Checking the Right Box at the Right Age: the Art of Pediatric Endocrine Testing Jean-Pierre Chanoine, MD Endocrinology and Diabetes Unit British Columbia s Children s Hospital
Objectives 1. Interpret the results of pediatric endocrine tests 2. Understand the usefulness of hormonal testing in an age-dependent fashion 2
Rationale Blood tests/imaging can be Invasive Time consuming Costly to the Gvt/(patient) Why are we ordering them? Experience in low resource setting Most commercial labs keep samples for up to 7 days 3
Cost of diagnostic tests (Canada 2015) TSH $ 9.90 FT3 $ 9.35 FT4 $ 12.12 Thyroid Receptor Ab $ 22.48 Thyroglobulin $ 27.90 Thyroid ultrasound $ 65 Thyroid scan (I 123) $ 180 + Uptake + $ 44 4
Thyroid axis Most thyroid conditions in pediatric patients are primary: Hashimoto thyroiditis (Primary hypothyroidism) Grave s disease (Primary hyperthyroidism) TSH is best screening test Exception: suspicion of central hypothyroidism (FT4) 5
Congenital hypothyroidism Goal: TSH in low normal range FT4 useful until TSH normalized to ensure that L-T4 is properly given Pitfalls Shift in the TSH-FT4 relationship in CH TSH 8 6 4 Follow-up: TSH, irrespective of FT4 FT4 not useful (usually higher compared to N children) FT3 not useful 2 0 0 5 10 15 20 FT4 6
Thyroid axis N range of FT4 very high in the neonate Often not mentioned by the laboratory Age pmol/l 1-30 days 10.0-40.0 31-364 days 7.8-18.4 1-5 years 7.9-18.8 5-10 years 7.9-20.3 10-15 years 7.5-17.2 15-18 years 7.6-15.6 >18 years 7.9-14.4 Pitfalls N range for FT4 varies between labs (BCCH lab reads lower than many labs) Neonatal screening for congenital hypothyroidism only detects primary hypothyroidism 7
Hyperthyroidism (Grave s Disease) Screening: TSH Below lower limit of normal in all patients Confirmation: TSH, FT4 TPO: confirms autoimmune process (1x) Thyroid Receptor Antibodies (prognosis) Follow up: FT4 after 3-4 weeks (Tapazole action) When TSH starts to be detectable: only TSH is needed 8
Hyperthyroidism (Grave s Disease) Pitfalls T3 thyrotoxicosis Gland preferentially secretes T3 Typically: TSH: < 0.03 FT4: 5 pmol/l (N: 8-15) FT3: 8 pmol/l (N: 4-6) - Follow FT3 and TSH until FT3 N and TSH detectable. Goal: N TSH, irrespective of FT4 9
Hypothyroidism (Hashimoto thyroiditis) Screening: TSH Confirmation: TSH, FT4, TPO ab (1x) Follow up: TSH Little role for FT4 during follow up, no role for FT3 Pitfalls Patient develops elevated TSH AND FT4 during FU: think poor compliance (L-T4 intake just prior to clinic) 10
Thyroid ultrasound Generally not useful tests Not useful if: Hyper/hypothyroid patients with diffusely enlarged gland (Grave s disease/hashimoto thyroiditis) Consider if: Nodule palpated or follow up of nodule FU of patients with history of irradiation 11
Practice guidelines recommendations regarding use of ultrasound for the evaluation of Generally not useful tests common thyroid conditions Source Thyroid dysfunction Thyroid nodular disease AACE No For guided FNA ATA No Head/neck irradiation f/u ACP No - Harrison s Principles of Internal Medicine No For guided FNA Cecil Textbook of Medicine No No Werner & Ingbar s The Thyroid No No Williams Textbook of Endocrinology No For guided FNA Endocrinology & Metabolism No No Textbook of Primary Care Medicine No No Primary Care Medicine No f/u of nodule Liel et al: J Gen Intern Med. 2005 August; 20(8): 766 768 12
Growth hormone (GH) axis - Circulating GH is very high in the fetus and has little effect on fetal growth - GH is part of the counter regulation mechanism in case of hypoglycemia (critical sample) 13
Growth hormone axis: Assessment of growth Growth hormone deficiency: Screening with IGF-1 Confirmation with 2 different GH stimulation tests (glucagon, arginine) Comments: - GH stimulation tests are not performed in commercial labs - Experienced nurse needed - Some children need to receive hormonal priming with estrogens prior to the test 14
Growth hormone axis Generally not useful tests Random GH: Not useful: usually very low in N children http://answerparty.com/ 15
Random GH: Exception 1 GH is constitutionnally elevated during the first week of life Normal cutoff for peak GH during stimulation tests in older children: 5.6 ng/ml Binder et al. JCEM 2010 16
Random GH: Exception 2 Gigantism, acromegaly (GH excess) - Serum GH Elevated 17
Growth hormone axis Pitfalls Hypothyroidism causes low GH thyroid hormones are required for GH production IGF-1 usually low in normal infants. Better screening test > 3 years nutrition dependent (low level in children with poor weight gain) 18
Adrenal axis Adults http://www.tpgonlinedaily.com/sleep-glorious-sleep/ 19
Adrenal axis Adrenal insufficiency Morning cortisol (7-8 AM) 9AM is NOT an AM cortisol N > 500 nmol/l rules out adrenal insufficiency ACTH stimulation test Low dose (central) High dose (primary, Addison) N peak > 500 nmol/l 20
Adrenal axis Adrenal excess (Cushing) Screening: 24 hour Urinary cortisol + creatinine - Overnight Dexamethasone test (1 mg at 11 PM followed by 7 AM cortisol) - Midnight cortisol (low) 21
Adrenal axis Generally not useful tests Random cortisol in an infant diurnal variation absent in neonates, develops around 4-6 months low cortisol in babies (low binding globulin CBG) Referral for elevated cortisol reflects stress of the patient Referral for low PM cortisol reflects diurnal variation 22
Other hormonal tests Generally not useful tests Prolactin In neonates (very high normal values) except if looking for very low values (absent pituitary) Mild elevations (PRL increases with stress) Progesterone Reflects ovulation 1,25 OH Vit D Reflects capacity of 1 hydroxylation by the kidney 25 OH Vit D better test for stores 23
Conclusion Hormonal tests are very useful for screening of endocrine conditions Generally not useful tests They are often age- and time- sensitive and results can be difficult to interpret if they are not requested at the right age and the right time of the day Discussion of difficult tests is welcome prior to referral 24