Endocrinology Metabolism

Primary hypothyroidism in adults

Are you sure your adult patient has primary hypothyroidism?

Establishing the diagnosis of hypothyroidism is, with a few very important caveats, straightforward. The decision to test for hypothyroidism should be based on various aspects of the clinical picture. Hypothyroidism can present in a myriad of ways. In mild hypothyroidism, there may be only one or two vague symptoms to suggest the diagnosis. As the disease progresses, more symptoms and subtle signs appear. The challenge is to decide who should be tested for hypothyroidism, as there is no single “typical” case.

In addition to the more common presentations, Tachman and Guthrie have described six rare but distinctive presentations of hypothyroidism. They include a patient with intestinal pseudo-obstruction due to poor visceral muscle tone, a woman with a von Willebrand-like bleeding disorder, another woman with pituitary enlargement, a 32 year old man with coronary artery disease hyperlipidemia and hypertension, a 38 year old woman with seizures and ataxia, and a 56 year old woman with striking cognitive and memory deficits and behavioral changes (myxedema madness).

Symptoms of hypothyroidism

There are many symptoms associated with hypothyroidism. These include puffy eyes, cold intolerance, coarse hair, constipation, poor memory, slow thinking, muscle cramps, weak muscles, depression, dry skin, and hypersomnolence. However, few are specific, and moreover, there are no symptoms that occur in all patients with hypothyroidism. Many chronic symptoms that appear to be typical of hypothyroidism also occur in euthyroid people.

Furthermore, symptoms that are more suggestive of hypothyroidism may occur only in a minority of hypothyroid patients. Specific symptoms often considered to be quite characteristic of hypothyroidism, particularly irregular menses and weight gain, may actually not be helpful in distinguishing between hypothyroid and euthyroid patients.

Signs of hypothyroidism

There are also many signs associated with hypothyroidism, but few, if any, are pathognomonic. Physical signs may be subtle or lacking and are generally related to the severity and duration of low thyroid hormone levels. An underlying reason for many of the signs of hypothyroidism is an increase in the protein-rich interstitial fluid compartment, which may be related to skin “puffiness”, periorbital edema, and the effusions that occur in the pericardial, plural, and peritoneal spaces. Increased interstitial pressure is probably also the basis for entrapment neuropathies, including carpel tunnel syndrome and distal paresthesias.

Other classic but non-specific signs of hypothyroidism are: dry skin, patchy hair loss, bradycardia, and delayed deep tendon relaxation phase. Other physical signs may suggest a history of a condition resulting in hypothyroidism, such as a thyroidectomy scar in the neck. A goiter may be present in patients with primary hypothyroidism that is not caused by surgery or neck radiation.

Causes of Hypothyroidism - Importance of medical and family history

The medical and family history can be very helpful in identifying patients in whom thyroid dysfunction should be assessed. Gender, age, family or personal history of thyroid diseases, recent pregnancy, presence of autoimmune diseases, medications and radiation history should all be noted. Hypothyroidism is far more common in women, and the prevalence of mild hypothyroidism increases in the elderly. Hashimoto’s thyroiditis, an autoimmune disease that is a major cause of hypothyroidism, is a familial disorder. Patients with other types of autoimmune diseases should be screened for thyroid dysfunction.

Pregnancy has an effect on thyroid autoimmunity. Remissions of thyroid dysfunction tend to occur in the second and third trimesters, and exacerbations tend to occur after delivery and in the first trimester. Women with a positive family history of autoimmune thyroid disease and have delivered within the previous year have a high risk for developing postpartum thyroiditis, in which hypothyroidism often occurs. Although it resolves in most patients, approximately 20% of patients with postpartum thyroiditis eventually develop permanent hypothyroidism.

In addition to the antithyroid drugs (methimazole, carbimazole, propylthiouracil), use of certain medications, such as amiodarone, lithium, interferon-α, and tyrosine kinase inhibitors have been associated with the development of hypothyroidism.

A history of Graves’ disease, radioactive iodine treatment or thyroid surgery should prompt thyroid function testing if this has not been recently done. Patients with a history of external radiation therapy, particularly children and adolescents, should have periodic thyroid function testing. Finally, there are also unusual causes of hypothyroidism, such as the "consumptive hypothyroidism" resulting from large hepatic hemangiomas, in which type 3 deiodinase activity is markedly elevated, causing inactivation of circulating thyroid hormones (T4 and T3).

Key laboratory and imaging tests

The diagnostic hallmarks of overt primary hypothyroidism are an elevated serum thyroid stimulating hormone (TSH) and a low serum total T4, free T4, or free thyroxine index (FTI). In early or subclinical hypothyroidism, TSH may be elevated while the free thyroxine is normal, but not high. A diagnosis of hypothyroidism, whether primary or secondary, should never be made on the basis of a TSH test alone. Patients in whom a diagnosis of hypothyroidism is made should have tests for serum anti-thyroid peroxidase (TPO) antibodies to assess for Hashimoto’s thyroiditis. The presence or absence of a goiter should be noted, and ultrasound may also be very useful, particularly in younger patients. A large goiter suggests the rare possibility of an inherited metabolic defect in thyroid hormone synthesis or chronic thyroiditis.

Other tests that may prove helpful diagnostically

Hypothyroidism may be associated with hyponatremia, hyperlipidemia, anemia, and elevations of creatine phosphokinase (CPK), predominately or entirely the MM isoenzyme. Patients with hypothyroidism may have an electrocardiogram showing sinus bradycardia, low voltage complexes, prolonged PR and QT intervals, and flattened or inverted T waves.

Management and treatment of hypothyroidism

Treatment of primary hypothyroidism

Levothyroxine is the preferred treatment of choice for most patients with primary hypothyroidism. The goal in treating primary hypothyroidism is to normalize the serum TSH. A full replacement dose of levothyroxine in adults is about 1.6 mcg/kg. Levothyroxine may be started at a lower dose of 50-75 micrograms a day, but pregnant women and patients in myxedema coma should be given higher doses to achieve the euthyroid state as rapidly as possible.

Conversely, in patients with severe coronary vascular disease and in the elderly, a lower initial dose, 25 to 50 mcg (0.025 to 0.050 mg) is recommended. Patients with hypothyroidism due to postpartum thyroiditis need to be monitored more carefully, as levothyroxine should be withdrawn if the patient becomes spontaneously euthyroid. A similar situation is occasionally encountered in patients with recurrent episodes of silent (painless) thyroiditis.

The symptoms of hypothyroidism in some patients may lag behind the achievement of biochemical euthyroidism. In addition, for reasons that are unclear, Hashimoto’s thyroiditis may be associated with a poorer quality of life, even when thyroid function tests are normal.

In patients who are taking levothyroxine, it is important to be cognizant of use of other medications or supplements which may increase thyroid hormone requirements. Examples include drugs which affect thyroid hormone absorption (calcium, coffee, iron, cholestyramine, colesevelam, sevelamer) and others that affect thyroid hormone metabolism (rifampin, phenytoin, carbamazepine, barbiturates).

In patients with longstanding primary hypothyroidism, it is customary to check a serum TSH once a year. Although the goal is a normal TSH level, it may not always be best to change the dose of thyroid hormone in these patients if the TSH is only mildly elevated or suppressed. Rather, if the patient is clinically euthyroid, the serum TSH can be repeated in 6-10 weeks. If the TSH abnormality persists, the dose of levothyroxine should then be adjusted.

Triiodothyronine (T3) should not be used, alone or in combination with T4, to treat pregnant women with hypothyroidism. Some have recommended combinations of T4 and T3 to treat select patients with hypothyroidism but we do not find convincing medical criteria for identifying such patients.

Treatment of subclinical hypothyroidism

Subclinical hypothyroidism is defined by a mildly elevated serum TSH and a normal serum total T4, free T4, or FT4 index. Although there is considerable debate about the exact cutoff TSH to begin treating subclinical hypothyroidism, small doses of levothyroxine may be administered to patients in whom the pattern of subclinical hypothyroidism is not transient. The exception are elderly patients whose serum TSH is <10 mIU/L and do not have signs, symptoms, or laboratory features of hypothyroidism.

What’s the Evidence?/References

Tachman, ML, Guthrie, GP. "Hypothyroidism: diversity of presentation". Endocr Rev. vol. 5. 1984. pp. 456-465.

(This paper highlights some unusual but very serious presentations of hypothyroidism requiring prompt recognition and treatment.)

Canaris, GJ, Steiner, JF, Ridgway, EC. "Do traditional symptoms of hypothyroidism correlate with biochemical disease". J Gen Intern Med. vol. 12. 1997. pp. 544-550.

(This paper illustrates the fact that patients with and without hypothyroidism may have the same "traditional" symptoms often associated with hypothyroidism but that patients with true hypothyroidism tend to have more of the traditional symptoms.)

Zulewski, H, Muller, B, Exer, P, Miserez, AR, Staub, JJ. "Estimation of tissue hypothyroidism by a new clinical score: evaluation of patients with various grades of hypothyroidism and controls". J Clin Endocrinol Metab. vol. 82. 1977. pp. 771-776.

(Excellent paper on the signs and symptoms of hypothyroidism, highlighting the need for a high index of suspicion as signs and symptoms are not specific and may be subtle, even in patients with biochemically overt hypothyroidism).

Emerson, CH. "Anthropomorphic thyroidopathies". Thyroid. vol. 20. 2010. pp. 1195-1197.

(Patients with obesity may have subtle changes in thyroid function tests but should not receive thyroid hormone unless they also have true hypothyroidism.)

Barbesino, G. "Drugs affecting thyroid function". Thyroid. vol. 20. 2010. pp. 763-770.

(This is a useful review of drugs that induce hypothyroidism and also of drugs that affect the dose requirements for thyroid hormone in patients with hypothyroidism.)

Stagnaro-Green, A, Abalovich, M, Alexander, E, Azizi, F, Mestman, J, Negro, R, Nixon, A, Pearce, EN, Soldin, OP, Sullivan, S, Wiersinga, W. "American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum". Thyroid.. vol. 21. 2011. pp. 1081-1125.

(This paper provides guidelines for detecting and treating hypothyroidism in women during and after their pregnancy.)

Torres, MS, Emerson, CH. "Myxedema Coma in Irwin and Rippe’s Intensive Care Medicine". Walters Kluwer Health, Lippincott Williams & Wilkins. 2012.

(This chapter describes the clinical features, diagnosis, and treatment of myxedema coma, covering not only thyroid hormone treatment, but also treatment of concomitant failure of organ systems.)

Cooper, DS, Garber, JR, Corbin, RH, Gharib, H, Hennessey, JV, Klein, I, Mechanick, JI, Pessah-Pollack, R, Singer, PA, Woeber, KA. "American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in adults". Thyroid. vol. 22. pp. 1200-1235.

(This is a recent and comprehensive guideline for the diagnosis and treatment of hypothyroidism from a taskforce of experts selected by the American Thyroid Association and the American Association of Clinical Endocrinologists.)

Ott, J, Promberger, R, Kober, F, Neuhold, N, Tea, M, Huber, JC, Hermann, M. "Hashimoto’s thyroiditis affects symptom load and quality of live unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter". Thyroid. vol. 21. 2011. pp. 161-167.

(This paper deals with the question of whether adverse symptoms in patients with Hashimoto's thyroidism are entirely due to biochemical hypothyroidism.)
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