A Case Study of Psychosis
In 2003, a 73-year-old-woman was admitted to the hospital while experiencing unprecedented visual and auditory hallucinations.[1] Since blood work indicated she was in a state of hypothyroidism, she was treated with both risperidone (for the hallucinations) and low-dose thyroid replacement medicine for the hypothyroid state.[2] After two-weeks, the patient discontinued risperidone, continuing only with the thyroid medication, and the hallucinations never returned.[3]
This clinical example is one case study in a mounting body of research correlating the relationship between thyroid and mental health. While it is estimated that 12% of Americans will develop a thyroid condition at some point in their lives,[4] 60% of those affected in the United States are not aware they may have a problem with their thyroid.[5]
Connections to Psychiatric Diagnoses
Hirtz et al., (2020) state that psychological impairments affect up to 30% of adults diagnosed with thyroid dysfunction.[6] Similarly, a study conducted by Herda et al., (2021) of 243 patients determined there was a close relationship between thyroid disease and mental health, including the diagnosis of behavior disorders.[7] However, though a relationship between thyroid disease and mental health disorders has been well-established in recent decades, it is often unclear which is developed first,[8] and patients can be diagnosed with a psychiatric designation before a thyroid condition is detected.[9]
The wide variety of presentations of thyroid dysfunction can sometimes lead to a delayed or missed diagnosis.[10] Yet thyroid function tests (TFTs) in psychiatric patients still remain debatable, in part because thyroid function markers can be affected by acute stress, illicit substances, psychiatric medications, and inflammatory responses.[11]
Image Source: Cleveland Clinic (2022) [12]
How the Thyroid Works
The thyroid gland is located in the neck and is butterfly-shaped.[13] Because the hormones produced by this gland regulate the way energy is used in the body, thyroid changes can affect nearly every organ, including the heart and brain.[14] This production is normally stimulated by the hypothalamus, which sends thyroid-stimulating hormones (TSH) into the bloodstream causing the thyroid to produce thyroxine (T4) and triiodothyronine (T3). T3 and T4 regulate how a body uses energy, which can impact a person’s temperature, weight, nervous system, and muscle strength.[15] In cases of hypothyroidism (i.e., underactive thyroid) the thyroid does not respond accurately to TSH, which causes T3 and T4 to remain low, while TSH accumulates.[16] In hyperthyroidism (i.e., overactive thyroid) there is an overproduction of the thyroid hormone, causingT3 and T4 to be elevated, while TSH remains low.[17]
Further, iodine is required for a body to properly produce thyroid hormones. Since iodine is an essential mineral (i.e., the body cannot produce it), table salt has been supplemented with iodine in the United States since the late 1920s.[18]
Hypothyroidism
Approximately 80% of thyroid disorders in the U.S. are caused by an underactive thyroid gland (hypothyroidism),[19] which is a result of the thyroid gland failing to sufficiently produce thyroid hormones.[20] Hypothyroidism is associated with a wide range of psychiatric and neuropsychological disorders including depression, anxiety, delusions of persecution, attention deficit, psychomotor retardation, and memory impairments.[21]
The knowledge that hypothyroidism affects mental health goes back over a century. It was first linked with psychosis by the Committee on Myxedema of the Clinical Society of London in 1888 when the committee found that half of the 109 patients they studied with myxedema (a physical phenomenon observed in some hypothyroid patients) had hallucinations and delusions, primarily when the disease was advanced.[22] This later led to the coining of the term “myxedema madness” in 1949 to describe the relationship between psychosis and hypothyroidism.[23]
Hyperthyroidism
An overactive thyroid can produce an excess of thyroid hormones (T3 and T4), which increases the body’s metabolism and is described as hyperthyroidism.[24] Symptoms of hyperthyroidism can include mood swings, tension, anxiety, interrupted sleep, lack of patience, and panic attacks.[25] Additionally, out of those diagnosed with hyperthyroidism, up to 69% have been found to experience depression.[26] Some symptoms of hyperthyroidism (e.g., weight loss, increased energy, and agitation) are similar to those observed in episodes of mania.[27] Grave’s disease, an autoimmune disorder that causes the body to produce too much thyroid hormone, is the most common cause of hyperthyroidism.[28]
Hashimoto’s Thyroiditis
Hashimoto’s Thyroiditis (HT) is an auto-immune disease in which the body’s immune system attacks the thyroid’s hormone producing cells.[29] The development of autoimmunity may be caused by stressful life events, puberty, giving birth or menopause.[30] In regions with sufficient iodine intake, such as in the United States, HT is the most common cause of hypothyroidism.[31] In some cases, HT may also cause a temporary enlargement of the thyroid gland leading to hyperthyroidism.[32]
Patients with HT tend to report symptoms of depression and anxiety, which may impact quality of life.[33] Research conducted by Leyhe & Mussig (2014) found that HT patients may experience cognitive and affective disturbances even when in a state of euthyroid (when thyroid levels are considered to be normal).[34] It is hypothesized that the high levels of thyroid antibodies, which are present in patients with Hashimoto’s encephalopathy (a rare disorder that may be associated with HT), may cause brain alterations and could result in lower psychological well-being.[35] Patients with Hashimoto’s encephalopathy suffer from mental health impairments and are sometimes misdiagnosed with psychiatric conditions since individuals affected may experience changes in their personality, depression, anxiety, emotional instability, or failure to understand basic concepts.[36]
Bipolar Disorder
Current research indicates there is a complex relationship between thyroid function and bipolar disorder (BD). In 2007, Vonk et al., found that autoimmune thyroiditis was related to both BD and to the genetic vulnerability that makes a person susceptible to developing BD.[37] Another study conducted by Cole et al., (2002) of patients in the depressed phase of bipolar 1 disorder found they were sensitive to thyroid fluctuations, even when results were considered to be in the normal range.[38] Similarly, a study conducted by Zhao et al., (2021) on 291 subjects with bipolar disorder found that there were significant differences in thyroid functions between participants experiencing manic episodes and those experiencing depressive ones.[39]
This relationship is further complicated by the effect of commonly prescribed psychiatric medications on thyroid function. Lithium, a prevalent treatment for BD, has been associated with hypothyroidism, the development of goiters, hyperthyroidism due to thyroiditis, and in rare cases Grave’s disease.[40] Similarly, quetiapine and valproic acid (two other medications used to treat BD) have both been shown to affect thyroid function.[41,42] Since thyroid abnormalities are common amongst patients with BD, and some of the medications used to treat BD, it is recommended that patients undergoing treatment regularly have their thyroid levels tested to prevent changes in mood due to hormone imbalances.[43]
Anxiety
Approximately 60% of people diagnosed with hyperthyroidism and 30% of those diagnosed with hypothyroidism are affected by anxiety.[44] The correlation between symptoms of thyroid malfunction and anxiety are so similar that Grave’s disease, an immune-system disorder that results in hyperthyroidism, can at times be misdiagnosed as a panic disorder.[45] An investigation conducted by Dr. Juliya Onofriichuk from Kyiv City Clinical Hospital, and summarized by the European Society of Endocrinology in 2020, found that patients experiencing panic attacks showed signs of inflammation of the thyroid gland even though thyroid function and levels fell within normal categories.[46] Dr. Onofriichuk noted this study illustrates the complex relationship between anxiety and the endocrine system and urges doctors to consider this relationship when treating patients with anxiety.[47]
Depression
An analysis conducted by Siegmann et al., (2018) found that the chances of developing symptoms of clinical depression were 3.3 times higher in patients diagnosed with hypothyroidism compared to healthy individuals in control groups.[48] This correlation between depression and hypothyroidism has been hypothesized for years, but results of studies are often conflicting, leaving the relationship difficult to determine.[49] Dayan & Panicker (2013) note that in subjects without thyroid disease, studies have indicated that there is no relationship between thyroid function and depression; yet those being treated for thyroid disease present a relationship between thyroid function and mental health.[50] Additionally, Asamoah (2020) adds that symptoms of depression are estimated to be reported by 60% of patients with hypothyroidism, and the symptoms of hypothyroidism are also similar to those with depression that it is sometimes difficult to distinguish between the two.[51]
When to Speak to a Doctor
Though the relationship between thyroid and mental health is well-documented, it is complex. If a person has a family history of thyroid disorders or is experiencing symptoms that may be the result of a thyroid-related condition, it is recommended they speak with a psychiatrist or primary care physician to determine if thyroid testing is needed.
Contributed by: Theresa Nair
Editor: Jennifer (Ghahari) Smith, Ph.D.
References
1 Heinrich TW, Grahm G. Hypothyroidism presenting as psychosis: Myxedema madness revisited. Prim Care Companion J Clin Psychiatry. 2003;5(6):260-266. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC419396/. Accessed Nov 10, 2022. doi: 10.4088/pcc.v05n0603.
2 Ibid.
3 Ibid.
4 Watson K. Are thyroid conditions and depression linked? Healthline Web site. https://www.healthline.com/health/thyroid-and-depression. Updated 2019. Accessed Nov 12, 2022.
5 Is thyroid disease causing your moodiness? St. Luke's Health Web site. https://www.stlukeshealth.org/resources/thyroid-disease-behind-your-mood-swings. Updated 2019. Accessed Nov 12, 2022.
6 Hirtz R, Keesen A, Hölling H, Hauffa BP, Hinney A, Grasemann C. No Effect of Thyroid Dysfunction and Autoimmunity on Health-Related Quality of Life and Mental Health in Children and Adolescents: Results From a Nationwide Cross-Sectional Study. Frontiers in endocrinology (Lausanne). 2020;11:454-454. doi:10.3389/fendo.2020.00454
7 Herda J, Okoński P, Parfin A, Wdowiak K, Kos M. Thyroid diseases and mental illness together with behavioural disorders versus mental illness together with behavioural disorders and thyroid diseases. Zdrowie publiczne. 2021;131(1):35-40. doi:10.2478/pjph-2021-0007
8 Ibid.
9 Heinrich & Grahm (2003)
10 Estabrook K. Hypothyroidism: An important diagnostic consideration for the psychiatrist. Psychiatric Times. 2013;30(7). https://www.psychiatrictimes.com/view/hypothyroidism-important-diagnostic-consideration-psychiatrist.
11 Garnier KA, Ismail KA, Moylan S, Harvey R. Thyroid function testing in an inpatient mental health unit. Australasian psychiatry : bulletin of the Royal Australian and New Zealand College of Psychiatrists. 2016;24(3):256-260. doi:10.1177/1039856215618522
12 Thyroid hormone. Cleveland Clinic Web site. https://my.clevelandclinic.org/health/articles/22391-thyroid-hormone. Updated 2022.
13 St. Luke’s Health (2019)
14 Hyperthyroidism (overactive thyroid). National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | National Institute of Health Web site. https://www.niddk.nih.gov/health-information/endocrine-diseases/hyperthyroidism. Updated 2021. Accessed Nov 16, 2022.
15 Triiodothyronine (T3) tests. Medline Plus | National Library of Medicine | NIH Web site. https://medlineplus.gov/lab-tests/triiodothyronine-t3-tests/#:~:text=T3%20is%20one%20of%20two,how%20your%20body%20uses%20energy. Updated 2021. Accessed Nov 28, 2022.
16 Thyroid Deficiency and Mental Health. Vol 23. Harvard Health Publications Group; 2007:4-5.
17 Hyperthyroidism (overactive). American Thyroid Association Web site. https://www.thyroid.org/hyperthyroidism/. Updated 2022. Accessed Nov 28, 2022.
18 Iodine deficiency. American Thyroid Association Web site. https://www.thyroid.org/iodine-deficiency/#:~:text=Iodine%20is%20an%20element%20that,cannot%20make%20enough%20thyroid%20hormone. Updated 2022. Accessed Nov 28, 2022.
19 Harvard Publications Group (2007)
20 Martino G, Caputo A, Vicario CM, et al. Interrelations between mental health, generic and thyroid-related quality of life in patients with Hashimoto’s thyroiditis receiving levothyroxine replacement. Mediterranean Journal of Clinical Psychology. 2021;9(2):1-22. doi:10.13129/2282-1619/mjcp-3072
21 Leyhe T, Müssig K. Cognitive and affective dysfunctions in autoimmune thyroiditis. Brain, behavior, and immunity. 2014;41(1):261-266. doi:10.1016/j.bbi.2014.03.008
22 Heinrich & Grahm (2003)
23 Ibid.
24 Staff MC. Hyperthyroidism (overactive thyroid). Mayo Clinic Web site. https://www.mayoclinic.org/diseases-conditions/hyperthyroidism/symptoms-causes/syc-20373659#:~:text=Hyperthyroidism%20(overactive%20thyroid)%20occurs%20when,treatments%20are%20available%20for%20hyperthyroidism. Updated 2020. Accessed Nov 28, 2022.
25 St. Luke’s Health (2019)
26 Watson (2019)
27 Garnier et al. (2016)
28 NIDDK (2021)
29 Staff MC. Hashimoto's disease - symptoms and causes. Mayo Clinic Web site. https://www.mayoclinic.org/diseases-conditions/hashimotos-disease/symptoms-causes/syc-20351855. Updated 2022. Accessed Nov 16, 2022.
30 Leyhe & Mussig (2014)
31 Ibid.
32 Hashimoto's disease. University of Michigan Health Web site. https://www.uofmhealth.org/conditions-treatments/endocrinology-diabetes-and-metabolism/hashimotos-disease. Accessed Nov 16, 2022.
33 Martino et al. (2021)
34 Leyhe & Mussig (2014)
35 Yalcin MM, Altinova AE, Cavnar B, et al. Is thyroid autoimmunity itself associated with psychological well-being in euthyroid Hashimoto’s thyroiditis? Endocrine journal. 2017;64(4):425-429. doi:10.1507/endocrj.EJ16-0418
36 Hashimoto encephalopathy. NORD (National Organization for Rare Disorders) Web site. https://rarediseases.org/rare-diseases/hashimoto-encephalopathy/. Updated 2018. Accessed Nov 28, 2022.
37 Vonk R, Schot ACvd, Kahn RS, Nolen WA, Drexhage HA. Is autoimmune thyroiditis part of the genetic vulnerability (or an endophenotype) for bipolar disorder? Biological Psychiatry. 2007;62(2):135-140. https://www.biologicalpsychiatryjournal.com/article/S0006-3223(06)01112-7/abstract. Accessed Nov 12, 2022. doi: 10.1016/j.biopsych.2006.08.041.
38 Cole DP, Thase ME, Mallinger AG, et al. Slower treatment response in bipolar depression predicted by lower pretreatment thyroid function. Am J Psychiatry. 2002;159(1):116-121. Accessed Nov 14, 2022. doi: 10.1176/appi.ajp.159.1.116.
39 Zhao S, Zhang X, Zhou Y, et al. Comparison of thyroid function in different emotional states of drug-naïve patients with bipolar disorder. BMC endocrine disorders. 2021;21(1):210-210. doi:10.1186/s12902-021-00869-5
40 Lazarus JH. Lithium and thyroid. BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM. 2009;23(6):723-733. doi:10.1016/j.beem.2009.06.002
41 Ramaswamy S, Siddiqui Z, Saharan S, Gabel TL, Bhatia SC. Quetiapine-induced hypothyroidism. J Psychiatry Neurosci. 2005;30(1):57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC543843/. Accessed Nov 18, 2022.
42 Epure D, Matei M, Nita S, Sandu M, Teleanu D, Teleanu R. SUBCLINICAL HYPOTHYROIDISM AND VALPROIC ACID TREATMENT IN CHILDREN WITH EPILEPSY. Research and science today. Published online 2014:129-.
43 Lambert CG, Mazurie AJ, Lauve NR, et al. Hypothyroidism risk compared among nine common bipolar disorder therapies in a large US cohort. Bipolar Disord. 2016;18(3):247-260. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089566/. Accessed Nov 18, 2022. doi: 10.1111/bdi.12391.
44 Thyroid disease and anxiety: What you need to know. Psych Central Web site. https://psychcentral.com/anxiety/depressed-or-anxious-check-your-thyroid. Updated 2022. Accessed Nov 18, 2022.
45 Yasuda M, Kumakura J, Oka K, Fukuda K. A case of thyroid storm caused by Graves’ disease misdiagnosed as panic attack due to panic disorder. BioPsychoSocial medicine. 2021;15(1):1-11. doi:10.1186/s13030-021-00211-4
46 Thyroid inflammation linked to anxiety disorders. European Society of Endocrinology | EurekAlert! Web site. https://www.eurekalert.org/news-releases/655029. Updated 2020. Accessed Nov 18, 2022.
47 Endocrinology ESo. Thyroid inflammation linked to anxiety disorders. https://medicalxpress.com/news/2020-09-thyroid-inflammation-linked-anxiety-disorders.html. Updated 2020. Accessed Nov 18, 2022.
48 Siegmann EM, Müller HHO, Luecke C, Philipsen A, Kornhuber J, Grömer TW. Association of Depression and Anxiety Disorders With Autoimmune Thyroiditis: A Systematic Review and Meta-analysis. JAMA psychiatry (Chicago, Ill). 2018;75(6):577-584. doi:10.1001/jamapsychiatry.2018.0190
49 Dayan CM, Panicker V. Hypothyroidism and Depression. European thyroid journal. 2013;2(3):168-179. doi:10.1159/000353777
50 Ibid.
51 Asamoah T. The link between hypothyroidism and depression. Good RX Health Web site. https://www.goodrx.com/conditions/hypothyroidism/depression. Updated 2020. Accessed Nov 18, 2020.