Children's Doctor

Endocrinology - Spring 2013

Thyroid Cancer Happens

Andrew J. Bauer, MD, FAAP

A 14-year-old female presents for a routine sports physical. She is a long-time patient of your practice and has been previously healthy, including normal growth and development and onset of menses at 12 years of age. Her height is at the 75th percentile and weight at the 65th percentile, both leveling off over the last 12 months. On exam you notice a mass in her anterior neck, midway between her chin and clavicles, about 1 cm off the midline to the left. The mass is about 1.5 cm in greatest dimension. On the same side, you palpate lymph nodes along the anterior edge as well as posterior to her sternocleidomastoid. The midline mass moves with swallowing and none of these lesions are painful. You do not feel any mass on the right, however; you palpate several smaller lymph nodes under the angle of her jaw. The remainder of her exam is normal.

The family is surprised by your findings. On more directed questioning she is asymptomatic and denies weight loss, night sweats, hoarseness, and dysphagia. She has not traveled recently and has no new pets at home. There are no cancers with increased incidence in the family. Her last exam for an acute illness about 6 months ago did not document similar findings.

Discussion: The diagnosis is papillary thyroid carcinoma. PTC is one of two subtypes of differentiated thyroid cancer (DTC): PTC and follicular thyroid cancer (FTC), with PTC comprising 85% to 90% of cases. DTC most frequently occurs as a sporadic condition although there are increasing reports of familial DTC which may occur in isolation or be a part of a tumor syndrome, including familial adenomatous polyposis, PTEN hamartoma syndrome, pleuropulmonary blastoma DICER1 syndrome, and others. Familial DTC is defined by 2 or more first-degree relatives having the disease with an associated 8- to 10-fold increased risk for other first-degree relatives developing DTC compared to the general population.

PTC is most commonly diagnosed after the incidental discovery of an asymptomatic thyroid nodule either during physical exam or during non-thyroid related head and neck imaging. PTC may also present as persistent cervical lymphadenopathy and, thus, a thyroid ultrasound (US) should be considered as part of the evaluation of persistent adenopathy prior to proceeding with biopsy.

For unknown reasons, there are an increasing number of both pediatric and adult patients being diagnosed with thyroid nodules as well as thyroid cancer, with thyroid cancer now the second-most frequently diagnosed malignancy in Caucasian girls aged 15 to 19. Risk factors include previous exposure to ionizing radiation (most frequently associated with treatment of a non-thyroid malignancy), iodine deficiency, and autoimmune thyroiditis.

When thyroid nodules are discovered in pediatric patients, there is a 5-fold higher risk of malignancy when compared to adults, approximately 25% to 30% vs. 5% to 10%, respectively. However, based on these estimates, the majority are benign; the challenge is to determine which patients warrant further evaluation and treatment. As with all diagnoses, a thorough history and physical exam are essential, focusing on review of known risk factors (discussed above) and documentation of the location and texture of the nodule(s) as well as any abnormal cervical lymph nodes. A thyroid and neck ultrasound provides further characterization of the nodule(s) and lymph nodes (See Figure 1). Based on these data, patients are then stratified to either undergo fine needle aspiration (FNA) biopsy or to continue clinical surveillance. The use of conscious sedation, US guidance, bedside confirmation of sample adequacy, and review by a cytopathologist with extensive experience in evaluating thyroid disease is essential for an accurate FNA diagnosis.

Figure 1: Ultrasound Images of the Thyroid and Cervical Lymph Nodes
 

ultrasound 1

A normal appearing thyroid gland (Is: isthmus) with adjacent structures (SCM: sternocleidomastoid muscle, C: cartoid artery, JV: jugular vein)

ultrasound 2

A complex, mostly cystic thyroid nodule in the right thyroid lobe. These complex nodules have a lower risk of malignancy.

ultrasound 3

Two large, hypoechoic nodules associated with poorly defined borders, the left-sided nodules showing macro- and microcalcifications.

ultrasound 4

An abnormal lymph node, round in shape with microcalcifications (shown) and increased peripheral blood flow (not shown). These features are very consistent with thyroid metastasis.

With appropriate evaluation and management, the prognosis of DTC in children and adolescents is excellent. This is true even for patients who present with local or distant metastases, which occur in 50% to 60% and 15% to 20%, respectively. Unfortunately, while disease-specific mortality is low, disease-specific morbidity is relatively high secondary to complications of surgery and therapy. These risks can be significantly reduced if patients are evaluated and cared for in a center organized, resourced, and experienced in managing patients with thyroid disease, including thyroid nodules and thyroid cancer. Access to a surgeon who performs more than 30 thyroid surgeries per year is the most important initial step in increasing the likelihood of good outcome. The selective use of radioiodine therapy is also a critical aspect of care. Long-term follow-up is essential, as up to 30% of patients experience recurrence over 3 to 4 decades of follow-up.

Our patient had a total thyroidectomy with central neck lymph node dissection. Post-operative staging revealed a small focus of uptake in the central neck that was treated with radioiodine therapy. She is currently back to her usual routine, on TSH-suppressive therapy, and being followed on an every 3-month surveillance plan. With continued care, she will have no limitations and will experience excellent long-term prognosis.

Referral Information

To refer a patient, call 215-590-3174. For information on thyroid nodules and thyroid cancer, as well as the Pediatric Thyroid Center, visit www.chop.edu/thyroid.

Online Figure 1: Functional Imaging

figure 2

Functional imaging allowing for greater delineation of anatomic location of persistent, metastatic thyroid cancer: 123-I diagnostic whole body scan (DxWBS) showing uptake in the central and lateral neck. The addition of SPECT-CT (single photon emission CT; images B-> F) to the 123-I scan provides exact anatomic location of the uptake allowing for improved surgical planning.

Late to Diagnosis: Turner Syndrome

Denise Gruccio, MSN, CRNP

A 9-year-old girl presents for annual well visit. Mother expresses a concern for her daughter’s short stature. By mother’s report, the girl has always been petite and is the shortest in her class. Family genetics for height indicate tall stature; she is notably small for the family.

Her past medical history is unremarkable other than an ongoing issue of reoccurring otitis media. Birth history indicates that she was born full term, SVD. Birth weight was 6 lbs, 6 ozs, and length was normal. Review of systems is unremarkable. Overall, she is described as very healthy. She denies any medical complaints. School performance is good but she requires additional support with math.

Physical examination reveals she is well appearing though short for age. Height is 2.5th percentile, and weight is 30th percentile. She is prepubertal. Her cardiac and respiratory exams are normal. Mild high arched palate is noted. Mild cubitus valgus is noted. The remainder of examination is unremarkable.

Discussion: The diagnosis is Turner syndrome (TS).

Turner syndrome is a syndromic condition resulting from complete or partial absence of the second sex chromosome. Diagnosis is made by chromosome analysis. The most common features of Turner syndrome include significant short stature, gonadal dysgenesis and ovarian failure leading to lack of or incomplete puberty, cardiac anomalies, and renal anomalies. Since short stature is the most common presenting sign of Turner syndrome, a chromosome analysis is indicated in all girls <5th percentile for height. Turner syndrome occurs in 1 of 2500 live female births. Other common phenotypic features include webbed neck, low hair line, low-set ears, high arched palate, pigmented nevi, dysplastic nails, ptosis, strabismus, shortened 4th and 5th metacarpals and metatarsals, and cubitus valgus (wide carrying angle). While 95% of girls with Turner syndrome have short stature, many have few or no other phenotypic features, often resulting in late or missed diagnosis.

Mosaicism can occur, leading to a milder presentation and often making recognition of the condition more difficult. Patients with mosaicism may have less significant short stature and may experience spontaneous pubertal onset but may not have enough ovarian function to complete the pubertal process. In such cases, failure to progress completely through the puberty process and achieve menarche often leads to medical attention.

Coarctation of the aorta and bicuspid aortic valves are the most common cardiac anomalies. Hypertension is also common. Renal anomalies include horseshoe kidneys or duplication of the collecting system. Urinary tract infections can be common if renal anomalies are present. Patients may also experience frequent/reoccurring otitis media. Pigmented nevi (benign) are common in girls with TS. Scoliosis is common, requiring ongoing screening. There is a higher incidence of autoimmune disorders, including acquired hypothyroidism, celiac disease, and diabetes. Screening for these conditions will be required every 1 to 2 years depending on age. Learning differences can occur at slightly higher incidence and may include visual spatial deficits, nonverbal learning disability, and attention deficit. Psychosocial issues may include difficulty with social skills and interactions with agematched peers.

Newly diagnosed patients with TS require endocrinology, genetics, and cardiology evaluations and a baseline renal ultrasound. Patients are managed by the Division of Endocrinology for treatment of growth and pubertal issues but also for overall disease management and surveillance. Treatment of short stature includes growth hormone therapy, which can improve final height. Hormonal therapy to initiate and maintain puberty is indicated if gonadal dysgenesis results in lack of spontaneous pubertal onset or incomplete puberty. Gonadal dysgenesis puts girls with TS at significant risk for infertility. Counseling and psychosocial support may be indicated to address issues related to short stature, delayed puberty, adjustment to diagnosis, and peer relationships. Support groups are valuable for patients and parents.

References and Suggested Readings

Bondy CA. Care of girls and women with Turner syndrome: a Guideline of the Turner Syndrome Study Group. JCEM. 2007;92(1):10-25.

Donaldson, MDC et al. Optimising management in Turner syndrome: from infancy to adult transfer. Arch Dis Child. 2006;91:513-520.

Referral Information

To refer a patient to the Turner Syndrome Program at CHOP or for information visit www.chop.edu/turnersyndrome or contact Denise Gruccio, MSN, CRNP, at 215-590-3174.

Online Table 1: Common Findings/Features of Turner Syndrome
Pertinent findings on review of systems

History of:
Reoccurring otitis media (past the age of 6-7)
Hearing loss
Urinary tract infection
Cardiac anomaly
Learning issues: non-verbal learning disability, visual spatial deficits, attention deficit
Social skills deficits

Phenotypic features

Short stature
Lack of pubertal onset
Low hair line
Low set ears
High arched palate
Dental overcrowding
Ptosis
Strabismus
Webbed neck
Broad chest
Hypoplastic nipples
Cubitus valgus (wide carrying angle)
Dysplastic nails
Shortened 4th and 5th metacarpals and metatarsals
Pigmented nevi

Subspecialty evaluations required

Endocrinology
Genetics
Cardiology
Renal ultrasound
Audiology
ENT
Ophthalmology
Dental/Orthodontia
Orthopedics
Dermatology
Learning Evaluation

Laboratory evaluation

Thyroid function tests
Hemoglobin A1c
Celiac panel
Lipid panel

Online Table 2: Clinical Diagnosis/ Presentation of Turner Syndrome by Age
In utero

Genetic testing:  amniocentesis, CVS
Cardiac defect noted on fetal ultrasound

Newborn period

Lymphedema of hands or feet
Webbed neck
Cardiac anomaly

School age

Short stature
Other phenotypic features

Adolescent

Short stature
Lack of pubertal onset
Pubertal onset but lack of progression
Primary amenorrhea

Patient-family education and support programs

Unique Needs of Teens with Diabetes

Katherine Murphy, RN, PhD

Amy Lee is a 16-year-old junior at a local high school where she is an average student, plays on the traveling soccer team, and plans to attend college or join the military after graduation. Over the past year, there has been a noticeable increase in tension between Amy and her parents. Amy feels that her parents are intrusive and unreasonable. Recently she has requested permission to obtain a learner’s permit and is dating a boy with whom she spends a significant amount of time. Amy’s parents do not approve of the boy and have good reason to believe that there is alcohol involved in some of Amy’s weekend activities.

This scenario includes many of the challenges that providers who care for adolescents encounter on a daily basis. Now add the overlay of type 1 diabetes: Amy has had diabetes since she was 3 years old and has worn an insulin pump since she was 7. Although her diabetes control has slipped (last Hba1c 8.2%), previously she was in excellent control (no hospitalizations for DKA, hypoglycemia; Hba1c 6.8-7.3%). Until Amy was 14, Mrs. Lee was the primary manager of Amy’s diabetes, and until recently Amy followed the rules and was very cooperative. She is now sullen, noncommunicative, and angry much of the time.

The Diabetes Center for Children at The Children’s Hospital of Philadelphia is developing a program specifically to support adolescents with diabetes and their families as they negotiate living with diabetes through the teen years. Building blocks for this program include:

  1. A multidisciplinary team with expertise in diabetes and adolescent issues

    While risk-taking behaviors involving smoking, drinking, driving, and reproductive health are common to all adolescents, the combination with diabetes presents significant additional risk. Teens need reliable information about the reciprocal impact of risk-taking behavior and diabetes, but also can benefit from social and problem-solving skills necessary to minimize their risks and manage social situations that affect diabetes. In addition, the clinical care of diabetic adolescents requires screening these vulnerable patients for depression and eating disorders.
  2. Coordinated care for adolescents with complications and co-morbidities of diabetes

    Routine screening for complications and co-morbidities of diabetes will identify a small number of adolescents who are positive for microalbuminuria, hypertension, and hyperlipidemia. While these conditions are routinely treated by the endocrinologist or internist in adult care, they are less frequently managed within the context of a pediatric endocrine visit. Adding adolescent/ pediatric medical specialists to the team facilitates the development and implementation of an evidence-based practice approach for screening and treating diabetes co-morbidities and complications. We expect this comprehensive coordinated model of care to ultimately increase patient adherence by eliminating the need for separate appointments with multiple specialists.
  3. An education program that is teen-focused and engages teens on a trajectory of increasing independence in diabetes management

    Preparing children to participate in their diabetes care starts in the elementary years, but is really critical in the teen years when youth become more independent and spend more time with peers. Instructional tools available for teaching about self care management tend to be written materials that are generic in nature. Offering varied educational approaches in developmentally appropriate formats more effectively engages pre-teens in learning self-care management and problem-solving skills. We are developing targeted, innovative interactive strategies using e-learning formats. This also involves helping parents adjust their relationship with their child to remain involved while allowing increasing independence. This delicate balance of letting go safely is supported by providers who understand the challenges of both diabetes and adolescence, and who can support parents as their role evolves from that of primary managers to consultant to their teens.
  4. A formal structure for ensuring a smooth transition into adult care that begins in early adolescence

    Preparing teens for entry into the adult care system requires changing the way clinicians relate to patients and their parents in a clinic visit. Adjusting the structure and dynamics of an appointment —by shifting focus from parent as historian to patient as the primary information source—can be especially challenging when a provider has been working with a family over many years. While this process begins before adolescence, it is in the teen years that the transition away from a parent/family-centered care interactiona really occurs. Negotiating time for the adolescent to be alone with the provider during the appointment is essential to allow him or her the opportunity to privately discuss concerns and issues. This transition to a teen-centered visit clearly signals a transfer of responsibility for important tasks including making appointments, understanding requirements for referrals, writing down questions, remembering to bring logs/meter to the visit and keeping track of supplies.

Referral Information

To refer a patient to the Diabetes Center for Children, call 215-590-3174 or email endoappts@email.chop.edu.

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