Hypothyroidism

Hypothyroidism has a prevalence of approximately 1-2%. 

Refers to an underactive thyroid gland resulting in retardation of growth and mental development when the thyroid gland fails to produce enough T4 to meet the body’s needs, the body fails to convert sufficient T4 to T3 in peripheral tissues, or the CNS fails to stimulate the thyroid gland.

Overt hypothyroidism is defined as a serum thyrotropin level greater than the upper normal limit with concomitant serum free thyroxine-T4-value less than the lower normal limit.

Overt hypothyroidism is less common than subclinical hypothyroidism.

Associated with hypercholesterolemia, hypertension and cardiovascular disease.

Hypothyroidism associated with poor appetite, cold intolerance, constipation, lethargy and may undergo weight gain. 

Prevalence increases with increasing impairment of kidney function.

For each 10ml/min/1.73 m2 decrement in GFR there is an 18% higher likelihhod of hypothyroidism.

Median age of onset is 67.6 years.

Increases with age.

Hypothyroidism diagnosed14 times more often in patients 50 to 60 years than age patients 0 to 30 years, and 33 times more frequently in those age more than 70 years.

Insufficient thyroid slows life sustaining body processes and damages organs and tissues, and can result in life-threatening complications.

Most often results from dysfunction of the thyroid itself, primary hypothyroidism, but can also occur as a result of defects along the hypothalamus/pituitary axis or from intake of lower than required doses of exogenous thyroid hormone in patients with primary hypothyroidism.

Major clinical findings include: intolerance to cold, fatigue, sleepiness, constipation, weight gain, slow tendon reflexes, non pitting edema (myxedema), and dry skin.

With severe disease may see hypothermia, bradycardia, hypoventilation, hypotension, hyponatremia and pericardial or pleural effusions.

 

Pericardial effusion is common in hypothyroidism.

 

Myxedema coma is the most severe form of hypothyroidism, with the hallmark symptom being altered mental status.

 

Unusual presentations of hypothyroidism include dementia, delirium, psychosis, aggression, and hallucinations.my

 

Hypothyroidism should be included in the differential diagnosis of every patient with hyponatremia. 

Causes include: chronic lymphocytic thyroiditis, known as Hashimoto�s disease, iatrogenic from thyroid surgery or radioactive iodine, medications including lithium, alpha-interferon, interleukin-2, iodine excess as seen with iodine containing contrast media and amiodarone, and iodine deficiency.

More than 90% of cases are primary type, either iatrogenic or related to autoimmune mechanisms.

Primary hypothyroidism associated with elevated TSH.

Central hypothyroidism is a reduction in circulating thyroid hormone resulting from inadequate stimulation of a normal thyroid gland by TSH.

Secondary hypothyroidism reflects pituitary disease.

Classified by the timing of its presentation, the level of endocrine dysfunction and it’s severity.

Associated with anemias which are not always the result of a single mechanism.

Anemia associated with hypothyroidism may be related to comorbidities, and may be micro, normo or macrocytic.

Associated with a higher incidence of iron deficiency anemia.

Patients with iron deficiency or who are unresponsive to oral iron need to have subclinical hypothyroidism ruled out.

Associated with pernicious anemia, celiac disease, and bacterial overgrowth syndromes.

Hypothyroidism, even with adequate erythropoietin levels, may result in hypo proliferation of red blood cells.

Hypothyroidism can cause hair loss, typically frontal, which is particularly associated with thinning of the outer third of the eyebrows.

Pituitary and hypothalamic disorders can cause this process as secondary hypothyroidism.

Highly prevalent in elderly women, affecting 2-3% of older women.

Second to diabetes as the most common endocrine disorder.

Prevalence as high as 18 cases per 1,000 persons in the general population.

Prevalence in general population approximately 4%.

Even mild hypothyroidism causes elevations in plasma TSH and a level of >20 mcU/mL establishes the diagnosis of primary hypothyroidism.

Once the diagnosis of primary hypothyroidism is made additional imaging or serologic testing is unnecessary.

Most otherwise healthy patients with hypothyroidism require thyroid hormone replacement in a dosage of 1.7mcg per kg per day .10 to 0.15 mg per day of levothyroxine), with requirements falling to 1 mcg per kg per day in the elderly.

Levothyroxine should be initiated in older patients and those at risk for cardiovascular compromise at 0.025 mg per day and increased by increments of .025-.05 mg every four to six weeks until TSH level is normal.

Subclinical hypothyroidism defined as the presence of a high serum TSH with a normal serum T4 level and is found in up the 10% of a screened population.

Subclinical hypothyroidism defined as a TSH level >5microIU/mL with a normal thyroxine level and is detected in 6-10% of women and 3% of men.

Subclinical hypothyroidism not well correlated with adverse clinical outcomes or of benefits of treatment.

In patients with subclinical hypothyroidism and antithyroid antibodies 5-7% progress to symptomatic hypothyroidism.

Subclinical hypothyroidism, mild thyroid failure, prevalence increases with age and is higher in women.

Subclinical hypothyroidism associated with impaired iron absorption.

Subclinical hypothyroidism prevalence after the sixth decade of life in men approaches that of women and has a combined prevalence of 10%.

Subclinical hypothyroidism prevalence in 8-10% and in 17% of women age 45-74 years and 75 years or older, respectively and in 6.2% of men older than 65 (Turnbridge WM et al).

Subclinical hypothyroidism associated with antithyroid antibodies in 80% of patients and 80% of patients with subclinical hypothyroidism the TSH level is less than 10 mIU/L.

Before the diagnosis os subclinical hypothyroidism can be established, other causes of elevated TSH must be excluded, including recovery of nonthyroidal disease, presence of heterophile antibodies that may interfere with the TSH assay, formation of biologically inactive TSH and thyroid resistance.

The major concern for subclinical is a progression to overtand the development of hyperlipidemia, cognitive impairment, cardiovascular events, but clinical studies does not support these concerns, and in some studies patients over the age of 85 yearsthis entity may be associated with prolonged survival (Takashima N).

In a study of 2290 community dwelling residents ages 70-79 with increased TSH levels and functionally mobile, and who were not taking thyroid medication: it was found that mild subclinical hypothyroidism was associated with better mobility(Simonsick EM).

Meta analyses indicate subclinical hypothyroidism associated with increased cardiovascular events and mortality, particularly in young to middle age individuals.

Hypothyroidism is a recognized cause of pulmonary hypertension, and treatment of this disorder can lead to reductions and pulmonary pressures.

Hypothyroidism can impair cardiac contractility, which improves with replacement therapy.

Respiratory muscles are affected by hypothyroidism and can explain hypercapnia.

Commonly associated with anemia, which is associated with a lower metabolic rate and leads to low oxygen extraction by tissues and decreased secretion of original point.

Anemia is typically normocytic when associated with hypothyroidism.

With age there is a shifting increased concentration of TSH (Surks MI).

Serum thyrotropin levels greater than 10mIU/L associated with elevated serum cholesterol levels.

Myxedema refers to patients with severe hypothyroidism.

Cretinism occurs in untreated congenital hypothyroidism with the patient presenting with mental retardation, short stature, deafness, and facial abnormalities.

The Leiden 85-Plus Study found no association between TSH levels and prevalence of disability in activities of daily living and those with higher TSH levels had less decline in activities of daily living over four years (Takashima N).

Level of sex hormone binding globulin is low.

Emergency treatment needed if bradycardia,, hypoventilation, hypothermia, or hypotension is present.

Treatment can exacerbate the presence of underlying cardiovascular disease.

Hypothyroidism may develop in end-stage renal disease, due to metabolic derangements associated with progressive uremia.

Hydrocortisone is given in emergency treatment of hypothyroidism because impaired adrenal function is present in severe disease.

Hypothyroidism and pregnancy associated with miscarriage, preterm delivery and reduced cognitive function in children.

Maternal hypothyroidism is associated with reduced IQ performance in children, and women with an elevated thyrotropin level in the 2nd trimester of pregnancy had children with IQ scores at age 7-9 years on average 4 points lower than children of euthyroid women.

About 15-20% of individuals taking levothyroxine are over treated and develop a low thyrotropin level.

Over treatment of hypothyroidism associated with increased risk of fractures and atrial fibrillation.

It is recommended that consideration of levothyroxine therapy be initiated at thyrotropin levels of 10 mIU/L or less when clear symptoms of hypothyroidism, positive thyroid antibodies, or evidence of atherosclerotic cardiovascular disease or heart failure is present.

Consumptive hypothyroidism is a result of accelerated degradation of circulating thyroid hormone at rates that exceed synthetic capacity of normal thyroid gland: seen in children with infantile hemangiomas and adults with massive GIST tumor burden.

In GIST tumors there is thyroid hormone inactivating D3 enzyme in tumors.

Treatment is managed by long term thyroid hormone replacement therapy.

Synthetic levothyroxine is often the initial drug of choice.

Comorbidities and the medication interactions can affect the absorption of levothyroxine and therefore the drugs efficacy.

Thyrotropin helps evaluate the efficacy of thyroid replacement therapy.

Routine measurement of thyrotropin levels allows for medication titration with the goal of euthyroidism.

Elevated thyrotropin levels in the setting of levothyroxine therapy may belie inadequate replacement for reasons other than suboptimal dosing.

Levothyroxine absorption occurs mostly in the small intestine at the jejunum and ileum.

Optimal absorption of thyroid occurs when the stomach is empty because gastric acid supports absorption.

The patient should take levothyroxine 60 minutes before food intake.

Cholestyramine inhibits the absorption of levothyroxine, as does ferrous sulfate, sucralfate, calcium carbonate, and proton pump inhibitors.

Comorbidities that affect absorption of levothyroxine include small bowel resection, inflammatory bowel disease, celiac disease, lactose intolerance, Helicobacter pylori infection, small intestine bacterial overgrowth and chronic gastritis.

Pregnancy and estrogen therapy increase thyroxine binding globulin and decreases free thyroxine and often requires dosage adjustment.