Evaluation of Thyroid Stimulating Hormone and Thyroid Hormones Concentrations in Females with Hypothyroidism and Hyperthyroidism

This study was designed to evaluate thyroid stimulating hormone (TSH) and thyroid hormones Concentrations. Setting of the present study was performed in Teaching Hospital in Erbil city Iraq from 1 st of October 2017 to 1 st of March 2018. A total of 433 female were participated for blood tests to estimate thyroid function. Only 323 (74.6%) cases showed overall variation in hormonal level and 110 (25.4%) cases were normal. According to educational statue most of cases were with Bachelor level (67%). Generally 291(90%) of cases were married. 52% of the cases were 41 to 45 age group and 14.2 % cases was in both 26 to 30 and 31-35 age groups. About 59 (18.3%) cases had high TSH level only 13 (4%) case is considered as hypothyroidism when examined by consultation and collaboration with senior physician, while 54 (16.7%) cases had low TSH level but 41(12.7%) cases were considered hyperthyroidism. The result shows that 4 (1.7%) case have high T3 level and 52 (16.09%) case have low T3 level. While 26(8.04%) case have high T4 level and 61 (18.9%) case have low T4 level. In conclusion, we believe that thyroid diseases are more prevalent in women in Erbil and hyperthyroidism patient was more than hypothyroidism.


INTRODUCTION
The thyroid gland is located in front of the larynx on either side and anterior to the trachea and is shaped like a butterfly. It produces thyroxine, a hormone that regulates the metabolic activity of the body. Over activity of the thyroid gland [Hyperthyroidism (thyrotoxicosis)] is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Signs and symptoms vary between people and may include speeding up of metabolism, weight loss, temperature elevation, nervousness and irritability, but under activity of the thyroid gland [Hypothyroidism (myxoedema)] which is a common endocrine disorder resulting from deficiency of thyroid hormone or, more rarely, from their impaired activity at tissue level leads to inadequate production of thyroid hormones and a slowing of metabolism, deepens the voice, causes weight gain, water retention, retards growth and mental development in children. Both conditions also alter hair and skin growth, bowel function and menstrual flow (Ilse, 2011;Beers et al., 2006).
In the United States hyperthyroidism affects about 1.2% of the population. About half of these cases have obvious symptoms while the other half do not. It occurs between two and ten times more often in women. The disease is more common in those over the age of 60 years. Subclinical hyperthyroidism modestly increases the risk of cognitive impairment and dementia (Rieben et al., 2016). While the prevalence of hypothyroidism is 0.3% to 0.4%, increasing with age, and more females are affected (Muller et al., 2008).
2-To evaluate variations in thyroid stimulating hormone and thyroid hormones levels.

3-To Estimate the levels of TSH,T 3 and T 4 among female with hypothyroidism and hyperthyroidism.
4-Stimulation and enhance abnormal thyroid function in female to initial treatment medications to slow down or increase thyroid hormone production.

MATERIALS AND METHODS Experimental design:
This study was designed to analyze the ordering pattern of thyroid tests related for 433 females (outpatient and in-patient) with different age groups that referred by clinicians to hormones lab in Erbil Teaching Hospital from 1 st of October 2017 to 1 st of March 2018 for thyroid function tests for the first time in order to diagnose whether they have a thyroid disorder. A structured questionnaire was used for the collection of information from the females. With the help of questionnaire, information relevant to the study about their personal history (educational status marital status, age, duration of any symptoms they feel, use of medication was taken and question regarding their regularity of menstrual cycle). Exclusion criteria included pregnant women and menopausal women (women were considered to be menopausal if more than one year had elapsed since their last menstrual period). Sample collection: Blood samples were collected with the help of professional technicians from the inner side of the elbow by using 5cc syringes. Then samples tubes were brought to hormones lab and incubated at 37 C o for 40 minutes. Then serum was centrifuged at 3000 rpm for 20 minutes and stored at -40 C o in eppendorfs till the time of assay. Technique used: Samples were analyzed by the Electrochemiluminesence immunoassay intended for use on Eleccsys and Cobas immunoassay analyzers. Machine was calibrated and the serum was prepared and processed according to manufacturer's instructions. Analysis of results was done to find out the percentage of abnormal reports. The criterions for abnormal reports were results higher or lower than the reference interval. Data entry and analysis: Each returned questionnaire was given an identity number (ID). Prior to data entry and analysis, the questions of study were coded. The data was entered into a Microsoft Excel Spreadsheet, after data cleaning; descriptive statistics (numbers and percentage) were calculated for all variables. T-test and chi square were used for analysis the data by Graph Pad Prism 6.
RESULTS AND DISCUSSION Blood tests for thyroid function are an important part of the process for diagnosing thyroid disease and treating thyroid conditions. From 433 female that referred by clinicians to hospital for these test 110 (25.4%) female were normal to these tests and 323(74.6%) were shows abnormality in these tests as shows in (Table 1).   The results of this study were found to be coincided with findings of many other studies which reported that the incidence of hypothyroidism in females is more Moreover, it was most common thyroid disorder and it is six times more common in women. A study was conducted on distribution of 25237 thyroid patients in different age and sex revealed that thyroid problems prevailed more in females 73%, the percentage of adult group (<40 ) was 64.0% then old age (>40) was 27%. (Khattak et al., 2001). Another study demonstrated that the prevalence of thyroid diseases occur nearly 10 times more common in females (Devdhar et al., 2007). Faisal; showed that spectrum of thyroid disorders among Iraqi females was 14.45% hypothyroidism. Mahadevan (2010) concluded that thyroid disorders were found to be higher in females. Also recent study on 300 patients thyroid dysfunction was present in 68% females and elderly population had more incidences (Senthil et al., 2015). Other researchers aimed to explore the impact of gender and age on Thyroid Function in a large Chinese cohort. Females had higher incidence of thyroid dysfunction with 35 years < age ≤ 45 years (Venkateshwarlu et al., 2013) and (Meng et al., 2015).

Table 4: Distribution of abnormal thyroid function females according to Age groups
From 323 cases 59 (18.3% ) case have TSH reading above 4.0 mIU/L is considered high TSH levels and typically indicates an underactive thyroid gland, which produces too little thyroid hormone. This is known medically as hypothyroidism which only 13 (4%) case in this study when examined by consultation and collaboration with senior physician at Teaching hospital.
The most common reason cause hypothyroidism are Hashimoto's Thyroiditis, problems with the Thyroid Itself or thyroid has been surgically removed, Medications, abnormal Growths in the thyroid, Problems in the Pituitary and Genetic Defects. Replacing thyroid hormone and altering diet are crucial for the safe and effective treatment of an underactive thyroid (Pappa and Alevizaki, 2013). While TSH values were lower 0.4 mIU/L in 54 (16.7%) of cases. The reason was typically indicates an over active thyroid gland, which produces too much thyroid hormone, but medically the clinicians consultation only diagnosed 41(12.7%) cases as hyperthyroidism, it can be caused by an autoimmune disease (known as Graves' disease), excessive iodine in the body, or an overdose of synthetic thyroid hormone (Mahadevan, 2010). Statistical analysis showed significant differences (P > 0.05) as shown in Fig. (1) and non significant differences for TSH cases Fig. (2).

Fig. 3: chi square by (GraphPad Prism 6) for T3 and T4 Level in study cases
Some clinical studies have found that both T3 and TSH levels can decline at the same time, particularly in obese individuals that lose weight (Dietlein et al., 2008;Kok et al., 2005). The results of (Al-Kattan et al., 2018) showed positive effects as a significant increase (P≤0.0001) in thyroid stimulating hormone and Thyroid hormones T4 and T3 in rabbit's serum that drenched 6ml pomegranate juice /Kg body.
Certain medications, such as metformin, are also known to independently lower TSH levels in diabetics and polycystic ovary syndrome (PCOS) patients with thyroid issues (Pappa and Alevizaki, 2013). This means that overall external stressors are known to influence TSH levels, independently of thyroid hormone levels, and TSH on it's own is not always a reliable indicator of thyroid health.
TSH levels can also be used to effectively monitor patients being treated with thyroid hormone. However, it should be noted that TSH results may be misleading during the several months required for full equilibration of thyroid physiology following initiation or significant alteration of a treatment regimen. Total or free T4 generally serve as the front-line assays during this period. Once equilibration has occurred, high TSH levels usually indicate under-treatment, while low values usually indicate over-treatment. Again, abnormal TSH values should be interpreted with the measurement of free thyroid hormone before modifying therapy because serum thyroid hormone levels change more quickly than TSH levels. Thus patients who have recently been started on thyroid hormone, or who have been noncompliant until shortly before an office visit may have normal T 4 and T 3 levels, though their TSH levels are still elevated. TSH levels may be affected by acute illness and several medications, including dopamine and glucocorticoids (Roelfsema et al., 2009).
The high prevalence rate of thyroid disorders around the world and also in Iraq seem to associate with iodide deficiency, other factors such as environmental contamination and genetic defect should be more effect. Then the governments in most countries have policy to use iodizing salt, also starting in Iraq since 1990 (Faisal, 2010). Thyroid diseases are more prevalent in women particularly between puberty and menopause, and women are more susceptible to the goitrogenic effect of iodine deficiency (Santin and Furlanetto, 2011).
These epidemiological studies suggested the role of female hormones such as oestrogen hormone in the pathogenesis of thyroid diseases. Oestrogen has a well-known to have indirect effect on thyroid gland by increasing the thyroxin binding globulin (Ben et al., 1987), and it's need with thyroid hormone in hypothyroid women (Arafah, 2001).

CONCLUSION
The diagnosis of thyroid dysfunction in these patients may be difficult because of different interpretation of thyroid function tests. There was a higher crude prevalence of hyperthyroidism as compared with hypothyroidism in the female with thyroid diseases in our study.