choice of Replacement therapy

The synthetic version of endogenous human thyroid hormone, levothyroxine is the routine replacement used for treatment of thyroid- stimulating hormone (TSH) deficiency. Its long plasma half- life (6– 10 days) ensures stable levels of thyroid hormones on once daily administration, and conversion to T3 in vivo results in appropriate blood levels of both T4 and T3. Liothyronine (T3; triiodothyronine) can be used, but has no advantage in most circumstances, and may raise safety concerns due to elevated free T3 levels indicating supraphysiological T3 exposure. Combined T4 and T3 replacement and the use of ‘natural’ thyroid extracts has been advocated in print and on the internet by a variety groups, but clinical trial evidence is limited and where available suggests no benefit.

commencing Levothyroxine Replacement

The starting dose and regime of levothyroxine replacement de pends on the clinical circumstances. Prior to commencing levothyroxine, it is essential to know the status of the ACTH- adrenal axis since starting levothyroxine without glucocorticoid replacement in a patient with severe ACTH deficiency may precipitate a hypoadrenal crisis. If ACTH deficiency is present, hydrocortisone must be started before levothyroxine. Thereafter, many patients with TSH deficiency have serum free T4 levels only slightly below the reference range, and in patients with such mild deficiency and no evidence of cardiovascular disease replacement can be simply commenced with a near- full replacement dose of levothyroxine 100 µg once daily. This dosage is comparable to the study that increased the dose from 1 mcg/ kg/ day to 1.6 mcg/ kg/ day, which led to weight loss, alleviation of hypothyroid symptoms, reduced body mass index (BMI), low density lipoprotein (LDL) cholesterol and serum creatine kinase levels. In patients with more profound reductions of serum free T4, a lower starting dose of 50 µg daily, increased after a few weeks to 100 µg may be better tolerated. In elderly patients, or any patient with known cardiovascular disease— particularly ischaemic heart disease, more caution is required: in most cases a starting dose of 25 mcg will be well tolerated, increased slowly in 25 mcg increments over several weeks until the target dose is achieved.

Monitoring Levothyroxine Replacement

Defining the optimal replacement dose of levothyroxine in TSH deficiency is problematic, and little scientific evidence is available to guide the clinician. Unlike primary hypothyroidism, where serum TSH is a sensitive marker of under- or over- replacement, there is no biochemical marker to indicate precise physiological levels of replacement for an individual patient— indeed serum TSH may be low, normal, or even slightly elevated in untreated TSH deficiency. Therefore, instead of relying on ‘reflex TSH strategy’, adjustment is based on the clinical response and on measurement of circulating thyroid hormone levels, which are limited by the very wide reference ranges in the normal population. Serum free T4 appears the most appropriate marker with which to adjust the levothyroxine dose and the conventional recommendation is to maintain free T4 in the middle or upper part of the reference range for normal individuals, although this is certainly not ‘evidence- based’ and begs the question of the criteria used to define TSH deficiency since it implies that patients with pituitary disease (and indeed 50% of the normal population!) with a free T4 in the lower half of the normal range might benefit from levothyroxine replacement therapy. Some workers have advocated using a levothyroxine dose based on body weight (1.6 µg/ kg) but in doing so increased free T4 levels close to the upper limit of the reference range.

On comparison of free T4 levels of secondary hypothyroid patients to that of patients with primary thyroid disease in our centre, it was found that TSH deficiency was substantially underdiagnosed and under- treated [17]. The twentieth to eightieth centile range for controls on levothyroxine was a free T4 level of 14– 19 pmol/ L (normal range 9– 26 pmol/ L) in our laboratory (in general, middle third of the range) and we propose to use this as target range for re placement levels in TSH deficiency in future.

Ultimately, such controversies regarding appropriate levothyroxine replacement dosage and monitoring can only be an swered by a controlled trial. In the meantime, a serum free T4 anywhere in the middle centiles of the normal range when the patient is asymptomatic is accepted, with an option to move the free T4 into the upper part of the reference range if the patient experiences symptoms suggestive of hypothyroidism.

Adverse effects of Levothyroxine Replacement

Although thyrotoxicosis of the primary gland is a well- documented risk factor for osteoporosis, bone density remains normal even in patients on deliberate supraphysiological replacement with levothyroxine. However, thyrotoxicosis is also a risk factor for cardiovascular disease and, although there is no direct evidence of such adverse effects of levothyroxine replacement, the association of sup pressed TSH levels and risk of atrial fibrillation in older patients in population- based studies indicates the need for caution to avoid unnecessary over- replacement.

اخر الاخبار

اخبار العتبة العباسية المقدسة

شركة براق القمّة تعرض نماذج صناعتها من الشاحنات في مهرجان عين الحياة الرابع

المجمع العلمي يطلق برنامج (القرآني الصغير) ضمن فعاليات مهرجان عين الحياة الرابع

مجموعة مشاتل الكفيل تعرض تشكيلة متكاملة من النباتات الظلية والموسمية في مهرجان عين الحياة الرابع

قسم الشؤون الدينية يختتم الدورة 57 لتأهيل منتسبي العتبة العباسية المقدسة الجدد

المزيد

الآخبار الصحية

عوامل تضعف القدرات الإدراكية لدى الإنسان

طريقة جديدة لتجديد خلايا الدماغ

دراسة بريطانية: الأطعمة النباتية عالية الجودة تقلل خطر فشل القلب

7 أطعمة يومية "تسمم" جسمك بالبلاستيك دون أن تشعر

المزيد

الآخبار التكنلوجية

اكتشاف أثري في أوريغون الأمريكية قد يعيد كتابة تاريخ البشرية

اكتشاف كائن بحري مدرع بلسان "حديدي" في بحر اليابان

نظام كوكبي "مقلوب" يحير علماء الفلك

بسبب الذكاء الاصطناعي.. هذه الوظائف "ستختفي" بعد أشهر قليلة ؟!

المزيد

مواضيع ذات صلة

Adult Growth Hormone Deficiency

Hypopituitary crisis

Glucagon’s Structure

Insulin and Its Glucose Transporter

Insulin Receptor

Insulin Structure

Biological Actions of T3

Adrenal Replacement in ACTH Deficiency

Rathke cleft cysts

Biological Actions of Oxytocin

GHD with Accompanying Features

Biological Actions of Arginine Vasopressin (AVP)