Thyroid disorders Flashcards
Autoimmune etiology
Painless thyroid enlargement
Predominant hypothyroid features
Positive TPO antibody
Hashimoto thyroiditis
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
Onset following a viral illness Painful thyroid enlargement(tender goiter) Transient hyperthyroid symptoms ↑ ESR & CRP ↓ Radioiodine uptake
Subacute granulomatous thyroiditis
Inflammatory infiltrate with macrophages & giant cells
↑ ESR & CRP
↓ Radioiodine uptake
Subacute granulomatous thyroiditis
Pretibial myxedema and ophthalmopathy are specific features of
Graves disease
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
symptomatic hyperthyroidism with elevated serum free thyroxine and suppressed TSH levels
Graves
↓ Total & T4
↑ TSH
Primary hypothyroidism:
Thyroid dysgenesis
TSH resistance
↑ TSH
↑ Total & T4
Thyroid hormone (T4/T3) resistance
↓ Total & T4
↓ TSH
Central hypothyroidism (ex, panhypopituitarism)
↓ Total & T4
↑ TSH
Transient due to maternal exposure
Iodine excess or deficiency
TSH receptor–blocking antibodies
Antithyroid medications
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.
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
Congenital hypothyroidism can eventually present with what 5 unique findings
Pot belly/ Enlarged fontanelle Protruding tongue puffy face umbilical hernia Dry skin
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).
↑Total & T4
↓ TSH
Neonate
neonatal Graves disease (transient from mom)
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
Enlargement of a ______ can lead to obstructive symptoms (dysphagia, dysphonia, dyspnea)
Occurs, typically during times of heightened thyroid stimulation (eg, puberty, pregnancy).
lingual thyroid
Hyperthyroidism causes increased bone turnover with net ____
bone loss
___ stimulates osteoClast differentiation, increased bone resorption, and release of calcium.
MAJOR RISK FOR _____ AND BONE FRACTURES.
T3
OSTEOPOROSIS
___ stimulates OsteoBlast which then release RANK-L to stimulate Osteoclasts
PTH
*vs T3 which activates OsteoClast directly
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
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
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
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
helpsmaintaina 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
