Disorders of the Thyroid Gland Flashcards
What happens when iodine availability is insufficient:
- T3 and T4 are inadequately synthesized
- TSH increases
- Goitrogenesis
- conversion of T4 to T3 is enhanced
________ is the inhibition of thyroid hormones biosynthesis by blocking Thyroglobulin iodination
Wolff-Chaikoff effect
what is thyrotoxicosis
Hypermetabolic state caused by elevated circulating levels of free T3 and T4.
describe Primary hyperthyroidism
to thyroid pathology. It is the thyroid itself that is behaving abnormally and producing excessive thyroid hormone
Secondary hyperthyroidism is the condition ______
where the thyroid is producing excessive thyroid hormone as result of overstimulation by thyroid stimulating hormone. The pathology is in the hypothalamus or pituitary
graves accounts for 85% of __________cases
Thyrotoxoicosis
Hyperthyroidism Presentation
increased BMR:
peripheral T4 —>T3, binds nuclear receptor, transcription of cellular genes
* weight loss ( increased appetite)
* heat intolerance
* Warm flushed smooth sweaty skin
-Overactive sympathetic system:
Warm flushed smooth sweaty skin in hyperthyroidism is due to
– increased blood flow & peripheral vasodilatation to increase heat loss
Overactive sympathetic system in hyperthyroidism is clinically manifested as
Tremor, nervousness, emotional changes, diarrhea with fat malabsorption/steatorrhea (hypermotility)
eyelid lag & staring gauze- sympathetic overstimulation of sup tarsal muscle
MSK in hyperthyroidism is clinically manifested as
Wasting, weakness (myopathy)
* Osteoporosis, Increased Serum calcium & Alkaline phosphatase
CVS in hyperthyroidism is DUE TO:
Earliest & most prevalent
increased beta-adrenergic receptor expression
CVS in hyperthyroidism is clinically manifested as
-Increased heart rate
-Increased contractility & myocardial oxygen demand
-peripheral vasodilation (dec. SVR)
- DEC. DBP, increase SBP/PP
Laboratory findings- Hyperthyroidism
- Increased serum T4, decreased serum TSH
- Increased I uptake ( dec. Thyroiditis & patient taking excess hormones)
- Hyperglycemia ( increased glycogenolysis)
- Hypocholesterolemia ( increased LDL receptor synthesis)
- Hypercalcemia ( increased bone turnover)
Exogenous Hyperthyroidism lab dx:
Increased Free thyroxine, decreased TSH, low or undetectable thyroglobulin
determine the dx:
eye symptoms
hyperthyroidism symptoms
proptosis/expthalamos
pretibial myexedema
opthalmopathy
TSH receptor antibodies
Graves disease
most common cause of endogenous hyperthyroidism (85%)
* 20-40 years
* F>M ( 10 times), 1.5 – 2% women in US
graves disease
graves disease genetic susceptibility
HLA DR3
graves disease inhibitory T-cell receptor
CTLA-4.
Pathogenesis of Graves disease
Autoimmune disorder – autoantibodies against multiple thyroid proteins- most importantly TSH receptor (thyrotropin)
-Thyroid-stimulating immunoglobulin (TSI) 90% patients (IgG antibody)
-Thyroid growth stimulating immunoglobulin
-TSH binding inhibitor immunoglobulin
graves disease triad manifestations:
- Hyperthyroidism - diffusely enlarged, hyper functional thyroid
- Infiltrative ophthalmopathy with resultant exophthalmos - 40% of
patients - A localized, infiltrative dermopathy (pretibial myxedema & exopthalmos)
pathogenesis for Exophthalmos & pretibial myxedema
Fibroblasts and adipocytes behind orbit and overlying skin express TSH receptor. (Glycosaminoglycan build up ( Chondroitin sulphate and hyaluronic acid)
what findings are directly linked to thyrotrophin receptor antibodies they are specific to
Graves disease and not found in other causes of hyperthyroidism.
Exophthalmos & pretibial myxedema-
Describe the GROSS morphology of Graves Disease
Gland diffusely and symmetrically enlarged
smooth surface. Capsule intact
C/s soft meaty- resembling muscle
Describe the Microscopy morphology of Graves Disease
-follicular epithelial cells are tall, columnar,
and crowded.
● Formation of small papillae. That lacks
fibrovascular cores.
● The colloid is pale, with scalloped margins.
● Lymphoid infiltrates ( T cells, scattered B cells
and plasma cells), are present throughout the
interstitium; germinal centers may be seen.
clinical features for hyperthyroidism
- Tachycardia and palpitations
- Nervousness & diaphoresis
- Heat intolerance
- Weakness & tremors
- Diarrhea
- Weight loss despite a good
appetite
-cardiac dysrhythmias and sudden death
acute, life-threatening complication of hyperthyroidism that presents with multisystem
involvement.
thyroid storm ( thyrotoxic crisis)
pathogenesis of GOITER
DIFFUSE MULTINODULAR
-Low-iodine diets (lack of seafood
or iodized salt)
Diets high in “goitrogens,“-
cabbage, cassava that block
iodine uptake
clinical presentation
F > M
* Frequently asymptomatic
* Goiter
* Enlarged thyroid gland
* Multiple colloid nodules
* Areas of degeneration
- Calcification
- Cyst formation
- Hemorrhage
Multinodular Goiter path:
-hormonally silent
-manifest as toxic multinodular
goiter or Plummer syndrome with
thyrotoxicosis secondary to
development of autonomous
nodules that function independent
of TSH stimulation.
- Low risk for malignancy
Multinodular Goiter macroscopic:
Multilobulated, asymmetrically enlarged glands, may attain massive size.
* cut surface: irregular nodules containing variable amounts of brown,
gelatinous colloid.
* Older lesions: fibrosis, hemorrhage, calcification, and cystic change
Multinodular Goiter microscopic:
Colloid-rich follicles lined by flattened, inactive epithelium.
* Areas of follicular epithelial hypertrophy and hyperplasia
Hypothyroidism occurring during infancy or early childhood
Cretinism
important preventable cause of mental retardation (cretinism)
newborn screened for hypothyroidism.
Causes of cretinism
- iodine deficiency
- maternal hypothyroidism (early pregnancy)
- dyshormonogenetic goitre (rare) -(Inborn metabolic errors in the fetus that interfere with the normal synthesis of thyroid hormones)
- lingual thyroid (thyroid removal )
cretinism clinical features
- Impaired CNS & bone
growth - Mental retardation
- Short stature
- Coarse facial features
- Protruding tongue
- Umbilical hernia
Hypothyroidism occurring in older children and adults.
Myxedema
most common cause of primary hypothyroidism
hashimoto thyroiditis
TSH or T4/T3 estimation is the most sensitive test for primary hypothyroidism
TSH
Myxedema clinical features
- Slow physical and
mental activity - Cold intolerance
- Overweight
- Low cardiac output
- Constipation and
decreased sweating - Cool pale thick skin
- Hypercholesterolemia
*diastolic HTN - sodium and water retention
hyporeflexia - loss of later eyebrows (hertoghe sign)
hypothyroidism lab features
!Free T4 - decreased
!TSH
– Primary hypothyroidism
* Increased
– Secondary hypothyroidism
* Decreased
hypercholesterolemia- decreased synthesis of LDL receptors
diagnosis:
Sudden fall in temperature
* Reduced heart rate
* Reduced blood pressure
* Confusion
* Coma
hyperthermia
Myxedema Coma
pathogenesis of Myxedema Coma
Severe complication of hypothyroidism occurring mostly in older female
patients;
* altered mental status with or without coma.
causes of myxedema coma
Precipitating factor is usually present, which may include urinary tract
infection or sepsis, trauma, or a side effect of medication.
classic signs of myxedema coma
Altered mentation, hypothermia, hypotension
* Signs and symptoms of hypothyroidism.
Disorder T4 Free T4 TSH
Graves
Increased Increased Decreased
Taking excess hormone :T4 Free T4 TSH
Increased Increased Decreased
Early phase thyroiditis :T4 Free T4 TSH
Increased Increased Decreased
Primary hypothyroidism:T4 Free T4 TSH
Decreased Decreased Increased
Secondary hypothyroidism
(hypopituitarism) :T4 Free T4 TSH
Decreased Decreased Decreased
Increased TBG –
(excess estrogen) :T4 Free T4 TSH
Increased Normal Normal
Reduced TBG –(Androgens/ anabolic steroids)
:T4 Free T4 TSH
Decreased Normal Normal
Most common non- iatrogenic/ non- idiopathic cause of hypothyroidism in USA
Hashimoto thyroiditis
pathogenesis of hashimoto
- Autoimmune disease
process - Antibodies against Thyroglobulin and
Thyroid peroxidase - Destruction of follicles → antigen exposure (usually hidden)
HLA-DR5
Hashimoto thyroiditis epidemiology
45 and 65 years of age
* F>M 10:1 to 20:1.
* Diffuse goiter
Risk for B cell lymphoma ( Marginal zone)
Hashimoto thyroiditis
Gross morphology of Hashimoto thyroiditis
Pale diffusely
enlarged thyroid gland
Microscopic morphology of Hashimoto thyroiditis
-Lymphocytic infiltration with germinal centers.
* Follicle atrophy
* Epithelial “Hürthle cells” changes
* Eosinophilic epithelial cells
Postpartum thyroiditis MOA
-Pregnancy is understood to be associated with reduced immunity to protect fetus from
unwanted exposure to maternal immune system.
-At the end of pregnancy the suppressed immunity is suddenly escalated, leading to the
slow evolution of autoimmune response to thyroid auto-antigens, resulting in thyroiditis.
Postpartum thyroiditis occurs during
-occurs within a year of pregnancy
* painless diffuse thyromegaly
* destruction is followed by sudden release of stored thyroid hormone in blood causes
hyperthyroidism transiently (1-3 months).–>hypothyroidism (4-8months) due to depletion of stores –> recovery to euthyroid state.
Postpartum thyroiditis lab values
Elevated thyroglobulin in hyperthyroid state – due to destruction of thyroid follicles &
release of colloid
* Decreased radioiodine uptake
* decreased blood flow on Doppler Ultrasound
* associated with HLA-D and HLA-B haplotypes.
* Thyroid peroxidase (TPO) auto-antibody is significantly associated
subacture thyroiditis is also knnown as
– Granulomatous Thyroiditis
– DeQuervain thyroiditis
epidemiology of subacute thyroiditis
- Second most common form of thyroiditis
- Most common cause of a painful thyroid
- Females > Males; 30-50 years
clinical features of subacute thyroiditis
post viral syndrome
-pain, fever, fatiigue, myalgia
assc. HLAB35
microscopy of subacute thyroiditis
Granulomatous inflammation to extravasated colloid with lymphocytes, histiocytes, multinucleated giant
cells.
- self limited prognosis
determine diagnosis:
-Rare disease of unknown etiology
- Destruction of thyroid gland
- Dense fibrosis and chronic inflammation
REIDEL’S THYROIDITIS
REIDEL’S THYROIDITIS associated with inflammatory fibrosclerotic conditions (____)
mediastinal or retroperitoneal fibrosis, sclerosing
cholangitis)
* F > M; Middle age
gross morphology of REIDEL’S THYROIDITIS
Tan gray, woody, avascular & no lobules apparent
microscopic morphology of REIDEL’S THYROIDITIS
- No normal lobular pattern
- Follicles are obliterated
- extensive inflammation - consists of plasma cells (IgG-4 producing), lymphocytes, macrophages and
eosinophils - dense fibrous tissue - infiltrates adjacent skeletal muscle/ airways mimicking malignancy
__________- ___________- _________is abnormal thyrid function test in normally functioning thyroid occuring in a setting of non thyroid illness
hospitalized pts
Euthyroid Side Syndrome
pathogenesis of Euthyroid Side Syndrome
dec. thyroid hormones may limit catabolissm during illness
- cytokines downregulate thyroid hormone synthesis
lab findings :Euthyroid Side Syndrome
dec T3
N/INC. T4
INC. Reverse T3
N/dec. TSH
dec. TBG
Scalloping of the coloid tissue is commonly found in biopsy of :
Graves disease
what is the rx for graves disease
B-blockers
thioamide
radioiodine ablation
what diagnosis presents with “hard as wood “ non tender thyroid gland
reidel fibrosing thyroiditis
