Huy A Tran

Pegylated interferon-α2β in combination with ribavirin does not aggravate thyroid dysfunction in comparison to regular interferon-α2β in a hepatitis C population: Meta-analysis

Background:  Interferon (IFN) has been well documented to cause thyroid dysfunction, especially in high risk patients and when combined with ribavirin (RBV). There is very sparse data to assess if pegylated IFN will further aggravate the thyroid disease risk in comparison to regular IFN. The purpose of this study was to assess the risk of developing thyroid disease with pegylated IFN (pIFN) versus regular IFN (rIFN) therapy (in combination with RBV). We also pooled our results with previous studies in a meta‐analysis.

The natural history of interferon-α2b-induced thyroiditis and its exclusivity in a cohort of patients with chronic hepatitis C infection

BACKGROUND Interferon-alpha2b (IFN-alpha2b) is well known to cause both hyper- and hypo-thyroidism. In the former, the commonest aetiology is thyroiditis. As there is no previous data to fully characterize the entity of IFN-related thyroiditis, the aim of this study is to document in detail its evolution in a cohort of hepatitis C patients treated with pegylated IFN-alpha2b and Ribavirin (RBV). METHODS A prospective observational study was conducted in patients who developed thyroid diseases whilst receiving combination of pegylated IFN-alpha2b and RBV for hepatitis C. The patients were followed with monthly thyrotropin (TSH). Where TSH was undetectable, free tetra- (fT4) and tri-iodothyronine (fT3) were added. Anti-thyroperoxidase (TPO), anti-thyroglobulin (Tg) and thyroid stimulating immunoglobulin (TSI) levels were also performed at diagnosis, during and at the end of IFN therapy. All patients were assessed and followed up closely with monthly TSH, fT4 and fT3 levels until the completion, after 6 and 12 months of treatment. RESULTS There were seven females and four males over a 30-month period. All patients were found to have thyroiditis. On average, the time to the development of thyroid disease was 10 weeks and duration of disease 9 weeks. All patients eventually recovered normal biochemical thyroid function although two required short-term supplementation. CONCLUSION Thyroiditis was found exclusively in our patients. Both the hyper- and hypo-thyroid phase can be short lived, extreme and transient in nature which warrants strict monthly TSH monitoring. Careful follow-up of all patients is mandatory as complete recovery is expected.

Development of thyroid diseases in the treatment of chronic hepatitis C with α-interferon may be a good prognosticator in achieving a sustained virological response: A meta-analysis

Background and Aim:  Thyroid dysfunction is the most common endocrinopathy associated with hepatitis C and its interferon‐based treatment. When undergoing treatment, interferon and ribavirin synergize to potently stimulate the immune system in order to eradicate the virus. One of the innocent bystanders in this accentuated response is the thyroid. The present study investigated whether thyroid dysfunction while undergoing combination treatment for hepatitis C is a favorable prognostic maker for a sustained virological response.

A novel missense LIPA gene mutation, N98S in a patient with cholesteryl ester storage disease

Lysosomal acid lipase plays an important role in maintaining cellular cholesterol homeostasis. Complete absence of lysosomal acid lipase activity results in Wolman disease and usually death in infancy, whereas partial deficiency of lysosomal acid lipase results in cholesteryl ester storage disease (CESD). We describe a 26 year-old female with CESD who presented with recurrent right upper quadrant abdominal pain. Abnormal liver function tests and a subsequent liver biopsy revealed features consistent with CESD. Sequencing of the LIPA gene revealed that she was a compound heterozygote for the previously reported exon 8 splice junction mutation and a novel missense mutation (N98S) in exon 4. The splice junction mutation allows some (approximately 3%) normal splicing to occur, and therefore gives rise to residual lysosomal acid lipase activity. Asn98 in lysosomal acid lipase is highly conserved among species and mutation of this residue could influence catalytic activity or accessibility to the active site. In summary, we describe a CESD patient compound heterozygous for the LIPA exon 8 splice junction mutation and a novel missense mutation, N98S.

The Spectrum of Autoimmune Thyroid Disease in the Short to Medium Term Following Interferon-alpha Therapy for Chronic Hepatitis C.

Autoimmune thyroid diseases are common manifestations of hepatitis C infection, exacerbated by interferon-based treatment. However, the occurrence and pattern of thyroid disease in the short/medium term following the completion of IFN-based therapy is relatively unknown and there are very few previous reports regarding the specific spectrum of autoimmune thyroid disease that may follow such therapy. We hereby report 3 cases which demonstrate the range of thyroid diseases that may occur following interferon therapy. The hypothesis advanced is that in the pathogenesis of these conditions there must be both triggering and sustaining mechanisms as thyroid diseases occur well outside the immediate effect window of pegylated interferon. This paper suggests the need to continue thyroid surveillance in IFN-treated HCV patients following the completion of therapy, perhaps for the first 6 months.

Vitamin D Levels Are Associated with Expression of SLE, but Not Flare Frequency

This study explores links between vitamin D deficiency (25(OH)D = 50 nmol/L) and serological autoimmunity (ANA > 1 : 80) and frequency of self-reported flares (SRF) in participants with clinical autoimmunity (SLE). 25(OH)D levels of 121 females were quantified and compared. The cohort consisted of 80 ACR defined SLE patients and 41 age and sex matched controls. Association analysis of log2 (25(OH)D) levels and ANA 80 positivity was undertaken via two-sample t-tests and regression models. Significant differences were found for 25(OH)D levels (mean: control 74 nmol/L (29.5 ng/ml); SLE 58 nmol/L (23.1 ng/ml), P = 0.04), 25(OH)D deficiency (P = 0.02). Regression models indicate that, for a twofold rise in 25(OH)D level, the odds ratio (OR) for ANA-positivity drops to 36% of the baseline OR. No link was found between SRF-days and 25(OH)D levels. Our results support links between vitamin D deficiency and expression of serological autoimmunity and clinical autoimmunity (SLE). However, no demonstrable association between 25(OH)D and SRF was confirmed, suggesting independent influences of other flare-inducing factors. Results indicate that SLE patients have high risk of 25(OH)D deficiency and therefore supplementation with regular monitoring should be considered as part of patient management.

Exacerbation of hepatitis C induced subclinical hypoadrenalism by Interferon-alpha2beta: A case report

Adrenal disease is an uncommon manifestation of hepatitis C infection and its related treatment regimen. This is a case of subclinical hypoadrenalism, probably induced by hepatitis C infection and further exacerbated by interferon-α2β and Ribavirin therapy. The adrenal deterioration during the treatment course was observed closely with 24-hour salivary profiles and 250 μg adrenocorticotropin stimulation tests using parallel serum and salivary cortisol concentrations. A number of possible pathogenic mechanisms are discussed, and the controversy over its management is emphasized.

The natural history of interferon-α induced thyroiditis in chronic hepatitis c patients: a long term study

BackgroundAutoimmune thyroid disease is a common complication of patients with chronic hepatitis C undergoing combination pegylated interferon-α and ribavirin treatment. A small proportion develops interferon-induced thyroiditis of which the long term natural history is unknown and how it compares with de novo thyroiditis. The aim of the study is to determine the natural history of thyroid disease including antibody profile in this particular setting 36 months from the completion of therapy.MethodsA cohort of 18 hepatitis C patients (mean age 45 ± 8 years (standard deviation)) who developed exclusively thyroiditis in this setting was followed every 12 months after the completion of therapy for 36 months. Investigations included thyrotropin, free tetra-iodothyronine, free tri-iodothyronine levels and thyroid autoantibodies.ResultsNone of the patients developed any long term thyroid disease. Two patients had a prolonged hypothyroid phase of the thyroiditis early after the completion of treatment but recovered fully. The remaining 16 patients remained euthyroid. Similarly, thyroid autoantibodies all declined and returned to reference range.ConclusionsThe long term natural history in this small series of interferon induced thyroiditis was benign. If a larger series confirms a similar outcome then there is no long term residual effect on thyroid function and follow-up testing would not be warranted.

Reversible hypothyroidism and Whipple's disease

BackgroundThe major cause of primary hypothyroidism is autoimmune mediated with progressive and permanent destruction of the thyroid gland resulting in life-long replacement therapy. Treatable and reversible hypothyroidism is unusual and here forth is such a case due to infection of the thyroid gland with Tropheryma whippleii, Whipple disease.Case presentationA 45 year-old female presented with symptoms and signs consistent with primary hypothyroidism, which was also confirmed biochemically. Her response to thyroxine replacement therapy was poor however, requiring a significantly elevated amount. Further investigation revealed the presence of Whipples disease involving the gastrointestinal trace and possibly the thyroid gland. Her thyroxine requirement decreased drastically following appropriate antimicrobial therapy for Whipples disease to the extent that it was ceased. Thyrotropin releasing hormone testing in the steady state suggested there was diminished thyroid reserve due to Whipples disease.ConclusionThis is the first ante-mortem case report studying the possible involvement of the thyroid gland by Whipples disease. Despite the normalization of her thyroid function test biochemically after antibiotic therapy, there is diminished thyroid reserve thus requiring close and regular monitoring.

Fulminant Clostridium Septicum myonecrosis in well controlled diabetes: a case report

Diabetic myonecrosis with Clostridium Septicum is uncommon but carries a high mortality rate. This commensal organism is part of the gastrointestinal tract flora and can become extremely virulent, often in the setting of immuno-suppression such as neutropenia, occult malignancy (commonly caecal) and poorly controlled diabetes. The case report is unusual in that there are few risk factors other than very mild neutropenia. This highlights the opportunistic character of the organism and recommends that a high index of suspicion and vigilance be carried out in the presence of fevers and sepsis, even in the well-controlled diabetic population.