Thyroid, parathyroid, gonadal, and pancreatic beta-cell function after bone marrow transplantation with chemotherapy-only conditioning

INTRODUCTION: Radiation and cytotoxic chemotherapy can provoke short- and long-term endocrine dysfunction. We studied the prevalence of thyroid, parathyroid, gonadal, and pancreatic beta-cell function in patients undergoing bone marrow transplantation (BMT). MATERIALS AND METHOD: Forty-six patients (12 women, 34 men), aged 1.5 to 49 years (mean, 15.1 years), were evaluated for thyroid, parathyroid, gonadal, and pancreatic beta-cell function before and 3, 6, and 12 months after BMT with a little busulfan-cyclophosphamide conditioning regimen. RESULTS: Thyroid and parathyroid function was unaltered by BMT. Leydig cell function was normal in 11 adult men (G5P5) before and at 3, 6, and 12 months after BMT, but injury to the germinal epithelium (oligo- or azoospermia) was seen before and 12 months after BMT. There was no relationship between serum FSH and germinal epithelial injury. Maturation was normal in six boys (G2P2 or G3P3 at BMT) 12 months post-BMT. Primary hypogonadism was seen in four adult women (B5P5) after BMT. One 14-year-old girl continued to have regular menstrual periods during the 24 months after BMT. Another girl (P1B1 pre-BMT) developed ovarian failure 12 months post-BMT. Pancreatic beta-cell function was normal pre- and post-BMT in 12 thalassemic patients with serum ferritin > 1000 ng/mL. CONCLUSION: BMT with chemotherapy-only conditioning seems primarily to affect gonadal function, without having any significant effect on thyroid, parathyroid, or pancreatic beta-cell function.     

Thyrotoxicosis and thyroiditis

Thyrotoxicosis is a common presentation of thyroid disease. The commonest cause is Graves’ disease. The clinical features including goitre, eye disease, causes and diagnosis of thyrotoxicosis are discussed. Treatment strategies of Graves’ disease include anti-thyroid drugs, radioiodine and thyroidectomy. It is important to adequately prepare patients prior to surgery to reduce the possibility of thyroid storm. The preferred surgical procedure today is a total thyroidectomy, although historically subtotal thyroidectomy was performed. Less common but relevant surgical causes of thyrotoxicosis are also discussed.Thyroiditis (thyroid inflammation) has a variety of causes. Hashimoto's thyroiditis may present with a transient thyrotoxicosis or long term hypothyroidism. Surgery is rarely required. Subacute thyroiditis thought to be secondary to a viral infection can cause a short-term yet marked thyrotoxicosis due to thyroid damage. Other causes such as amiodarone-induced thyrotoxicosis can be more difficult to manage due to the underlying heart disease and may require thyroidectomy.     

Lung transplantation after allogeneic marrow transplantation in pediatric patients: the Memorial Sloan-Kettering experience.

BACKGROUND: Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) and are associated with severe morbidity and mortality. METHODS: We report on four patients who developed chronic, progressive, and irreversible lung disease 1 to 3 years after allogeneic BMT in childhood. These patients had chronic graft-versus-host disease (n=3) or radiation-related pulmonary fibrosis (n=1). Three patients underwent double lung transplants and one patient underwent a single lung transplant 2 to 14 years after BMT. RESULTS: All four patients tolerated the lung transplantation procedure well and showed significant clinical improvement with normalization of pulmonary function tests by 1 year posttransplant. One patient died from infectious complications 3 years after lung transplantation, and one patient died after chronic rejection of the transplanted lungs 6 years posttransplant. Two patients remain alive without significant respiratory impairment 2 and 7 years after lung transplantation. CONCLUSION: We conclude that lung transplantation offers a viable therapeutic option for patients who develop respiratory failure secondary to BMT.     

Amiodarone therapy before heart transplantation as a predictor of thyroid dysfunction after transplantation.

BACKGROUND: In recent years we have observed new cases of thyroid disease occurring after heart transplantation (HTx). In these patients, the presence of this disease complicates their post-transplant course and occasionally results in life-threatening thyrotoxicosis. The present study examines the incidence and risk factors of thyroid disease in these patients with special emphasis on the use of amiodarone before HTx. Recommendations for follow-up of thyroid disease in HTx patients are discussed. METHODS: A study was performed on a cohort of 380 patients who received HTx in Rotterdam between January 1, 1985 and April 1, 2001. Twenty patients (5%) developed thyroid dysfunction after HTx, 10 of whom had been treated with amiodarone before HTx. RESULTS: Cumulative survival curves showed that most patients (60%) developed thyroid dysfunction within the first year after HTx (median interval between HTx and diagnosis was 9 months). Using univariate Cox regression analysis, amiodarone was a significant predictor for the development of thyroid dysfunction (hazards ratio 5.2, 95% confidence interval 2.5 to 10.8). After adjustment for age, gender, heart disease and Quetelet index, amiodarone remained a significant predictor. CONCLUSIONS: Our study clearly shows that, despite discontinuation of amiodarone treatment at the time of the HTx procedure, patients remain at risk for developing thyroid disease. HTx recipients treated with amiodarone before HTx should therefore be monitored carefully for development of thyroid dysfunction, especially within the first post-transplant year.     

Thyrotoxicosis during pregnancy.

The diagnosis of thyrotoxicosis during pregnancy is difficult on clinical grounds only. The determination of free thyroid hormones or free thyroid hormone indices is important and is possibly supplemented by the TRH stimulation test. Thyrotoxicosis during pregnancy should always be treated actively. The authors recommend subtotal thyroidectomy if there are indications for surgical therapy (nodular goitre or large diffuse goitre). Otherwise treatment with thyrostatic agents is used. After operation during pregnancy, substitution with thyroid hormones should be given throughout the pregnancy in order to avoid deterious effects of possible maternal hypothyroidism. Antithyroid treatment should be continued till after delivery. Beta-receptor blockers are used only as adjuncts but are not recommended as the sole therapy.     

Six weeks of continuous intravenous cyclosporine and short-course methotrexate as prophylaxis for acute graft-versus-host disease after allogeneic bone marrow transplantation

The feasibility and toxicity of six-week continuous intravenous 3 mg/kg/day cyclosporine (CsA) treatment in conjunction with a short course of methotrexate (MTX) was studied in 69 consecutive patients after HLA genotypically identical bone marrow transplantation. In light of the uncertain efficacy of prolonged oral CsA immunoprophylaxis in preventing de novo chronic graft-versus-host disease (GVHD). CsA treatment was terminated three months after BMT. Sixty-one (88%) patients received the full intravenous regimen and no patient exclusions were necessary due to intolerable adverse effects. Weekly median blood CsA concentrations ranged between 820 ng/ml in the first and 648 ng/ml in the sixth week of treatment. No significant correlation existed between blood CsA concentrations and CsA dosages. Major adverse effects of the regimen included hypertension in 36%, acute nephrotoxicity in 36%, acute hepatotoxicity in 41%, and central nervous system toxicity in 4% of the patients. Since hepatotoxicity occurred predominantly in the early posttransplant period (median onset day 9), the relatively high incidence of this untoward effect might have been additionally caused by MTX and/or the preparative regimen. Blood CsA concentrations and CsA dosages did not significantly correlate with serum creatinine or total and conjugated bilirubin levels. In addition, blood CsA and serum creatinine levels did not differ between hypertensive and normotensive patients. Acute GVHD developed in 16% of the patients. Median CsA doses and blood CsA concentrations were identical for each week after BMT for patients contracting acute GVHD as compared with those without acute GVHD. In 55 patients surviving without acute or secondary chronic GVHD, the cumulative probability of de novo chronic GVHD after termination of CsA treatment was 13%. In conclusion, this regimen was tolerable and provided constant blood CsA concentrations for six posttransplant weeks that were not adversely influenced by the development of acute GVHD. Restriction of CsA treatment to the first three months after BMT appeared not to increase the risk of de novo chronic GVHD, which challenges regimens employing oral CsA immunoprophylaxis for 6-12 months after BMT.     

Thyroid disease and surgery

Thyroid disease remains a common disorder worldwide. In the UK thyrotoxicosis has a prevalence of 2% in women and 0.2% in men. Thyroid diseases affect the function of the thyroid gland. It is associated with thyroid hormone dysfunction and/or thyroid gland enlargement, which may be either benign (nodules or a goitre) or malignant. Thyroid function is divided into normal thyroid hormone activity (euthyroid), reduced thyroid activity (hypothyroidism), and increased thyroid activity, over activity (hyperthyroidism, which if uncontrolled can lead to thyrotoxicosis). These patients are frequently encountered in anaesthesia and an understanding of the pathophysiology of thyroid disease and its associated signs, symptoms and associated complications is essential. In the article we will consider thyroid anatomy, pathophysiology and anaesthetic management.     

Laparoscopic fenestration of posttransplant lymphoceles

BACKGROUND: A lymphocele is a common finding after renal transplantation and occurs in up to 20% of patients. The majority of patients are asymptomatic. However, once a lymphocele has become symptomatic (e.g., through transplant dysfunction) this condition has to be treated. We report our 9-year experience with laparoscopic lymphocele fenestration and discuss the current management options for posttransplant lymphoceles. METHODS: Since 1993, 19 patients (11 males and 8 females; median age 56 years, range 22-68 years) of a total of 31 patients with a symptomatic posttransplant lymphocele have undergone laparoscopic fenestration of their lymphocele at a median of 66 days (range, 19-111 days) following successful renal transplantation in our department. As a first-line treatment, a percutaneous pigtail drainage catheter was inserted in all patients. In case of failure in resolving the fluid collection, the next step included sclerotherapy by instillation of tetracycline or ethanol into the lymphocele cavity in some cases. In patients with a persistent lymphocele, a laparoscopic lymphocele fenestration via a transabdominal approach was undertaken to achieve adequate drainage. RESULTS: Primary laparoscopic lymphocele fenestration was successful in all except two patients, who required a conversion. The median operating time was 36 min (range, 20-70 min). Following the procedure, renal transplant function remained stable or returned to individually normal levels in all patients. Median duration of hospital stay was 4 days (range, 1-13 days). At median follow-up of 27 months, all patients were alive with a functioning transplant. CONCLUSIONS: Laparoscopic lymphocele fenestration is reserved for patients in whom temporary drainage with or without sclerotherapy failed to resolve the fluid collection. In these cases the laparoscopic approach offers obvious technical and clinical advantages compared to open operative techniques.     

Thyrotoxicosis and thyroiditis

Thyrotoxicosis is the clinical syndrome of excess circulating thyroid hormones and is most commonly caused by conditions in which excessive thyroid hormone synthesis (hyperthyroidism) occurs such as Graves' disease, toxic multinodular goitre and solitary toxic nodule. Thyrotoxicosis may also be due to release of stored thyroid hormones, without an increase in synthesis, which occurs in thyroiditis. The aetiology, pathogenesis, diagnosis, investigation and management of conditions causing thyrotoxicosis and thyroiditis are reviewed in this chapter. Rare causes of thyrotoxicosis are briefly described.     

Changing of hepatitis B virus markers in patients with bone marrow transplantation

The hepatitis B virus (HBV) infection and its resulting hepatic abnormalities are very high in prevalence among the Taiwan population. They also seem to compose a major problem to patients subjected to bone marrow transplantation (BMT) due to intensive chemoradiotherapy. In this study, the sera of 42 patients were investigated before and after BMT to detect the presence of HBV markers and to test their liver function (LF). Being followed-up for 3-12 months after BMT, 12 out of 27 were found to have altered HBV markers according to the classification of the following: seroconversion of HBsAg, clearance of HBsAb, appearance of HBeAg, clearance of HBeAb, and acute hepatitis. Thirty-seven out of 42 patients (88.1%) were found in routine LF test to develop one or more abnormality; however, 90% of them turned normal within one year after BMT. Only one patient died of complications associated with fulminant hepatitis. In conclusion, the previous hepatic damage from HBV infection appears unlikely to increase the risk of posttransplant morbidity and mortality.     

Bronchiolitis obliterans organizing pneumonia (BOOP) with suspected liver graft-versus-host disease after allogeneic bone marrow transplantation

We report on a patient with chronic myelogenous leukemia who developed bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow transplantation (BMT). A 19-year-old Japanese male complained of dry cough and dyspnea 7 months after BMT. The chest X-ray and computed tomography revealed patchy infiltrates bilaterally. Lung function test, lung biopsy and bronchoalveolar lavage were consistent with the diagnosis of BOOP. The patient also suffered from suspected graft-versus-host disease (GVHD) of the liver, after discontinuation of cyclosporine. Furthermore, prednisolone proved effective against the BOOP and the liver dysfunction. These findings indicate that BOOP is a possible pulmonary manifestation of chronic GVHD, and that immunological mechanisms may have effected the onset of BOOP after BMT in this case. Received: 18 May 2000 Revised: 30 October 2000 Accepted: 23 May 2001     

Cyclosporine in human bone marrow transplantation. Serum concentration, graft-versus-host disease, and nephrotoxicity

Serum concentrations of cyclosporine were studied in 42 patients given cyclosporine for the prevention of graft-versus-host-disease (GVHD) following allogeneic bone marrow transplantation (BMT). Serum trough levels for cyclosporine were determined in each patient at least once weekly during the first 3 months and were compared with the occurrence of GVHD and with nephrotoxicity. Cyclosporine was given as 20 mg/kg i.m. or as a 24-hr infusion for the first 5-7 days. This was followed by a single daily oral dose of 12.5 mg/kg for 6 months. Cyclosporine was then gradually reduced and stopped after one year. After a median observation period of 2 years 25 of the 42 patients (59%) are alive. Twenty six patients (62%) developed GVHD, which was stage II or more in 11 (26%) and fatal in 2 patients (5%). Five patients developed GVHD 6-8 weeks after withdrawal of cyclosporine one year after BMT. All patients improved after restarting cyclosporine. No correlation between cyclosporine serum concentration and GVHD was observed, but patients with GVHD had greater fluctuations of their serum trough levels. Serum creatinine increased in all patients soon after BMT and was correlated with cyclosporine serum concentration during the first month. Serum creatinine, however, rose further despite lower cyclosporine concentrations in the second month. These results show that cyclosporine effectively reduces the severity, but not the incidence, of GVHD suggesting that there is a subset of cells resistant to cyclosporine. The therapeutic range, however, between high doses (which are often associated with nephrotoxicity) and the minimal effective dose of cyclosporine, has yet to be defined.     

Assessment of thyroid function with hormone assays

Measurement of serum thyroid hormone and TSH levels provide diagnostic information in the majority of patients with thyroid dysfunction. The test strategy in hyperthyroidism differs from that in hypothyroidism. Serum T4 is a good test for hyperthyroidism in patients with normal thyroid hormone-binding protein levels. When binding proteins are abnormal serum free T4 is a much more accurate test for hyperthyroidism than serum T4. Serum T3 and the TSH response to TRH are useful tests for the early diagnosis of hyperthyroidism. Serum TSH is a very sensitive indicator of primary hypothyroidism rising already at the subclinical stage of the disease. Serum T4 and free T4, but not serum T3, are useful for the verification of clinical hypothyroidism. Determination of the TRH-stimulated TSH level is important for the differential diagnosis of pituitary and hypothalamic hypothyroidism. It is imperative to recognize that thyroid tests are often abnormal in various non-thyroidal diseases and that administration of drugs can affect these tests. Serum rT3 is of some value for the assessment of thyroid function in patients with non-thyroidal disease.     

The renal-sparing efficacy of basiliximab in adult living donor liver transplantation.

The purpose of this study is to find out whether basiliximab administration will improve postoperative renal function by delaying the start of tacrolimus and decreasing of dosage requirement for tacrolimus in adult living donor liver transplantation (LDLT). Forty-five adult LDLT recipients were enrolled in the study. The induction group (n = 27) was given basiliximab 20 mg on days 0 and 4; tacrolimus administration was delayed until renal function improved. The control group (n = 18) did not receive basiliximab; tacrolimus was given on the first postoperative day. Trough levels of tacrolimus in the induction and control groups were aimed to be maintained at 5-10 ng/ml and 10-15 ng/ml during the first week after transplant, respectively. The median follow-up was 22 months (range 10-34 months). The preoperative conditions were poorer in the induction group (Child C, 56% vs. 33%, P = 0.01; UNOS 2a, 15% vs. 0%, P = 0.02). The intraoperative blood loss was also higher in the induction group than in the control group (median 2,180 ml vs. 495 ml, P < 0.01). The median delay in tacrolimus administration in the induction group was 36 hours (range 24-108 hours). Serum creatinine levels at second and third postoperative months were significantly lower in the induction group. The creatinine clearance rate in the induction group was higher at the third month posttransplant (median 72 vs. 57 ml/minute, P = 0.04). The incidence of renal insufficiency was significantly lower in the induction group at the third month posttransplant (26% vs. 67%, P < 0.01). Blood cholesterol level at the sixth month posttransplant was lower in the induction group (median 152 vs. 196 mg/dl P = 0.03). The incidences of acute cellular rejection, bacteremia, and cytomegalovirus (CMV) infection were similar in both groups. In conclusion, for pretransplant critical patients with more intraoperative blood loss, basiliximab induction could prevent early renal dysfunction by delaying the start of tacrolimus and reducing the dose requirement of tacrolimus without increasing graft rejection and infection. Furthermore, it also improved renal function as well as lowered cholesterol levels within 6 months after transplantation.     

Outcomes of Renal Transplantation Following Bone Marrow Transplantation

This single center retrospective study was undertaken to determine the outcome of kidney transplantation (KT) after bone marrow transplantation (BMT) and also to determine the need for immunosuppressive therapy after KT when the BMT marrow donor is the KT donor. Kidney transplantation was performed in 10 patients with BMT nephropathy (BMTN). In six patients, the KT donor was the BMT donor; these individuals were given no long-term immunosuppression. Four other patients received KT from donors who were not the marrow donor (two living donors, two cadaveric donors). After median follow up of 34 months, no patient had an episode of acute rejection. All graft losses (n = 4) resulted from patient death. Three were because of infectious processes, including two infectious deaths in patients not on immunosuppression. Median estimated actuarial patient and graft survival (Kaplan-Meier) was 105 months. We conclude that patients with BMTN who receive KT from their marrow donor do not require immunosuppression. Whether immunosuppressive therapy is given or not, outcome appears to be determined largely by BMT-related immune dysfunction.     

Allogeneic hematopoietic cell transplantation from alternative donors in children with myelodysplastic syndrome: is that an alternative?

Allogeneic hematopoietic cell transplantation (HCT) in children with myelodysplastic syndrome (MDS) remains a challenge due to the toxic conditioning regimens administered to minimize the risk of relapse in the HLA-matched or of graft rejection in the HLA-mismatched settings. In the absence of matched sibling donors, alternative donors such as unrelated and/or partially matched family sources remain risky, yet the only available, options. Herein we report the results of HCT from alternative donors in 14 children with different subtypes of MDS (juvenile myelomonocytic leukemia [JMML] n = 9; myelodysplastic syndrome [MDS] refractory anemia n = 3; MDS refractory anemia with excess of blasts in transformation n = 2) transplanted at our institution. The median time from diagnosis to HCT was 9 months (range 4 to 90 months). The variety of HCT types included: unrelated peripheral blood progenitor cell transplantation (PBPCT) (n = 2), partially matched family donor T-cell-repleted BMT/PBPCT (n = 6), and haploidentical T-cell-depleted PBPCT (n = 6). Five of 14 patients remain alive at 7 to 37 months posttransplant (including two patients after partially matched family donor BMT, two patients after haploidentical T-cell-depleted-PBPCT, and one after unrelated-PBPCT, respectively). The major complications were: primary graft failure in the haploidentical T-cell-depleted-setting or graft-versus-host disease (GvHD) in T-cell-repleted partially matched family or unrelated settings, respectively. Despite the high transplant-related mortality rate in this series, allogeneic HCT from alternative donors remains an interesting solution for children with MDS who lack matched sibling donors. Due to improved immune reconstitution, despite an increased risk of GvHD, T-cell-repleted transplants from single HLA-mismatched family donors remain a valuable option for children without matched donors. Splenectomy prior to HCT may positively affect the posttransplant course in patients with overt splenomegaly for example those afflicted with JMML.     

Late-onset renal failure after liver transplantation: role of posttransplant alcohol use

BACKGROUND: Late-onset renal failure is being increasingly recognized as a complication in patients undergoing liver transplantation for hepatitis C virus (HCV). However, its precise incidence, predisposing risk factors, and impact on outcome after liver transplantation, have not been defined. METHODS: The development of late-onset renal failure (defined as serum creatinine persistently >2.0 mg/dl, occurring more than 6 months posttransplant) was assessed in 120 consecutive liver transplant recipients who survived at least 6 months after transplantation. Fifty-seven percent (68/120) of the patients had undergone transplantation for liver disease due to HCV. The median follow-up was 5 years. RESULTS: Late-onset renal failure developed in 28% (33/120)of the patients. Posttransplant alcohol use (P=0.0001), posttransplant diabetes (P=0.0042), and recurrent HCV hepatitis (P=0.019) were significantly associated with late onset renal failure. In multivariate analysis, alcohol use (O.R. 10.7, 95%; CI 2.4-35.9, P=0.001) and diabetes (O.R. 2.1, 95%; CI 1.1-9.9, P=.03) were independently significant predictors of late onset renal failure. When only patients transplanted for HCV were analyzed, posttransplant alcohol use (P=0.004) was the only significant independent predictor of late-onset renal failure. HCV genotype 1b, as compared with other HCV genotypes, was associated with a higher rate of late-onset renal failure in patients with HCV; 70% of the patients with genotype 1b versus 32% of those with 1a and 33% of those with 2b, developed late onset renal failure (P=0.03). At a median follow up of 5 years, mortality in patients with HCV with late-onset renal failure was 52% as compared with 2% in those without renal failure (P=.0001). CONCLUSION: Late-onset renal failure in patients with HCV portended a grave outcome. Alcohol use was an independent predictor of late-onset renal failure in patients with HCV and represents a potentially modifiable risk factor for late-onset renal failure in these patients.     

Thyrotoxicosis and thyroiditis

Thyrotoxicosis is a common condition resulting from excess of circulating thyroid hormones in the blood. The most frequent cause of thyrotoxicosis is Graves' disease and the clinical features include goitre and eye disease. The treatment strategies in Graves’ disease involve anti-thyroid drugs, radioiodine and thyroidectomy. Thyroiditis (inflammation of the thyroid) is caused by release of stored thyroid hormones and may also result in thyrotoxicosis. The aetiology, pathogenesis, diagnosis, investigation and management of conditions causing thyrotoxicosis and thyroiditis are reviewed in this chapter. Rare causes of thyrotoxicosis are highlighted.     

Liver transplantation for Budd-Chiari syndrome

BACKGROUND: Budd-Chiari syndrome (BCS) is a clinical condition characterized by hepatic venous outflow obstruction secondary to an underlying systemic predisposition to thrombosis. METHODS: We reviewed our experience of 19 adult patients who underwent orthotopic liver transplantation for BCS from April 1988 to May 1999 to assess their long-term outcome and specific complications related to this procedure. RESULTS: Of these patients, 13 presented with chronic and 6 with acute liver failure. At presentation predisposing factors included polycythemia rubra vera in five, an undefined myeloproliferative disorder in four, essential thrombocythemia in two, presence of lupus anticoagulant in one, antiphospholipid antibody positivity in one, post-gestational in one, oral contraceptive pill in one, and idiopathic in four. Five patients had undergone previous porto-systemic shunt. Of the 19 patients, 16 are alive at a median follow-up of 89 months (range 1-119) with 2 patients developing disease recurrence at 4 months and 7 years posttransplant, respectively. Four patients have been retransplanted: one for progressive graft dysfunction due to nodular regenerative hyperplasia secondary to azathioprine toxicity, two for hepatic artery thrombosis (one soon after and the other 47 months posttransplant), and one for recurrent BCS. Three patients have died: one from an intra-abdominal bleed secondary to acute hemorrhagic pancreatitis 8 years posttransplant, another from acute myeloid leukemia at 6 years posttransplant, and the third patient from graft failure secondary to severe rejection 1 month posttransplant. CONCLUSION: Liver transplantation for BCS provides good long-term survival with acceptable morbidity. Long-term survival may be prejudiced by progression of the underlying hematological disorders.     

Thyrotoxicosis and thyroiditis

Thyrotoxicosis is a common condition resulting from excess of circulating thyroid hormones in the blood. The most frequent cause of thyrotoxicosis is Graves' disease and the clinical features include goitre and eye disease. The treatment strategies of Graves' disease involve anti-thyroid drugs, radioiodine and thyroidectomy. Thyroiditis (inflammation of the thyroid) is caused by release of stored thyroid hormones and may also result in thyrotoxicosis. The aetiology, pathogenesis, diagnosis, investigation and management of conditions causing thyrotoxicosis and thyroiditis are reviewed in this article. Rare causes of thyrotoxicosis are highlighted.