Feature Story

July 2004
Feature Story

Seth L. Haber, MD

As LUCK would have it

The Laboratory Utilization Committee of the Kaiser Permanente Medical Care Program, or LUCK, enlists the support and backing of clinicians to reduce laboratory costs. In recent newsletters, the committee brought the clinicians up to date on thyroid testing and testing for syphilis. LUCK, which is composed predominantly of clinicians, gets the consensus and support of the leading groups, in this case the chiefs of endocrinology for the thyroid guidelines and the chiefs of infectious disease and neurology for the syphilis guidelines.

Here are the committee’s guidelines for thyroid testing:

Hypothyroidism

• Routine/systematic screening for hypothyroidism is not recommended.
• Test symptomatic individuals, people with nonthyroid autoimmune disease, people with strong family histories of thyroid disease and/or goiters. Women and older individuals have higher disease prevalence, so the threshold for thyroid testing (with TSH) should be lower in these groups.
• TSH is the best test for detecting hypothyroidism.
• FT₄ testing is not generally helpful unless pituitary/hypothalamic disease is suspected.
• TSI, total T₃, free T₃, free T₄, or T₃ by dialysis, thyroglobulin, and antithyroglobulin antibodies are almost never necessary in hypothyroid patients. Contact an endocrinologist if considering these tests.
• Interpretation of TSH values
  1. TSH > 10 mIU/L: Repeat TSH with FT₄ before starting lifelong L-thyroxine replacement.
  2. TSH 3.0-9.9 mIU/L, symptomatic.
  • L-thyroxine use in fatigued patients with a single minimally elevated TSH is not encouraged.
  • Repeat TSH with FT₄ before starting lifelong L-thyroxine replacement.
  • For confirmed minimally elevated TSH in a patient with possible hypothyroid symptoms (usually fatigue), low-dose L-thyroxine treatment with the smallest dose possible to normalize the TSH (0.5-2.0 mIU/L) may be prescribed.
  3. TSH 3.0-9.9 mIU/L, asymptomatic.
• Follow with periodic TSH testing.
• L-thyroxine may be started if strong family history of auto immune thyroid disease or goiter is present or TPO (thyroid peroxidase) antibodies are present.
• Start L-thyroxine therapy at 50-125 µg/day (1.5 µg/kg/day) or 25 µg/day if high risk for coronary artery disease.
1. After initiating L-thyroxine replacement, check TSH every six weeks (not sooner) and titrate L-thyroxine dose by 12.5-25 µg/day increments until TSH is normal (0.5-2.0 mIU/L), then followup yearly TSH.
2. T₄ levels are not recommended for patients on thyroid hormone replacement therapy unless they have central (pituitary) hypothyroidism.
3. Average full replacement L-thyroxine dose in patients < 60 years of age is 112-137 µg/day; older than 60 years is 100-125 µg/day. If TSH remains elevated on doses > 150 µg/day, strongly consider noncompliance before raising dose further.

Hyperthyroidism

This is the testing strategy for symptomatic patients with suggestive clinical findings:

• High clinical suspicion: Order FT₄ and TSH. High FT₄, low TSH (< 0.01 mIU/L) plus symptoms confirms hyperthyroidism. Treat with a beta-blocker if tachycardia and no contraindications. Consider adding antithyroid medications in symptomatic, clinically apparent Graves’ disease. Order thyroid uptake and scan (nuclear medicine) in patients without clear diagnosis. If TSH is mildly suppressed (0.01-0.2 mIU/L) and FT₄ is normal, consider other causes for symptoms, and either repeat labs or proceed with uptake/scan to clarify the diagnosis. Discuss unclear cases with an endocrinologist.
• Low clinical suspicion: Order TSH. If TSH is normal and no clinical findings, then hyperthyroidism is unlikely. If TSH is low (< 0.2 mIU/L), add FT₄ to saved sera and proceed as above.
• Do not order TSI, total T₃, free T₃, free T₄ by dialysis, free T₃ by dialysis, thyroglobulin, or anti thyroglobulin antibodies without prior endocrine consultation.

Thyroid nodule/goiter

Imaging studies are not indicated in the evaluation of thyroid nodules.

Order TSH for all people with thyroid nodules.

• If TSH < 0.2 mIU/L, obtain a thyroid radioactive iodine scan to exclude a hyperfunctioning nodule or a toxic multinodular goiter.
• If TSH > 0.2, refer the patient for possible thyroid biopsy (endo crine, radiology, or pathology).
• For thyroid nodules > 1 cm identified incidentally on imaging studies, refer to an endocrinologist for evaluation and possible thyroid biopsy.

Thyroid cancer

An endocrinologist should follow most patients with a history of thyroid cancer. Most patients with thyroid cancer are routinely given suppressive doses of L-thyroxine to achieve a low TSH.

Do not change the dose of L-thyroxine in patients with a history of thyroid cancer without consulting with the patient’s endocrinologist.

Syphilis testing

Here are the committee’s guidelines for syphilis testing:

In recent years the Treponema pallidum particle agglutination test, or TPPA, has replaced the micro he mag glu tinin-T.pallidum, or MHA-TP, for confirmation of a positive rapid plasma reagin, or RPR. The TPPA is as sensitive and more specific than the fluorescent treponemal antibody absorption test, or FTA-abs. In addition, the epidemiology of syphilis has changed. Therefore, our approach to syphilis testing needs to be updated in accordance with public health and CDC recommendations.

• Dementia: General screening for syphilis is not recom mend ed.* If syphilis is suspected, use serum rapid plasma reagin test, or RPR, only.

Tertiary syphilis has been nearly nonexistent for the past 20 years, and California is a low-incidence area for infection. Unless a patient has a history of prior untreated syphilis or there is a strong clinical suspicion of syphilis, testing should not be done. In testing for syphilis, the serum RPR is the appropriate test. While it is true that the RPR may be negative in some cases of tertiary neurosyphilis, the prevalence of this disease has dropped so low that a positive TPPA is more likely to be false-positive, old treated syphilis having nothing to do with the current disease. A positive RPR has a higher positive predictive value than a TPPA and is considered the most cost-effective test. If the patient has more specific symptoms of neurosyphilis (that is, tabes), consider a TPPA in the setting of a negative RPR.

1. Strokes are a manifestation of secondary syphilis, so the RPR is extremely sensitive and should be done only if the patient has risk factors (under 50, HIV infection, men having sex with men).
2. For uveitis, hearing loss, and other possible manifestations of neurosyphilis, serum RPR is the test of choice for the same reasons.


• The TPPA is the only confirmatory test for a positive RPR. It is always done automatically by our lab if the RPR is positive, so it does not need to be ordered separately. The FTA-abs is not used as a reflex test in patients with a positive RPR and negative TPPA. If the RPR is positive and the TPPA is negative, it is a false-positive RPR.
• The serum FTA-abs no longer has a place in routine testing. It should not be used to confirm a positive RPR and should never be used as a screening test. If an FTA is ordered on the serum, the laboratory will perform a TPPA test. Specimens will be held one week in case there are problems with the protocol.
• Cerebrospinal fluid FTA testing may still be useful for ruling out neuro syph ilis.

CSF syphilis testing: VDRL, cell count and differential, glucose and protein. Get infectious disease consultation if considering the FTA test.

Browsing the Internet

Several Web sites are devoted to the needs of pathologists in teaching, training, job seeking, and practice. One of the most useful I’ve found, www.PathologyOutlines.com, is an obvious labor of love by Nat Pernick, MD, of Bingham Farms, Mich., using the University of Iowa’s Web site. It includes most of an updatable, 41-chapter online/ outline textbook, with a lot of good illustrations, references, and links.

James L. Bennington, MD, provides reviews of recently published books of interest to pathologists on his Scientific Symposiums Web site, www.Scientificsymposiums.com. The reviews are from the major peer-reviewed journals, making this the Reader’s Digest of books. You can search this unique database by author, topic, field, or ISBN publication number. The information can be printed or downloaded to your computer, or both, after which there are links to the journal in which the review was published and to both the Stanford Medical Bookstore (see "Discounts on books") and Amazon. com, if you want to purchase the book.

The primary purpose of Dr. Bennington’s Web site is to list the outstanding seminars in surgical pathology, dermatopathology, and clinical pathology that scientific symposiums offer to pathologists on the "Big Island," Kauai, and Maui in Hawaii, as well as Hilton Head Island in South Carolina. But the book reviews are a unique free service.

Please send me a list of your favorite Web sites, and I’ll publish the best-for the benefit of us all.

Correction: RDO, not RDX

Barry R. Rittman, PhD, co-editor, and Hermina Bogerink, editor of "Hard Times: The Communique of the Hard Tissue Committee of the National Society for Histotechnolgy," pointed out that when I referred to my using RDX as a rapid decalcifying solution (December 2003), it should have been RDO. RDX is a highly toxic chemical with no use in the histology laboratory, much less in decalcification. Also, RDO does not contain potassium permanganate. If you want more information about RDO, log on to www.rdo-apex.com/instruct.html.

Get rid of the acid

Nancy E. Warner, MD, my mentor, counselor, and friend for close to five decades, reminded me that one of the many things she taught me is that, when decalcified tissues fail to stain with hematoxylin, and overstain with eosin, the culprit is acidity and not "poor fixation."

The solution to the problem is to take personal responsibility, if necessary, to wash the tissues under running water for hours to days. You can stop when the pH of the specimen, tested with pH paper, approximates 7.0. Only then can you embed, cut, and stain the tissues. If the tissues have already been embedded, you might try deparaffinizing the tissue on the slide and wash it gently for a few hours.

Discounts on books

This is to remind you that the Stanford Medical Bookstore gives CAP members a 10 percent discount on medical books. For two special sale months, generally April and September, that discount becomes 15 percent. Call 650-614-0280 to place your orders. The manager, Janet L. Gawley, is at extention 313.

CAP members heading for Phoe nix in September for CAP ’04 will be able to order books from the Stanford Bookstore in the College’s exhibit booth. That’s another good reason for visiting the College exhibit at the all-new and dynamic annual meeting.

Dr. Haber is emeritus chief of the Department of Pathology, The Kaiser Permanente Medical Center, Santa Clara, Calif., and clinical professor of pathology at Stanford University School of Medicine. He can be reach ed at 1375 Pitman Avenue, Palo Alto, CA 94301; phone 650-321-3441; e-mail slhaber@ stanford.edu; and fax 650-321-6773.