neuropsychiatric cp of thyroid disease.pptx

New lecture about how the thyroid disease can present by neuro symptom and psych symptom

1. Thyroid: Clinical relevance in psychiatry. Dr.Cijo Alex

2. Overview Introduction Applied anatomy and physiology Clinical features of thyroid disorders Role of thyroid in -Depression -Psychosis -Cognitive dysfunction -MR - Anxiety Thyroid dysfunction induced by psychotropic medications Therapeutic indications ,dosing and clinical guidelines for thyroid replacement. Conclusion

3. Introduction Thyroid disorders are common , up to 5% of population. The thyroid axis is involved in the regulation of cellular differentiation and metabolism in virtually all nucleated cells , so that thyroid disorders have wide spread manifestations. Thyroid gland one of the most common endocrine glands related with psychiatric disorders Abnormal thyroid hormone levels are found in 33% of psychiatric patients compared to 5% in general population. Almost all thyroid abnormalities in psychiatric patients are in women.

4. Functional Anatomy & Physiology The thyroid is a highly vascular gland located in the neck ,anterior to trachea ,between cricoid cartilage and suprasternal notch. Consists of two elongated lateral lobes interconnected by an isthmus. The Thyroid gland secretes predominantly thyroxine (T4) and a small amount of triiodothyronine (T3). Iodide is the key substrate to maintain thyroid function.

5. The HPT Axis

6. The most common thyroid disorders include 1)Hypothyroidism. 2)Hyperthyroidism.

7. Hypothyroidism : Inadequate synthesis of thyroid hormones Overt : Low T3 & T4 , High TSH : Symptomatic Sub clinical : biochemical evidence of thyroid hormone deficiency in patients with few or no apparent clinical features of hypothyroidism N- T3 & T4 , High TSH : Asymptomatic

8. Subclinical hypothyroidism By definition subclinical hypothyroidism refers to biochemicalevidence of thyroid hormone deficiency with no or few apparent clinical features. No universally accepted guidelines exist for managing this condition. However there is no risk in thyroxine supplementation in such cases and may be useful in preventing a full blown hypothyroidism.

9. Clinical features of Hypothyroidism Weight gain, Fatigue,Cold intolerence Constipation Bradycardia,Hypertension Malar flush,Myxoedema,Dry skin and Hair. Menorrhagia,Infertility,Impotence Delayed DTR,Cerebellar Ataxia. Depression,Psychosis ( Myxoedema madness)

10. Clinical features of Hyperthyroidism Weight loss, Heat intolerance. Diarrhoea Tachycardia Sweating, Palmar erythema . Gynaecomastia , Impotence. Tremors,Hyperreflexia Anxiety, Irritability,Emotional lability .

11. Neuropsychiatric manifestations of thyroid disorders. Primary thyroid disorders including both hypothyroidism and hyperthyroidism may be accompanied by various neuropsychiatric manifestations ranging from mild depression and anxiety to overt psychosis. Dysphoria , anxiety, irritability, emotional lability, tremors, proximal muscle weakness , and impairment in concentration constitute the classical neuropsychiatric symptoms occurring in hyperthyroidism  On the other hand, hypothyroid patients frequently demonstrate features of depression, cognitive dysfunction, apathy, and psychomotor slowing. In severe forms of hypothyroidism, clinical symptoms may mimic that of melancholic depression and dementia 

12. -Dementia ( Cognitive Deficits-MC 50%) -Affective Disorders -Depression(40%) -Acute Mania-Rare -Anxiety Disorders (30%) - Psychosis ( Myxoedema madness)(<5%) - -Mental Retardation(cretinism) -Depersonalization & Derealization ( Case reports ) - Late Luteal Phase Dysphoric Disorder. Neuropsychitry of Neurometabolic & Neuroendocrine Disorders –Kaplan And Sadocks Comprehensive Textbook of Psychiatry –Ch 2.14;612-13

13. Role of Thyroid in depression Some studies have reported that upto 10% of patients with depression are having hypothyroidism as a co morbidity. As correctly said , its difficult to be euthymic unless some one is in euthyroid state. Thyroid supplementation can covert an antidepressant resistant person into a responsive person.So it holds great role in treatment resistant depression, as an adjuvant to antidepressants. No evidence exists till now that correlates with thyroid function and its efficacy in augmentation therapy. Ie,irrespective of the thyroid function, thyroxine supplementation can be used as an adjuvant in treating depressed patients. However the MOA of thyroxine in treating depression is still not clear. Ref:Consise textbook of clinical psychiatry ,Kaplan & Saddock,IIIrd Edition ,Pg:553

14. Epidemiology - 17.3%preexisting hypothyroidism 13.3% in general population. ( Engum et al, 2002) Manifestations: Subsyndromal depressive symptoms only Treatment resistant depression Rapid cycling affective disorder Atypical depression Clinical features : Typical picture - mental lethargy & general dulling of personality Cognitive deficits - more prominent Typical mood change - towards apathy, irritability Usually family history of hypothyroidism is + ve

15. Subclinical Hypothyroidism and Depression Less severe Doubles -Risk of major depression. Reduce -efficacy of antidepressant treatment Response to T3 augmentation better - Kaplan And Sadock’s : Comprehensive Textbook of Psychiatry 9th Edition 2008 Subclinical hypothyroidism - renamed as “Minimal Thyroid Insufficiency (MTI)” Approximately 5-15 % of patients with subclinical hypothyroidism progress to overt hypothyroidism per year ( Wiersinga et al, 1995)

16. Many meta analyses and RCT have reconfirmed the role of thyroid supplementation in refractory depression. Ref:R . Aronson, H. J. Offman , R. T. Joffe , and C. David Naylor, “ Triiodothyronine augmentation in the treatment of refractory depression: a meta-analysis,” Archives of General Psychiatry, vol. 53, no. 9, pp. 842–848, 1996.

17. Depression Vs Hypothyroidism : When depression starts in the Neck. When someone develops depression, the brain usually becomes the focus of attention. But it can be in fact only hypothyroidism which also shares some clinical features of depression. Although researchers aren't entirely sure why there is a link between hypothyroidism and depression, it is likely that some people are taking antidepressants when they should really be taking thyroid medication alone. Ie , Hypothyroidism can be the sole cause of low mood . So can we call it depression or is it just a feature of hypothyroidism? This question gains importance especially when the biological underpinnings of depression is being under covered. Ref: http://www.health.harvard.edu/newsletters/Harvard_Mental_Health_Letter/2011/July/when-depression-starts-in-the-neck

18. Role of thyroid in psychosis Studies have shown that 5 to 15% of myxedematous patients show psychotic features. Asher in 1949 first described myxedema madness. Psychosis usually emerges years after onset of physical findings C/F include delusions, visual and auditory hallucinations , perseveration , loosening of associations and paranoia.

19. Onset - acute/ subacute , fluctuating, paranoid Perceptual abnormality - visual and other hallucinatory distortions Associated mental slowing & cognitive impairment (esp., recent memory) Rapidly developing myxedema - agitation, irritability, alternate periods of restlessness and lethargy, hyper sexuality psychosis (Hall et al, 1983)

20. Role in cognitive dysfunction Hypothyroidism can lead to impaired consciousness , memory disturbances and psychomotor slowing. Most commonly affected- working memory and executive function. Elderly - Progressive dementia (Pseudo dementia) Improve with thyroid supplements Chronic thyroid hormone deficiency - not always reversible -Irreversible damage in the CNS

21. Role of thyroid in MR Neonatal hypothyroidism can result in MR (Cretinism)and is preventable if diagnosis is made at birth. Seen in children who live in the iodine deficient regions Prevalence: 1 in 3000 to 4000 newborns. Often born to mothers with Iodine deficiency. C/F: Majority are normal at birth In <10% diagnosis is based on prolonged jaundice, feeding problems, enlarged tongue, delayed bone maturation & umbilical hernia.

22. Mental and growth retardation Permanent neurological damage- If treatment delayed. Diagnosis based on the measurement of the TSH & T4. Early & adequate treatment - Normal IQ levels. Iodine deficiency- One of the most common causes of the preventable mental deficiency (Harrison-text book of internal medicine 17 th edn ; Ch 335;)

23. Psychiatric disorders due to hyperthyroidism Depression Anxiety Disorders(10-20%) Hyperthyroid dementia (Cognitive impairment)(5-10%) Hypomania or mania(2-5%) Psychosis(2-5%) Neuropsychitry of Neurometabolic & Neuroendocrine Disorders –Kaplan And Sadocks Comprehensive Textbook of Psychiatry –Ch 2.14;612-13 Delirium Insomnia

24. Role of Thyroid in anxiety Hyperthyroidism can lead to features of anxiety. Rarely hypothyroidism can also cause anxiety. Many experts believe that imbalances in serotonin, dopamine, and GABA in the brain are potential causes of anxiety features and thyroid may be playing a vital role in their regulation Ref:http ://www.mayoclinic.com/health/thyroid-disease/AN00986

25. Prevalence rate 62% ( Kathol et al, 1986 ) Anxiety disorders dominate in hyperthyroidism Generalized anxiety syndrome : 40% of thyrotoxic Patients. (Hall et al, 1986) Episodic anxiety, with subjective awareness of tachycardia or arrhythmia Correlation exists with both the physical symptoms of hyperthyroidism and the level of the circulating thyroid hormone unlike depressive symptoms ( Kathol et al.,1986)

26. Thyroid Abnormality in other Psychiatric conditions. Periodic Catatonia : periodic catatonia ( Gjessing et al, 1935) Premenstrual Syndrome : S tudy of baseline and TRH-stimulated thyroid function in 45 healthy women - 13.3%- subclinical hypothyroidism ( Korzekwa et al.1996) ADHD : Increased prevalence of thyroid abnormalities in children with ADHD than controls. (Weiss et.al 93)

27. Post partum : At six weeks following delivery 43% of antibody positive women experience mild to moderate depressive episode compared to 28% of antibody negative women in a double blind study 145 antibody positive women and 229 antibody negative women. (Harris et al, 1992) Post traumatic stress disorder Persistent and disproportionate elevation in both total and free T3 in relation to free T4. (Mason et al 1994) Eating disorder : Studies of the effects of reduced caloric intake on healthy adult female noticed Euthyroid profile (normal plasmaT4 & decreased plasma T3) . ( Fichter et al.,1986)

28. Psychotropic drugs causing Thyroid dysfunction Lithium Carbamazepine TCA’s Quetiapine

29. Role of thyroid in Li therapy Li is a drug used as a mood stabilizer and an adjuvant antidepressant . It can cause reversible hypothyroidism. So TFT is advisable before initiating and during Li therapy.

30. Endocrine effects of Lithium Clinical Hypothyroidism- 2 to 15% Subclinical- 19% Chemical- 50% Goitre - 5% Hyperthyroidism- 0.7% - Mohandas et.al.,Lithium use in Special Populations.Indian Journal of Psychiatry 49(3);Jul-Sep,2007

31. Management of Lithium Induced Hypothyroidism

32. CBZ Increases T4 and T3 metabolism through induction of hepatic microsomal enzyme Negligible incidence of clinical hypothyroidism Thyroid supplementation : Rarely needed. TCAs - Blocking uptake of thyroid hormone into the neurons. - Kaplan And Sadock’s : Comprehensive Textbook of Psychiatry 9th Edition 2008

33. Therapeutic indications and guidelines of Thyroid supplementation Thyroid hormones are indicated as adjuvant antidepressants and in rapid cycling BP 1 disorder. Also used in replacemnt therapy for patients with Li treatment. Common AE. -Unusual at the augmention doses. - Headache,increase in BP,sweating ,tremors C/I -Cardiac diseases, HTN

34. Most trials with tricyclic antidepressant. Case – reports with SSRI. First placebo controlled trial – by Prange & his colleagues in 1969/70; by adding T3 to imipramine in the depressed patient. T3 has been evaluated more extensively than T4 as an augmentation strategy for treatment resistant depression. Kaplan And Sadock’s : Comprehensive Textbook of Psychiatry 9th Edition 2008

35. Comparison of lithium & Triiodothyronine augmentation of TCA’s Joffe et al, 1993 50 outpatients; unipolar non psychotic depression; failed 5 weeks of TCA ( Desipramine or Imipramine ) Randomized double blind, placebo controlled study of 2 wks duration Both liothyronine & lithium were effective than placebo ≥ 50% reduction in HDRS Baumgartner et al 1994 Open case series of 6 non-RCAD Patient’s who were treatment refractory Excellent prophylactic response on adding high dose T4

36. Dosing and clinical guidelines. Usual augmentation dose – 25 to 50 ug . An adequate trial should last for 2-3 weeks. If successful,should be continued for 2 months.

37. T3– Started at 25µg/day single dose After 1 week- insufficient response, no side effect increase to 37.5- 50µg/ day in divided doses After 2 weeks • Responders- Continue for 2 months and then taper it off • Non responders- Taper 12.5µg every 3-7 days T4– Started at 100µg/day After 1 week –insufficient response increase by 25-50µg every week Maximum 500µg/day Response usually within 2weeks. If none taper by 50µg every 3 days

38. Common Adverse effects Abrupt discontinuation– Iatrogenic hypothyroidism. Minor side effect (usually reported) warmth, Flushing ,sweating, palpitation weakness, diarrhea insomnia, anxiety. More severe – cardiac decompensations , arrhythmias, CHF .( Caution in Elderly ) Long term – muscle wasting, weight loss, osteoporosis

39. Conclusion Role of thyroid in psychiatry remains only partially known. Until there are large randomized treatment trials that address the important clinical questions involved in the diagnosis and management of sub clinical thyroid disease, we will have to rely on imperfect and necessarily vague recommendation.

40. Thank You