A 66-year-old man with abnormal thyroid function tests

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Figure 1
Peripheral conversion of thyroxine (T₄) to triiodothyronine (T₃), reverse T₃, and diiodothyronine (T₂) by deiodinase types 1, 2, and 3 (D1, D2, D3) in healthy people and in patients with nonthyroidal illness.

TABLE 1

Initial laboratory results

Test	Value^a	Reference range
Hemoglobin	15.9 g/dL	13.5–17.5 g/dL
White blood cell count	16.7 x 10⁹/L	4.5–11.0 × 10⁹/L
Neutrophils	85%	40%–75%
Lymphocytes	10%	20%–45%
Monocytes	3%	2%–10%
Eosinophils	1%	1%–6%
Basophils	1%	0%–1%
Platelet count	260 x 10⁹/L	150–400 × 10⁹/L
Sodium	136 mmol/L	135–145 mmol/L
Potassium	5.1 mmol/L	3.5–5.2 mmol/L
Blood urea nitrogen	15 mg/dL	7–20 mg/dL
Creatinine	1.0 mg/dL	0.5–1.1 mg/dL
Glucose	110 mg/dL	70–140 mg/dL
Calcium	9.5 mmol/L	8.9–10.1 mmol/L
Albumin	3.7 g/dL	3.5–5.5 g/dL
Alanine aminotransferase	32 U/L	7–35 U/L
Aspartate aminotransferase	30 U/L	7–35 U/L
Troponin I	0.21 ng/mL	0.00–0.40 ng/mL
Brain natriuretic peptide	73 pg/mL	< 125 pg/mL
Sputum gram stain	Negative	Negative
Sputum culture and sensitivity	Pending	No gtrth
Blood culture	Pending	No gtrth
Partial pressure of oxygen	54 mm Hg	75–100 mm Hg
Oxygen saturation	88%	94%–100%
Arterial blood pH	7.37	7.35–7.45
Partial pressure of carbon	50 mm Hg	35–45 mm Hg
dioxide
Serum bicarbonate	28 mmol/L	22–28 mmol/L

TABLE 2

Thyroid function test results in patients with nonthyroidal illness

Thyroid test	Result	Mechanisms
Thyroid-stimulating hormone (TSH)	Normal, high, or low	Low TSH because of: • Suppression of hypothalamic-pituitary axis by inflammatory cytokines • Abnormal TSH glycosylation • Decreased leptin resulting in low thyrotropin-releasing hormone, resulting in low TSH • Increased hypothalamic and pituitary type 2 iodothyronine deiodinase (D2) activity resulting in increased local T₃ and thus decreased TSH Transient TSH increase during recovery from acute illness can be seen
Serum free thyroxine (T₄)	Normal, high, or low	Increased “direct” free T₄ possibly because of inhibitors of T₄ to its binding proteins⁶ Decreased free T₄ index possibly because of very low binding protein concentrations⁷
Total T₄	Normal or low	Decreased total T₄ because of: • Low production of its binding proteins • Decreased binding to thyroxine-binding globulin (inhibitors of T₄ binding, glycosylated thyroxine-binding globulin) • Low TSH
Total triiodo-thyronine (T₃)	Low	Decreased type 1 iodothyronine deiodinase (D1) activities (by cytokines, increased cortisol, free fatty acids, and drugs) Low production of thyroxine-binding globulin Decreased binding to thyroxine-binding globulin (inhibitors of T₃ binding, glycosylated thyroxine-binding globulin) Low TSH
Reverse T₃	High^a	Increased type 3 iodothyronine deiodinase (D3) activity Decreased D1 activity

↵a Except in patients with end-stage renal disease and in some patients with acquired immune defi ciency syndrome.

TABLE 3

Clinical causes of decreased D1 activity

Condition or drug	Comment
Low caloric intake, malnutrition	The most common inhibitory factor of type 1 iodothyronine deiodinase (D1)
Nonthyroid illness	Even if it is mild
Drugs
Propylthiouracil	Not methimazole
Glucocorticoids	Eg, 4 mg of dexamethasone decreases total T₃ by 30% in several days
Beta-adrenergic antagonists	Propranolol, metoprolol, atenolol, and alprenolol (not nadolol or sotalol)
Oral cholecystographic agents (eg, sodium ipodate)	Not available in United States
Amiodarone	Could compete with thyroxine (T₄) for the deiodinative site
Liver disease	Liver tissue expresses high levels of D1
Selenium deficiency	D1 is a selenoprotein
Neonatal period	Especially in premature and low-birth-weight infants