis but none relating to treatment of acute heart failure. The principles of diagnosis and treatment of cardiac iron loading in TM are directly relevant to other iron-overload conditions, including in particular Diamond-Blackfan anemia, sideroblastic anemia, and hereditary hemochromatosis. Heart failure is the most common cause of death in TM and primarily results from cardiac iron accumulation. The diagnosis of ventricular dysfunction in TM patients differs from that in nonanemic patients because of the cardiovascular adaptation to chronic anemia in non–cardiac-loaded TM patients, which includes resting tachycardia, low blood pressure, enlarged end-diastolic volume, high ejection fraction, and high cardiac output. Chronic anemia also leads to background symptomatology such as dyspnea, which can mask the clinical diagnosis of cardiac dysfunction. Central to early identification of cardiac iron overload in TM is the estimation of cardiac iron by cardiac T2* magnetic resonance. Cardiac T2* <10 ms is the most important predictor of development of heart failure. Serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement. Assessment of cardiac function by noninvasive techniques can also be valuable clinically, but serial measurements to establish trends are usually required because interpretation of single absolute values is complicated by the abnormal cardiovascular hemodynamics in TM and measurement imprecision. Acute decompensated heart failure is a medical emergency and requires urgent consultation with a center with expertise in its management. The first principle of management of acute heart failure is control of cardiac toxicity related to free iron by urgent commencement of a continuous, uninterrupted infusion of high-dose intravenous deferoxamine, augmented by oral deferiprone. Considerable care is required to not exacerbate cardiovascular problems from overuse of diuretics or inotropes because of the unusual loading conditions in TM. The current knowledge on the efficacy of removal of cardiac iron by the 3 commercially available iron chelators is summarized for cardiac iron overload without overt cardiac dysfunction. Evidence from well-conducted randomized controlled trials shows superior efficacy of deferiprone versus deferoxamine, the superiority of combined deferiprone with deferoxamine versus deferoxamine alone, and the equivalence of deferasirox versus deferoxamine.

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A Low Dose Adrenocorticotropin Test (1 μg ACTH) for the Evaluation of Adrenal Function in Children with ß-Thalassemia Receiving Hypertransfusion with Suboptimal Iron-chelating Therapy

Cited by 17 publications

References 4 publications

A Significant Proportion of Thalassemia Major Patients Have Adrenal Insufficiency Detectable on Provocative Testing

A Significant Proportion of Thalassemia Major Patients Have Adrenal Insufficiency Detectable on Provocative Testing

The pituitary–adrenal axis in adult thalassaemic patients

Cardiovascular Function and Treatment in β-Thalassemia Major

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