Hypothyroidism: What every patient needs to know
- Part 2 -

Dr Y Premchandra Singh *

Overview of the thyroid system :: Pix - Wikipedia/Mikael Haggstrom

E. Indications of treatment in subclinical Hypothyroidism

1) Symptomatic Patients Four small, short-term interventional studies that address this issue . The overall one may expect only 25 to 35% of patients with subclinical hypothyroidism to improve significantly while on levothyroxine replacement therapy

2) The American Association of Clinical Endocrinologists (AACE)

Guidelines : The guidelines state that treatment is indicated in patients with TSH levels above 10 mIU/mL or in patients with TSH levels between 5 and 10 mIU/mL in conjunction with goiter and/ or positive antithyroid peroxidase antibodies, as these patients have the highest rates of progression to overt hypothyroidism.

3) Pregnancy : The Endocrine Society recommends thyroxine replacement in pregnant women with subclinical hypothyroidism.

4) Treatment of subclinical hypothyroidism : It has been shown to reduce total cholesterol, non-HDL cholesterol, and apolipo-protein B, and to decrease arterial stiffness and systolic blood pressure.

In patients with concomitant subclinical hypothyroidism and iron deficiency anemia, iron supplementation may be ineffective if LT4 is not given.

5) Assisted Reproduction : Finally, treatment with L-thyroxine before conception has been shown to reduce the miscarriage rate and to increase live birth rate in women with subclinical hypothyroidism undergoing assisted reproduction.

F. TREATMENT

What is Triiodothyronine (T3?)

(T3) is the biologically active thyroid hormone composed of a phenyl ring attached via an ether linkage to a tyrosine molecule. It has two iodine atoms on tyrosine (inner) ring and one iodine atoms on its phenyl (outer) ring (3,3',5-triiodo-Lthyronine).

In normal humans, T3 is also released from the thyroid, but approximately 80% is derived from the peripheral tissues by enzymatic removal of a single 5 iodine atom from T4 (outer ring or 5? monodeiodination). This reaction is catalyzed by deiodinase 1 (D1) and (D2). The total production rate is 30 to 40 mcg per day. The extra thyroidal T3 pool contains about 50 mcg (75 nmoles), most of which is intracellular. T3 is degraded, mostly by deiodination, much more rapidly than T4 (about 75 percent per day).

The actions of triiodo-thyronine occur about four times as rapidly as those of thyroxine, with a latent period as short as 6 to 12 hours and maximal cellular activity occurring within 2 to 3 days.

Treatment of Hypothyroidism other than T3

Since the generation of biologically active T3 by the peripheral conversion of T4 to T3 was documented in 1970 (Braverman LE), sodium levothyroxine is the preparation of choice to restore well-being and euthyroidism in hypothyroid patients, replacing desiccated thyroid and other forms of Lthyroxine and L-triiodothyronine combination therapy, T4 is a pro hormone with very little intrinsic activity. It is deiodinated in peripheral tissues to form T3, the active thyroid hormone.

This deiodination process accounts for about 80 percent of the total daily production of T3 in normal subjects; as a result, serum T3 concentrations are within the normal range in hypothyroid patients receiving adequate T4. Absorption is diminished by meals and competing medications . Since 70 % of a dose absorbed and, because the plasma half-life of T4 is long (seven days), once-daily treatment 60 minutes before breakfast or at bedtime 4 hours after the last meal on an empty stomach, is superior to achieve euthyroidism.

The initial dose can be the full anticipated dose (1.6 mcg/kg/day) in young, healthy patients, but older and cardiac patients should be started on a lower dose (12.5 to 50 mcg daily). Dose adjustments are guided by serum TSH determinations 4– 8 weeks initially, with the aim to ameliorate symptom, normalize TSH secretion within the normal reference range (approximately 0.5 to 5.0 mU/ L) and to avoid adverse consequences of overtreatment, which are atrial fibrillation and accelerated bone loss(Sawin CT 1994).

G. Discussion

What is difficult with hypothyroidism is finding the right dosage and restoring thyroid levels to normal. In fact, finding "physiological dose" for each individual can be so difficult, it has led to hypothyroid patients demanding more attention and seeking alternatives.

Should I also take T3?

Certain books, articles and websites reported that T3 supplementation helps with "brain fog" and other symptoms like depression; there was also a trend in the Psychiatry world to add T3 to antidepressant therapy. Furthermore, a small study on T3 supplementation in Lithuania which concluded that substitution of T3 for T4 may have more salutary effects on the brain and other tissues than an equivalent amount of T4.

Unluckily, the study was incorrectly interpreted to verify that T3 supplementation improved quality of life. In addition, a post analysis of the study revealed many design and interpretational flaws. Since 1999 there have been at least 11 larger and very well-designed clinical trials investigating whether the T3 or T3/T4 combination offers any benefit to hypothyroid patients, failed to verify that there is any benefit in the combination T3/T4 therapy.

The substitution of L-T3 for L-T4 at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity. This intervention could be relevant for hypothyroid patients affected by co morbid conditions such as cardiovascular disease, diabetes, dyslipidemia, or obesity, where weight control and aggressive lowering of serum cholesterol are particularly important.

However, presently, the prolonged use of L-T3 alone for the treatment of hypothyroidism cannot be advocated in a clinical setting, because thrice-daily dosing is not practical and may affect patients' adherence with treatment. Recent Meta analysis of double blind cross over studies which show no benefit of T3+T4 therapy over T4 therapy and is not recommended.

In conclusion, use of T4 only therapy is suggested and not to advocate the use of T3 or T3/T4 combination in usual hypothyroidism as a part of the standard of care in light of the evidence based medicine.

Concluded