Thyroid Disease Flashcards
What is the general pathway for stimulating thyroid hormone release?
Release of TRH by Hypothalamus
Triggers release of TSH by Anterior Pituitary
Triggers release of T3 and T4 from Thyroid
**Iodine dependent
What is cretinism?
Epidemiological features?
Congenitally severely stuntend physical and mental development secondary to untreated fetal thyroid hormone deficiency, secondary to maternal hypothyroidism
100,000 born every year
Epidemiology of Iodine Deficiency
Affects 50 million children worldwide
1.6 billion people at risk
Tasmanians are at risk of iodine deficiency - our soils are iodine poor
RDI of iodine:
Children: 90-120ug/day
Adults: 150ug/day
Pregnancy: 250ug/day
Where is dietary iodine derived from?
Derived from iodine in soil and water, thus present in:
- Milk
- Seafood
- Seaweed
- Drinking water
Consequences of iodine deficiency
Goitre Reduced fertility High risk of miscarriage Growth retardation Hearing and speech impairments mental retardation
Iodine Prophylaxis
ID considered inexcusable due to ease with which iodine can be supplemented - and very cheaply
Best way = iodinised salt
- Cheap and easy to make
- Universally and readily consumed
Other methods to supplement:
- Iodine tablets
- Iodinised milk and bread and oil
- Iodinised water
Cellular mechanisms of TSH
What problems can occur with TSH binding and causing T3 and T4 secretion?
Released from Ant. Pit.
Binds to G Protein-coupled TSH-receptors (TSH-R) in thyroid gland cells
Stimulates T3 and T4 secretion
Problems:
- Autoantibodies against TSH-R = TSH-RAb
- These may be stimulatory or blocking - Mutations of TSH-R
- Can produce a variety of clinical syndromes
How are T3 and T4 carried in circulation?
Mainly protein-bound >99%
Bound to:
- Albumin
- TBPA (thyroid binding pre-albumin)
- TBG (thyroid binding globulin)
Relatively more free T3 than T4
FT3 and FT4 are the ones measured in TFTs, along with TSH levels
TFT Interpretation: Normal values, and what is measured and when
Normally, TSH levels are measured:
Euthyroid = normal TSH levels: 0.4-4.0
Hypothyroid = high TSH levels: >5.0
Hyperthyroid = low TSH levels: <0.05
FT3 and FT4 are usually only measured when making a diagnosis of abnormal thyroid function
Or, if HPA axis is impaired
What are the forms of ‘subclinical’ Thyroid dysfunction
Can sometimes still represent clinically significant conditions, that can be missed
Subclinical Hypothyroidism: (aka ‘compensating’ or ‘prehypothyroidism’)
- High TSH (>5.0) but T3 and T4 are normal
Subclinical Hyperthyroidism:
- Low TSH (<0.05) but normal T3 and T4
Grave’s Disease: Autoimmune Hyperthyroidism
Hyperthyroidism.
Incidence: 0.05-0.5%
Risk Factors: Females and FHx
Clinically: Symptoms typical of hyperthyroidism, eye signs, goiter
Diagnosis: Low TSH, presence of TRAB (>70%), with Tc Scan
*TRAB stimulatory antibody
Treatment: Two options
- Temporary - Antithyroids
- Definitive - Resection and Radioactive Iodine
Prognosis: Most (75%) return to Euthyroid within 2 years of diagnosis
Postpartum Thyroid Thyroiditis
Presents with Hypothyroidism, Hyperthyroidism, or Hyperthyroidism->Hypothyroidism sequale
Incidence: 5-9% women post-partum
Typically occurs 6 weeks to 6 months post-partum
Risk Factors: IDDM, increased ATPO/TRAB, Prior PPTD, FHx
Clinically: Symptoms of Hyper or Hypothyroidism, depression
Presentation:
- Hypothyroidism (50% cases) -> persists in ~1/4
- Hyperthyroidism-> Hypothyroidism (30%)
- Hypothyroidism (20%)
Treatment: Nil, or temporary Antithyroids or Thyroid replacement, depending on presentation. Note that long-term Hypothyroidism will occur in ~20%
Prognosis: Recurrance in 70%
Hashimoto’s Disease
Autoimmune Hypothyroidism
Incidence: 0.5-2%
Risk Factors: Females, FHx
Clinically: Symptoms of hypothyroidism, +/- Goitre
Diagnosis: Based on clinical presentation, high TSH and low T3, T4, and presence of ATPO (>80%)
Treatment: Thyroid replacement - Thyroxine
Prognosis: Usually life-long replacement
What is TPO?
Thyroid Peroxidase
Enzyme present mainly in the thyroid which liberates iodine, enabling T3 and T4 production
ATPO - autoantibody against thyroid peroxidase is a risk marker for hypothyroidism
What are the goals of thyroxine therapy?
Dose adjusted to keep TSH within idealt herapeutic range: 0.05-2 (which is only valid if pituitary functioning normally, of course)
TSH regulation is the main goal - even if T4 ends up being high. *Remember also that the exogenous T4 is replacing the endogenous T3 as well, so will probably read higher.
E.g. TSH = 0.10 with FT4 of 26 (9-20) = satisfactory
Must reduce Thyroxine dose if TSH low, even if FT4 is in normal range.
E.g. TSH = 0.02 with FT4 of 15 (9-20) = unsatisfactory
Classification of Thyroid Nodules:
Considerations?
May be:
- Symptomatic
- Palpable incidental finding
- Impalpable indicental finding (i.e. on US)
Most pressing concern = risk of malignancy
Most are benign:
- colloid nodules in MNG
- cysts
- adenomas
Prevalence of Thyroid Nodules: General and in TAS
Generally, Thyroid nodules discovered as incidental findings at autopsy have been reported at rates as high as 30-60%
In Tasmania, quite high rates of thyroid nodules - higher for women
Incidence increases with age
(males have a bit of a peak which subsides again, before steadily rising with age again. This peak occurs at ~40-50 years of age)
Protocol for Investigations and Management of Thyroid Nodules
- Thyroid Nodule Discovered
- Measure TSH
3a. If TSH is LOW ( Treat
- If Tc Scan = COld -> Need to conduct FIne Needle Aspirate Biopsy (FNAB)
3b. If TSH is NORMAL (0.4-4.0), need to conduct FNAB
Outcomes:
- 15% of FNABs are non-diagnostic and thus requires repeat FNAB
- 70% are BENIGN -> Management involves OBSERVATION
- 5% are MALIGNANT and 10% are SUSPICIOUS -> Both require COMPLETE RESECTION
*Risks not taken with suspicious nodules, because FNAB takes such a small sample, cannot guaruntee no malignancy exists
Thyroid Carcinomas: General Stats
TCs = most common endocrine malignancy
Papillary Thyroid Carcinomas (PTC) = most common, accounting for 65-80%
Follicular Thyroid Carcinomas (FTC) = 15-30%
Medullary Thyroid Carcinomas (MTC) = 5%
Others account for remaining 2-5%
Prognosis of Thyroid Carcinomas:
Papillary (65-80% TCs) and Follicular (15-30% TCs) TCs have generally good prognosis if appropriate management occurs
PTCs have 10-year survival rate of >90%
Incidences of PTC
Papillary Thyroid Carcinomas
Generally rising in incidence.
- Due to iodine nutrition?
- Due to iodinising radiation?
400% increase in TAS over last 30 years
General management of PTC
- Complete Thyroid Resection
- Radioiodine (PTC, FTC)
- Ongoing T4 replacement - thyroxine drug therapy
Describe ‘occult’ Thyroid Carcinomas: General Stats
Occult TCs = Asymptomatic, Impalpable TCs that are 90%
Overall, occult papillary thyroid carcinomas are believed to have very little risk of progression
