Hypothyroid/thyroiditis Flashcards
Thyroid Gland
general
Largest endocrine gland
It is located below the larynx and wraps around the anterior and lateral sides of the trachea
Consists of two large lobes connected by a narrow anterior isthmus
thyroid
Thyroid follicles
Filled with colloid
Lined by follicular cells
Secrete 2 thyroid hormones
Thyroxine (T4)
Triiodothyronine (T3)
Thyroid
Parafollicular cells or C cells
Located between the follicular cells
Secrete calcitonin which lowers blood calcium levels
Thyroid Hormones
T4 and T3
Include T4 and T3
Thyroid hormones are produced when the thyroid gland is stimulated by TSH (thyrotropin) from the anterior pituitary (80% is T4 and 20% is T3)
T3 is the primary active thyroid hormone
200-300x more active than T4
T4 circulates through the body and is converted (on demand) by your cells into the active T3 thyroid hormone
Stored thyroid hormones in the follicular lumen are bound to a protein called thyroglobulin (TG)
Bound hormones cannot diffuse into cells
Unbound or “free” hormone can bind thyroid receptors and exert effects (metabolic rate and temperature regulation)
Inhibition of the conversion of T4→T3
Aging
Fasting/Calorie restriction
Any type of inflammation
Lack of sleep
Stress
Acute & chronic conditions (kidney and liver)
Intestinal problems (IBD)
Obesity
Medications: amiodarone, propranolol, propylthiouracil
Alcohol
Functions of Thyroid Hormones
Increased metabolism
Increased transcription of cell membrane Na+/K+ adenosinetriphosphatase (ATPase) → oxygen consumption
Enhanced fatty acid oxidation andheatgeneration
Gluconeogenesis,glycolysis,lipolysis
Functions of Thyroid Hormones
Growth and development
Protein synthesis
Regulates cholesterol and triglyceride metabolism
Affectsbrain, reproductive system, and bone development and growth
Factors that increase the conversion of T4 to T3
are zinc, selenium, Vitamin A, and Vitamin E
Functions of Thyroid Hormones
Interrelated actions with catecholamines
Thyroid hormones enhance responsiveness to catecholamines (“fight or flight response”)
What are the 3 catecholamines?
↑ Expression of catecholaminereceptors
Functions of Thyroid Hormones
Regulates pituitary hormone synthesis(feedback loop)
:)
Hypothyroidism
general
Failure of the thyroid gland to produce sufficient thyroid hormones to meet metabolic demands
Common clinical disorder
Affecting 1 in 300 persons in the United States - 85% are women
Incidence increases with age
5% of individuals over age 60 are affected
hypothyroid
types
(4 meds can induce)
Types:
Primary gland failure (primary hypothyroidism)
Congenital abnormalities, autoimmune destruction, iodine deficiency, and infiltrative diseases
Iatrogenic forms
Thyroid surgery, radioiodine therapy, and neck irradiation
Medication-induced
Amiodarone, lithium, propylthiouracil,methimazole
Insufficient thyroid gland stimulation by the pituitary gland (secondary hypothyroidism or “central hypothyroidism”) or the hypothalamus (tertiary hypothyroidism)
Congenital hypothyroidism
Clinical Presentation
6 P’s
Pale
Puffy face
Protuberant tongue
Poor brain development
Pot-bellied
Protruding umbilicus
hypothyroid
Sx
Arthralgias/myalgias
Cold intolerance
Constipation
Depression
Difficulty concentrating/mental slowness
Dry skin
Fatigue
Hair thinning/hair loss
Menstrual irregularities/infertility
Weight gain (despite loss of appetite)
slow, low metabolism
hypothyroid
PE findings
Signs:
Bradycardia
Cognitive impairment
Delayed deep tendon reflexes
Thin or brittle hair
Goiter (often with Hashimoto thyroiditis)
Lateral eyebrow thinning
Macroglossia
Periorbital and/or peripheral edema
Thyroid Screening
Evaluate for thyroid dysfunction in all patients with symptoms of hypothyroidism
Asymptomatic patients with risk factors for hypothyroidism may be screened
The American Thyroid Association recommends measuring thyroid function in all adults beginning at age 35 years and every 5 years thereafter; more frequent screening may be appropriate in high-risk or symptomatic individuals
The American Academy of Family Practice does not recommend screening for hypothyroidism in asymptomatic adults
Thyroid
Risk Factors
History of autoimmune disease
History of head or neck irradiation
Previous radioactive iodine therapy
Presence of a goiter
Family history of thyroid disease
Treatment with drugs known to influence thyroid function
Primary Hypothyroidism
labs for Dx
Inability of the thyroid gland to produce adequate amounts of thyroid hormone
Subclinical:
Elevated TSH
Normal T3/T4
Overt:
Elevated TSH
Low T4/low-normal T3
primary hypothyroidism
Antibody testing
Includes thyroid peroxidase (TPOs) and thyroglobulin (TBGs) antibodies
Helps in subclinical hypothyroidism orgoiter and if there is active thyroiditis
Presence of antibodies → autoimmune hypothyroidism (Hashimoto thyroiditis)
Secondary hypothyroid
Dx
Secondary Hypothyroidism
Insufficient thyroid gland stimulation by the pituitary gland
Present in only 5% of cases
Decreased TSH
↓ FT3/FT4levels
hypothyroid
Tx with dosing and what to avoid
Most patients require lifelong thyroid hormone therapy
Levothyroxine – biologically equivalent to thyroxine (T4)
Initial dose 1.6 mcg/kg PO daily
Taken in the morning, 30 minutes before eating or bedtime dosing
Check TSH level every 4-6 weeks and titrate dose appropriately
Goal: TSH level of 1-2
Calcium and iron supplements should not be taken within 4 hours of taking levothyroxine
Maintain either brand-name or generic products, but do not switch back and forth
Poor adherence to therapy is the most common cause of persistently elevated TSH levels
hypothyroid Tx
Persistent symptoms despite TSH level in the lower normal range
Combination T3/T4 therapy may be used in select patients
Armour thyroid
Levothyroxine plus liothyronine (Cytomel)
Myxedema coma
general
Rare, but life-threatening condition
Most severe manifestation of hypothyroidism
Occurs when the body’s compensatory responses to hypothyroidism are overwhelmed by a precipitating factor
Infection, medications, surgery, trauma, hypoglycemia, failure to reinstate thyroid replacement therapy
Myxedema coma
Clin man
Myxedematous face: generalized puffiness, macroglossia, ptosis, periorbital edema
Nonpitting edema of the lower extremities
Deterioration of mental status – confusion, psychosis, and rarely coma
Hypothermia < 35.5°C (95.9°F)
Admission to the ICU
Ventilatory, electrolyte, and hemodynamic support, thyroid replacement
The patient does not need to be comatose to be diagnosed with myxedema coma
Thyroiditis
general
General term that refers to “inflammation of the thyroid gland”
Encompasses several etiologies that present in different ways
Autoimmune thyroiditis (Hashimoto thyroiditis)
Painful subacute thyroiditis
Each etiology has a specific pathologic mechanism
Hashimoto Thyroiditis
general
Also known as chronic lymphocytic thyroiditis
Most common form of thyroiditis
Autoimmune thyroid disease resulting in the destruction and failure of the thyroid gland
Epidemiology:
Age of onset is usually between 30-50 years
More common in ♀>♂
Exact trigger is unknown, although genetic and environmental factors play a role
Hashimoto Thyroiditis
hashimotos
etiology
Genetics
Genetic risk factors:
Associated with mutations in HLA-DR3 and DR5 genes
Disease clusters found in families suggest genetic susceptibility
↑Incidenceinpatientswith Down’s syndrome and Turner’s syndrome
hashimotos
patho
Autoimmune destruction is initiated; progressive depletion ofthyroid epithelial cells
Thyroidcell destruction mediated by:
CD8+cytotoxic cells
Local production ofcytokines
Antibodiesmade tothyroglobulin (Tg) and thyroid peroxidase (TPO)- only need one not both antibodies
hashimotos
Lymphocytic infiltration and fibrosisofthyroid cells → follicles are disrupted and releaseof stored thyroid hormones:
Transient ↑ ofthyroxine(T4) andtriiodothyronine (T3)
Compensatory ↓thyroid-stimulating hormone (TSH) follows →T3/T4stores gradually decline
End result: ↑ TSH +hypothyroidism (often permanent)
hashimotos
Risks
Increased risk of:
Developing other autoimmune diseases
B-cell lymphoma of the thyroid gland due to chronic inflammation
Typically presents with a triphasic clinical course
hashimotos
3 phases
Phases:
1. “Hashitoxicosis” - initial transient hyperthyroidism
2. Subclinical hypothyroidism
3. Overt hypothyroidism
hashimotos
Hypothyroidism signs
+/-Goiter *
Dry, coarseskin;alopecia; cool extremities
Puffy face, hands, and feet (nonpittingedema/myxedema)
Bradycardia
hashimotos
Hypothyroidism common symptoms
Fatigue, cold intolerance, weight gain
Dryskin, hair loss
Difficulty concentrating and poormemory
Hoarse voice, impaired hearing
Constipation
Menstrual irregularities (menorrhagia, thenoligomenorrhea oramenorrhea)
Paresthesia
hashimotos
Labs during 3 phases
Thyroid hormone levels will differ in each phase:
Hashitoxicosis: ↓ TSH + ↑ freeT3/T4
Subclinical hypothyroidism: ↑ TSH + normal freeT3/T4
Overt hypothyroidism: ↑ TSH + ↓ freeT3/T4
↑ Thyroid peroxidase antibody level (TPO Ab) – 90% of cases
High levels of TPO Ab predicts progression to symptomatic hypothyroidism
↑ Thyroglobulin antibodies (Tg Ab) – 40% of cases
thyroiditis
Thyroid ultrasound
Differentiate between thyroiditis form multinodular goiter, thyroid nodules, or malignancy
thyroiditis
Radioactive iodine uptake (RAIU)
low uptake → cold thyroid
checking for malignancy
thyroiditis
Fineneedle aspiration
If there is a dominant nodule or suspicion ofmalignancy
Thyroid uptake scans
Radiologic diagnostic tool used to determine thethyroidfunction and pathology
Uses radioactive iodine (I-123 or I-131)
Thyroiditis versus other thyroid diseases):
A: normal
B: Graves’ disease: diffuse increased uptake in both thyroid lobes
C: toxic multinodular goiter: “hot” and “cold” areas of uneven uptake
D: toxic adenoma: increased uptake in a single nodule with suppression of the surrounding thyroid
E: thyroiditis: decreased or absent uptake
thyroiditis
Hashitoxicosis
Tx
Antithyroid medication should not be used
Nonspecific beta-blockers to block peripheral conversion of T4 → T3
Overt hypothyroidism
Tx for young healthy pts and elderly
Adjust by how much?
Goal TSH
Levothyroxine - synthetic form ofT4 that is peripherally converted toT3
1.6 mcg/kg PO daily for young and healthy patients
25 mcg per day in the elderly
Adjust dose by 12.5 or 25 mcg every 4-6 weeks until clinically euthyroid; may also reduce goiter size
Goal: TSH level of 1-2
Absorptionreduced by antacids,iron,calcium
Elevated TPO antibody levels and subclinical hypothyroidism
Tx
Levothyroxine 25-50 mcg PO daily
Adjust dose by 12.5 or 25 mcg every 4-6 weeks until clinically euthyroid
Painful Subacute Thyroiditis
general
Transient thyrotoxic state characterized by anterior neck pain
Often follows an upper respiratory viral infection → triggers an inflammatory destruction of thyroid follicles
Most recover, but 1/3 evolve into overt hypothyroidism over a 10-year period
♀>♂
Painful Subacute Thyroiditis
Initial Clinical Presentation
Neck pain in the area of the thyroid (cardinal feature) that may radiate to the jaw
Diffuse thyroid enlargement (goiter)
Dysphagia
Increased sweating
Tremor
Weight loss
Fever
Tachycardia
Painful Subacute Thyroiditis
Labs during Thyrotoxic phase
Iodine uptake?
Lasts 4-8 weeks
↓ TSH
Initially ↑ free T4 and T3 (T4>T3 -transient hyperthyroidism is due to passive release of stored thyroid hormone)
↑ ESR and CRP
Thyroid scan with radioactive iodine uptake
Low uptake of iodine
Painful Subacute Thyroiditis
Labs during Hypothyroid phase
Variable length
↑ TSH
↓ free T4 and T3
Painful Subacute Thyroiditis
Tx
The thyroid gland spontaneously resumes normal thyroid hormone production after several months in most cases
Beta blockers may be used for patients with significant hyperthyroid symptoms
Thyroid hormone supplementation is only needed for patients who are symptomatic or have clear signs of hypothyroidism (levothyroxine)
Painful Subacute Thyroiditis
Relief of thyroid pain
First-line therapy options:
Aspirin (acetylsalicylic acid) 2,600 mg/day in divided doses
Ibuprofen 3,200 mg/day in divided doses
If no improvement of neck pain after 4 days or patient has severe neck pain
Corticosteroids 40 mg/day x 5-7 days, then slowly tapered over 30 days
