Low Radioactive Iodine Uptake Research Articles

Immunotherapy-Induced Thyroiditis in Cancer Patients

Hyperthyroid patients may have increased or decreased radioiodine uptake on I-123 uptake and scan, which helps to differentiate the etiology of the hyperthyroid state. Thyroiditis is an uncommon complication of cancer immunotherapy and, in this situation, is likely secondary to an autoimmune response. The typical presentation of thyroiditis, regardless of the etiology, is elevated T4 and/or T3, low TSH and low radioactive iodine uptake. Herein we report a case of cancer immunotherapy-induced thyroiditis in a 34-year-old female diagnosed with right breast grade 2 invasive ductal carcinoma with ER and PR positive, Her2neu negative tumor markers. Due to her ER-positive tumor, 8-cycles of chemo-immunotherapy with Paclitaxel + Pembrolizumab were prescribed. The patient began to complain of intermittent palpitations halfway through her treatment, and her TSH after 6 cycles of treatment was <0.01 U/ml. She had negative TSI or anti-TPO (Pre-treatment TSH- 1.54 U/ml) antibodies. I-123 thyroid uptake and scan demonstrated faint thyroid activity with very low I-123 uptake, consistent with thyroiditis. Her treatment was ultimately continued and continued close monitoring of thyroid function tests was recommended.

Clinical Profile of Patients with Hyperthyroidism in Zagazig University Hospitals

Hyperthyroidism is a condition that occurs due to over production of thyroid hormones by the thyroid gland . It can be categorized according to thyroid hormone levels into overt and subclinical hyperthyroidism. Also could be classified into, normal (or high) and low thyroid radioactive iodine uptake according to radioiodine uptake. So, the aim of this study was to evaluate the difference in the clinical profile between hyperthyroid patients and its relation to thyroid scan imaging. Also to avoid prescribing antithyroid medications to patients with thyroiditis, this could lead to hypothyroidism . Materials and methods: This is a prospective cohort study for patients with hyperthyroidism. Patients have been enrolled from Endocrinology Outpatient Clinic at Zagazig University Hospitals in the period from December 2018 to October 2020. Results: patients were divided into two major groups, overt hyperthyroidism (group 1) and subclinical hyperthyroidism (group 2). All patients of group (1) had abnormal thyroid gland examination but, only 50 % of group (2) patients had showed abnormal gland examination (p= <0.001). 83 .3% of patients of group (1) had high thyroid uptake and 62.5 % of patients of group (2) had high thyroid uptake (p=0.108). There was highly statistical significance between the two groups as regard F. T4( P = <0.001) and F .T3 (p = < 0.001 ) , but no difference in TSH( p =0.223) . Conclusion: The thyroid scan had cross linkage with abnormal thyroid function ,

Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter.

Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. 40 patients (14 male, 26 female, age 57-80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. The mean RAIU increased significantly from 30.44 ± 7.4% to 77.22 ± 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation.

Letter to the Editor Amiodarone-induced thyrotoxicosis with paroxysmal supraventricular (ectopic atrial) tachycardia: and review of the literature

Letter to the Editor Amiodarone-induced thyrotoxicosis with paroxysmal supraventricular (ectopic atrial) tachycardia: and review of the literature

Recombinant TSH and Lithium Overcomes Amiodarone-Induced Low Radioiodine Uptake in a Thyrotoxic Female

Introduction:Recombinant human thyroid-stimulating hormone(rhTSH) increases radioactive iodine uptake(RAIU) in selected populations, while lithium is used as an adjunct to radioactive iodine (RAI) therapy in Graves’ disease with low RAIU. In this report, both drugs used in combination, overcame low iodine-131 uptake in a Graves’ patient.Clinical Case:A 39-year old female with Graves’ disease, acquired thionamide-induced agranulocytosis, and severe hypokalemia, subsequently went into cardiorespiratory arrest. On resuscitation, she had ventricular tachyarrhythmias which were cardioverted using amiodarone. She was subsequently placed on IV hydrocortisone amiodarone and propranolol. On admission, she was normotensive, tachycardic, and afebrile. She had fine tremors, hyper reflexia, and diffuse, non-tender thyromegaly. Initial investigations showed normal complete blood count, hypokalemia and elevated alanine transaminase levels. Levels of thyroid stimulating hormone were low (0.03 uIU/L, N = 0.27-3.75). Thyroid ultrasound showed diffuse thyromegaly with uniform echopattern and normal color flow Doppler, radioiodine uptake showed low uptake at 0400h and 2400h (6% and 7%, respectively). In preparation for RAI therapy, she was given lithium 900mg/day for 12 days to increase RAI retention. To increase iodine-131 uptake, two doses of 0.9mg rhTSH were injected intramuscular, 24 hours apart, before RAI therapy. Repeat RAIU after the second dose of rhTSH showed more than a 5-fold increase in 0400h uptake compared with the baseline (32% vs. 6%). Exactly 24 hours after the second dose of rhTSH, she was given 25mCi of iodine-131. Thereafter, the patient’s clinical and biochemical markers continued to improve. She became hypothyroid and is currently on levothyroxine replacement therapy.Conclusions:This case demonstrates the efficacy of combining rhTSH and lithium to overcome amiodarone-induced low iodine-131 uptake in Graves’ disease.

A Case of Painless Thyroiditis Followed by Graves' Disease

A 30-year-old man was admitted to our hospital because of fatigue, palpitation and severe weakness of both legs. The admission laboratory findings revealed thyrotoxicosis, and I thyroid scintigraphic imaging revealed a low radioactive iodine uptake. He was treated for painless thyroiditis for about 4 months. However, thyrotoxic state had continued and radioactive iodine uptake was markedly increased in the follow up scan. Painless thyroiditis often relapses, but rarely develops into Graves’ disease. This is a rare case in which painless thyroiditis was followed by Graves’ disease. (Endocrinol Metab 27:147-150, 2012)

Lithium carbonate pre-treatment in 131-I therapy of hyperthyroidism

The aim of the present work was to investigate the influence of lithium carbonate on the kinetics of radioiodine in the thyroid gland, and the long-lasting effect of radioiodine therapy pre-treated with lithium carbonate in patients with different types of hyperthyreosis and low baseline 24-h thyroidal radioactive iodine uptake (RAIU). The examinations were performed in two groups of patients: in a control group with RAIU 〉 30% and in patients with RAIU 〈 30%. All groups were comparable with regard to age, sex, duration and type of disease (Graves' disease, autonomous node, multinodular goitre). The control group was treated (without lithium) according to described protocol. The second group was pre-treated with lithium carbonate in a dose of 1.0 g/day for 6 days before radioiodine and 3 days thereafter. A significant increase in iodide uptake in the thyroid gland was observed during intake of lithium carbonate in 106 out of 128 patients. A decrease of T(3), FT(3), T(4), and FT(4) levels and no significant changes in concentration of TSH were observed as an effect of lithium carbonate treatment. Three years of follow-up show that the results of radioiodine therapy with short lasting lithium carbonate intake are better in the first year and are similar in the second and third years in comparison to the control group. Lithium pre-treatment in hyperthyroid patients with low baseline uptake of radioiodine can increase iodine retention in the thyroid gland independently of the primary disease and permits the use of lower doses of radiation in the therapy.

Radioiodine 131I Treatment for Large Nodular Goiter: Recombinant Human Thyrotropin Allows the Reduction of Radioiodine 131I Activity to Be Administered in Patients with Low Uptake

(131)I therapy is effective in reducing the volume of large nodular goiters (thyroid volume [TV]), mainly after stimulation with recombinant human thyrotropin (rhTSH). The amount of (131)I to be administered inversely depends on thyroid radioactive iodine uptake (RAIU). In patients with low RAIU, we evaluated the efficacy of (131)I treatment at lower doses with respect to those calculated on the basal RAIU, after rhTSH stimulation. Eighteen consecutive patients (17 women and 1 man, 49-83 years) with large nodular goiter were included in the study. At enrollment, 24th h RAIU, TSH, free thyroxine, free triiodothyronine, thyroglobulin antibodies, thyroid peroxidase antibodies, TSH receptors antibodies, urinary iodine, and TV were measured. RAIU was <40% in 11 patients (lower uptake group [LUG]) and >40% in 7 (higher uptake group [HUG]). RAIU difference in the two groups was significant (p < 0.0001). LUG patients were treated with rhTSH (0.03 mg i.m.) and RAIU was measured again after 24 hours. The administered amount of (131)I was aimed to give the thyroid a dose of 100 Gy, by the formula: (131)I activity = 370 MBq × TV (mL)/RAIU(%), taking into account RAIU value after rhTSH for LUG patients. Patients were re-evaluated 3 and 12 months after therapy. At enrollment, LUG and HUG patients did not differ for TV, free thyroxine, free triiodothyronine, TSH, and urinary iodine. LUG patients were older than HUG patients (p = 0.027). In LUG, the uptake increased after rhTSH (42.8% [36%-47.5%] vs. 30% [23.4%-31.6%], p = 0.0044). The (131)I activity was 1073 MBq (740-1103 MBq) in LUG and 851 MBq (677-918 MBq) in HUG (p = 0.22, NS), vs. 1300 MBq (1077-2150 MBq) in LUG, based on RAIU before rhTSH. At 3 and 12 months after radioiodine, TV was reduced to 74% [59%-84%] and 53% [42%-72%] in LUG and 75% [70%-77%] and 65% [54%-74%] in HUG, respectively. The reduction was significant with respect to the basal, both at 3 and 12 months, but not different between the two groups. One single dose of 0.03 mg of rhTSH increased the thyroid RAIU by 40% in patients with nodular goiter and low basal uptake. This allowed a mean reduction of 36% (26%-42%) in the administered (131)I activity without loss of effectiveness. In patients with low RAIU, rhTSH pre-treatment may optimize (131)I therapy.

Toxic Multinodular Goiter with Low Radioactive Iodine Uptake

A 74-year-old woman was referred to our hospital for goiter and persistent thyrotoxicosis. She had no signs of ophthalmopathy. She was not taking thyroid hormone. Thyroid CT revealed multiple nodules. The thyroid gland was not detected on (99m)Tc scintigraphy, (123)I uptake rate was 4.5% at 24 hours without hot nodules, and aberrant goiter was negative. After partial thyroidectomy, she was treated with levothyroxine. TRAb was undetectable during the disease course, and focal destructive change or chronic lymphocytic thyroiditis on the pathological specimens was not evident. We report a rare case of toxic multinodular goiter with low radioactive iodine uptake.

Approach to the Patient with Amiodarone-Induced Thyrotoxicosis

Amiodarone, a benzofuranic iodine-rich antiarrhythmic drug, causes thyroid dysfunction in 15-20% of cases. Although amiodarone-induced hypothyroidism poses no particular problem, amiodarone-induced thyrotoxicosis (AIT) is a diagnostic and therapeutic challenge. There are two main forms of AIT: type 1, a form of iodine-induced hyperthyroidism, and type 2, a drug-induced destructive thyroiditis. However, mixed/indefinite forms exist that may be caused by both pathogenic mechanisms. Type 1 AIT usually occurs in abnormal thyroid glands, whereas type 2 AIT develops in apparently normal thyroid glands (or small goiters). Diagnosis of thyrotoxicosis is easy, based on the finding of increased free thyroid hormone concentrations and suppressed TSH levels. Thyroid radioactive iodine (RAI) uptake values are usually very low/suppressed in type 2 AIT, most commonly low or low-normal, but sometimes normal or increased in type 1 AIT despite the iodine load. Color flow Doppler sonography shows absent hypervascularity in type 2 and increased vascularity in type 1 AIT. Mixed/indefinite forms may have features of both AIT types. Thionamides represent the first-line treatment for type 1 AIT, but the iodine-replete gland is not very responsive; potassium perchlorate, by inhibiting thyroid iodine uptake, may increase the response to thionamides. Type 2 AIT is best treated by oral glucocorticoids. The response very much depends on the thyroid volume and the severity of thyrotoxicosis. Mixed/indefinite forms may require a combination of thionamides, potassium perchlorate, and steroids. RAI is usually not feasible in AIT due to low RAI uptake values. Thyroidectomy represents a valid option in cases resistant to medical therapy.

Sunitinib-Induced Thyrotoxicosis Followed by Persistent Hypothyroidism with Shrinkage of Thyroid Volume

Sunitinib, a tyrosine kinase inhibitor, has been approved for the treatment of cancers, such as advanced renal cell carcinoma (RCC). On the other hand, sunitinib treatment is known to induce thyroid dysfunction in a substantial proportion of patients treated for advanced RCC; in fact, hypothyroidism is a frequent complication. However, little is known about sunitinib-induced thyrotoxicosis and destructive thyroiditis. Here, we report a patient with RCC who developed transient overt thyrotoxicosis followed by hypothyroidism due to sunitinib treatment. A 58-year-old woman, who had been treated with chronic thyroiditis, was diagnosed as having left RCC with bone metastasis to the rib. The patient underwent resection of the left kidney and the bone metastasis lesion. However, 3 months later, bone metastasis to the rib recurred, and sunitinib treatment was started. At 6 weeks of sunitinib therapy, the patient developed transient thyrotoxicosis, followed by persistent hypothyroidism. In the thyrotoxic phase, the patient was diagnosed as having destructive thyroiditis based on an increased thyroglobulin level, a low radioactive iodine uptake, increased free thyroxine level, and suppressed thyroid-stimulating hormone level. The thyroid volume in the hypothyroid phase was 68% of that in the thyrotoxic phase. In conclusion, the present report suggests that sunitinib-induced persistent hypothyroidism may be a consequence of preceding destructive thyroiditis with transient thyrotoxicosis. The decreased volume of the thyroid during the hypothyroid phase indicates irreversible organ damage in the present patient, thereby resulting in persistent hypothyroidism. Thus, periodic surveillance of thyroid function is mandatory during sunitinib therapy.

Congenital Hypothyroidism and Late-Onset Goiter: Identification and Characterization of a Novel Mutation in the Sodium/Iodide Symporter of the Proband and Family Members

Iodide transport defects (ITDs), rare causes of congenital hypothyroidism (CH), have been shown to arise from abnormalities of the sodium/iodide symporter (NIS). We describe a 16-year-old girl with CH caused by an ITD resulting from a novel mutation of NIS. A 16-year-old girl with CH diagnosed by a neonatal screening program received early treatment with L-thyroxine replacement therapy. A (123)I scan had failed to reveal any iodide uptake by the thyroid and salivary glands; thus, thyroid agenesis was diagnosed. Thyroglobulin (Tg) was not measured when she was a neonate or infant. Unexpectedly, at the age of 14.5 years, a nodular goiter and high serum Tg concentrations (303 ng/mL; normal, <50) were identified. Her thyroid radioactive iodine uptake was very low as was the saliva to plasma iodide ratio (0.5). Analysis of her NIS gene revealed an in-frame six-nucleotide deletion of the coding sequence (1206-1211delGTCGGC) corresponding to the deletion of amino acids 287 and 288 of the human NIS protein located at the beginning of the VIII transmembrane segment. The proband was homozygous for this deletion, whereas both unrelated parents and her brother were heterozygous. COS-7 cells transfected with the mutant NIS failed to concentrate iodide, confirming that the mutation was the direct cause of the ITD in this patient. We describe a patient with CH caused by a previously not described mutation of the NIS gene that was inherited from her parents. We therefore recommend that thyroid ultrasonography be performed in CH patients with low radioactive iodine uptake and elevated serum Tg.

Thiamazole as an adjuvant to radioiodine for volume reduction of multinodular goiter

Background: Radioiodine (131I) is an alternative to surgery for the treatment of multinodular goiter (MNG). Frequently, high activities of 131I are required for effective thyroid volume reduction (TV), due to the low and heterogeneous radioactive iodine uptake (RAIU). Thiamazole (MTZ) may be used as an adjuvant to 131I, by increasing RAIU. Objective: To evaluate the effects of MTZ in the treatment of MNG with 131I, in terms of TV reduction. Design/methods: Nine female patients (aged 73.8 ± 7.4 years) with MNG (eight with subclinical hyperthyroidism) were treated with MTZ. Doses started at 10 – 20 mg, and were adjusted monthly based on thyroid hormone levels. RAIU and TV were measured at baseline, and repeated when TSH levels > 6 mU/l were achieved. At that time, 1.11 GBq of 131I were administered. Results: Patients were treated with MTZ for 2.8 ± 0.8 months. When a tracer activity of 131I was administered, the mean serum TSH was elevated to 11.7 ± 5.4 mU/l. MTZ led to significant increases in 24-h RAIU, from 21.3 ± 8.1% to 78.3 ± 15.3% (p < 0.001). One year after 131I, median TV decreased from 97 ml (range 47 – 555 ml) to 56 ml (range 13 – 350 ml), a mean reduction of 46.2 ± 17.8% (p = 0.012). Eight patients (89%) had subclinical hyperthyroidism, which was reversed in all patients after 1 year. Five patients (56%) developed overt hypothyroidism, and no clinical adverse events were observed. Conclusion: Pretreatment with MTZ targeting against an increased serum TSH did not impair the effects of 131I. In our patients with MNG, MTZ increased RAIU and possibly enhanced 131I efficacy, leading to significant TV reduction and reversion of hyperthyroidism in all patients.

Radioactive Iodine in the Treatment of Type-2 Amiodarone-Induced Thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) is usually classified into two types: type 1, in which a high iodine content triggers the autonomous production of thyroid hormone; and type 2, in which destructive thyroiditis causes the release of preformed thyroid hormone. AIT is a difficult management problem that sometimes requires ablative thyroid therapy. The use of radioactive iodine (RAI) therapy in patients with type-1 AIT who had a 24-hour radioactive iodine uptake (RAIU) value of >10% has been previously reported. Despite its documented efficacy at usual doses (10-30 mCi) in patients with type-1 AIT, the efficacy of RAI in those with type-2 AIT has never been questioned, because type-2 patients usually have low RAIU. We thought that high adjusted-dose RAI might be an attractive alternative to thyroid gland ablation in patients with type-2 AIT. Four patients with type-2 AIT who required thyroid ablation were included in the study. These individuals were either poor candidates for surgery or had refused surgery. The size of the thyroid gland in all subjects was within normal limits, and each thyroid was characterized by a homogenous echotexture on ultrasonography, the absence of vascularity on Doppler sonography, a low (<4%) 24-hour RAIU value and the absence of thyroid autoantibodies-all of which are characteristic of type-2 AIT. The patients were initially treated with thionamides and glucocorticoids. All patients except one achieved euthyroidism before RAI therapy. All four patients received one dose of RAI (range 29-80 mCi) and followed up for 12 months. No exacerbation of thyrotoxicosis was noted after RAI therapy. Hypothyroidism (in three patients) or euthyroidism (in one patient) was achieved in first six months. In patients with type-2 AIT, RAI treatment may be the therapy of choice for thyroid gland ablation.

What Influences Early Hypothyroidism After Radioiodine Treatment for Graves' Hyperthyroidism?

The objective of this study was to evaluate the factors influencing the occurrence of early hypothyroidism after radioiodine treatment of Graves' hyperthyroidism. Of 147 patients with Graves' disease (GD) treated with radioactive I-131 (RAI) in our thyroid clinic between July 2003 and December 2004, 84 were followed at 2 and 4 to 5 months after treatment. The age range was 12 to 75 years and the dosage range in these patients was 7.4 to 29.9 mCi. Twenty-four were males and 60 were females. Factors possibly contributing to post-RAI hypothyroidism are: dosage of I-131, age, gender, size of the gland, initial serum free T4, free T3, thyroid-stimulating hormone (TSH) levels, pretreatment with antithyroid drugs, radioactive iodine uptake, and duration of disease. All patients had low TSH, elevated FT4, and elevated radioactive iodine uptake (RAIU) at 4 and/or 24 hours. Of the 84 patients followed, 46% of the males and 62% of the females became hypothyroid at 4 to 5 months (57% of the total). Twenty-one patients remained hyperthyroid and 14 patients became euthyroid. Multivariate analysis of these 84 patients showed no statistically significant single contributing factor for the development of early hypothyroidism. The early onset of hypothyroidism after RAI in GD is very common (57%) and unpredictable. Thus, after RAI treatment, all patients must be closely monitored for the development of this disorder.

SYNDROMES OF THYROTOXICOSIS WITH LOW RADIOACTIVE IODINE UPTAKE

It is very important to diagnose correctly the etiology of thyrotoxicosis, because the course and treatment of thyrotoxicosis with low radioactive iodine uptake differ significantly from that of hyperthyroidism due to Graves' disease or toxic nodular goiter. Many causes of subacute thyroiditis have been identified producing a characteristic course of transient hyperthyroidism, followed by hypothyroidism, and usually recovery. Ectopic hyperthyroidism includes factitious thyroid hormone ingestion, struma ovarii, and, rarely, large deposits of functioning thyroid cancer metastases. Iodine-induced hyperthyroidism may be associated with low radioiodine uptakes. Amiodarone-associated hyperthyroidism may be the result of subacute thyroiditis or iodine-induced hyperthyroidism; assessment and treatment can be quite challenging.

A circulating, biologically inactive thyrotropin caused by a mutation in the beta subunit gene.

Mutation of a critical carboxy-terminal cysteine residue (C105V) in the thyrotropin-beta (TSH-beta) subunit gene was found in two related families with central hypothyroidism. Affected patients had low thyroid hormone levels and radioactive iodine uptake in the thyroid gland associated with measurable serum TSH. Thyrotropin-releasing hormone-stimulated TSH secretion did not increase thyroid hormone production in these patients as compared to their unaffected siblings, suggesting that the mutant TSH was biologically inactive in vivo. Recombinant TSH harboring this mutation was confirmed to be biologically inactive in an in vitro bioassay. Based on crystallographic structure of chorionic gonadotropin, a disulfide bond between C19 and C105 in the TSH-beta subunit is predicted to form the "buckle" of a "seat belt" that surrounds the common alpha subunit and maintains the conformation and bioactivity of the hormone. This natural mutation of the TSH-beta subunit confirms the importance of the seat belt in the family of pituitary and placental glycoprotein hormones.

Sequence Analysis of the Thyrotropin (TSH) Receptor Gene in Congenital Primary Hypothyroidism Associated with TSH Unresponsiveness

Congenital primary hypothyroidism due to thyrotropin (TSH) unresponsiveness is a very rare disorder and only a few cases have been documented previously. To elucidate whether structural abnormalities in the TSH receptor (TSHR) could be a primary underlying mechanism of this disorder, we analyzed nucleotide sequence of the entire coding region of the TSHR gene in three patients diagnosed with congenital primary hypothyroidism associated with TSH unresponsiveness. Diagnosis of TSH unresponsiveness was largely made based on the following criteria: (a) congenital primary hypothyroidism with autosomal recessive inheritance, (b) a nongoitrous thyroid gland in a normal position with low thyroidal radioactive iodine uptake, (c) normal in vitro TSH bioactivity or absent in vivo response to exogenous TSH, and (d) absence of thyroid autoantibodies. The TSHR cDNA was successfully obtained from RNA of peripheral mononuclear leukocytes with reverse transcription and polymerase chain reaction, and was sequenced directly. Comparison of these nucleotide sequences with the normal TSHR sequence revealed no difference in the predicted amino acid sequence with a heterozygous polymorphism in codon 601 in one patient, indicating absence of TSHR structural abnormalities in these patients. Our results indicate that congenital primary hypothyroidism associated with TSH unresponsiveness is unlikely to be due to mutations in the TSHR-structure gene.

Hyperthyroidism With a Low Radioactive Iodine Uptake

Hyperthyroidism With a Low Radioactive Iodine Uptake

Hyperthyroidism with a low radioactive iodine uptake

To the Editor.— In small doses, inorganic iodide can function to inhibit thyroglobulin proteolysis. In larger doses, it can also block iodination of tyrosine residues within the thyroglobulin molecule. In either case, a hypothyroid state can be induced (Wolff-Chaikoff effect), which is usually transient and subject to escape. This escape phenomenon is not universal. Individuals who have abnormal thyroid tissue (autoimmune thyroiditis, or acquired after radioactive iodine therapy) often will remain hypothyroid with inorganic iodide treatment. 1 Amiodarone therapy may also result in prolonged hypothyroidism. Iodide administration may therefore cause a persistent decrease in thyroid hormone production. 2 More frequently, 3 iodide has also been shown to induce thyrotoxicosis (iod-Basedow effect) and cause immunologic aberrancies. Iodide treatment of hyperthyroidism will not achieve euthyroidism in up to 25% of individuals. 2 The radioactive iodine uptake in this group will remain low due to a dilutional effect from the exogenous iodide, despite