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A case of masked toxic adenoma in a patient with non-thyroidal illness
© Cho et al.; licensee BioMed Central Ltd. 2014
Received: 23 April 2013
Accepted: 30 December 2013
Published: 2 January 2014
Non-thyroidal illness (NTI) refers to changes in thyroid hormone levels in critically ill patients in the absence of primary hypothalamic-pituitary-thyroid dysfunction, and these abnormalities usually resolve after clinical recovery. However, NTI can be accompanied by primary thyroid dysfunction. We report herein a case of a woman with NTI accompanied by primary hyperthyroidism.
A 52-year-old female was admitted to the intensive care unit with heart failure and atrial fibrillation. She had a longstanding thyroid nodule, and a thyroid function test revealed low levels of triiodothyronine and free thyroxine as well as undetectable thyroid stimulating hormone (TSH). She was diagnosed with NTI, and her TSH level began to recover but not completely at discharge. The thyroid function test was repeated after 42 months to reveal primary hyperthyroidism, and a thyroid scan confirmed a toxic nodule.
This case suggests that although NTI was diagnosed, primary hyperthyroidism should be considered as another possible diagnosis if TSH is undetectable. Thyroid function tests should be repeated after clinical recovery from acute illness.
Non-thyroidal illness (NTI) or euthyroid sick syndrome (ESS) is defined as a change in thyroid function during starvation or illness including a central reduction in thyroid stimulating hormone (TSH) secretion, decreased plasma triiodothyronine (T3) levels and decreased thyroxine (T4) and T3 binding in serum . It is a relatively common syndrome, affecting about 70% of hospitalized patients  and may occur with virtually any illness . Abnormalities in thyroid function can occur within hours of acute illness, and the magnitude of reduction in thyroid hormone levels correlates with disease severity and mortality. Serum T3 and free T4 levels are independent predictors of survival [4–6], and low levels of T3 are a poor prognostic factor of short- and long-term survival in patients with heart failure, acute myocardial infarction or acute stroke outside the intensive care unit (ICU) setting [7, 8]. The pathophysiological mechanism responsible for NTI is complex and changes in the hypothalamic–pituitary–thyroid axis are the effect of various factors. Treatment of NTI with thyroid hormone is controversial, and abnormalities in thyroid function tests usually resolve after clinical recovery . Primary thyroid dysfunction can be accompanied by NIT, and a follow-up thyroid function test is essential after recovery from illness to ascertain normalization. Here, we present a case of a woman with NTI who was later diagnosed with primary hyperthyroidism.
Our patient had symptoms and signs of heart failure and atrial fibrillation. She had an asymmetric goiter, her T3, free T4 and TSH levels all decreased significantly; thus, she was diagnosed with NTI. TSH began to increase at discharge, but none of the thyroid hormone levels normalized. There was a follow-up loss of the thyroid function tests until 42 months after discharge. Testing revealed primary hyperthyroidism and a thyroid scan confirmed a functioning toxic nodule. Thus, primary hyperthyroidism, particularly toxic adenoma, should be considered in patients with NTI who have an undetectable level of TSH and a huge nodule with an atrophic remaining thyroid gland.
NTI is a syndrome that reflects alterations in thyroid hormone levels during various illnesses . Decreased total and free T3 levels with normal levels of TSH can be observed in the acute phase of critical illness (low T3 syndrome). Circulating T4 levels transiently rise during the acute phase of illness and normalize again when recovery follows quickly. However, patients who are severely ill and suffering from diseases that do not allow immediate recovery, present with reduced circulating total and free T4 concentrations. Reverse T3 increases due to impaired T4 conversion to T3 via peripheral deiodination. As the disease progresses, a dramatic fall in total T4 and T3 occurs (low T4 syndrome) , and about 50% of patients with NTI have decreased TSH levels, resulting from a reduction in thyroid releasing hormone secretion by the hypothalamus and indicating changes in hypothalamic–pituitary regulation . Whether these changes are adaptive physiological mechanisms to conserve energy or consequences of the underlying illness is still a matter of debate [5, 11]. However, treating NTI with thyroid hormones does not appear to be necessary, even though there is some controversy. For these reasons, routine thyroid function tests are not recommended in the intensive care setting unless a suspicion for thyroid dysfunction is based on history or a clinical evaluation. In the present case, a thyroid function test was ordered to evaluate atrial fibrillation and goiter.
The resolution of abnormal thyroid hormone levels after clinical recovery has been well documented. However, primary thyroid dysfunction can accompany NTI. TSH level may provide some clues for detecting underlying thyroid disease. Spencer et al. [12, 13] reported that TSH can be low but detectable or high but < 20 μIU/mL in patients with NTI. The likelihood ratio for primary hyperthyroidism is 7.7 if TSH is undetectable, and the likelihood ratio is 11.1 for primary hypothyroidism if TSH > 20 μIU/mL . Thus, TSH level should be considered in relation to the possibility of thyroid disease, and follow-up studies are mandatory, particularly if the value is not mildly abnormal. In our case, the patient had an undetectable level of TSH, and a thyroid ultrasonogram revealed a large cystic dominant nodule in the right thyroid lobe with atrophy of the opposite lobe. Although she was diagnosed with NTI, primary hyperthyroidism due to the toxic nodule should have been considered and a follow-up thyroid function test should have been performed after discharge.
Various drugs used in the hospital, particularly in the ICU, can alter thyroid function tests. Dopamine reduces serum TSH if used for a prolonged time . Dobutamine, given in pharmacologic doses, also lowers TSH, even though TSH levels remain within the normal limits in subjects with a normal baseline TSH level . Amiodarone is another drug that can cause alterations in thyroid function tests. Although most patients (>70%) on amiodarone remain euthyroid, the drug can lead to either amiodarone-induced hypothyroidism or amiodarone-induced thyrotoxicosis. High-dose glucocorticoids and octreotide also transiently suppress TSH, although central hypothyroidism does not appear to occur with these drugs [17, 18]. Attention should be paid when interpreting thyroid function tests if any of these drugs have been used. Our patient never received any of these drugs.
A toxic nodule is a solitary, autonomously functioning thyroid nodule. The pathogenesis includes mutations in the TSH receptor leading to enhanced stimulation of thyroid follicular cell proliferation and function . A thyroid nodule generally large enough to be palpable is present with suppressed TSH level, as in the present case. Patients initially have subclinical hyperthyroidism but when the adenoma grows to a significant size, frank hyperthyroidism develops, and elevated serum thyroid hormone levels accompany this condition . Thyrotoxicosis is usually mild. A thyroid nodule appears on ultrasonography as a hypo-echogenic nodule with an atrophic thyroid gland. A thyroid scan is a definitive diagnostic test, demonstrating increased radioiodine uptake in the hyperfunctioning nodule and decreased uptake in the remaining gland. Radio-iodine ablation is usually the treatment of choice. Surgical resection of the adenoma or lobectomy to preserve thyroid function is another treatment option .
NTI is a very common syndrome in the intensive care setting, and routine thyroid function testing is generally not recommended. However, if there is a high suspicion for underlying thyroid disease, a thyroid function test should be performed and interpreted with caution. Thyroid function tests should be repeated after recovery from acute illness to ascertain euthyroid status. An evaluation for primary thyroid disease is essential, particularly when TSH is undetectable or >20 μIU/mL.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
The authors have nothing to disclose.
- Melmed SPK, Larsen PR, Kronenberg HM: Williams Textbook of Endocrinology. 2011, Philadelphia, PA: Saunders Elsevier, 327-405. 12Google Scholar
- Bermudez F, Surks MI, Oppenheimer JH: High incidence of decreased serum triiodothyronine concentration in patients with nonthyroidal disease. J Clin Endocrinol Metab. 1975, 41 (1): 27-40. 10.1210/jcem-41-1-27.View ArticlePubMedGoogle Scholar
- Adler SM, Wartofsky L: The nonthyroidal illness syndrome. Endocrinol Metab Clin North Am. 2007, 36 (3): 657-672. 10.1016/j.ecl.2007.04.007. viView ArticlePubMedGoogle Scholar
- De Marinis L, Mancini A, Masala R, Torlontano M, Sandric S, Barbarino A: Evaluation of pituitary-thyroid axis response to acute myocardial infarction. J Endocrinol Invest. 1985, 8 (6): 507-511.View ArticlePubMedGoogle Scholar
- De Groot LJ: Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J Clin Endocrinol Metab. 1999, 84 (1): 151-164. 10.1210/jc.84.1.151.View ArticlePubMedGoogle Scholar
- Ray DC, Drummond GB, Wilkinson E, Beckett GJ: Relationship of admission thyroid function tests to outcome in critical illness. Anaesthesia. 1995, 50 (12): 1022-1025. 10.1111/j.1365-2044.1995.tb05943.x.View ArticlePubMedGoogle Scholar
- Iervasi G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini M, L'Abbate A, Donato L: Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation. 2003, 107 (5): 708-713. 10.1161/01.CIR.0000048124.64204.3F.View ArticlePubMedGoogle Scholar
- Iglesias P, Munoz A, Prado F, Guerrero MT, Macias MC, Ridruejo E, Tajada P, Diez JJ: Alterations in thyroid function tests in aged hospitalized patients: prevalence, aetiology and clinical outcome. Clin Endocrinol (Oxf). 2009, 70 (6): 961-967. 10.1111/j.1365-2265.2008.03421.x.View ArticleGoogle Scholar
- Mebis L, Van den Berghe G: Thyroid axis function and dysfunction in critical illness. Best Pract Res Clin Endocrinol Metab. 2011, 25 (5): 745-757. 10.1016/j.beem.2011.03.002.View ArticlePubMedGoogle Scholar
- Plikat K, Langgartner J, Buettner R, Bollheimer LC, Woenckhaus U, Scholmerich J, Wrede CE: Frequency and outcome of patients with nonthyroidal illness syndrome in a medical intensive care unit. Metabolism. 2007, 56 (2): 239-244. 10.1016/j.metabol.2006.09.020.View ArticlePubMedGoogle Scholar
- Wartofsky L, Burman KD, Ringel MD: Trading one “dangerous dogma” for another? Thyroid hormone treatment of the “euthyroid sick syndrome”. J Clin Endocrinol Metab. 1999, 84 (5): 1759-1760. 10.1210/jc.84.5.1759.PubMedGoogle Scholar
- Spencer C, Eigen A, Shen D, Duda M, Qualls S, Weiss S, Nicoloff J: Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. Clin Chem. 1987, 33 (8): 1391-1396.PubMedGoogle Scholar
- Spencer CA, LoPresti JS, Patel A, Guttler RB, Eigen A, Shen D, Gray D, Nicoloff JT: Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. J Clin Endocrinol Metab. 1990, 70 (2): 453-460. 10.1210/jcem-70-2-453.View ArticlePubMedGoogle Scholar
- Attia J, Margetts P, Guyatt G: Diagnosis of thyroid disease in hospitalized patients: a systematic review. Arch Intern Med. 1999, 159 (7): 658-665. 10.1001/archinte.159.7.658.View ArticlePubMedGoogle Scholar
- Kaptein EM, Spencer CA, Kamiel MB, Nicoloff JT: Prolonged dopamine administration and thyroid hormone economy in normal and critically ill subjects. J Clin Endocrinol Metab. 1980, 51 (2): 387-393. 10.1210/jcem-51-2-387.View ArticlePubMedGoogle Scholar
- Lee E, Chen P, Rao H, Lee J, Burmeister LA: Effect of acute high dose dobutamine administration on serum thyrotrophin (TSH). Clin Endocrinol (Oxf). 1999, 50 (4): 487-492. 10.1046/j.1365-2265.1999.00678.x.View ArticleGoogle Scholar
- Nicoloff JT, Fisher DA, Appleman MD: The role of glucocorticoids in the regulation of thyroid function in man. J Clin Invest. 1970, 49 (10): 1922-1929. 10.1172/JCI106411.View ArticlePubMedPubMed CentralGoogle Scholar
- Colao A, Merola B, Ferone D, Marzullo P, Cerbone G, Longobardi S, Di Somma C, Lombardi G: Acute and chronic effects of octreotide on thyroid axis in growth hormone-secreting and clinically non-functioning pituitary adenomas. Eur J Endocrinol. 1995, 133 (2): 189-194. 10.1530/eje.0.1330189.View ArticlePubMedGoogle Scholar
- Parma J, Duprez L, Van Sande J, Cochaux P, Gervy C, Mockel J, Dumont J, Vassart G: Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature. 1993, 365 (6447): 649-651. 10.1038/365649a0.View ArticlePubMedGoogle Scholar
- Hegedus L, Bonnema SJ, Bennedbaek FN: Management of simple nodular goiter: current status and future perspectives. Endocr Rev. 2003, 24 (1): 102-132. 10.1210/er.2002-0016.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6823/14/1/prepub
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