Top 20 Thyroid Articles
TOP 20 - THYROID ARTICLES
The following is a list of twenty outstanding
articles which have occurred in the thyroid literature during the past few
years. These articles have been selected by Jerome M. Hershman, M.D.,
Professor of Medicine UCLA School of Medicine;
Chief, Endocrinology and Metabolism Division VA Greater Los Angeles Healthcare System;
prior editor of the journal "Thyroid".
Dr. Hershman may be contacted at comment.
Reprint (PDF) Version of this entire Review
Screening for Thyroid Dysfunction
||Canaris GJ, Manowitz NR, Mayor G, Ridgway EC.|
Colorado thyroid disease prevalence study.
Arch Intern Med. 2000;
participants in a statewide health fair in Colorado in 1995 were evaluated
for thyroid dysfunction. The prevalence of elevated TSH levels in this
population was 9.5%, and the prevalence of decreased TSH levels was 2.2%.
Six percent were taking thyroid hormone. Of those not on therapy,
hypothyroidism was found on 0.4%, subclinical hypothyroidism in 8.5%,
hyperthyroidism in 0.1%, and subclinical hyperthyroidism in 0.9%. The
survey discloses the high frequency of thyroid functional disease in our
Ladenson PW, Singer PA, Ain
KB, Bagchi N, Bigos ST, Levy EG, Smith SA, Daniels GH:
Association guidelines for detection of thyroid dysfunction.
Intern Med. 2000; 160:1573-5.
Standards of Care Committee of the American Thyroid Association recommends
that all adults over age 35 be screened for thyroid dysfunction by TSH
measurement every 5 years.
Ross DS (ed)
of thyroid function and disease.
Endocrinol Metab Clin North Am. 2001
This volume contains
excellent reviews of all of the thyroid diagnostic tests.
Palomaki GE, Allan WC, et al.
Maternal thyroid deficiency during
pregnancy and subsequent neuropsychological development of the child.
Engl J Med 1999 Aug 19; 341(8):549-55
neuropsychological performance of children, age 8, whose mothers had
elevated TSH during pregnancy, were compared with progeny of mothers with
normal TSH. The children of mothers with untreated hypothyroidism had
lower IQ and scored lower than the control children in 7 of 13 tests of
intellectual ability and school performance. I believe the results
indicate that pregnant women should have TSH measurement and be treated if
TSH is elevated.
In a subsequent paper they reported that of those with TSH>6 mU/L,
the incidence of fetal death was 4.4-fold greater than in those with
(Allan WC, Haddow JE, Palomaki GE, et al. Maternal thyroid
deficiency and pregnancy complications: implications for population
screening. J Med Screen 2000; 7(3):127-30)
Singh N, Singh PN, Hershman
Effect of calcium carbonate on the absorption of
JAMA 2000 Jun 7; 283(21):2822-5
Nalini Singh and her colleagues
at the VA Greater Los Angeles Healthcare System showed that, when calcium
carbonate was ingested with levothyroxine, it reduced the absorption of
the levothyroxine, resulting in elevation of serum TSH. Since many
post-menopausal women with hypothyroidism also take calcium carbonate for
osteoporosis, it is important to advise that the levothyroxine and calcium
carbonate are not ingested simultaneously.
need for thyroxine in women with hypothyroidism during estrogen
N Engl J Med 2001 Jun 7;
In a group of 18 postmenoopausal
women on thyroxine replacement therapy, treatment with estrogen increased
serum TSH and decreased the free T4 levels. In 7 of the 18, serum TSH
increased to more than 7 mU/L. The author concludes that estrogen therapy
increases the need for levothyroxine replacement in some women with
practice. Subclinical hypothyroidism.
N Engl J Med 2001 Jul 26;
David Cooper has written an
excellent review of subclinical hypothyroidism. The bottom line: nearly
all patients with elevated serum TSH should be given a trial of thyroid
Haugen BR, Pacini F,
Reiners C, et al.
A comparison of recombinant human thyrotropin and
thyroid hormone withdrawal for the detection of thyroid remnant of
J Clin Endocrinol Metab 1999 Nov;
This is the result of the second
phase 3 trial of recombinant human TSH for evaluation of patients with
differentialted thyroid cancer. Scans after recombinant hTSH were almost
as frequently positive as those after withdrawal of thyroid hormone; the
difference between the two methods was not significant. Combining
stimulated thyroglobulin with scanning detected all recurrences..
Hundahl SA, Cady B,
Cunningham MP, et al.
Initial results from a prospective cohort study
of 5583 cases of thyroid carcinoma treated in the United States during
Cancer 2000 Jul 1; 89(1):202-17.
The American College of Surgery
cancer database collected 5,583 cases of thyroid carcinoma treated in the
US during 1996. The data show that the relative frequencies of the
different cancers are: 81% papillary, 10% follicular, 3.6% Hurthle cell,
0.5% familial medullary, 2.7% sporadic medullary, and 1.7% anaplastic.
Surprisingly, only 53% of the cases had fine-needle aspiration of the
thyroid gland. (FNA should be performed in nearly all patients with
thyroid nodules before surgery.)The vast majority of patients with
differentiated thyroid carcinoma presented with Stage I and II disease and
relatively small tumors. For all histologies, near-total or total
thyroidectomy constituted the dominant surgical treatment. Residual tumor
after the surgery could be documented in 11% of cases, hypocalcemia in 10%
of cases, and recurrent laryngeal nerve injury in 1.3% of cases.
Complications were mostly frequently associated with total thyroidectomy
combined with lympth node dissection. Thirty-day mortality was 0.3%; when
anaplastic cancer cases were eliminated, it decreased to 0.2%.
Bartolazzi A, Gasbarri A,
Papotti M, et al.
Application of an immunodiagnostic method for
improving preoperative diagnosis of nodular thyroid lesions.
2001 May 26; 357(9269):1644-50.
This study from the Karolinska
Institute, the founding institution of thyroid FNA, tested immunostaining
for galectin-3 on 1009 thyroid lesions (tissue specimens and cytological
cell-blocks) and 226 fresh cytological samples obtained preoperatively by
ultrasound-guided fine-needle aspiration of thyroid nodules (prospective
analysis). The sensitivity and specificity of galectin-3 immunodetection
in discriminating benign from malignant thyroid lesions were more than 99%
and 98% respectively. Immunostaining for galactin 3 discriminated
follicular carcinoma (positive stain). Papillary carcinomas were also
positive. If this holds up in routine cytology labs, it will be a great
advance in diagnosis.
Morris LF, Waxman AD,
The nonimpact of thyroid stunning: remnant ablation
rates in 131I-scanned and nonscanned individuals.
J Clin Endocrinol
Metab 2001 Aug; 86(8):3507-11.
Thyroid stunning has been
reported as the temporary impairment of thyroid tissue after a 111-MBq (3
Mci) or greater diagnostic 131I dose that decreases the final absorbed
dose in ablative therapy. To assess whether a stunning effect has any
impact on therapeutic outcomes, the authors compared initial treatment
ablation rates in patients who received 111- to 185-MBq 131I diagnostic
scans (n = 37) before ablative doses of 3700-7400 MBq with ablation rates
in patients who did not receive any 131I before the initial treatment dose
(n = 63). Ablation rates were 64.9% for scanned patients and 66.7% for
nonscanned patients, a nonsignificant difference. Nonscanned patients with
metastatic lesions (n = 23) were ablated at a higher rate (78.3%) than
scanned patients (n = 9) (66.7%), but the difference was not significant
(P = 0.50). It is possible that the reported stunning phenomenon,
specifically its impact in temporarily impairing tissue, has been
overemphasized. (However, quantitative studies show reduction of the
uptake in therapy doses after previous diagnostic doses. This is still an
Pacini F, Agate L, Elisei
R, Capezzone M, et al.
Outcome of differentiated thyroid cancer with
detectable serum Tg and negative diagnostic (131)I whole body scan:
comparison of patients treated with high (131)I activities versus
J Clin Endocrinol Metab 2001 Sep; 86(9):4092-7.
Detectable serum Tg levels
associated with negative diagnostic (131)I whole body scan are not
infrequently found in patients with differentiated thyroid cancer. Several
researchers have shown that in these patients the administration of high
(131)I activity (100 mCi or more) increases the sensitivity of a
posttherapy diagnostic (131)I whole body scan performed a few days later
and allows the detection of neoplastic foci not seen with diagnostic doses
of (131)I. Empirical radioiodine treatment has also been advocated by some
researchers, but its therapeutic effect is controversial. In our
institute, positive serum Tg/negative diagnostic (131)I whole body scan
patients were not treated with high (131)I activities before 1984;
afterward, almost all patients with positive serum Tg/negative diagnostic
(131)I whole body scan patients were treated with radioiodine, and a
posttherapy diagnostic (131)I whole body scan was performed. In the
present retrospective study the authors compared the outcome of these two
groups of patients, 42 treated and 28 untreated, followed for mean periods
of 6.7 +/- 3.8 and 11.9 +/- 4.4 yr, respectively. In the treated group the
first posttherapy diagnostic (131)I whole body scan was negative in 12
patients and positive in 30 patients. (131)I treatment was further
administered only in the latter group. At the end of follow-up in treated
patients a complete remission (normalization of serum Tg off L-thyroxine
and negative diagnostic (131)I whole body scan) was observed in 10
patients (33.3%). In 9 cases (30%) posttherapy diagnostic (131)I whole
body scan became negative, and serum Tg was reduced but still detectable;
in 11 patients (36.6%) serum Tg was detectable, and posttherapy diagnostic
(131)I whole body scan was positive. The resolution of (131)I uptake in
lung metastases was observed in 8 of 9 cases (88.8%) and in cervical node
metastases in 11 of 18 cases (61.1%). In patients treated only once
because the posttherapy diagnostic (131)I whole body scan was negative
(n=12), 2 patients (16.7%) were in apparent remission, 7 (58.3%) had
detectable Tg values without evidence of disease, 2 (16.7%) showed lymph
node metastases in the mediastinum, and 1 patient (8.3%) died because of
lung metastases. Of the 28 untreated patients, none with radiological
evidence of disease, serum Tg off L-thyroxine therapy became undetectable
in 19 cases (67.9%), significantly reduced in 6 cases (21.4%), and
unchanged or increased in 3 patients (10.7%), 1 of whom developed lung
metastases 14 yr after the diagnosis.
In summary, the results
indicate that in patients with detectable serum Tg and negative diagnostic
(131)I whole body scan, treatment with high doses of (131)I may have
therapeutic utility in patients with lung metastases and, to a lesser
extent, in those with lymph node metastases. However, in view of the
frequent normalization of Tg values in untreated patients, we believe that
treatment with (131)I should be considered according to the result of the
first posttherapy scan. If positive in the lung, (131)I treatment should
be continued up to total remission; surgical treatment should be preferred
in patients with node metastases, and no treatment should be used in those
with thyroid bed uptake or no uptake.
Csako G, Byrd D, Wesley RA,
Sarlis NJ, Skarulis MC, Nieman LK, Pucino F.
Assessing the effects of
thyroid suppression on benign solitary thyroid nodules. A model for using
quantitative research synthesis.
Medicine (Baltimore) 2000 Jan; 79(1):
Systematic review of the
available information with a modified, largely quantitative method of
research synthesis disclosed that an initial trial of thyroid hormone
suppression therapy leads to clinically significant (> or = 50%)
reduction of nodule size or arrest of nodule growth in a subset of
patients with benign solitary thyroid nodules. In fact, in addition to
objective improvements due to decreasing nodule size, L-T4 suppression
therapy may benefit patients by reducing perinodular thyroid volume.
Consequently, both pressure symptoms and cosmetic complaints may improve.
(This objective review concludes that thyroid suppressive therapy is
efficacious, a controversial point of view with which I
Wesche MF, Tiel-V Buul MM,
Lips P, Smits NJ, Wiersinga WM.
A randomized trial comparing
levothyroxine with radioactive iodine in the treatment of sporadic
J Clin Endocrinol Metab 2001;
The authors of this Dutch study
randomized 32 patients with nontoxic nodular goiter to receive I-131
therapy and another 32 to receive thyroxine suppression, and followed them
for 2 years. Their mean age was 50 years. The I-131 dose was 120
microcuries/ml and the initial T4 dose was 2.5 ?g/kg. The T4 dose was
adjusted to achieve a serum TSH between 0.01 and 0.1 mU/L. Mean thyroid
volume was about 60 ml (17-260 ml). Goiter was decreased by 44% at 2 years
in those receiving I-131. The response was inversely related to goiter
size; the larger the goiter, the smaller the relative decrease in size.
With levothyroxine thrapy, there was not a significant decrease in goiter
size for the group as a whole. However, 43% responded to T4 therapy with a
decrease of 22% at two years. If patients who started with suppressed TSH
were excluded, the response rate would have been 52% (11/21). The large
suppressive T4 doses used caused a significant fall in BMD in the lumbar
spine and hip. The authors conclude that I-131 therapy is more effective
and better tolerated than levothyroxine suppression of TSH.
wrote an interesting editorial about this study in which
she summarized the 7 published studies of radioiodine therapy for sporadic
nontoxic goiter :
J Clin Endocrinol Metab. 2001 Mar;86(3):998-1005
Samuels MH. Evaluation and treatment of sporadic nontoxic goiter--some
answers and more questions.
Recognizing, understanding, and treating postpartum thyroiditis.
Endocrinol Metab Clin North Am 2000 Jun; 29(2): 417-30,
This is an excellent concise
review of post-partum thyroiditis and its ramifications.
Bauer DC, Ettinger B,
Nevitt MC, Stone KL
Risk for fracture in women with low serum levels of
Ann Intern Med.
Women with TSH <0.1 mU/L,
during an approximately 4-year followup, had a 3-fold increased risk for
hip fracture and a 4-fold increased risk for vertebral fracture compared
with women who had normal TSH.
Parle JV, Maisonneuve P,
Sheppard MC, Boyle P, Franklyn JA.
Prediction of all-cause and
cardiovascular mortality in elderly people from one low serum thyrotropin
result: a 10-year cohort study.
Lancet 2001 Sep 15; 358(9285): 861-5.
Jayne Franklyn and her
colleagues followed a cohort of 1191 people over age 60 who had been
screened by serum TSH measurement. 71 (6%) had subnormal serum TSH, and 20
of these were <0.1 mUL. During a 10 year follow-up, the mortality of
those with subnormal TSH was 2.3-2.6-fold greater from circulatory and
cardiovascular disease. This occurred at 2 to 5 years follow-up. To me,
the results imply that subnormal TSH should be treated.
practice. Subclinical hyperthyroidism.
N Engl J Med. 2001;345:512-6.
Anthony Toft wrote an excellent
review of this disorder. He recommends I-131 therapy for patients with
subclinical hyperthyroidism and atrial fibrillation.
Bartalena L, Pinchera A,
Management of Gravesí ophthalmopathy: reality and
Endocr Rev 2000 Apr;21(2):168-99
This is a thorough review of the
difficult problem of management of Gravesí eye disease by the group which
has done the best work in this area in the past decade.
Shen DH, Kloos RT,
Mazzaferri EL, Jhiang SM.
Sodium iodide symporter in health and
Thyroid 2001 May; 11(5): 415-25
This an excellent review of the
burgeoning literature on the sodium iodide symporter with a strong