Pseudo-central hypothyroidism. (Case Report).

Abstract

Central hypothyroidism is an exceedingly rare form of hypothyroidism that results from a variety of conditions affecting the hypothalamus and the pituitary gland. The classic biochemical abnormality seen in these patients includes a low serum level of circulating thyroxine ([T.sub.4]) concomitant with an inappropriately low level of thyrotropin. Because patients with isolated triiodothyronine ([T.sub.3]) toxicosis also present with this biochemical pattern, it is important to measure [T.sub.3] levels in such patients before making a diagnosis of central hypothyroidism.

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Central hypothyroidism is a rare form of hypothyroidism in which there is a low serum level of circulating thyroxine ([T.sub.4]) concomitant with an inappropriately low thyrotropin level. Hypothalamic and/or pituitary disease can cause this condition. In patients who have isolated triiodothyronine ([T.sub.3]) toxicosis, suppressed thyrotropin and low [T.sub.4] levels can suggest central hypothyroidism unless [T.sub.3] is measured. We describe a patient who was referred to our endocrine clinic for the evaluation of central hypothyroidism and was found to have iatrogenic [T.sub.3] toxicosis.

Discussion

Isolated [T.sub.3] toxicosis is usually seen in conjunction with states of endogenous hyperthyroidism such as Graves disease, toxic adenoma, or toxic multinodular goiter. (1) These patients have elevated [T.sub.3] and suppressed thyrotropin levels. The [T.sub.4] levels are usually normal but may be low. Hence, if [T.sub.3] is not measured in these patients, the biochemical parameters indicate central hypothyroidism. Although factitious thyrotoxicosis due to ingestion of [T.sub.4] is frequently encountered in clinical practice, (2) only a handful of cases of factitious [T.sub.3] toxicosis have been described in the literature. (3,4) Because the dose of [T.sub.3] that our patient was taking usually does not suppress thyrotropin, we questioned the patient about overmedication, and she denied taking more than the prescribed amount. Hence, our patient cannot be classified as having factitious thyrotoxicosis.

For decades, psychiatrists have prescribed [T.sub.3] to patients as an adjunct to standard antidepressant therapy. (5) The addition of [T.sub.3] has been reported to result in augmentation of the antidepressant effects of tricyclic antidepressants, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors. (5) The importance of close monitoring of these patients cannot be overemphasized, because our patient was clearly symptomatic with [T.sub.3] values in the supraphysiologic range. High levels of thyroid hormone can result in complications such as cardiac arrhythmias (6) and osteoporosis (7) in high-risk populations (eg, elderly and postmenopausal women). Therefore, extreme caution should be exercised by psychiatrists in prescribing [T.sub.3] for these high-risk patients. Furthermore, even in young and premenopausal patients, (5) doses of [T.sub.3] that result in supraphysiologic serum levels may produce thyrotoxic symptoms that decrease quality of life (as in our patient). Therefore, if pati ents with depression are prescribed liothyronine sodium, they should be monitored closely for the development of thyrotoxic symptoms, and the dose should be titrated to keep serum thyrotropin levels within the normal range. In addition to a careful clinical evaluation, triiodothyronine levels should always be measured before making a diagnosis of central hypothyroidism. Furthermore, psychiatrists should be cautious in treating their patients with [T.sub.3] and should periodically question such patients about symptoms suggestive of side effects of the medication.

Accepted April 30, 2002.

References

(1.) Sterling K, Refetoff S, Selenkow HA. [T.sub.3] thyrotoxicosis: ThyrotoxicosiS due to elevated serum triiodothyronine levels. JAMA 1970;213:571-575.

(2.) Cohen JH III, Ingbar SH, Braverman LE. Thyrotoxicosis due to ingestion of excess thyroid hormone. Endocr Rev 1989;10:113-124.

(3.) Dahlberg PA, Karlsson FA, Wide L. Triiodothyronine intoxication. Lancet 1979;2:700.

(4.) Sylvia Vela B, Dorin RI. Factitious triiodothyronine toxicosis. Am J Med 1991;90:132-134.

(5.) Joffe RT. The use of thyroid supplements to augment antidepressant medication. J Clin Psychiatry 1998;59(Suppl 5):26-31.

(6.) Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994;331:1249-1252.

(7.) Solomon BL, Wartofsky L, Burman KD. Prevalence of fractures in postmenopausal women with thyroid disease. Thyroid 1993;3:17-23.

RELATED ARTICLE: Key Points

* In central hypothyroidism, both thyrotropin and free [T.sub.4] levels are low. Thyrotropin levels can be inappropriately normal.

* Patients with isolated [T.sub.3] toxicosis also have low thyrotropin along with low free [T.sub.4].

* We recommend measuring [T.sub.3] levels in all patients with this biochemical presentation before making a diagnosis of central hypothyroidism.

Case Report

A 49-year-old woman was referred to the endocrine clinic for evaluation of central hypothyroidism. A month earlier, during a routine appointment with her gynecologist, she had complained of fatigue, lethargy, and weight gain. She reported occasional palpitations. Hypothyroidism was suspected, and thyroid function tests were performed. The tests revealed a thyrotropin level of 0.6 [micro]IU/ml (normal, 0.5-4.5 [micro]IU/ml) and a free [T.sub.4] value of 0.3 ng/dl (normal, 0.7-1.6 ng/dl). The results were consistent with central hypothyroidism. The patient denied any history of head trauma, surgery, or radiotherapy. There were no symptoms of adrenal insufficiency, and her menstrual cycles were regular. The patient had a 3-year history of depression, for which she was taking fluoxetine. A week before the patient's clinic visit, during a telephone conversation with the patient's gynecologist, it was decided to check her [T.sub.3] levels (considering her symptoms of occasional palpitations) before obtaining imagin g studies. Free [T.sub.3] level was elevated at 519 pg/dl (normal, 230-420 pg/dl). Isolated [T.sub.3] toxicosis due to Graves' disease, toxic adenoma, or toxic multinodular goiter was suspected. During evaluation in the endocrine clinic, a review of the patient's medications revealed that she had been taking liothyronine sodium (cytomel), 12.5 [micro]g bid for the previous 7 months as prescribed by her psychiatrist to augment the antidepressant effect of fluoxetine. An examination revealed that the patient had tachycardia (102 beats/min) but did not have proptosis, lid retraction, lid lag, or tremors. The thyroid gland was normal in size and without any palpable nodules, tendemess, or bruit. The patient's reflexes were hyperactive. The patient was told to stop taking [T.sub.3], and her psychiatrist was informed regarding her symptoms and serum [T.sub.3] levels.

From the Division of Endocrinology and the Division of Obstetrics and Gynecology, Johns Hopkins University Bayview Medical Center, Baltimore, MD, and the Division of Endocrinology, Federal University of Parana, Curitiba, Brazil.

Reprint requests to Shehzad Basaria, MD, Division of Endocrinology and Metabolism, Johns Hopkins University Bayview Medical Center, 4940 Eastern Avenue, A-5-E, Suite 503, Baltimore, MD 21224.

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