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Mohammed Nadeem, Ritu Sharma, Shravan Meena

Department of Biochemistry, Churu Medical College, Rajasthan; Department of Biochemistry, Government Medical College, Kota, Rajasthan; Department of Biochemistry, Sikar Medical College, Rajasthan

Anxiety disorders refer to the group of mental disorders characterized by feelings of anxiety and fear, including generalized anxiety disorder (GAD), panic disorder, phobias, social anxiety disorder, obsessivecompulsive disorder (OCD) and post-traumatic stress disorder (PTSD). Anxiety disorders are the most common form of mental illness, and affect one in 20 people at any given time.

The hypothalamic-pituitary-adrenal axis (HPA axis) is one of the body’s main systems that control response to stress. It acts through the hormone cortisol, which is produced in the adrenal cortex and affects many tissues including the brain. Corticotropin-releasing hormone (CRH) is an episodically released hormone that is secreted by the hypothalamus1 and is mainly responsible for the regulation of the HPA system cascade. Under acute physical or psychological stress, CRH triggers the release of adrenocorticotropic hormone (ACTH) from the pituitary, which activates the release of glucocorticoids (e.g., cortisol) from the adrenal cortex2. 

The association between thyroid dysfunction and mood disorders is well recognized. If the anxiety symptoms may be due to a thyroid dysfunction, the use of medication might have masked this underlying cause. So, although the anxiety symptoms were alleviated, the cause for it, which might have been thyroid dysfunction, would go untreated. This might result in temporary remission, which on discontinuation of medication can cause a relapse. The clinician should be able to differentiate anxiety associated with medical illness from primary anxiety disorder.3 

Limited published data of this topic has been conducted in the southern part of India. Hence the present study was conducted to determine serum levels of cortisol and thyroid stimulating hormone (TSH) in GAD Patients.


The present cross sectional study was conducted after approval of institutional ethics committee. This study was conducted in the department of Psychiatry at a tertiary care hospital. Sixty consecutive outpatients between the ages of 18 to 60 years, diagnosed with GAD by a consultant psychiatrist according to ICD-10 criteria were included for the study as the study group. Similarly, sixty age and sex matched healthy controls either friend or relative of the patients were included in the control group. Written informed consent was taken from the research participants prior to the commencement of the study.

Inclusion Criteria:

1. Those who gave written informed consent

Exclusion Criteria:

1. Past and present history of any other psychiatric and substance use disorder( except nicotine and caffeine) in GAD patients.

2. Past and present history of any psychiatric disorder for control group.

3. Any other chronic medical, neurological, endocrinal and surgical problem.

All the participants were assessed for serum TSH and serum cortisol. Five ml blood sample was collected in morning hour between 7 to 9AM. ELISA method was used to assess Serum cortisol. Serum TSH was estimated by electro chemiluminescence immunoassay, data was gathered and means were analysed by student’s t test.


Total 60 samples along with age matched control were measured in this study. The mean age of the study group was 23.53 years and that of control group was 23.2 years. Figure 1 shows the comparison of serum cortisol level between control group and study group. The mean serum cortisol of subjects was 284.83±103.47 ng/mL and that of control group was 129.97±80.17 ng/mL. (p<0.0001)(Figure1). The mean TSH level of subjects was 1.39±0.85 μIU/mL and that of control group was 2.43±1.04 μIU/mL. (p<0.0001) (Figure 2)


The present study was conducted on 30 GAD patients attended department of Psychiatry, Geetanjali Medical College and Hospital, Udaipur (Rajasthan). In this study, a significant increase in serum cortisol level was observed in patient group compared to control group(p<0.0001). A significant decreased level of TSH was observed in patient group compared to control group (p<0.001). The results indicate that GAD patients have increased serum level of cortisol and decreased serum levels of TSH as compared to healthy controls. These results are in agreement with previous reports. Benseñor et al4 observed an association of subclinical hypothyroidism with panic disorder, OR =2.55; 95% confidence, 105/0994; and an inverse association between hypothyroidism and GAD at OR=0.75; 95% CI, 059-096. The results are corroborative to our study observations. Similar observation was noted by Yu et al.5 Observed results of hypothyroidism/hyperthyroidism were highly compatible with behaviors of anxiety and depression. 

Rao et al6 observed that thyroid disorders have a strong association with psychiatric disorders, in the study a patient with mixed affective disorder and hypothyroidism was successful in relation to antithyroid medication and mood stabilizers. Keller et al7 reported high cortisol levels in GAD, and levels are higher in elderly individuals with GAD. Physiological aging is associated with a relative increase in the activity of the HPA axis associated with a reduction of mineralocorticoid and glucocorticoid receptors. Mantella et al8 demonstrated that patients diagnosed with GAD displayed increased serum cortisol levels and higher peak cortisol compared with control subjects. Rockel et al9 in hyperthyroid patients observed a significant increase in anxiety, a sense of not feeling well, and emotional irritability as well as a tendency towards depressiveness, and an increased lack of vitality and activity comparing to healthy controls. Robertas et al10 mentioned in their study that the vast majority of patients with hyperthyroidism displayed a psychiatricdisorder such as anxiety, mania, or depression.

Limitations: small sample size, consecutive sampling technique and single centre. It would have been better if standard scale to be used for assessment of GAD and to rule out other psychiatric disorders.


Mental health issues are commonly seen in hormonal disorders. Thyroid dysfunction especially hypothyroidism may associate with generalized anxiety disorder. Alteration in serum cortisol was also seen. There is need of further studies to establish diagnostic or therapeutic importance of these biomarkers in GAD.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

Ethical conduct of research

Authors declare that they received Institutional ethical approval for their scientific work


1. Walker JJ, Terry JR, Lightman SL. Origin of ultradianpulsatility in the hypothalamic– pituitary– adrenal axis. Proc Biol Sci. 2010; 277(1688):1627–33.

2. Strohle A, Holsboer F. Stress responsive neurohormones in depression and anxiety. Pharmacopsychiatry 2003; 36 (Suppl. 3):S207–S214.

3. Subbannayyaa T, Subbannayyab LK, Kamathc SU, Kamathd A. The need to rule out thyroid dysfunction in anxiety disorders. Middle east journal of psychiatry and alzheimers 2012;3(2):3-7.

4. Bensenor IM, Nunes MA, Sander Diniz MF, Santos IS, Brunoni AR, Lotufo PA. Subclinical thyroid dysfunction and psychiatric disorders: Cross-sectional results from the Brazilian Study of Adult Health (ELSA-Brasil) Clin Endocrinol (Oxf) 2015;84:250–6.

5. Yu D, Zhou H, Yang Y, Jiang Y, Wang T. The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats. Horm Behav 2015;69:106–15.

6. Rao MG, Rohilla J, Varambally S, Raveendranathan D, Venkatasubramanian G. Hyperthyroidism presenting as mixed affective state. Gen Hosp Psychiatry 2012;34(6):703.e13-4.

7. Hazarika J, Kalita KN, Sharma M, Saikia S. Thyroid profile in depression: a cross-sectional study from North-East India. Int J Res Med Sci. 2017;5(3):1066-70.

8. Mantella RC, Butters MA, Amico JA, Mazumdar S, Rollman BL, Begley AE, et al. Salivary cortisol is associated with diagnosis and severity of late-life generalized anxiety disorder. Psychoneuroendocrinology 2008;33(6):773–78.

9. Rockel M, Teuber J, Schmidt R, Kaumeier S, Hafner H, Usadel KH. [Correlation of “latent hyperthyroidism” with psychological and somatic changes]. Klin Wochenschr, 1987;65:264-73.

10. Robertas B, Arthur J, Prange Jr. Thyroid disease and mental disorders: cause and effect or only co morbidity? Curr Opin Psychiatry 2010;23(4):366-68.

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