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Clinical Pathology

Disorders of Thyroid Gland: Hypothyroidism & Hyperthyroidism

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Disorders of Thyroid Gland: Hypothyroidism & Hyperthyroidism
Disorders of Thyroid Gland: Hypothyroidism & Hyperthyroidism

Among the endocrine disorders, disorders of the thyroid are common and are only next in frequency to diabetes mellitus. They are more common in women than in men. Functional thyroid disorders can be divided into two types depending on the activity of the thyroid gland: hypothyroidism (low thyroid hormones), and hyperthyroidism (excess thyroid hormones).

Any enlargement of the thyroid gland is called as a goiter. Terminology related to thyroid disorders is shown in Box 863.1.

Box 863.1 Terminology in thyroid disorders
  • Primary hyper-/hypothyroidism: Increased or decreased function of thyroid gland due to disease of thyroid itself and not due to increased or decreased levels of TRH or TSH.
  • Secondary hyper-/hypothyroidism: Increased or decreased function of thyroid gland due to increased or decreased levels of TSH.
  • Tertiary hypothyroidism: Decreased function of thyroid gland due to decreased function of hypothalamus.
  • Subclinical thyroid disease: A condition with abnormality of thyroid hormone levels in blood but without specific clinical manifestations of thyroid disease and without any history of thyroid dysfunction or therapy.
  • Subclinical hyperthyroidism: A condition with normal thyroid hormone levels but with low or undetectable TSH level.
  • Subclinical hypothyroidism: A condition with normal thyroxine and triiodothyronine level along with mildly elevated TSH level.

Hyperthyroidism

Hyperthyroidism is a condition caused by excessive secretion of thyroid hormone. Causes of hyperthyroidism are listed in Table 863.1.

Table 863.1: Causes of hyperthyroidism
  1. Graves’ disease (Diffuse toxic goiter)
  2. Toxicity in multinodular goiter
  3. Toxicity in adenoma
  4. Subacute thyroiditis
  5. TSH-secreting pituitary adenoma (secondary hyperthyroidism)
  6. Trophoblastic tumours that secrete TSH-like hormone: choriocarcinoma, hydatidiform mole
  7. Factitious hyperthyroidism

Clinical Characteristics

Clinical characteristics of hyperthyroidism are nervousness, anxiety, irritability, insomnia, fine tremors; weight loss despite normal or increased appetite; heat intolerance; increased sweating; dyspnea on exertion; amenorrhea and infertility; palpitations, tachycardia, cardiac arrhythmias, heart failure (especially in elderly); and muscle weakness, proximal myopathy, and osteoporosis (especially in elderly).

The triad of Graves’ disease consists of hyperthyroidism, ophthalmopathy (exophthalmos, lid retraction, lid lag, corneal ulceration, impaired eye muscle function), and dermopathy (pretibial myxoedema).

Box 863.2: Thyroid function tests in hyperthyroidism
  • Thyrotoxicosis:
    – Serum TSH low or undetectable
    – Raised total T4 and free T4.
  • T3 toxicosis:
    – Serum TSH undetectable
    – Normal total T4 and free T4
    – Raised T3

Laboratory Features

In most patients, free serum T3 and T4 are elevated. In T3 thyrotoxicosis (5% cases of thyrotoxicosis), serum T4 levels are normal while T3 is elevated. Serum TSH is low or undetectable (< 0.1 mU/L) (Box 863.2).

Undetectable or low serum TSH along with normal levels of T3 and T4 is called as subclinical hyperthyroidism; subtle signs and symptoms of thyrotoxicosis may or may not be present. Subclinical hyperthyroidism is associated with risk of atrial fibrillation, osteoporosis, and progression to overt thyroid disease.

Features of primary and secondary hyperthyroidism are compared in Table 863.2.

Table 863.2: Differences between primary and secondary hyperthyroidism
ParameterPrimary hyperthyroidismSecondary hyperthyroidism
Serum TSH Low Normal or high
Serum free thyroxine High High
TSH receptor antibodies May be positive Negative
Causes Graves’ disease, toxic multinodular goiter, toxic adenoma Pituitary adenoma

Evaluation of hyperthyroidism is presented in Figure 863.1.

Evaluation of hyperthyroidism
Figure 863.1: Evaluation of hyperthyroidism. TSH: thyroid stimulating hormone; FT4: free T4; FT3: free T3; TRAb: TSH receptor antibody; TRH: Thyrotropin releasing hormone

Hypothyroidism

Hypothyroidism is a condition caused by deficiency of thyroid hormones. Causes of hypothyroidism are listed in Table 863.3. Primary hypothyroidism results from deficient thyroid hormone biosynthesis that is not due to disorders of hypothalamus or pituitary. Secondary hypothyroidism results from deficient secretion of TSH from pituitary. Deficient or loss of secretion of thyro-tropin releasing hormone from hypothalamus results in tertiary hypothyroidism. Secondary and tertiary hypothyroidism are much less common than primary. Plasma TSH is high in primary and low in secondary and tertiary hypothyroidism. Differences between primary and secondary hypothyroidism are shown in Table 863.4.

Table 863.3: Causes of hypothyroidism
  1. Primary hypothyroidism (Increased TSH)
    • Iodine deficiency
    • Hashimoto’s thyroiditis
    • Exogenous goitrogens
    • Iatrogenic: surgery, drugs, radiation
  2. Secondary hypothyroidism (Low TSH): Diseases of pituitary
  3. Tertiary hypothyroidism (Low TSH, Low TRH): Diseases of hypothalamus
Table 863.4: Differences between primary and secondary hypothyroidism
ParameterPrimary hypothyroidismSecondary hypothyroidism
Cause Hashimoto’s thyroiditis Pituitary disease
Serum TSH High Low
Thyrotropin releasing hormone stimulation test Exaggerated response No response
Antimicrosomal antibodies Present Absent
Box 863.3: Thyroid function tests in hypothyroidism
  • Primary hypothyroidism
    – Serum TSH: Increased (proportional to degree of hypofunction)
    – Free T4: Decreased
    – TRH stimulation test: Exaggerated response>
  • Secondary hypothyroidism
    – Serum TSH: Decreased
    – Free T4: Decreased
    – TRH stimulation test: Absent response
  • Tertiary hypothyroidism
    – Serum TSH: Decreased
    – FT4: Decreased
    – TRH stimulation test: Delayed response

Clinical features of primary hypothyroidism are: lethargy, mild depression, disturbances in menstruation, weight gain, cold intolerance, dry skin, myopathy, constipation, and firm and lobulated thyroid gland (in Hashimoto’s thyroiditis).

In severe cases, myxoedema coma (an advanced stage with stupor, hypoventilation, and hypothermia) can occur.

Laboratory Features

Laboratory features in hypothyroidism are shown in Box 863.3.

Normal serum thyroxine (T4 and FT4) coupled with a moderately raised TSH (>10 mU/L) is referred to as subclinical hypothyroidism. It is associated with bad obstetrical outcome, poor cognitive development in children, and high risk of hypercholesterolemia and progression to overt hypothyroidism.

Evaluation of hypothyroidism is presented in Figure 863.2

Evaluation of hypothyroidism
Figure 863.2: Evaluation of hypothyroidism. TSH: thyroid stimulating hormone; FT4: free T4; TRH: Thyrotropin releasing hormone

References

  • Demers LM. Thyroid disease: pathophysiology and diagnosis. Clin Lab Med 2004;24:19-28.
  • Heuck CC, Kallner A, Kanagasabapathy AS, Riesen W. Diagnosis and monitoring of diseases of thyroid. World Health Organization. 2000 WHO/DIL/0.004.
  • Kaplan MM. Clinical perspectives in the diagnosis of thyroid disease. Clin Chem 1999;45:1377-83
  • Lazarus JH, Obuobie K. Thyroid disorders—an update. Postgrad Med J 2000;76:529-36.
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