DSA7: Abnormal TFTs and Thyroid Nodules

1. Thyroglobulin (Tg) is secreted into colloid (storage)
2. Inorganic iodide (I-) is transported into the follicular cells (trapping), transported to the internal surface and is incorporated into tyrosine from thyroglobulin
3. Forms mono and di-iodotyrosi

Normal thyroid hormone synth...

Low T3/T4
Primary:
- Congenital thyroid problems
- Low T3/4
- High TSH
Secondary: Problem w pituitary
- Acquired through autoimmune or trauma/insult to thyroid
- Low T3/4
- Low TSH
Hallmarks
- Fatigue
- Apathetic expression
- Weight gain
- Menorrhagia
- C

Hypothyroidism....

Reduction of thyroid hormone synth dt dysgenesis of thyroid or dishormonogenesis; most commonly caused by thyroid dysgenesis
Hallmarks of cretinism
- Intellectual disability
- Lethargy
- Hoarse cry
- Hypothermia
- Feeding problems
- Constipation
- puffy,

Congenital Hypothyroidism....
- Hallmarks
- Dx
- Tx

MCC of congenital hypothyroid
Hallmarks
- Sx of hypothyroid (cretinism)
Dx
- TSH
- Thyroid US or thyroid scan w radionuclide uptake
- Low umbilical cord T4
Tx
- Thyroid hormone replacement therapy
-

Thyroid disgenesis....
- Hallmarks
- Dx
- Tx

Maternal thyroid hormone crosses the placenta

Why do the majority of neonates with congenital hypothyroid have no symptoms?

Congenital hypothyroidism dt metabolism defects in T4 synth; MC is intrathyroid peroxidase deficiency
Hallmarks
- Hypothyroid (cretinism)
- Goitrous enlargement of thyroid
Dx
- Genetic studies
Tx
- Thyroid hormone replacement therapy

Thyroid dyshormonogenesis....

Defects in transport of iodine across the apical membrane (into the follicular colloid) dt mutation of Pendrin pump gene (SLC26A4)
Also results in sensorineural hearing loss in the cochlea

Pendred syndrome....

MCC of primary hypothyroid in the US
Hallmarks
- Short phase of hyperthyroid dt tissue destruction
- Extensive lymphocytic infiltrate within germinal centers.
- Permanent hypothyroid
- Gland is very firm
Dx
- High TSH with low free T4
- Presence of anti-t

Autoimmune hypothyroid (Hashimoto thyroiditis)....

Hashimoto's disease

Hypothyroid with a very firm, non-enlarged gland?

Hashimoto's autoimmune thyroiditis
Iodine deficiency

MCC of hypothyroid in the US?
MCC of hypothyroid worldwide?

Multinodular goiter
Thyroglobulin hyposecretion
Parafollicular cell hyperplasia

Cadmium toxicity is associated with....

Replacement of normal thyroid parenchyma with dense fibrotic tissue with fibrosis of adjacent structures in the neck
Hallmarks
- 30% of pts are hypothyroid
- Painless, rapidly growing thyroid
- Fixed and hard described as "stony" or "woody"
Dx
- Biopsy is

Riedel Thyroiditis....
- Hallmarks
- Dx
- Tx

Hypothyroid dt iodine excess; inhibits organification
Usually self-limiting but patients with abnormal thyroids already become hypothyroid if given iodine for more than a few days

Wolff-Chaikoff Effect...

Following a viral infection, thyroid becomes inflamed and releases large amounts of T4 (hyperthyroid). Once stores of thyroglobulin are exhausted, a euthyroid phase and then hypothyroid phase ensues
Hallmarks
- Painful thyroid radiating to jaw
- Thyroid T

Subacute (DeQuervian's) Thyroiditis...

Thyroid def dt disease of pituitary (dec TRH) or hypothalamus (dec TSH)
Hallmarks
- Hypothyroid sx w coexisting pituitary sx
Dx
- Low T4 with low TSH
Tx
- Levothyroxine

Central Hypothyroid....

T4
T3 (shorter halflife)
- T3 spikes can be concerning for elderly patients or those w cardiac issues
- Generally not recommended

Levothyroxine...
Liothyronine...

Severe hypothyroid usually complicated by infection, MI, cold exposure or opioids; medical emergency
(opposite of thyroid storm)
Hallmarks
- Altered mental status
- Hypothermia
- Hypotension
- Bradycardia
- Hypoventilation
Dx
- TSH
- T4
- Cortisol
- ACTH

Myxedema Coma....

Thyroid hormones suddenly low in a pt w a healthy thyroid dt some other systemic illness. Seen in pt w critical illness
- Free T3 and 4 low
- Reverse T3 will be high
Do not tx w thyroid replacement therapy (THRT)

Sick Euthyroid syndrome...

Inc TSH in the setting of normal free T4; eventually becomes overt hypothyroidism
Hallmarks
- Vague, nonspecific hypothyroid sx
- Hx Hashimoto's thyroiditis
- anti-TPO antibodies
Dx
- TSH >10 indicates need for tx

Subclinical Hypothyroid....

Women
Smoking
Graves disease
Toxic nodular goiter
Toxic adenoma

Risks for hyperthyroidism....

Autoimmune thyroid disease; antibodies bind TSH receptor and make it constitutively active!
Hallmarks
- Hyperthyroid: heat intolerance, weightloss, sweating, anxietym HTN
- Exopthalmos (grittiness and excess tearing, conjunctival injection, diplopia)
- Pr

Graves dz....

Antibodies also active on fibroblast modulation. Activated T cells infiltrate orbit and stimulate fibroblasts
- Enlargement of extraocular muscles dt fibroblast secretion of GAGs and collagen
Tx w tobacco abstinence, euthyroid, artificial tears, radiother

Grave's disease exopthalmopathy....
- Tx

Antero-lateral part of the legs have pretibial myxedema dt inc fibroblast activity and deposition of GAGs in the dermis
Hallmarks
- Non-inflamed, pink/purple, waxy plaque with orange-skin appearance.
- Appears after leg trauma
- Can be nodular/mimic eleph

Thyroid dermopathy (myxedema)...

Clubbing of the fingers dt swelling of fingers and toes in patients w hyperthyroidism
Tx w local steroid injection and IVIG

Thyroid Acropachy...

Polpylthiouracil (PTU)
Methimazole
Blocks synth of thyroid hormone by inh thyroid peroxidase and peripheral 5'-deiodinase
Tx
- graves hyperthyroid
- Thyroid storm (tx w PTU inpatient and discharge w methimazole)
SEs
- Agranulocytosis (loss of PMNs)
- Rash

Thionamides....
- Drugs
- Mech
- Uses
- SEs
- CIs

Taken up by thyroid, resulting in thyroid cell death dt emission of beta particles
Tx hyperthyroid (Grave's dz)
**Start w thionamides (5-7 days) to achieve euthyroid before RAI ablation
SEs
- Tissue destruction initially increases thyroid hormone release

Radioiodine 131...
- Mech
- Uses
-

- Airway obstruction
- Severe dysphagia
- Severe graves opthalmopathy
- Pregnant women who can't tolerate thionamides
SEs
- Permanent hypothyroid/hypoparathyroid
- Recurrence
- Recurrent laryngeal nerve pasly

When is thyroid surgery indicated....
- SEs?

Surgery
RAI 131
Beta blockers

Tx?

Transient hyperthyroid, followed by hypothyroid; usually seen in the post-partum period
Tx w
- Beta blockers
- Occasional thionamides

Painless thyroiditis....

Defective thyroid hormone receptor (TR)-beta gene; THRB mutation-exon 10 hotspot
Dx
- genetic testing
Tx
- Treat symptoms rather than tx thyroid levels

Thyroid Hormone Resistance...

Hyperthyroid following admin of iodine supplements (also an SE of amiodarone dt its high-iodine content and toxic thyroid effects)
Gland functions autonomously without TSH stimulation
Usually seen in people traveling from iodine deplete areas to iodine ri

Jod-Basedow Phenomenon...

Monodermal teratoma composed of thyroid tissue
Hallmarks
- Pelvic pain/mass
- Sx of hyperthyroid
Dx
- postop biopsy
Tx
- Oophorectomy

Struma ovarii...

- Childhood head and neck radiation
- Being male
- Nodule >4cm
- Total body irradiation
- Rapid growing neck mass
- Hoarseness
- Family or personal hx of thyroid CA
- Thyroid cancer syndromes (MEN)
- Iodine deficient area
- Age younger than 20 or older th

Factors that indicate a thyroid nodule is malignant....

High sus (malignant):
- taller > wider
- solid, hypoechoic
- partially cystic
- irreg margins
- calcifications (micro and rim)
- hypervascular
- extension outside of the thyroid
Benign
- Purely cystic or spongiform

US analysis of thyroid nodules...

For all differentiated thyroid cancers >1cm

When is total thyroidectomy recommended?

Radioactive Iodine therapy (RAI); used to treat metastatic thyroid CA

If there is no extension of malignancy beyond the thyroid, then there is no need for....

Suppresses TSH; thyroid cancers have TSH receptors. Levothyroxine has a negative feedback effect on the pituitary so it secretes less TSH.
**Not useful for medullary (c-cell) CA bc it doesnt have TSH receptors

How does levothyroxine help tx thyroid CA?

- Psammoma bodies
- Clear, glassy nuclei dt groove infoldings of the nuclear membrane
- Responds to TSH suppression
- Nodal metastasis

Hallmarks of papillary thyroid cancer...

- Hematogenous metastasis
- Inc production of thyroglobulin by cancerous follicular cells
- Small, uniform nuclei
- Responds to TSH suppression
- Invades capsule and bld vessels

Hallmarks of follicular carcinoma....

Variant of follicular cell cancer
Histo
- Large, polygonal cells with large nuclei and prominent nucleoli
- Eosinophilic, finely granular cytoplasm
Hallmarks
- Invades thyroid capsule and vessels
- Hematogenous spread
- Mean age 55 yo

H�rthle cell cancer....

Hyperthyroid state

Warm/moist skin, lid lag, inc HR, goiter and proximal mm weakness sounds like....

Both Hashimoto's and Grave's

TPO antibody is assoc w...

Grave's disease

TSI (thyroid stimulating immunoglobulin) antibody is assoc w....

Hashimoto's thyroiditis

Anti-thyroglobulin antibody is assoc w....

Grave's dz

Goiter, thrill and bruit over the thyroid, exopthalmos, proximal mm weakness sounds like....

Manifestation of excess thyroid hormone from any source

Thyrotoxicosis...

F (But all patients who are hyperthyroid have thyrotoxicosis)

(T/F) All patients with thyrotoxicosis are hyperthyroid

Hyperthyroid
Thyroiditis
Exogenous ingestion of thyroid hormone

Causes of thyrotoxicosis....

Autoregulation effect; where ingestion of large amounts of iodine acutely inhibits thyroid hormone production despite TSH levels
- "Wolff-ChaikOFF" - T4 goes down
Escape from the WC effect; Hyperthyroid after iodine supp that is unregulated by the normal

Wolff-Chaikoff Effect....
Job-Basedow Phenomenon....

(actue) Hashimoto's thyroiditis
Thyroid uptake and scan
Erythrocyte sedimentation rate (ESR); more inflammatory

51 yo M co palpitations, insomnia and weightloss x 8 lbs despite good appetite.
PE w lid-lag, enlarged, nontender thyroid. Brisk reflexes. Slight resting tremor.
TSH is very low
T4 is high
Anti-TPO antibodies present
Anti-thyroglobulin antibodies are nega

Propothiouracil (PTU) for first trimester
- Liver toxicity
Methimazole for second and third trimesters
- Aplasia cutis

What drug is used to tx a 35 yo F w hx uncontrolled Grave's dz if she is 10 weeks pregnant?

Subtotal thyroidectomy

How to tx a first trimester hyperthyroid F if she cant tolerate PTU?

Postpartum thyroiditis
Painless thyroiditis
Hyperthyroid phase followed by hypothyroid phase
TPO antibodies
TG antibodies

Silent thyroiditis aka.... (there are two)

nonfunctional; a hyposecreting nodule is more likely to be malignant

A (nonfunctional/functional) thyroid nodule is more likely to be malignant

A normal
B Grave's dz
C Toxic multinodular goiter
D Toxic adenoma
E. Thyroiditis (silent or hashimotos)

Observe bc this is subclinical hyperthyroid

You've identified a hyper-functioning thyroid nodule. FT4 and 3 are normal. What do you do next?

Perform ultrasound to see if it has malignant characteristics.
If it does then perform FNA biopsy

What to do if a thyroid fx scan shows a cold nodule?

malignancy

Solid hypoechoic or partially cystic nodule with one or more of the following features: irregular margins, microcalcifactions, taller than wide, rim calcifiactaion with small extrusive soft tissue component, evidence of extrathyroidal extension and hyperv

F (indicates infection/inflamm)

(T/F) Thyroid nodule tenderness is assoc w malignancy

Up the dose of LT bc baby will need some!

What should happen to a mother who is controlled hypothyroid, on Levothyroxine, during pregnancy?

0.5-4.5
<2.5

Normal TSH?
Normal TSH during pregnancy?

post-partum hemorrhage causing hypotension and necrosis of the pituitary bc it gets its bld supply from the HT

Sheehan's syndrome....

Pituitary isn't working properly (secondary hypothyroid) and the hypothalamus is secreting extra TRH to compensate but this is also stimulating prolactin secretion

TSH and Free T4 are both low in a patient with hypothyroid sx but the prolactin is slightly elevated.
What is going on?

Measures the inactive form of T3

Reverse T3 is....

Propranolol
Propothiouracil inpatient (Methimaxole on discharge)
IV fluids
Iodine

Tx thyroid storm....

TOTAL THYROIDECTOMY (for anything larger than 1 cm)

If a person has thyroid cancer, the FIRST treatment (which may be supplemented with others) is....

Papillary
Follicular
Medullary
Anaplastic
(this is also the ranking for prognosis; best to worst)

Thyroid cancers ranked most to least common...

...

Carcinoma: Capsule invaded
Adenoma: Capsule not invaded

Follicular carcinoma vs adenoma....