Thursday, August 18, 2011

Hepatitis C- Thyroid dysfunction

Prior to starting HCV antiviral therapy people with hepatitis C may be predisposed to developing thyroid abnormalities because of an increased rate of thyroid autoantibodies found in individuals infected with the virus.

Side effect; Thyroid dysfunction

Because interferon "peginterferon" can sometimes result in thyroid dysfunction during therapy; Thyroid function tests should be obtained at baseline and every 12 weeks during antiviral treatment, and after treatment completion.

The side effect of interferon may directly affect the thyroid gland and cause the gland to become overactive or underactive. The symptoms of thyroid dysfunction are loss of appetite, weight gain or loss, fatigue, digestion problems, and concentration, among other important functions.

Update-Nov 2011

Hepatitis C- Rare case of pegylated IFN-α induced destructive thyroiditis followed by Graves' disease
IFN-α can induce both autoimmune and non-autoimmune thyroiditis. However, we observed a rare side effect of IFN-α therapy as IFN-α-induced destructive thyroiditis followed by transient Graves' disease in a patient with HCV infection...view full text here


In a study published May 24, 2011 in BMC Endocrine Disorders researchers wanted to determine if autoimmune thyroid disease (TD) during treatment improved the chance of achieving sustained virologic response.

The aim of the study was to assess the chance of achieving sustained virologic response (SVR) in patients who developed autoimmune thyroid disease TD during treatment when compared with those who did not. You can view the full data here.

The below July 2011 abstract found that in patients who develop hypothyroidism "underactive, low thyroid" because of HCV infection or during treatment had a 3.83 more chance of not reaching SVR.

Source: Endocr Regul
Central hypothyroidism in patients with chronic hepatitis C and relation with interferon-alpha treatment

Zantut-Wittmann DE, Pavan MH, Pavin EJ, Goncales FL; Endocrine Regulations 45 (3), 157-61 (Jul 2011)

Since some authors referred to panhypopituitarism or central hypothyroidism during the treatment of chronic hepatitis C virus (HCV) infection using interferon-α, it is intended to evaluate the prevalence of central hypothyroidism (CH) in HCV patients before and during interferon-α therapy.

Patients and Methods.
We evaluated 308 HCV patients treated with standard interferon-α (IFN) and/or pegylated-interferon-α (PEG-IFN) associated with ribavirin. Free thyroxine (FT4) and thyrotropin (TSH) levels were measured before, during and after treatment. Central hypothyroidism was diagnosed when the level of FT4 was lower than normal values with concomitant normal or lower TSH as verified at least in two consecutive measures

Before treatment, 18 (5.8 %) patients presented central hypothyroidism. Twelve patients maintained laboratory changes during the treatment and 17 new patients developed central hypothyroidism. Among the 29 patients (9.4 %) with central hypothyroidism , 11 used IFN, six used PEG-IFN and 12 patients used two or more therapeutic schedules. The differences in gender, age, cirrhosis, viral genotype, duration of treatment and the type of interferon used were not statistically significant. The absence of sustained virologic response was associated with central hypothyroidism (OR=3.83).

HCV patients may develop central hypothyroidism due to viral infection or during the interferon treatment. These patients presented 3.83 times more chance of not obtaining sustained virologic response.

Discontinuation of HCV therapy

In the next abstract is was determined that thyroid dysfunction associated with interferon can be managed without stopping HCV therapy.

Endocrine Abstracts (2011) 25 P323
Spectrum of thyroid dysfunction in interferon-α treated hepatitis C-positive patients
Carla Moran1, Maggie Nicholls1 & Paddy Mallon1,21Mater Misericordiae Hospital, Dublin, Ireland; 2University College Dublin, Dublin, Ireland.

The reported incidence of thyroid dysfunction associated with interferon-α (IFNα) treatment for hepatitis C infection varies widely between countries.1 To our knowledge the spectrum of thyroid dysfunction in IFNα-treated Irish patients has not been described outside of an anti-D-related, hepatitis C-infected cohort.

We reviewed thyroid function tests (TFTs) from all Hepatitis C positive patients undergoing IFNα treatment over a 2 year period.
64 patients were included (41 males, 23 females).
The majority of patients were Irish (48), the remainder were Eastern European (12), Italian (2), Mongolian (2).

Of 11 patients (17.2%) developed abnormal TFTs (9 female, 6 Irish). The mean age was 35 years (range 20–60). The incidence of thyroid dysfunction was 12.5% for Irish patients, 33% for Eastern Europeans. Mean treatment duration at time of diagnosis of thyroid dysfunction was 18 weeks.

Transient subclinical hypothyroidism occurred in 3 patients; TSH levels ranged from 4.3 to 7.1 mIU/l (RR 0.3–4.0 mIU/l) and none required treatment. Two patients developed hypothyroidism requiring eltroxin, one of whom was profoundly hypothyroid (TSH 83.6 mIU/l, FT4 7.9 pmol/l, TPO Ab positive). Two developed transient hypo- and hyperthyroidism respectively, which spontaneously resolved. Two patients developed thyrotoxicosis due to destructive thyroiditis (TSH <0.1 mIU/l, FT4 18–26 pmol/l, TPO Ab positive) with subsequent transient hypothyroidism, requiring temporary eltroxin treatment. The remaining two patients developed transient hyperthyroidism, later reverting to permanent hypothyroidism requiring eltroxin.

We detected clinically relevant thyroid dysfunction at a frequency similar to previous studies. Thyroid dysfunction was more common in female patients and those of Eastern European origin. All patients continued IFNα treatment and euthyroid status was achieved with medical intervention. These data suggest that frequency of TFT testing could possibly be reduced in male patients and may need to be increased in Eastern European patients. Those who develop thyroid dysfunction can be managed without discontinuation of IFNα therapy.Endocrine Abstracts (2011) 25 P323

Thyroid function tests, a little help from Dr. Pullen
Visit his informative blog here

TSH – Understanding Thyroid Function Tests

TSH is the abbreviation for Thyroid Stimulating Hormone. Measurement of TSH level is the standard test used by physicians to both screen for and monitor treatment of hypothyroidism. Understanding the TSH test results is quite simple once you know how the body regulates your thyroid function. The process begins in the hypothalamus, the portion of the brain just above the pituitary gland. The hypothalamus senses the level of thyroid hormone, and drives the process. If you need more thyroid hormone, the hypothalamus secretes a hormone called Thyroid Releasing Hormone (TRH) into the microcirculation from the hypothalamus, down the stalk of the pituitary and to the pituitary gland. The TRH signals the pituitary to secrete TSH into the bloodstream. The TSH goes through the bloodstream and stimulates the thyroid gland to put out thyroid hormone. So if your body needs more thyroid hormone as determined by the hypothalamus, the amount of TSH released by the pituitary increases dramatically. In most symptomatic hypothyroid patients the TSH level is markedly elevated. A normal TSH level is approximately 0.4 – 4.5. In hypothyroidism typically the TSH level will be much higher, with levels of 15-300 quite common. We have more trouble deciding the significance of minor elevations of TSH, in the <10 range. In patients on thyroid replacement therapy for hypothyroidism most physicians aim for a TSH level in the low normal range, from 0.4-2.0. If patients feel well with upper normal TSH levels these are fine too. (range varies from lab to lab, by gender, in pregnancy, etc.) Most experts recommend monitoring a TSH level about annually in patients on thyroid replacement therapy as the dose required can vary from time to time in any individual.

So it’s really simple: An elevated TSH indicates an underactive thyroid or under-treated hypothyroid condition. A low, or suppressed, TSH indicates an overactive thyroid, or an over-treated hypothyroid state. Sometimes, especially with a slightly suppressed TSH it is helpful to measure the levels of thyroid hormone in the bloodstream. In past years this was difficult, due to the large range of normal for total T4 and total T3 in different individuals. This huge range is in part because most of the circulating thyroid hormone is protein bound, and not available at any given moment to bind to the thyroid hormone receptors. Prior to the development and refinement of the TSH assay for routine use this was a big problem.

Fortunately in addition to the development of the highly sensitive TSH assays, we now have affordable measures of Free T4 and Free T3 levels. T4, or levothyroxine, is the thyroid hormone stored and released by the thyroid gland in largest quantities. T3, or triiodothyronine, is the more physiologically active thyroid hormone, and is a metabolite of T4. Both T3 and T4 circulate in the bloodstream both as protein bound and free or non-protein bound hormones. The free, or unbound form is the form that functions to control metabolic rate. In years past, before we had lab measurements of Free T4 and Free T3 we estimate the free amount by what was called the Free Thyroxine Index, a number calculated by multiplying the total T4 by the thyroid binding capacity. This was notoriously inaccurate and really plays no role in modern thyroid management. I still see non-endocrinologist, non-primary care physicians order a FTI (also called T7) level at times. Now in the circumstance when we need to know the level of circulating thyroid hormone levels we order a Free T4, and sometimes a Free T3 level and avoid the confusion of protein bound thyroid.

So now you know:
High TSH à Low thyroid hormone status.
Low TSH à High thyroid hormone status.

More Information; How Your Thyroid Works

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