eMedicine Specialties > Endocrinology > Thyroid
Hypothyroidism: Differential Diagnoses & Workup
Updated: Jul 23, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Other Problems to Be Considered
The list of differential diagnoses for hypothyroidism is long because the most frequent presenting symptoms are nonspecific.
Workup
Laboratory Studies
Third-generation TSH assays are readily available and are generally the most sensitive screening tool for primary hypothyroidism.
The generally accepted reference range for normal serum TSH is 0.40-4.2 mIU/L. In NHANES III (1988-1994), of 17,353 people evaluated, 80.8% had a serum TSH below 2.5 mIU/L; TSH concentrations rose with advancing age.7
TSH levels peak in the evening and are lowest in the afternoon, with marked variations due to physiologic conditions such as illness, psychiatric disorders, and low energy intake.
If TSH levels are above the reference range, the next step would be to measure total T4 with a measure of binding proteins. Thyroxine is highly protein bound (99.97%) with approximately 85% bound to thyroid-binding globulin (TBG), approximately 10% bound to transthyretin or thyroid-binding prealbumin, and the remainder bound loosely to albumin.
The levels of these binding proteins can vary by hormonal status, inheritance, and in various disease states. Hence, free T4 assays are becoming popular as they measure unbound (ie, free hormone). However, free T4 assays can be unreliable in the setting of severe illness. No currently available kit actually measures unbound T4 directly. Free thyroid hormone levels can be estimated by calculating the percentage of available thyroid hormone-binding sites (T3 resin uptake) or by measuring the concentration of TBG. A free thyroxine index (FTI) serves as a surrogate of the free hormone level. The FTI is the product of the T3 resin uptake and total T4 levels.
Patients with primary hypothyroidism have elevated TSH levels and decreased free hormone levels. Patients with elevated TSH levels but normal free hormone levels or estimates are considered to have mild or subclinical hypothyroidism.
Primary hypothyroidism is virtually the only disease that is characterized by sustained, rising TSH levels. As the TSH level increases early in the disease, an increased conversion of T4 to T3 occur, this maintains T3 levels. In early hypothyroidism, TSH levels are increased, T4 levels are normal to low, and T3 levels are normal.
Evaluation of the presence of thyroid autoantibodies (antimicrosomal or anti-TPO antibodies) and antithyroglobulin (anti-Tg) may be helpful in determining the etiology of hypothyroidism or in predicting future hypothyroidism. In addition, anti-TPO antibodies have been associated with a higher risk of infertility and miscarriage.
In patients with nonthyroid disease who are severely ill, TSH secretion is normal or decreased, total T4 levels are decreased, and total T3 levels are markedly decreased. This can be confused with secondary hypothyroidism. In these patients, the primary abnormality is the decreased peripheral production of T3 from T4. They have an increased reverse T3, which can be measured. Other abnormalities seen in patients who are critically ill include decreased TBG levels and abnormalities in the hypothalamic-pituitary axis. During recovery, some patients have transient elevations in serum TSH concentrations (up to 20 mIU/L). Hence, thyroid function should not be evaluated in a critically ill person unless thyroid dysfunction is strongly suspected, and, if so, screening with TSH alone is insufficient.
In patients with hypothalamic or pituitary dysfunction, TSH levels do not increase in appropriate relation to the low free T4 levels. The absolute levels may be in the normal or even slightly elevated range but inappropriately low for the severity of the hypothyroid state. Hence, when secondary or tertiary hypothyroidism is suspected, a serum TSH measurement alone is inadequate; a free T4 should be measured.
The TRH stimulation test is rarely needed currently because of improved TSH assays.
Imaging Studies
Ultrasonographic scanning of the neck and thyroid can be used to detect nodules and infiltrative disease. It has little use in hypothyroidism per se unless a secondary anatomic lesion in the gland is of clinical concern. Hashimoto thyroiditis is usually associated with a heterogeneous ultrasonographic image. It can be rarely associated with lymphoma of the thyroid. Serial images with fine-needle aspiration of suspicious nodules may be useful.
Radioactive iodine uptake (RAIU) and thyroid scanning are not useful in hypothyroidism because these tests require some level of endogenous function in the hypofunctioning gland to provide information. Patients with Hashimoto thyroiditis may have relatively high early uptake (after 4 h) but do not have the usual doubling of uptake at 24 hours consistent with an organification defect.
Patients undergoing whole-body F18-fluorodeoxyglucose positron emission tomography (FDG-PET) for nonthyroid disease often show significant thyroid uptake as an incidental finding.8 In general, diffuse uptake by the thyroid on FDG-PET is considered a benign finding and is typical of thyroiditis and/or hypothyroidism.
Procedures
Fine-needle aspiration biopsy
Thyroid nodules are often found incidentally during physical examination, chest radiograph, CT scan, or MRI. Thyroid nodules can be found in patients who are hypothyroid, euthyroid, or hyperthyroid. Fine-needle aspiration (FNA) biopsy is the procedure of choice to evaluate suspicious nodules.
About 5-6% of solitary nodules are malignant. Suspicious nodules are those that are larger than 1 cm in diameter or those with suspicious features found on a sonogram (eg, irregular margins, intranodular vascular spots, microcalcifications).
Risk factors for thyroid nodules include age greater than 60 years, history of head or neck irradiation, or family history of thyroid cancer.
Histologic Findings
Autoimmune thyroiditis causes a decrease in intrathyroidal iodine stores, an increased iodine turnover, and defective organification. Chronic inflammation of the gland causes progressive destruction of the functional tissue with widespread infiltration by lymphocytes and plasma cells with epithelial cell abnormalities. In time, dense fibrosis and atrophic thyroid follicles replace the initial lymphocytic hyperplasia and vacuoles. Functional tissue destruction and infiltration may also be caused by previous administration of radioiodine, surgical fibrosis, metastasis, lymphomatous changes, sarcoidosis, tuberculosis, amyloidosis, cystinosis, thalassemia, and Riedel thyroiditis.
More on Hypothyroidism |
| Overview: Hypothyroidism |
 Differential Diagnoses & Workup: Hypothyroidism |
| Treatment & Medication: Hypothyroidism |
| Follow-up: Hypothyroidism |
| References |
| Further Reading |
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Further Reading
Related eMedicine topics:
Autoimmune Thyroid Disease and Pregnancy
Congenital Hypothyroidism
Embryology of the Thyroid and Parathyroids
Hyperthyroidism [Endocrinology]
Hyperthyroidism [Pediatrics: General Medicine]
Hypothyroidism [Pediatrics: General Medicine]
Hypothyroidism and Myxedema Coma
Hypothyroid Myopathy
Thyroid Anatomy
Thyroid Disease
Thyroid Nodules
Clinical guidelines:
Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. The Endocrine Society - Disease Specific Society. 2007. 79 pages. NGC:005884
Screening for congenital hypothyroidism: U.S. Preventive Services Task Force reaffirmation recommendation statement. United States Preventive Services Task Force - Independent Expert Panel. 1996 (revised 2008 Mar). 6 pages. NGC:006354
Screening for thyroid disease: recommendation statement. United States Preventive Services Task Force - Independent Expert Panel. 1996 (revised 2004 Jan 20). 7 pages. NGC:003266
Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. Consensus Conference Panel on Subclinical Thyroid Disease - Independent Expert Panel. 2004 Jan 14. 11 pages. NGC:003902
Update of newborn screening and therapy for congenital hypothyroidism. American Academy of Pediatrics - Medical Specialty Society
American Thyroid Association - Professional Association. 2006 Jun. 14 pages. NGC:005029
Clinical trials:
Evaluation of Patients With Thyroid Disorders
Generic vs. Name-Brand Levothyroxine
Growth Hormone and GnRH Agonist in Adolescents With Acquired Hypothyroidism
Maternal Hypothyroidism in Pregnancy
Neurocognitive and Metabolic Effects of Mild Hypothyroidism
Keywords
hypothyroidism, thyroid, thyroiditis, thyroid hormone, thyroid function, thyroid nodule, thyroid treatment, thyroid goiter, thyroid medication, thyroid medicine, thyroid problem, myxedema coma, cretinism, hypothyrosis, hypothyroidea, thyrotropin, TSH, tertiary hypothyroidism, thyrotropin releasing-hormone, TRH, thyroxine, T4, triiodothyronine, T3, Hashimoto disease, Hashimoto thyroiditis, primary hypothyroidism, secondary hypothyroidism, congenital hypothyroidism, cold intolerance, weight gain, menstrual disturbances, periorbital puffiness, goiter, autoimmune thyroiditis, iodine deficiency, de Quervain thyroiditis, subacute thyroiditis, postpartum autoimmune thyroid disease, amiodarone, interferon alpha, thalidomide, stavudine, central hypothyroidism, subclinical hypothyroidism
