Tissues Is Controlled By Thyroid Hormone

Published Date: 02 Nov 2017

The metabolic role of many tissues is controlled by thyroid hormone, and under activity

or over activity of the gland are the most common of all the endocrine problems.

Thyroid hormones control the activity of the cell and regulate body temperature,

appetite, sleep, and mental health. A decrease in level of thyroid hormone results in

myxedema. Although disease may vary from very mild to severe, hypothyroid patients

may suffer from anemia, malaise, intolerance to cold, hyperlipidemia, fluid retention,

and depression. A high level of thyroid hormone causes hyperthyroidism. Classical

symptoms include insomnia, intolerance to heat, weight loss, and rapid heart rate. Now

it has been recognized that both of these conditions whether hypothyroid or

hyperthyroid also affect bone structure and mineralization.

In hypothyroidism the duration of the bone metabolism is increased: the duration of

the osteoclastic resorption phase is doubled, whereas the time for osteoblastic

bone formation and secondary mineralization is prolonged four times. These changes

result in low bone turnover and an overall gain in bone mass and mineralization. This

differs from hyperthyroidism in which , bone resorption and formation are both increased

and the turnover cycle is shortened: the duration of the resorption phase is reduced by

60% and the formation phase is shortened by 30%. The process of initiation of bone

formation cycle is also visibly increased and bone resorption is increased to a greater

degree than bone formation. The ultimate result of these changes is a 10% loss of

bone per remodeling cycle in established hyperthyroidism leading to high bone

turnover and osteoporosis. This suggests that the change in bone associated with osteoporosis is linked with excess of thyroid hormone .

It is very important to recognize the bone involvement in hyperthyroid and

subclinical hyperthyroid patients, because this is one of the major problems in such

patients. Bone involvement and deteroriation in its structure may not be easily identified

by physicians and specialists in the absence of a simple, easily available and accurate

method of screening.

Bauer et al (2001) were of the view that patients with low TSH had higher risk of

vertebral and hip fractures than women with normal TSH.

Zaidi et al (2009) attributed the bone loss in hyperthyroid patients partly to TSH

deficiency rather than to hyperthyroid state. This view was supported by the presence of

TSH receptors in bone.

In the present study it was demonstrated that if Quantitative Ultrasonography was

done in routine clinical practice on patients of hyperthyroidism and subclinical

hyperthyroidism, it could help to screen out bone changes in these group of patients,

and could identify patients who could be further worked up.

Udayakumar (2006) suggested that the worst effects of thyroid hormones were seen in areas of cortical bone , like neck and forearm.

Vestergaard and Mosekilde (2003) also suggested that thyroid hormones increase the

bone turnover and make such patients more susceptible to fracture.

Devlin (2001) in his research emphasized that radiomorphic methods were not that accurate

and hence doubtful.

Krieg et al(2003)also by using DBM Sonic 1200 discriminated women with a hip fracture

history from those without osteoporotic fracture.

We used DBM scanner software to calculate the bone mineral density, by dividing the bone mineral content by the area of the region of interest. The bone mineral density was then compared to reference data that was specific to the scanner, and the results were expressed as the T- score and the Z-score.

Marshall D et al (1996) in several studies done on post menopausal women found that bone mineral density was associated with an increased risk of fracture that was equal to

approximately 1.5 to 3.0 to the power of decreased standard deviation of the T - score.

Age of euthyroid patients ( 26.28 ± 6.52 ) was significantly less (p=0.003) than those of

Hyperthyroid ( 31.23 ± 9.608 ) and Subclinical hyperthyroid patients ( 35.23 ± 10.150 ).

p value differed between FT3, FT4 and TSH ( p value <0.001*) in all three groups.

Hoffler et al (2000) suggested through their study that the properties of bone lamella were

independent of age and sex , which suggested that bone mass and structure contributed to the mechanical properties of bone.

Murphy et al. (2010) suggested that patients with thyroid status in the upper normal range have a reduced BMD and an increased risk of non vertebral fracture .Patients with higher FT3 and FT4 had lower BMD at the hip and an increased bone loss. When adjustment was made for age, BMI and BMD women with higher FT3 or FT4 the risk of non vertebral fracture increased to 20 - 30% whereas higher TSH reduced its risk to 35%. This showed that patients of subclinical, and hyperthyroid groups did differ in their bone architecture which is very similar to what we have seen in our research.

Tauchmanovà et al. 2004; suggested through various studies done on endogenous subclinical hyperthyroidism and bone health , that bone mineral density was decreased at sites rich in cortical bone such as distal radius but little defect was found in men or premenopausal women.

The mean Ad SoS value was 2060.58 ± 136.327m/s in hyperthyroid group as compared

to 2159.68±97.366m/s in euthyroid group (p value₌ 0.002 ) which showed a clear

decline in bone structure in hyperthyroid group. The mean Ad So S value in subclinical

hyperthyroid group was 2061.87 ± 85.357m/s as compared to 2159.68±97.366m/s in

euthyroid group (p- value 0.003), which showed that there is a change in bone

architecture in patients of subclinical hyperthyroidism. Patients of Subclinical

hyperthyroidism with mean Ad SoS of 2061.87 ± 85.357m/s when compared with

Hyperthyroid patients 2060.58 ± 136.327m/s (p value ₌0.999) suggested that although both

these groups. differ from euthyroid patients but there was no significant difference

between these two groups regarding Ad S o S. Also no significant difference was found

between dominant and non dominant hand which suggested that it was sufficient to

measure AdSoS of one hand only.

Alexandersen , et al. (2005) were of the view that fractures may be present or absent in patients with similar bone mineral density , so bone strength depends not only on bone density but also on bone architecture.

QUS that was used is based on the theory that when sound waves pass through

porous structures such as bone they are either absorbed, scattered and travel in a

manner that depends upon elasticity, stiffness, volume and density of material.

In cancellous bone has there is a strong interrelationship between elasticity, density, and

architecture of cancellous bone. That is why its difficult to identify the property that is

responsible for change in ultrasonic measurements. Since QUS cannot be expected to

detect cancellous bone fragility in the absence of major density or architectural changes

that is why the resultant increase in fragility was not detected by QUS.

Mehta et al (2001) in their study on femurs of growing rats showed that ultrasonic

velocity measurements can predict the strength of whole bone and also established a

connection between material level ultrasound velocity and whole bone mechanical

strength.

Since Ad SoS also depends on body size and mean width of the fingers i e bone plus

soft tissues. This suggests that skeletal mass may influence ultrasound velocity. So

it is possible that if our patient finger thickness was close to the wavelength of

ultrasound a dispersion which occurred during measurement, decreased the ultrasound

velocity with decreasing finger thickness. According to the correlation between Ad So S

and mean width of the fingers, at least 25% of the observed increase of Ad SoS can

be explained by finger anatomy alone.

There was a difference in T – score of euthyroid ( 0.6032±1.41651), hyperthyroid

( -0.8572±1.95537) and subclinical hyperthyroid patients(-0.8873±1.21953) p value < 0.001.

Post Hoc comparison of T – score showed that there was a significant variation in T – score of Euthyroid as compared to subclinical and hyperthyroid patients ( p value=0.001) .However there was no significant difference between hyperthyroid and subclinical hyperthyroid group (p value 0.997 ).

T-score is an important part of the measurements done to screen a person for osteoporosis . because it shows the bone mineral density at the site when compared to a young person who is considered as normal reference mean. Normal value is -1 or higher. Osteopenia is suggested if it is between -1 and -2.5. A person would be suspected of osteoporosis if the value is -2.5 or lower .where as a normal person would be having a T - score greater than -1. Since T – Scores determine the degree of bone loss and helps to predict the risk of bone fractures our study showed that that there was a greater bone loss in hyperthyroid and subclinical hyperthyroid patients as compared to euthyroid.

Van de ven and Erdstieck 2008 said that hyperthyroidism is one of the diseases responsible for bone loss and increased fracture risk. There is a appreciable bone loss with higher biochemical markers of bone turnover .This also depends on the duration of the disease and the disturbance of biochemical parameters.

There was a difference in Z – score between hyperthyroid ,( -0.5106±2.0 8609)

Euthyroid 1.1000(0.6600-2.1300) and subclinical hyperthyroid group (-0.0957 ± 1.14502 ) p - value 0.001. Binkley NC, (2002) suggested that that T – score was not matched for certain populations and it was the z- score that was better indicator of the bone mineral density. A Z-score is used to compare your results to others of your same age, weight,

ethnicity, and gender. This it was useful to determine if there was something unusual that was contributing to the bone loss of the patients.

A z-score is also influenced by thyroid abnormalities, malnourishment ,any medical treatment, smoking. Factors other than age might be involved if a person is having a z- score of less than -1.5. Since euthyroid differed from both hyperthyroid and subclinical group regarding their Z -score, this showed that this difference in z – score was playing a

major role in bone changes difference between these groups.

Post hoc comparisons of Z - score showed that there is a significant difference between Euthyroid and hyperthyroid group (p – value 0.002 ) and also between euthyroid and subclinical hyperthyroid group ( p value < 0.001). This showed that there is a difference in bone architecture between these groups .However no significant difference was observed between subclinical and hyperthyroid groups (p-value 0.598) .The Z - score matches bone mineral density of a patient to a typical individual whose age is matched. It thus shows the relative risk of fracture for each standard deviation below mean for age, race and gender. So if a person has a z – score of -1 he has 2.5 times the chance of a fracture than a person having a z-score of zero. In our study it showed that hyperthyroid and subclinical hyperthyroid patients had decreased bone density as compared to patients of same age group .It can also be useful to determine whether an underlying disease or condition is causing bone loss.

Gugelielmi G ,et al (2005) said that bone transmission time is the interval between first received signal that is propagated through soft tissue only.

Although there was a difference in bone transmission time between these the

three groups euthyroid ( 1.7136 ± .30258 ) ,hyperthyroid ( 1.5190 ± .26467) and subclinical

( 1.5190 ± .26467 ) p - value 0.003. On post hoc comparisons there was a difference

between euthyroid and hyperthyroid group ( p – value 0.005), and also between

euthyroid and subclinical hyperthyroid group. ( p value 0.016 ). There was no

difference of bone transmission time between hyperthyroid and subclinical

hyperthyroid group(0.924 ) which confirmed the findings of AdSoS.

Ultrasound bone profile index did not vary among the three groups.(p-value

0.058). BMI varied between euthyroid (22.3360±5.22589), hyperthyroid

(21.3258 ± 4.25033) and subclinical hyperthyroid group (24.24±4.92) (p-value of 0.04).On

post hoc comparison there was no difference between euthyroid and subclinical

hyperthyroid group but there was a significant difference between hyperthyroid and

subclinical hyperthyroid group.( p-value0.035). There was no significant difference

in serum calcium levels between euthyroid ,( 6.7204±.63586), hyperthyroid

(6.9816±.43436) and subclinical hyperthyroid patients.(6.5900(6.3600-7.2650) p value

was 0.252. Dhanwal et al (2011) suggested that majority of the patients in the west

have normal serum calcium levels and the mean serum calcium levels are higher than

controls. However they reported hypocalcemia in Indian patients. This is also seen in our

study where calcium levels are also low . This can be explained by, that those patients

which were included in our study were not evaluated for vitamin D deficiency which

might have contributed to low calcium levels. Although these changes are slight in

thyroid disorders but it is possible that they are important for the patient in long

term. Negative calcium and phosphorous balance in hyperthyroid patients may lead to

osteopenia and increase the risk of secondary osteoporosis. The study could be further

extended by measuring ionized calcium instead of total calcium and correlating it with

duration and severity of thyroid disorders.

However there was a significant difference between serum phosphate of hyperthyroid

4.40 ± 0.66, euthyroid 4.03 ±0 .77 and subclinical patients 3.82 ± 0.52 (p-value 0.004). Post hoc comparison showed that the euthyroid patients did not differ from hyperthyroid and subclinical hyperthyroid patients, but there was a significant difference between hyperthyroid and subclinical hyperthyroid patients(p-value 0.003).

Calcium and phosphorous levels can be used as an index of bone turnover. Unfortunately the status of total body phosphorous pool is reflected only indirectly by concentration of phosphate in extracellular fluid , which contains less than 5% of body

phosphorous. Thus although serum phosphate concentration generally used to show hypophosphatemia as severe, ,moderate or mild the serum phosphate level may be normal or high in the presence of profound intracellular phosphate deficiency . Conversely it may be low when intracellular phosphate is relatively normal ,

as following a sudden movement of extracellular phosphate into the cell. Also certain conditions also effect shift of phosphate into cells or bone .These include if person is recovering from starvation or acidosis. Since starvation was not excluded so this might have led to low phosphate levels.

A p –value of 0.002 , showed that there is a difference of serum alkaline phoshatase among euthyroid (185.00(155.00-243.00), hyperthyroid330.00 (230.00-384.00) and subclinical hyperthyroid 289.00(178.00-354.00).Post hoc test showed that euthyroid differed from hyperthyroid (p value < 0.001) and also from Subclinical hyperthyroid group (p-value 0.025). However no significant difference was found between Hyperthyroid and subclinical hyperthyroid group.

LIMITATIONS

1.We examined only a small population so the preliminary results should be extended

through larger sample studies.

2.Direct comparison with other studies can be difficult due to different experimental

conditions, measurement sites and probe calibration.

3. Moreover, pathologies and treatments were unknown for our study population.

4.The study also included the lack of measurement of material properties such as

elasticity . Ultrasonic techniques in the mega hertz range can be used to assess elastic

properties of cortical bone, but elastic constants measured in this frequency range

correspond to homogenized constants, depending not only on bone properties at the

tissue level but also on the POR.