Recombinant Human Thyrotropin Research Articles

Consultation with the Specialist: Thyroid Nodules

Based on strong research evidence, thyroid nodules in children and teenagers are more likely to be malignant than in adults. Based on strong research evidence, a history of ionizing radiation to the head or neck is an independent risk factor for the development of thyroid malignancies. There is strong research evidence, including a recent meta-analysis, supporting the use of fine-needle aspiration biopsy in the evaluation of all pediatric and adolescent patients presenting with a thyroid nodule. The surgical management and postoperative care of pediatric and adolescent patients who have well-differentiated thyroid carcinomas remains controversial, because the rarity of the disease limits the ability to conduct randomized, prospective research studies. Numerous studies have demonstrated that, despite presenting with more advanced disease, pediatric and adolescent patients with thyroid carcinoma have a higher survival rate than adults. The American Thyroid Association has issued strong evidence-based recommendations for the management of medullary thyroid carcinoma, including RET mutation testing and early prophylactic total thyroidectomy in children with high-risk mutations.

Long-Term Follow-Up of At Least Five Years After Recombinant Human Thyrotropin Compared to Levothyroxine Withdrawal for Thyroid Remnant Ablation with Radioactive Iodine

Long-Term Follow-Up of At Least Five Years After Recombinant Human Thyrotropin Compared to Levothyroxine Withdrawal for Thyroid Remnant Ablation with Radioactive Iodine

The Value of Diagnostic Whole-Body Scanning and Serum Thyroglobulin in the Presence of Elevated Serum Thyrotropin During Follow-Up of Anti-Thyroglobulin Antibody–Positive Patients with Differentiated Thyroid Carcinoma Who Appeared to Be Free of Disease After Total Thyroidectomy and Radioactive Iodine Ablation

In the presence of anti-thyroglobulin antibodies (TgAb), serum thyroglobulin (Tg) might be underestimated. Therefore, the American Thyroid Association does not recommend serum Tg after thyroid hormone withdrawal or recombinant human thyrotropin administration (stimulated Tg) and diagnostic whole-body scanning (DxWBS) in TgAb-positive patients who have serum Tg values while on thyroxine (Tg-on-T4) of <1 ng/mL. The objective of this study was to determine, in patients with differentiated thyroid cancer (DTC) who appeared to be free of disease after surgery and ablative treatment, but who had positive serum TgAb, the value of performing DxWBS and obtaining serum Tg under stimulated Tg conditions. There were 121 women and 15 men in the study. By selection criteria, all of them had total thyroidectomy with apparent complete tumor resection, remnant ablation with (131)I (1.1-5.5 GBq), and a post-(131)I therapy WBS that were negative for ectopic (131)I uptake. On assessment 8-12 months after (131)I ablation, their clinical exam needed to be normal, their Tg-on-T4 needed to be <1 ng/mL, and the test for TgAb needed to be positive. Stimulated Tg, neck ultrasound (US), and DxWBS were obtained from all patients. Patients with stimulated Tg >1 ng/mL without disease on US and DxWBS were evaluated by other imaging methods. In 10 (7.3%) patients, stimulated Tg was >1 ng/mL. The DxWBS revealed metastases in two of these patients, and other imaging methods showed disease in three others. Stimulated Tg was <1 ng/mL in 126 patients. DxWBS revealed metastases in three of these patients, and US detected lymph node metastases in four with a negative DxWBS. Tg stimulation combined with DxWBS revealed evidence for disease in 13 (9.5%) patients. When excluding patients with a positive US, DxWBS revealed metastases in four patients, and stimulated Tg of >1 ng/mL led to detection of persistent disease by other imaging methods in two more patients. Performing stimulated Tg and DxWBS at the same time seems to be useful after initial therapy in DTC patients with TgAb who do not otherwise appear to have persistent disease, even when US is negative.

Radioiodine Thyroid Remnant Ablation after Recombinant Human Thyrotropin or Thyroid Hormone Withdrawal in Patients with High-Risk Differentiated Thyroid Cancer

To supplement limited relevant literature, we retrospectively compared ablation and disease outcomes in high-risk differentiated thyroid carcinoma (DTC) patients undergoing radioiodine thyroid remnant ablation aided by recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal/withholding (THW). Our cohort was 45 consecutive antithyroglobulin antibody- (TgAb-) negative, T3-T4/N0-N1-Nx/M0 adults ablated with high activities at three referral centers. Ablation success comprised negative (<1 μg/L) stimulated serum thyroglobulin (Tg) and TgAb, with absent or <0.1% scintigraphic thyroid bed uptake. “No evidence of disease” (NED) comprised negative unstimulated/stimulated Tg and no suspicious neck ultrasonography or pathological imaging or biopsy. “Persistent disease” was failure to achieve NED, “recurrence,” loss of NED status. rhTSH patients (n = 18) were oftener ≥45 years old and higher stage (P = 0.01), but otherwise not different than THW patients (n = 27) at baseline. rhTSH patients were significantly oftener successfully ablated compared to THW patients (83% versus 67%, P < 0.02). After respective 3.3 yr and 4.5 yr mean follow-ups (P = 0.02), NED was achieved oftener (72% versus 59%) and persistent disease was less frequent in rhTSH patients (22% versus 33%) (both comparisons P = 0.03). rhTSH stimulation is associated with at least as good outcomes as is THW in ablation of high-risk DTC patients.

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.

Lack of TSH stimulation in patients with differentiated thyroid cancer – possible causes

Differentiated thyroid cancer is one of the most common endocrine cancers. Typical standard treatment includes total thyroidectomy with partial lymphadenectomy, then depending on the indications, treatment with iodine isotope 131-I. A prerequisite to conduct the therapy is to obtain endogenic thyroid-stimulating hormone (TSH) stimulation (TSH > 30 µU/ml). We describe two patients with differentiated thyroid carcinoma in whom no rise in serum TSH was observed after withdrawal of thyroxine. In one patient TSH deficiency was due to partial hypopituitarism secondary to a tumor of the pituitary gland. In the second patient the TSH level was suppressed by metabolically active thyroid tissue within bilateral ovarian teratomas. The problems with TSH growth after withdrawal of thyroxine requires additional studies to identify the cause. Above two possible reasons for the lack of TSH stimulation after withdrawal of thyroxine were presented. In the case of non-TSH stimulation due to hypopituitarism both control tests and isotope treatment should be carried out using stimulation by recombinant human TSH (rhTSH).

Severe Symptomatic Hyponatremia following Low Iodine Diet for Radioactive Iodine-131 Therapy in Patient with Papillary Thyroid Cancer: A Case Report and Review of Literature

Background: Standard treatment for well differentiated thyroid cancer is surgery followed by adjuvant radioactive iodine-131 (RAI) therapy. To concentrate RAI in thyroid tissue, levothroxine therapy is withheld for 3-4 weeks prior to RAI therapy along with low iodine diet (LID), which results in short term hypothyroidism, which ultimately can result into mild to severe symptomatic hyponatremia with fatal complications. It is very rare complication; has been reported only in four case reports so far. Case presentation: Here in we present a case report of 62 years Saudi, known hypertensive female on thiazide diuretic with diagnosis of papillary thyroid cancer (pT2N0M0), who was admitted for RAI therapy after total thyroidectomy. Patient was on low iodine diet for 3 weeks and she was given recombinant human thyrotropin (rhTSH) for two days prior to admission. On second day of admission (18 hours of RAI therapy), she was found confused, disoriented and was unable to recognise her family members. Blood chemistry showed low serum sodium concentration (105 mEq/L). Further investigations confirmed hypotonic hyponatremia and she was managed accordingly and she made full recovery within 48 hours of diagnosis. Conclusion: Although low iodine diet related hyponatremia is rare complication, but consequences can be worse in patients undergoing RAI therapy, especially elderly patients who are on diuretics. Therefore, physicians should recognize this rare side effect for prompt intervention.

Thyroid bone disease

Thyroid bone disease

Assessment of recombinant human thyrotropin application in following-up patients with well-differentiated thyroid carcinoma

The most sensitive indicators for detecting recurrence of well-differentiated thyroid cancer (DTC) are 131I whole body scintigraphy (WBS) and measurement of serum thyroglobulin (Tg). In order to perform it, it is necessary to raise the level of endogenous tiroid-stimulating hormon (TSH), which can be achieved by L-thyroxine withdrawal for 3-5 weeks or administration of recombinant human thyrotropin (rhTSH) without requiring the discontinuation of thyroid hormone therapy. The aim of this study was to assess the effect of rhTSH using in comparison to the traditional thyroid hormone withdrawal in the follow-up of patients with DTC. This retrospective study included 44 patients, mean age 48.8 years, with DTC divided into 2 groups. The group I consisted of patients (n = 31) in which the analysis in the follow-up (WBS with 131I, TSH, Tg and antiTgAt) made in the hypothyroid state, and group II patients (n = 13) in which they made after the administration of rhTSH. The presence of 13 symptoms and signs of hypothyroidism was investigated on the day of giving 131I. Quality of life was evaluated using a modified form: the quality of life scale (SF-36) completed on the day of giving 131I. In both groups, serum TSH reached a very good stimulation level, but significantly higher in the group II (group I 30.3-101.5 microlU/mL, group II 68.6-192.0 microlU/mL, p < 0.05). In both groups, TSH-stimulated Tg was higher (group I 0.1-546.0 ng/mL, group II 0.1-7517 ng/mL) comapred to value during the L-thyroxine therapy (group I 0.1-495.0 ng/mL, group II 0.1-2785 ng/mL). There was no difference in technical quality of WBS obtained from both groups. The patients in the group I had attended 8-13 symptoms of hypothyroidism, while patients in group II did not have symptoms of hypothyroidism. The patients after application of rhTSH, showed statistically significantly better quality of life as compared with those who showed to have L-thyroxine withdrawal, (74-91 points vs 43-62 points; p < 0.05). The rhTSH was well tolerated, with nausea occurring in only one patient. Administration of rhTSH in the follow-up of patients with DTC prevents the debilitating effects of hypothyroidism contributing to the maintenance of metabolic homeostasis of the organism and preserves the quality of life. RhTSH is safe, effective and easy to use, but is still an expensive product in our country.

Role of Recombinant Human Thyrotropin (rhTSH) in the Treatment of Well-Differentiated Thyroid Cancer

Since the introduction of radioiodine (RAI) for treatment of well-differentiated thyroid cancer (DTC) more than 50years ago, prolonged periods of hypothyroidism were routinely used as part of the treatment regimen. Recombinant human TSH (rhTSH) was introduced in the 1990s as a tool to elevate the serum TSH without the need for thyroid hormone withdrawal and symptomatic hypothyroidism. After being initially approved as a diagnostic tool for use in RAI scanning and stimulated thyroglobulin testing, rhTSH was approved as an adjunct to RAI remnant ablation in patients without distant metastases in Europe in 2005 and in the US in 2007. Following successful use of rhTSH for diagnostic purposes, it has been extensively studied for use with therapeutic doses of RAI in the setting of RAI remnant ablation and is now an integral part of DCT therapy. The use of rhTSH in clinical practice in the last decade was coupled with the growing interest in an individualized, risk-stratified approach to the management of patients with DCT. While traditional treatment for DTC included surgery and RAI therapy for all patients, many more recent studies demonstrated the value of selective use of RAI only in patients who will probably benefit from treatment. This manuscript reviews the evolving role of rhTSH in the current risk adapted climate of thyroid cancer management with particular emphasis on the use of rhTSH as an aid to RAI therapy.

Evaluation of whole-body retention of iodine-131 (131I) after postoperative remnant ablation for differentiated thyroid carcinoma – thyroxine withdrawal versus rhTSH administration: A retrospective comparison

Previous studies demonstrated that preparation with recombinant human thyroid-stimulating hormone (rhTSH) for thyroid remnant ablation results in lower extrathyroidal radiation compared to hypothyroidism. The results of 50 radioiodine therapies (RITs) under rhTSH, regarding iodine half-life, were evaluated and compared with 50 RITs performed on patients with hypothyroidism following thyroxine withdrawal. The patients were treated with 3700 MBq (100 mCi) of (131)I. Forty-eight hours after RIT, patients were measured with a radiation detector at a 1-meter (m) distance for evaluation of the effective dose (μSv/h). TSH and thyroglobulin (Tg) maximal values were also compared. rhTSH-stimulated patients had a significantly lower whole-body retention of (131)I (8.5±7.3 μSv/h), extrapolated from the measurements of the effective dose at a 1-m distance, compared to endogenously stimulated patients (13.6±8.1 μSv/h; p=0.001). Furthermore, TSH mean and Tg median levels were significantly higher in the rhTSH-stimulated patients (89.9±15.3 mU/l and 7.7 ng/ml, respectively) compared to the hypothyroid group (59.2±25.1 mU/l and 3.3 ng/ml; p<0.001 and p=0.003, respectively). Compared to thyroid hormone withdrawal, the use of rhTSH prior to RIT was associated with significantly lower whole-body retention of (131)I and with greater efficacy in reaching TSH levels greater than 30 mU/l, confirming data previously described.

Thyroid Cancer Patients Treated with 131I: Radiation Dose to Relatives After Discharge from the Hospital

Thyroid cancer patients treated with radioiodine are potential source of radiation exposure for other individuals. Thus, we evaluated the radiation dose received by family members of thyroid cancer patients treated with (131)I after hospital discharge. Seventy-six family members of 56 thyroid cancer patients were included in the study. Thyroid cancer patients were given 3.7 GBq of (131)I and remained in a radiation protection ward for 3 days. Radiation protection recommendations were given to patients and relatives. Life conditions were recorded and radiation doses were monitored using a personal dosimeter. At discharge, the mean residual activity was 188 MBq. The mean radiation dose delivered to relatives during the 7 days after discharge was low (51.5 μSv) and was similar with either recombinant human thyrotropin (rhTSH) (59 μSv) or withdrawal (50 μSv) (p = 0.37). With our current practice, radiation doses to relatives are low and well below international recommendations.

Outcome of differentiated thyroid cancer after initial treatment

Incidence of differentiated thyroid cancer has increased in the last two decades. This type of cancer is now being diagnosed at an earlier stage. Treatment strategy has been modified. The goals of this study were to analyze the outcome of differentiated thyroid cancer after initial treatment (surgery and radioiodine ablation) in patients evaluated and followed up in a single centre between l999 and 2009, to compare these results with others as well as to monitor the adoption of international recommendation. 107 patients having T1-T2 differentiated thyroid cancer were studied. Mean follow-up time was 63 months. After surgery patients were prepared using thyroid hormone withdrawal or recombinant human thyrotropin, then 1.1-3.7 GBq 131-iodine was administered. First year evaluation consisted of ultrasound as well as serum thyrotropin and thyroglobulin (plus thyroglobulin antibody) determinations. Ablation success rate was 83% and the five year survival was 100%. There was not any cancer specific death. In the future somewhat more radical surgery and less remnant ablation is needed with unified follow-up protocol.

Health‐related quality of life among thyroid cancer survivors: a systematic review

Treatment and follow-up care procedures of thyroid cancer impose great challenges on survivors and could potentially affect their health-related quality of life (HRQoL). Two authors systematically reviewed the available literature on HRQoL of thyroid cancer survivors. A PubMed literature search for original articles published until February 2011 was performed. Twenty-seven articles, published between 1997 and 2010, which met the predefined inclusion criteria, were subjected to a quality checklist. All selected studies, except one, were of adequate or good quality. Surgery had a negative impact on short-term HRQoL scores, but these scores returned to preoperational levels when time since surgery increased. Long-term thyroid hormone therapy (levothyroxine) can lead to abnormalities like hyperthyroidism. HRQoL was most affected during thyroid hormone withdrawal for radioiodine remnant ablation or follow-up procedures. The use of recombinant human thyroid stimulating hormone instead of hormone withdrawal leads to considerable improvements in HRQoL during follow-up testing. The results for (long-term) survivors were contradicting. While most (long-term) survivors report some specific long-lasting health problems, some studies found a lower HRQoL for thyroid cancer survivors compared with a healthy population or other reference groups, whereas other studies found similar HRQoL levels. This review indicates that thyroid cancer survivors generally have a similar or slightly worse HRQoL compared with the normative population; however, they report some specific medical problems after cancer treatment and follow-up tests, which have a direct negative impact on their current HRQoL and could affect their long-term HRQoL. Specific longitudinal survivorship studies are lacking.

Thyroid Remnant Estimation by Tc-99m-Sestamibi Scanning Predicts the Effectiveness of rhTSH-Stimulated I-131 Ablation in Patients With Differentiated Thyroid Carcinoma

To evaluate the relationship between postsurgical cervical Tc-99m-sestamibi scan uptake and the rate of successful remnant ablation after recombinant human-thyrotropin (rhTSH)-aided-I-131 ablation in patients with differentiated thyroid carcinoma (DTC). In all, 154 DTC patients who underwent total thyroidectomy and rhTSH-aided remnant ablation with I-131 (3.7 GBq) were enrolled. Tc-99m-sestamibi scans were performed during continuing thyroid hormone administration in all cases. Thyroid ablation was assessed after 6 to 12 months by rhTSH-stimulated I-131-whole-body scan and thyroglobulin measurement. The rate of successful ablation, occurrence of radioiodine-induced thyroiditis, and length of hospitalization were correlated with the Tc-99m-sestamibi scintigraphy results. Tc-99m-sestamibi uptake was significantly lower in ablated versus nonablated patients (P<0.0001). A visually positive scan and a Tc-99m-sestamibi uptake greater than 0.9% predicted a high-risk of unsuccessful ablation, prolonged hospitalization, and the occurrence of radioiodine-induced thyroiditis. Tc-99m-sestamibi scintigraphy is a simple and feasible tool to evaluate thyroid remnants and to predict radioiodine ablation results in patients with DTC.

Treatment room length-of-stay and patient throughput with radioiodine thyroid remnant ablation in differentiated thyroid cancer

We sought to empirically compare treatment room length-of-stay and patient throughput for recombinant human thyroid-stimulating hormone (rhTSH)-aided thyroid remnant ablation with thyroid hormone withdrawal (THW)-aided ablation in patients with differentiated thyroid carcinoma (DTC). We retrospectively reviewed charts of all eligible (near) totally thyroidectomized patients with DTC undergoing ablation and 1-year ablation success evaluation at our tertiary referral centre from January 2003 to February 2009 (N=274). M1 disease caused exclusion unless discovered by a postablation scan or present when rhTSH was the only tolerable stimulation method. We extracted data on the length-of-stay, defined as the time between treatment room admission and discharge, and patient throughput, defined as patients ablated per treatment room per week. The treatment room discharge criterion was a whole-body dose rate of less than 60 μSv/h at 50 cm. The treatment groups (rhTSH, n=187; THW, n=87) had mostly statistically similar characteristics, but differed in primary tumour status distribution. In addition, at ablation, the rhTSH patients had a greater prevalence of prior diagnostic scintigraphy, higher mean serum TSH, and shorter interval since surgery, and received a 5.6% larger mean ablation activity. On average, rhTSH patients had a significantly lower peak whole-body dose rate (57.1 vs. 83.4 μSv/h at 50 cm; P<0.0001) and a significantly shorter treatment room stay than did the THW patients (1.41 vs. 2.02 days; P<0.001). rhTSH use allowed significantly more patients to be ablated per room per week (2.7 vs. 1.2; P<0.001). Relative to THW, rhTSH use to aid ablation reduced mean treatment room length-of-stay by almost one-third and more than doubled the average weekly patient throughput, both of which were significant differences.

Thyroglobulin measurement in fine‐needle aspiration biopsy of metastatic lymph nodes after rhTSH stimulation

Thyroglobulin measurement in the washout of the needle used in fine-needle aspiration cytology (FNAC) has been proposed for the early detection of lymph node metastasis both in patients with or without serum thyroglobulin antibodies; however, up to now, there have been no reports that recombinant human thyrotropin (rhTSH) stimulation modifies thyroglobulin measurement in lymph node aspirates. We described, after rhTSH stimulation, the switching from undetectable to detectable levels of thyroglobulin in fine-needle aspiration fluid from a suspected metastatic lymph node in 2 patients. We hypothesized that thyroglobulin levels in the lymph node increased after rhTSH stimulation. The excess thyroglobulin saturates all thyroglobulin antibody binding sites and becomes detectable, explaining why it was undetectable when TSH was suppressed. On the basis of our experience, we suggest submitting to thyroglobulin measurement in the washout of the needle used in FNAC all patients with detectable serum thyroglobulin antibody after rhTSH stimulation.

Acute effect of TSH on oxygenation state and volume of erythrocytes from subjects thyroidectomized for differentiated thyroid carcinoma

We previously reported the presence in the membrane erythrocyte of a TSH receptor (TSHR), a G-protein coupled receptor, which responds to TSH with increased cAMP level. Since there is evidence for a role of G protein receptors as oxygen sensor(s) implicated in cell volume regulation, we hypothesized that erythrocyte TSHR, by TSH stimulation, could modify the erythrocyte volume and the oxygenation state of erythrocytes. We determined the effect of TSH on the gas analysis in 35 thyroidectomized patients for stage I differentiated thyroid cancer enrolled for recombinant human thyroid-stimulating hormone (rhTSH) test during chronic treatment with synthetic l-thyroxine. Moreover, we explored the influence of TSH on the shape of erythrocytes. Venous blood-gas analysis before and after TSH were determined with a pH/blood gas electrolyte and 682 CO-Oxymeter. In a subgroup of subjects ( n = 10), the isolated red blood cells (RBC) were analyzed by flow cytometry for morphological changes. After TSH stimulation, we found a significant decrease in PCO 2 ( P < 0.001), an increase in pH ( P < 0.01) and an increase of % O 2-Hb ( P < 0.05) and pO 2 ( P < 0.05). By flow cytometry, the erythrocytes after TSH showed a significant enrichment on the mean number in the selected region R1 corresponding to bigger volumes ( P < 0.05, n = 10). Finally, by contrast phase microscopy, when the cell area was measured, a mean increased volume was observed in erythrocytes after TSH compared to the basal before TSH ( P < 0.05). In conclusion, our results indicate that acute stimulation of TSH by rhTSH modifies the oxygenation state and volume of erythrocyte.

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.

Inability of recombinant human thyrotropin to predict the evolution from subclinical hypothyroidism to overt disease. A pilot study.

The use of recombinant human TSH (rhTSH) is indicated to evaluate thyroid carcinoma patients. In recent years, some authors have reported that rhTSH could serve as a dynamic test of thyroid reserve. The aim of the present study was to determine whether or not rhTSH can predict the evolution from subclinical hypothyroidism (SH) to overt hypothyroidism. Twenty-one women who met the diagnostic criteria of SH were enrolled. All patients received a single dose of rhTSH (0.1 mg). Basal blood samples for TSH, free T4 (fT4), thyroglobulin (Tg), and anti-thyoperoxidase and anti-Tg antibodies were obtained before and 1 day after rhTSH administration. All patients were followed for 2 yr, and blood samples were obtained every 6 months. Twenty-four hours after rhTSH administration, the TSH level increased to >20 mU/l in 14 patients; the serum peak TSH levels remained <10 mU/l in only 5 patients. On follow-up, 7 women (33%) required L-T4 replacement therapy for overt hypothyroidism or a persistent TSH level >10 mlU/l. None of the parameters analyzed differed significantly between patients who developed overt hypothyroidism from those who had persistent SH. The response of thyroid function tests to a single low dose of rhTSH is not useful in identifying those patients with SH who will develop overt hypothyroidism over a 2-yr period.