Thyroid

New FDA approval: drug therapy for anaplastic thyroid cancer

New FDA approval: drug therapy for anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is a rare and aggressive type of thyroid cancer. It accounts for about 1-2% of all thyroid cancers. NIH estimates 54,000 new cases of thyroid cancer and 2,000 deaths from the disease in the US in 2018. 

The tafinlar + mekinist combination is now approved for the treatment of BRAF V600E mutation-positive ATC that cannot be addressed surgically or has already spread to other organs. Tafinlar and Mekinist have also been approved for two other BRAF V600 mutation-positive metastatic malignancies; melanoma and non-small cell lung cancer.

GT

Cancer immunotherapy causes hypothyroidism

Cancer immunotherapy causes hypothyroidism

Nivolumab is an effective immunotherapy for advanced malignancies such as gastric cancer, renal cell carcinoma, unresectable metastatic melanoma, non-small cell lung cancer, hodgkin lymphoma and head/neck cancer. However it has also been noted to cause endocrinopathies like type 1 diabetes and pituitary, adrenal and thyroid dysfunctions.

Current study shows that nivolumab-induced inflammatory hypothyroidism is relatively rare at about 5% in 6 months, and was mainly seen in participants with elevated baseline thyroid antibodies. This suggests that the anti-PD1 monoclonal Ab therapy causes hypothyroidism in predisposed individuals, thus initial evaluation of TPO and Tg antibodies may be warranted prior to starting nivolumab.

GT

Hyperthyroid and ventricular fibrillations

Hyperthyroid and ventricular fibrillations

This case shows a positive correlation between thyroid levels and J-wave amplitude in a patient experiencing ventricular fibrillations. Pronounced J-waves in multiple EKG leads can predict lethal arrhythmias, thus early diagnosis and treatment are necessary. More research would be needed however to clarify or solidify the cause-effect dance between hyperthyroidism and elevated J-waves. 

GT

Congenital malformations in Grave's disease

Congenital malformations in Grave's disease

Traditional approach is to use propylthiouracil (PTU) for Grave's disease during the first trimester. This article points otherwise, that both methimazole and PTU can increase the risk of congenital malformations when used in the first three months of pregnancy. I suspect more research would be needed before changing guidelines or standard of care.

GT

Elevated thyroid hormone associated with dementia in the elderly

Elevated thyroid hormone associated with dementia in the elderly

Over 2,500 adults aged 70-80 without baseline dementia were followed for 9 years. Patients with subclinical hyperthyroidism and very low TSH, as defined by TSH < 0.10, were found to be at high risk of cognitive decline. On the contrary, subclinical hypothyroidism and subclinical hyperthyroid with TSH 0.1-0.5 were not associated with an increased incidence of dementia. 

Although findings are associative, and not causative, it would still be reasonable to avoid "advanced" subclinical hyperthyroidism in adults >70 years of age. Low dose methimazole could be useful in these individuals assuming absence of medication adverse effects. 

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Thyroid-cholesterol axis in overweight children

Thyroid-cholesterol axis in overweight children

A group of 330 overweight or obese children, without thyroid anomalies, were followed for TSH, free T4 versus CVD identifiers; total cholesterol (TChol), LDL-cholesterol (LDL), triacylglycerol (TAG), and monocyte chemotactic protein 1 (MCP1).

Tests were measured before and after one year of lifestyle intervention, including weight loss. Study finds that TSH, but not free T4, correlates positively with CVD markers, suggesting direct involvement of TSH in lipoprotein metabolism.

It is speculated that TSH receptors, present in hepatocytes, are responsible for direct cholesterol synthesis and lower bile acid production under TSH stimulation. Future studies could address interventional outcomes of thyroid hormone on TSH and CVD risk factors.

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Small thyroid cancers, how to monitor?

Small thyroid cancers, how to monitor?

Thyroid papillary micro-carcinoma is defined as an isolated cancer with diameter no larger then 1.0 cm. It is considered to have good long-term prognosis. Analyses reveal that these small cancers could be more aggressive than expected. Authors also find that cancer volume, rather than diameter, expansion is the best structural tool in identifying tumors at risk of progression.

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Thyroid Cancer: Incidence & Mortality Are UP

Thyroid Cancer: Incidence & Mortality Are UP

Among patients in the United States diagnosed with thyroid cancer from 1974-2013, the overall incidence of thyroid cancer increased 3% annually, with increases in the incidence rate and thyroid cancer mortality rate for advanced-stage papillary thyroid cancer. These findings are consistent with a true increase in the occurrence of thyroid cancer in the United States.

JAMA

Subclinical Hypothyroidism and Hypothyroxinemia during pregnancy

Subclinical Hypothyroidism and Hypothyroxinemia during pregnancy

This is any important investigation if thyroid hormone supplementation in pregnant women with subclinical hypothyroidism or hypothyroxinemia improves cognition in children. Although results are negative, I believe the study is not complete for two reasons:

1.  Levothyroxine was not initiated until around week 17 of gestation. For more meaningful results, thyroid hormone should be started before pregnancy or very early in the first trimester.

2.  Longer follow up of 10-15 years would be more appropriate in evaluating children's cognition and IQ scores.

GT

Amiodarone & Thyroid, 2016 ATA Guidelines

Amiodarone & Thyroid, 2016 ATA Guidelines

Amiodarone induced thyrotoxicosis could be productive or destructive, called AIT1 and AIT2 respectively. AIT1 hyperthyroidism is primarily due to excessive iodine supplied by the amiodarone, whereas AIT2 is secondary to thyroid inflammation leading to uncontrolled release of preformed hormone. Distinguishing between the two types clinically, biochemically or by imaging studies is often difficult. Common treatments are methimazole, prednisone, surgery or a combination of the three. Amiodarone could also be discontinued if approved by the heart specialist.  

In 2016, American Thyroid Association published guidelines on diagnosis and management of hyperthyroidism, including the amiodarone scenario. The publication provides great explanations and rationales on how to approach amiodarone induced thyrotoxicosis. Please read recommendations and excerpts below for more details.

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2017 ATA Guidelines: Thyroid & Pregnancy (Part 2)

2017 ATA Guidelines: Thyroid & Pregnancy (Part 2)

ATA has "developed evidence-based recommendations to inform clinical decision making in the management of thyroid disease in pregnant and postpartum women. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with these disorders"

Part 2 of recommendations are listed with slightly modified wording for easier and succinct reading:

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2016 Endocrine Society Guidelines: Central Hypothyroidism

2016 Endocrine Society Guidelines: Central Hypothyroidism

Central Hypothyroidism is a very rare cause of reduced thyroid production, mainly secondary to pituitary anomaly. Infections, tumors, cysts, autoimmunity, surgery and radiation are usually responsible for the abnormal TSH secretion by the pituitary gland.

Endocrine Society released guidelines on diagnosis and management of central hypothyroidism in November 2016. Please find below excerpts with slightly modified wording for easier and succinct reading.

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Hyperthyroidism in the womb - a rare case.

Hyperthyroidism in the womb - a rare case.

This publication reports a rare and counterintuitive case of neonatal hyperthyroidism: mother has underactive thyroid, while the unborn baby has an overactive one. Although the mother has hypothyroidism from hashimoto's thyroiditis, she produces TSI (thyroid stimulating immunoglobulin) triggering excessive thyroid hormone formation by the fetus.

Paradoxically the mother was treated with both medications; levothyroxine for her hypothyroidism and methimazole for her fetus’ hyperthyroidism.

GT

Low-risk thyroid cancer: surgery or no surgery?

Low-risk thyroid cancer: surgery or no surgery?

This original study suggests thyroidectomy for low-risk cancers measuring >1.5 cm rather >1.0 cm as currently recommended by ATA; to avoid unnecessary surgeries, cost and complications. 

In stead, authors propose “active surveillance” in carcinomas <1.5 cm. About 700 thyroid cancer patients were analyzed over a 10 year period.

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2017 ATA Guidelines: Thyroid & Pregnancy (part 1)

2017 ATA Guidelines: Thyroid & Pregnancy (part 1)

ATA has "developed evidence-based recommendations to inform clinical decision making in the management of thyroid disease in pregnant and postpartum women. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with these disorders"

Part 1 of recommendations are listed with slightly modified wording for easier and succinct reading:

GT