Hyperthyroidism and Fracture Risk

Coletta Hargis Hyperthyroidism
Protruding eyes are associated with hyperthyroidism

According to the authors of a meta-analysis, individuals with subclinical hyperthoidism are at an increased risk of various fractures.  Researchers examined data from some 70,298 people, 4,09s of them with subclinical hypothyroidism and 2,219 with subclinical hyperthyroidism, enrolled in 13 prospective cohort studies.  After adjusting for age, sex and other fracture risk factors, the researchers found that individuals with subclinical hyperthyroidism had a 28% increase in risk of any fracture, and a 36% increased risk of hip fracture, compared to people with normal thyroid function.

Subclinical hyperthyroidism, defined as a thyroid-stimulating hormone (TSH) level of less than .45 mlU/L, with normal FT4 levels, was also tied with a 16% increase in the risk of nonspine fracture.  Men with subclinical hyperthyroidism were more than 3.5 times more at risk of spine fracture, although the increase was insignificant in women.  Lower TSH was associated with higher fracture rates, and the analysis showed a 61% increase in the risk of hip fracture, and more than a 3.5-fold increase in spine fracture risk among those people with a TSH of less than .10 mlU/L.  The analysis yielded no link between subclinical hypothyroidism and fracture risk, and comparing fracture risk between individuals treated with thyroxine at baseline and untreated participants also showed no significant impact of thyroxine therapy on the outcomes of fractures.

In prospective cohort studies, data associating between subclinical thyroid dysfunction and fracture risk contradict each other, since the inclusion of participants with overt thyroid disease and small sample sizes of participants with thyroid dysfunction or fracture events.  The researchers of the study proposed three mechanisms through which thyroid dysfunction could affect fracture risk.  For one, thyroid hormones have been shown to have effects on osteoclasts and osteoblasts, with thyroid status in the upper-normal range or excess thyroid hormones leading to accelerated bone turnover with bone loss and increased fracture risk.  In addition, subclinical hyperthyroidism could increase the risk of falls through affecting muscle strength and coordination, with thyroxine supplementation being suggesting as impacting the risk of fracture.

The authors of the study pointed out that endogenous subclinical hyperthyroidism can go undetected for years, since symptoms of subclinical hyperthyroidism are frequently nonspecific or even absent, a phenomenon that has to potential to lead to a greater length of time for adverse associations with bone metabolism.  The author also stressed the limitations of the observational data that they had gathered.  For example, thyroid function was only assessed at baseline, and some individuals may have progressed to overt thyroid dysfunction over the course of the study.  In addition, there remained a lack of uniform definition of fracture type across the cohorts.  The researchers said that their findings supported current guideline recommendations that anybody 65 or older with subclinical hyperthyroidism and a TSH persistently lower than .1 mlU/L should be treated, which in turn should be considered for those individuals with low TSH but nonetheless above .1 mlU/L.

Fetal Overgrowth Syndrome Markers Discovered

Coletta Hargis BWS
A child with BWS, showing the enlarged tongue characteristic of the disorder.

Both humans and cattle share a similar epigenetic fetal overgrowth disorder that occurs more frequently after assisted reproduction procedures.  This disorder is called Beckwith-Widemann syndrome (BWS) in humans, and Large Offspring syndrome (LOS).  In both humans and cattle, it can result in the overgrowth of fetuses and enlarged babies.  While rare, this naturally occurring syndrome can cause physical abnormalities, and often result in both the deaths of both babies and mothers.  Recently, however, researchers at the University of Missouri have identified a number of genes that contribute to LOS in cattle.  According to Rocío Melissa Rivera, an associate professor in the MU College of Agriculture, Food and Natural Resources, identifying these genes in cattle will help to identify genes that cause BWS in humans.

Both physically and molecularly, BWS and LOS have a lot in common with each other.  According to Rivera, by identifying LOS genes, researchers can take steps toward discovering which genes cause BWS in humans.  Since these disorders have been associated with pregnancies from in vitro, knowing which genes cause these disorders will allow doctors to choose embryos for implantation that don’t have the molecular markers for BWS.  BWS results in babies that grow and gain weight at an abnormal rate in both the womb and early childhood.  Many children suffering from BWS have enlarged tongues, abdominal wall defects, suffer from asymmetric growth and are at a higher risk for cancer.  However, apart from the most severe cases, BWS isn’t fatal to humans unless they develop undetected cancer from it.

LOS in cattle has many characteristics similar to BWS, including rapid growth, weight gain in the womb, large tongues and abdominal wall defects.  Unlike BWS, however, LOS is often much more deadly, since many calves can die within a week of birth due to an inability to support their own weight and size.  Since in vitro is common in cattle breeding, LOS is a potential problem for many breeders.  This means that it’s particularly important for breeders to be able to identify the genetic causes of LOS, so that they can avoid impregnating their cattle with embryos predisposed to the disorder.  Overall, this will allow the breeding process to be much more efficient and safe.