INTRODUCTION:

Thyroid gland is located anteriorly in the lower neck, covering the distance from the fifth cervical vertebra to the first thoracic. The shape is either H or U and divided into two lobes connected with a median isthmus. Their length is approximately 50 to 60 mm, while the gland weighs 25 to 30 g.¹ It is one of the largest glands in the human body and is also one of the most important.^1,2

Thyroid gland producing hormones are Triiodothyronine (T₃) and Thyroxine (T₄), under regulation of thyroid stimulating hormone (TSH) which is produced in pituitary gland and regulated in turn by thyrotrophic releasing hormone (TRH), finally produced in Hypothalamus. Moreover, Thyroid gland secrets the hormone calcitonine which is implicated in homeostasis of blood calcium level. Thyroid gland is considered to be the cornerstone of entire endocrine system.¹

T₃ and T₄ in plasma are reversibly bound to protein and primarily it binds to thyroxin binding globulin (TBG). Only 0.04% of total T4 and0.4% of T₃exist in the free form. The primary pathway for the peripheral metabolism of thyroxin is deiodination. Deiodination of T₄may occur by monoiodination of the outer ring producing 3, 5, 3-triiodothyronine T_3, which is three to four times more potent than T_4.³

Hypothyroidism is diagnosed when the thyroid gland does not produce enough hormones for the necessity of the organism. T₃ (triiodothyronine) and T₄ (thyroxin), which is responsible for regulating the metabolism and maintaining normal functioning of the organism. Hypothyroidism is characterized by the reduction or by low production of T3 (triiodothyronine) and T4 (thyroxin) hormones. There are still no medicines which are capable of increasing the synthesis or release of thyroid hormones; as such the medical treatment is based on the reposition of the hormones with deficient production.³

MINI-MENTAL STATE EXAM:

The Mini-Mental State Exam (MMSE) is a brief test of cognitive impairment used widely to screen for dementia. The MMSE is the almost universally accepted and often used as a screening test for signs of cognitive impairment. It tests various abilities, including attention, memory, language and comprehension, figure drawing, and basic orientation. Maximum score is 30 and a score below a cut-off of 24 is often used to indicate possible dementia.⁴

While it is most useful for detecting dementia, low scores may be due to a number of conditions including delirium and depression. The test is very sensitive to education, age, and cultural background; for instance a score of 20 may be normal for a 90 year old who had limited schooling. The test does not deliver 100% sensitivity so a score of 28 may be obtained in a well educated person with other features and an eventual diagnosis of dementia.⁵

Thyroid hormone treatment can prevent or decrease the depressive symptoms and the decline in cognition that accompanies extended residence. This observation is particularly interesting because recently an article has described positive mood changes with a combined treatment of T4and T3. Partial substitution of triiodothyronine for thyroxin may improve mood and neuropsychological function; that finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.⁶

The thyroid gland plays a fundamental role in normal human development and maintenance, and it is therefore not surprising that genetic and acquired disorders of thyroid metabolism often include important neurological dysfunction. Congenital hypothyroidism clearly demonstrates this association between abnormal thyroid function and neuro- logical deﬁcits. Other neurological features seen in congenital and later onset hypothyroidism include anxiety, depression, carpal tunnel syndrome, peripheral neuropathy, headache, visual ﬁeld defects, and coma.⁷

MATERIAL AND METHODS:

The study site was carried out in the department of general medicine at Vivekanandha Medical Care Hospital, Tiruchengode. Patients of subclinical hypothyroidism without neurological disorder, Patients of overt hypothyroidism without neurological disorder, Normal Euthyroid persons were included in the study, Pediatrics Patients, Comatose patients, Chronic Illness patients, Patients with neurological disorder, pregnant women were excluded from the study. The study was approved by Institutional Ethical Committee of Vivekanandha Medical Care Hospital. It's a cross-sectional observational case-control study of 82 patients who met the criteria for hypothyroidism.

Similarly 82 subjects’ age, sex and education-matched healthy controls were taken. Patient demographics and treatment chart were noted by using data entry form. Cognitive functions were assessed by using Folstein Mini Mental Examination (MMSE). Then the hypothyroid patients were divided into subclinical and overt hypothyroidism individually compared with control group. Data entry and analysis was done using by graph pad instat. Compare the scores of both test and control groups by using the Paired t-test and ANOVA P<0.05 was considered as statistically significant.

RESULTS:

Patients Demographics:

Table 1. Age wise distribution among study population (n=164)

Age in years	Number of patients	Percentage (%)
21-30	4	2
31-40	4	2
41-50	4	2
51-60	2	1
>60	5	3

Table 2. Gender wise distribution among study population

Gender	Number of subjects	Percentage (%)
Male	48	29
Female	116	71

Table 3. BMI among the study populations

BMI	Number of Patients	Percentage (%)
Under weight	5	3.05
Normal weight	75	45.73
Over weight	63	38.42
Obese	21	12.80

Table 4. Percentage comparison of cognitive impairment status between euthyroid participants and hypothyroid patients

Degree of impairment	Patients with hypothyroidism		Euthyroid participants
Degree of impairment	Number of patients	Percentage (%)	Number of patients	Percentage (%)
Normal	22	26.83	46	56.10
Mild	46	56.10	34	41.46
Moderate	14	17.07	02	2.44
Severe	0	0	0	0

p value is <0.0001 considered extremely significant between hypothyroid patients and control MMSE score.

Table 5. MMSE score comparison between euthyroid participants and hypothyroid patients

Score	Degree of impairment	Average MMSE Score
Score	Degree of impairment	Patients with hypothyroidism	Control
25-30	Questionably significant	26.5±1.3	26.7±1.2
20-25	Mild	22.3±1.3	22.6±1.4
10-20	Moderate	17.1±1.9	21.6±2.8
0-10	Severe	0	0
p value		<0.0001

Table 7. Comparison based on the MMSE score between Over thypothyroidsm patients and euthyroid participants

Degree of impairment	Average MMSE score	Patients of overt hypothyroidism		Control
Degree of impairment	Average MMSE score	Number of patients	Percentage (%)	Number of patients	Percentage(%)
Significant	26.7 ± 1.30	16	43.24	46	56.10
Mild	22 ± 1.37	16	43.24	34	41.46
Moderate	16.8 ± 2.39	5	13.52	02	2.44
Severe	0	0	0	0	0
Mean MMSE score	23.32±3.72			24.94±2.49

p value is <0.05 considered significant between overt hypothyroid patients and control MMSE score.

Table 8. Comparison based on the MMSE score between patient’s overt hypothyroidism and subclinical hypothyroidism

Degree of impairment	Patients with subclinical hypothyroid		Patients with overt hypothyroidism
Degree of impairment	Number of patients	Percentage (%)	Number of patients	Percentage (%)
Normal	6	13.33	16	43.24
Mild	30	66.67	16	43.24
Moderate	9	20	5	13.52
Severe	0	0	0	0
Mean MMSE Score ±SD	21.93±2.93		23.32±3.72

p value is <0.05 considered significant between overt hypothyroid patients and subclinical hypothyroidism patients MMSE score.

Table 9. Percentage Comparison of cognitive impairment status based on the history hypothyroidism

History of hypothyroidism	MMSE score
	Normal		Mild		Moderate		Mean± SD
	Number of patients	Percentage (%)	Number of patients	Percentage (%)	Number of patients	Percentage (%)	Mean± SD
<3 years	9	10.97	10	12.20	0	0	24.78± 2.05
3-5 years	9	10.97	7	8.36	0	0	24.5 ± 1.86
6-10 years	5	6.10	21	25.60	4	4.88	22.07 ± 2.49
>10 years	1	1.22	6	7.32	10	12.20	19.06± 3.36

DISCUSSION:

Hypothyroidism is most common endocrine disorder and it is more common in women than men. The study comprised of 164 subjects out of which 82 diagnosed as hypothyroidism, Similarly 82 age and gender wise matched healthy controls (euthyroid participants) were taken. For those 82 hypothyroid patients the mean age was 40±14.3. Among 164 subjects 28.65% (47) participants were in the age group of 21-30 years. Among the study population 29% (48) subjects were male and 71% (116) were female. The prevalence of hypothyroidism was highest in the females as compared to males.⁸

Weight gain is the classical symptom of hypothyroidism⁹. In this study we have included euthyroid participants even though the overall BMI assessment shows that 38.42% (63) subjects were overweight and 12.80% (21) subjects were obese. This study coincides with the study conducted by Mahnaz Rakhshan et al., (2017)⁹but we have used MMSE scale in this study. Results showed that hypothyroid patients have significant differences in all aspects of mental health compared with the normal people.

In this study 26.83% (22) were having normal, 56.10% (46) were having mild cognitive impairment, 17.07% (14) were having moderate cognitive impairment, and none of the patients were having severe cognitive impairment. MMSE assessment of control group reveals 56.10% (46) normal, 41.46(34) mild, 2.44(2) moderate cognitive impairment, none of the patient were having severe cognitive impairment The average MMSE score of hypothyroid patients was 22.56±3.36, average MMSE score of control group is 24.94±2.48. When compared the both group shows (p <0.0001) extremely significant.

It remains unclear whether SCH leads to significant mood and cognitive impairments in most elderly patients.¹⁰Subclinical hypothyroidism is not associated with widespread or severe cognitive dificits.¹¹In this study among 82 hypothyroid patients 45 were having subclinical hypothyroidism. By the assessment of MMSE score for this group reveals 66.67% (30) were having mild cognitive impairment, 20% (9) were having moderate cognitive impairment and none of them were having severe impairment. The average MMSE score of subclinical hypothyroidism patients was 21.93±2.93, average MMSE score of control group is 24.94±2.48. When compared the both group shows (p<0.001) significant.

Overt hypothyroidism can affect a range of cognitive domains. That is decrement in general intelligence, attention/concentration, memory, language, psychomotor functions. Memory is the most consistently affected domain.¹¹ In this study among 82 hypothyroid patients 37 was having overt hypothyroidism. By the assessment of MMSE score for this group reveals 43.24% (16) were having mild cognitive impairment, 13.52% (5) were having moderate cognitive impairment and none of them were having severe impairment. The average MMSE score of overt hypothyroidism patients was 23.32±3.72, average MMSE score of control group is 24.94±2.48. When compared the both group shows (P<0.0031) significant. The average MMSE score of overt hypothyroidism patients was 23.32±3.72, average MMSE score of subclinical hypothyroidism patients was 21.93±2.93. When compared the both group shows (p <0.05) significant.

The assessment of MMSE score based on the history of hypothyroidism reveals <3 years were having 12.20% (10) patients were having mild cognitive impairment, 8.36% (7). The mean vale for MMSE score of patients having history of hypothyroidism less than three years was 24.78±2.05, history of hypothyroidism between 3 to 5 years was 24.5±, 6-10 years having mean value of 22.07 ±2.49, and more than 10 years have 19.06±3.36. Comparing all the groups shows p <0.0001 considered extremely significant among all the groups.

CONCLUSION:

Present study indicating hypothyroidism patients have low MMSE score than euthyroid participants which reveals hypothyroidism was significantly associated with cognitive impairment. Our finding reveals that Subclinical hypothyroidism was significantly associated with mild cognitive impairment more research is required to determine the nature and extent of this association. Present study also reveals patients who have chronic thyroid damage leads to higher risk of cognitive impairment.

ACKNOWLEDGEMENTS:

We would like to express our special thanks to the Director of Ponnaiyah Ramajayam Institute of Science and Technology, Thanjavur, Tamilnadu, India. And my heartfelt thanks to beloved Physician Dr. S. Arthanareeswaran, M.D, General Medicine Vivekanandha Medical Care Hospital, Tiruchengode.

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Received on 11.05.2019 Modified on 10.06.2019

Research J. Pharm. and Tech. 2019; 12(10):4763-4766.

DOI: 10.5958/0974-360X.2019.00821.7