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PubMed1998

A randomized trial of short-term treatment of Graves' disease with high-dose carbimazole plus thyroxine versus low-dose carbimazole.

OBJECTIVE: The optimal treatment regimen with thionamide drugs remains a matter for debate. We have investigated whether high doses of carbimazole, when compared with low doses, reduce relapse rates of Graves' disease. DESIGN: In an open label, randomized, prospective trial of treatment of Graves' disease we compared high doses of carbimazole (6 months of 100 mg carbimazole per day plus thyroxine) to low-dose carbimazole treatment (starting at 25 mg and titrating the carbimazole dose with the aim to maintain serum thyroid function test results within the normal reference range). PATIENTS: Thirty-seven patients with a first episode of Graves' disease were enrolled. MEASUREMENTS: During the 6 months of treatment we evaluated the rate of normalization of serum thyroid function tests, changes in serum thyroid auto-antibody levels and the rate of side-effects during treatment. After completion of the 6-month treatment course patients were observed for 2 years for evidence of relapse of Graves' disease. RESULTS: There were no differences between the two groups either in the rate of normalization of serum thyroid function tests or in serum thyroid auto-antibody levels during treatment. Of the 17 patients randomized to high-dose treatment seven suffered treatment side-effects, compared to only one of the 20 patients receiving low-dose treatment (P < 0.006). There was no significant difference in 2-year post-treatment remission rates on an intention-to-treat basis between the two treatment groups (18.7% vs. 5.9%, P = NS). However, for those patients who completed 6 months of treatment (high-dose group = 9, low-dose group = 16), multivariate survival analysis demonstrated a significantly longer median relapse-free interval (P < 0.04) in the high-dose group (27 weeks; 25th percentile: 9.6 weeks, 75th percentile: 75 weeks) versus the low-dose group (6 weeks; 25th percentile: 4.8 weeks, 75th percentile: 13.1 weeks). CONCLUSIONS: High-dose carbimazole treatment delays, but does not prevent, relapse from Graves' disease in those patients able to tolerate the treatment. However, it leads to more frequent side-effects than conventional dose treatment.

Adult↗

PubMed2006

Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison.

PURPOSE: Carbimazole ameliorates hyperthyroidism but reduces radioiodine uptake and adversely affects the outcome of simultaneous radioiodine therapy. We explored whether withdrawal of carbimazole for 3 days can restore the outcome of radioiodine treatment without concurrent exacerbation of hyperthyroidism. By generating three groups with comparable radioiodine uptake, we also investigated whether the effect of carbimazole depends on the radioiodine uptake. METHODS: Stratified by a radioiodine uptake >30%, 227 consecutive adult patients were prospectively assigned to radioiodine therapy (target dose 200 Gy) without, on or 3 days off carbimazole. Patients were clinically (Crooks-Wayne score) and biochemically (T(3), fT(4), TSH) followed up after 3, 6 and 12 months. Primary endpoint was outcome 12 months after radioiodine therapy. RESULTS: A total of 207 patients completed follow-up (toxic nodular goitre, n=117; Graves' disease, n=90). The overall success rate was 71.5%. Patients without and 3 days off carbimazole had similar biochemical (81.4% and 83.3%, respectively; p=0.82) and clinical outcomes [median (range) Crooks-Wayne score 0 (0-16) and 1 (0-10), respectively; p=0.73], which were both higher than in patients on carbimazole [42.6%, p<0.001; Crooks-Wayne score 3 (0-30), p<0.03]. Time to achieve cure was delayed on carbimazole. No changes in thyroid hormone levels occurred after 3 days' discontinuation of carbimazole. Logistic regression revealed that all observed cure rates were independent of entity, sex, age, thyroid volume, radioiodine uptake, radioiodine half-life, fT(4), T(3) and TSH. CONCLUSION: Patients under carbimazole treatment can be referred for radioiodine therapy after withdrawal of carbimazole for only 3 days. Three days of carbimazole withdrawal is long enough to restore the success of radioiodine therapy and short enough to avoid the risk of exacerbation of hyperthyroidism.

Adult↗

PubMed1999

Radioiodine therapy in Graves' disease patients with large diffuse goiters treated with or without carbimazole at the time of radioiodine therapy.

We sought to ascertain how high the success rates of radioiodine therapy are for Graves' disease patients with large diffuse goiters when aiming for a constant absorbed dose of 250 Gy. Thirty-six patients with a thyroid volume of 50-110 mL were evaluated for changes in thyroid function and appearance 3, 6, and 12 months after radioiodine therapy. Success was defined as definitive elimination of hyperthyroidism following therapy (hypothyroidism corrected with thyroxine on diagnosis); failure as persistent/recurrent hyperthyroidism after 12 months. Overall success rate was 50%. However, a subgroup of 20 patients without simultaneous carbimazole (carbimazole-off) showed a highly significantly larger success rate (85%) than the 16 patients with simultaneous carbimazole (carbimazole-on) at the time of radioiodine therapy (6.3%, p < 0.000005). Successful cases showed a significantly higher volume reduction after radioiodine than failures (75.5% vs. 35.4%, p < 0.00005). Stepwise logistic regression showed that therapy failure was related to administration of carbimazole during radioiodine therapy (p < 0.0250 and absorbed dose (p < 0.05), but not thyroid function (free triiodothyronine [FT3] and free thyroxine [FT4]), initial thyroid volume or thyrotropin-receptor antibody (TRAb) value. However, a significant correlation of therapy success to absorbed dose (r = 0.69, p < 0.005) could be shown only for carbimazole-off patients, but not for the others. Finally, multivariate factor analysis consistently showed that therapy success was correlated only to absorbed dose and antithyroid drugs, not to initial thyroid volume, TRAb value, or thyroid function. Thyroid volume per se is not responsible for the lower success rate in Graves' disease patients with large goiters because even a comparable group of 32 Graves' disease patients with small thyroid glands (< or =20 mL) and without simultaneous carbimazole showed a success rate of 87.5%. The high failure rate in the carbimazole-on patients (absorbed dose comparable to carbimazole-off) is due to the simultaneous administration of carbimazole. Therefore, if clinically feasible, we recommend discontinuing carbimazole at least one day before beginning radioiodine therapy.

Adult↗

PubMed1998

Evaluation of olfactory and auditory system effects of the antihyperthyroid drug carbimazole in the Long-Evans rat.

Carbimazole (2-carbethoxythio-1-methylimidazole) is a thiocarbamide drug used in the treatment of hyperthyroidism in humans. Side effects associated with carbimazole treatment are reported to include impaired taste, impaired olfaction, and hearing loss. The structurally similar antihyperthyroid drug methimazole (1-methyl-2-mercaptoimidazole), also reportedly associated with impaired taste and olfaction in humans, has recently been demonstrated by this laboratory to be an olfactory toxicant by both the oral and intraperitoneal routes of exposure in rodents. A systematic evaluation of sensory system effects of these compounds, either in rodents or humans, is not available in the literature. Male Long-Evans rats were used to evaluate the auditory and olfactory toxicity of carbimazole by two routes of exposure. Histopathological evaluation of nasal cavities from rats administered carbimazole via i.p. and oral routes revealed olfactory mucosal damage and early evidence of repair; a no-observed effect level (NOEL) of 100 mg/kg was observed for orally administered carbimazole. Further, these studies demonstrate evidence for the generation of the olfactory toxic metabolites of carbimazole by the olfactory mucosa itself, as incubation of carbimazole with an olfactory S9 preparation resulted in NADPH-dependent degradation of carbimazole. Evaluation of the auditory startle response in carbimazole-treated rats revealed no deficits, demonstrating that carbimazole does not cause a global loss of hearing in rats.

Administration, Oral↗

PubMed1993

Comparison of the disposition of carbimazole and methimazole in clinically normal cats.

The oral disposition of the antithyroid drugs methimazole and carbimazole were compared in nine clinically normal cats. After the administration of 5 mg of methimazole, serum concentrations of methimazole increased in all the cats, with mean drug concentrations reaching peak values (1.37 micrograms ml-1) at 30 minutes. After administration of 5 mg carbimazole, serum concentrations of carbimazole remained low, but serum methimazole became readily measurable, with mean drug concentrations reaching peak values (0.79 microgram ml-1) at 120 minutes. When serum concentrations of methimazole attained after administration of the two antithyroid drugs were compared, the mean maximum serum methimazole concentration achieved after administration of methimazole was approximately twofold higher than peak concentrations measured after administration of carbimazole. In addition, the mean area under the serum concentration curve (AUC) after administration of methimazole was approximately twofold higher than the mean AUC determined after administration of carbimazole. When the differences in molecular weight between the two drugs was taken into consideration, however, these methimazole:carbimazole ratios of 2:1 were nearly equivalent to the molar ratio of the 5 mg doses of the drugs given (1.63). Results of this study indicate that carbimazole is nearly totally converted to methimazole after oral administration to cats, similarly to the findings in man. The finding of less available serum methimazole after administration of a 5 mg tablet of carbimazole than after methimazole is also consistent with published antithyroid drug dosages needed to control hyperthyroidism in cats.

Administration, Oral↗

PubMed1998

Insulin autoantibodies before and after carbimazole therapy in Asian Indian patients with Graves' disease.

Carbimazole therapy can induce insulin autoantibodies (IAA) in Japanese Graves' disease patients, a phenomenon possibly linked to their immunogenetic profile. This phenomenon is not observed in Caucasians. We assessed IAA levels in 114 North Indian Graves' disease patients before and after carbimazole therapy (mean duration 6.2 +/- 3.9 months). The functional significance of IAA was assessed in 46 of them by first phase (sum of +1 and +3 min) insulin response to intravenous glucose (IVGTT) and an oral glucose tolerance test (OGTT) undertaken before commencement of the carbimazole therapy. IAA were measured using a radiobinding assay and expressed as the assay precision unit, S.D. scores (S.D.S), over healthy controls. Before treatment 22 of 114 (19.3%) patients were IAA positive (mean +/- S.D., 5.9 +/- 3.2 S.D.S). After carbimazole therapy a further 11 (9.6%) showed positive for IAA (mean +/- S.D., 3.5 +/- 1 S.D.S). Of the 22 patients who were IAA positive before treatment, 12 became negative after carbimazole therapy. The fasting insulin and first phase insulin responses were similar in IAA positive and IAA negative Graves' disease patients (mean +/- S.D., 61.7 +/- 35.9 versus 88.3 +/- 46.6 pmol/l, P = 0.123 and 1127 +/- 696 versus 1033 +/- 430 pmol/l, P = 0.716, respectively). The OGTT results were comparable in the IAA positive and the IAA negative groups. Thus, North Indian Graves' disease patients, who resemble Caucasians in their HLA haplotypes, behave like Japanese in their tendency to become IAA positive with carbimazole therapy. A subset of the patients who were IAA positive before treatment also demonstrated negative IAA (12/22) after carbimazole therapy.

Adult↗

PubMed2003

Carbimazole-related gastroschisis.

OBJECTIVE: To report a case of gastroschisis in a newborn secondary to carbimazole exposure in utero. CASE SUMMARY: A 25-year-old white woman was treated for Graves disease with carbimazole throughout pregnancy. A boy was born prematurely by vaginal delivery, with a gastroschisis without associated malformative syndrome. Death occurred in the 25th hour of life after surgical repair. DISCUSSION: Carbimazole is completely metabolized to methimazole after absorption. Carbimazole or methimazole intake during pregnancy has been associated with an increased incidence of scalp aplasia. Abdominal wall defects secondary to carbimazole or methimazole exposure in utero seem to be a rare occurrence. However, other cases of abdominal wall defects have been reported in 4 newborns, 2 of them associated with scalp aplasia. An objective causality assessment revealed that the relationship between the gastroschisis and the exposure to carbimazole in utero was possible. CONCLUSIONS: It is important to emphasize the possible risk of abdominal wall defects in newborns to pregnant women taking carbimazole or methimazole.

Adult↗

PubMed2006

Concomitant agranulocytosis and hepatotoxicity after treatment with carbimazole.

OBJECTIVE: To describe a case of agranulocytosis and severe hepatotoxicity associated with carbimazole treatment. CASE SUMMARY: A 37-year-old woman was diagnosed with severe hyperthyroidism resulting from Graves' disease. Treatment with carbimazole 30 mg/day was initiated. Within 15 days following the start of therapy, both minor (eg, pruritus, rash, urticaria, fever, arthralgias) and potentially life-threatening (eg, agranulocytosis, severe mixed hepatotoxicity with severe cholestatic jaundice) adverse effects developed. The patient's symptoms and laboratory abnormalities resolved following withdrawal of carbimazole. Treatment with other antithyroid drugs was not attempted, and (131)I ablation of the thyroid was successfully performed. Thyroid function was maintained with standard follow-up care. Agranulocytosis, identified following bone marrow biopsy, was treated with granulocyte colony-stimulating factor. DISCUSSION: Agranulocytosis and hepatotoxicity are rare adverse effects associated with carbimazole treatment and are usually dose- and age-related. The likelihood that carbimazole induced these undesirable events in our patient is rated as probable based on the Naranjo probability scale. We believe this case to be the first to describe minor and major adverse effects related to carbimazole therapy in a patient with Graves' disease. CONCLUSIONS: Major adverse effects associated with carbimazole are infrequent. However, clinicians need to be aware that the effects described here, including severe liver failure and bone marrow toxicity, may occur in patients receiving this drug.

Adult↗

PubMed1998

Evidence for carbimazole as an antioxidant?

There is evidence in the literature to support the view that antioxidants are involved in the pathogenesis of Graves disease and that antioxidants may act as free radical scavengers. This study has compared the effects of a 12 month course of conventional Carbimazole therapy on peripheral blood antioxidant levels with those of a 12 month course of a higher dose treatment regime. Fifty seven patients were enrolled into the study. Those in Group 1 (n = 23) received a 12 month course of 60 mg/day Carbimazole. Those in Group 2 (n = 34) received 45 mg/day for the first month, 30 mg/day for the second and 20 mg/day for the remaining 10 months of treatment. T3 was added in both groups after 2-4 months to maintain patients euthyroid. Baseline samples were also obtained from 30 control subjects. Blood samples were taken for the measurement of plasma thiol (PSH), lysate thiol (LSH), superoxide dismutase (SOD) and caeruloplasmin (CP) and for routine thyroid function tests (TT4, TT3 and TSH). In untreated Graves' patients, serum levels of PSH and SOD were reduced and levels of LSH increased compared to controls. Following 2 months high dose Carbimazole therapy there was a significant increase in PSH levels and a significant reduction in CP levels compared to presentation levels. In the more conventional dose Group 2 patients PSH levels also rose significantly during the first 2 months of treatment. Levels for both groups were still significantly lower than the control group. After 12 months high dose Carbimazole therapy PSH levels had decreased so that they no longer differed from untreated levels. LSH and SOD levels still remained abnormal. CP levels continued to fall. Similar findings were obtained in those patients receiving the more conventional course of treatment. At no point was their any significant difference in antioxidant levels between the two treatment groups. The abnormal levels of antioxidants in the serum of untreated Graves' patients confirm their involvement in the pathogenesis of Graves' disease. Carbimazole therapy appeared to have only short term effects on the peripheral blood levels of the antioxidants measured. Carbimazole appeared to act only on the extra cellular markers of antioxidant activity (PSH, CP) although the disease itself had marked intracellular effects (LSH, SOD). These findings suggest that Carbimazole does not act as a free radical scavenger.

Adult↗

PubMed2005

Carbimazole-induced hypothyroidism causes the adrenal atrophy in 10 days' prenatally treated albino rats.

OBJECTIVE: To investigate the effects of carbimazole-induced hypothyroidism, and simultaneous administration of thyroxine (thyroid hormone analogue) on the adrenal glands of 10 days' prenatally treated albino rats. DESIGN: A comparative study. PLACE AND DURATION OF STUDY: Department of Anatomy, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre (JPMC), Karachi, from 15th July 2001 to 31st August 2001. PATIENTS AND METHODS: Ten days old albino rats of either gender, which were delivered by their respective mothers which were originally obtained from Charles River Breeding Laboratories, Brooklyn, Massachusetts, USA, and were cross bred, housed and maintained on the balanced diet in the Animal House of BMSI, JPMC, Karachi. Eighteen prenatally treated albino rats of 10 days old were used in the experiment and divided into three groups: X, Y and Z, comprising 06 animals in each group, i.e. from carbimazole treated mothers (X), carbimazole plus thyroxine treated mothers (Y), and controlled mothers (Z). At the end of 10th postnatal day all the animals were sacrificed, their adrenal glands were removed, fixed, sectioned, and stained with H&E. The adrenal histology with relation to its width of cortex, zones and number of cells in different zones of cortex were studied. RESULTS: Carbimazole-induced hypothyroidism causes the adrenal atrophy in the adrenals of 10 days' prenatally treated albino rats by decreasing the total width of cortex and its zones especially zona fasciculata. CONCLUSION: Carbimazole-induced hypothyroidism by carbimazole causes the shrinkage of adrenal cortex in 10 days prenatally treated albino rats.

Adrenal Glands↗

PubMed1978

Low dose lithium-carbimazole in the treatment of thyrotoxicosis.

Fifteen patients with thyrotoxicosis were treated with low dose sustained release lithium carbonate 400 mg, combined with carbimazole 40 mg daily, and the therapeutic response was followed over a two week period. This response was compared with that obtained in a similar group of patient treated with carbimazole alone. Li-carbimazole treatment brought about a fall in the mean total serum T4 of 57.4% compared with a drop of 32.8% in patients treated with carbimazole alone. The mean serum T3 fell by 69.4% in the Li-carbimazole group compared with 47.3% in the group treated with carbimazole only. No lithium adverse effects were encountered.

Antithyroid Agents↗

PubMed2000

Feline hyperthyroidism: spectrum of clinical presentions and response to carbimazole therapy.

OBJECTIVE: To determine the spectrum of clinical presentations of hyperthyroidism in cats and response to carbimazole therapy by analysis of historical, clinical and laboratory data. DESIGN: A prospective clinical study involving client-owned cats presenting to a private veterinary practice in Australia. PROCEDURE: Twenty-five cats diagnosed as hyperthyroid during a 23-month period participated in the study with owner consent. Therapy with carbimazole was instituted and revisits were scheduled 2, 6 and 13 weeks after diagnosis. The cats were physically examined and underwent haematological and serum biochemical testing at each revisit. Owners were also asked to assess clinical signs in their cats in the periods between veterinary examinations. Cats with underlying renal disease were managed by alterations or cessation of carbimazole therapy. RESULTS: A high prevalence of lethargic or inappetent cats without detectable underlying nonthyroidal illness was found. There was also a high prevalence of cats less than 10-years-old and cats in good body condition. Fourteen cats treated with carbimazole and monitored for 13 weeks responded favourably to therapy. Side-effects were minor and uncommon. Cats with underlying renal disease that became apparent during the study, responded well to alterations or cessation of carbimazole therapy. CONCLUSION: The trend towards more subtle clinical presentations of hyperthyroid cats reported previously continued in this study. The findings of the current study do not appear to support the traditional view of hyperthyroid cats as being old, hyperactive, hungry and thin. Carbimazole therapy was found to decrease the prevalence of almost all clinical abnormalities in 14 cats and side-effects were minor and uncommon. This study demonstrates the usefulness of medical management of hyperthyroidism in the cat when radioiodine therapy is not possible due to renal compromise or other factors.

Animals↗

PubMed2002

Acute pancreatitis, hepatic cholestasis, and erythema nodosum induced by carbimazole treatment for Graves' disease.

A 33-year old female was diagnosed as Graves' disease and started on carbimazole. One month later when she was already euthyroid only on carbimazole therapy, she developed acute pancreatitis associated with mild cholestatic hepatitis and erythema nodosum. Carbimazole therapy was interrupted, pancreatic and liver function gradually improved and became normalized two weeks later. Other potential etiological causes of acute pancreatitis, hepatitis and erythema nodosum were excluded. Rechallenge with a single dose of carbimazole led to a new episode of acute pancreatitis and cholestatic hepatitis one day later. The appearance of different hypersensitivity reactions including pancreatitis, hepatitis and erythema nodosum, together with the observation that the interval between drug intake and onset of symptoms became shorter with repeated exposure to carbimazole, point to an immune-mediated mechanism. Carbimazole has to be added to the list of drugs capable of inducing acute pancreatitis, and should be emphasized the need to discontinue this medication as soon as there is evidence of pancreatic dysfunction.

Acute Disease↗

PubMed1993

Effect of L-thyroxine and carbimazole on brain biogenic amines and amino acids in rats.

Effect of L-thyroxine and carbimazole on brain biogenic amines and amino acids content and circulating levels of thyroid hormones has been investigated in rats. L-thyroxine treatment caused marked elevation of 5-HT, histamine and glutamate along with the decline in the level of GABA whereas administration of carbimazole had a contrary effect on rat hypothalamus. Further, L-thyroxine administration also raised histamine as well as glutamate content and decreased GABA level in thalamic region of the rat brain but carbimazole treatment reduced 5-HT and glutamate content in this area of the rat brain. Similarly, cortical content of 5-HT and histamine also increased following L-thyroxine administration whereas carbimazole treatment lowered 5-HT, histamine and glutamate levels. Simultaneously, there was a considerable rise in the circulating levels of T3 and T4 in L-thyroxine-treated rats and a marked reduction in their levels in carbimazole-treated rats. There is a positive correlation between these amines and the thyroid hormone level. Thus, the results suggest that L-thyroxine and carbimazole administration cause marked alteration in biogenic amines and amino acids in rat brain, which may have an important role in the functioning of thyroid gland.

Amino Acids↗

PubMed2006

[Transdermal carbimazole for the treatment of feline hyperthyroidism].

Orally administered antithyroid drugs are frequently used to treat hyperthyroidism in cats; however, the non-cooperative behaviour of some cats may make it difficult to administer tablets. The aim of this study was to develop a carbimazole ointment for application to the inner pinna of the ear and to test its effectiveness in 13 cats with hyperthyroidism. Laboratory investigations were performed before, and 4, 8, and 12 weeks after start of the treatment. Laboratory data for 9 cats were available at the end of the observation period. The starting dose of carbimazole ointment was 5 mg once daily. If no complications occurred, the dose was increased to 5 mg twice daily from the 6th day onwards. Further dose adjustments were mainly based on the plasma thyroxine (T4) concentration. The median plasma T4 concentration at the end of the observation period (24 nmol/l) was significantly lower than that before treatment (152 nmol/l). The dosage of carbimazole needed to achieve euthyroidism ranged from 4 to 17 mg twice daily. Treatment with carbimazole ointment resulted in disappearance of signs of hyperthyroidism; plasma concentrations of urea and creatinine increased significantly. The results of this study indicate that twice daily administration of carbimazole ointment to the inner pinna of the ear is an effective treatment for hyperthyroidism in cats. This provides the veterinarian with a new and promising treatment option. Because carbimazole ointment has not been registered, according to European law it can only be used for the treatment of hyperthyroidism in cats if other licensed medications have been tried and if there is a therapeutic need.

Administration, Cutaneous↗

PubMed2003

Effects of carbimazole on morphology of rat adrenals.

OBJECTIVE: Study was conducted to investigate the effects of (i) carbimazole and (ii) simultaneous administration of thyroxine (thyroid hormone analogue) on the morphology of rat adrenals. DESIGN: A prospective case-control study. PLACE AND DURATION OF STUDY: Department of Anatomy,Basic Medical Sciences Institute (BMSI), JPMC, Karachi, during a period of six weeks. METHODOLOGY: The study was conducted on albino rats originally obtained from Charles River Breeding Laboratories, Brooklyn, Massachusetts, USA, and were cross bred, housed and maintained on balanced diet in the Animal House of BMSI, JPMC, Karachi. Eighteen adult albino rats used in the experiment were divided into three groups, i.e. A, B and C, each comprising 6 animals as control, carbimazole-treated, and carbimazole plus thyroxine-treated animals respectively. At the end of six weeks treatment all the animals were sacrificed and their adrenal glands removed, fixed, sectioned and stained with H&E and Sudan black. The histology of adrenals, width of cortex and its zones, and number of cells in different zones of cortex was studied. RESULTS: Carbimazole affects the morphology of adult rat adrenals by decreasing the total width of cortex and its zones especially the zona fasciculata with decrease in number of cells. It also showed the increase in fat contents on Sudan black staining. CONCLUSION: Carbimazole causes shrinkage of the adrenal cortex.

Adrenal Glands↗

PubMed1990

Insulin autoantibodies in Graves' disease--before and after carbimazole therapy.

Insulin autoantibodies (IAA) are well documented in patients with insulin-dependent diabetes (IDDM) prior to the administration of insulin and in patients with reactive hypoglycaemia--the insulin autoimmune syndrome (IAS). It has been suggested that IAA can be induced by the administration of drugs containing sulphydryl groups, such as carbimazole, and they have been frequently described in Graves' disease. An alternative explanation is the clustering of autoantibodies in autoimmune disease. We studied 39 patients (37 females, two males, age range 14 to 61 years; mean 33.8 years) with proven Graves' disease and no previous treatment with carbimazole. Fifteen of the 39 patients had a family history of other autoimmune diseases. IAA and thyroid autoantibodies were assayed at diagnosis and monthly thereafter while on treatment with carbimazole, for up to 6 months. IAA were measured using a direct-binding solid-phase ELISA and specificity was confirmed by absorption studies using insulin covalently coupled to Sepharose beads. At diagnosis 33 of the 39 patients (85%) were positive for thyroid microsomal antibodies, 13 (33%) were positive for thyroglobulin antibodies, and 4 (10%) were positive for IAA. All IAA-positive patients had microsomal antibodies at diagnosis, and two had thyroglobulin antibodies in addition. After 4 months on carbimazole, the frequency of thyroid microsomal autoantibodies was unchanged (83%), while that of anti-thyroglobulin antibodies had fallen (8.6%). All four IAA-positive patients remained positive, and studies of binding to human, porcine and bovine insulin demonstrated that one serum, initially human insulin specific, later became cross-reactive with all three. We conclude that low titres of IAA are found in Graves' disease, and are associated with the presence of autoimmunity rather than the carbimazole. Symptomatic hypoglycaemia, however, is rare in Caucasian patients.

Adolescent↗

PubMed2000

Neutropenia and anaemia due to carbimazole-dependent antibodies.

Carbimazole-dependent antibodies to erythrocytes were detected in the sera of three anaemic patients who had been treated with carbimazole for hyperthyroidism. By the use of Rhnull-typed erythrocytes, we could show that some of these were directed against the proteins of the Rh complex. Carbimazole-dependent antibodies eluted from erythrocytes showed no binding to other blood cells. One patient also presented with neutropenia and mild thrombocytopenia. Additional carbimazole-dependent antibodies against the neutrophil-specific Fcgamma receptor IIIb (FcgammaRIIIb, CD16b) and the broadly expressed platelet endothelial cell adhesion molecule 1 (PECAM-1; CD31) were detected in this patient's serum. Surprisingly, the PECAM-1-reactive drug-dependent antibodies were also detectable in the sera of the other two patients with normal leucocyte and platelet counts. We assume that carbimazole can induce cell lineage-specific drug-dependent antibodies that cause cytopenia and also drug-dependent antibodies against the broadly expressed PECAM-1 molecule that may cause mild but not severe cytopenia.

Aged↗