16 Endocrinology

16.1 Hypoglycemia

Hypoglycemia definition

Age-dependent criteria (based on regional agreement):

Birth to < 48 hrs of life: 45mg/dL
≥ 48 hrs of life: 60mg/dL

Family Care Center approach to hypoglycemia screening

[Download]

Target population

GA < 37 weeks
BW ≥ 4,000g
BW ≤ 2,500g
IDM
Other infants identified at the discretion of the provider

0-4 hours of life

Goal: Glucose ≥ 35 mg/dL

Hypoglycemia screening guidelines for asymptomatic at risk newborns: 0-4 hours

4-24 hours of life

Goal: Glucose ≥ 45 mg/dL

Critical labs for refractory hypoglycemia

Indication

Consider obtaining critical laboratory tests for infants requiring a glucose infusion rate greater than 10 mg/kg/min, when, based on gestational and chronological age, they would not typically require intravenous fluids.

Laboratory tests to order

Tier 1

#ID	Code	Description	Tube	Volume
1	82947A	Serum glucose	PST4 green top	0.4ml
2	83525B	Insulin	GLD6 gold top	0.4ml
3	82533A	Cortisol	GLD6 gold top	0.4ml
4	82010A	Beta-hydroxybutyric acid	GLD6 gold top	1ml
5	83003B	Human growth hormone	RED7 red top	1ml
6	80051P	Electrolyte panel	PST4 green top	0.2ml

Tier 2

#ID	Code	Description	Tube	Volume
1	84210B	Pyruvic acid	Special tube/handling instructions: contact lab	1ml
2	82140B	Ammonia	Special tube/handling instructions: contact lab	0.4ml
3	82024B	ACTH	Special tube/handling instructions: contact lab	1ml
4	82533U	Cortisol, Neonatal	RED7 red top	0.4ml
5	84443B	TSH	GLD6 gold top	0.4ml
6	84439B	T4, free	GLD6 gold top	0.4ml
7	82725B	Free fatty acids	RED7 red top	0.6ml
8	82017B	Acylcarnitine profile, plasma	GRN5 green top	1ml
9	82139C	Amino acids, plasma	GRN5 green top	2ml
10	83918C	Organic acids, urine	Urine container	15ml

Tier 3

Blood gas for pH, BE, and lactate

Possible blood specimen source

Capillary:

Heel stick

Venous:

Freshly placed PIV
UVC
PowerPICC (not routinely seen in our NICU)

Arterial:

Radial/ulnar artery puncture
UAC
PAL

Procedure for inducing hypoglycemia (need to discuss further)

Identify the lab tests, verify order entry.
Determine the total volume needed.
Physicians should be mindful of the practicality of the exsanguinated volume.
Identify the source of blood specimen.
D10W 2mL/kg bolus syringe available at bedside.
Discontinue IV fluid.
Check POC glucose every 30min until level < 55mg/dL.
Check POC glucose every 15min until level < 45mg/dL.
Obtain blood specimen.
Check POC glucose. If < 40mg/dL, administer D10W 2mL/kg bolus once.
Restart IV fluid.
Check POC glucose every 30min until > 60mg/dL.

Sliding scale for IV dextrose weaning

Need consensus

Wean by 2ml/hr for AC POC Glucose >80 (or 75)
Wean by 1mL/hr for AC POC Clugose 70-80 (or 65-75)
Increase by 1mL/hr for AC POC glucose 50-60 (or 45-55)
Increase by 2mL/hr for AC POC Glucose < 50 (or <45), and notify MD
Once off IV, continue to check sugars until >60 on 3 consecutive checks.

16.2 Secondary Screening for Neonatal Thyroid Conditions

Indications and Screening

Indication	Screening needed
Monochorionic twins/Multiple (Same-sex if chorionic status not known)	TSH at 2 weeks of age
ANY congenital heart disease diagnosis (exclude PDA) with infant hospitalized to at least day 14	TSH at 2 weeks of age
Very low birth weight (≤ 1500 grams)	TSH at 2, 4, and 6 weeks of age if still hospitalized
Down syndrome	TSH at 2 weeks
Mother with history of or active hyperthyroidism/Graves disease	See: Managing Neonatal Graves Disease flowchart
Signs or symptoms of hypothyroidism (e.g., unexplained lethargy, bradycardia, jaundice, or constipation; abnormal neck imaging)	TSH and Free T4 as soon as symptoms are recognized
Signs or symptom of central hypothyroidism or hypopituitarism (e.g., craniofacial/midline defects, certain genetic syndromes, recurrent hypoglycemia, recalcitrant hypotension, micropenis)	TSH and free T4 along with other pituitary tests when signs or symptoms are recognized
Mother with hypothyroidism or Hashimoto thyroiditis and no history of Graves disease	Routine newborn screen only

Important

Screening TSH ≥10 mIU/L is abnormal: immediately repeat TSH adding free T4 as well and discuss results once available with endocrinology promptly.
If the test will be performed as outpatient, please order the test and document under problem list thyroid disorder screening V77.0A
Consider TSH only in premature infants (without reflex free T4). Appropriate Health Connect Order: TSH, NO REFLEX (order 84443O).
If considering tests for strong suspicion of hypothyroidism or hypopituitarism, discussion with endocrinology is recommended for all results. If suspicion for pathology is low, discuss with endocrinology if results are outside reference range.

Guide for interpretation of thyroid function studies

Note

Normal values are not fully established in the first 2 months of life and interpretation may differ if tests are done for screening or for symptomatic/diagnostic purposes. Free T4 levels may be less in NICU due to illness unrelated to thyroid disease. Significant topical iodine exposure may transiently alter thyroid function tests. Interpret with caution.

Asymptomatic screening (0-60 days old)

TSH

Hypothyroidism screening: < 10mIU/L
maternal Graves/hyperthyroidism: use lab-provided reference

Free T4

Use lab-provided reference

Symptomatic/diagnostic testing

TSH

Newborn ≤ 3 days old: 1-20 mIU/L
Newborn > 3 days old: use lab-provided reference

Free T4

Newborn ≤ 14 days old: 1.4-2.8 ng/dL
Newborn > 14 days old: use lab-provided reference

16.3 Screening Guidelines for Neonatal Graves Disease

flowchart TD
  A["Mom with Graves Disease (hyperthyroidism) or history of Graves disease (hyperthyroidism)"] --> B["Obtain Thyroid Receptor Ab (TR Ab) or TSI in 2<sup>nd</sup>/3<sup>rd</sup> Trimester"]
  B --> C["Positive or unknwon TR Ab/TSI or<br>Negative TR Ab but active maternal hyperthyroidism<br><em>and/or</em><br>Treated with anti-thyroid drugs (PTU/methimazole)"]
  B --> D["NO current anti-thyroid treatment<br><em><u>and</u></em><br>NEGATIVE TR Ab/TSI in 2<sup>nd</sup>/3<sup>rd</sup> Trimester"]
  C --> E[High risk neonate]
  D --> F[No screening needed]
  E --> G["Obtain TR Ab/TSI in cord blood or nursery<br><em>If not done</em>: Order TR Ab/TSI, freeT4, TSH for outpatient draw in first 7 days of life"]
  G --> H["+ TR Ab/TSI = High risk neonate<br><em>(Observe for clinical symptoms of hyper/hypothyroidism)</em>"]
  G --> I["Negative TR Ab/TSI = Low risk neonate"]
  H --> J["Draw TSH and free T4 at 3-7 days<br><em>(if not done prior, or if symptomatic)</em>"]
  I --> K["No further work-up necessary"]
  J --> L["Abnormal results: send Dr. Advice to Peds Endo<br><em>(TSH < 1mIU/ml and/or free T4 > 2ng/dl is abnormal)</em>"]
  J --> M["Normal TSH, free T4 for age"]
  M --> K

Note

Though TSI is acceptable it is preferred to screen with TR Ab (TSH receptor binding antibody)

16.4 Ambiguous Genitalia

Differential diagnosis

XY individual

Defects in gene producing transcription factors along the pathway of testicular differentiation
Defects in androgen synthesis & production
Defect in androgen receptor response
Disrupted müllerian inhibition

XX individual

Gonadal overproduction of androgens due to mutations involved in gonadal (ovarian) development
Adrenal overproduction of androgens
Placental aromatase deficiency
Maternal exogenous exposure to androgens

Physical findings to trigger workup

Frankly atypical genital appearance

Subtle presentation

Male

micropenis:
- Full-term: stretched penile length < 2.5cm
- Preterm: normal stretched penile length (cm) = -2.27 + 0.16 x GA in week
severe hypospadias (with or without cryptorchidism or micropenis)

Female

clitoromegaly: width > 6mm or length > 9mm
posterior labial fusion, with anogenital ratio > 0.5
gonads palpable in the labioscrotal folds or the inguinal region

Workup

First days of life

STAT ORDERS

Serum eletrolytes
Serum glucose level
Random cortisol
17-OHP: value affected by prematuirty, maternal steroid intake
Renin
Karyotyping

ROUTINE ORDERS

Ultrasound of the abdomen/pelvis
Growth hormone level (in the first 15 days of life)
Prolactin (can help diagnose growth hormone deficiency)
Free T4, free T4 by dialysis (can help diagnose hypopituitarism)

After 1 week of age and before 6-9 months of age (mini-puberty)

Assess pituitary gonadotropin function

Pediatric LH
FSH

Assess gonadal function

Estradiol
Testosterone
Dihydrotestosterone
Anti-Müllerian hormone
- reference range: boys > 30ng/mL; girls < 10ng/mL
- Higher AMH than female range (XX individual) indicates Sertoli cells present (ovotesticular DSD)
- AMH below typical male range (XY individual) indicates defect in testicular function

Additional Workup

Skeletal survey
MRI of the Sella with and without contrast

Consultation

Pediatric endocrinology
Pediatric urology
Psychology
Genetics
Social worker
Medical ethics

Congenital adrenal hyperplasia (CAH) treatment

Fluid:
- D5NS without K at 1-2x maintenance
- consider 10mL/kg NS bolus if dehydrated
Glucocorticoids (hydrocortisone):
- Start at 50mg/m²/day IV divided q4-6 hrs
Mineralocorticoirds:
- Start fludrocortisone at 0.1mg qDay
NaCl supplement: Start at 3-4 mEq/kg/day (4mEq/mL solution)

16.5 Undescended Testicle

For unilateral undescended (or non-palpable) testicle

No need to order ultrasound
Refere to Peds Urology for evaluation (there is a new hire at Fontana)
May wait until 3 months of age to refer as some will descend by that time
If there are othe rmalformations of the external genitalia (hypospadias) with undescended testicle(s), obtain labs as below an refer to Peds Urology without waiting until 3 months.

For bilateral undescended (or non-palpable) testicle

flowchart TD

A["Perform exam carefully and  
   repeatedly in a warm, relaxed state"] --> C["Yes"]
A --> B["No"]
B --> D["If the exam is unclear or uncertain,  
         it is best to <strong>obtain ultrasound</strong>  
         first, per Peds Endo"]
           
D --> E["If true bilateral undescended testes  
         on ultrasound report, endocrine work-
         up should be ordered next."]
         
C --> F["If the provider is comfortable  
         in making the clinical assessment 
         without aid of ultrasound, then  
         endocrine workup should be 
         ordered next."]
        
F --> G["<div align='left';>
        1. Testosteron, pediatric
        2. LH, pediatric
        3. FSH
        4. AMH (anti-Mullerian hormone)
        5. Karyotype
        6. 17-OH progesterone
            
        Call Peds Endo. 
        
        Do NOT discharge baby or give sex assignment  
        until workup evaluated by Peds Endo.
        </div>
"]

E --> G

D --> H["If testes are high scrotum or   
         low in the inguinal canal,  
         refer to Peds Urology for exam   
         and follow-up.  
         Newborn screen for CAH."]