Pediatric Endocrine

Peak onset for T1DM

4-6 years and 10-12 years

autoimmune markers for T1DM

- Islet cell autoantibodies (ICA)

- autoantibodies to GAD (GAD65)

- autoantibodies to insulin (IAA)

- autoantibodies to the tyrosine phosphatases IA-2 and IA-2b

-Zinc Transport Zn T8

Who does the ADA recommended screening for T2DM in children?

- all children (starting at age 10 or puberty, whichever occurs first) with a BMI > 85th percentile or a BMI > 95th percentile with one or more risk factor

How often should a child that meets the criteria be screened for T2DM?

minimum every 3 years (ADA)

AAP recommends every 2 years

Fasting blood glucose levels (normal, prediabetes, and diabetes) same for kids and adults

normal: < 100

Pre: 100-125

DM: > or = 126

Specific symptoms of T1DM

-weight loss

-more acute onset

-present in DKA

How many times a day should children with T1DM check their glucose levels?

6-10

Preprandial and bedtime/overnight glucose goals in children

pre-prandial: 90-130 mg/dL

bedtime/overnight: 90-150 mg/dL

A1C goal for children with DM

-depends on their age and how well they can detect hypoglycemic symptoms

<7% if on oral meds (T2DM), most children

<7.5% if on insulin (T1DM), can't articulate, younger

<8% if hx of hypoglycemia or low life expectancy

Treating a new onset diabetes in overweight child could be tricky because it is not obvious whether it is T1 or T2. Explain how you would start management based on the following scenario:

A1C < 8.5%

No Ketosis/Acidosis (no ketones, pH >7.3, CO2 > 18)

start metformin BID and titrate as tolerated (aiming for 2000 mg/day)

Treating a new onset diabetes in overweight child could be tricky because it is not obvious whether it is T1 or T2. Explain how you would start management based on the following scenario:

A1C > or = 8.5%

No Ketosis/Acidosis (no ketones, pH >7.3, CO2 > 18)

start basal insulin at 0.5 units/kg/day

start metformin BID and titrate as tolerated (aiming for 2000 mg/day)

Treating a new onset diabetes in overweight child could be tricky because it is not obvious whether it is T1 or T2. Explain how you would start management based on the following scenario:

In DKA or HHS (Kussmaul, fruity breath, BG>250, pH<7.3, CO2<18)

-fluids and IV insulin then transition to SQ

1. Fluids (IV 0.9% NS 15-20 mL/kg bolus)

2. Cardiac Monitoring

3. Potassium (20-40 mmol potassium/L)

4. Insulin (no bolus, start drip at 0.05 to 0.1 U/kg/hr) (we want K+ >3.5 before giving insulin)

-switch to SQ once DKA resolves, continue IV for 15 minutes after initiation of SQ insulin

Criteria for pt being in DKA

BG > 250 mg/dL

pH < 7.3

CO2 < 18 mEq/L

S/S of DKA

polyuria, polydipsia

weight loss, fatigue

dyspnea- Kussmaul respirations

N/V

Dehydration

Fruity smelling breath

Resolution of DKA

BG < 200 mg/dL

pH > 7.3

CO2 > 18 mEq/L

After you stabilize the new onset child, what do you order to tell if they have T1 or T2 DM?

pancreatic autoantibodies

If the pancreatic autoantibodies is positive, what do you do with their therapy?

- treat T1DM

- D/C the metformin

If the pancreatic autoantibodies is negative, what do you do with their therapy?

-treat like T2DM

-wean off insulin (if started)

-continue the metformin

A1C goal for children with T2DM on oral agents alone

< 7%

DM medications that are FDA approved for children

-insulin

-metformin (ages 10 and up)

-GLP1s (semaglutide or liraglutide ages 12 and up)

-SGLT2 (empagliflozin ages 10 and up)

DOC for T2DM in children

metformin

What two diseases should be screened for at diagnosis of T1DM?

-autoimmune thyroid disease

-celiac disease

What disease is the most common autoimmune disorder associated with diabetes?

autoimmune thyroid disease

At the time of diagnosis, about _____% of children with T1DM have thyroid autoantibodies

25%

What thyroid dysfxn is most commonly associated in children with T1DM?

hypothyroidism

How is thyroid disease screened for?

-check autoantibodies at time of diagnosis of DM

-continue monitoring TSH for the next 1-2 years

How is celiac diseases screened for in pts with T1DM?

serum levels of IgA and tissue transglutaminase antibodies

What additional care should children with both T1DM and T2DM recieve?

- monitor BP at every visit (lifestyle modifications)

- dyslipidemia (fasting lipid profile; statins 10 and up)

- nephropathy (annual albumin to creatinine ratio)

- neuropathy (annual foot exam)

- retinopathy (annual eye exam)

-immunizations and annual flu vaccine

What is the thyroid hormone important for in pediatrics?

- normal brain myelination in the first 2-3 years of life

- normal skeletal growth

- regulation of metabolic rate

True or False

Children can develop both hyperthyroidism and hypothyroidism

true

Are thyroid disorders a part of the newborn screening?

yes

S/S of Hyperthyroid vs Hypothyroid

Hyper (high T4)

-weight loss

-heat intolerance

-hyperactivity (academic issues)

-sweating

-tachycardia

-diarrhea

Hypo (low T4)

-weight gain

-cold intolerance

-lethargy (academic issues)

-dry skin

-exercise intolerance

-constipation

-GROWTH FAILURE

-delayed pubertal development

What stimulates and inhibits the release of TSH

stimulates release of TSH = TRH

inhibits the release of TSH = -free (unbound) T3 and T4, stress, dopamine, somatostatin

What stimulates and inhibits T3/T4?

stimulates T3/T4 = increased TSH, increased iodine

inhibits T3/T4 = Decreased levels of TSH, Decreased blood iodine, Hyperglycemia

_____ is the most sensitive and specific to thyroid dysfunction.

TSH

______ along with _____ is the most accurate assessment of thyroid function

Free T4 along with TSH

True or False

Hyperthyroidism in neonatal period is common

FALSE

Hyperthyroidism in neonatal period is RARE

When the TSH is low in neonatal periods, it is most often due to what?

maternal hyperthyroidism

If the TSH is NOT < _____ you can be confident that the infant is NOT hyperthyroid

If the TSH is > 0.1 = infant is NOT hyperthyroid

TSH was taken on a neonate, the level came back as 0.5. Do we think the infant is hyperthyroidism?

No

The TSH is > 0.1, so the infant is NOT hyperthyroidism

How do TSH and T3/T4 levels fluctuate in neonates?

- they surge as they are exposed to cold environment and clamping of the umbilical cord (surge the first 24-48 hrs)

- they decline and stabilize in a few weeks as hypothalamic-pituitary-thyroid axis develops

How does the fluctuation of the TSH and T3/T4 levels in neonates affect the newborn screening?

it is hard to know if the screening was done too soon and has false results

if the TSH was taken when the baby was first born and the TSH and Free T3/T4 were in their surge, it could lead to a falsely high level resulting in misdiagnosed phone calls

What two epilepsy medications can suppress TSH resulting in a low Free T4?

carbamazepine (Tegretol)

oxcarbazepine (Trileptal)

Congenital hypothyroidism

results in poor physical and mental development; formerly called cretinism

What is one of the most treatable causes of intellectual disability and cognitive impairment?

congenital hypothyroidism

Is congenital hypothyroidism more common in males or female infants?

females

Most newborn babies with congenital hypothyroidism have no S/S due to protection from the mother's transfer. But they may have some S/S which could include...

-prolonged jaundice

-hypotonic posture (floppy, low tone)

-myxedematous facies (puffy face)

-macroglossia (tongue out)

-umbilical hernia

-lethargy, poor feeding

-large posterior fontanelle

-skin mottling/dry skin

-hoarse cry

If a baby is super lethargic and sleepy, won't feed, low body tone, unable to keep limbs elevated, what should be on your differential dx?

congenital hypothyroidism

Is congenital hypothyroidism detected on neonatal screening?

yes

-typically the TSH is ordered with a reflex T4 (but may be both)

-typically done via heel stick

If the initial screening for congenital hypothyroidism is abnormal, then the pts are referred for wht additional screening?

serum TSH and free T4

What do labs look like for SECONDARY (central) hypothyroidism?

low free T4

normal or low TSH

What causes secondary hypothyroidism in infants?

- can be due to isolated TSH deficiency, but more likely in infants with other pituitary hormone deficiencies

- pts have issue with pituitary, midline defects, hx of pituitary or hypothalamic injury

How is primary hypothyroidism treated?

levothyroxine (T4) at 10-15 mcg/kg/day

How is secondary hypothyroidism treated?

refer for evaluation of pituitary function

Is Hashimoto Thyroiditis more common in female or male infants?

females

What population of children is Hashimoto Thyroiditis more common in?

-trisomy 21 (Down Syndrome)

-Turner syndrome

-autoimmune polyglandular syndrome

S/S of Hashimoto Thyroiditis in children

- decline in growth velocity

- short stature

- delayed pubertal development

- fatigue

- lethargy

- other symps in adult hypothyroidism

What is the most common physical exam finding of Hashimoto Thyroiditis in children?

goiter

How is diagnosis of Hashimoto Thyroiditis made?

- low T4

- high TSH

___________ antibodies are seen in 85-90% of children with Hashimoto Thyroiditis

Antithyroid peroxidase (TPO)

also common is antithyroglobulin antibodies

Treatment of Hashimoto Thyroiditis

levothyroxine

weight based dosing changes by age

Is graves disease common in children?

no, it is rare

Approximately 80% of pediatric cases of graves disease occurs after what age?

after age 11

Is graves disease more common in female or male infants?

female

Children with what syndromes are more likely to develop graves disease?

Down syndrome and Turner syndrome

S/S of graves disease

- failure to gain weight (weight loss)

- exophthalmos

- lid lag

- tremors

- cognitive dysfunction

- proximal muscle weakness

Labs for graves disease

-high T4

- low TSH

How often is the TSH-R [stim] Ab present in graves disease in children? What about the TSH-R [block] Ab present in Hashimoto's?

TSH-R [stim] Ab = 94% of children with Graves

TSH-R [block] Ab = 9% of children with Hashimoto's

first line treatment for graves disease

antithyroid drug = methimazole

For pts with graves disease who do not experience remission with methimazole, what are their options?

- radioactive iodine for those > 10 years old

- surgical near-total thyroidectomy in younger pts

Red Flags for Thyroid Disorder

-abnormal newborn screening test

-growth failure

-unexplained weight loss

-enlarged thyroid

-new onset of fatigue

- heat or cold intolerance

-tachycardia

> 2 S/S of hypo/hyperthyroidism

Most common adrenal insufficiency in children is due to what?

congenital adrenal hyperplasia

Classic Congenital Adrenal Hyperplasia (CAH)

-rare

-results of a group recessive genetic mutations that lead to a shift from adrenal corticosteroid production to adrenal androgen production

Two most common.forms of CAH

21-hydroxylase deficiency (95%)

11-beta hydroxylase deficiency

"non-classic" CAH

-partial deletions

-child can survive infancy without replacing cortisol

-may not be detected until adolescence or later

-recognized due to precocious puberty, short stature, severe acne, hirsutism, amenorrhea, and hyperpigmentation

The most common form of CAH pts are lacking ____________________

21-hydroxylase

Role of 21-hydroxylase

glucocorticoid (cortisol) and mineralocorticoid (aldosterone) synthesis

The lack of 21-hydroxylase results in a decrease in what?

low cortisol

low aldosterone

The lack of cortisol results in what other hormonal change....

elevated levels of ACTH

The lack of aldosterone results in....

"salt wasting" (decrease Na+ and water)

Hyperkalemia (increase K+)

The increase in ACTH increases production of....

androgen

In 21-hydroxylase deficiency, is the excess androgen more noticeable in males or females?

females

- in females, the excess androgens will cause virilized infants with ambiguous genitalia

-males will appear "normal"

Infants with 21-hydroxylase deficiency (leading to severe cortisol and androgen deficiency) if gone unrecognized will result in what?

adrenal crisis by 2-3 weeks of age

S/S of adrenal crisis

abdominal pain

N/V

dehydration

shock

hyponatremia (low Na2+)

hyperkalemia (high K+)

11-Beta deficiency results in a build up of what?

increase deoxycorticosterone

The increase in deoxycorticosterone causes what S/S?

HTN

hypokalemia (low K+)

Are cortisol levels low in 11-Beta hydroxylase deficiency?

yes

low cortisol = high ACTH = high androgen = virilized female infants

Overall process/labs 21-hydroxylase deficiency

-low 21-hydroxylase deficiency

-decrease in cortisol and aldosterone

-decrease cortisol = increase ACTH = increase androgens = virilized females and "normal" males

-decrease aldosterone = salt wasting (low Na and H2O) and hyperkalemia

Overall process/labs of 11-Beta hydroxylase deficiency

-11-Beta hydroxylase deficiency

-low cortisol and high deoxycorticosterone

-decrease cortisol = increase ACTH = increase androgens = virilized females and "normal" males

-increase deoxycorticosterone = HTN and hypokalemia

Difference in potassium in 21-hydroxylase deficiency vs. 11-Beta hydroxylase deficiency

21-hydroxylase deficiency = hyperkalemia (high K+)

11-Beta hydroxylase deficiency = hypokalemia (low K+)

What test can help diagnose CAH?

17-hydroxyprogesterone (17-OH)

If elevated 17-OH is detected early in pregnancy, what medication can be given to the mother to suppress the fetal ACTH and reduce the androgen production?

dexamethasone

-refer for this decision to be made

-dexamethasone has ADRs

-weight risk vs benefit

Is CAH in newborn screening panel?

yes

If an infant has an elevated 17-OH in newborn panel, this indicates they have CAH. How do you tell which deficiency?

- 21-hydroxylase deficiency is most common

- you can evaluate concentration of 11-deoxycortisol and corticosterone for diagnose 11-Beta hydroxylase deficiency

Treatment of 21-hydroxylase deficiency

hydrocortisone (glucocorticoid) AND fludrocortisone (mineralcorticoid)

Treatment of 11-Beta hydroxylase deficiency

just hydrocortisone (glucocorticoid)

What therapy is used to decrease some the symptoms of excess androgens?

antiandrogen therapy

-can be done in both 21-hydroxylase deficiency and 11-Beta hydroxylase deficiency

Is primary adrenal insufficiency (addison's) common in children?

no

Rare

If a child is diagnosed w/ Addison's disease, they should be evaluated for _______________________

autoimmune polyglandular syndrome

_______________ adrenal insufficiency is the result of low ACTH

secondary