Thyroid Β· Hypo & Hyper
Thyroid Disorders
Hypothyroidism slows everything down; hyperthyroidism speeds everything up. The brain and growth plate pay the price.
π¨ Analogy
Thyroid hormone is the body's metabolic thermostat β it sets the rate at which every cell burns fuel. Turn the thermostat down (hypothyroidism) and the whole house slows: heart rate drops, bowels stop moving, brain fog sets in, and growth stalls. Turn it up too high (hyperthyroidism) and the house runs hot and frantic β heart races, weight drops despite increased appetite, sleep becomes impossible, and the nervous system fires constantly. The pituitary is the programmer controlling this thermostat via TSH β when the thermostat is broken, TSH either shouts louder (β) or goes quiet (β).
Hypothyroidism
| Feature | Congenital | Acquired (Hashimoto's) |
|---|---|---|
| Cause | Thyroid dysgenesis (most common), dyshormonogenesis, iodine deficiency | Autoimmune thyroiditis β TPO + anti-thyroglobulin antibodies |
| Age | Newborn β caught on newborn screen | Adolescent females most common; school-age possible |
| Symptoms | Prolonged jaundice, hypotonia, large fontanelle, macroglossia, constipation, hoarse cry, umbilical hernia, poor feeding, cretinism if untreated | Fatigue, weight gain, cold intolerance, constipation, dry skin, hair loss, bradycardia, delayed puberty, poor growth, goiter |
| Labs | β T4, β TSH | β T4 (or normal), β TSH, + TPO antibodies, + anti-Tg antibodies |
| Newborn Screen | β β T4 + β TSH detected at 24β48h | Not screened β clinical diagnosis |
| Treatment | Levothyroxine β start within 2 weeks of birth β (brain development critical) | Levothyroxine if symptomatic or TSH >10; monitor if subclinical |
| Associated | Down syndrome, Turner syndrome screening | Down, Turner, T1DM, celiac, other autoimmune |
Hyperthyroidism β Graves' Disease
Graves' Disease β Key Facts
- Most common cause of hyperthyroidism in children
- Autoimmune β TSI (thyroid-stimulating immunoglobulin) mimics TSH β β T3/T4
- Female > Male (5:1); peak adolescence
- Associated: other autoimmune diseases, family history
- Diffuse goiter β almost always present
- Exophthalmos (proptosis) β pathognomonic for Graves'
- Pretibial myxedema (rare in children)
Symptoms β "Everything Fast"
- Heat intolerance, sweating
- Weight loss despite β appetite
- Tachycardia, palpitations, β BP
- Tremor, nervousness, emotional lability
- Diarrhea, frequent stools
- Poor sleep, fatigue paradoxically
- Accelerated bone age, advanced puberty
- Declining school performance
- Labs: β free T4, β T3, β TSH β, + TSI antibodies
Management
1
Antithyroid drugs β first-line
Methimazole (preferred in children). PTU β second-line (hepatotoxicity risk). Beta-blockers for symptomatic relief (propranolol).
2
Radioactive iodine (RAI)
Definitive β destroys thyroid tissue. Preferred for definitive treatment in adolescents. Results in hypothyroidism β lifelong levothyroxine.
3
Thyroidectomy
Surgical option for large goiter, cancer concern, or RAI contraindicated. Risks: hypoparathyroidism, recurrent laryngeal nerve injury.
β οΈ Thyroid Storm
- Rare but life-threatening exacerbation β fever, extreme tachycardia, agitation, vomiting, hypertension, altered mental status, cardiac failure
- Triggers: surgery, infection, trauma, radioiodine in unprepared patient
- Tx: propylthiouracil (PTU) + Lugol's iodine + beta-blocker + corticosteroids + supportive ICU care
π‘ Hypo vs. Hyper β Quick Lab Summary
Hypothyroidism: β TSH + β T4. Hyperthyroidism: β TSH + β T4. TSH moves opposite to thyroid function β it's the feedback signal. High TSH = thyroid failing = pituitary shouting. Low TSH = thyroid overactive = pituitary going quiet.
Autoimmune Β· Insulin Deficient
Type 1 Diabetes Mellitus (T1DM)
Autoimmune destruction of beta cells β no insulin, no cellular fuel uptake, and a body in metabolic freefall.
π¨ Analogy
Insulin is the key that unlocks the cell door for glucose. In T1DM, the immune system attacks and destroys the factory (pancreatic beta cells) that makes the keys. Without keys, glucose piles up in the bloodstream (hyperglycemia) while cells starve. The body panics and starts burning fat for fuel β creating ketones as byproducts. When ketones accumulate faster than they can be cleared, the blood becomes acidic: diabetic ketoacidosis (DKA). DKA is the crisis that often brings T1DM to diagnosis.
Pathophysiology & Who
- Autoimmune destruction of pancreatic Ξ²-cells β absolute insulin deficiency
- Autoantibodies: GAD65, IA-2, ZnT8, insulin autoantibodies (IAA)
- HLA-DR3 and HLA-DR4 associated
- Peak onset: 5β7 years and 10β14 years (puberty)
- Most common metabolic disease of childhood
- Associated: celiac disease (10%), autoimmune thyroiditis (20%), Addison's
Classic Presentation β "3 Ps + Weight Loss"
- Polyuria β osmotic diuresis from glucosuria
- Polydipsia β compensatory thirst
- Polyphagia β cellular starvation despite high glucose
- Weight loss β catabolism, loss of glucose in urine
- Fatigue, blurry vision
- New-onset enuresis in previously dry child
- ~25β40% present in DKA at diagnosis
Diagnosis
- Random glucose β₯200 mg/dL + symptoms
- Fasting glucose β₯126 mg/dL on 2 occasions
- HbA1c β₯6.5%
- 2-hr glucose β₯200 on OGTT
- Check: autoantibodies (GAD65, IA-2), C-peptide (low in T1DM), fasting insulin (low)
- Distinguish from T2DM: younger, lean, autoantibodies +, C-peptide low
- Screen at diagnosis: celiac (TTG-IgA), thyroid (TSH), celiac antibodies
Management
- Insulin β lifelong, always required
- Basal-bolus regimen: long-acting (glargine/detemir) + rapid-acting (lispro/aspart) with meals
- Insulin pump (CSII) β continuous subcutaneous infusion; preferred for many children
- Continuous glucose monitor (CGM) β standard of care
- Closed-loop ("artificial pancreas") β CGM + pump automated
- Target HbA1c: <7% for most children
- Carb counting, sick day rules, glucagon kit for severe hypoglycemia
- Annual: HbA1c (q3 months), lipids, UA (microalbuminuria), ophthalmology after 5 years
Diabetic Ketoacidosis (DKA)
DKA β Definition & Diagnosis
- Triad: hyperglycemia + ketosis + metabolic acidosis
- Glucose >200 mg/dL (often >300β600)
- Ketonemia/ketonuria
- pH <7.30 + bicarbonate <15 mEq/L
- Severity: mild (pH 7.20β7.30), moderate (7.10β7.20), severe (<7.10)
- Triggers: new diagnosis T1DM, missed insulin, infection, stress
DKA β Clinical Features
- Nausea, vomiting, abdominal pain (can mimic acute abdomen)
- Kussmaul respirations β deep, labored breathing to blow off COβ β
- Fruity/acetone breath β exhaled ketones β
- Dehydration β dry mucous membranes, decreased skin turgor, tachycardia
- Altered mental status (severe)
- Labs: β glucose, β pH, β HCOβ, β anion gap, β BUN/Cr, β ketones
- KβΊ may be normal or high initially (transcellular shift) β becomes low with treatment
DKA Management
1
IV fluid resuscitation
10β20 mL/kg NS bolus for shock. Then replace deficit slowly over 24β48h (NOT faster β cerebral edema risk). NS or LR.
2
Insulin infusion
Start AFTER fluids (at least 1h). Regular insulin 0.05β0.1 units/kg/hr. Goal: β glucose by 50β75 mg/dL/hr. Do NOT push glucose down too fast.
3
Potassium replacement
Add KβΊ to fluids once urine output confirmed + KβΊ <5.5. Insulin drives KβΊ into cells β hypokalemia. Monitor EKG.
4
Add dextrose to fluids
When glucose reaches ~250β300 mg/dL β continue insulin to clear ketones but add D5 to prevent hypoglycemia.
5
Monitor for cerebral edema
Most feared complication. Headache + altered mental status during treatment β mannitol or 3% saline immediately. Cause: fluid shifts. Avoid rapid fluid or rapid glucose correction.
β οΈ Cerebral Edema in DKA
- Most common cause of death in pediatric DKA
- Occurs 4β12h into treatment
- Signs: headache, change in mental status, papilledema, cushing triad (β BP, β HR, irregular breathing)
- Risk factors: younger age, new-onset DM, rapid fluid correction, low PCOβ at presentation
- Treatment: 3% hypertonic saline OR mannitol immediately
- Prevention: slow correction (48h), avoid hypotonic fluids
Insulin Resistance Β· Adolescent
Type 2 Diabetes Mellitus (T2DM)
Insulin resistance + relative insulin deficiency β the metabolic consequence of obesity in adolescence.
T2DM vs. T1DM β Key Differences
| Feature | T1DM | T2DM |
|---|---|---|
| Mechanism | Autoimmune Ξ²-cell destruction | Insulin resistance + relative deficiency |
| Body habitus | Lean (usually) | Obese (usually) |
| Onset | Often acute (DKA) | Insidious, often asymptomatic |
| Autoantibodies | Positive | Negative |
| C-peptide | Low/absent | Normal or elevated |
| Acanthosis nigricans | No | Yes (insulin resistance marker) |
| Family history | Autoimmune | Strong T2DM family history |
Screening Criteria
- Screen overweight/obese children (BMI β₯85th percentile) who have β₯1 risk factor:
- First/second-degree relative with T2DM
- High-risk race/ethnicity (Hispanic, Black, Native American, Asian, Pacific Islander)
- Signs of insulin resistance: acanthosis nigricans, HTN, dyslipidemia, PCOS
- Maternal gestational diabetes or T2DM
- Start screening at age 10 or onset of puberty
- Repeat every 3 years; annually if risk factors
- Tests: fasting glucose, HbA1c, or OGTT
Management β Step Ladder
1
Lifestyle modification β always
β Calories, β physical activity, β sugary drinks, dietary counseling. Central to all stages.
2
Metformin β β first-line medication
FDA approved for T2DM β₯10 years. Reduces hepatic glucose output. Start low, titrate. SE: GI upset, lactic acidosis (rare). Hold if contrast dye or surgery.
3
GLP-1 agonists (liraglutide/semaglutide)
FDA approved for adolescents. Weight loss benefit. Add if metformin insufficient.
4
4
Insulin
If HbA1c >9% at diagnosis, symptomatic hyperglycemia, or ketosis β start insulin. May be able to wean as insulin resistance improves with weight loss.
Complications & Monitoring
- HbA1c every 3 months until stable, then every 6 months
- Annual: fasting lipids, UA (microalbuminuria), ophthalmology, foot exam
- BP at every visit
- Screen for NAFLD: ALT/AST
- HHS (hyperglycemic hyperosmolar state) β rare but more common in T2DM than T1DM; no significant ketosis; extreme hyperglycemia + hyperosmolarity + severe dehydration
Growth Β· Pituitary
Growth Disorders
GH deficiency Β· Constitutional delay Β· Short stature β know your growth velocity and bone age.
π¨ Analogy
Growth is like a construction project with a master schedule. Bone age is the building inspector's progress report β it tells you how far along the bones have developed compared to calendar age. If bone age matches chronological age but height is short, the building materials (hormones) are deficient. If bone age is delayed but everything is on track proportionally, the construction crew (growth program) just started late β that's constitutional delay. The growth velocity (how fast the child is growing each year) tells you if active construction is happening or if the project has stalled.
| Feature | GH Deficiency | Constitutional Delay | Familial Short Stature |
|---|---|---|---|
| Height | Short, falling off curve | Short but parallel to curve | Short, parallel to curve |
| Growth velocity | ββ (<4 cm/year) | Normal or mildly β | Normal |
| Bone age | Delayed | Delayed β | Normal (= chronological age) |
| Puberty | Delayed | Delayed | Normal timing |
| Final height | Short without treatment | Normal adult height eventually | Short (matches family) |
| Family history | No | Yes (late bloomers) | Yes (short parents) |
| IGF-1 / IGFBP-3 | ββ | Low-normal for age | Normal |
| Treatment | GH therapy β | Reassurance; sex hormone if distressed | None unless GH deficient |
GH Deficiency β Diagnosis
- Screening: IGF-1 + IGFBP-3 (low suggests GHD)
- GH stimulation test β gold standard (peak GH <10 ng/mL after stimulation)
- Bone age X-ray (left hand/wrist) β delayed in GHD
- MRI brain/pituitary β rule out craniopharyngioma, pituitary hypoplasia, radiation effects
- Causes: idiopathic (most common), pituitary tumor, craniopharyngioma, radiation, trauma
GH Therapy β Indications
- GH deficiency (classic)
- Turner syndrome
- Prader-Willi syndrome
- Chronic renal insufficiency
- Small for gestational age (SGA) not catching up
- Idiopathic short stature (ISS) β if height <β2.25 SD
- Given daily SC injection; monitor IGF-1 levels
- Side effects: pseudotumor cerebri, slipped capital femoral epiphysis (SCFE), glucose intolerance
Puberty Β· Timing Disorders
Precocious Puberty Β· Constitutional Delay
Puberty that starts too early or too late β know the normal timing, then identify the outliers.
Normal Puberty Timing
- Girls: thelarche (breast buds) β normal 8β13 years; menarche 2β3 years later
- Boys: testicular enlargement (>4mL/Tanner 2) β normal 9β14 years
- Adrenarche (pubic/axillary hair) β precedes gonadarche by 1β2 years
- Growth spurt: girls peak ~12 years; boys peak ~14 years
Precocious Puberty
- Definition: secondary sex characteristics before age 8 in girls, age 9 in boys
- Central (GnRH-dependent): HPG axis activated early; FSH + LH elevated; bone age advanced
- Girls: idiopathic (most common 90%)
- Boys: almost always has organic cause (CNS tumor, hamartoma)
- Peripheral (GnRH-independent): sex hormone excess without HPG axis; LH/FSH suppressed
- CAH, McCune-Albright, adrenal/ovarian tumor, exogenous estrogen/androgen
- Workup: bone age, LH, FSH, estradiol/testosterone, GnRH stimulation test, MRI brain (boys or neurologic sx)
- Treatment: GnRH agonist (leuprolide) β suppresses HPG axis; preserves adult height
Delayed Puberty
- Definition: no secondary sex characteristics by age 13 (girls) or 14 (boys)
- Constitutional delay (most common in boys): bone age delayed, family history of "late bloomers," normal FSH/LH, normal eventual height β reassure
- Hypogonadotropic hypogonadism: β FSH/LH β hypothalamic/pituitary cause; Kallmann syndrome (anosmia + delayed puberty)
- Hypergonadotropic hypogonadism: β FSH/LH β gonadal failure; Turner syndrome, Klinefelter syndrome
- Workup: LH, FSH, estradiol/testosterone, prolactin, TSH, bone age, karyotype if indicated
Benign Variants β Don't Over-treat
- Premature thelarche: isolated breast development <8 years, no other signs, no bone age advancement, FSH/LH normal β reassure, monitor
- Premature adrenarche: early pubic/axillary hair + body odor without other pubertal signs; normal bone age; rule out CAH (β DHEA-S) β usually benign
- Neither requires treatment β both require follow-up
Adrenal Β· Cortisol Deficiency
Adrenal Insufficiency
Primary vs. central β both dangerous, both require stress dosing. Know the crisis management cold.
Primary vs. Central AI
| Feature | Primary (Addison's) | Central (Secondary) |
|---|---|---|
| Lesion | Adrenal glands | Pituitary/hypothalamus |
| Cortisol | ββ | ββ |
| Aldosterone | β (salt-wasting) | Normal |
| ACTH | ββ (feedback) | β or low-normal |
| Hyperpigmentation | Yes β (β ACTH β β MSH) | No |
| Electrolytes | β Na, β K (salt-wasting) | Usually normal |
| Common causes | Autoimmune (Addison's), CAH, infection | Corticosteroid suppression β, pituitary tumor/surgery |
Symptoms β Chronic AI
- Fatigue, weakness, weight loss
- Anorexia, nausea, abdominal pain
- Salt craving (primary AI)
- Hyperpigmentation β skin creases, scars, oral mucosa (primary only)
- Hypotension, dizziness
- Hypoglycemia (especially in children)
- Labs: β cortisol, β Na, β K (primary), β ACTH (primary), β ACTH (central)
- Gold standard: ACTH stimulation test (cosyntropin) β blunted cortisol response
β οΈ Adrenal Crisis β Emergency
- Triggered by: illness, surgery, trauma, missed doses, stress in patient with AI
- Presentation: severe hypotension/shock, vomiting, severe weakness, altered mental status, hypoglycemia, hyponatremia, hyperkalemia
- Treatment β do NOT delay for labs:
- 1. Hydrocortisone 50β100mg/mΒ² IV STAT (or IM if no IV access)
- 2. IV fluids: normal saline bolus (20 mL/kg)
- 3. IV dextrose for hypoglycemia
- 4. ICU monitoring
- Sick day rules: 2β3Γ usual steroid dose during illness, fever, or surgery
Maintenance Management
- Hydrocortisone β cortisol replacement (2β3Γ daily; highest dose in AM)
- Fludrocortisone β aldosterone replacement (primary AI only)
- Salt supplementation in infants (primary AI)
- Medical alert bracelet β mandatory
- Emergency injection kit at home (IM hydrocortisone)
- Most common cause in children: exogenous steroid suppression (after prolonged steroid use)
β οΈ Steroid Suppression β Board Classic
Child on chronic corticosteroids (asthma, nephrotic syndrome, IBD) who abruptly stops steroids β adrenal crisis. The HPA axis is suppressed β it cannot mount a cortisol response to stress. Always taper steroids slowly. Stress dose before surgery or severe illness.
Board Quick Quiz Β· Flip to Reveal
Endocrine Flash Cards
tap any card to flip β
Newborn with prolonged jaundice, hypotonia, macroglossia, umbilical hernia, constipation. Labs show β T4, β TSH. Diagnosis and treatment?
Congenital hypothyroidism. Start levothyroxine within 2 weeks of birth β critical window for brain development. Caught on newborn screen.
TSH is β and T4 is β. Is this hypothyroid or hyperthyroid? What does this pattern mean?
Hypothyroid. TSH is the pituitary's signal to the thyroid. High TSH = pituitary shouting because the thyroid is underperforming. TSH moves OPPOSITE to thyroid function.
Adolescent female with weight loss, tachycardia, tremor, exophthalmos, and diffuse goiter. Diagnosis and first-line treatment?
Graves' disease. First-line: methimazole + propranolol for symptom control. Definitive: radioactive iodine or thyroidectomy.
10-year-old with 3 weeks of polyuria, polydipsia, weight loss, random glucose 380 mg/dL. What autoantibodies confirm the diagnosis?
T1DM. Autoantibodies: GAD65, IA-2, ZnT8, insulin autoantibodies (IAA). C-peptide will be low. Start insulin β lifelong requirement.
Child in DKA develops headache and altered mental status 6 hours into treatment. What happened and what do you give?
Cerebral edema β most feared complication of DKA treatment. Give 3% hypertonic saline or mannitol immediately. Caused by fluid shifts from overly rapid correction.
In DKA, potassium is 5.8 at admission. Insulin infusion is started. What happens to potassium and what do you watch for?
KβΊ will drop β insulin drives KβΊ into cells. Initially high from acidosis-driven shift. Once urine output confirmed and KβΊ <5.5 β add KβΊ to fluids. Monitor EKG for hypokalemia.
Obese 14-year-old with acanthosis nigricans, fasting glucose 118, HbA1c 6.2%. Autoantibodies negative. Diagnosis and first-line medication?
T2DM (prediabetes/T2DM based on values). First-line medication: metformin. Plus lifestyle modification always. GLP-1 agonists if insufficient.
Short boy, bone age delayed 2 years, growth velocity 3 cm/year, family history of "late bloomer" dad. Diagnosis?
Constitutional delay of growth and puberty. Bone age delayed = still has growth potential. Will reach normal adult height. Reassure. Short-term sex hormones if significantly distressed.
7-year-old girl with breast development, pubic hair, and bone age advanced by 2 years. LH and FSH elevated. Diagnosis and treatment?
Central precocious puberty. GnRH-dependent. Treatment: GnRH agonist (leuprolide) β suppresses HPG axis, preserves adult height. MRI brain not always required in girls but done if neurologic sx.
Child with known adrenal insufficiency develops vomiting and high fever. Parents ask what to do at home. What do you instruct?
Stress dosing: give 2β3Γ the usual hydrocortisone dose. If vomiting and cannot take oral meds β IM hydrocortisone injection kit. Go to ED if not improving. Never skip steroids during illness.
What distinguishes primary adrenal insufficiency from central (secondary) AI?
Primary (Addison's): β ACTH β hyperpigmentation + salt-wasting (βNa, βK) + β aldosterone. Central: β ACTH β no pigmentation, no salt-wasting, aldosterone normal. ACTH is the key differentiator.
GH therapy is indicated for which conditions besides GH deficiency?
Turner syndrome Β· Prader-Willi syndrome Β· Chronic renal insufficiency Β· SGA not catching up Β· Idiopathic short stature (if height <β2.25 SD). Side effect: SCFE, pseudotumor cerebri.