Thyroid Dysfunction after HSCT

Transcription

1 Thyroid and Gonadal EBMT Slide template Dysfunction in the Adult Barcelona after HSCT 7 February 2008 Philipp Schwarze Paediatric Haematology/Oncology Paediatric Endocrinology University Children s Hospital Tübingen Germany Thyroid Dysfunction after HSCT Compensated Hypothyroidism Primary/Secondary/Tertiary Hypothyroidism Autoimmune Thyroid Disease (Autologous or Allogeneic HSCT) (Hypo- or Hyperthyroidism) Thyroid Carcinoma as Secondary Neoplasm Budapest,Hungary 1-3 Nov

2 Occurrence of Thyroid Dysfunction Prolonged chronic graft-versus-host disease is a risk factor for thyroid failure in long-term survivors after matched sibling donor stem cell transplantation for hematologic malignancies Savani BN, Koklanaris EK, Le Q, Shenoy A, Goodman S, Barrett AJ Time to Hypothyroidism [months] 2009 Risk Factors for Thyroid Dysfunction 2009 Budapest,Hungary 1-3 Nov

3 Conditioning with Chemotherapy 2005 Chronic GvHD Prolonged chronic graft-versus-host disease is a risk factor for thyroid failure in long-term survivors after matched sibling donor stem cell transplantation for hematologic malignancies Savani BN, Koklanaris EK, Le Q, Shenoy A, Goodman S, Barrett AJ Associations between prolonged IST and Overt (C) and Subclinical (D) Hypothyroidism 2009 Budapest,Hungary 1-3 Nov

4 Autoimmune Thyroid Disease (AITD) Author/year HSCT GvHD Latency Donor AITD/yr Type of AITD Aldouri/1990 allog m Hashimoto T./-14 Hashimoto T. 1 Wyatt/1990 allog. no 36m Hashimoto T./-- Hashimoto T. 1 Carlson/1992 autol. no Hashimoto T. 4 Vialettes/1993 allog. yes 36 Hashimoto T./+4 Hashimoto T. 1 Thomsen/1995 allog m Hashimoto T./+0.2 Hashimoto T. 1 Kishimoto/1996 allog. yes 5m Hashimoto T./+0 Hashimoto T. 1 Karthaus/1997 allog. yes 13m Hashimoto T./-10 Hashimoto T. 1 Lambertenghi/1997 autol. no 26m Hashimoto T. 1 Marazuela/2000 allog. yes 13 TAK/TPOAK/TSH-R Hashimoto T. 1 Lee/2001 allog. yes 13 Hashimoto T./-- Hashimoto T. 1 Kami/2001 allog. 5 yes/3 no 2-10m Hashimoto T. 8 Mulligan/1987 allog. yes 36m Graves D. 1 Holland/1991 allog. no 96m Graves D./+8 Graves D. 1 Ichihashi/1992 allog. no 28m Graves D./+0.1 Graves D. 1 Takeshita/1999 allog. yes 24 Graves D./-- Graves D. 1 Berisso/1999 allog. yes 24 Graves D./-9 Graves D. 1 Hsiao/2001allog. yes Graves D. 1 Olivares/2002 allog Graves D. 1 Autologous HSCT 2005 Budapest,Hungary 1-3 Nov

5 Acute Thyrotoxicosis 2001 Secondary Thyroid Carcinoma 2007 Budapest,Hungary 1-3 Nov

6 Secondary Thyroid Carcinoma 2009 Summary Thyroid Function Thyroid Dysfunction is frequent after HSCT Compensated Hypothyroidism L-T4 Treatment if TSH remains elevated or increases Autoimmune Thyroid Disease Secondary Neoplasm: Thyroid Carcinoma TSH/fT4 at 0/6/12m/yearly, Ultrasound 0/12m/yearly Budapest,Hungary 1-3 Nov

7 Risk Factors for Gonadal Dysfunction Chemotherapy - Cyclophosphamide - Melphalan - Busulfan - Cisplatin - Radiotherapy Dose and Fractionation Sex and Age Radiotherapy and Fractionation Days to first elevated gondadotrophin level or hormone replacement 1998 Budapest,Hungary 1-3 Nov

8 Influence of Sex 1998 Influence of Age Days to first elevated gondadotrophin level or hormone replacement 1998 Budapest,Hungary 1-3 Nov

9 Gonadal Dysfunction in the Female Hypergonadotropic Hypogonadism (primary) Hypogonadotropic Hypogonadism (secondary/tertiary) follicle: granulosa and thecal cells and germ cells FSH and LH Levels after HSCT Days to first elevated gondadotrophin level or hormone replacement Budapest,Hungary 1-3 Nov

10 Ovarian Failure after Radiation 2005 Ovarian Failure after Radiation 2005 Budapest,Hungary 1-3 Nov

11 Marker of Ovarian Failure 2008 Treatment of Ovarian Failure Transdermal Patch Combination Oral Contraceptive Budapest,Hungary 1-3 Nov

12 Gonadal Dysfunction in the Male Hypergonadotropic Hypogonadism (primary) Hypogonadotropic Hypogonadism (secondary/tertiary) Sertoli Cell Function Leydig Cell Function Sertoli Cell vs. Leydig Cell Function SC more sensitive to the effects of chemotherapy SC more sensitive to the effects of radiotherapy - spermatogonia 0.1 Gy - spermatocytes 2-3 Gy - spermatozoa 4-6 Gy Budapest,Hungary 1-3 Nov

13 FSH and LH Levels after HSCT Days to first elevated gondadotrophin level or hormone replacement 1998 Testes Volumes 2000 Budapest,Hungary 1-3 Nov

14 Treatment of Testicular Failure Transdermal Patch/Gel Intramuscular Injections Summary Gonadal Function Gonadal Dysfunction is frequent after HSCT Hypergonadotropic Hypogonadism Transdermal Patch or Combination Oral Contraceptive Transdermal Pach/Gel or Intramuscular Injection Female: Evaluation of Recovery (1-2 years) LH/FSH, Estradiol/Testosterone, AMH (Female) Budapest,Hungary 1-3 Nov