Antioxidant effects of α-lipoic acid against epididymal oxidative damage in adult offspring rats exposed to maternal hypothyroidism stress.

It is well known that the epididymis promotes post-testicular sperm maturation events. However, its malfunction during congenital hypothyroidism is relatively less understood as compared to the testis. The present study evaluated the probable effect of α-lipoic acid on epididymal oxidative stress parameters in rats exposed to antithyroid drug, carbimazole during fetal period. Time-mated pregnant rats in unexposed and carbimazole (1.35 mg/Kg body weight exposed were allowed to deliver pups and weaned. At postnatal day 100, the F1 male pups were assessed for epididymal endpoints. Among the epididymal regions, significant elevation of lipid peroxidation levels, superoxide anion, and hydrogen peroxide contents with a concomitant reduction in the activity levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and reduced glutathione levels were observed in cauda epididymis of carbimazole exposed rats over controls. Significant elevation in sperm DNA fragmentation (comet assay), accelerated cauda epididymal sperm transit time and reduction in epididymal sialic acid content was observed in carbimazole exposed rats. RT-qPCR studies revealed that embryonic exposure to carbimazole resulted in down regulation of androgen receptor, nuclear factor eryrthoid 2 like 2, 5α-reducatse 1 mRNA levels, while up regulation of caspase 3 mRNA was observed in epididymal regions of rats. In addition, fetal exposure to carbimazole resulted in disorganization of cauda epididymal architecture in rats. Conversely, supplementation of α-lipoic acid (70 mg/Kg bodyweight) during PND 3 to 14 restored epididymal functions in carbimazole exposed rats and the ameliorative effects of lipoic acid could be attributed to its antioxidant and steroidogenic effects.

The protective impact of hesperidin against carbimazole-induced hypothyroidism, via enhancement of inflammatory cytokines, histopathological alterations, and Nrf2/HO-1.

The aim of this study was to evaluate the anti-inflammatory, antioxidant, and antiproliferative effects of hesperidin (HSP) and eltroxin (ELT) on hypothyroidism (HPO) induced by carbimazole (CBZ) in white male albino rats. Thirty-two adult rats were categorized into four groups: Group 1, no treatment (control); Group II, treated with CBZ (20 mg/kg); Group III, treated with HSP (200 mg/kg) + CBZ; and Group IV, treated with ELT (0.045 mg/kg) + CBZ. All treatments were provided as oral daily doses for 90 days. Thyroid hypofunction was significantly manifested in Group II. However, increased levels of thyroid hormones, antioxidant enzymes, nuclear factor erythroid 2-related factor 2, heme oxygenase 1, and interleukin (IL)-10, and a decrease in the level of the thyroid-stimulating hormone were observed in Groups III and IV. On the contrary, decreased levels of lipid peroxidation, inducible nitric oxide synthase, tumor necrosis factor α, IL-17, and cyclooxygenase 2 were detected in groups III and IV. The histopathological and ultrastructural findings were ameliorated in Groups III and IV; on the contrary, Group II presented with significant increases in the height and number of layers of the follicular cells. Immunohistochemistry demonstrated a marked increase in thyroglobulin and significant decreases in the levels of nuclear factor kappa B and proliferating cell nuclear antigen in Groups III and IV. These results confirmed the effectiveness of HSP as an anti-inflammatory, antioxidant, and antiproliferative agent in rats with hypothyroidism. Additional studies are required to assess its potential as a novel agent against HPO.

Transcriptomic profiling identified altered expression of genes associated with testicular functions in adult F1 rats exposed to carbimazole during fetal period.

The central goal of this study was to investigate the alterations in transcriptome of testis in F1 generation adult rats exposed to carbimazole prenatally. At post-natal day 100, the testis of rats delivered to carbimazole exposed (time-mated pregnant rats orally administered with carbimazole from gestation day 9 to 21) and control (untreated pregnant rats) groups were subjected to transcriptomic analysis using NGS platform. A total of 187 differentially expressed (up regulated: 49 genes; down regulated: 138) genes were identified in carbimazole exposed rats over controls and the major processes associated with these altered testicular transcripts were examined. Functional clustering analysis suggest that the involvement of identified DEGs were linked to intrinsic and extrinsic apoptotic pathways, mitochondrial solute carriers slc25a members, nuclear receptors/zinc family members, steroidogenic pathway and cholesterol synthesis, and growth factors and protein kinases and thus represent potential mediators of the developmental toxic effects of carbimazole in F1 generation rats. Based on the findings, it can be concluded that prenatal exposure to carbimazole prominently affects expression of multiple transcripts implicating key regulatory events associated with testicular functions, spermatogenesis and steroidogenesis in rats at their adulthood. These results support our earlier findings and hypothesis. This background information obtained at the testicular transcriptome during gestational hypothyroidism might be helpful for future studies and experiments to gain additional in-depth analysis and to develop strategies to protect F1 generation male reproductive health. SIGNIFICANCE: The rationale for the paper described thyroid gland changes in the off springs. Antithyroid drugs are widely used to control thyroid disorders and used to control thyroid hormone levels during surgeries. Carbimazole is one of the antithyroid drugs and is a parent molecule of methimazole. Both the drugs can able to cross placenta. During fetal period, the development of thyroid gland is not completely formed and hence, the fetus entirely depends on the maternal thyroid hormones. Therefore, it is conceivable that the disturbances at the level of maternal thyroid hormones could interfere with the development of vital organs such as testis and glands including thyroid gland (Kala et al., 2012). To address this notion, the present study was designed and executed.

Metformin alleviates the dysregulated testicular steroidogenesis and spermatogenesis induced by carbimazole in levothyroxine-primed rats.

Most of the published experiments about carbimazole (CMZ)-induced testicular injury are constructed in normal healthy animals, which lakes the translational identification. Despite metformin (MET) having advantageous effects on injured testicles, its impact on thyroid function is arguable. In the current levothyroxine (LT4)/CMZ model, Wistar rats were primed by LT4 for sixty days. CMZ was then given individually or simultaneously with different doses of MET, 100, 200, and 400 mg, daily for thirty days. Serum was assessed for thyroid profile panel, sex hormones, and gonadotropin levels. Testicular tissues were examined for steroidogenesis, spermatogenesis, inflammation, and apoptosis. Histopathology of thyroid and testes were examined, besides thyroidal nuclear factor (NF)-kB expression. MET in a dose-response manner improved the LT4/CMZ-induced testicular toxicity by increasing the steroidogenic acute regulatory protein (StAR), and 17-ß-hydroxysteroid dehydrogenase (17ßHSD) activities, the proliferating cell nuclear antigen (PCNA), sperm count and motility, sex hormones, and gonadotropin levels. MET-400 mg markedly decreased the elevated NF-kB expressions, tumour necrosis factor (TNF)-α, caspase-3, and BAX, and increased BCL-2. LT4/CMZ could be used as translational animal modelling. MET displayed a dose-dependent ameliorative effect on the LT4/CMZ model without significant harmful effects on thyroid functions. MET-testicular protective roles in diabetics with thyroidal diseases should be explored.

The Protective Effect of Turmeric against Carbimazole Induced Toxicity in Male Rats.

Carbimazole is a widespread drug utilized for treating hyperthyroidism. However, carbimazole usage could be associated with adverse effects such as liver damage and nephritis in rats. At the same time, turmeric, as a medical plant, has many antioxidant effects against liver and kidney toxicity. This study aimed to explore the protective effect of turmeric against carbimazole-induced toxicity in rats. The experiment was carried out on 24 male Wistar rats. They were separated into four groups, each with six animals, as follows: 1. Control group: represents a healthy animal, and each rat is only given standard food and distilled water for 30 days. 2. Carbimazole group: drenched orally 0.5 mg carbimazole daily for 30 days. 3. Turmeric group: drenched orally 100 mg turmeric powder daily for 30 days. 4. Carbimazole and turmeric group: drenched orally carbimazole 0.5 mg and turmeric 100 mg daily for 30 days. The study demonstrated a significant effect of turmeric powder in reducing the toxicity of carbimazole in both the kidney and liver biochemical parameters, in addition to the evidence of histological sections. Turmeric powder has the ability to reduce and prevent renal and hepatic toxicity induced by carbimazole overdose, which gives turmeric medical value.

Complexation of uranyl (UO2)2+ with bidentate ligands: XRD, spectroscopic, computational, and biological studies.

Three new uranyl complexes [(UO2)(OAc)2(CMZ)], [(UO2)(OAc)2(MP)] and [(UO2)(OAc)2(SCZ)] were synthesized and characterized by elemental analysis, FT-IR, UV-Vis spectroscopy, powder XRD analysis, and molar conductivity. The IR analysis confirmed binding to the metal ion by the sulfur and ethoxy oxygen atoms in the carbimazole (CMZ) ligand, while in the 6-mercaptopurine (MP) ligand, the sulfur and the N7 nitrogen atom of a purine coordinated binding to the metal ion. The third ligand showed a 1:1 molar ratio and bound via sulfonamide oxygen and the nitrogen of the pyrimidine ring. Analysis of the synthesized complexes also showed that acetate groups had monodentate binding to the (UO22+). Density Functional Theory (DFT) calculations at the B3LYP level showed similar structures to the experimental results. Theoretical quantum parameters predicted the reactivity of the complexes in the order, [(UO2)(OAc)2(SCZ)] > [(UO2)(OAc)2(MP)]> [(UO2)(OAc)2(CMZ)]. DNA binding studies revealed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(CMZ)] have the highest binding constant (Kb) among the uranyl complexes. Additionally, strong binding of the MP and CMZ metal complexes to human serum albumin (HSA) were observed by both absorbance and fluorescence approaches. The antibacterial activity of the complexes was also evaluated against four bacterial strains: two gram-negative; Escherichia coli and Klebsiella pneumonia, and two gram-positive; Staphylococcus aureus and Streptococcus mutans. [(UO2)(OAc)2(MP)] had the greatest antibacterial activity against Klebsiella pneumonia, the gram-positive bacteria, with even higher activity than the standard antibiotic. In vitro cytotoxicity tests were also performed against three human cancer lines, and revealed the most cytotoxic complexes to be [(UO2)(OAc)2(SCZ)], which showed moderate activity against a colon cancer cell line. Thus, uranyl addition enhances the antibacterial and anticancer properties of the free ligands.

Pharmacodynamic Response to Anti-thyroid Drugs in Graves' Hyperthyroidism.

Objective: Graves' disease is the commonest cause of hyperthyroidism in populations with sufficient dietary iodine intake. Anti-thyroid drugs (ATD) are often used as the initial treatment for Graves' hyperthyroidism, however there is a paucity of data relating the dose of ATD therapy to the effect on thyroid hormone levels, increasing the risk of both over- and under-treatment. We aimed to determine the pharmacodynamic response to the ATD carbimazole. Design: Retrospective cohort study. Methods: Participants were patients (n = 441) diagnosed with Graves' disease at Imperial College Healthcare NHS Trust between 2009 and 2018. The main outcome measure was change in thyroid hormone levels in response to ATD. Results: Baseline thyroid hormone levels were positively associated with TSH receptor antibody titres (P < 0.0001). Baseline free triiodothyronine (fT3) were linearly related to free thyroxine (fT4) levels in the hyperthyroid state (fT3 = fT4*0.97-11), and fell proportionately with carbimazole. The percentage falls in fT4 and fT3 per day were associated with carbimazole dose (P < 0.0001). The magnitude of fall in thyroid hormones after the same dose of carbimazole was lower during follow up than at the initiation visit. The fall in thyroid hormone levels approximated to a linear response if assessed at least 3 weeks after commencement of carbimazole. Following withdrawal of antithyroid drug treatment, the risk of relapse was greater in patients with higher initial fT4, initial TSH receptor antibody titre, males, smokers, and British Caucasian ethnicity. Conclusion: We identify a dose-response relationship for fall in thyroid hormones in response to carbimazole to aid in the selection of dose for Graves' hyperthyroidism.

Thyrotoxic Neuropathy: A rare cause of acute flaccid paraplegia.

Acute polyneuropathy is a rare manifestation of severe hyperthyroidism. We report a 22-year-old Omani male who presented to the Sohar Hospital, Sohar, Oman, in 2016 with acute-onset rapidly progressive flaccid areflexic paraplegia as the presenting manifestation of thyrotoxicosis. Nerve conduction studies revealed mixed axonal and demyelinating polyneuropathy in both the motor and sensory nerves. Treatment of the hyperthyroidism with ß-blockers and carbimazole along with physiotherapy resulted in the patient's full recovery and the alleviation of his symptoms. Besides highlighting this rare association, this report underscores the importance of including thyroid function tests in the evaluation of patients with acute polyneuropathy.

Influence of prior carbimazole on the outcome of radioiodine therapy in pediatric and adolescent Graves' disease.

OBJECTIVE OF THE STUDY: Therapeutic options for pediatric Graves' disease (PGD) include antithyroid drug therapy (ATD) as the first line and radioiodine (I-131) therapy as the second line of treatment. To date, controversies persist regarding the true effect of prior ATD in the outcome of I-131 therapy in PGD. This study evaluated the effect of prior carbimazole treatment on the outcome of I-131 therapy in PGD. METHODS: This is a retrospective study covering the years 1995-2012, with a median follow-up of 75 months. Records of 114 children (84 girls and 30 boys, age range: 5-20 years, mean 24-h radioiodine uptake, 58%) who had clinically and biochemically proven Graves' disease irrespective of prior ATD therapy were included. All patients were treated with fixed doses of 5 mCi (185 MBq) I-131 for Graves' disease; 74 had undergone prior carbimazole treatment (group 1) and 40 were drug naive (group 2). The endpoint of follow-up was stable euthyroid or hypothyroid in patients. The effect of prior carbimazole treatment on the outcome of I-131 therapy in PGD patients was evaluated. The success of radioiodine therapy was defined as the cure of hyperthyroidism. Variables were analyzed to identify the potential predictive factors for euthyroidism/hypothyroidism after treatment. RESULTS: The cure rate was 70% in group 1 and 83% in group 2 with a single dose of radioiodine (P=0.299). The success rate achieved at the end of 1-year follow-up in group 1 and group 2 was 81 and 87%, respectively (P=0.401). No independent predictor was associated with success or failure of treatment. At the median follow-up of 75 months (range: 12-216 months), 76% of patients were hypothyroid on replacement doses of levothyroxine and 24% still continued to be euthyroid. CONCLUSION: Prior carbimazole treatment does not alter the outcome of radioiodine therapy in PGD.

Carbimazole is an inhibitor of protein synthesis and protects from neuronal hypoxic damage in vitro.

Oxygen deprivation during ischemic or hemorrhagic stroke results in ATP depletion, loss of ion homeostasis, membrane depolarization, and excitotoxicity. Pharmacologic restoration of cellular energy supply may offer a promising concept to reduce hypoxic cell injury. In this study, we investigated whether carbimazole, a thionamide used to treat hyperthyroidism, reduces neuronal cell damage in oxygen-deprived human SK-N-SH cells or primary cortical neurons. Our results revealed that carbimazole induces an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) that was associated with a marked inhibition of global protein synthesis. Translational inhibition resulted in significant bioenergetic savings, preserving intracellular ATP content in oxygen-deprived neuronal cells and diminishing hypoxic cellular damage. Phosphorylation of eEF2 was mediated by AMP-activated protein kinase and eEF2 kinase. Carbimazole also induced a moderate calcium influx and a transient cAMP increase. To test whether translational inhibition generally diminishes hypoxic cell damage when ATP availability is limiting, the translational repressors cycloheximide and anisomycin were used. Cycloheximide and anisomycin also preserved ATP content in hypoxic SK-N-SH cells and significantly reduced hypoxic neuronal cell damage. Taken together, these data support a causal relation between the pharmacologic inhibition of global protein synthesis and efficient protection of neurons from ischemic damage by preservation of high-energy metabolites in oxygen-deprived cells. Furthermore, our results indicate that carbimazole or other translational inhibitors may be interesting candidates for the development of new organ-protective compounds. Their chemical structure may be used for computer-assisted drug design or screening of compounds to find new agents with the potential to diminish neuronal damage under ATP-limited conditions.

Antithyroid drug carbimazole and its analogues: synthesis and inhibition of peroxidase-catalyzed iodination of L-tyrosine.

Synthesis and biological activity of the antithyroid drug carbimazole (CBZ) and its analogues are described. The introduction of an ethoxycarbonyl group in methimazole and its selenium analogue not only prevents the oxidation to the corresponding disulfide and diselenide but also reduces the zwitterionic character. A structure-activity correlation in a series of CBZ analogues suggests that the presence of a methyl substituent in CBZ and related compounds is important for their antithyroid activity.

Effects of different treatments for hyperthyroidism on the hypothalamic-pituitary-adrenal axis.

To investigate the effects of iopanoic acid (IA) and carbimazole on increased activity of the hypothalamic-pituitary-adrenal (HPA) axis in hyperthyroidism, we studied 14 women with hyperthyroidism caused by Graves' disease (n + 11) or toxic multinodular goitre (n + 3) before and after carbimazole or IA treatment. Seven normal women comprised the control group. Changes in thyroid-stimulating hormone, total and free thyroid hormones, arginine vasopressin (AVP), urinary free cortisol, adrenocorticotrophin (ACTH) and cortisol in response to human corticotrophin-releasing hormone (hCRH; 100 microg, i.v.) were estimated under basal conditions and after treatment with IA (3 g/day; n + 7) for 7 days or carbimazole (30 mg/day; n + 7) for 1 month. A higher ACTH response, with normal cortisol secretion, was observed in hyperthyroid patients in response to hCRH compared with the control group. After 7 days treatment, IA induced a significant reduction in total tri-iodothyronine (T(3)) and free T(3) to normal levels and a stronger ACTH response to hCRH, whereas plasma and urinary cortisol levels remained unchanged. Patients treated with carbimazole showed normalization of thyroid hormone levels, a reduction in basal and stimulated ACTH secretion and higher urinary free cortisol levels compared with pretreatment levels. Neither IA nor carbimazole treatment had any effect on AVP levels in hyperthyroid patients. In conclusion, hyperthyroid patients showed HPA axis hyperactivity of central origin with reduced cortisol responses, which were reversed by carbimazole treatment. The differential effects of IA and carbimazole on HPA function indicate that thyroid hormones have a role in modulation of the HPA axis.

Iodide excess exerts oxidative stress in some target tissues of the thyroid hormones.

Environmental iodine deficiency continues to be a significant public health problem worldwide. On the other hand, iodide excess results principally from the use of iodine-containing medicinal preparations or radiographic contrast media. For this reason we intended to explore iodide excess impairment on prooxidant/antioxidant balance of the thyroid gland, hepatic tissue and in blood and the effect of selenium administration on oxidative stress markers under the same circumstances. Experiments were performed for 10 days with white, male, Wistar rats, as follows: group 1: control-normal iodine supply group; 2: high iodine diet, group; 3: high iodine diet and selenium; group 4: high iodine diet and Carbimasole. Oxidative stress markers such as lipid peroxides were determined in thyroid gland, hepatic tissue and in blood. Measuring H+ donor ability of the sera and catalase activity in thyroid gland and in hepatic tissue assessed antioxidant defense. Iodide excess had prooxidant effects, leading to an increased lipid peroxides level and catalase activity in target tissues and in blood and to a decreased H+ donor ability of the sera. Selenium supplementation had opposite effects. Present data allow us to conclude that the alterations due to iodide excess in thyroid gland, hepatic tissue and in blood are mediated through oxidative stress.

Graves' disease and coexisting struma ovarii: struma expression of thyrotropin receptors and the presence of thyrotropin receptor stimulating antibodies.

Struma ovarii is a rare cause of hyperthyroidism and particularly rare in patients with coexisting Graves' disease. We describe a 28-year-old female who presented with symptoms and signs of hyperthyroidism (free thyroxine [FT(4)] 39 pmol/L, thyrotropin [TSH] < 0.05 mU/L) and associated ophthalmopathy, consistent with Graves' disease. The patient relapsed twice: once after initial successful management with carbimazole and subsequently after subtotal thyroidectomy. Radioisotope scanning showed focal uptake bilaterally in the neck and believing this was the source of thyroid hormone excess, carbimazole was restarted. A left ovarian mass was found on ultrasound during the investigation of unrelated nephrotic syndrome resulting from focal segmental glomerulosclerosis. A 555-g struma ovarii was removed surgically. Hypothyroidism developed postoperatively (FT(4) 9.7 pmol/L, TSH 36 mU/L). Circulating TSH receptor stimulating antibodies were positive and immunohistochemical studies confirm the presence of TSH receptors on the struma ovarii. The demonstration of TSH receptors on the struma ovarii increases previous speculation that struma ovarii growth and function may be augmented by the circulating TSH receptor stimulating antibodies of Graves' disease.

Assessment of povidone-iodine disinfectant compatibility with antimicrobial incise drape and adhesion inhibition on the skin using a gas chromatography/mass spectrometry approach.

According to orthopedists' reports, substitution of the original for a generic povidone-iodine (PVP-I) disinfectant could have led to some adhesion problems of antimicrobial incise drapes on the field of operation with the consequence of increasing the infection risk. Three methods have been used to assess the case: (a) a gas chromatography/mass spectrometry (GC-MS) approach quantifying methimazole formation from carbimazole, (b) in vitro adhesion experiments on a smooth glass plate surface and (c) the analysis of intrasurgical procedures. GC-MS results confirmed the higher potency of the original compared to the generic PVP-I. In vitro comparison of the adhesion on a PVP-I-pretreated glass surface showed no difference between the disinfectants and no significant destruction of the adhesive layer. However, due to different surgery preparation procedures, the remaining free skin surface granting sufficient adhesion differed if the intervening surgeon himself or his assistant prepared the field of operation. As a conclusion, the original PVP-I disinfectant is confirmed as the first-choice disinfectant for the field of operation. Adhesion problems were arising with new surgical staff and thus different preparation procedures. Exchanging PVP-I disinfectants cannot explain the adhesion problems of drapes and antimicrobial incise foils on the skin.

Testicular germ cell tumour presenting as thyrotoxicosis.

A case is reported of a patient who presented to his family doctor with a short history of cough with signs and symptoms of thyrotoxicosis. Carbimazole treatment had little effect and his symptoms worsened to include severe shortness of breath. He was investigated further and found to have multiple lung and liver metastases from an unknown primary site. Biopsy and subsequent post-mortem investigations revealed a testicular tumour and a grossly elevated serum human chorionic gonadotrophin (hCG) concentration. The biochemical and clinical thyrotoxicosis is presumed to be due to the thyrotrophic activity of excess hCG secretion, in a situation analogous to that seen in hydatidiform mole or in hyperemesis gravidarum.

Effect of hypothyroidism and thyroxin replacement on growth of long bones in prenatally treated albino rats.

OBJECTIVE: To study the effect of induced hypothyroidism and thyroxin replacement on bone growth. DESIGN: An animal study carried out on experimental Albino rats. PLACE AND DURATION OF STUDY: The study was carried out in the Department of Anatomy, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre (JPMC), Karachi, from June 1999 to May 2002. METHOD: Pregnant female Albino rats obtained from the animal house of Basic Medical Sciences Institute, JPMC, Karachi were treated with carbimazole and carbimazole plus thyroxin from 10th day of gestation till parturition. Another group of pregnant rats did not receive any treatment and acted as controls. Pups born to the treated as well as control animals were sacrificed on 10th postnatal day and fixed in formal saline. They were then processed through 95% ethanol and acetone, bulk stained with alizarin red and cleared in 4% KOH to reveal their bony and cartilaginous elements. The ulna and tibia of both sides were disarticulated from the treated and control animals and measured for intact bone length and diameter. The measurements of the three groups were then compared statistically. RESULTS: The retardation in length observed at the end of experimental period in ulna was by 13.67% and in tibia by 27.84% in carbimazole treated group while in carbimazole plus thyroxin treated group the reduction in length of ulna was 5.08% and of tibia 3.91% when compared with their age matched controls. CONCLUSION: Prenatal hypothyroidism has an adverse effect on bone growth and results in reduction of long bone length.

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.