At a Glance

Patients with thyroid stimulating hormone (TSH) deficiency, one type of central hypothyroidism, often present with symptoms similar to the more common primary hypothyroidism, including fatigue, lethargy, cold intolerance, and weight gain.

Other symptoms of hypothyroidism seen in TSH deficiency include brittle fingernails; coarsening and thinning hair; puffy eyes; pale, dry skin; weakness; and constipation. Hoarseness; menstrual disorders; puffy hands, face and feet; thickening of the skin; thinning of eyebrows; increased cholesterol levels; muscle and/or joint aches and stiffness; slowed speech; and decreased hearing are symptoms usually expressed later in the course of the disease. There are no symptoms that differentiate TSH deficiency from other types of hypothyroidism. TSH deficiency is however more difficult to diagnose than primary hypothyroidism because in the case of TSH deficiency TSH levels cannot be used as a guide.

Most patients with central hypothyroidism also have findings consistent with deficiency or excess of other pituitary hormones (see chapter on hypopituitarism). The most common cause of central hypothyroidism is pituitary mass lesions. Treatment, such as surgery or radiation therapy for these lesions, can also lead to central hypothyroidism. Other causes include pituitary tumor, anatomical defect, gland regression, and genetics.

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In some rare cases, patients present with TSH deficiency and no findings of any other pituitary hormonal deficiency or pituitary abnormality. This instance is known as isolated TSH deficiency.

There have been cases, although rare, of a congenital form of isolated TSH deficiency. Patients with congenital isolated TSH deficiency shows signs of cretinism such as mental and growth retardation (see chapter on congenital hypothyroidism).

Another very rare cause of isolated TSH deficiency is drug-induced TSH deficiency and is seen in patients treated with a retinoid X receptor ligand (bexarotene), which selectively inhibits TSH secretion.

Although cases of isolated TSH deficiency, congenital isolated TSH deficiency, and drug-induced isolated TSH deficiency have occurred, by far the majority of patients with TSH deficiency hypothyroidism have coexisting deficiencies in other pituitary hormones.

There also exists a transient form of central hypothyroidism. This condition can occur in three clinical situations:

  • Serum TSH levels can remain low for a period of time after treatment of hyperthyroidism with an antithyroid drug, radioiodine, or surgery. Serum free T4 (FT4) can also be affected and fall below normal during this time.
  • Serum TSH concentrations may also be low after the discontinuation of T4 therapy.
  • Lastly, patients with severe nonthyroidal illness can have transient central hypothyroidism.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

To diagnosis TSH deficiency, FT4 and TSH tests should be performed. Serum FT4 levels will be low, and serum TSH levels will be inappropriately low, normal, or possibly even slightly elevated (up to 10mU/L).

The use of thyrotropin releasing hormone (TRH)-stimulation testing has decreased substantially due to greater sensitivity of TSH tests, but TRH stimulation can still be beneficial in diagnosing central hypothyroidism. Central hypothyroidism is characterized by a blunted TRH response (<2 fold rise). Normally, TSH would rise 2-4 times above baseline, but the same blunted TRH response can be seen in subclinical hyperthyroidism and general pituitary failure.

In particular, TRH stimulation has been recommended in the diagnosis of congenital central hypothyroidism in neonates so that appropriate therapeutic intervention can be undertaken quickly.

A normal increase in prolactin is seen after TRH stimulation in isolated TSH deficiency.

Patients with central hypothyroidism lack a nocturnal surge of TSH.

MRI of the pituitary and hypothalamic region should also be performed in patients with evidence of central hypothyroidism,

Patients with isolated TSH deficiency sometimes show the presence of anti-pituitary antibody.

Mutations in gene coding for the TSH-beta subunit can cause an isolated congenital TSH deficiency. Specifically, these patients have a single base substitution in the amino acid sequence regulating the TSH-beta subunit.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Misinterpretation due to the inclusion of biologically inactive TSH isoforms in TSH assays can lead to a missed diagnosis of central hypothyroidism. TSH assays include biologically inactive TSH isoforms, which are secreted when the pituitary is damaged or when hypothalamic TRH stimulation is deficient.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Patients with either central or primary hypothyroidism can exhibit low FT4 levels and slightly high TSH levels; therefore, it is important to differentiate between the two diagnoses. Serum antithyroid peroxidase (TPO) antibody concentration is one test that can be used to differentiate between central and primary hypothyroidism. In primary hypothyroidism, TPO levels are increased, whereas the absence of anti-TPO antibodies in conjunction with other pituitary hormone abnormalities suggests central hypothyroidism.

Hyperprolactinemia may be present in both central and primary hypothyroidism.

Patients with central hypothyroidism may need higher doses of T4 than those with primary hypothyroidism.

Pituitary-adrenal function should be evaluated before a patient with central hypothyroidism starts T4 therapy. T4 may accelerate cortisol metabolism. If a patient who also has adrenal insufficiency receives T4 before adrenal hormone replacement, an adrenal crisis could occur.