Maria Concetta Galati

Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I‑CET) position statement and guidelines

The current management of thalassemia includes regular transfusion programs and chelation therapy. It is important that physicians be aware that endocrine abnormalities frequently develop mainly in those patients with significant iron overload due to poor compliance to treatment, particularly after the age of 10 years. Since the quality of life of thalassemia patients is a fundamental aim, it is vital to monitor carefully their growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment. Abnormalities should be identified and treatment initiated in consultation with a pediatric or an adult endocrinologist and managed accordingly. Appropriate management shall put in consideration many factors such as age, severity of iron overload, presence of chronic liver disease, thrombophilia status, and the presence of psychological problems. All these issues must be discussed by the physician in charge of the patients care, the endocrinologist and the patient himself. Because any progress in research in the field of early diagnosis and management of growth disorders and endocrine complications in thalassemia should be passed on to and applied adequately to all those suffering from the disease, on the 8 May 2009 in Ferrara, the International Network on Endocrine Complications in Thalassemia (I-CET) was founded in order to transmit the latest information on these disorders to the treating physicians. The I-CET position statement outlined in this document applies to patients with transfusion-dependent thalassemia major to help physicians to anticipate, diagnose, and manage these complications properly.

Growth hormone secretion in adult patients with thalassaemia

Background and Objectives  Growth retardation and short stature are frequent clinical features of patients with beta‐thalassaemia major. Dysfunction of the GH–IGF‐1 axis has been described in many thalassaemic children and adolescents with short stature and reduced growth velocity. Several studies have demonstrated that recombinant GH treatment improves growth velocity in these patients, although response to the treatment is variable and not predictable. A reassessment of the GH–IGF‐1 axis must be performed in young adults with childhood‐onset GH deficiency (GHD), after attainment of final height, to select those who are candidates for replacement therapy as adults. To our knowledge there are no data available on retesting the GH–IGF‐1 axis in adult thalassaemic patients with childhood‐onset GHD. The aim of our study was to investigate GH secretion in adult thalassaemic patients with childhood‐onset GHD.

Final height in short polytransfused thalassemia major patients treated with recombinant growth hormone

We measured the final height (FH) of 25 short polytransfused thalassemia major (Th) patients (18 males) with a reduced GH reserve treated for 3.3±1.2 yr with recombinant GH (rhGH), 0.2 mg/kg/week sc. At baseline, all patients were clinically prepubertal; their chronological (CA) and bone ages (BA) were 13.6±2.0 and 11.4±1.6 yr, respectively. In 9 out of 18 males and 5 out of 7 females, the onset of puberty occurred spontaneously during the treatment. At the end of the rhGH administration, the height of the enrolled children was not significantly increased when calculated for CA (HxCA), while it was significantly decreased (p=0.004) when calculated for BA (HxBA); the BA increase (3.29±1.65 yr) was significantly higher (p<0.001 ) than the height age increase (2.16±0.98 yr). The FHxCA showed a significant increase (p=0.001) compared to both baseline and the end of therapy, while the FHxBA was significantly decreased (p<0.001) compared with the corresponding value at baseline. At the end of therapy, both HxCA and HxBA resulted positively related to the BA at baseline (r=0.50 and 0.42, p=0.012 and 0.034, respectively). FH was positively correlated with CA (r=0.63, p=0.001), BA (r=0.68, p<0.001) and HxBA (r=0.59, p=0.002) evaluated at baseline, and with both HxCA and HxBA (r=0.82 and 0.74, respectively, p<0.001), evaluated at the end of treatment. A negative correlation was found between FH and the length of treatment (r=−0.56, p=0.004). Our data seem to exclude that prolonged rhGH therapy could improve FH in Th patients; on the contrary, a negative effect may be hypothesized.

An ICET- A survey on Hypoparathyroidism in Patients with Thalassaemia Major and Intermedia: A preliminary report

Hypoparathyroidism (HPT) is a rare disease with leading symptoms of hypocalcemia, associated with high serum phosphorus levels and absent or inappropriately low levels of parathyroid hormone (PTH). In patients with thalassemias it is mainly attributed to transfusional iron overload, and suboptimal iron chelation therapy. The main objectives of this survey were to provide data on the prevalence, demographic and clinical features of HPT in thalassemia major (TM) and intermedia (TI) patients living in different countries, and to assess its impact in clinical medical practice. A questionnaire was sent to all Thalassemia Centres participating to the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) Network. Seventeen centers, treating a total of 3023 TM and 739 TI patients, participated to the study. HPT was reported in 206 (6.8%) TM patients and 33 (4.4%) TI patients. In general, ages ranged from 10.5 to 57 years for the TM group and from 20 to 54 years for the TI group. Of the 206 TM patients and 33 TI patients with HPT, 117 (48.9%) had a serum ferritin level >2.500 ng/ml (54.3% TM and 15.1% TI patients) at the last observation. Hypocalcemia varied in its clinical presentation from an asymptomatic biochemical abnormality to a life-threatening condition, requiring hospitalization. Calcium and vitamin D metabolites are currently the cornerstone of therapy in HPT. In TM patients, HPT was preceded or followed by other endocrine and non-endocrine complications. Growth retardation and hypogonadism were the most common complications (53.3% and 67.4%, respectively). Although endocrine complications were more common in patients with TM, non-transfused or infrequently transfused patients with TI suffered a similar spectrum of complications but at a lower rate than their regularly transfused counterparts. In conclusion, although a large international registry would help to better define the prevalence, comorbidities and best treatment of HPT, through the result of this survey we hope to give a clearer understanding of the burden of this disease and its unmet needs. HPT requires lifelong therapy with vitamin D or metabolites and is often associated with complications and comorbidities. Therefore, it is important for endocrinologists and other physicians, who care for these patients, to be aware of recent advances of this disorder.(www.actabiomedica.it)

Vitamin D and Risk for Vitamin A Intoxication in an 18-Month-Old Boy

An 18-month-old boy presented with abdominal pain, vomiting, diarrhea, and poor appetite for 6 days. He had been given a multivitamin preparation once daily, containing 50.000 IU of vitamin D and 10.000 IU of vitamin A for a wide anterior fontanelle for about three months. He presented with hypercalcemia, low levels of parathyroid hormone (PTH), and very high serum 25-hydroxyvitamin D (25-OHD) levels. Renal ultrasound showed nephrocalcinosis. He did not have sign or symptom of vitamin A intoxication. Patient was successfully treated with intravenous hydration, furosemide, and prednisolone. With treatment, serum calcium returned rapidly to the normal range and serum 25-OHD levels were reduced progressively. In conclusion the diagnosis of vitamin D deficiency rickets without checking 25-OHD levels may cause redundant treatment that leads to vitamin D intoxication (VDI).