Management of Patients Symptomatically Unresponsive to Levothyroxine: Natural Desiccated Thyroid Extract or the Combination of Levothyroxine and Liothyronine? A Research Priority.

Around 5-10% of hypothyroid patients continue to experience profound and sometimes disabling symptoms, including fatigue, depression and impaired cognition, in spite of being adequately replaced biochemically. The use of the combination of levothyroxine and liothyronine and natural desiccated thyroid extract is controversial for reasons of costs, a lack of evidence of additional benefit over levothyroxine alone, and potential safety concerns. Clinical guidelines caution against the use of both, and advise that only in exceptional cases may a short trial be considered. Natural desiccated thyroid extract is not licensed for use in the UK. However, key deficiencies in the existing evidence-base together with improved understanding of the pharmacology of levothyroxine resistance, indicates that now is the right time for a definitive clinical trial to address this important area of uncertainty.

Salivary gland hypofunction in tyrosylprotein sulfotransferase-2 knockout mice is due to primary hypothyroidism.

BACKGROUND: Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This prompted a detailed analysis to compare salivary gland structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative MRI imaging documented that salivary glands in Tpst2-/- females were (≈) 30% smaller than wild type or Tpst1-/- mice and that the granular convoluted tubules in Tpst2-/- submandibular glands were less prominent and were almost completely devoid of exocrine secretory granules compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine-induced salivary flow and salivary α-amylase activity in Tpst2-/- mice of both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti-sulfotyrosine Western blots of salivary gland extracts and saliva showed no differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the salivary gland hypofunction is due to factor(s) extrinsic to the salivary glands. Finally, we found that all indicators of hypothyroidism (serum T4, body weight) and salivary gland hypofunction (salivary flow, salivary α-amylase activity, histological changes) were restored to normal or near normal by thyroid hormone supplementation. CONCLUSIONS/SIGNIFICANCE: Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism.

Successful treatment of vitiligo with a sex steroid-thyroid hormone mixture.

Four patients with generalized vitiligo were successfully treated by oral administration of a sex steroid-thyroid hormone (Metharmon-F, 2 tablets daily). Histopathologically, the repigmented skin showed increased numbers of melanocytes and melanin granules in the keratinocytes.

[Ultrasonic and scintigraphic changes of the euthyroid goiter in the course of drug therapy. I]. / Modificazioni ultrasonografiche e scintigrafiche del gozzo eutiroideo in corso di trattamento farmacologico. Nota I.

We studied the ultrasonographic and scintigraphic changes of thyroid gland of 81 goitreous patients before and after treatment with exsiccated thyroid. About 57.8% of goitres showed a reduction of size, while no change was observed in 30% of patients; a further growth of the gland was seen in 13% of patients in spite of therapy. A difference between ultrasonography and scintigraphy in evaluating after-treatment follow-up was also noted, and a different response of nodules and diffuse hyperplasia to treatment assessed.

Myocardial infarction, severe reversible ischemia, and shock following excess thyroid administration in a woman with normal coronary arteries.

In the absence of fixed coronary artery disease, thyrotoxicosis is rarely associated with acute myocardial infarction and/or ischemia. There are no known reports on the association of acute myocardial infarction with iatrogenic or factitious thyrotoxicosis in the absence of fixed coronary artery stenosis or coronary artery spasm. A 68-year-old woman, clinically in a state of thyrotoxicosis as a result of taking 0.3 g/d of exogenous thyroid replacement, sustained a severe, reversible myocardial ischemic event. Echocardiographic and scintigraphic evaluations demonstrated a large apical dyskinetic region. Subsequently, after the original dose of levothyroxine sodium was reduced to 0.15 mg and the patient became euthyroid, two-dimensional echocardiography and scintigraphic and cardiac catheterization studies demonstrated normal left ventricular contractility and normal coronary anatomy. Coronary artery spasm was not induced by ergonovine maleate therapy. Exogenous thyroid administration may directly influence myocardial oxygen supply and demand, exclusive of coronary artery disease and coronary spasm. A critical imbalance may then result in acute myocardial ischemia and reversible left ventricular segmental wall motion abnormalities.

[A case of pituitary hyperplasia associated with primary hypothyroidism].

A thirteen-year-old girl was admitted complaining of short stature and anemia. The low titers of her serum T3 and T4 and the abnormally high TSH level represented primary hypothyroidism. Although she had normal sellar size, CT demonstrated an intra- and suprasellar round mass with homogeneous enhancement. With thyroid replacement therapy the enhanced mass diminished on CT within 5 months, and her symptoms regressed. Twelve cases with radiological diminution of pituitary mass or visual field improvement after thyroid replacement therapy are reviewed. They were considered to be pituitary hyperplasia, rather than pituitary adenoma, caused by long-standing untreated hypothyroidism. In four of them, the pituitary mass on CT was diminished after the therapy. Characteristic CT findings of pituitary hyperplasia, including our case, was a round isodensity mass with homogeneous enhancement in the midline of the pituitary region. In the experimental studies, pituitary hyperplasia is based on the feedback mechanism of hypothalamic-pituitary-thyroid axis, and ultimately autonomous pituitary adenoma may occur. Pituitary mass with hypothyroidism, visual field defect, amenorrhea or galactorrhea tend to be mistaken for prolactinoma or non-functioning adenoma with pituitary hypothyroidism. Thorough endocrinological examination must be carried out. The first choice of treatment for this type of pituitary mass should be thyroid replacement therapy. If there is no improvement of visual field, no regression of pituitary mass on CT, or continuing high TSH levels, then pituitary surgery must be considered.