Lithium as an adjunct to radioiodine therapy in Graves' disease for prolonging the intrathyroidal effective half-life of radioiodine. Useful or not?

AIM: Evaluation of intrathyroidal kinetics of radioiodine with and without lithium as adjunct with respect to the increase in radiation dose delivered to the thyroid. PATIENTS, METHODS: 267 patients in three groups were included in the study. Group I with 227 patients served as control group, Group II with 21 patients and Group III with 19 patients were distinguished by an intrathyroidal half-life of radioiodine below 3.5 days in the diagnostic test. Patients in Group III received 885 mg lithium carbonate a day for 2 weeks as adjunct to radioiodine therapy. Both diagnostic and therapeutic radioiodine kinetics were followed up by at least 10 uptake measurements within a minimum of 48 h. Kinetics of radioiodine were defined mathematically as balance of the thyroidal iodine intake and excretion by a two-compartment model. RESULTS: Under therapy the maximum uptake of radioiodine was reduced by nearly 10% in all groups, in Group I, the effective half-life as well as the product of maximum uptake x effective half-life as an equivalent of radiation dose independent of thyroid volume was lowered in the same magnitude. In Group II, the energy-dose equivalent remained constant under therapy. With adjunct lithium in Group III, the effective half-life was prolonged significantly by factor 1.61 +/- 0.49 and the volume-independent energy-dose equivalent by factor 1.39 +/- 0.37. No severe side effects of lithium were observed. CONCLUSION: Using lithium as adjunct to radioiodine therapy increases the radiation dose delivered to the thyroid by 39% on average and nearly 30% of radioiodine activity can be saved in these patients. Lithium is recommended in patients with very short effective half-life in the diagnostic test in order to reduce the activity required and whole-body radiation dose.

[Results of a risk adapted and functional radioiodine therapy in Graves' disease]. / Ergebnisse einer risikoadaptierten und funktionsorientierten Radioiodtherapie bei Morbus Basedow.

UNLABELLED: Aim of this study was to find out, if results of a functional orientated radioiodine therapy in Graves' disease could be optimized using a risk adopted dose concept. PATIENTS, METHOD: 351 patients with Graves' disease were treated for the first time between 11/97 and 8/01. The basic dose was 125 Gy, which was increased up to 250 Gy in a cumulative manner depending on clinical parameters (initial thyroid metabolism, thyroid volume, immunoreactivity). Two different methods of dosimetry were used. Occasional thyreostasis was withdrawn two days before the radioiodine test was started. Follow up was done on average 8 +/- 2.4 (4-17.2) months. TSH > or = 0.27 microIU/mL confirmed as a measure of the success. RESULTS: With improved pretherapeutic dosimetry and a mean target dose of 178 +/- 31 Gy (n=72) therapeutic success occurred in 66.7%, in 51.4% euthyreosis was restalled and in 15.3% of patients hypothyroidism was seen (TSH > 4.20 microIU/mL). With simplified pretherapeutic dosimetry and a mean target dose of 172 +/- 29 Gy (n=279) results were moderately impaired (63.8%, 40.1% and 23.7%). With increasing target dose therapeutic failure increased, as insufficiently adopted risk factors for therapeutic failure turned out the initial thyroid metabolism, the TcTU(s) as the (h)TRAb titer. CONCLUSION: Functional orientated RIT can be optimized by including illness specific characteristics, principal limitations are a high initial thyroid metabolism, a large thyroid volume and a high (h)TRAb-titer.

A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A.

One hundred and eighty-one families with multiple endocrine neoplasia type 2A (MEN-2A) or familial medullary thyroid carcinoma (FMTC) have been investigated for mutations in the ret protooncogene in Germany. In 8 families with FMTC or MEN-2A, no mutation could be detected in the cysteine-rich domain encoded in exons 10 and 11 of the ret protooncogene. DNA sequencing of additional exons (no. 13-15) revealed rare noncysteine mutations in 3 families (codons 631, 768, and 844). In contrast to these rare events, heterozygous missense mutations in exon 13, codons 790 and 791, were found in 5 families (4 with MTC only; 1 family with MTC and pheochromocytoma) and 11 patients with apparently sporadic tumors. Two different mutations in codon 790 (TTG-->TTT, TTG-->TTC; Leu790Phe) and one mutation in codon 791 (TAT-->TTT; Tyr791Phe) created a phenylalanine residue. We conclude that codons 790 and 791 of the ret protooncogene represent a new hot spot for FMTC/MEN-2A causing mutations. With the discovery of these considerably common mutations in codons 790 and 791 and the identification of some rare mutations, 100% of the German FMTC/MEN-2A families could be characterized by a mutation in the ret protooncogene.

[Paradoxical effect of radioiodine therapy in functional thyroid autonomy and mild immunothyropathy]. / Paradoxe Effekte der Radiojodtherapie bei funktioneller Schilddrusenautonomie und milder Immunthyreopathie.

AIM: To examine all cases with Graves' disease after radioiodine therapy of autonomously functioning thyroid tissue (AFFT) in order to find the cause. METHODS: We retrospectively studied 1428 pts who were treated between 11/93 and 3/97 with radioiodine for AFTT and who underwent at least one control examination. RESULTS: 15 (1.1%) of all pts developed Graves' disease 8.4 (4-13) months after radioiodine therapy. There was no direct suggestion of Graves' disease (TRAK negative, no endocrine ophthalmopathy) in any pt at the time of radioiodine therapy. More detailed analysis of anamnestic data, however, revealed evidence that immunothyropathy predated radioiodine therapy in 11 of the 15 pts. Paradoxical effects of radioiodine therapy manifested as an increase in immunothyropathy in 14 pts, a deterioration in metabolism in 11 pts and a first occurrence of endocrine ophthalmopathy in 5 pts. CONCLUSION: Exacerbation of preexisting, functional primarily insignificant immunothyropathia is held responsible in most cases for the observed paradoxical effects after radioiodine therapy, resulting in radiation-induced manifest Graves' disease; however no therapeutical consequences are recommended.

[Results of TcTUs-optimized radioiodine therapy in multifocal and disseminated autonomy]. / Ergebnisse der TcTUs-optimierten Radioiodtherapie bei multifokaler und disseminierter Autonomie.

AIM: The presented study prospectively evaluates the efficacy of optimized radioiodine therapy in patients (pts) with multifocal (MFA) and disseminated (DISA) autonomy. The target dose was related to the total thyroid volume and was increased in moderate and nonlinear increments from 150 to 300 Gy dependent on the pretherapeutic Tc-99m pertechnetate thyroid uptake under suppression (TcTUs). Patients with focal autonomy were treated with a target dose independent of TcTUs and were used as control group. METHODS: The data of 641 pts (518 women, 123 men) were evaluated, 466 pts with MFA or DISA and 175 pts with focal autonomy. In pts with MFA and DISA the target dose was increased in four steps: TcTUs < 3%: 150 Gy, > 3-6%: 200 Gy, > 6-12%: 250 Gy and > 12%: 300 Gy. In pts with focal autonomy a fixed target dose of 300 or 400 Gy was applied. The radioactivity to be administered was calculated using a modified Marinelli formula. The follow-up examination was performed at the earliest after four, on average after eight months. Normalization of TSH was the only criterion for successful therapy. RESULTS: The success rate in pts with latent or manifest hyperthyroidism in focal autonomy was 91.5%, therapy was not successful in 5.1% and hypothyroidism occurred in 3.4%. The average success rate in pts with MFA and DISA was 91.5%, therapy failed in 7.5% and a very low rate of 1% with hypothyroidism was seen. CONCLUSION: The presented optimized therapy concept with calculated, nonlinear increase of the target dose according to the TcTUs-level guaranteed even in MFA and DISA a high success rate comparable to that in focal autonomy along with a very low rate of hypothyroidism.

Reliability in tests of the eustachian tube function.

With the aid of a quantitative impedance method and a pressure chamber, the capacity of the Eustachian tube to equilibrate pressure differences across the tympanic membrane was repeatedly determined in 20 otologically healthy men. The test-retest reliability was calculated from five determinations of static pressure equilibration of over- and underpressures of 10 cmH2O and 10 determinations of equilibration of dynamic pressure changes. The pressure opening level of the tube during pressure increase in the middle ear was significantly lowered in the initial determinations. The residual pressure in the middle ear after maximum equilibrating efforts during pressure increase in the chamber was also significantly lowered. For the rest, the test-retest reliability was good. Ears with perfect tubal function had better test-retest reliability for all parameters tested than ears with poorer function. The significance of repeated measurements and the value of reliability determinations are discussed.

The effect of pressure change rate on the eustachian tube function in pressure chamber tests.

The capacity of the Eustachian tube to equilibrate pressure differences across the eardrum was tested repeatedly at different rates of pressure change with the aid of a quantitative impedance method in a pressure chamber. Three recordings of the active and passive pressure equilibration functions were made during chamber pressure changes of 0.3, 0.7 and 1.5 kPa-1s in 53 ears in 28 otologically healthy subjects. The middle ear pressures at which the active and passive equilibrations were achieved increased with increasing rates. The test-retest reliability was not rate dependent as regards the passive pressure equilibration functions, but tended to deteriorate with increasing rates for the active equilibration functions. Advantages and disadvantages of the different rates in such tests are discussed.

Effects of different body positions on the Eustachian tube function in the selection of airmen.

The Eustachian tube function of 52 applicants accepted for flight training had earlier been comprehensively tested during simulated flights in a pressure chamber in the sitting position. Despite the fact that all were otologically healthy, the wide range of pressure-equilibrating capacity in the sitting position was even more pronounced when they were rested in recumbency, and in every type of test the pressure-equilibrating capacity was reduced. For instance, 17% of the recumbent subjects could not equilibrate at all during simulated descent as compared to 8% in the sitting position; 81% of the ears were Toynbee positive in the sitting position and only 69% in recumbency. The advantages of the recumbent compared to the seated test position are discussed.

Comparison of Eustachian tube function measured by the microflow method and a new quantitative impedance method.

Eustachian tube function in 25 applicants for flight training was tested during simulated flights using two methods alternately; the integrating microflow method with a stationary pressure chamber, and a new quantitative impedance method in combination with a new mobile pressure chamber. All ears were tested by both methods. The results of the various tests did not differ significantly between methods. The reliability of the measurements was good and almost equal in both methods. Several practical advantages with the new impedance method in combination with the mobile pressure chamber make it preferable.

Effect of flight on the Eustachian tube function and the tympanic membrane system--a follow-up study.

The Eustachian tube function in 32 aviation trainees was comprehensively tested in simulated flights in a pressure chamber on three occasions during their training. Their mean flight experience between tests comprised 150 h in jet training planes and 260 h in jet fighters. Their capacity to clear the ears in descent did not improve convincingly between tests, but the pressure opening level in ascent was significantly lowered. The elasticity of the eardrum system was significantly increased. The results suggest that the first test, before the flight training, is reliable for selection purposes. Reasons for difficulties in finding good agreement between test results and results of actual flight training are discussed.

Eustachian tube function in selection of airmen.

A comprehensive study of Eustachian tube function in 84 aspirants accepted for flight training was made. Using a pressure chamber, both static and dynamic pressure changes, as in ascent and descent, were applied to test the tubal pressure equilibrating capacity in the sitting position. While all 84 were otologically healthy, a wide range in the pressure equilibrating capacity was found--20% could not equilibrate static over- and underpressures of 10 cm H2O completely, 8% could not equilibrate at all during simulated descent, 3 subjects reported acute vertigo during simulated ascent in combination with high unilateral middle ear pressure. Asymmetry between ears of single subjects in pressure equilibrating capacity was also found to a large extent. It was not possible to identify subjects with poor equilibrating capacity by simple tests like Valsalva's or Toynbee's manoeuvres. The results may indicate that today's criteria for Eustachian tube function in the selection of airmen can be made more efficient.

The use of thyrogen in the treatment of differentiated thyroid carcinoma: an intraindividual comparison of clinical effects and implications of daily life.

AIM: Withdrawal of levothyroxine with resultant hypothyroidism is still used in preparation for I-131 diagnostic whole-body scan (DWBS) and thyroglobulin (TG)-measurement in patients afflicted with differentiated thyroid cancer (DTC). Recombinant human thyroid-stimulating hormone (rhTSH) enhances TSH stimulation obviating the clinical and economical consequences of hypothyroidism. Primary aim of this study was an intraindividual comparison of diagnostic follow-up measurements under these two sets of conditions by taking clinical and socio-economic parameters into account. Second aim was to determine a clear patient preference for the one method or the other. METHODS: This non-interventional observational study included patients (n=192 signed informed consent, n=128 protocol compliant patients without need for therapeutic intervention) with DTC first treated by thyroidectomy and radioiodine ablation. Control visits including I-131 DWBS were planned at 3-6 months post-thyroidectomy after a phase (KU 1) of thyroid hormone withdrawal (THW) and again after 6-12 months later in a euthyroid state under exogenous stimulation with rhTSH (KU 2). Study design was open, prospective and multicentric. Data collected consisted of patient information (SF-12 (®) Health Survey), thyroid-specific results of clinical examinations and several aspects of daily life, e. g., employment, days of absence from work and other economic aspects. RESULTS: In contrast to KU 1, in KU 2 there is a highly significant improvement (p<0.0001) in all studied clinical symptoms and aspects of managing daily life. A significant increase of the SF-12 (®) health survey score could also be identified. Mental score showed a higher increase than physical score. Included patients were less absent from work before KU 2, (absent 4.5%, median 4 days in euthyroid state [range 2-5 d]), vs. before KU 1 (absent 47.8%, median 10 days in hypothyroid state [range 1-30 d]). After KU 2 7.7% of the euthyroid patients was absent from work (median 5 days) while 37.5% was after KU 1 (median 6 days). CONCLUSION: Included patients benefited subjectively and objectively from the use of rhTSH for diagnostic procedures in the treatment of DTC. A clear preference (127 of 128) of analyzed patients could be identified for exogenous stimulation with rhTSH.

Regional drug information service benefits: free versus fee-for-service.

Health providers in a four-state area who had utilized the Nebraska Regional Drug Information Service were surveyed to determine: (1) if providers would pay a fee for drug information services; and (2) if they would prefer a per-call fee or an annual subscription fee. Of 1,000 questionnaires mailed, approximately 500 were returned and analyzed. Results indicated that 52% of those responding felt that the drug information service provided direct benefits to patients. The service fee preferred most was $2.00 to $5.00 per call or $25.00 per year. Actual operating cost data showed that a per-call charge of $2.50 would not permit the service to break even. However, it was projected that the service would break even if it charged an annual fee of $25.00.

Pressure chamber tests for selection of aircrew.

The Eustachian tube function requested from flying personnel today is generally regarded as acceptable if hearing and otoscopic findings are normal and there is no history of ear disease. Since increasing performance of modern aircrafts place more rigorous demands on the equilibrating capacity of the Eustachian tube and difficulty to clear the ears already is the most common cause of temporary grounding among flying personnel, the present requirements for tubal function might gradually get more and more inefficient. Inability to equilibrate in flight may lead to temporarily reduced hearing, acute ear pain and alternobaric vertigo that will affect the pilot's capacity and thus constitute a problem of flight safety. A testing procedure that makes it possible to continuously measure the middle ear pressure in subjects with intact eardrums during simulated flights in a pressure chamber would introduce a possibility to find basic medical standards of Eustachian tube function to be used in the selection of flying personnel. Student pilots, accepted for primary flight training, were examined in the present study by such a method. A comparison is made with the results of other tests of the Eustachian tube function in order to find out the relevance of the latter tests in the selection of flying personnel. The results are presented and discussed.