A Potpourri of Cases in Pediatric Endocrinology

Educational Objectives

The goal of this program is to improve endocrine evaluation in the pediatric population. After hearing and assimilating this program, the clinician will be better able to:

1. Optimize bariatric surgery evaluation in children with obesity according to guidelines.
2. Evaluate children for central precocious puberty.
3. Treat congenital hypothyroidism using levothyroxine.

Summary

Obesity and diabetes mellitus (DM): the unequivocal hyperglycemia can be associated with symptoms, ketosis, and weight loss; insulin resistance and aripiprazole (Abilify) can also simulate hyperglycemia; insulin is recommended for hemoglobin A1C (HbA1C) >8.5% (the dose is 0.5 units/kg); metformin is typically started at 500 mg and titrated up over 4 wk to reduce adverse effects; pediatric evidence suggests a dose of 1000 mg twice a day or 2000 mg a day

Bariatric surgery evaluation: the American Academy of Pediatrics (AAP) guidelines recommend bariatric surgery evaluation for all patients >13 yr of age who meet the criteria (from the American Society for Metabolic and Bariatric Surgery), including a body mass index (BMI) of ≥120% of 95th percentile and a major comorbidity (eg, polycystic ovarian syndrome), or a BMI of ≥140% of 95th percentile, without a qualifying comorbidity; no contraindications should be there; patients can be referred evaluation

Data: the Teen-LABS study (Inge et al [2016]) found weight loss achieved by sleeve gastrectomy and gastric bypass in children was similar (the mean weight loss was about 25% to 30% of the baseline); children had more remission of comorbidities than adults, suggesting bariatric surgery at a younger age; Bjornstad et al (2020) compared children in the Teen-LABS study with a group undergoing medical treatment in the TODAY study who would qualify for bariatric surgery; after bariatric surgery, the weight loss was significant; 5 yr later, the BMI remains the same in the surgery group and the medication group; the mean HbA1C continued to rise in the TODAY group (needing insulin), while in surgery group the HbA1C went down to the nondiabetic or prediabetic range (discontinuing DM medications); insulin sensitivity significantly improved after bariatric surgery and did not change in the TODAY study; bariatric surgery success is often measured by weight loss, but health changes are more important (eg, significant metabolic improvements can occur without much weight loss)

Learning points: confirm DM diagnosis and type, especially in suspected type 2 DM; high doses of insulin is required because of the insulin resistance during puberty (hypoglycemia is rare in this patient population); bariatric surgery should be offered as a potential treatment option early in the clinical course; DM remission tends to occur after bariatric surgery, before maximal weight loss

Obesity and constitutional growth advancement: children are typically taller than expected throughout childhood, even before puberty, with growth velocity at the high end of the pubertal range; bone age can be mildly advanced but steady over time; puberty at the early end of normal or slightly early, with no underlying pathologic concerns; usually finish growing before their peers; growth charts — children with constitutional growth advancement generally grow faster than average, experience a growth spurt early, and then slow down early; the growth delay curve helps explain the concept of slow growth in children

Recommendation to assess for comorbidities: assess blood pressure and other factors at puberty or 10 yr of age (whichever is earlier); there is a very low risk for dyslipidemia before puberty (requiring intervention), but the risk for type 2 DM or fatty liver disease increases during puberty; assess lipid panel, HbA1C, liver transaminases, sleep apnea, and blood pressure; hypothyroidism should be assessed only if there is a family history or other risk factor (which is not the cause of obesity)

Obesity and subclinical hypothyroidism: patients with obesity often experience mild to moderate elevation of thyrotropin (TSH) and triiodothyronine (T3; may be a consequence of obesity); repeat TSH, especially in children with a family history; consider obtaining thyroid peroxidase antibody; hypothyroidism is more likely to occur if TSH remains elevated and a positive TPO results

Learning points: obesity predisposes children to early puberty; certain populations are more likely to have early puberty; evaluate for pathologic causes; also associated with social determinants of health and environmental exposures

Premature adrenarche: pubic hair at <8 yr of age; no signs of estrogen; check for exogenous steroid use in the household; consider the appropriateness of the androgen concentration for that puberty stage; androgens may be slightly elevated in a patient with early pubic hair (not several times the upper limit of normal); premature adrenarche can be common because of puberty of infancy; differentiate between pathology and nonpathology causes; progressing Tanner stage for pubic hair and growth acceleration (height high for the mid parental height) are concerning; check for other features of elevated testosterone, eg, behavior, mood changes; adrenal tumors are mostly related to predisposition to genetic syndrome (test parents if a mutation is found)

Central precocious puberty (CPP): pathologic causes of early puberty are more common in boys than girls; headaches, rapid growth velocity, increase in BMI, age, and male sex are some risk factors; CPP is associated with elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels (which are suppressed in peripheral precocious puberty); adrenarche would not elevate LH and FSH levels; magnetic resonance imaging can be ordered to assess pubertal testicular volume; hypothalamic obesity may cause elevated BMI (increasing over time); consider evaluating for hypothalamic brain tumor, eg, pilocytic astrocytoma; a gonadotropin-releasing hormone agonist can be used for the treatment of CPP; the average age for boys to start puberty is 11.5 yr

Clinical hyperthyroidism: Graves disease is a type of hyperthyroidism that involves eye disease (because of an autoimmune process); it is considered an endocrine emergency because of the risk for thyrotoxicosis (can evolve rapidly); early treatment initiation is important; causes — include Graves disease, viral thyroiditis, hashitoxicosis, hyperfunctioning thyroid nodule, and ingestion; signs include polyuria or polydipsia; treatment — methimazole and possibly a β-blocker (if symptomatic); adverse effects of methimazole include urticaria, reactive arthritis, serum sickness, and hepatitis or liver failure; can cause bone marrow suppression; counsel patients to stop the medication immediately if they show any of these signs; prognosis of Graves disease — about 33% of patients have persistent hyperthyroidism; definitive treatment is recommended; the risks for hyperthyroidism are more significant than hypothyroidism; nonadherence to methimazole can lead to thyroid toxicosis and cardiac arrhythmias; the definitive treatment includes radioiodine

Learning points: Graves disease is the most common cause of hyperthyroidism in youth; consider ingestion if there is a family history (associated with low thyroid globulin level)

Congenital hypothyroidism: thyroid hormone is important for linear growth in babies; congenital hypothyroidism occurs in 1 in 2500 to 4000 live births; screening protocols vary by state in the United States; all states require a screen on day of life 2; the second test requirement varies; some states screen with TSH with a reflex to thyroxine (T4), and some states screen with T4 with a reflex to TSH; screening with T4 allows screening for central hypothyroidism (which can cause fewer intellectual disability challenges); thyroid agenesis or dysgenesis are the most common causes; not inherited generally; inherited forms are milder; ≈10% are transient (a milder genetic disorder or maternal antibody transmission through the placenta); repeating the serum test differentiates it from the normal TSH surge; frequent dose adjustments are often needed during rapid growth; check laboratories every 3 mo during infancy, every 6 mo while growing, and then every year after fully grown; check 4 to 6 wk after each dose adjustment

Levothyroxine: dose of 10 to 15 μg per kg of body weight is recommended; usually start at 37.5 μg for healthy babies with elevated TSH (lower dose if less elevated); do not recommend prescribing a liquid form (as levothyroxine comes out of solution easily); can give crushed tablet (in a syringe with formula, breast milk, or water); iron and calcium supplements interfere with the absorption; recommended to give it on an empty stomach; early treatment is important to prevent developmental delay and growth failure; levothyroxine has a long half-life, so missed doses can be adjusted the next day

Calcium: hypoparathyroidism — FISH test demonstrates a 22q11 deletion consistent with DiGeorge syndrome; hypoparathyroidism may cause hypocalcemia; parathyroid hormone is important to cause 1α-hydroxylation of vitamin D; treatment includes calcitriol (an activated vitamin D) and calcium; once hypoparathyroidism is treated and calcium levels increase (calcium supplements are not needed anymore); can often be transient in newborns; acute hypocalcemia is more likely to be associated with symptoms like tetany, seizures, and tingling lips; assess for other features once a patient is diagnosed with DiGeorge syndrome

Readings

Bjornstad P, Hughan K, Kelsey MM, et al. Effect of surgical versus medical therapy on diabetic kidney disease over 5 years in severely obese adolescents with type 2 diabetes. Diabetes Care. 2020 Jan;43(1):187-195. doi: 10.2337/dc19-0708; Hampl SE, Hassink SG, Skinner AC, et al. Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity. Pediatrics. 2023;151(2):e2022060640. https://doi.org/10.1542/peds.2022-060640; Inge TH, Courcoulas AP, Jenkins TM, et al. Weight loss and health status 3 years after bariatric surgery in adolescents. N Engl J Med. 2016;374:113-123. DOI: 10.1056/NEJMoa1506699; Rose SR, Wassner AJ, Wintergerst KA, et al. Congenital hypothyroidism: screening and management. Pediatrics. 2023;151(1):e2022060420. https://doi.org/10.1542/peds.2022-060420; Rosenfield RL. Normal and premature adrenarche. Endocr Rev. 2021;42(6):783–814. doi: 10.1210/endrev/bnab009; Wang Q, Wu D, Zeng Q, et al. Diagnostic value of single LH and LH/FSH ratio at 60 minute after GnRHa stimulation test for central precocious puberty. Indian J Pediatr. 2024. https://doi.org/10.1007/s12098-024-05137-7.

Disclosures

For this program, members of the faculty and the planning committee reported nothing relevant to disclose. Dr. Kelsey's lecture includes information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Kelsey was recorded at Pediatrics in the Islands: Clinical Pearls 2024, held on October 28, 2024, in Waikoloa, HI, and presented by the Children’s Hospital Los Angeles Medical Group. For information on upcoming CME activities from this presenter, please visit https://www.chla.org/chla-medical-group/cme-conferences. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

PD711202

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.