Iodine-induced hypothyroidism in euthyroid subjects with a previous episode of subacute thyroiditis

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.     

The iodide perchlorate discharge test in women with previous post-partum thyroiditis: relationship to sonographic appearance and thyroid function

BACKGROUND Post-partum thyroid disease occurs in 50% of anti-thyroid peroxidase (TPO) antibody positive women (detected at 16 weeks' gestation) and is characterized by a transient episode of hyper, hypo or hyper-hypo thyroidism. In approximately 20% of these women the hypothyroidism is permanent. However, the extent of long-term thyroid dysfunction, possibly mediated by immune attack, in those anti-TPO Ab + ve women who have had only transient or no thyroid dysfunction during the postpartum period is not clear. OBJECTIVE We have therefore studied the frequency of iodide organification defects by iodide perchlorate discharge testing, and of thyroid morphological abnormalities by ultrasound scanning in euthyroid women following their episode of post-partum thyroiditis (PPT). DESIGN The study group comprised 17 women with previous PPT (PPT +ve) and 12 women who had positive anti-TPO antibodies during pregnancy but who did not develop PPT (PPT-ve). Women were studied 15-47 months following their episode of PPT. RESULTS Iodide perchlorate discharge tests were positive (more than 10% discharge) in 7 (41 %) PPT + ve and 5 (42%) PPT-ve subjects (P = NS). Morphological abnormalities on thyroid ultrasound were detected in 7 of 14 (50%) PPT + ve and 7 of 9 (77%) PPT-ve subjects (P = NS). There was a strong association between abnormalities of iodide organification and morphology: of 11 subjects with positive iodide perchlorate discharge tests, 10 had abnormal (positive) ultrasound scans; of 12 subjects with negative iodide perchlorate discharge tests 8 had negative ultrasound scans (P= 0.013, Fisher's exact test). CONCLUSIONS Long-term subtle defects of thyroid function and morphology are common in women with anti-TPO antibodies in pregnancy, whether or not they develop postpartum thyroiditis. The clinical significance of these findings is unclear but a continuing thyroid pathological process is suggested.     

Clinical manifestations of postpartum thyroid disease.

Postpartum thyroiditis (PPT) occurs in 5%-9% of unselected postpartum women; hyperthyroidism and hypothyroidism develop, the latter being permanent, in up to 25 %-30% of women. PPT is strongly associated with antithyroid peroxidase (anti-TPO) antibodies, but 50% of anti-TPO positive women do not develop thyroid dysfunction. Symptom analysis has shown that lack of energy and irritability were the most frequent hyperthyroid symptoms whereas lack of energy, aches and pains, poor memory, dry skin, and cold intolerance were the significant hypothyroid features. Some of these symptoms were more frequently observed than in antibody-negative controls even when these patients were euthyroid and in anti-TPOAb positive women who did not develop PPT at all. The diagnosis of PPT is based on the observation of abnormal thyroid function tests in a postpartum anti-TPOAb-positive woman: transient hyperthyroidism occurs at 14 weeks and hypothyroidism at 19 weeks postpartum. Diffuse or multifocal hypoechogenicity of the thyroid is seen on echography and a thyroid destructive process is evidenced by an increase in serum thyroglobulin and urinary iodine excretion. In addition to the 25%-30% of women who develop permanent hypothyroidism at 3 years, recent data indicate that 50% of women who have developed PPT will be hypothyroid 7-9 years later. The long-term risk is only 5% for those anti-TPOAb positive women not developing thyroid dysfunction postpartum. The risk of recurrent PPT is 70% if previous PPT was experienced and 25% if the patient was euthyroid after the first pregnancy.     

Approach to the patient with postpartum thyroiditis

Postpartum thyroiditis (PPT) is the occurrence of de novo autoimmune thyroid disease, excluding Graves' disease, in the first year postpartum. The incidence of PPT is 5.4% in the general population, and it is increased in individuals with other autoimmune diseases such as type 1 diabetes mellitus. The classic presentation of PPT of hyperthyroidism followed by hypothyroidism is seen in 22% of cases. The majority of women with PPT experience an isolated hypothyroid phase (48%), with the remainder experiencing isolated thyrotoxicosis (30%). Up to 50% of women who are thyroid antibody positive (thyroid peroxidase antibody and/or thyroglobulin antibody) in the first trimester will develop PPT. Symptoms are more common in the hypothyroid phase of PPT and include fatigue, dry skin, and impaired memory. Despite multiple studies exploring the relationship between PPT and postpartum depression, or postpartum depression in thyroid antibody-positive euthyroid women, the data are conflicting, and no firm conclusions can be reached. Long-term follow-up of women who had an episode of PPT reveals a 20-40% incidence of permanent primary hypothyroidism. In a single study, selenium administration significantly decreased the incidence of PPT, but replication of the findings is needed before the recommendation can be made that all pregnant thyroid peroxidase antibody-positive women receive selenium. The indication for treating the hyperthyroid phase of PPT is control of symptoms, whereas treatment of the hypothyroid phase of PPT is indicated for symptomatic relief as well as in women who are either breastfeeding or attempting to conceive.     

Iodine-induced subclinical hypothyroidism in euthyroid subjects with a previous episode of amiodarone-induced thyrotoxicosis.

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.     

Thyroid dysfunction in a prospectively followed series of patients with progressive systemic sclerosis

Thirty-nine patients with progressive systemic sclerosis (PSS) in stable clinical conditions were extensively evaluated for the presence of thyroid disease. Two patients had previously undetected hypothyroidism while 7 additional patients had normal serum thyroid hormone levels but an exaggerated TSH response to thyrotropin-releasing hormone (TRH) administration, consistent with subclinical hypothyroidism. Four of the 9 subjects with abnormal TRH responses had positive antithyroid antibodies and of the remaining 5, 4 had been on chlorambucil or prednisone. Basal TSH and TSH response to TRH were significantly higher in PSS patients as a group when compared to a control group and increased with increasing duration of PSS. Serum antithyroid antibodies (antithyroglobulin and/or antimicrosomal antibodies) were positive in 18% and thyroid scans were abnormal in 18% of the patients. The euthyroid sick syndrome was not seen. Our findings indicate an increased frequency of, sometimes previously unsuspected, clinical and subclinical hypothyroidism in stable PSS patients which appears to be autoimmune in nature and becomes more prevalent with increased PSS duration. Careful and regular monitoring of the thyroid function in PSS patients is advisable.     

Induction of autoimmune hypothyroidism and subsequent hyperthyroidism by TSH receptor antibodies following subacute thyroiditis: a case report.

A 45 year-old man had a typical episode of subacute thyroiditis with tender goiter, depressed radioiodine uptake (RAIU) and elevated erythrocyte sedimentation rate. The titer of TSH binding inhibitor immunoglobulin (TBII), which had been 8.6% at initial presentation, rose to 14.9% in 2 weeks. TBII consisted of high titers (94%) of TSH stimulation-blocking antibodies (TBAb) and negative thyroid stimulating antibodies (TSAb). About 2 months after the first visit, TBII titers had risen to 48.9% and were persistently elevated for 5 months with high TBAb activity. The patient developed hypothyroidism with a maximum serum TSH level of 54.5 microU/ml. TBII and TBAb titers then gradually decreased, and the patient spontaneously recovered from hypothyroidism. Eighteen months after the episode of subacute thyroiditis, he became hyperthyroid with elevated TSAb and negative TBAb values. Doppler ultrasonography showed increased blood flow in the thyroid, and RAIU at 24 h was 53%. He was treated with antithyroid drugs, and soon became euthyroid. This case indicates that subacute thyroiditis can induce thyroid autoimmunity, and that the character of TSH receptor antibodies (TSHRAb) in these patients can change thereby modifying their thyroid function.     

Increased sensitivity to the inhibitory effect of excess iodide on thyroid function in patients with beta-thalassemia major and iron overload and the subsequent development of hypothyroidism

OBJECTIVE: Patients with beta-thalassemia frequently develop primary hypothyroidism and other endocrine disorders due to iron overload. We studied whether administration of excess iodide to patients with apparently normal thyroid function could uncover an underlying thyroid disease. DESIGN AND METHODS: Twenty-five patients, 10 prepubertal (mean age 11+/-3 years) and 15 adults (mean age 23+/-5 years) with normal thyroid hormone and TSH levels, a normal response of TSH to TRH and negative thyroid peroxidase antibodies received 20mg iodide three times daily for three weeks, and thyroid hormone and TSH levels were measured weekly during, and for three weeks after, iodide administration and every 3 months thereafter for the next 5 years. RESULTS: During iodide administration there was a significant decrease in thyroid hormone concentrations which remained within normal levels, and a significant increase in TSH concentrations which in 14 out of 25 (56%) patients reached the hypothyroid level. Baseline TSH values were higher in those patients who developed subclinical hypothyroidism (2.31+/-0.71mU/l vs 1. 34+/-0.64mU/l, P=0.0016). Subclinical hypothyroidism developed in 70% of prepubertal and in 47% of adult patients. Serum ferritin was elevated in all patients. Nine of the fourteen patients (64.3%) who developed subclinical hypothyroidism during iodide administration developed hypothyroidism during the 5-year follow-up compared with only one of the eleven patients with a normal response to iodide (P=0.004). CONCLUSIONS: Patients with beta-thalassemia should not be exposed to excess iodide due to increased sensitivity to its inhibitory effects on thyroid function. The susceptible individuals frequently develop permanent hypothyroidism in the following years.     

Postpartum thyroiditis: long-term follow-up.

OBJECTIVE: To determine the incidence of persistent hypothyroidism (PH) after a long follow-up in 45 patients with postpartum thyroiditis (PPT) from a nonselected population of 641 pregnant women (PPT incidence 7.8%) and the clinical and biochemical factors associated with PPT evolution. DESIGN AND PATIENTS: The 45 women who developed PPT were followed for 8.1 +/- 2.2 years after delivery. MEASUREMENTS: Age at delivery, family and personal history, smoking, newborn gender, breast-feeding, and PPT course were recorded. Thyrotropin (TSH) and free thyroxine (T(4)) concentrations and antithyroid antibodies were evaluated at each visit. PH was considered when it persisted one year after being diagnosed. RESULTS: Fourteen of 45 patients with PPT developed PH with a probability of 56% after a PPT episode with hypothyroidism. None of the patients who developed hyperthyroidism alone during PPT evolved to PH. PH risk was higher if the newborn was a girl (relative risk [RR] 3.88) and increased for each additional TSH unit during PPT and for every additional year of the mother's age. CONCLUSIONS: The probability of developing PH after a PPT with hypothyroidism episode is 56%. PPT screening in all women permits us to establish levothyroxine treatment, if necessary, before a new pregnancy.     

Postpartum thyroiditis

Postpartum thyroiditis (PPT) is the occurrence, in the postpartum period, of transient hyperthyroidism and/or transient hypothyroidism, with most women returning to the euthyroid state by 1 year postpartum. The prevalence of PPT varies from 1.1 to 16.7%, with a mean prevalence of 7.5%. Women with type I diabetes mellitus have a three-fold increase in the prevalence of PPT. PPT is an autoimmune disorder which is a transient form of Hashimoto's thyroiditis occurring postpartum as a consequence of the immunologic flare following the immune suppression of pregnancy. Women experience symptoms in both the hyperthyroid and hypothyroid phase, but the association between PPT and postpartum depression remains undefined. Approximately 25% of women with a history of PPT will develop permanent hypothyroidism in the ensuing 10 years. Treatment for the hyperthyroid phase, when required, is a short dose of beta-blockers. Women with a TSH greater than 10 mU/l, or between 4 and 10 mU/l with symptoms or attempting pregnancy, require thyroid hormone replacement. Whether or not to screen for PPT remains controversial.     

The mechanism of spontaneous hypothyroidism in patients with Graves' disease after antithyroid drug treatment

The natural course of Graves' disease results in hypothyroidism in up to 20% of patients previously treated with antithyroid drugs. The precise mechanisms are not known, although autoimmune destruction of thyroid tissue has been proposed. We studied sequentially obtained serum samples from three patients with hyperthyroid Graves' disease previously treated with an antithyroid drug who became hypothyroid to determine possible causes of their hypothyroidism. Antithyroglobulin and antithyroid microsomal autoantibodies, TSH binding inhibitory immunoglobulin (TBII), thyroid-stimulating antibody (TSAb), and thyroid stimulation-blocking activity were measured. Autoantibodies were markedly elevated throughout the clinical course in all three patients. Patient 1 had no TBII and blocking activity and extremely high TSAb when she was euthyroid as well as hypothyroid. Hypothyroidism was probably the result of autoimmune thyroid destruction. In patient 2, TSAb disappeared, and TBII and blocking activity increased markedly when she developed hypothyroidism, which thus appeared to result from blocking antibodies. Patient 3 had intermittent periods of hyper- and hypothyroidism before becoming and remaining euthyroid. While initially hypothyroid, TBII was weakly positive, and TSAb was strongly positive; subsequently, when hyperthyroidism recurred, TBII and TSAb were strongly positive. Hypothyroidism appeared to result from focal autoimmune thyroiditis. Patients with hyperthyroid Graves' disease may develop hypothyroidism later by different means. Autoimmune thyroiditis, diffuse or focal, with thyroid destruction is one mechanism. The appearance of antibodies that block TSH stimulation may be another.     

Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone-induced hypothyroidism

Iodine excess is associated with a low thyroidal radioiodine uptake due to dilution of the radioisotope by the increased stable iodide pool. We studied thyroidal uptake of radioisotopes in cardiac patients with iodine excess due to amiodarone treatment. 99mTc-pertechnetate scintigraphy was performed in 13 patients receiving long term amiodarone therapy. Five patients had a clearly visible thyroid gland, and 8 patients had no or a very faint thyroid image. All patients with positive scans had an increased plasma TSH level, whereas all patients with negative scans had a normal or absent TSH response to TRH. Thyroidal uptake and discharge of 123I were studied in 30 other patients. Group I (n = 11) had normal plasma TSH responses to TRH and no iodine excess, group II (n = 7) had normal TSH responses to TRH and excess iodine from metrizoate angiography in the previous month, group III (n = 7) had normal or decreased TSH responses to TRH while receiving long term amiodarone therapy, and group IV (n = 5) had increased TSH responses to TRH while receiving long term amiodarone therapy. The mean radioiodine uptake value in group I [5.4 +/- 0.8% (+/- SE) at 60 min] was higher than those in group II (2.3 +/- 0.7%; P = 0.009) and group III (0.8 +/- 0.3%; P = 0.0005), but not different from that in group IV (5.3 +/- 1.2%; P = NS). Radioiodine discharge after perchlorate (expressed as a percentage of the 60 min uptake) in group I (10.1 +/- 2.2%) was lower than those in group II (24.9 +/- 10.6%; P = 0.05) and group III (28.8 +/- 5.3%; P less than 0.005), whereas discharge in group IV (58.0 +/- 6.1%) was greater than those in group II (P less than 0.05) and group III (P less than 0.01). In conclusion, 1) thyroid visualization by 99mTc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients. 2) The organification defect induced by iodine excess is greater in iodide-induced hypothyroidism than in eu- or hyperthyroidism. These findings may be explained by the increased TSH secretion in hypothyroidism and/or by decreased thyroidal concentration of an unknown specific iodinated compound (whose concentration and action vary with the total organic iodine content of the thyroid) that mediates the inhibition of iodide transport.     

Evaluation of thyroid functions with respect to iodine status and TRH test in chronic autoimmune thyroiditis

Objective: Chronic autoimmune thyroiditis (CAT) is the most common form of thyroiditis in childhood and a frequent cause of acquired hypothyroidism. The objective of this study was to evaluate the thyroid status of childrenand adolescents with CAT with respect to iodine status and diagnostic values of thyrotropin-releasing hormone (TRH) test. Methods: Seventy-one children (mean age: 11.6 years) were studied in a retrospective analysis. Free thyroxine (T4), thyrotropin (TSH), TSH response to TRH test, thyroid autoantibodies, thyroid sonography, and urinary iodine excretion (UIE) were evaluated. Results: At diagnosis, 8.5% of patients had overt hypothyroidisim and 36.6% subclinical hypothyroidism; 5.6% had overt hyperthyroidisim and 8.5% had subclinical hyperthyroidism. Of them, 40.8% were euthyroid. Median UIE was 51 mg/L in overt hypothyroidism and 84 mg/L in subclinical hypothyroidism. The values were 316 mg/L and 221 mg/L in overt and subclinical hyperthyroidism, respectively. Basal TSH showed a strong correlation with peak TSH level on TRH test. Thirty-four percent of patients with normal basal TSH level showed an exaggerated TSH response. Conclusion: Iodine deficiency was seen more in cases with hypothyroidism, while excess of iodine was observed to be more frequent in hyperthyroid patients. Iodine status was a strong predictorof the thyroid status in CAT. TRH test may be helpful in further delineating patients with subclinical hypothyroidism. Conflict of interest:None declared.     

Iodine excess and hyperthyroidism.

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.     

Prevalence and characteristics of postpartum thyroid dysfunction in Tehran

OBJECTIVE: To determine the prevalence of postpartum thyroiditis (PPT), one of the autoimmune disorders of the thyroid which usually occurs in women in the first year after parturition. PPT presents with periods of transient thyrotoxicosis and hypothyroidism, in many cases resulting in permanent hypothyroidism. DESIGN: The study involved 1040 mothers who had contacted five health centers in Tehran for vaccination of their children. METHODS: Signs and symptoms of hypothyroidism and thyrotoxicosis, and the presence of goiter (using the World Health Organization classification), were sought. Serum T3, T4, TSH, anti-TPO and anti-Tg antibodies were measured at 3, 4.5, 6 and 9 months after parturition. In those with hypothyroidism or thyrotoxicosis and a matched group of normal women, thyroid sonography was performed. RESULTS: The prevalence of thyroiditis was 11.4%. Hypothyroidism and thyrotoxicosis occurred in 68 and 42 mothers respectively. Nine had thyrotoxicosis followed by hypothyroidism. There was one case of Graves' disease. Out of 68 hypothyroid patients, 33 women underwent treatment with levothyroxine (because of the severity of symptoms) for 12 months. Six women showed increased TSH at 6 weeks after discontinuation of thyroxine. Stage II goiter (World Health Organization classification) were observed in 21.8% of patients and in 6.7% of pospartum euthyroid women (P<0.001). Positive anti-TPO was found in 61.5% of patients and in 19% of the control group; positive anti-Tg was found in 58% of patients and in 6% of the control group (P<0.001). Sonographic changes were observed in 96% of the patients and in 7% of the control group (P<0.001). There was no significant correlation between the occurrence of thyroiditis and parity, the age of the mother, a previous history of thyroid disease in the patient or family, breast-feeding, or the gender of the child. CONCLUSION: The results of this study show a high prevalence of PPT in Tehranian women. This may be due to the length and frequency of follow-up and/or the transition from low to adequate iodine intake. The major difference with respect to other studies is the low frequency of the biphasic form of PPT.     

Natural course of autoimmune thyroiditis in Thai children

Forty-seven pediatric patients with autoimmune thyroiditis were followed for an average of 5.18+/-2.89 years. The diagnosis was based on a firm goiter and a positive test for antithyroid antibodies. Initially, 23 patients had euthyroidism, 11 overt hypothyroidism, 6 compensated hypothyroidism and 7 with low TSH. All patients had clinical euthyroidism, except two who had overt hypothyroidism. The thyroid function tests, the size of the thyroid gland and the thyroid antibodies were regularly evaluated. After the follow-up, 26 patients had untreated euthyroidism, 12 with overt hypothyroidism received eltroxin for maintenance of euthyroidism, while 4 had compensated hypothyroidism and 5 low TSH levels. All had clinical euthyroid. The thyroid size was reduced in 12 patients (26%) while 4 (9%) had normal-sized gland. The goiter size in 35 patients (74%) remained unchanged. The antithyroglobulin and antimicrosomal antibody titers fluctuated higher in patients with overt hypothyroidism. Eltroxin was given only to those having overt hypothyroidism with diminished goiter size in 8 patients (73%).     

Thyroid function and amiodarone. Consequences on dysthyroidism testing

Amiodarone induces a decrease in serum T3 whereas T4 and rT3 increase. An increase of the thyroid iodine content (TIC) is observed in all patients at the exception of those who develop hypothyroidism under treatment. Actually, no method are available to predict an induced thyroid toxicosis (ITT) and there is no reason to perform systematically thyroid function tests except if past of the patient or clinical or morphological thyroid examinations suggest thyroid abnormality. In case of suspicion of ITT it is necessary to perform T4, T3 determinations and a TRH test. TIC measurement can be useful in order to eliminate a subacute or silent thyroiditis. Hypothyroidism is generally observed in patients with autoimmune thyroiditis. Antithyroid antibodies and TSH determinations after some months of treatment can detect subclinical hypothyroidism which is due to a high susceptibility to iodide.     

SPONTANEOUS HYPOTHYROIDISM IN SYMPTOMLESS AUTOIMMUNE THYROIDITIS. A LONG-TERM FOLLOW-UP STUDY

A follow-up study was performed on subjects with symptomless autoimmune thyroiditis in order to obtain information on the natural course of the disease. Seven out of the twenty-two subjects with symptomless autoimmune thyroiditis became hypothyroid within 4–48 months of observation, whereas fifteen subjects were still euthyroid after an observation period of 26–102 months. The yearly incidence of hypothyroidism in symptomless autoimmune thyroiditis was 7–3%. The basal serum thyrotrophin (TSH) level as well as the response in serum TSH to thyrotrophin releasing hormone (TRH) was initially elevated in all subjects who developed hypothyroidism. The annual incidence of hypothyroidism was 26% in the subjects with an initially elevated TSH level. Serum TSH was initially normal in all but one of the eleven subjects with symptomless autoimmune thyroiditis in whom it was measured, and who remained euthyroid. In this group the TRH response was initially slightly exaggerated in three out of ten subjects. It was not performed in five subjects. During the follow-up, serum TSH and its response to TRH also became normal in these cases. An elevated basal serum TSH value is thus highly indicative of subsequent hypothyroidism, and these subjects with symptomless autoimmune thyroiditis should be carefully followed-up.     

Diagnosis of hidden central hypothyroidism in survivors of childhood cancer

To determine how often central hypothyroidism remains undetected by routine out-patient tests of thyroid hormone, we studied 208 pediatric cancer survivors referred for evaluation because of signs of subtle hypothyroidism or hypopituitarism. Of the 208 (68 females and 140 males), 110 had brain tumors, 14 had other head/neck tumors, 11 had solid tumors remote from head and neck, and 73 had leukemia. Patients were evaluated 1-16 yr (mean, 6.1+/-4.1 yr) after tumor diagnosis. The nocturnal TSH surge and response to TRH were measured. Of 160 patients with free T4 in lowest third of normal, 34% had central hypothyroidism (blunted TSH surge or low/delayed TSH peak or delayed TSH decline after TRH); 9% had central hypothyroidism with mild TSH elevation (mixed hypothyroidism). Another 16% had mild primary hypothyroidism (TSH, 5-15 mU/L). Of 48 with free T4 in the upper two thirds of normal, 14% had central hypothyroidism; 17% had mild primary hypothyroidism. Incidence of central, mixed, and mild primary hypothyroidism 10 yr after tumor diagnosis was significantly related to total cranial radiation dose (P < 0.0001). Of 62 patients with central hypothyroidism, 34% had not developed GH deficiency. TSH surge identified 71%, and response to TRH identified 60% of those with central hypothyroidism. More than half of the slowly growing patients who have received cranial or craniospinal radiation for childhood cancer develop subtle hypothyroidism. In our study group, 92% of patients with central hypothyroidism and 27% with mixed hypothyroidism would have remained undiagnosed using baseline thyroid function tests alone. Both TSH surge and response to TRH must be evaluated to identify all of these patients.