THYROID Flashcards
CAUSES OF GOITER (enlarged thyroid gland)
- Biosynthetic defects: associated with reduced efficieny of thyroid hormone synthesis —> increased TSH —> thyroid growth
- Iodine deficiency
- Autoimmune disease: Grave’s (from TSH-R mediated effects of TSI and Hashimoto’s thyroiditis (due to acquired defects in hormone synthesis —> elevated TSH —> thyroid growth
- Nodular disease: disorder growth of thyroid cells (hyperplasticity or neoplastic)
- Nodules replace normal thyroid parenchyma
- More common in areas of borderline iodine deficiency
MULTINODULAR GOITER
DIFFUSE NONTOXIC (SIMPLE) GOITER / COLLOID GOITER
- Absence of nodules and hyperthyroidism
- Presence of uniform follicles that are filled with colloid
- Most commonly caused by iodine deficiency (ENDEMIC GOITER)
- SPORADIC GOITER (non endemic regions)
- JUVENILE GOITER (in teenagers
ENVIRONMENTAL GOITROGENS
> Cassava root which contains thiocyanate
Vegetables of cruciferae family (Brussels sprouts, cabbage, cauliflower)
Milk
PEMBERTON’S SIGN
facial and neck congestion due to jugular venous obstuction when arms are raised above the head
SUBCLINICAL THYROTOXICOSIS
low TSH and normal FT3, FT4 -> suggest thyroid autonomy or undiagnosed Grave’s disease
DIAGNOSIS OF IODINE DEFICIENCY
Low urinary iodine <50 yg/L
TREATMENT OF DIFFUSE NON TOXIC (SIMPLE) GOITER / COLLOID GOITER
IODINE REPLACEMENT
SUBTOTAL or NEAR TOTAL THYROIDECTOMY —> if with tracheal compression or obstruction of thoracic inlet
FOLLOWED BY LEVOTHYROXINE
- Nodules in a thyroid of normal size
- Women > men, increase prevalence with age
- Iodine deficient regions
NON TOXIC MULTINODULAR GOITER
NON TOXIC MULTINODULAR GOITER HISTOLOGY
- Spectrum: hypercellular, hyperplasticity regions to cystic areas filled with colloid
- Extensive fibrosis, hemorrhage or lymphocytic infiltration
NON TOXIC MULTINODULAR GOITER DIAGNOSIS
- Distorted thyroid architecture
- Varying size of multiple nodules
- TFTs usually normal
- PFTs to assess functional effects of compression
- CT or MRI to evaluate anatomy of goiter and extent of substernal extension or tracheal narrowing
- Barium swallow reveal extent of esophageal compression
- Ultrasound identify nodules should be biopsied based on size and sonographic pattern
NON TOXIC MULTINODULAR GOITER TREATMENT
Conservative management
T4 suppression
- is rarely effective for reducing goiter size and risk of subclinical or overt thyrotoxicosis
Radiodine
- used when surgery is contraindicated, decrease MNG volume and selectively ablate regions of autonomy
- Usually 3.7 MBA (0.1 mCi) per gram of tissue
Glucocorticoids or surgery
- When acute compression occurs
- Presence of functional autonomy
- Subclinical or mild overt hyperthyroidism
- Elderly with atrial fibrillation or palpitations, tachycardia, nervousness, tremor or weight loss
- Precipitators: exposure to iodine, contrast dyes
TOXIC MULTINODULAR GOITER
TOXIC MULTINODULAR GOITER
> TSH low, Free T4 normal or minimal increase, T3 elevated > T4
Thyroid scan: heterogenous uptake with multiple regions of increased and decreased uptake
24 hour uptake of radioidine: in the upper normal range
Ultrasound: assess prescreens of discrete nodules corresponding to areas of decreased uptake (cold nodules)
TREATMENT OF TOXIC MULTINODULAR GOITER
Antithyroid drugs
- Normalized thyroid function
- Useful in elderly or ill patient with limited life span
- Spontaneous remission does not occur and long term treatment needed
Radioidoine
- Treatment of choice
- Treat areas of autonomy as well as decreasing mass of goiter by ablating functioning nodules
Surgery
- Provide definitive treatment of underlying thyrotoxicosis as well as goiter
- Should be EUTHYROID PRIOR SURGERY
- solitary, autonomously functioning thyroid nodule
- Functional effects of mutations that stimulate TSH-R signaling pathway or the GsA subunit genes
- Thyrotoxicosis is mild
- Only detected when nodule is >3 cm
- Subnormal TSH level
- Thyroid nodule without clinical features of Grave’s disease or other causes of thyrotoxicosis
HYPERFUNCTIONING SOLITARY NODULE/ TOXIC ADENOMA
DEFINITIVE DIAGNOSTIC TEST FOR TOXIC ADENOMA / HYPERFUNCTIONING SOLITARY NODULE
THYROID SCAN
-Focal uptake in hyperfunctioing nodule and diminished uptake in remainder of gland as activity of normal thyroid is suppressed
TREATMENT TOXIC ADENOMA / HYPERFUNCTIONING SOLITARY NODULE
Radioiodine ablation
- Treatment of choice
- 370-11100 MBA [10-29.9 mCi} 131I
Surgical resection
- Effective and limited to lobectomy, preserving thyroid function and minimize risk of hypoparathyroidism and damage to recurrent laryngeal nerves
Antithyroid drugs and beta blockers
- Normalized thyroid function but not optimal long-term treatment
Common cause of hypothyroidism worldwide
IODINE DEFICIENCY
Most common cause of hypothyroidisim in Iodine sufficient areas
HASHIMOTO and IATROGENIC (Treatment of Hyperthyroidisim)
Causes of Neonatal HYPOthyroidisim
> Thyroid gland dysgenesis 60%
Inborn errors of thyroid hormone synthesis 30%
TSH-R antibody mediated 5%
Clinical Manifestations
> prolonged jaundice
> feeding problems
> hypotonia
> enlarged tongue
> delayed bone maturation
> umbilical hernia
> permanent neurologic damage
> cardiac malformations
AUTOIMMUNE HYPOTHYROIDISIM
- women > men
- Japanese
- Mean age: 60 years
- Risk factors: high iodine, low selenium intake, decreased exposure to microorganisms in childhood
- Smoking cessation (transiently increase incidence)
- Alcohol intake (protective)
CLASSIFICATION OF AUTOIMMUNE HYPOTHYROIDISM
- Hashimoto’s or goitrous thyroiditis: associated with goiter
- Atrophic thyroiditis: minimal residual thyroid tissue
- Subclinical hypothyroidism: normal thyroid hormone levels maintained by a rise in TSH
- Clinical hypothyroidism or overt hypothyroidism: unbound T4 levels fall an TSH levels rise further, symptoms are apparent, TSH >10 miU/L
best documented genetic risk factors for autoimmune hypothyroidism
HLA-DR (3,4,5) polymorphisms
Clinically used markers of thyroid autoimmunity
Antibodies to TPO and Thyroglobulin (Tg)
- Steroid-responsive syndrome associated with TPO antibodies, myoclonus, slow-wave activity on EEG
Hashimoto’s encephalopathy
Laboratory Evaluation for Autoimmune Hypothyroidisim
- NORMAL TSH —> Excludes primary (but not secondary) hypothyroidism
- ELEVATED TSH —> do FT4 to confirm clinical hypothyroidisim
- T4 —> inferior to TSH when used as screening test, will not detect subclinical hypothyroidism
- Increased creatine phosphokinase, elevated cholesterol, triglycerides, anemia
IATROGENIC HYPOTHYROIDISM
- Detected by screening before symptoms develop
- 1st 3-4 months after radio iodine treatment for Grave’s disease —> transient hypothyroidism may occur due to reversible radiation damage
- Low dose thyroxine may be withdrawn if recovery occurs
- Unbound T4 levels —> better measure of thyroid function than TSH in months following radio iodine treatment
IODINE DEFICIENCY
- Responsible for endemic goiter and cretinism
- Uncommon cause of adult hypothyroidism unless iodine intake is very low or if with thiocyanates in cassava or selenium deficiency
- Tx: Iodized salt or bread or a single bolus of oral or intramuscular iodized oil
CHRONIC IODINE EXCESS
- Induce goiter and hypothyroidism
- Patients treated with amiodarone, lithium
SECONDARY or CENTRAL HYPOTHYROIDISM
- In the context of anterior pituitary hormone deficiencies’
- Diagnosis: low unbound T4
- Goal of treatment: maintain T4 levels ini upper half of the reference interval because TSH levels cannot be used to monitor therapy
TREATMENT OF HYPOTHYROIDISM: No residual thyroid function
Levothyroxine 1.6 ug/kg body weight (100-150 ug)
TREATMENT OF HYPOTHYROIDSIM: After treatment of Grave’s disease
Levothyroxine 75-125 ug/day
TREATMENT OF HYPOTHYROIDISM: <60 years old without evidence of heart disease
Levothyroxine 50-100 ug/day
TREATMENT OF HYPOTHYROIDISM: elderly with CAD
12.5-25 ug/day with similar increments every 2-3 months until TSH is normalized
MISSED DOSES OF T4 MANAGEMENT
- Due to long half life (7 days) , can take two doses of skipped tablets at once
OTHER CAUSES OF INCREASE LT4 REQUIREMENT
- Malabsorption (Celiac disease, small-bowel surgery, atrophic or H.pylori gastritis)
- Oral estrogen containing medications
- SERMS
- Ingestion with a meal
- Bile acid sequestrates
- Ferrous sulfate, calcium supplements, sevelamer, sucralfate
- PPI, Lovastatin, Aluminum hydroxide
- Rifampicin, Amiodarone, Carbamazepine, Phenytoin, TKIs
SUBCLINICAL HYPOTHYROIDISM IN PREGNANCY: Target TSH
Target TSH: maintain in normal range but <2.5 mIU/L prior to conception
SUBCLINICAL HYPOTHYRODISM IN PREGNANCY: Monitoring
Monitoring:
1. Immediately after pregnancy is confirmed,
2. Every 4 weeks during 1st half of pregnancy
3. Every 6-8 weeks depending on whether LT4 dose adjustment after 20 weeks of gestation
LT4 dosage: increase from once daily to nine doses per week as soon as pregnancy is confirmed
MYXEDEMA COMA
- Reduced consciousness, seizures, hypothermia 23C
- History of treated hypothyroidism with poor compliance or undiagnosed
- Almost always occurs in elderly
- Precipitated by: drugs that impair respiration: sedatives, anesthesia, antidepressants, pneumonia, CHF, MI, GI bleed, CVA, sepsis, exposure to cold
TREATMENT OF MYXEDEMA COMA: MEDICAL
- LEVOTHYROXINE
single IV bolus 200-400 ug LT4 as loading dose
Daily oral dose of 1.6 ug/kg/day reduced by 25% if administered IV as maintenance dose - Liothyronine(T3) IV or via NGT since T4 —>T3 conversion is impaired in myxedema coma
- Loading dose: 5-20 ug liothyronine
- maintance: 2.5-10 ug every 8 hours
TREATMENT OF MYXEDEMA COMA: SUPPORTIVE
- External warming: if temp <30
- Space blankets to prevent heat loss
- Hydrocortisone 50 mg every 6 hours - due to impaired adrenal reserve in profound hypothyroidism
- Treat underlying: antibiotics,
- Ventilatory support with regular ABG during 1st 48 hours
- Hypertonic saline or IV glucose if with severe hyponatremia or hypoglycemia
AVOID HYPOTONIC IV FLUIDS -> Exacerbate water retention secondary to reduced renal perfusion and inappropriate vasopressin secretion
AVOID SEDATIVES
- Most valuable tool for diagnosis and evaluation with nodular thyroid disease
- Guidelines recommend for ALL PATIENTS SUSPECTED OF HAVING THYROID NODULES
THYROID ULTRASOUND
ULTRASOUND FINDINGS BENIGN vs MALIGNANT THYROID NODULES
A. MALIGNANCY
- Hypoechoic sold nodules
- Infiltrative borders
- Micro calcifications (>90% cancer risk)
B. NON MALIGNANT
- Isoechoic solid nodules (5-10% cancer risk)
- Spongiform nodules (multiple small internal cystic areas or simple cysts (<3% cancer risk)
- Not used routinely if with thyroid nodules
- Performed if serum TSH is SUBNORMAL
- Determine if functioning or non functioning thyroid nodules
THYROID SCINTIGRAPHY
HOT vs COLD THYROID NODULES
A. FUNCTIONING or HOT NODULES
- Almost never malignant
- FNA not indicated
B. NON FUCTIONING or COLD NODULES
- Do not produce thyroid hormone
- Malignant
- anti bodies that stimulate the TSH-R in Grave’s disease
- Used to predict both fetal & neonatal thyrotoxicosis caused by transplacental passage of high maternal levels of TRAb or TSI (3x upper limit of normal) in last trimester
TRAb (TSH receptor antibody)
- detect autoimmune thyroid disease. Anti-Tg less common
- 80% of Graves and almost all patients with autoimmune hypothyroidism have TPO antibodies
Antibodies against TPO and Tg
- increased in all types of thyrotoxicosis EXCEPT thyrotoxicosis factitia
- Reflect thyroid tissue destruction and released of Tg
- Main role: follow up of thyroid in cancer patients
-After total thyroidectomy and radio ablation, Tg should mbe <0.2 ng/ml in absence of anti-Tg antibodies - If measurable levels —> incomplete ablation or recurrent cancer
Serum Tg
CAUSES OF ELEVATED TSH
- Hypothyroidism - most common
- TSH secreting pituitary tumor
- Thyroid hormone resistance
- Assay artifact
HYPEREMESIS GRAVIDARUM
- Severe nausea, vomiting and risk of volume depletion
- Antithyroid drugs not indicated unless concomitant Grave’s disease is suspected
- Tx: parenteral fluid replacement
CHANGES IN THYROID FUNCTION during PREGNANCY
- Increase in hCG during 1st trimester —> weakly stimulate TSH-R —> reciprocal fall in TSH
- Estrogen induced rise in TBG during 1st trimester (sustained during pregnancy)
- Alteration in immune system —> onset, exacerbation or amelioration of underlying autoimmune thyroid disease
- Increased thyroid hormone metabolism by placental type III deiodinase
- Increase urinary iodide excretion —> impaired thyroid hormone production in areas of marginal iodine sufficiency
WOLF-CHAIKOFF EFFECT
- Excess iodide transiently inhibits thyroid iodide organification
Recommended Dietary Allowance (RDA) IODINE
> Pregnant women: 220 ug/day
Breastfeeding women: 290 ug.day
