In this section, information is provided on diseases and their treatments that appear to be associated with an increased risk of developing thyroid dysfunction.
Addison's disease is a form of autoimmune destruction of the adrenal gland, resulting in deficiency of glucocorticoid (cortisol) and mineralocorticoid (aldosterone) steroid hormones. Patients with autoimmune adrenal insufficiency may also develop hyperthyroidism or co-existing hypothyroidism, with the latter condition known as Schmidt's Syndrome. Patients with suspected combined deficiency of both glucocorticoid and thyroid hormones should ensure that glucocorticoid supplementation is initiated first prior to treatment with thyroid hormone.
Celiac Disease is an intestinal disorder characterized by sensitivity to gliadin, and antibody formation against the absorptive cells in the intestinal lining, leading to malabsorption of nutrients, weight loss, and diarrhea. The exact reasons why some patients are genetically predisposed to exhibit gluten sensitivity and antibody formation remain unclear Current concepts of celiac disease pathogenesis. Gastroenterology. 2000 Jul;119(1):234-42. Some patients already taking thyroxine may present with TSH elevations due to malabsorption of thyroid hormone as outlined in Celiac disease presenting as resistant hypothyroidism. Thyroid. 2005 Apr;15(4):386-8.
The majority of patients improve following institution of a gluten-free diet. Patients with celiac disease have an increased incidence of antibodies to endocrine cells, and a higher incidence of autoimmune disease such as thyroid disease and diabetes. In some studies, the incidence of thyroid disease is 3x higher in patients with celiac disease. See Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study. Am J Gastroenterol. 2001 Mar;96(3):751-7. Hypothyroidism is more common than hyperthyroidism in patients with celiac disease, as in Celiac disease and autoimmune thyroid disease. Gut. 1994 Jun;35(6):844-6. Some studies suggest that the prevalence of autoimmune antibody formation is increased when patients are not following a gluten free diet. See Importance of gluten in the induction of endocrine autoantibodies and organ dysfunction in adolescent celiac patients. Am J Gastroenterol. 2000 Jul;95(7):1742-8. Conversely, patients with multiple autoimmune endocrine diseases appear to have a higher incidence of celiac disease, as revealed in Celiac disease and autoimmune endocrinologic disorders. Dig Dis Sci. 1999 Jul;44(7):1428-33. Nevertheless, the vast majority of patients with autoimmune thyroid disease will not develop celiac disease, as indicated in Autoimmune thyroid diseases and celiac disease. Eur J Gastroenterol Hepatol. 1998 Nov;10(11):927-31 however some investigators have suggested that physicians maintain a high degree of suspicion for the possible presence of Celiac disease in patients with autoimmune thyroid problems Coeliac disease in patients with autoimmune thyroiditis. Digestion. 2001;64(1):61-5
Diabetes is generally classified as either Type 1 diabetes, formerly known as juvenile or insulin-dependent diabetes, or Type 2, more commonly developing in adult patients. Type 1 diabetes develops as a result of autoimmune destruction of the islet b cells, the insulin producing cells in the endocrine pancreas. Patients with Type 1 diabetes often have circulating antibodies against their islet cells, and thyroid antibodies are commonly detectable in subjects with Type 1 diabetes. Accordingly, hypothyroidism and hyperthyroidism are much more common in patients with Type 1 diabetes, as illustrated in Thyroid Dysfunction in Patients With Type 1 Diabetes: A longitudinal study. Diabetes Care. 2003 Apr;26(4):1181-5.
As Type 2 diabetes and thyroid diseases are both extremely common in the population at large (5-10% of all individuals will develop one or both diseases), the co-existence of type 2 diabetes and thyroid disease in many individuals is also common. A survey of the association between diabetes and autoimmune thyroid disease in children and adolescents contains a lot of information on this topic. See Thyroid Autoimmunity in Children and Adolescents With Type 1 Diabetes: A multicenter survey. Diabetes Care. 2002 Aug;25(8):1346-1350. The levels of thyroid hormones can affect the levels of glycosylated hemoglobin, a marker for the degree of glycemic control, with levels of A1C higher in patients with hypothyroidism and A1C levels were decreased by thyroid hormone replacement Effects of thyroid hormone on glycated hemoglobin and glycated albumin levels in non-diabetic subjects with overt hypothyroidism. Diabetes Care. 2010 Sep 7. [Epub ahead of print]
Down's Syndrome, or Trisomy 21, is a genetic disorder that affects one child in every 800 births in the U.S. and is the most prevalent chromosomal abnormality found in humans. Patients may exhibit some degree of intellectual impairment and are at increased risk of developing several well-defined abnormalities that affect other organ systems. Patients with Down's syndrome have an increased risk of developing thyroid disease, predominantly hypothyroidism, but occasionally hyperthyroidism, usually autoimmune in nature, hence regular screening and early intervention with thyroid hormone replacement seems prudent once a consistent TSH elevation is detected. Even babies with Down's Syndrome exhibit frequent abnormalities in levels of thyroid hormones, as shown in Lower neonatal screening thyroxine concentrations in down syndrome newborns. J Clin Endocrinol Metab. 2003 Apr;88(4):1512-5. See also Thyroid dysfunction in children with Down's syndrome. Acta Paediatr. 2001 Dec;90(12):1389-93. and Thyroid function tests in adults with Down's syndrome. Acta Endocrinol (Copenh). 1978 May;88(1):48-54 and Thyroid dysfunction in Down syndrome. Am J Dis Child. 1985 Jun;139(6):636-9 and Thyroid dysfunction and high thyroid stimulating hormone levels in children with Down's syndrome. J Pediatr Endocrinol Metab. 2002 Nov-Dec;15(9):1543-8.
Hodgkin's disease is a type of lymphoma or tumor of the lymphatic system that is usually treated with radiation and/or chemotherapy. As the neck and mediastinum are frequently in the radiation field, the thyroid gland is often exposed to radiation, resulting in an increased risk of many types of thyroid disorders. Patients with Hodgkin's disease who received radiation to the neck area are at increased risk for development of hypothyroidism, hyperthyroidism, thyroid nodules, and thyroid cancer. Accordingly, follow-up on an annual basis should include some assessment of thyroid structure and function. See Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab. 2000 Sep;85(9):3227-32 and Thyroid diseases after treatment of Hodgkin's disease. N Engl J Med. 1991 29;325(9):599-605.
Hives and urticaria are common disorders of the skin frequently seen in patients with autoimmune thyroid disease. Although many patients with urticaria will also have positive thyroid antibodies and perhaps hypothyroidism or hyperthyroidism, treatment or correction of the thyroid disorder has not been universally shown to influence the course of the itching and urticaria. See Chronic urticaria and autoimmune thyroid disease: is there a link? Autoimmun Rev. 2003 Mar;2(2):69-72. Nevertheless, in a non-randomized study of 20 patients with chronic idiopathic urticaria treated with suppressive doses of thyroxine, significant improvement was noted in 16 patients after 12 weeks of therapy, as described in Improvement of chronic idiopathic urticaria with l-thyroxine: a new TSH role in immune response? Allergy. 2005 Apr;60(4):489-93.
Hypokalemic periodic paralysis is a rare condition associated with hyperthyroidism, low potassium levels, and severe transient muscle weakness, generally thought to be due to genetic abnormality in muscle ion channel function. A non-familial form, thyrotoxic hypokalemic periodic paralysis, has bee described, and many patients have mutations in a potassium channel, Ki2 2.2 Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis Cell. 2010 Jan 8;140(1):88-98
ITP (Idiopathic thrombocytopenic purpura) is a disorder of blood platelets, a circulating fragment of blood cells responsible for ensuring that our blood coagulation system responds appropriately to blood vessel injury by helping blood clots form. When the levels of platelets become abnormally low, or when platelets don't work properly, the risk of bleeding may be increased. Patients with ITP often have circulating antibodies directed against their platelets, in a manner analogous to patients with Graves' disease (GD) that have antibodies directed against their thyroid gland. Both ITP and Graves' disease are autoimmune disorders, and the precise reasons why some immune systems produce these antibodies remains unclear. Nevertheless, patients with GD have a slightly increased risk of developing ITP, and conversely, patients with ITP will have an increased risk of developing autoimmune thyroid disease. There does not seem to be a consistent relationship between progression of ITP and treatment of GD Variable presentation of thrombocytopenia in Graves' disease. Arch Intern Med. 1982 Aug;142(8):1460-4.) although in some instances, treatment of the hyperthyroidism will be associated with improvement in platelet counts. See Graves disease associated with autoimmune thrombocytopenic purpura. Arch Intern Med. 1997 May 12;157(9):1033-6.
Kidney diseases. Although the mechanisms linking the development of hypothyroidism with reduced kidney function are not clear, a large survey of patients detected a highly significant relationship between abnormal kidney function and the presence of hypothyroidism. See Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int. 2005 Mar;67(3):1047-52.
Myasthenia Gravis (MG) is an autoimmune disease characterized by weakness in one or more muscle groups. The disease may be primarily restricted to the eyes (ocular myasthenia) or more generalized involving additional muscle groups. MG is associated with the detection of antibodies against the acetylcholine receptor. These antibodies impair the action of the neurotransmitter chemical acetylcholine which regulate muscle contraction and function. Treatment of the disease is directed at suppressing formation of the antibodies, removing the antibodies, or enhancing the duration of action of acetylcholine. Some patients with MG may also have tumors of the thymus (thymomas) which are often removed surgically to effect therapeutic improvement. Many patients with myasthenia also have co-existing autoimmune thyroid disease. The incidence of both hypothyroidism and hyperthyroidism is increased in patients with MG. Conversely, patients with autoimmune thyroid disease have a slightly increased risk of MG. Both Graves' disease (GD) and MG may affect the eyes, impairing normal eye movement and function. Some patients will have both diseases affecting the eyes at the same time, which can prove challenging diagnostically and therapeutically. See Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis. Thyroid. 2000 Sep;10(9):799-802.
Multiple Sclerosis (MS) is a demyelinating disorder of the nervous system. The cause of MS is unknown, but there is evidence for involvement of the immune system in the development of MS in many patients. Autoimmune thyroid disease may be more common in male patients with MS, but the reasons for this association are not understood. See Prevalence of autoimmune thyroiditis and non-immune thyroid disease in multiple sclerosis. J Neurol. 2003 Jun;250(6):672-5.
Pernicious Anemia (PA) is a disease of the red blood cells that arises as a consequence of defective absorption of vitamin B12, an essential co-factor for hemoglobin and red blood cell production. Patients will present with a decreased hemoglobin level (anemia) and increased size of their red blood cells. In more severe cases, neurological abnormalities of the peripheral nerves may also be present. PA is also an autoimmune disease that develops as a result of defective production of intrinsic factor, a key protein produced by stomach cells that is required for absorption of vitamin B12 from our gastrointestinal tract. Patients with PA also have an increased likelihood of developing Hashimoto's thyroiditis or Graves disease.
Pituitary disease may co-exist with thyroid disease for several reasons. Patients with hypothalamic or pituitary dysfunction may experience compromise of the normal regulatory mechanisms that control thyroid hormone secretion (TRH and TSH) and may develop secondary hypothyroidism. Rarely, pituitary tumors may produce excess TSH, resulting in secondary hyperthyroidism, characterized by elevated levels of thyroid hormones and a non-suppressed TSH. Autoimmune inflammation of the pituitary, known as lymphocytic hypophysitis, may also be associated with co-existing hypo- or hyperthyroidism.
Premature ovarian failure is a condition characterized by premature cessation of ovulation and the early onset of menopause in otherwise healthy women. Patients with this disease often have circulating anti-ovarian antibodies and also exhibit an increased likelihood of developing Hashimoto's thyroiditis or Graves' disease.
Psoriasis or Psoriatic arthritis is characterized by
characteristic skin lesions or patterns of joint inflammation,
respectively, and has been associated with higher rates of concomitant
autoimmune thyroid disease and hypothyroidism High
prevalence of thyroid autoimmunity and hypothyroidism in patients with
psoriatic arthritis. J
Rheumatol. 2006 Oct;33(10):2026-8.
Pulmonary Hypertension is not classically viewed as an autoimmune disorder. Nevertheless, the prevalence of autoimmune thyroid disorders and thyroid gland dysfunction is surprisingly high in patients with this illness, as outlined in High Prevalence of Autoimmune Thyroid Disease in Pulmonary Arterial Hypertension. Chest. 2002 Nov;122 (5): 1668-1673.
Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder characterized by joint inflammation, fatigue, and occasionally, progressive destruction of joint cartilage if the disease is progressive over time. Patients with RA also have circulating autoantibodies against various proteins (Rheumatoid Factor etc) and commonly have antithyroid antibodies. Hence, patients with RA are also at increased risk of developing Hashimoto's thyroiditis or Graves disease. See Familial aggregation of autoimmune thyroiditis in first-degree relatives of patients with juvenile autoimmune thyroid disease. Thyroid. 2003 Mar;13(3):297-300. and Increased Prevalence of Antithyroid Antibodies and Subclinical Hypothyroidism in Children with Juvenile Idiopathic Arthritis. J Rheumatol. 2006 Jan;33(1):164-166
Sarcoidosis is a poorly understood inflammatory disease characterized by the presence of collections of inflammatory cells, known as granulomas, that may affect a number of different organ systems. See Prevalence of hypothyroidism and graves disease in sarcoidosis. Chest. 2006 Aug;130(2):526-32
Systemic Lupus Erythematosis (SLE) is a multisystem autoimmune inflammatory disease characterized by the formation of multiple autoantibodies against different cell proteins and nucleic acids. Also known as lupus, SLE can affect the joints, skin, blood vessels, kidneys, heart, lungs and central nervous system. Patients with SLE also have a higher incidence of other related autoimmune diseases such as Hashimoto's thyroiditis and Graves' disease. Many patients with SLE will have antithyroid antibodies, but may not necessarily develop thyroid disease. See Autoimmune thyroid disease in systemic lupus erythematosus. Ann Rheum Dis. 2002 Jan;61(1):70-2. Similarly, patients with Rheumatoid arthritis or Sjogrens syndrome may also exhibit both arthritis and thyroid dysfunction, as outlined in Thyroid dysfunction in primary Sjogren's syndrome: a long-term followup study. Arthritis Rheum. 2003 Dec 15;49(6):804-9. Patient's with SLE may also exhibit an increased risk of developing papillary thyroid cancer Thyroid cancer in systemic lupus erythematosus: a case-control study J Clin Endocrinol Metab. 2010 Jan;95(1):314-8.
Turner's Syndrome, also known as gonadal dysgenesis is a genetic disorder (45X is most common genotype) that occurs in women and is characterized by the presence of amenorrhea and failure of secondary sexual development. Many patients will also have autoimmune thyroid disease (about 16-20% and thyroid antibodies (about 40%). Surveillance of thyroid function is recommended for patients with Turner's syndrome Care of Girls and Women with Turner Syndrome: A Guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2006 Oct 25; [Epub ahead of print]. For an overview, see Autoimmune thyroid syndrome in women with Turner's syndrome-the association with karyotype. Clin Endocrinol (Oxf). 2001 Aug;55(2):223-6.
Vitiligo is an autoimmune disease characterized by depletion of pigment cells in the skin, resulting in the development of white hypopigmented patches in affected areas. Many patients will exhibit both vitiligo and thyroid disease, usually either Hashimoto's thyroiditis, or Graves' disease. Treatment of the thyroid disease has no effect on the course or progression of the vitiligo. Both adults and children with vitiligo have an increased incidence of thyroid disorders such as Hasimoto's thyroiditis Increased prevalence of chronic autoimmune (Hashimoto's) thyroiditis in children and adolescents with vitiligo. J Am Acad Dermatol. 2005 Aug;53(2):220-3