Agoitrous Graves’ Hyperthyroidism with Markedly Elevated Thyroid Stimulating Immunoglobulin Titre displaying Rapid Response to Carbimazole with Discordant Thyroid Function / Journal of the ASEAN Federation of Endocrine Societies

@#We characterize the clinical and laboratory characteristics of 5 patients with Graves’ thyrotoxicosis whose serum free thyroxine (fT4) concentration decreased unexpectedly to low levels on conventional doses of carbimazole (CMZ) therapy. The initial fT4 mean was 40.0 pM, range 25-69 pM. Thyroid volume by ultrasound measured as mean 11 ml, range 9.0-15.6 ml. Initial TSI levels measured 1487% to >4444%. Serum fT4 fell to low-normal or hypothyroid levels within 3.6 to 9.3 weeks of initiating CMZ 5 to 15 mg daily, and subsequently modulated by fine dosage adjustments. In one patient, serum fT4 fluctuated in a “yo-yo” pattern. There also emerged a pattern of low normal/low serum fT4 levels associated with discordant low/mid normal serum TSH levels respectively, at normal serum fT3 levels. The long-term daily-averaged CMZ maintenance dose ranged from 0.7 mg to 3.2 mg. Patients with newly diagnosed Graves' hyperthyroidism who have small thyroid glands and markedly elevated TSI titres appear to be “ATD dose sensitive.” Their TFT on ATD therapy may display a “central hypothyroid” pattern. We suggest finer CMZ dose titration at closer follow-up intervals to achieve biochemical euthyroidism.

Conversion of primary hypothyroidism to hyperthyroidism:A case report / Journal of the ASEAN Federation of Endocrine Societies

@#A 51-year-old Caucasian male developed Graves’ thyrotoxicosis following long-standing treatment for hypothyroidism. After a short period of treatment with carbimazole, he developed agranulocytosis and required total thyroidectomy. In this relevant case report, we review several pathogenetic mechanisms that explain the transformation of autoimmune hypothyroidism into Graves’ disease and the possible approaches to the management of agranulocytosis secondary to antithyroid medications. Further studies are required to determine the best way to manage severe thyrotoxicosis when agranulocytosis develops due to antithyroid medications.

Clinical, biochemical & cytomorphologic study on Hashimoto’s thyroiditis.

Background & objectives: Despite, the extensive salt iodization programmes implemented in India, the prevalence of goiter has not reduced much in our country. The most frequent cause of hypothyroidism and goiter in iodine sufficient areas is Hashimoto’s thyroiditis (HT). This study records the clinical presentation, biochemical status, ultrasonographic picture and cytological appearance of this disease in a coastal endemic zone for goiter. Methods: Case records of patients with cytological diagnosis of HT were studied in detail, with reference to their symptoms, presence of goiter, thyroid function status, antibody levels and ultrasound picture. Detailed cytological study was conducted in selected patients. Results: A total of 144 patients with cytological proven HT/lymphocytic thyroiditis were studied. Ninety per cent of the patients were females and most of them presented within five years of onset of symptoms. Sixty eight per cent patients had diffuse goiter, 69 per cent were clinically euthyroid and 46 per cent were biochemically mildly hypothyroid. Antibody levels were elevated in 92.3 per cent cases. In majority of patients the sonographic picture showed heterogeneous echotexture with increased vascularity. Cytological changes were characteristic. Interpretation & conclusions: our study showed predominance of females in the study population in 21-40 yr age group with diffuse goiter. We suggest that in an endemic zone for goiter, all women of the child bearing age should be screened for HT.

Carbimazole-induced myositis in the treatment of Graves' disease: a complication in genetically susceptible individuals?

A 24-year-old Chinese woman with Graves' disease presented with myositis two months after treatment with carbimazole. The patient's myositis resolved with hydration and cessation of carbimazole. No other causes of myositis were found, and a change in the medication to propylthiouracil was uneventful. Review of the literature suggests a possible genetic susceptibility, as the majority of reported cases are Asian in origin, similar to patients who present with thyroid periodic paralysis. Changing the antithyroid drugs (ATDs) administered, decreasing the dose of pre-existing ATDs in the treatment regimen or addition of levothyroxine has been shown to result in clinical improvement of this complication. These observations suggest various mechanisms of carbimazole-induced myositis in the treatment of Graves' disease, including the direct effect of ATDs on myocytes, immune-related responses secondary to ATDs and rapid decrements in thyroid hormone with ensuing myositis.

Weight homeostasis & its modulators in hyperthyroidism before & after treatment with carbimazole.

Background & objectives: Hyperthyroidism is associated with increased food intake, energy expenditure and altered body composition. This study was aimed to evaluate the role of adipocytokines in weight homeostasis in patients with hyperthyroidism. Methods: Patients (n=27, 11men) with hyperthyroidism (20 Graves’ disease, 7 toxic multinodular goiter) with mean age of 31.3±4.2 yr and 28 healthy age and body mass index (BMI) matched controls were studied. They underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids. Patients were re-evaluated after 3 months of treatment as by that time all of them achieved euthyroid state with carbimazole therapy. Results: The LBM was higher (P<0.001) in healthy controls as compared to hyperthyroid patients even after adjustment for body weight (BW), whereas total body fat was comparable between the two groups. Serum leptin levels were higher in patients with hyperthyroidism than controls (22.3±3.7 and 4.1±0.34 ng/ml, P<0.001), whereas adiponectin levels were comparable. Plasma acylated ghrelin was higher in patients than in controls (209.8±13.3 vs 106.2±8.2 pg/ml, P<0.05). Achievement of euthyroidism was associated with significant weight gain (P<0.001) and significant increase in lean body mass (P<0.001). The total body fat also increased but insignificantly from 18.4±1.8 to 19.9±1.8 kg. There was significant decrease (P<0.05) in serum leptin and acylated ghrelin but adiponectin levels remained unaltered after treatment. Serum leptin positively correlated with TBF and this correlation persisted even after adjustment for BW, BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin did not correlate with the presence or absence of hyperphagia. Interpretation & conclusion: Patients with hyperthyroidism predominantly had decreased lean body mass which increased after achievement of euthyroidism with carbimazole. The hyperphagia and the alterations in weight homeostasis associated with hyperthyroidism were independent of circulating leptin and ghrelin levels.

Recent review on medical treatment of thyroid disease

Thyroid disorder is a common disease. Graves' disease is the most frequent cause of thyrotoxicosis and pharmacological treatment is current trends worldwide. Because of the severe adverse effects of propylthiouracil, methimazole or carbimazole should be selected as the drug of choice except for special situations such as women in the first trimester of pregnancy, thyroid storm, or in patients with severe side effects to methimazole. Treatment should continue for 12 to 18 months, but duration can be adjusted depending on the patient. For hypothyroidism, synthetic levothyroxine is the mainstay of treatment. In order to avoid overtreatment, the dosage of levothyroxine should be determined in consideration of the patient's age, sex, bodyweight, general condition, and comorbidities. In subclinical hypothyroidism, thyroid hormone replacement is suggested in patients with thyroid stimulating hormone concentrations >10 mIU/L. For non-elderly patients with high titers of thyroid autoantibodies, patients with dyslipidemia, pregnant patients, and women with infertility or ovulatory dysfunction, treatment with levothyroxine can be considered.

Thyrotoxic periodic paralysis in a Saudi patient complicated by life threatening arrhythmia

Thyrotoxic periodic paralysis [TPP] is rare in non-Orientals, and sporadic case reports were reported world-wide. Eight cases were reported in Arabs, including 3 Saudis. We present an additional case of TPP in a 38-year-old Saudi man, and review the literature on TPP in Arabs. Our patient presented with complete flaccid quadriplegia, 5 weeks after he was diagnosed with Graves' disease that was treated with carbimazole and propranolol. He was hyperthyroid, and his potassium was extremely low [1.5 mmol/L]. During initial evaluation in the emergency room, he developed transient asystole manifested by syncope. He was resuscitated and his hypokalemia was corrected, and he had a full recovery. This case emphasizes the notion that TPP can occur in patients of any ethnic background. The development of serious cardiac complications in our patient underscores the importance of early and correct diagnosis of this potentially life-threatening complication of hyperthyroidism

histologic study of carbimazole-induced hyperplasia of adenohypophysis with protective role of thyroxine in male albino rats

To assess the frequency and degree of pituitary hyperplasia in albino rats made hypothyroid by Carbimazole, and the association of severity of pituitary enlargement, and the response to treatment with thyroxine. To determine the microscopic changes occurring in beta basophil cells [Thyroid stimulating hormone and Adreno corticotrophin hormone producing cells] of Anterior Pituitary gland by giving an anti-thyroid drug, Carbimazole and Carbimazol plus, thyroxin on anterior pituitary glands of male albino rats with increasing time period. Experimental study. Anatomy Department, Basic Medical Sciences Institute, Jinnah Postgraduate-Medical Centre Karachi. Forty five healthy, young adult male albino rats were selected for the study. They were distributed into 3 main groups of 15 rats each. Group A served as control while Group B received injection Carbimazole 6 micro g m/G body weight subcutaneously daily. Group-C were treated with injection Carbim arole 6 micro g m/G body weight subcutaneously plus injection Thyroxin 5 micro g m intraperitoneally daily for their respective period of treatment. Each group was further subdivided into three sub-groups according to the period of treatment they received i.e. 2,4 and 6 weeks at the end of which animals were sacrificed. The Pituitary glands were dissected out after processing and staining [Wilson-Ezrin method]. The tissues were subjected to detailed micrometric examination. The-results are based on changes in morphometric study of number and diameter of Beta Basophil cells in anterior Pituitary gland. Mean value of number of Basophils were-increased significantly [P <0.001] in group B [Carbimazole treated] i.e 151.0 +/- 3.38 than group A [control] i.e 82.2 +/- 3.48. While in group C [Carbimazole plus Thyroxin treated] the number of cells were decreased i.e 117.6 +/- 3.83 than group B but were more than group A. Beta Basophil cell size [diameter] was also increased significantly [P <0.001] in group B i.e 17.64 +/- 1.06 than group A 14.45 +/- 3.28. In group C Beta Basophil cell size was 16.16 +/- 2.02, which was more than group A but less than group C. The number and size of Beta Basophils in group C was significant [P<0.05], when compared with corresponding controls. In conclusion these results strongly suggest that Carbimazole-induced hyperplasia and hypertrophy of Anterior pituitary gland may be prevented by simultaneous treatment with Thyroxin. Long standing treatment with Carbimazole in hyperthyroid patients as in Graves disease should accompany, small doses of Thyroxin as well, to avoid the enlargement of Anterior Pituitary gland during their treatment

Remission of Grave's disease after oral anti-thyroid drug treatment

To evaluate remission rate of anti-thyroid drug treatment in patients with Grave's disease, and to study the factors associated with remission. A cross sectional study. The Endocrine Department of the Aga Khan University Hospital, Karachi from 1999 to 2000. Seventy four patients of Grave's disease were recruited who were prescribed medical treatment. Grave's disease was diagnosed in the presence of clinical and biochemical hyperthyroidism along with anti-microsomal [AMA] and anti-thyroglobulin antibodies [ATA] and thyroid scan. These patients were prescribed oral anti-thyroid drugs using titration regime and followed at 3, 6, 12 and 18 months. Patients were categorized into two groups: "remission group" and "treatment failure group" and results were compared using a chi-square test, t-test and logistic regression model with significance at p < 0.05. A majority of the patients were females [62.6%, n=46]. During the follow-up period of 18 months, 41.9% patients went into remission. Univariate analysis showed that the initial free T4 level was significantly different [p < 0.05] in patients in remission and treatment failure groups. Multivariate analysis showed only initial free T4 level was a significant predictor of outcome. Positive AMA patients [n=27] had higher treatment failure [odds ratio: 2.55: 95%, CI 0.69 - 9:31], although the difference was not statistically significant [p = 0.13]. Remission rates with oral anti-thyroid agents is markedly high. Patients should be offered alternate treatment options to those who do not enter remission during a period of 12-18 months of treatment, those who develop relapse, and those who have aggressive disease on initial presentation

Carbimazole induced ANCA positive vasculitis.

Anti-thyroid drugs, like carbimazole and propylthiouracil (PTU) are commonly prescribed for the treatment of hyperthyroidism. One should be aware of the side effects of antithyroid medications. Antineutrophil cytoplasmic antibody (ANCA)--associated vasculitis is a potentially life-threatening adverse effect of antithyroidmedications. We report a patient with Graves' disease who developed ANCA positive carbimazole induced vasculitis. The episode was characterized by a vasculitic skin rash associated with large joint arthritis, pyrexia and parotiditis but no renal or pulmonary involvement. He was referred to us for neurological evaluation because he had difficulty in getting up from squatting position and was suspected to have myositis. Carbimazole and methimazole have a lower incidence of reported ANCA positive side effects than PUT. To the best of our knowledge this is the first ANCA positive carbimazole induced vasculitis case reported from India.

Early treatment with low fixed dose (5 mCi) radioiodine therapy is effective in Indian subjects with Graves' disease.

There is little consensus regarding the most appropriate dosage regimen for radioiodine treatment in Graves' disease. The authors evaluated the efficacy of low fixed dose (5mCi) of radioiodine therapy, in terms of its cure rate and promptness of control, as well possible factors influencing the outcome. One hundred and twenty five consecutive patients with Graves' disease with persistent disease activity despite receiving carbimazole were treated with 5 mCi fixed dose of I131. Patients, who remained hyperthyroid at 1 year, received a second dose of 7.5 mCi of I113. After first dose 73.6% were cured (36.8% hypothyroid and 36.8% euthyroid), while 26.4% patients did not respond. Those who achieved cure had significantly lesser goiter size (84.6% with grade I goiter and 70.7% with grade II) and had received significantly shorter duration of prior carbimazole therapy (22 +/- 10 months versus 63 +/- 27 months) (p < 0.01). Age, sex, baseline T3, T4, 24 hour I131 uptake did not affect the cure rate. Mean time to response was 7 +/- 4 months. One hundred and three (82.4%) patients were cured after 2 doses while only 22 (17.6%) were nonresponsive. Hence, low fixed dose (5mCi) radio active iodine (RAI) therapy seems to be effective in Graves' disease particularly in patients with small sized goiter and short duration of pretherapy with thionamides.

Apathetic hyperthyroidism presenting as shock and complete heart block

Apathetic thyrotoxicosis is an exceedingly rare presentation of thyroid storm. The clinical picture is one of apathy rather than hyperactivity, and cardiovascular manifestations predominate though abnormal atrioventricular [AV] conduction specially complete heart block are very rare. We report a case of a 28 year-old Indian staff nurse presenting with loss of consciousness, shock and complete heart block which promptly resolved after the thyrotoxicosis was treated by oral carbimazole and few doses of hydrocortisone

Myelodysplastic syndrome and pancytopenia responding to treatment of hyperthyroidism: peripheral blood and bone marrow analysis before and after antihormonal treatment.

Hematological disorders, especially single lineage abnormalities, have been described in hyperthyroidism. Pancytopenia has been reported, without myelodysplastic syndrome or megaloblastic anemia. We studied the peripheral blood smear and the bone marrow aspiration and biopsy of a 65-year-old lady, who presented with pancytopenia and thyrotoxicosis due to multinodular goiter. She denied ingesting any toxic medication. At diagnosis: WBC: 2500/ul, platelets count: 58,000/ul, hemoglobin level: 6.5 g/dl. The bone marrow was moderately hyper cellular with moderate myelofibrosis and arrested hematopoiesis. The TSH level was: 0.02 mIU/l (N: 0.25-4), the fT3: 18 pmol/l (N: 4-10), the routine serum immunologic tests were negative. After treatment with single agent neomercazole (carbimazole), complete recovery of the blood cell counts was obtained within one month. The bone marrow aspiration, performed three months after starting therapy, showed normal hematopoiesis. The thyroid function tests returned to normal and no autoimmune reaction was detected on routine serum testing. Persistent response was observed six months later under medical treatment. The patient has refused surgical treatment. Reversible myelodysplastic syndrome may also be part of the changes in blood picture of patients with hyperthyroidism, probably due to direct toxic mechanism.

Surgical treatment of hyperthyroidism in the north of Iraq: reduction in mortality and morbidity with a planned approach. Results of 544 operations with special reference to pre-operative treatment with carbimazole and thyroid hormones

To reduce mortality and morbidity to the lowest levels by a planned preparation of the patient for operation; treatment must be individualized and depends on the patient's age and general state of health, the size of the goitre, the underlying pathological process, and the patient's ability to obtain follow-up. A prospective study. Erbil Teaching Hospital [University Hospital] during the period from January 1994 to September 2004, Erbil-Iraq [population 2 million]. 632 patients with hyperthyroidism. All patients with hyperthyroidism [632] presenting to the department of surgery at Erbil teaching hospital during the period from January 1994 to September 2004; 544 were treated surgically and 88 were treated medically and with radio-iodine. Side effects of the anti-thyroid treatment [Thiocarbamide] were observed in 42 cases [7.7%]. Most patients were treated for an average of between 1 to 6 months. Thus it was possible to operate on the patient at a time suitable for the patient, surgeon and hospital. Carbimazole was the most frequently used anti-thyroid drug in Erbil Teaching Hospital. Surgery resulted in rapid cure of hyperthyroidism in 90% of patients and allowed for rapid relief of compressive symptoms. Frequency of hypothyroidism was similar to that of those treated with radioiodine [15.5%]; 10% developed recurrent thyrotoxicosis [p > 0.054]. Complications included permanent vocal cord paralysis [2.3%], permanent hypoparathyroidism [0.5%], temporary hypoparathyroidism [2.5%], and significant postoperative bleeding [1.4%]. The mortality rate was almost zero. Surgical therapy, in this study, was reserved for young individuals, patients with a large nodule [or nodules] or obstructive symptoms, patients with dominant non-functioning or suspicious nodules, patients who were pregnant, patients in whom radioiodine therapy had failed, or patients who required a rapid resolution of the thyrotoxic state. Sub-total thyroidectomy resulted in rapid cure of hyperthyroidism in 90% of our patients and allowed for rapid relief of compressive symptoms. This planned approach showed that the mortality rate between the years 1985 to 1993 was 7%, while the mortality rate reduced almost to zero between 1994 to 2004; the morbidity was reduced from 17% to about 4% during the same period

Reversible cardiomyopathy.

We report a case of reversible dilated cardiomyopathy, in a middle-aged male. The patient presented with severe left ventricular dysfunction and atrial fibrillation. Inspite of vigorous medical therapy there was only mild clinical improvement. Subsequently laboratory test results diagnosed it as hyperthyroidism and then specific thyrostatic treatment was added. There was a prompt clinical and hemodynamic improvement in the form of reversal of left ventricular dysfunction and achievement of sinus rhythm at the end of two weeks.

Juvenile hyperthyroidism: an experience.

OBJECTIVE: To analyze the clinical profile of juvenile hyperthyroidism at presentation, their treatment outcome; predictors of remission and relapse. METHODS: Retrospective analysis of medical records of 56 patients with juvenile hyperthyroidism seen over a period of 16 years. A cohort of 38 females and 18 males with mean (+/-SD) age of 14.9 +/- 3.4 years (range 3 to 18 years) was analyzed. RESULTS: Majority of patients was in the age group of 12-16 years. Common symptoms observed at presentation were weight loss (82.1%), excessive sweating (78.6%), heat intolerance (76.8%), increased appetite (73.2%) and diarrhea in 48.2%. In addition, accelerated linear growth was observed in 7.1% of patients. Goiter was present in 98.2% of children; 94.5% of which was diffuse and 4.8% was multinodular. The mean ((+/-SD) T3 was 4.8 +/- 3.4 ng/mL (N, 0.6-1.6), T4 was 218 +/- 98 ng/mL (N, 60-155) and TSH was 0.44 +/- 0.36 (N, 0.5-5.5 microIU/mL). TMA positivity seen in 36.9% of patients. All patients were treated with carbimazole; subsequently 4 patients required thyroidectomy and one required radioactive iodine ablation. Mean (+/-SD) duration of follow-up in our patients was 4.9 +/- 3 years, ranging between 1.6 to 16 years and mean (+/-SD) duration of treatment was 34.4 +/- 22.6 months (range 12 to 120 months). Mean (+/-SD) duration to achieve euthyroidism was 5.2 +/- 4.7 months, ranging between 1-33 months. On intention to treat analysis, remission with carbimazole was achieved in 47.6%, remaining patients failed to achieve remission with drug treatment. CONCLUSION: Graves disease is the commonest cause of juvenile hyperthyroidism. Carbimazole is safe, effective, cheap, and easily available form of therapy. It is occasionally associated with serious side effects but requires prolonged follow up.

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

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. A comparative study. Department of Anatomy, Basic Medical Sciences Institute [BMSI], Jinnah Postgraduate Medical Centre [JPMC], Karachi, from 15th July 2001 to 31st August 2001. 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 and E. The adrenal histology with relation to its width of cortex, zones and number of cells in different zones of cortex were studied. 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. Carbimazole-induced hypothyroidism by carbimazole causes the shrinkage of adrenal cortex in 10 days prenatally treated albino rats

Paroxysmal kinesigenic dyskinesia manifestation of hyperthyroidism.

Sporadic paroxysmal kinesigenic dyskinesia (PKD) secondary to thyrotoxicosis is an extremely rare entity. A 36-year-old female presented with the features of PKD. Her investigations revealed thyrotoxicosis. Her dyskinesia did not respond to carbamazepine but remitted with the anti-thyroid drug, neomercazole. Perhaps hyperthyroidism-related PKD is a result of a metabolic disturbance of the basal ganglia circuits rather than a permanent and irreversible change.

Thyrotoxic hypokalaemic paralysis in a pregnant Afro-Caribbean woman. A case report and review of the literature

This paper reports the case of a 21-year-old Afro-Caribbean pregnant woman with hyperthyroidism and hypokalaemic quadriparesis and reviews the literature on the topic. Thyrotoxic periodic paralysis is a very rare condition in the Caribbean. This case reminds West Indian physicians to consider this rare condition in any patient that presents with paralysis