HYPOTHYROIDISM Flashcards
What is hypothyroidism?
Hypothyroidism results from any disorder that leads to insufficient secretion of thyroid hormones from the thyroid gland.
Name the four causes of congenital hypothyroidism.
- Absent or under-developed thyroid gland<br></br>2. Dyshormogenesis - genetic defects in the synthesis of thyroid hormones, resulting in hypothyroidism with goitre<br></br>3. Iodine deficiency during pregnancy<br></br>4. Maternal transmission of antithyroid drugs
List three causes of primary hypothyroidism.
- Hashimoto’s thyroiditis<br></br>2. Iodine deficiency<br></br>3. Iatrogenic causes (e.g., post-ablative therapy, surgery)
What are the clinical features related to decreased metabolic rate in hypothyroidism?
Tiredness/malaise, weight gain, cold intolerance, decreased sweating, coarse, sparse hair, brittle nails, cold, dry skin, constipation, bradycardia, hypothyroid myopathy, delayed relaxation of deep tendon reflexes, hyperlipidemia (xanthelasmas), hypercarotenemia.
Define myxoedema and list symptoms related to generalised myxoedema in hypothyroidism.
Myxoedema refers to the accumulation of mucopolysaccharide in subcutaneous tissues. Symptoms include doughy skin texture, puffy appearance, myxoedematous heart disease, periorbital edema, pretibial myxoedema, entrapment syndromes, peripheral neuropathy, macroglossia, deep hoarse voice, myxoedema coma.
What is the most common cause of hypothyroidism in iodine-sufficient regions?
Hashimoto’s thyroiditis.
Name the thyroid antibodies associated with autoimmune hypothyroidism.
Anti-TPO antibody (95%), Anti-thyroglobulin (60%), TSH receptor antibody (blocking) (10-20%).
How is myxoedema coma managed?
Passively rewarm, cardiac monitoring for arrhythmias, close monitoring of urine output, fluid balance, central venous pressure, blood sugars, oxygenation, broad-spectrum antibiotics, thyroxine cautiously, hydrocortisone if adrenal failure.
What are the long-term complications of autoimmune hypothyroidism?
Increased risk of developing other autoimmune diseases and increased risk of developing B-cell NHL in the affected gland.
How is levothyroxine dosage adjusted in elderly patients with a history of ischemic heart disease?
Start levothyroxine at 25-50 µg daily and adjust every 4 weeks according to response.
In secondary hypothyroidism, what are the levels of TSH, Free T4, and T3?
TSH is low (or ‘normal’), and Free T4 and T3 are low.
Name three symptoms related to decreased metabolic rate in hypothyroidism.
- Tiredness/malaise<br></br>2. Weight gain, despite decreased appetite<br></br>3. Cold intolerance
What are the dermatological symptoms associated with hypothyroidism?
Coarse, sparse hair, brittle nails, cold, dry skin
What gastrointestinal symptoms are commonly seen in hypothyroidism?
Constipation
Describe the cardiovascular symptom associated with hypothyroidism.
Bradycardia - slow pulse
What is hypothyroid myopathy, and what are its symptoms?
Hypothyroid myopathy is characterized by myalgia, stiffness, and cramps.
What is the significance of delayed relaxation of deep tendon reflexes in hypothyroidism?
It is a neurological symptom associated with hypothyroidism.
Name the lipid-related symptom seen in hypothyroidism.
Hyperlipidemia - xanthelasma
What is hypercarotenemia, and how is it related to hypothyroidism?
Hypercarotenemia is the presence of high levels of carotene in the blood. It is related to hypothyroidism and is associated with a yellowish discoloration of the skin.
Define myxoedema and list symptoms related to generalised myxoedema in hypothyroidism.
Myxoedema refers to the accumulation of mucopolysaccharide in subcutaneous tissues. Symptoms include doughy skin texture, puffy appearance, myxoedematous heart disease, periorbital edema, pretibial myxoedema, entrapment syndromes, peripheral neuropathy, macroglossia, deep hoarse voice, myxoedema coma.
What symptoms are associated with myxoedematous heart disease?
Dilated cardiomyopathy, bradycardia, dyspnea, pericardial effusion, worsening of heart failure
What is the significance of periorbital edema in hypothyroidism?
Periorbital edema is a symptom of hypothyroidism, distinguishing it from hyperthyroidism.
Name symptoms related to hyperprolactinemia in hypothyroidism.
Menorrhagia, later oligo or amenorrhea
What are the additional symptoms associated with hypothyroidism?
Goiter (in Hashimoto thyroiditis) or atrophic thyroid (in atrophic thyroiditis), impaired cognition, depression, vitiligo, obstructive sleep apnea.
What is the term for the condition in congenital hypothyroidism characterized by dwarfism and limited mental functioning?
Cretinism
What are the thyroid hormone levels in primary hypothyroidism?
TSH is high, and Free T4 and T3 are low.
List some other abnormalities associated with primary hypothyroidism.
- Macrocytosis (↑ MCV)<br></br>2. ↑ Creatinine kinase<br></br>3. ↑ LDL cholesterol<br></br>4. Hyponatremia (due to ↓ renal tubular water loss)<br></br>5. Hyperprolactinemia
Name the thyroid antibodies associated with autoimmune hypothyroidism and their percentages.
- Anti-TPO antibody - 95%<br></br>2. Anti-thyroglobulin - 60%<br></br>3. TSH receptor antibody (blocking) - 10-20%
What are the thyroid hormone levels in secondary hypothyroidism?
TSH is low (or ‘normal’), and Free T4 and T3 are low.
What caution is advised in restoring metabolic rate in hypothyroidism?
Normal metabolic rate should be restored gradually to avoid precipitating cardiac arrhythmias.
How is levothyroxine initiated in younger patients with primary hypothyroidism?
Start levothyroxine at 50-100 µg daily and gradually increase.
What is the recommended initial levothyroxine dosage for elderly patients with a history of ischemic heart disease (IHD) in primary hypothyroidism?
Start levothyroxine at 25-50 µg daily and adjust every 4 weeks according to response.
When should TSH be checked after any dose change in primary hypothyroidism?
TSH should be checked 2 months after any dose change.
How often should TSH be checked once stabilized within the normal range in primary hypothyroidism?
TSH should be checked every 12-18 months once stabilized within the normal range.
How is levothyroxine dose titrated in secondary hypothyroidism?
Titrate the dose of levothyroxine to the total T4 (tT4) level, aiming for the higher end of normal since TSH is unreliable due to low TSH production.
What is myxoedema coma, and who does it typically affect?
Myxoedema coma is a severe, life-threatening condition that typically affects elderly women with long-standing but frequently unrecognized or untreated hypothyroidism.
What is the mortality rate associated with myxoedema coma despite early diagnosis and treatment?
The mortality rate is up to 60% despite early diagnosis and treatment.
Name two investigations conducted in myxoedema coma.
- ECG (Electrocardiogram): Bradycardia, low voltage complexes, varying degrees of heart block, T wave inversion, prolongation of the QT interval.<br></br>2. ABGs (Arterial Blood Gases): Type 2 respiratory failure (hypoxia, hypercarbia, respiratory acidosis).
What is the prevalence of co-existing adrenal failure in myxoedema coma patients?
Co-existing adrenal failure is present in 10% of patients with myxoedema coma.
How is myxoedema coma managed?
Management includes passively rewarming (aim for a slow rise in body temperature), cardiac monitoring for arrhythmias, close monitoring of urine output, fluid balance, central venous pressure, blood sugars, and oxygenation. Broad-spectrum antibiotics are administered, and thyroxine is cautiously given, along with hydrocortisone if adrenal failure is present.
What are the long-term complications of autoimmune hypothyroidism?
- Increases the risk of developing other autoimmune diseases.<br></br>2. Increased risk of developing B-cell non-Hodgkin lymphoma (NHL) in the affected gland.
Define hypothyroidism.
Hypothyroidism refers to insufficient production of thyroid hormones, triiodothyronine (T3), and thyroxine (T4).
What is primary hypothyroidism, and how does it affect TSH, T3, and T4 levels?
Primary hypothyroidism involves abnormal thyroid function, leading to inadequate thyroid hormones. In this condition, TSH is high, while T3 and T4 are low.
Describe secondary hypothyroidism and its impact on TSH, T3, and T4 levels.
Secondary hypothyroidism, or central hypothyroidism, occurs when the pituitary produces inadequate TSH, resulting in under-stimulation of the thyroid gland. In this case, TSH, T3, and T4 are all low.
What is the most common cause of hypothyroidism in the developed world?
Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the developed world.
Name two antibodies associated with Hashimoto’s thyroiditis.
Anti-thyroid peroxidase (anti-TPO) antibodies and anti-thyroglobulin (anti-Tg) antibodies are associated with Hashimoto’s thyroiditis.
What is the most common cause of hypothyroidism in the developing world?
Iodine deficiency is the most common cause of hypothyroidism in the developing world.
Name treatments for hyperthyroidism that can potentially cause hypothyroidism.
Carbimazole, propylthiouracil, radioactive iodine, and thyroid surgery can potentially cause hypothyroidism as side effects of hyperthyroidism treatments.
How does lithium affect thyroid hormones, and what potential effects can it have?
Lithium inhibits the production of thyroid hormones and can cause a goitre and hypothyroidism.
What is the impact of amiodarone on thyroid hormone production?
Amiodarone interferes with thyroid hormone production and metabolism, usually causing hypothyroidism, but it can also lead to thyrotoxicosis.
What is often associated with secondary hypothyroidism, leading to a lack of other pituitary hormones?
Secondary hypothyroidism is often associated with hypopituitarism, resulting in a lack of other pituitary hormones, such as ACTH.
Name some causes of secondary hypothyroidism.
Tumors (e.g., pituitary adenomas), surgery to the pituitary, radiotherapy, Sheehan’s syndrome (major post-partum hemorrhage causing avascular necrosis of the pituitary gland), trauma.
What are the universal features of hypothyroidism presentation?
Weight gain, fatigue, dry skin, coarse hair and hair loss, fluid retention (including edema, pleural effusions, and ascites), heavy or irregular periods, constipation.
What can iodine deficiency cause in hypothyroidism?
Iodine deficiency can cause a goiter in hypothyroidism.
What happens to the thyroid gland in Hashimoto’s thyroiditis?
Hashimoto’s thyroiditis can initially cause a goiter, after which there is atrophy (wasting) of the thyroid gland.
What is the mainstay of treatment for hypothyroidism, and what is the synthetic version of T4 called?
Oral levothyroxine is the mainstay of treatment for hypothyroidism. Levothyroxine is a synthetic version of T4 and metabolizes to T3 in the body.
How is the dose of levothyroxine titrated in hypothyroidism management?
The dose of levothyroxine is titrated based on the TSH level, initially every 4 weeks.
What action is taken if the TSH result is high in hypothyroidism management?
If the TSH result is high, the levothyroxine dose is too low, and the action is to increase the dose.
What action is taken if the TSH result is low in hypothyroidism management?
If the TSH result is low, the levothyroxine dose is too high, and the action is to reduce the dose.
What is liothyronine sodium, and when is it rarely used in hypothyroidism management?
Liothyronine sodium is a synthetic version of T3 and is very rarely used under specialist care where levothyroxine is not tolerated.
What is secreted by the paraventricular nuclei (PVN) in the hypothalamus to initiate the hypothalamic-pituitary-thyroid axis?
Thyrotropin-releasing hormone (TRH)
After secretion, where does TRH go, and what cells does it stimulate in the adenohypophysis?
TRH goes into the hypophyseal portal system and stimulates thyrotropes in the adenohypophysis. These cells secrete thyroid-stimulating hormone (TSH) into the bloodstream.
What is the role of TSH at the follicles of the thyroid gland?
TSH goes to the follicles of the thyroid gland and binds to receptors (TSH-R) on the cell membrane. TSH-R stimulates specific genes in the nucleus to produce thyroglobulin, which is released into the luminal space. Iodide uses sodium-iodine symporters to enter the cell and luminal space. TSH-R also stimulates thyroid peroxidase, converting iodide to iodine, which combines with thyroglobulin, producing iodinated thyroglobulin. The iodinated thyroglobulin is endocytosed back into the follicular cell. Proteases cleave thyroid hormone (T3 and T4) out of iodinated thyroglobulin, releasing it into the blood.
How does thyroid hormone diffuse across cell membranes, and what is the fate of T4 inside cells?
Thyroid hormone diffuses across cell membranes. Once inside cells, the majority of T4 is converted to T3 by deiodinases.
What is the primary action of T3 once it binds to intracellular receptors and interacts with DNA?
T3 binds to intracellular receptors and binds to DNA, modifying cellular activity.
What are the general effects of thyroid hormone on all cells?
It increases sodium-potassium ATPases, stimulates glycogenolysis, glycolysis, and lipolysis, modifying cellular activity.
In the liver, how does thyroid hormone affect LDL (low-density lipoprotein)?
Thyroid hormone stimulates LDL uptake by increasing the number of LDL receptors (LDL-R). It also regulates the production of steroid hormone binding globulins, such as thyroxine binding globulin.
What changes does thyroid hormone induce in the heart?
Thyroid hormone increases beta-receptor sensitivity, leading to an increase in heart rate and contractility. It also maintains vasomotor tone.
How does thyroid hormone influence bone metabolism?
It maintains a balance between bone resorption via osteoclasts and bone deposition via osteoblasts. Additionally, it maintains bone maturation and development.
What effect does thyroid hormone have on the sympathetic nervous system in the brain?
It increases sympathetic nervous system activity.
What are the effects of thyroid hormone on the gastrointestinal (GI) tract?
It increases GI motility and GI secretions.
How does thyroid hormone affect skeletal muscles?
It maintains normal muscle contraction, stimulates muscle development and regeneration, and maintains calcium ATPases on the sarcoplasmic reticulum.
What role does thyroid hormone play in the integumentary system?
It maintains good blood flow to the skin, hair, and nails, stimulates growth, and maintains good blood flow to sebaceous glands and eccrine sweat glands, stimulating secretions.
How does thyroid hormone influence fibroblasts?
It maintains the production of glycosaminoglycan and other extracellular proteins in fibroblasts.
What are the overall effects of thyroid hormone on target organs, as shown in Figure 3?
It regulates muscle contraction, development and regeneration, blood flow to the integumentary system, and the production of extracellular proteins in fibroblasts.
What happens in primary hypothyroidism due to the destruction of the thyroid gland?
Thyroid hormone leaks out of injured cells, producing transient hyperthyroidism, which is followed by the development of hypothyroidism.
What are the causes of primary hypothyroidism associated with Hashimoto thyroiditis?
Hashimoto thyroiditis is most common in women and involves the production of anti-TPO antibodies and anti-thyroglobulin antibodies, which destroy thyroid follicular cells.
What is the Wolff-Chaikoff effect, and how does it affect thyroid hormone production?
The Wolff-Chaikoff effect is a negative feedback mechanism induced by high iodine loads, inhibiting iodine uptake into follicular cells, thyroid peroxidase, and proteases, effectively decreasing thyroid hormone production.
What are the causes of central hypothyroidism?
Hypofunction of the hypothalamus and anterior pituitary leads to decreased TRH and TSH, respectively. Causes include trauma and lesions to the hypothalamus, as well as tumors and infarction of the anterior pituitary.
What leads to congenital hypothyroidism?
Abnormal development of the thyroid gland causes congenital hypothyroidism. Causes include maternal autoimmune-mediated thyroid destruction, thyroid agenesis or dysgenesis, and sporadic dyshormonogenetic goiter.
What are the metabolic effects of decreased thyroid hormone?
Decreased metabolism results in weight gain, decreased appetite, decreased body temperature, decreased Na/K ATPase activity, decreased ATP demand, decreased glycogenolysis, decreased glycolysis, and decreased lipolysis.
How does hypothyroidism affect the heart?
Hypothyroidism leads to decreased beta-receptor sensitivity, decreased heart rate, minimal decrease in contractility, and increased vasoconstriction, resulting in bradycardia and hypertension.
What impact does hypothyroidism have on bone growth and maturation?
Hypothyroidism results in decreased bone growth and maturation, leading to short stature.
How does hypothyroidism affect the brain and nervous system?
Hypothyroidism leads to a decrease in sympathetic nervous system activity, causing lethargy, fatigue, weakness, depression, memory deficits, and delayed relaxation of deep tendon reflexes (Woltman sign).
What gastrointestinal effects are associated with hypothyroidism?
Hypothyroidism results in decreased GI motility and secretions, causing constipation.
How does hypothyroidism impact skeletal muscles?
Hypothyroidism leads to decreased muscle contractions and growth, decreased expression of calcium ATPases, myopathy (muscle pain), release of creatine kinase, proximal muscle weakness, and the presence of myoedema (localized edema due to muscle damage).
What changes occur in the integumentary system in hypothyroidism?
Hypothyroidism results in decreased blood flow to the skin, hair, and nails for growth, leading to thin and brittle hair, thin and brittle nails, and decreased sweating and sebum production, causing dry skin.
How does hypothyroidism affect the liver and lipid levels?
Hypothyroidism leads to a decrease in the number of LDL receptors, resulting in decreased LDL uptake and increased LDL in the blood.
What impact does hypothyroidism have on the reproductive system?
Hypothyroidism leads to a decrease in thyroid hormone stimulation of the hypothalamus.
How does hypothyroidism affect fibroblasts?
In hypothyroidism, the balance between glycosaminoglycan production and degradation is lost, leading to pretibial myxedema. This progresses to periorbital edema and carpal tunnel syndrome and can further progress to generalized edema. Glycosaminoglycans hold a lot of water, contributing to the edematous presentation.
What is the typical presentation of hypothyroidism in fibroblasts?
The imbalance in glycosaminoglycan production usually presents as pretibial myxedema, progressing to periorbital edema and carpal tunnel syndrome. Eventually, generalized edema may occur.
How does hypothyroidism affect the thyroid gland, leading to goiter?
In hypothyroidism, there is a loss of balance between glycosaminoglycan production and degradation, which can result in goiter.
How can primary and central hypothyroidism be differentiated?
Differentiation involves assessing free T4 levels; if low in both, further evaluation of TRH and TSH is crucial. Low TRH may indicate hypothalamic dysfunction (lesion or trauma), and low TSH may suggest pituitary issues (tumor or infarction). High TSH and TRH with low T4 indicate pituitary responsiveness to low T4 levels.
What tests help differentiate the causes of primary hypothyroidism?
Differentiating between causes involves specific tests for each condition. Hashimoto thyroiditis is associated with positive anti-TPO and anti-thyroglobulin antibodies. Postpartum thyroiditis, subacute granulomatous thyroiditis, and drug-induced thyroiditis are associated with positive antibodies and changes in serum thyroglobulin. Riedel’s Thyroiditis presents with a painless hard thyroid, possible compression of nearby structures, and elevated serum IgG4. Iodine deficiency is confirmed by checking serum iodine levels. Congenital hypothyroidism is identified through neonatal screening within 24-48 hours after birth, showing increased TSH and decreased Free T4.
What associated conditions should be checked in primary hypothyroidism?
Conditions associated with primary hypothyroidism include increased LDL due to decreased LDL receptor uptake, increased creatine kinase (CK) due to myopathy and muscle damage, decreased glucose due to decreased glycogenolysis and gluconeogenesis, and possibly decreased sodium due to increased ADH release.
What is the main treatment for hypothyroidism?
The main treatment for hypothyroidism is levothyroxine, a synthetic form of T4. It can be taken up by cells and converted to T3, exerting its metabolic effect. Dosage efficacy is monitored with TSH levels, aiming for normal TSH levels.
How is levothyroxine dosage adjusted in different situations?
Factors that alter levothyroxine dosage include increased dosage needed if on estrogen (which increases TBG and decreases freely circulating levothyroxine) and decreased dosage needed if on corticosteroids (which decrease TBG and increase freely circulating levothyroxine).
What are the common causes of myxedema coma?
Myxedema coma can be caused by various factors, including infection (sepsis), surgery, and trauma. These stressors can precipitate a severe and life-threatening state in individuals with untreated or inadequately managed hypothyroidism.
What are the main clinical features of myxedema coma?
The main clinical features of myxedema coma include hypotension/shock, which is a result of the loss of sympathetic nervous system (SNS) drive and severe bradycardia. Other features include bradycardia (due to loss of SNS drive), delirium or altered mental status, coma, and hypothermia (due to decreased metabolic activity). These manifestations reflect the profound impact of myxedema coma on physiological functions.
What is the recommended treatment for myxedema coma?
The treatment for myxedema coma involves intravenous administration of levothyroxine (T4) and liothyronine (T3) to rapidly restore thyroid hormone levels. Additionally, intravenous hydrocortisone is administered until concomitant adrenal insufficiency has been ruled out. Addressing and treating the underlying causes, such as infection or trauma, is essential for stabilizing the patient.
