ENDOCRINE DISORDERS IN THALASSEMIA MAJOR: QUALITY OF LIFE BEYOND SURVIVAL
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1 ENDOCRINE DISORDERS IN THALASSEMIA MAJOR: QUALITY OF LIFE BEYOND SURVIVAL 1,2 Carmen Barbu, 1,2 Alice Albu, 3 Larisa Nitu, 3 Daniela Voicu, 1,3 Florentina Vladareanu, 2 Suzana Florea and 1,2 Simona Fica 1Carol Davila University, 2 Elias Hospital Endocrinology department, 3 National Institute of Hemathology, Bucharest, Romania
2 HOW TO TAKE CARE OF HIM? M.C. 19 years old thallasemic male Splenectomy Hemocromatosis Chronic type C hepatitis Short stature (-3DS) Hypogonadotropic hypogonadism Primary hypothyroidism Secondary osteoporosis (DXA, Z score=-3,9ds) Objective: to determine the prevalence of endocrine complications among betatalassemia major patients and the factors predictive for their appearance. Patients and Methods: cross-sectionalsectional study on 99 patients (48 F/51 M) with betatalassemia major, with mean age of 2,45±7,8 yrs referred to Elias Hospital s Endocrinology Department from National Institute of Transfusional Hemathology between 24 and 211. We evaluated all patients by clinical exam and hormonal and biochemical parameters (FSH, LH, estradiol/testosterone, TSH, FT4, 8 AM plasma cortisol, OGTT, serum calcium and phosphorus levels, serum alkaline phosphatase, PTH (in those with abnormal Ca/P) In a subset of patients: whole body Dual-energy X-ray absorptiometry (DXA) tests for GH reserve: insulin hypoglycemia test, clonidine/arginin infusion test
3 72 PATIENTS IN OUR GROUP WERE IN THE SECOND AND THIRD DECADE OF LIFE male(n) female(n) 4 2 <1 years 1-2years 21-25years >25years THE PREVALENCE OF ENDOCRINOPATHIES AMONG STUDIED PATIENTS 19,5% 8,5% with endocrinopathies without endocrinopathies
4 PREVALENCE OF ENDOCRINE DISTURBANCES AMONG THALASSEMIC PATIENTS sec hypogonadism short stature sec osteoporosis prim hypothyroidism insulin resistance prim hpt DM Endocrine disorders Nr. patients CONSEQUENCES OF HYPOGONADISM (67%)* 33% 24% 18% 25% delayed puberty arrested puberty hypogonadism after complete sexual maturation without hypogonadism * In all cases hypogonadotropic hypogonadism
5 RELATHIONSHIPS BETWEEN IRON OVERLOAD AND PUBERTAL DEVELOPMENT early chelation and 5 4 good compliance 3 with chelator 2 treatment have a 1 positive impact on pubertal 4 development, proba 3 bly mediated by 2 reduced iron 1 load, especially in prepubertal period. FERRITIN (ng/ml) ATIENTS (%) COMPLIANT P pubertal delay prepubertal ferritin (<1 yrs) pubertal delay P<,1 64 normal puberty pubertal ferritin (1-16 yrs) normal puberty Albu A et al, ESPE meeting 29 8 patients with delayed puberty had progression of sexual development during treatment Patients I II III IV Tanner stages end of treatment before treatment Fica and all, Sinaia, 27
6 Time course of growth velocity in patients with delayed puberty 3,5 ) Gro owth velocity (cm/6 month 3 2,5 2 1,5 1, month of treatment Fica and all, Sinaia, 27 Estroprogestative treatment did not significantly changed mean values of liver enzymes comparing to previous period AST/ALT (UI/l) p=ns p=ns 2 AST ALT before treatment during treatment Fica and all, Sinaia, 27
7 PREVALENCE OF SHORT STATURE AMONG STUDIED PATIENTS 39% 61% with short stature without short stature A subgroup of 6 patients with short stature were evaluated for GH deficiency by insulin tolerance test and arginin test and we found subnormal GH responses in all those patients. ETHYOLOGY OF THE SHORT STATURE IN THALLASEMIC PATIENTS 1% 8% 6% 4% 2% % females males Hypothyroidism I GH deficiency Arrested puberty Delayed puberty Fica and all, Sinaia, 27
8 SHORT STATURE WAS ASSOCIATED TO PRECOCIOUS HYPOGONADISM Precociou us hypogonadism(%) p<,5 5 81,2 normal stature short stature Albu A 29 ECE Istanbul LOW IGF 1 IN PATIENTS WITH SHORT STATURE IGF1 (ng/ml) 2 1 p=,1-1 NO YES short stature Albu A 29 ECE Istanbul
9 FERRITIN LEVEL/ANEMIA CONTROL AND SHORT STATURE p=,6 feritina (ng/ml) p<,5 Mean haemoglobin g/dl NO YES 5 NO YES short stature short stature Albu A 29 ECE Istanbul SHORT STATURE AND LIVER TESTS P<,5 2 p<,1 ALT (UI/L) 2 1 AST (UI/L) 1-1 NO YES -1 NO YES short stature short stature Albu A 29 ECE Istanbul
10 GH DEFFICIENCY Due to age at evaluation, compliance and the control of the main disease, only 6 pts were assessed dfor GH secretion (ITT, arginina, test la clonidina) ALL OF THEM SHOWED A LOW GH PEAK(GH<1 ng/ml) Albu A 29 ECE Istanbul FOLLOW UP OF A BOY WITH SHORT STATURE AND GHD WITH TREATMENT Nov ½ yrs I=133 cm, tanner P1G1, bone age 1 yrs Sept ½ yrs I=172 cm, Tanner P3G3, bone age 14 yrs
11 THE PREVALENCE OF HYPOTHYROIDISM AND HYPOPARATHYROIDISM 22% 78% without hypothyroidism with hypothyroidism 8% 92% without hypopth with hypopth ABNORMAL GLUCOSE METABOLISM: 2,9% OF THE STUDIED PATIENTS 16,3% 2,3% 2,3% 79,1% IFG IGT DM NGM IFG impaired fasting glycemia, IGT impaired glucose tolerance, DM diabetes mellitus, NGM normal glucose metabolism
12 TOTAL BODY DXA 2% low BMD normal BMD 8% Mean age 2,45±7,8 (range:1-34) BONE DENSITY SCANING (DXA) IN A 18 YEARS OLD THALASSEMIC MAJOR MALE PATIENT WITH SEVERE SECONDARY OSTEOPOROSIS (WHOLE BODY Z SCORE= -3,5DS)
13 ANTIRESOBTIVE TREATMENT IN LOW BMD 4,8 % mean increase in BMD per year with oral bisphosphonates No fracture reported during the follow up period of time CLINICAL AND PARACLINICAL PARAMETERS ASSOCIATED WITH ENDOCRINE COMPLICATIONS P<,1 P<,5 P<,5 P<,5 P<,5 P<,1 Without endocrinopathies With endocrinopathies Without endocrinopathies With endocrinopathies Without endocrinopathies With endocrinopathies
14 POOR COMPLIANCE WITH HAEMATOLOGICAL TREATMENT WAS SIGNIFICANTLY ASSOCIATED WITH ENDOCRINE COMPLICATIONS patients (%) ,7 31,33 with endocrinopathies Good compliance 19,6 81,4 without endocrinopathies Poor compliance DISTRIBUTION OF PATIENTS BASED UPON AGE AND SERRUM FERRITIN LEVELS 9 8 ferritin ng/ml age (years) endocrinopathies 1 endocrinopathy 2 endocrinopathies 3 endocrinopathies
15 CONCLUSIONS 8% from our patients with major beta thallasemia had at list one endocrinopathy; the most frequent beeing sec hypogonadism, GH defficiency, hypothyroidism but also DM and hypopth Main consequences of endocrine diseases were: low BMD in 8% and short stature in 67% Prevalence of endocrinopathies was significantly correlated to main disease poor control Early endocrine evaluation and treatment are susscesfull in improving the quality of life of thallasemic patients
16 MULTUMESC PENTRU ATENTIE ENDOCRINE SUPPORT IN MAJOR β THALASSEMIA Administration of hormone replacement therapy (oestrogen- progesterone, testosterone, thyroid, growth hormones) Improvement in growth development and sexual maturation; Prevention of osteoporosis: oral calcium and vitamin D supplements, hormone replacement therapy in patients t with hypogonadotropic hypogonadism; Antiresorptive therapy (biphosphonates) Improvement in BMD and quality of life in selected cases; Fertility agents Induction of spermatogenesis;
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