Subclinical hypothyroidism: Causes, Symptoms, Diagnosis, Treatment and Prediction

Also called mild thyroid failure, it refers to a state in which patients do not show the symptoms of hypothyroidism.

These patients also have an average amount of circulating thyroid hormone.

The only abnormality is an increase in TSH in your blood test.

This implies that the pituitary gland is working very hard to maintain an average circulating thyroid hormone level. The thyroid gland requires additional stimulation by the pituitary gland to produce adequate hormones.

It can be expected that most of these patients progress to hypothyroidism, especially if the TSH is above a certain level.

This condition occurs between 3% and 8% of the general population. It is more common in women than men, increasing with age.

The possibility of it being a cardiovascular risk factor has been debated.


Large-scale randomized studies are needed for evidence-based recommendations regarding detecting mild thyroid insufficiency and levothyroxine therapy for this condition.

One of the myths surrounding subclinical hypothyroidism is that the laboratory profile of elevated serum TSH and normal free thyroid hormone levels represents “compensated hypothyroidism.”

The reasoning behind this idea is that, since the circulating levels of thyroid hormones are within the normal range with only elevated serum TSH, the affected subject is euthyroid because the TSH increase stimulates and causes the thyroid gland to produce normal levels of thyroid hormone.

Certainly, elevated serum TSH levels stimulate even a diseased thyroid gland to produce and release more thyroid hormone.

However, as long as the serum TSH level remains elevated, thyroid hormone levels are not genuinely normal for that individual.

The kinetics of eliminating thyroid hormones and TSH from the circulation makes such a conclusion inevitable.


The causes of subclinical hypothyroidism are similar to those of hypothyroidism. The most common cause is autoimmune thyroid disease.

Patients with a family history of autoimmune thyroid disease have an increased risk of developing subclinical and overt hypothyroidism.

Subclinical hypothyroidism can occur after any thyroid injury, such as after a partial thyroidectomy for a thyroid nodule or radioactive iodine therapy for hyperthyroidism.

Medications that alter thyroid function, such as iodine and iodine-containing medications, can induce hypothyroidism, which, to begin with, can be subclinical.

It can also occur in the case of pituitary tumors and some more rare genetic diseases, such as mutations of the TSH receptor gene.

Clinical manifestations


Mild thyroid insufficiency is often asymptomatic; however, almost 30% of patients with this condition may have symptoms suggesting a deficiency of thyroid hormone.

The prevalence study of Colorado’s thyroid disease measured serum TSH levels and conducted symptom surveys in more than 25,000 residents of the state.

Elevated serum TSH values ​​were found in 9.5% of all subjects and 8.9% of those not yet under thyroid hormone treatment.

75% of these individuals had serum TSH levels of 5-10 mU / L.

In response to a validated survey regarding the symptoms of thyroid hormone deficiency, the 2,336 subjects who identified with mild thyroid failure reported that they most often had:

  • Dry Skin.
  • Poor memory
  • Slow thinking
  • Muscular weakness.
  • Fatigue.
  • Muscle cramps.
  • Intolerance to the cold.
  • Swollen eyes.
  • Constipation and hoarseness

It is important to note that while euthyroid subjects experienced an average of 12.1% of all symptoms listed, overtly hypothyroid issues had 16.6% of these symptoms, and subjects with mild thyroid insufficiency reported an intermediate 13.7% of symptoms.

This suggests a “dosage effect” between thyroid hormone levels and symptoms.

According to these findings, a Swiss study involving 332 women reported that 24% of the 93 subjects with mild thyroid insufficiency exhibited typical symptoms of hypothyroidism.

These studies also emphasize the difficulty of diagnosing primary hypothyroidism using only clinical symptoms.

Euthyroid subjects and patients with mild or overt hypothyroidism had constellations of similar symptoms.

Despite the statistical significance in large groups, it may be difficult for an individual patient to distinguish a euthyroid subject from one with mild or overt thyroid disease.

Neurobehavioral abnormalities and neuromuscular function:

Other cross-sectional studies have shown neurobehavioral and specific neuromuscular dysfunction in patients with mild thyroid insufficiency.

It has been reported that depression, memory loss, cognitive decline, and various neuromuscular conditions occur more frequently in patients.

Objective dysfunction of the peripheral nerve, manifested by decreased conduction amplitude in peripheral nerves and an abnormal stapedial reflex, has been demonstrated in these patients.

Skeletal muscle abnormalities, including elevated serum creatine phosphokinase levels, increased circulating lactate levels during exercise, and repetitive discharges in surface electromyography, have also been reported.

Finally, there is intriguing evidence that mild thyroid insufficiency in pregnant women may result in the reduced intellectual development of their euthyroid offspring.

Cardiac-pulmonary function:

It has been reported that myocardial function in several studies is subtly altered in patients with mild thyroid insufficiency.

At rest during exercise, the functional abnormalities identified include impaired myocardial contractility and diastolic dysfunction.

It has also been shown that the texture of the myocardium is abnormal by video densitometric analysis.

In a comprehensive study of exercise capacity, it was observed that patients with mild thyroid insufficiency had a significant deterioration of stroke-related stroke volume, cardiac index, and maximum aortic flow velocity.

Pulmonary tests in these patients revealed decreased vital capacity, reduced anaerobic thresholds, and decreased oxygen uptake at the anaerobic threshold.

These data clearly show that the cardiovascular function in mild thyroid insufficiency is slightly altered and is not identical to that of the euthyroid state.

The critical question is whether these differences result in clinically significant performance impairment in affected patients.

Cardiovascular risk factor:

Mild thyroid insufficiency has been widely evaluated as a cardiovascular risk factor.

It has been shown that the condition is associated with elevated serum levels of total cholesterol and low-density lipoprotein cholesterol (LDL) in most, but not all, studies and with high density reduced lipoprotein cholesterol in some studies.

Some reports have suggested that even high serum TSH values ​​can adversely affect serum lipid and lipoprotein levels.

The relationship between TSH and LDL cholesterol appears to be more significant in individuals with underlying insulin resistance.

A recent study reported that patients with mild thyroid insufficiency, and even subjects with high values ​​of normal serum TSH, have evidence of endothelial dysfunction, manifested by flow-mediated endothelium-dependent vasodilation.

An older case-control study involving older women suggested an association between mild thyroid insufficiency and peripheral vascular disease.

A 20-year follow-up study of the original Whickham Survey found no association between initial hypothyroidism, elevated serum levels of TSH or antithyroid antibodies, and the development of coronary artery disease.

In contrast, a more recent report from the Rotterdam Study concluded that patients with mild thyroid insufficiency have a significantly higher prevalence of aortic atherosclerosis and myocardial infarction.

After adjustment for multiple known risk factors for coronary artery disease, the authors found that mild thyroid insufficiency is an independent risk factor and of equal importance for myocardial infarction.


The thyroid hormones typically measured are free thyroxine ‘T4’, total triiodothyronine ‘T3’, and the thyroid-stimulating hormone ‘TSH,’ which is released from the pituitary gland.

TSH begins to increase when the pituitary gland recognizes a short supply of thyroid hormone.

Subclinical hypothyroidism is diagnosed only if the TSH level is elevated above the average, typically around 4.5 mU / L, but the measured circulating thyroid hormones (T4 and T3) fall within the normal range.

Most patients with serum TSH reach ten mU / L, but they are asymptomatic even if they get to this point.

The typical pattern of laboratory tests for subclinical hypothyroidism may be different in the case of the pituitary disease in which TSH production is affected.

In the case of pituitary tumors with subclinical hypothyroidism, blood tests may show a low, inappropriately normal, or slightly elevated TSH.


Sometimes, a laboratory test suggesting subclinical hypothyroidism can spontaneously normalize over 6 to 12 months.

If patients have many symptoms suggestive of thyroid hormone deficiency, one may consider starting treatment with thyroid hormone to see if symptoms are alleviated.

However, replacing thyroid hormone in patients with subclinical hypothyroidism with moderate TSH elevations, especially if they are higher than 8-10 mIU / L, is not always the best-recommended approach, especially in elderly patients with cardiac arrhythmias or at risk of arrhythmias, and in patients with osteoporosis.

An individualized decision is made in each case, and your doctor will discuss the risks and benefits of the treatment in each case.

The goal of treatment is to replace a sufficient amount of thyroid hormone to reduce TSH within the normal range.

Subclinical hypothyroidism is always treated during pregnancy and preferably when a patient tries to conceive.

Hypothyroidism in pregnancy is treated differently than in people who are not pregnant.

It is recommended to consult your endocrinologist as soon as you know you are pregnant if you were previously informed that you have subclinical hypothyroidism.

The decision to treat subclinical hypothyroidism when TSH is less than ten mIU / L is based on the patient’s presentation.

Symptoms and clinical signs, other comorbidities such as cardiovascular disease, lipid abnormalities, and osteoporosis are important factors that must be considered when making this decision.


Many patients with subclinical hypothyroidism eventually progress to overt hypothyroidism.

Some factors that may suggest an increased risk of progression to overt hypothyroidism are the presence of antithyroid antibodies and high TSH levels greater than 12 mU / L.

The risk of developing hypothyroidism in women with positive antibodies and high TSH is around 4% per year compared to 2% -3% per year with a single risk factor.

Spontaneous recovery can occur in patients with subclinical hypothyroidism, but the frequency is unknown.

Patients with lower TSH levels are more likely to have a spontaneous recovery.