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Affiliation：Monash University,Victoria 3806,3165,Australia(Leon Piterman，Hui Yang)；University of Melbourne,Victoria 3010,Australia(Fiona Judd，Grant Blashki) ；Alfred Hospital,Victoria 3004,Australia(Sasha Fehily)

The relationship between hormones and mental states is well known,as are the basic neuro-humoral pathways (hypothalamic-pituitary-end organ axes) which mediate hormonal changes.However,the precise mechanisms by which such hormonal changes lead to mental state changes have not been clearly identified.Some syndromes with causal links to endocrine abnormalities have been well recognized and described such as Thyroid disease,Cushing′s syndrome,and Addison′s disease.By contrast,although anxiety and depressive symptoms are often reported to be associated with diseases such as Diabetes,Menopausal Syndrome,and Testosterone deficiency states,this varies considerably from individual to individual and the pathways that mediate such psychological distress are less well understood.Nevertheless from a practical perspective,in most cases rectifying the hormonal problem usually leads to some improvements in the mental health of the individual.

It is important to be aware that some drugs used to treat mental illnesses may also impact on endocrine function.The most common are the anti-psychotics which cause weight gain and may trigger the metabolic syndrome including diabetes.Lithium treatment may be associated with thyroid deficiency and abnormalities in calcium metabolism necessitating regular monitoring of thyroid function,renal function and calcium levels.

This paper focuses on the relationship between thyroid disease and mental illness.Both hyperthyroidism and hypothyroidism may present with psychiatric symptoms.Although not inevitably the case,hypothyroidism is more usually linked with depression and hyperthyroidism tends to be more closely linked with anxiety symptoms.In younger patients the symptoms are often classical,yet in older people they may be masked by an array of typical and atypical physical symptoms making diagnosis more elusive.A cautious approach is to consider routine thyroid function testing of all patients with anxiety /depression,especially if there is an hint of thyroid symptoms or signs[1].

1 Case Study

Mrs Chong is a 28 year old mother of 2 young children aged 5 and 2.She is married to an engineer and she works part time as a medical laboratory technician.She has a long history of generalized anxiety disorder and is excessively worried about the well being of her children.Over the past month her anxiety has been worse,for the first time she has been experiencing panic attacks,and she has taken diazepam from time to time.She has also noted weight loss of 2 kg over this period of time and a dislike for the hot weather.Climbing stairs has caused shortness of breath on several occasions.She also is having trouble sleeping and feels her heart pounding and finds herself tearful and depressed at times.

2 Initial questions

2.1 Question1：What additional symptoms will you search for in the history?

2.2 Question2：What will be the focus of your clinical examination?

2.3 Question3：What is your probability diagnosis?

2.4 Question4：What tests will you order?

3 Answers

3.1 Answer1：What additional symptoms will you search for in the history? It is important to take a full a psychiatric history particularly asking about other symptoms of anxiety and depression including appetite disturbance,loss of energy,troubles with concentration and memory,lack of interest in and enjoyment in activities,and depressive cognitions such as feelings of worthlessness,guilt and hypochondriacal thoughts.If it appears her symptoms are all explained by worsening anxiety or the onset of depression,you should check for possible triggers that may have exacerbated both.

Given that some of her symptoms cannot readily be attributed to anxiety and depression (e.g.dislike of hot weather and shortness of breath) it is necessary to explore other possible causes for her presentation.For example.,weight loss,dislike for hot weather and possible palpitations raise suspicion of thyrotoxicosis.So it is also worth checking for symptoms such as loose bowel motions,muscular pains or weakness,neck soreness or noticing a lump in the neck need to be raised.

3.2 Answer2：What will be the focus of your clinical examination? A thorough clinical examination is required,in the mental state examination you need to check affect and mood and also thought content.In the physical examination a full examination is required with particular emphasis on the cardiovascular system and the neck.In this case Mrs Chong′s findings were:BP 120/70 P 110 and regular,afebrile,heart and lungs were normal on examination.Examination of the neck revealed some noticeable swelling of the thyroid gland and tenderness over the gland.There was no associated cervical lymph node enlargement.

3.3 Answer3：What is your probability diagnosis? The probability diagnosis is thyrotoxicosis.Of note she has a history of generalized anxiety disorder and these symptoms seem to have been exacerbated by the thyroid dysfunction.There are several causes of thyrotoxicosis.These include,Hashimoto′s (auto immune) thyroiditis,non specific thyroiditis (possibly viral),Primary Graves disease and a toxic thyroid nodule.Rarely factitious thyrotoxicosis may be present in patients inappropriately taking thyroxine for weight reduction.

3.4 Answer4：What tests will you order? This differential diagnosis list needs further clarification using blood tests and ultrasound or scans.Appropriate tests include; Full Blood count and ESR,CRP,Electrolytes including Calcium,ECG to check heart rhythm,Thyroid function tests,Thyroid antibodies a Thyroid ultrasound,and if available,a Thyroid Scan.

4 Test results

The results indicate a normal blood film apart from a mild lymphocytosis,but elevated ESR of 55 and CRP 60.Electrolytes are normal,ECG shows a sinus tachycardia,Thyroid antibodies are negative and Thyroid function tests as follows:Free T430.5 pmol/L( 11-21),free T38.5 pmol/L (3.2-6.4),TSH 0.3 mU/L ( 0.5-5.5).Ultrasound shows diffuse enlargement of the thyroid gland with no localized lesions.

5 Further questions

5.1 Question5：What it the likely diagnosis ?

5.2 Question6：What is treatment plan based on these results?

6 Further answers

6.1 Answer5：What it the likely diagnosis ? Based on these findings the most likely diagnosis is subacute thyroiditis possibly viral in aetiology.Importantly you also note she has ongoing problems with her anxiety.

6.2 Answer6：What is treatment plan based on these results? The treatment plan will need to address both her anxiety as well as the new problem of thyrotoxicosis.It is important to reduce the peripheral manifestations of thyrotoxicosis as well as controlling the release of the thyroid hormone.Where the GPs are not confident in managing the patient on their own referral or consultation with an endocrinologist is essential[1-2].

However,in managing Mrs Chong,provided she has no history of asthma or other contraindications,she may be started on a beta-blocker for example,propranolol is often used in this clinical setting.This should slow the heart rate,reduce the sweats and the loose bowel motions as well as reducing some of the peripheral manifestations of anxiety.

In addition commencing neomercazole at an initial starting dose will slow T4production but this may take 1-2 weeks to produce an effect.Ongoing monitoring of thyroid function as well as full blood count to ensure there are no complications from neomercazole is required (Note that rarely it can cause a serious blood dyscrasia,so

patients are advised if they get a sore throat or infection,easy bruising or mouth ulcers to contact the doctor immediately.)

Length of treatment required is variable.In this case of subacute thyroiditis treatment may last several months and there is a risk that once the inflammatory process stops that Mrs Chong may go from being hyperthyroid to hypothyroid and need some thyroid hormone replacement[3].Eventually she may return to a euthyoid (normal thyroid level) state.During this time it will be important to monitor her mood,as depressive symptoms often develop with hypothyroidism,as well as physical symptoms of thyroid deficiency and of course thyroid function tests.

Treating her thyroid problems may or may not lead to an improvement in her anxiety symptoms.As she has a pre-existing anxiety disorder you will not expect her anxiety problems to necessarily resolve completely,but as she becomes less thyrotoxic they may improve to some extent back to her baseline level.

As this improvement may take some time,she may require additional treatment for her anxiety in the interim.Your choice of treatment will be influenced by what treatments (either pharmacological or psychological) she has found helpful in the past.If you decide to use diazepam to manage the current exacerbation of her symptoms it is essential that this be for short-term treatment only due to tolerance and the potential for addiction.If she requires longer-term medication,a selective serotonin reuptake inhibitor is the treatment of choice.

7 Comments

This case illustrates the need for GPs to be vigilant when managing patients with established psychiatric diagnoses.New physical illness may develop at any time and if such illnesses share symptoms with the psychiatric condition,they are easily missed.Thyroid disease is common particularly in women and despite the likely ongoing nature of her generalized anxiety disorder,diagnosing a physical cause for worsening of her anxiety enables an opportunity for provide more comprehensive treatment which addresses the physical and mental aspects of her presentation,This biopsychosocial approach also boosts patient trust in the GP-patient relationship.

1 John Murtagh.Murtagh′s textbook of general practice[M].5th edition.Australia：McGraw Hill，2011:211-218.

2 Simon NM,Blacker D,Korbly NB,et al.Hypothyroidism and hyperthyroidism in anxiety disorders revisited:New data and literature review[J].J Affect Disord,2002,69(1-3):209-217.

3 Demet MM,Ozmen B,Deveci,et al.Depression and anxiety in hyperthyoidism[J].Arch Med Res，2002，33(6):552-556.