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Resource Network of The Iodine Movement
Iodine and Disease
IODINE AND HYPOTHYROIDISM pg 2
Iodine excess and hyperthyroidism.
Roti E, Uberti ED.
Thyroid. 2001 May;11(5):493-500. Review.
150 microg iodine are daily required for thyroid hormone synthesis. The thyroid gland has intrinsic
mechanisms that maintain normal thyroid function even in the presence of iodine excess. Large
quantities of iodide are present in drugs, antiseptics, contrast media and food preservatives.
Iodine induced hyperthyroidism is frequently observed in patients affected by euthyroid iodine
deficient goiter when suddenly exposed to excess iodine. Possibly the presence of autonomous
thyroid function permits the synthesis and release of excess quantities of thyroid hormones. The
presence of thyroid autoimmunity in patients residing in iodine-insufficient areas who develop
iodine-induced hyperthyroidism has not been unanimously observed. In iodine-sufficient areas,
iodine-induced hyperthyroidism has been reported in euthyroid patients with previous thyroid
diseases. Euthyroid patients previously treated with antithyroid drugs for Graves' disease are
prone to develop iodine-induced hyperthyroidism. As well, excess iodine in hyperthyroid Graves'
disease patients may reduce the effectiveness of the antithyroid drugs. Occasionally
iodine-induced hyperthyroidism has been observed in euthyroid patients with a previous episode
of post-partum thyroiditis, amiodarone destructive or type II thyrotoxicosis and recombinant
interferon-alpha induced destructive thyrotoxicosis. Amiodarone administration may induce
thyrotoxicosis. Two mechanisms are responsible for this condition. One is related to excess iodine
released from the drug, approximately 9 mg of iodine following a daily dose of 300 mg amiodarone.
This condition is an iodine-induced thyrotoxicosis or type I amiodarone-induced thyrotoxicosis. The
other mechanism is due to the amiodarone molecule that induces a destruction of the thyroid
follicles with a release of preformed hormones. This condition is called amiodarone-induced
destructive thyrotoxicosis or type II thyrotoxicosis. Patients developing type I thyrotoxicosis in
general have preexisting nodular goiter whereas those developing type II thyrotoxicosis have a
normal thyroid gland. The latter group of patients, after recovering from the destructive process,
may develop permanent hypothyroidism as the consequence of fibrosis of the gland.
Effects of excess iodine administration on thyroid function in euthyroid patients with a previous
episode of thyroid dysfunction induced by interferon-alpha treatment.
Minelli R, Braverman LE, Giuberti T, Schianchi C, Gardini E, Salvi M, Fiaccadori F, Ugolotti G, Roti
Clin Endocrinol (Oxf). 1997 Sep;47(3):357-61.
OBJECTIVE: To determine the effects of pharmacological quantities of iodide (SSKI) on thyroid
function in euthyroid patients previously treated with recombinant interferon-alpha (rIFN-alpha) for
chronic viral hepatitis B and C (HCV), a cytokine which may induce thyroid dysfunction.
DESIGN: Thyroid function tests were carried out in 16 euthyroid patients, 8 of whom had previously
developed thyroid dysfunction during rIFN-alpha therapy for HCV, before, during and after the
administration of 10 drops of saturated solution of potassium iodide (SSKI) (approximately 350 mg
PATIENTS: All 16 patients had been treated in the past with rIFN-alpha for HCV. Eight patients had
developed rIFN-alpha induced abnormalities in thyroid function (5 inflammatory thyrotoxicosis, 1
Graves' disease, and 2 impaired thyroid organification of iodide) and 8 had not developed thyroid
MEASUREMENTS: After baseline serum free T4 (FT4) and free T3 (FT3) concentrations, basal
and TRH stimulated TSH concentrations, and TSH-receptor (TSH-R-Ab) and thyroid peroxidase
(TPO-Ab) antibodies were measured, 10 drops saturated solution of potassium iodide (SSKI,
approximately 350 mg iodide) were given daily for 60 days and the above parameters assessed
during and after SSKI was discontinued.
RESULTS: Five of 8 patients with a previous history of rIFN-alpha induced thyroid dysfunction
developed mild iodide induced abnormalities of thyroid function (subclinical hypothyroidism (slightly
elevated basal and TRH stimulated serum TSH concentrations with normal serum FT4 and FT3
concentrations) or hyperthyroidism) compared with the 8 patients who had no previous evidence of
thyroid dysfunction during rIFN-alpha therapy.
CONCLUSIONS: In view of the present observations, it is prudent to avoid the administration of
excess iodine to euthyroid subjects with a previous episode of thyroid dysfunction during
rIFN-alpha therapy, adding a new group of patients susceptible to iodine induced thyroid disease.
Effects of iodine on thyroid function.
Braverman LE, Roti E.
Acta Med Austriaca. 1996;23(1-2):4-9. Review.
The role of iodine in the management of Graves' disease.
Braverman LE, Roti E.
Endocr Pract. 1995 May-Jun;1(3):200-4.
The use and misuse of thyroid hormone.
Roti E, Minelli R, Gardini E, Braverman LE.
Endocr Rev. 1993 Aug;14(4):401-23. Review.
Thyroid hormones are frequently prescribed for appropriate and, at times, inappropriate
conditions. It has been estimated that 1.2% of the total population in Sweden receives synthetic
levothyroxine (L-T4) (l), and 18 million prescriptions for thyroid hormone preparations are filled
annually in the United States, corresponding to more than 1% of all medical prescriptions (2).
Therefore, it is important to review the various thyroid hormone preparations (Table l), the
therapeutic indications (Table 2), the misuse of thyroid hormone (Table 3), controversial uses of
thyroid hormone (Table 4), the thyroid function tests to evaluate the correct treatment dose, and
the possible side effects of treatment."
Combination of T4 and iodine. In Germany, several investigators have evaluated the effect of a
combination of T4 and iodine in the treatment of euthyroid endemic goiter. These preparations,
which contain 100 mcg L-T4 and 100 mcg iodide as potassium iodide, are, to our knowledge,
available only in Germany (27). The reported studies (27-30) do not prove that this combination is
more effective than L-T4 alone in reducing goiter volume. This might be due to the fact that TSH-
suppressive doses of L-T4 decrease the thyroid iodine pump and, therefore, the iodine content in
the thyroid would probably not increase when iodine is administered in conjunction with L-T4 (27).
Effects of chronic iodine administration on thyroid status in euthyroid subjects previously treated
with antithyroid drugs for Graves' hyperthyroidism.
Roti E, Gardini E, Minelli R, Bianconi L, Salvi M, Gavaruzzi G, Braverman LE.
J Clin Endocrinol Metab. 1993 Apr;76(4):928-32.
In view of the adverse effects of the administration of pharmacological quantities of iodine to
euthyroid patients with a history of a wide variety of thyroid disorders, it has been suggested that
iodine-containing medications and radioopaque dyes containing iodine should be avoided, if
possible, in patients with underlying thyroid disease. We have now prospectively studied the
effects of pharmacological doses of a saturated solution of potassium iodide (SSKI) on thyroid
function in euthyroid patients with a previous history of hyperthyroid Graves' disease successfully
treated with antithyroid drugs. Ten euthyroid women (mean age, 56 yr) who had hyperthyroid
Graves' disease successfully treated with methimazole 36.4 +/- 4.7 months earlier were evaluated
before, during, and after the administration of 10 drops SSKI daily for 90 days. The following
thyroid function tests were obtained: serum T4, T3, TSH, TSH receptor antibody (TSH-RAb), and
antithyroid peroxidase antibody (AbTPO) concentrations; TRH tests; and iodine perchlorate
discharge tests. Serum T4, T3, basal and TRH-stimulated TSH, and TSH-RAb values were normal
before SSKI administration, but serum AbTPO levels were markedly positive in 7 and iodine
perchlorate discharge tests were positive in 4 of these 10 women. During SSKI administration,
basal and TRH-stimulated serum TSH values increased above normal in 2 women with normal
serum T4 and T3 concentrations; thyroid hormone values and TRH tests were normal in the other
8 patients and similar to values observed in 4 euthyroid women without a history of thyroid disease
given SSKI. Serum AbTPO increased slightly, but significantly, during SSKI administration in the 7
women with positive values at baseline (P < 0.05). TSH-RAb remained undetectable. After SSKI
withdrawal, the 10 women were reevaluated 60 and 120 days later. Two women developed a
blunted TSH response to TRH, but normal serum T4 and T3 concentrations, and 2 women
developed overt hyperthyroidism, with undetectable basal and TRH-stimulated serum TSH and
elevated serum T4 and T3 concentrations, requiring methimazole therapy. All values in the
remaining 6 women were similar to those present before SSKI administration. These results
suggest that some euthyroid patients with a history of antithyroid drug therapy for Graves' disease
may develop thyroid dysfunction during and after excess iodine administration. The development
of subclinical hypothyroidism during SSKI administration was not clinically important, but the
occurrence of overt hyperthyroidism after SSKI was discontinued did require antithyroid drug
therapy. It is advisable, therefore, to avoid iodine-containing substances in euthyroid patients with
a history of antithyroid drug therapy for Graves' disease.
Selenium administration does not cause thyroid insufficiency in subjects with mild iodine deficiency
and sufficient selenium intake.
Roti E, Minelli R, Gardini E, Bianconi L, Ronchi A, Gatti A, Minoia C.
J Endocrinol Invest. 1993 Jul-Aug;16(7):481-4.
Selenium is a trace element essential for the activity of type I 5'-deiodinase which converts
thyroxine (T4) to 3,5,3'-triiodothyronine (T3). In iodine deficient hypothyroid children at low
selenium dietary intake the supplementation of selenium induced a significant decrement of serum
FT4 and T4 concentrations and an increase of serum TSH concentrations. Since in western
countries selenium tablets begin to be largely consumed as a diet integrator, we have
administered 100 micrograms/day of selenium as selenium methionine to 8 euthyroid female
subjects with a positive iodine-perchlorate discharge test who had a previous episode of subacute
or postpartum thyroiditis. We have studied subjects with positive iodine-perchlorate discharge test
since the test indicates the existence of a subtle defect of thyroid hormone synthesis and therefore
these subjects are prone to develop thyroid dysfunction. In contrast to previous findings in
hypothyroid children at low iodine and selenium dietary intake, the supplementation of selenium
did not decompensate thyroid hormone synthesis of euthyroid subjects with reduced thyroid iodine
organification. The lack of any effect of selenium on thyroid hormone synthesis even in subjects
with subtle thyroid hormone synthesis defect may be due to the fact that these subjects had a
sufficient selenium dietary intake before selenium supplementation and an only marginally reduced
dietary iodine intake.
Iodine-induced subclinical hypothyroidism in euthyroid subjects with a previous episode of
Roti E, Minelli R, Gardini E, Bianconi L, Gavaruzzi G, Ugolotti G, Neri TM, Braverman LE.
J Clin Endocrinol Metab. 1992 Nov;75(5):1273-7.
Amiodarone-induced thyrotoxicosis (AIT) occurs most frequently in patients with underlying thyroid
disease and is generally believed to be due to the iodine contamination of amiodarone and iodine
released by the metabolism of the drug. We and others have suggested that the thyrotoxicosis
may also be secondary to amiodarone-induced thyroiditis. To further determine the etiology of AIT,
we administered large doses of iodides [10 drops saturated solution of potassium iodide (SSKI)
daily] to 10 euthyroid patients long after an episode of AIT believed to be due at least in part to
amiodarone-induced thyroiditis. Six of these 10 patients had an abnormal iodide-perchlorate
discharge test before SSKI administration, indicating a subtle defect in the thyroidal organification
of iodide. During SSKI administration, 6 patients developed marked iodine-induced basal and/or
TRH-stimulated serum TSH elevations, 2 had suppressed basal and TRH-stimulated TSH values,
and 2 had normal TSH responses compared to SSKI-treated euthyroid subjects with no history of
amiodarone ingestion or thyroid disease. Serum T4 and T3 concentrations remained normal and
unchanged during SSKI administration in both the AIT patients and control subjects. These results
strongly suggest that excess iodine may not be the cause of the hyperthyroidism associated with
amiodarone therapy, especially in those patients with probable amiodarone-induced thyroiditis.
Furthermore, like patients with a previous history of subacute thyroiditis and postpartum thyroiditis,
the present results suggest that some patients with a previous history of AIT may be at risk to
develop hypothyroidism when given excess iodine.
Iodine-induced hypothyroidism in euthyroid subjects with a previous episode of subacute thyroiditis.
Roti E, Minelli R, Gardini E, Bianconi L, Braverman LE.
J Clin Endocrinol Metab. 1990 Jun;70(6):1581-5.
The effects of the administration of pharmacological quantities of iodide on thyroid function in 18
euthyroid patients with a previous history of painful subacute thyroiditis (SAT) were evaluated, and
the results compared to those of iodide administration to 12 euthyroid patients with a previous
history of thyroid surgery (TX) for benign nodular thyroid disease. After baseline thyroid function
tests, saturated solution of potassium iodide (SSKI; 10 drops; 300 mg iodide) was administered
daily for 120 days, and serum T4, T3, and TSH concentrations were assessed 15, 30, 60, 90, 120
days and 2-4 months after SSKI was discontinued. Iodide perchlorate discharge tests were carried
out before SSKI administration, and TRH tests were performed on the last day of iodide
administration. Two SAT subjects developed clinical evidence of hypothyroidism with markedly
elevated serum TSH concentrations, and SSKI was discontinued on days 60 and 90, respectively.
Thirteen of 18 SAT patients had at least 1 abnormal thyroid function test (iodide perchlorate
discharge test, elevated serum TSH concentration, and abnormal TSH response to TRH)
compared to 2 of 12 TX patients. These findings strongly suggest that euthyroid subjects with a
previous history of SAT are prone to develop iodide-induced hypothyroidism, suggesting that
subtle abnormalities in the thyroid organification of iodide and subsequent thyroid hormone
synthesis persist years after the episode of SAT.
Environmental factors affecting autoimmune thyroid disease.
Safran M, Paul TL, Roti E, Braverman LE.
Endocrinol Metab Clin North Am. 1987 Jun;16(2):327-42.
A number of environmental factors affect the incidence and progression of autoimmune thyroid
disease. Exposure to excess iodine, certain drugs, infectious agents and pollutants, and stress
have all been implicated.
Comparative effects of sodium ipodate and iodide on serum thyroid hormone concentrations in
patients with Graves' disease.
Roti E, Robuschi G, Manfredi A, D'Amato L, Gardini E, Salvi M, Montermini M, Barlli AL, Gnudi A,
Clin Endocrinol (Oxf). 1985 Apr;22(4):489-96.
Patients with thyrotoxic Graves' disease were treated daily for 10 d with 1 g sodium ipodate, an
iodine rich X-ray contrast agent which impairs outer ring (5'-) deiodination of T4 to T3, or with 12
drops of a saturated solution of potassium iodide (SSKI). T4, T3 and reverse T3 (rT3)
concentrations were measured before, during, and 5 and 10 d after the administration of each
drug. SSKI therapy induced a decrease in the serum T4 concentration from 14.7 +/- 1.3
microgram/dl (mean +/- SE) to a nadir of 7.9 +/- 0.9 on days 9 and 10 of therapy, all values
reaching the normal range by day 9; a decrease in the serum T3 concentration from 402 +/- 43
ng/dl to a nadir of 143 +/- 20 on day 10, remaining elevated in all patients until day 5 and
decreasing into the normal range in all except one patient on days 9 and 10; and no change in the
serum rT3 concentration. Serum T4 and T3 concentrations returned to baseline values 10 d after
withdrawal of SSKI. In contrast sodium ipodate therapy induced only a modest decrease in the
serum T4 concentration from 15.1 +/- 0.7 micrograms/dl to a nadir on day 9 of 11.3 +/- 1.0 and
serum T4 remained above the normal range in most patients until day 8; a striking and rapid
decrease (within 12 h) in the serum T3 concentration from 340 +/- 36 ng/dl to mean values ranging
from 79 to 85 during the last 5 d of therapy, with most values below the normal range during the
last 3 d; and a marked increase in the serum rT3 concentration from 111 +/- 15 ng/dl to a peak
value of 376 +/- 59 on day 5. (ABSTRACT TRUNCATED AT 250 WORDS)
Five patients with iodine-induced hyperthyroidism.
Rajatanavin R, Safran M, Stoller WA, Mordes JP, Braverman LE.
Am J Med. 1984 Aug;77(2):378-84.
Iodine-induced hyperthyroidism has been frequently described when iodine is introduced into an
iodine-deficient area. However, it may also occur in patients with and without previous thyroid
disease residing in iodine-sufficient areas. Five patients with iodine-induced hyperthyroidism seen
in a 12-month period are described. All were exposed to iodine in the form of commonly used
drugs (Betadine, Iodo-Niacin, amiodarone, and radiographic contrast dyes). The cause of
iodine-induced hyperthyroidism is unclear, but it is probably more common in patients with goiters
containing previously existing areas of autonomous function or iodine-poor thyroglobulin.
Iodine-induced hyperthyroidism usually abates after iodine withdrawal in patients with multinodular
goiters or normal thyroid glands. The hyperthyroidism is usually treated with beta-blockers and
antithyroid thionamide drugs, although reinstitution of iodine to block thyroid hormone release or
corticosteroids occasionally may be necessary. Iodine-containing drugs should be given with
caution to patients with underlying thyroid disease.
Effect of iodine administration on thyroid function in diabetic patients.
Robuschi G, Emanuele R, Cavalli Sforza LT, Arsenio L, Strata A, Gnudi A, Roti E.
Acta Diabetol Lat. 1984 Oct-Dec;21(4):357-60.
Iodide-induced hypothyroidism has been observed in subjects treated with compounds with mild
antithyroid activity. The hypoglycemic agent tolbutamide belongs to the aminoheterocyclic group, a
class of compounds with antithyroid effect. Thus it was thought interesting to study the effect of
large doses of iodide on thyroid function in diabetics chronically treated with tolbutamide. Basal
thyroid function as assessed by clinical examination and iodothyronine and TSH concentrations
was normal in all patients. Furthermore, in diabetics treated with tolbutamide, hormone
concentrations were not different from those of patients treated with insulin or diet. Serum T4, T3
and TSH did not show any significant variation throughout the investigation period. Our results
suggest that thyroid function is not affected by chronic treatment with tolbutamide even when large
doses of iodide are administered.