PubMed · 9174721
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S Refetoff. 1997. Resistance to thyroid hormone.. https://pubmed.ncbi.nlm.nih.gov/9174721/
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This paper describes a method for extraction of tapazol, thiouracil, methylthiouracil, propylthiouracil and mercaptobenzimidazol (MBI) from thyroid tissue. The solid-phase extraction procedure is optimized to obtain the maximum results for the main thyreostats including MBI. Different combinations of sample application, column conditioning and wash steps were tested. The analytes were extracted from the matrix with methanol. After solid-phase extraction they were derivatised with 7-chloro-4-nitrobenzo-2-furazan. Determination is carried out using liquid chromatography-electrospray mass spectrometry. The identification of the analytes was performed according to the final revision of the EU criteria (93/256/EC decision). The detection capability was 20 microg kg(-1) for all mentioned thyreostats.
OBJECTIVES: Graves' disease (GD) complicates 0.1% to 0.2% of pregnancies, but congenital thyrotoxicosis is rare occurring in one in 70 of these pregnancies independent of maternal disease status. Antenatal prediction of affected infants is imprecise; however, maternal history, coupled with a high maternal serum TSH receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome. Mortality is reported to be as high as 25% in affected infants and would therefore be expected to be higher in premature infants. This study illustrates that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence of antenatal risk assessment and management of thyrotoxicosis in this setting is complex. DESIGN AND PATIENTS: The records of premature neonates born at the three main maternity units in Brisbane, between January 1996 and July 1998 diagnosed with congenital thyrotoxicosis were reviewed. Data were recorded on gestational age, birth weight (B Wt), maternal thyroid history and current status, and neonatal course. Thyroid function and TBII status was assessed using standard biochemical assays. RESULTS: Seven neonates from five pregnancies were identified (four female, three male). Mean gestational age was 30 week (25--36 week) and median B Wt was 1.96 kg (0.50--2.62 kg). Only one mother received formal antenatal counselling by a paediatric endocrine service and had a TBII (54%) measured prior to delivery. Three of five mothers had elevated TBII measured after diagnosis in their offspring (57%, 65%, 83%) and in one mother, a TBII was not performed. All mothers were biochemically euthyroid at delivery. Mean age at diagnosis was 9 days (1--16 days) and mean age at commencement of treatment was 12 days (7--26 days). Two infants received propylthiouracil and five received a combination of carbimazole and propranolol. Four became biochemically hypothyroid, in three this resolved with cessation of the antithyroid drug (ATD), and one required ongoing T4 supple-mentation. Only one infant required treatment for cardiac failure and there were no deaths in this cohort. CONCLUSIONS: This is a large series of extremely small and premature infants with neonatal thyro-toxicosis. Presentation was nonspecific. The diagnosis was delayed because of low birth weight, prematurity, multiple birth and/or an unrecognized maternal history of Graves' disease. The treatment of neonatal thyrotoxicosis was difficult in these extreme low birth weight infants yet no infant died and significant morbidity was confined to high output cardiac failure in one infant. With antenatal recognition of past or active Graves' disease, assessment of maternal TSH receptor binding immunoglobulin index prior to delivery and postnatal monitoring of cord TSH and venous fT4 and TSH on days 4 and 7 rapid treatment of affected infants may have further reduced neonatal morbidity.
In the last years the diagnosis of Grave's disease has become easier and accelerated due to new laboratory and instrumental tests. The therapeutic possibilities improved also by using antithyroidal drugs, surgery and radioiodine application subsequently. In a retrospective study 278 outpatients with Graves disease, treated and controlled by our centre for thyroid diseases in 1992-1999, were investigated to evaluate the initial and leading subjective symptoms which led the patients to seek medical help ("guide symptoms"). These obtained guide symptoms were compared with the objective "clinical signs" observed at the beginning of the disease. Weight loss turned out to be the most frequent (26%) guide symptom, whereas tachycardia (> 90 beats/min) and moist skin were the most frequently observed clinical signs (71 and 61% respectively). The beginning of therapy, dosage of drugs, length of application and results of treatment are critically evaluated, with special emphasis on the rate and time of remission, on the frequency of recurrences and on the success of additional treatments such as surgery and/or radioiodine application. Pharmacological treatment alone induced a persistent remission (at least 6 months of euthyroidism) in 156 patients (in 113 after the first and in 43 after the 2nd drug trial). Surgery was successful in 46, radioiodine application in 40 patients. The sequential use of drug therapy, surgery and radioiodine as it is performed in our institution leads to a permanent remission in 242 of 278 (= 87%) patients.