Department of Endocrine Neoplasia and Hormonal Disorders NEWSLETTER Volume 3, Issue 1, 2010 Pediatric Endocrine Tumors ® Steven G. Waguespack, M.D., FAAP, FACE Associate Professor Department of Endocrine Neoplasia and Hormonal Disor- ders; Division of Pediatrics Endocrine tumors Pediatric Endocrine Tumors, An Overview represent a minority of Pituitary Tumors all neoplasms observed Pituitary adenomas (PA) represent less than in the pediatric popu- 3% of all supratentorial tumors diagnosed dur- lation and are gener- ing childhood. Over 75% of PAs occur in children ally clinically benign older than 12 years, and females are more com- or low-grade cancers, monly affected than males. Pituitary tumors are although a small percentage of these tumors are usually diagnosed secondary to symptoms of high-grade malignancies requiring multimodal- hormone excess or mass effect, such as visual ity therapies. Although rare, pediatric endocrine disturbance (classically a bitemporal hemiano- tumors are important clinical entities that can psia), headache, or ophthalmoplegia. Patients have unique clinical presentations and genet- may also present with delayed growth and pu- ic causes. As with any rare childhood disease, bertal development due to pituitary hormone treatment is best provided at referral centers hypersecretion, as seen with hyperprolactine- with multidisciplinary expertise in the manage- mia, or hyposecretion, as seen with large PAs ment of such tumors. The Pediatric Endocrine that compress the normal adenohypophyseal Tumor Program at the Children’s Cancer Hos- tissue. The initial workup of a PA is similar to pital of the University of Texas M. D. Anderson adults and includes imaging of the sella turcica, Cancer Center is a multidisciplinary program a comprehensive hormonal evaluation to assess that provides primary evaluation and treat- for hyper- and hypopituitarism, and visual field ment to children and young adults suspected testing for children with large tumors that ap- PERSPECTIVES to have or who are already diagnosed with thy- proach the optic chiasm. Prolactinomas are the roid neoplasms, adrenal tumors, pituitary ad- most common PA in childhood, representing enomas, and/or hereditary tumor syndromes. about 50% of cases, followed by ACTH-secret- Our team currently consists of two board-cer- ing adenomas (Cushing disease), somatotroph tified adult and pediatric endocrinologists, Ste- adenomas (gigantism/acromegaly), and lastly, ven Waguespack, M.D. and Anita Ying, M.D., and clinically nonfunctioning PAs. In contradistinc- Sarah Bottomley, RN, MSN, CPNP, a pediatric tion to adults, (continued on Page 2) nurse practitioner who works closely with both Drs. Waguespack and Ying. Table of Contents This issue of EndoPerspectives is focused on pediatric endocrine tumors. We start with a general overview of the most common endo- Pediatric Endocrine Tumors Page 1 crine neoplasms encountered in the pediatric Upcoming Events Page 2 population. Dr. Ying and Ms. Bottomley review Notes from the Endocrine Faculty Page 4 late effects of endocrine tumors and their treat- Team ment. Thereasa Rich, M.S., C.G.C., reviews the MEN Patient Education Conference Page 4 genetic syndromes most commonly associated ENDO Late Effects of Endocrine Tumors Page 5 with pediatric endocrine tumors and emphasiz- Genetic Counseling and Genetic As- es the role of genetic counseling when taking care of these children. pects of Pediatric Endocrine Tumors Page 6 The Thyroid Nodule Clinic Page 8 (Waguespack, continued from Page 1) oncogene: multiple endocrine neoplasia type nonfunctioning PAs represent only <5% of 2a (MEN2A) and type 2b (MEN2B). In addition Upcoming Events pediatric pituitary tumors. Although the clini- to the almost complete penetrance of MTC, cal presentation of PAs during childhood is 50% of patients with MEN2A and MEN2B de- AACE 19th Annual Meet- often different compared with adults, the ap- velop pheochromocytomas and up to 30% of ing and Clinical Congress proach to diagnosis and treatment of these MEN2A patients have parathyroid adenomas, April 21-25, 2010 neoplasms is similar. although these tumors are rarely diagnosed Sheraton Boston Hotel and during childhood. Patients with MEN2B have the John B. Hynes Veterans a distinct phenotype with a characteristic fa- Memorial Convention Center cial appearance, Marfanoid body habitus, and Boston, MA (http://www. a generalized ganglioneuromatosis, mani- aace.com/meetings/cal- fested most obviously by the presence of oral endar/calendar.php) mucosa neuromas. LWPES 2010 Annual Meet- Children with thyroid cancer usually pres- ing May 1-3, 2010. Vancou- ent with an asymptomatic thyroid mass and/ ver, Canada. (http://www. or cervical lymphadenopathy. Lymph node lwpes.org/meetingsEvents/ metastases are present in the majority of PTC pdf/2010LWPESschedule. cases and lung metastases are identified in pdf) up to 20% of cases; metastases to other sites occur but are rare. ATA Spring Meeting of the American Thyroid Association May 13- 16, 2010. Minneapolis, MN (www.thyroid.org) PTC 8-year-old with Cushing disease and a cys- The Endocrine Society tic pituitary macroadenoma (arrows). LN ENDO 2010, June 19-22, LN 2010. San Diego, CA. Thyroid Tumors (www.endo-society.org) Benign Thyroid Tumors Benign thyroid tumors represent up to 80% 14th International Thy- of all thyroid nodules presenting in the pedi- roid Congress Sept. 11- atric population. The younger a child is at the 16, 2010. Paris, France. (www.itc2010.com) time of presentation, the more likely it is for a solitary nodule to be malignant. The work North American Neuro- up of a thyroid nodule in a child includes the Endocrine Tumor Society laboratory assessment of thyroid function, Annual Conference ultrasound to assess the nodule and regional CT scan of a 6-year-old with papillary thyroid October 29-30, 2010. lymph node characteristics, and fine needle cancer (PTC) and bulky bilateral lymph node Santa Fe, New Mexico aspiration (usually under ultrasound guid- (LN) metastases. (www.nanets.net) ance) for definitive diagnosis. Solid lesions with increased blood flow and the presence Despite a more advanced presentation, 14th Asia-Oceania Con- of microcalcifications are more likely to be children with thyroid cancer usually have an gress of Endocrinology malignant whereas pure cystic lesions are excellent prognosis with anticipated survival December 2-5, 2010. over decades. Part of this clinical phenom- Kuala Lumpur, Malaysia almost always benign. Nuclear scintigraphy (www.aoce2010.com) with 123I or Tc-99m pertechnetate is gener- enon may be due to mutational differences ally not useful in the diagnostic evaluation, between children and adults, in addition to MEN 2010 12th Interna- except in the event of a suppressed TSH. the fact that pediatric PTC is usually very io- tional Workshop on Mul- Malignant Thyroid Tumors dine avid, typically leading to successful treat- tiple Endocrine Neoplasia Malignant neoplasms of the thyroid are ment of distantly metastatic disease after one Sept. 16-18, 2010. Gubbio, Italy (www.men2010.com) rare in the pediatric population, with an in- or more courses of radioactive iodine (RAI) cidence of ≤1 case/million/year in children therapy. under ten years of age to 15.4 cases/million/ Total thyroidectomy and a compartment-ori- year in adolescents ages 15-19, which is the ented lymph node dissection, as indicated, are most commonly affected pediatric age group. best accomplished by surgeons with extensive Over 90% of thyroid cancers occurring in experience in the management of thyroid ma- childhood are papillary thyroid cancer (PTC). lignancies. In DTC, radioiodine (using 131I) is Medullary thyroid carcinoma (MTC) is a very often administered a few weeks after surgery uncommon disease in childhood that almost to ablate any residual normal thyroid tissue always occurs in the context of one of two and treat any residual thyroid cancer that is hereditary endocrine tumor syndromes that iodine-avid; children with MTC do not require arise secondary to activating mutations of the radioiodine ablation. The thyroid stimulating RET (REarranged during Transfection) proto- hormone (TSH) level is suppressed by giving Continued on Page 3 2 (Waguespack, continued from Page 1) to present at an age <5 years. They have a female predomi- supraphysiologic levothyroxine doses in DTC but the TSH is nance and are functional tumors (producing androgens and/ kept normal in MTC. Long-term follow up involves monitor- or glucocorticoids, typically) in >90% of cases. ACT may also ing of tumor markers (thyroglobulin in DTC and calcitonin/ present as an abdominal mass or pain. In children, ACT are as- carcinogenic embryonic antigen in MTC) as well as routine sociated with the Li-Fraumeni syndrome (germline inactivat- imaging based upon the initial extent of disease presenta- ing mutations in the p53 tumor suppressor gene), the Beck- tion. Neck US is generally the most useful imaging modality. with-Wiedemann syndrome (BWS), hemihypertrophy other Traditional chemotherapy has generally not been shown to than that seen as part of BWS, and rarely congenital adrenal be effective in thyroid cancer, but newer anti-cancer agents, hyperplasia. Other rare causes of nodular adrenocortical dis- the oral tyrosine kinase inhibitors, are showing promise in the ease, which usually present with Cushing syndrome, include treatment of children with disease not amenable or respon- Carney’s complex and macronodular adrenal hyperplasia. sive to standard therapeutic approaches. PHEO