Endocrinology

Question 1

diabetes mellitus

Answer 1

• Fasting blood sugar over 126 mg/dL
• or
• Non-fasting blood sugar over 200 (Sporadic hyperglycemia, usually during illness or after steroids, is common in children)
• HbA1C > 6.5% is suggestive, but needs to be confirmed with hyperglycemia.
• Positive result on glucose tolerance test- Rarely done in pediatrics.

Question 2

type 1 DM

Answer 2

• Insulin deficiency
  
  • Low C-peptide
• Autoimmune destruction of pancreatic β cells
• Most common endocrine problem in children
  
  • 1 in 300-500 people under 18 years of age
• Postprandial hyperglycemia is first finding
• Prone to ketosis with more complete insulin deficiency
• Higher rates in Caucasian populations
• Associated with other autoimmune illness (ex. thyroid disorders, Celiac)
• Clinical presentation:
  
  • Polyuria
    
    • may manifest as enuresis
  • Polydipsia
  • Polyphagia
    
    • often with paradoxical weight loss
  • Dehydration/ketosis
    
    • abdominal pain
    • vomiting
    • worsening mental status/fatigue
    • breath & sweat ketosis
• Diabetic Ketoacidosis (DKA) – most kids who have type 1 present in DKA
  
  • Metabolic Acidosis: arterial pH < 7.3, bicarbonate <15 mEq/L
  • Ketosis: Ketones in blood (>3mmol/L) or urine (moderate-large)
  • Hyperglycemia >200 mg/dL
• Often the presenting diagnosis for T1DM.
• Leading cause of morbidity and mortality in children with T1DM
• Laboratory Findings
  
  • Elevated glucose level
  • Electrolytes:
    
    • Anion Gap
    • Hyponatremia (Can be exaggerated by high glucose)
    • Potassium will be falsely normal/high (Total body low)
    • Renal dysfunction if long standing
  • Urinalysis – very cheap and easy test! One of the most useful tests!
    
    • glycosuria
    • • ketones
        
        • You should NEVER see ketones in urine in a normal kid
    • low pH
  • Auto-antibodies and insulin-like growth factor (not needed in the initial period)
• “Honeymoon” period often follows original diagnosis where the pancreas is still able to produce a significant amount of insulin.
• First presentation of DKA is often set off by acute illness. The stress of illness causes the body to require more insulin than is needed for it’s basal function.
• Long term treatment goals:
  
  • glucose control
    
    • insulin regimen
    • diet
  • Avoid complications in chronic management
    
    • renal failure
    • visual impairment
    • cardiovascular disease
    • iatrogenic hypoglycemia
    • ketosis during dehydrating circumstances

Question 3

diabetic ketoacidosis

Answer 3

• Treatment of DKA
  
  • IV Fluid Rehydration
    
    • Often helps reduce acidosis and glucose levels
    • Must be done gently. Rapid or excessive IV fluid repletion can cause cerebral edema and be fatal.
    • Careful electrolyte restoration.
      
      • Monitor electrolytes carefully and replete.
  • Restoration of anabolic state
    
    • Insulin- restores euglycemia and halts ketone production
  • You would never use hypertonic saline because the kid is actually isotonic, it just looks like they aren’t

Question 4

type II DM

Answer 4

• Insulin Resistance
  
  • hyperinsulinemia
  • reduced sensitivity to insulin
• Gradual onset of symptoms
  
  • DKA presentation uncommon due to presence of insulin
• Growing more common in younger ages
  
  • correlation with worsening of American obesity epidemic
• Risk factors for type II diabetes:
  
  • Family history
  • Ethnicity (African American and Latino populations at higher risk)
  • Weight
  • Polycystic ovarian syndrome
• Diagnosis
  
  • random glucose concentration > 200mg/dl
  • fasting plasma glucose > 126 mg/dl
  • glucose tolerance testing
    
    • 2-hour plasma glucose > 200 mg/dl
  • glycated hemoglobin (Hgb_A1C) is used as a screening test (and is used for diagnosis in adults)
• Co-moribidities
  
  • dyslipidemia
  • hypertension
  • obesity
• Treatment: Glucose control and lifestyle modification
  
  • lifestyle
  • diet
  • exercise
  • metformin
    
    • reduces hepatic glucose production
    • increases sensitivity to insulin
• reduces intestinal glucose absorption

Question 5

neonatal hypoglycemia

Answer 5

• Very common in first 3 days of life, as metabolic needs outstrip energy stores
• In neonates, serum level <40 mg/dL is abnormal (we think) however some lower values in the 1^st 4 hours of life may be normal.
• If symptomatic with low glucose this is ALWAYS abnormal
  
  • Jittery, lethargic, seizures
• Differential diagnosis
  
  • Hyperinsulinism (infant of diabetic mother)
  • Causative illness (shock, heart failure, liver dysfunction)
  • Intoxication (alcohol), drug effects
  • Inadequate substrate (SGA, poor feeding)
  • Counter-regulatory hormone deficiency
  • metabolic disorder inhibiting normal response
    
    • gluconeogenesis
    • glycogenolysis
    • fatty acid oxidation
    • organic acid metabolic disorder
    • galactosemia
• Management
  
  • Give glucose:
    
    • Feed the infant for mild to moderate hypoglycemia
    • Give IV glucose for severe, persistent or symptomatic illness
  • Normal hypoglycemia should resolve in 24-48 hours, if it persists additional workup should be considered:
    
    • “Critical Sample” – Send blood and urine when hypoglycemic to assess the insulin and metabolic response

Question 6

adrenal gland

Answer 6

• Endocrine organ that produces hormones important for salt homeostasis, stress response, and sexual characteristics.

Question 7

congenital adrenal hyperplasia

Answer 7

• Family of disorders that is caused by inactivity of key enzymes involved in adrenal hormone production.
• These disorders result in decreased production of cortisol. As a result there is an increased release of CRH and ACTH that leads to adrenal hyperplasia.
• The 3 most common are:
  
  • 21-hydroxylase deficiency
  • 11-beta hydroxylase deficiency
  • 17-alpha hydroxylase deficiency

Question 8

21-hydroxylase deficiency

Answer 8

• By far the most common form of CAH.
• Presents with virilized genitalia in females. Males may not have a detectable phenotype.
• Internal genitalia will be normal. Which is why ultrasound is useful to demonstrate presence of uterus and ovaries in virilized females.
• Tested for on the state genetic screen.
• Babies generally present with vomiting, lethargy and in salt-wasting crisis.
• Labs will show low sodium levels from salt wasting due to lack of aldosterone.
• Treatment: glucocorticoid, mineralocorticoid replacement and possible surgical correction of external genitalia.

Question 9

Addison disease

Answer 9

• Primary adrenal insuficiency
• Autoimmune destruction of adrenal cortex
• glucocorticoid and mineralocorticoid deficiencies
• Episodes of shock during severe illness
• Treated with oral glucocorticoids and mineralocorticoids

Question 10

Adrenal crisis

Answer 10

• An emergency to be aware of in any patient who has adrenal insufficiency.
• Can present with hypotension, lethargy, and shock.
• In times of stress or illness the body has an increased cortisol need that people with AI cannot compensate for.
• People with AI need stress dose steroids during these times. Anyone with known AI should have a “sick plan”.

Question 11

panhypopituitarism

Answer 11

• The pituitary gland produces 7 hormones that are integral in the function of the body.
  
  • Anterior: TSH, ACTH, FSH, LH, GH, Prolactin
  • Posterior: ADH, Oxytocin
• Loss of the pituitary gland can occur due to trauma or shock that compromises the blood supply.
  
  • in children, special attention paid to growth hormone replacement
  • thyroxine replacement
  • glucocorticoid replacement
  • diabetes insipidus (free water loss, hypernatremia) is treated with desmopressin
  • attention to sex hormone replacement depending on age & gender

Question 12

thyroid organogenesis

Answer 12

• thyroid develops from 3^rd and 4^th pharyngeal pouches starting in the 4^th week of gestation
• by the 7^th week the thyroid has migrated and the thyroglossal duct degenerates

Question 13

congenital hypothyroidism

Answer 13

• during first two weeks of life
  
  • large fontanelles
  • hypothermia
  • poor feeding
  • prolonged jaundice
• beyond 1 month of age
  
  • darkened, mottled skin
  • labored breathing
  • diminished stool frequency
  • lethargy
• after 3 months
  
  • umbilical hernia
  • infrequent, hard stools
  • dry skin with carotenemia
  • macroglossia
  • generalized swelling (myxedema)
• 90% due to thyroid dysgenesis: athyreosis, ectopia, or hypoplasia
• Generally diagnosed via Newborn screening in the US and usually treated before symptomatic.
• Symptomatic infants adopted from other countries may present for care.
• False positive newborn screens are seen particularly in premature infants.

Question 14

acquired hypothyroidism

Answer 14

• 6 months to 3 years:
  
  • deceleration of linear growth
  • umbilical hernia
  • dry skin with carotenemia
  • macroglossia, hoarse cry
• During childhood:
  
  • Goiter
  • delayed eruption of teeth, shedding of primary teeth
  • muscle weakness, pseudohypertrophy
  • infrequent, hard stools
  • precocious sexual development: breast development or enlarged testes without sexual hair
  • generalized swelling (myxedema) – may cause weight gain

Question 15

causes of acquired hypothyroidism

Answer 15

• Hashimoto’s (autoimmune) thyroiditis
  
  • AKA lymphocytic thyroiditis
  • Most common cause
• drug-induced hypothyroidism via medications
  
  • in breastmilk
  • lithium, propylthiouracil (PTU), methimazole
• endemic goiter (iodine deficiency)
• irradiation
• excision

Question 16

hashimoto’s thyroiditis

Answer 16

• Hashimoto’s thyroiditis (chronic lymphocytic, chronic autoimmune thyroiditis)
  
  • insidious onset
  • firm, freely moveable, painless goiter
  • hoarseness, dysphagia
  • Growth retardation
  • T4, FT4 may be normal
    
    • may be elevated (hashitoxicosis, early) or depressed (late)
  • TPOAb and TGAb usually present, though titers often low
  • L-thyroxine may decrease size of goiter, but otherwise not needed in euthyroid patient.
  • hypothyroidism is the end result of autoimmune thyroiditis, usually in 2^nd or 3^rd decade. Treat with thyroid replacement medication.

Question 17

rare thyroiditises

Answer 17

• acute suppurative thyroiditis
  
  • infection via patent thyroglossal duct
• subacute (de Quervain’s) thyroiditis
  
  • caused by mumps, EBV, influenza, echovirus, coxsackievirus, and adenovirus

Question 18

thyroid lab tests and imaging

Answer 18

• TSH
  
  • Age dependent especially in neonates
  • TSH surge can cause false positives in neonatal screen for hypothyroidism
• T4
  
  • primarily bound to thyroxine-binding globulin, but also binds with lesser affinity to other proteins
  • free unbound T4 is active, enters cells and converted to T3 (active)
  • total T4 can be abnormal while FT4 is normal:
    
    • if TBG levels are abnormal
    • certain drugs bind TBG (anticonvulsants)
    • pregnancy or estrogen can stimulate TBG

Question 19

classifying hypothyroidism

Answer 19

• primary: due to defective or absent thyroid
• secondary: due to defective TSH synthesis or action (hypothalamic or pituitary hypothyroidism)

Question 20

diagnosis of hypothyroidism

Answer 20

• low FT4 diagnoses hypothyroidism
• high TSH diagnoses 1º hypothyroidism
• low FT4, low/normal TSH suggests central pituitary hypothyroidism
• hypothalamic hypothyroidism can result in mildly high TSH but TSH is incompletely glycosylated due to lack of TRH, therefore has decreased biological activity

Question 21

treatment of hypothyroidism

Answer 21

• must be individualized due to individual differences in absorption and metabolism
• overtreatment can result in early closure of cranial sutures
• should not be given at the same time as soy or iron-enriched formulas, supplemental iron or calcium, or fiber supplements, since these impair absorption
• careful monitoring of TSH/FT4 until values normalize
• after 3 years of age, annual monitoring of TSH (1º hypothyroidism) and FT4 (2º or central hypothyroidism) is adequate

Question 22

hyperthyroidism

Answer 22

• overactive thyroid
• 95% of childhood cases are due to Graves disease
  
  • autoimmune, antibody-mediated stimulation of thyroid
  • thyroid stimulating immunoglobulins (TSI) directed against TSH receptors
• can manifest as thyrotoxicosis

Question 23

graves disease

Answer 23

• autoimmune disorder
• occurs in 1 in 5000 children
  
  • most commonly seen in adolescents
  • only 2% present before age 10
• at least 5 times more common in females than males
• family history is common
• can occur in conjunction with other endocrine disorders
• difficulty concentrating and sleeping, nervousness, fatigue
• facial flushing, sweating, heat intolerance
• tremors, palpitations
• weight loss despite increase appetite; diarrhea
• proximal muscle weakness
• palpitations, tachycardia, systolic HTN with wide pulse pressure, overactive precordium
• goiter (diffusely enlarged, soft), proptosis
• menstrual irregularities
• lab findings
  
  • elevated T4 and FT4; TSH low
  • I-123 uptake elevated, not suppressed with T3
  • TGAb and TSI often found (95%)
• advanced skeletal maturation, premature closure of cranial sutures
• osteoporosis with longstanding hyperthyroidism

Question 24

treatment of hyperthyroidism

Answer 24

• Urgent management:
• β-blockers
  
  • large doses of propranolol can decrease conversion of T4 to T3
• iodide for acute management
  
  • blocks effect of TSH on thyroid, reduces iodine trapping, reduces vascularity, inhibits release of hormone
• Thioamides reduce hormone production, may take 2-3 weeks to see response
  
  • propylthiouracil (PTU): blocks peripheral conversion of T4 to T3
  • methimazole (MMI): longer half-life
  • both cross placenta, but PTU preferred during pregnancy
  • both present in breastmilk, but concentrations so low that they are not a contraindication
• radioiodine ablation: oral I-131 concentrates in thyroid
  
  • cure rate 90%
  • for those who have significant side effects from medication, or who do not achieve remission with drug therapy
  • permanent hypothyroidism occurs in 40-80%
  • avoided in young children since risk of thyroid cancer after radiation greatest in children < 5 years
• surgical thyroidectomy (subtotal or total)
  
  • for those who fail medical therapy, have significant side effects, have large (>80g) goiters, or severe opthalmopathy
  • cure rate 90%, but has potential for complications including hypoparathyroidism, recurrent laryngeal nerve damage, permanent hypothyroidism

Question 25

neonatal hyperthyroidism

Answer 25

* newborns of affected mothers are at risk for thyrotoxicosis because TSIs cross the placenta * duration after birth depends on half-life of maternal antibodies, ranging from weeks to months * can present with arrhythmias, heart failure, exopthalmos * long-term sequelae include craniosynostosis, cognitive defects, rebound hypothyroidism * treatment includes iodide, followed by PTU or MMI * reserpine or propranolol may be needed for arrhythmias * transection of thyroid isthmus may be considered if there is RDS due to tracheal compression

Question 26

calcium and phosphorus

Answer 26

* Parathyroid hormone is secreted in response to low calcium * PTH raises serum calcium and lowers phosphate * **low PTH** in the setting of **low calcium** and high phosphate confirms a problem with PTH production (hypoparathyroidism) * hypoparathyroidism often results from DiGeorge syndrome

Question 27

rickets

Answer 27

* Can be the result of inadequate calcium (calcipenic) or inadequate phosphorus (phosphipenic). * Calcipenic rickets is the most common form of acquired rickets. * Nutritional rickets is generally from Vitamin D deficiency. * More skin pigment and less sun exposure both lead to higher risk. * Vitamin D supplementation is recommended for ALL children. (400IU/day 0-1yr. 600IU/day \>1yr) Part of the evaluation for children with suspected abuse