Thyroid disorders Flashcards by Stephanie Escobar

Autoimmune etiology
Painless thyroid enlargement
Predominant hypothyroid features
Positive TPO antibody

Hashimoto thyroiditis

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Lymphocytic infiltrate with well-developed germinal centers
Hürthle cells (large eosinophilic cells filled with granular cytoplasm)

represent follicular epithelial cells that have undergone metaplastic change in response to inflammation.

Hashimoto thyroiditis

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Onset following a viral illness
Painful thyroid enlargement(tender goiter)
Transient hyperthyroid symptoms
↑ ESR & CRP
↓ Radioiodine uptake

Subacute granulomatous thyroiditis

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Inflammatory infiltrate with macrophages & giant cells
↑ ESR & CRP
↓ Radioiodine uptake

Subacute granulomatous thyroiditis

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Pretibial myxedema and ophthalmopathy are specific features of

Graves disease

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caused by an autoimmune response directed against the TSH receptor that results in the accumulation of glycosaminoglycans within the affected tissues.

Pretibial myxedema and Graves ophthalmopathy

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symptomatic hyperthyroidism with elevated serum free thyroxine and suppressed TSH levels

Graves

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↓ Total & T4

↑ TSH

Primary hypothyroidism:
Thyroid dysgenesis
TSH resistance

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↑ TSH

↑ Total & T4

Thyroid hormone (T4/T3) resistance

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↓ Total & T4

↓ TSH

Central hypothyroidism (ex, panhypopituitarism)

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↓ Total & T4
↑ TSH
Transient due to maternal exposure

Iodine excess or deficiency
TSH receptor–blocking antibodies
Antithyroid medications

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the most common cause of primary congenital hypothyroidism. In this condition, TSH is elevated and thyroxine (T4) is low.

Thyroid dysgenesis
(hypoplasia, aplasia, ectopy)

*treatment with levothyroxine prevents the development of neurocognitive dysfunction.

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Asymptomatic at birth, but weeks to months later the baby begins to develop
Lethargy, poor feeding
Enlarged fontanelle
Protruding tongue, puffy face, umbilical hernia
Constipation
Prolonged jaundice
Dry skin

Congenital hypothyroidism

Symptoms develop after maternal thyroxine wanes

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Congenital hypothyroidism can eventually present with what 5 unique findings

Pot belly/ Enlarged fontanelle
Protruding tongue
puffy face
umbilical hernia
Dry skin

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Transplacental transfer of TSH receptor–stimulating antibodies in a mother with Graves disease can cause
______ .

Symptoms include tachycardia and irritability
↑Total & T4
↓ TSH

transient neonatal hyperthyroidism (neonatal Graves disease).

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↑Total & T4
↓ TSH
Neonate

neonatal Graves disease (transient from mom)

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In Congenital hypothyroidism, accumulation of \_\_\_\_\_ cutaneously and internally results in 
nonpitting edema (eg, "puffy" face)
umbilical hernia
protruding tongue
large anterior fontanelle.

In addition, T4 is essential for normal ___ development and ______ during early life, and infants are at risk of severe and irreversible intellectual disability.

matrix substances

brain
myelination

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Enlargement of a ______ can lead to obstructive symptoms (dysphagia, dysphonia, dyspnea)

Occurs, typically during times of heightened thyroid stimulation (eg, puberty, pregnancy).

lingual thyroid

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Hyperthyroidism causes increased bone turnover with net ____

bone loss

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___ stimulates osteoClast differentiation, increased bone resorption, and release of calcium.

MAJOR RISK FOR _____ AND BONE FRACTURES.

OSTEOPOROSIS

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___ stimulates OsteoBlast which then release RANK-L to stimulate Osteoclasts

PTH

*vs T3 which activates OsteoClast directly

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Outline the steps to Hyperthyroid induced bone loss

starting with T3

T3 activates osteoclasts DIRECTLY
Bone is reabsorbed
Serum calcium elevated
PTH is now lowered
Less activation of Vit. D
Increased Ca excretion/ Decreased Ca absorption
Triggers Bone reabsorption

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Outline the steps to Hypothyroidism (TSH resistance) starting with TRH

Hypothalamus releases TRH 
Ant. Pit releases TSH
Thyroid gland TSH receptor is insensitive
Low levels of T3/T4 excreted
Triggers increased TRH and TSH release

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Outline the steps to Thyroid Hormone resistance on PERIPHERAL TISSUE starting with TRH

Hypothalamus releases TRH 
Ant. Pit releases TSH
Thyroid gland secretes T3/T4
Thyroid Hormone Receptor on peripheral tissue broken
T3/T4 levels perceived as low
Triggers increased TRH and TSH release

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Outline the physiological effects of Calcitonin starting from an Elevated serum calcium level

Elevated serum Calcium level detected by Thyroid Thyroid parafollicular C cells release Calcitonin Decreased osteoClast activity (bone reabsorption & Increased calcium Urinary excretion Lowered serum calcium levels

What relases calcitonin?

Thyroid parafollicular C cells

Calcitonin is regulated primarily by

circulating calcium levels (not thyroid)

Thyroid peroxidase (TPO) is a multifunctional enzyme that catalyzes the _____ of iodide _____ of Thyroglobulin (TGB), _____ reaction between 2 iodized tyrosine residues.

oxidation (to iodine) iodination coupling

Antibodies against TPO seen in

chronic lymphocytic (Hashimoto) thyroiditis

______ is a common cause of diffuse goiter.

Hashimoto thyroiditis

↑ T3 and T4 (thyroxine) levels ↓ TSH ↓ Thyroglobulin ↓ radioiodine uptake

Exogenous thyrotoxicosis *Use of T3 supp. (liothyronine) shows elevated T3 only.

↓ total thyroxine (T4) normal free T4 normal TSH

Thyroxine-binding globulin (TBG) deficiency euthyroid does not require treatment

helps maintain a constant free T4 level.

Thyroxine-binding globulin (TBG)

Postviral inflammatory response (recent h/o being ill) Destruction of thyroid follicles with release of preformed thyroid hormone FEVER & TENDER GOITER

Subacute (granulomatous, de Quervain) thyroiditis *pt has fever

``` ↑ T4, ↓TSH (hyperthyroid phase) ↑ thyroglobulin ↑ ESR ↓ radioiodine uptake ```

Subacute (granulomatous, de Quervain) thyroiditis *pt has fever ↑ thyroglobulin indicates inflammation/damage to thyroid gland

The disease is self-limited and resolves in <6 weeks, Initial hyperthyroid phase → hypothyroid phase → return to euthyroid

Subacute (granulomatous, de Quervain) thyroiditis

initially characterized by a neutrophilic infiltrate with microabscess formation Then becomes more generalized inflammatory infiltrate with macrophages and multinucleated giant cells.

Subacute (granulomatous, de Quervain) thyroiditis *The inflammatory process is reflected by elevated serum acute-phase markers (CRP/ESR).

Early: ↓ T3, normal TSH & T4 Late: ↓ T3, ↓TSH, ↓ T4

Euthyroid sick syndrome

A common pattern of thyroid function markers seen in Acutely, severely ill patients Mild central hypothyroid (↓ T3) state; asymptomatic

Euthyroid sick syndrome

Suppression of 5'-deiodinase by glucocorticoids and inflammatory cytokines (eg, TNF-alpha, IL-1, IFN-beta) Decreased peripheral conversion of T4 to T3 Decreased TRH secretion

Euthyroid sick syndrome

does peripheral conversion of T4 to T3

5'-deiodinase

Gross inspection of ______ may reveal formation of visible papillae Microscopic inspection of papillae shows a fibrovascular core, often with laminar calcifications (psammoma bodies).

papillary thyroid cancer

Cells with pale nuclei with finely dispersed chromatin, giving them an empty or ground-glass appearance *(Intranuclear inclusions and grooves can be seen due to invagination of the nuclear membrane)

Orphan Annie eye nuclei (papillary thyroid cancer) *(coffee bean looking)

``` Medullary thyroid cancer + Pheochromocytoma + Parathyroid hyperplasia ```

Multiple endocrine neoplasia type 2 (MEN2A)

``` Medullary thyroid cancer + Pheochromocytoma + Marfanoid habitus/mucosal neuromas ```

Multiple endocrine neoplasia type 2 (MEN2B)

is a neuroendocrine tumor that arises from parafollicular calcitonin-secreting C cells. It is characterized by nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits derived from _____

Medullary thyroid cancer calcitonin

Medullary thyroid cancer arises from

parafollicular calcitonin-secreting C cells | *hypocalcemia is not seen though

extracellular amyloid deposits | nest/sheets of polygonal or spindle-shaped cells

Medullary thyroid cancer

an aggressive tumor with a very poor prognosis. It is most common in older patients (age >60). Cytologic features include markedly pleomorphic cells, including irregular giant cells and biphasic spindle cells. Rapidly enlarging neck mass can cause dyspnea, dysphagia, hoarseness.

Anaplastic thyroid cancer Poor prognosis/ TP53 mutation

Thyrotoxicosis ↓ TSH ↑ Thyroglobulin ↑ Radioiodine uptake

Increased thyroid hormone production | ex: Graves disease

Thyrotoxicosis ↓ TSH ↑↑ Thyroglobulin ↑ Radioiodine uptake

Destruction of thyroid follicles (ex: subacute thyroiditis) ↑ Thyroglobulin (inflammation or destruction of gland) ↑ Radioiodine uptake (Making a lot T4/T3) ↓ TSH because a lot of T3/4 is being released from destruction of gland

Thyrotoxicosis ↓ TSH ↓ Thyroglobulin ↓ Radioiodine uptake

Exogenous thyroid hormone

Thyrotoxicosis ↑ TSH ↑ Thyroglobulin ↑ Radioiodine uptake

Central hyperthyroidism | ex: pituitary adenoma

a large glycoprotein in thyroid follicles that serves as a source of tyrosine residues for thyroid hormone synthesis. Small amounts of it are normally released with thyroid hormone, although greater quantities may be released in states of increased thyroid hormone synthesis or follicular destruction.

Thyroglobulin

Muscle pain, cramps & weakness involving the proximal muscles Delayed tendon reflexes & myoedema Features of hypothyroidism ↑ CK

Hypothyroid myopathy ↑creatine kinase (CK) level suggests a myopathic process with myocyte damage and release of muscle enzymes into the circulation

Fatigue, weight gain, bradycardia, brittle nails myalgias, proximal muscle weakness, delayed relaxation of deep tendon reflexes. The diagnosis can be confirmed with an ______

Hypothyroid myopathy elevated TSH level

decreases the peripheral conversion of T4 to T3

Propylthiouracil | *methimazole does not have this effect

↑ T4 | ↓ TSH

primary hyperthyroidism

Decrease the formation of thyroid hormones via inhibition of thyroid peroxidase (TPO)

Thioamides (methimazole, propylthiouracil)

Patient has Hyperthyroidism and is pregnant what to give

Propylthiouracil not a teratogen ( but causes maternal liver toxicity) so should be used in the 1st Trimester 2-3rd trimester start Methimazole Methimazole is a TERATOGEN in the 1st trimerster causing aplasia cutis/skin, esophageal atresia, facial anomalies.

Hyperthyroidism causes up regulation of _____ expression, leading to increased catecholamine effect. _______ are used to blunt the adrenergic manifestations of hyperthyroidism while awaiting definitive management (surgery, radioiodine).

beta-adrenergic receptor Beta blockers

_____ reduce conversion of T4 to triiodothyronine (T3), the more active form of thyroid hormone, by inhibiting 5'-monodeiodinase in peripheral tissues. Peripheral conversion of T4 to T3 is also decreased by ________ and Propylthiouracil.

Lipid-soluble beta blockers (including propranolol) glucocorticoids