Endocrine Features of Fibrous Dysplasia/McCune-Albright Syndrome
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1 Endocrine Features of Fibrous Dysplasia/McCune-Albright Syndrome Alison Boyce, MD on Skeletal Disorders and Mineral Homeostasis, NIDCR, NIH FD and Family Conference 2017
2 Fibrous Dysplasia/McCune-Albright syndrome: A complex bone and endocrine disorder fibrous dysplasia rickets GH excess precocious puberty Cushing s syndrome hyperthyroidism Bone, pituitary, gonads, thyroid, adrenal, other
3 Onset of manifestaeons of affected Essues Fibrous dysplasia Café-au-lait Precocious Pub. Thyroid Phosphate Growth hormone Cushing s subclinical clinically evident spontaneous resolueon possible Age Most affected and unaffected Essues can be idenefied in childhood
4 Precocious Puberty in MAS Cyst Ovary ovarian cysts Recurrent ovarian cysts Breast development, growth acceleraeon Vaginal bleeding when cysts resolve
5 Precocious Puberty in MAS Estrogen causes early closure of growth plates Treatment is needed to: Prevent disabling short stature in adulthood Prevent psychosocial consequences of early sexual maturaeon AVOID SURGERY
6 Current Treatment OpEons Tamoxifen (Eugster et al, 2003) Alters estrogen receptor 12 month trial, 25 girls with MAS Decreased: linear growth, bone age advancement and vaginal bleeding increased: uterine volume Letrozole (Feuillan et al, 2007) Prevent estrogen 36 month pilot study, 9 girls with MAS decrease: growth rate, bone age advancement and vaginal bleeding one case of ovarian torsion
7 Extended efficacy of letrozole in NIH cohort length of treatment bone age advancement 3 S u b j e c t s n = 22 mean Tx = 4.3y B o n e A g e ( y e a r s ) / C h r o n o l o g i c A g e ( y e a r s ) 2 1 p < S t a r t E n d Y e a r s O n L e t r o z o l e P o s t L e t r o z o l e Estrada et al, EJE 2016
8 MAS Testicular Disease Leydig cell hyperplasia Leydig cell hyperplasia with Sertoli component TesEcular lesions in ~85% Precocious puberty in ~15% Treatment: Spironolactone + letrozole NO SURGERY! Cancer has been rarely reported Ongoing monitoring
9 Thyroid Disease in MAS US in ~66%; hyperthyroidism in ~30% T3 increased T3/T4 (>20) Kids with US may develop hyperthyroidism later goiter characterisec ultrasound Collins JCEM 2003, Celi JCEM 2008
10 Thyroid Disease in MAS Management Short-term: methimazole Long-term: Surgery prefer high-volume center May regrow iodine cancer reported Collins JCEM 2003, Celi JCEM 2008
11 Growth Hormone Excess GH & PP PP ~15% of Growth may be subtle, confounded by FD & endocrinopathies
12 GH excess: deformity and vision loss macrocephaly FD patent obliterated FD opec canal sphenoid bone opec foramen blind ProphylacEc opec nerve decompression is not indicated Lee, NEJM, 2002 (n=38) Watchful waieng is superior to surgery (meta-analysis) Amit, PLos ONE 2011 GH excess is a risk factors for vision loss Cutler, Neurosurgery, 2006 Early GH excess treatment prevents morbidity Boyce Collins, JCEM 2013 (n=129)
13 GH excess management issues: macrocephaly, vision & hearing loss macrocephaly canal compression Treatment: pegvisomant) surgery (hypophosectomy, always difficult) (cancer risk)
14 Cushing s syndrome Presents age <1 year Early recogni@on is essen@al! Adrenalectomy if possible Caveat: spontaneous resolu@on in ~1/3 Neurodevelopmental sequelae Brown et al, JCEM, 2010
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