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Comment on Dangerous Dogmas in Medicine: The Nonthyroidal Illness Syndrome

Gundersen Lutheran Medical Center La Crosse, Wisconsin 54601

I read with interest the excellent review by L. J. DeGroot (1) regarding the nonthyroidal illness syndrome (NTIS). I am concerned, however, that his argument for administering T₃ and T₄ to patients with this syndrome may cause harm to some patients. My colleagues and I reported three elderly patients with unexplained hypotension during or shortly after surgery (2). Despite hypotension, they had inappropriately low plasma cortisol levels (10, 12, and 6 µg/dL, respectively) and responded dramatically to the administration of glucocorticoids. Two patients also had secondary hypothyroidism and gonodatropin deficiency. After recovery, pituitary function including corticotropin (ACTH) secretion returned to normal. In a subsequent prospective study, we identified five patients older than 65 yr of age who displayed evidence of ACTH deficiency after abdominal surgery (3). These patients had plasma cortisol levels less than 15 µg/dL despite hypotension and displayed prompt hemodynamic improvement with glucocorticoid therapy. They also had evidence of TSH and gonadotropin deficiency. After recovery, the low hormone levels improved. Other investigators have also reported occult adrenal insufficiency in patients with serious medical (4) as well as surgical (5) illnesses.

The mechanism for transient adrenal insufficiency in my patients is unclear, but it is interesting to note that tumor necrosis factor , a cytocrine associated with NTIS, can inhibit corticotropin-releasing-hormone (CRH)-induced ACTH secretion (6).

The evaluation of critically ill patients is difficult because the clinical manifestations of adrenal insufficiency are not specific and are frequently attributed to the patient’s underlying disease. Insulin-induced hypoglycemia and administration of metapyrone are standard tests for assessing the hypothalamic-pituitary-adrenal (HPA) axis. Clinicians, however, are understandably reluctant to induce hypoglycemia in seriously ill patients. Because patients suspected of adrenal insufficiency must be promptly treated with glucocorticoids, the metapyrone test is impractical because glucocorticoid therapy must be withheld to perform the test. In a recent study, my colleagues and I found the low-dose cosyntropin test difficult to interpret in seriously ill post-operative patients (7). Therefore, the laboratory confirmation of adrenal insufficiency in seriously ill patients may be difficult (4, 7).

Recent observations (reviewed in refs. 4, 7) suggest that subtle adrenal insufficiency in critically ill patients may be more frequent than usually appreciated. Whether this syndrome is similar to NTIS is not clear. Nonetheless, because the administration of thyroid hormones to hypothyroid patients with unrecognized adrenal insufficiency may precipitate serious hypotension and other symptoms, the administration of T₄ and T₃ to patients with NTIS, as recommended by DeGroot, should be done only after adrenal insufficiency has been excluded. If adrenal function testing is inconclusive, physicians should consider administrating glucocorticoids to patients treated with thyroid hormones.

Footnotes

Received February 23, 1999. Address correspondence to: Robert H. Caplan, Section of Endocrinology, Gundersen Lutheran Medical Center, La Crosse, Wisconsin 54601.

References

1. DeGroot LJ. 1999 Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J Clin Endocrinol Metab. 84:151–164.[Free Full Text]
2. Kidess AI, Caplan RH, Reynertson RH, Wickus GG, Goodnough DE. 1993 Transient corticotropin deficiency in critical illness. Mayo Clin Proc. 68:435–441.[Medline]
3. Merry WH, Caplan RH, Wickus GG, et al. 1994 Acute adrenal failure due to transient corticotropin deficiency in postoperative patients. Surgery. 116:1095–1100.[Medline]
4. Lambert SWJ, Bruining HA, DeLong FH. 1997 Corticosteroid therapy in severe illness. N Engl J Med. 337:1285–1292.[Free Full Text]
5. Streeten DHP, Anderson Jr GH, Donaventura MM. 1996 The potential for serious consequences from misinterpreting normal responses to rapid adrenocorticotropin test. J Clin Endocrinol Metab. 81:285–290.[Abstract]
6. Gaillard RC, Turnill D, Sappino P, Moller AF. 1990 Tumor necrosis factor inhibits the hormonal response of the pituitary gland to hypothalamic releasing factors. Endocrinology. 127:101–106.[Abstract/Free Full Text]
7. Richards ML, Caplan RH, Wickus GG, Lambert PJ, Kisken WA. 1999 The rapid low-dose (1 µg) cosyntropin test in the immediate postoperative period: Results in elderly subjects after major abdominal surgery. Surgery. 125:431–440.[Medline]

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