In Brief

Thyroid disease is commonly found in most types of . This article defines the prevalence of thyroid disease in diabetes and elucidates through case studies the assessment, diagnosis, and clinical management of thyroid disease in diabetes.

Diabetes Control in Thyroid Disease

Thyroid disease is a pathological state abnormality. Several studies, including that can adversely affect diabetes con- the Colorado study, have documented trol and has the potential to negative- a higher prevalence of thyroid disease Jennal L. Johnson, MS, RNC, FNP, ly affect patient outcomes. Thyroid in women, with prevalence rates rang- BC-ADM, CDE disease is found commonly in most ing from 4 to 21%, whereas the rate in forms of diabetes and is associated men ranges from 2.8 to 16%.1 with advanced age, particularly in Thyroid disease increases with age. In and underlying the Colorado study, the 18-year-olds autoimmune disease in type 1 dia- had a prevalence rate of 3.5% com- betes. This article defines the preva- pared with a rate of 18.5% for those lence of thyroid disease in diabetes, ≥ 65 years of age. discusses normal physiology and The prevalence of thyroid disease in screening recommendations for thy- diabetes has been estimated at 10.8%,2 roid disease, and elucidates through with the majority of cases occurring as case studies the assessment, diagnosis, (~ 30%) and subclini- and clinical management of thyroid cal hypothyroidism (~ 50%).2 Hyper- disease and its impact on diabetes. thyroidism accounts for 12%, and postpartum thyroiditis accounts for Thyroid Disease Prevalence 11%.2 Of the female patients with The prevalence of thyroid disease in , 30% have thyroid dis- the general population is estimated to ease, with a rate of postpartum thy- be 6.6%, with hypothyroidism the roid disease three times that of the most common malady.1 Participants normal population. Ostensibly, this is attending a health fair in Colorado (n because of the higher prevalence of = 25,862) were screened for thyroid thyroid disease in women, as well as disease, using thyroid-stimulating hor- the link to autoimmune disease. Once mone (TSH) and thyroxine (T4) mea- one autoimmune disease occurs, it is surements. Of the participants, 9.5% not uncommon for a different autoim- were found to have an elevated TSH mune disease to be present. level. Also, 6% of study participants There are also reports that the were diagnosed with thyroid disease prevalence of thyroid disease in type 2 before the screening. However, 40% diabetes is higher than in the general of those already diagnosed had elevat- population.3 Whereas the Fremantle ed TSH levels, indicating inadequate Diabetes Study found a 8.6% preva- treatment. In the undiagnosed popula- lence of subclinical hypothyroidism in tion with TSH elevations, 9.9% were women with type 2 diabetes in found to have an unrecognized thyroid Australia,4 a study of the prevalence 148 Diabetes Spectrum Volume 19, Number 3, 2006 8 of autoimmune thyroid disease in type children. Iodine deficiency leads to ations in thyroid secretion Coexisting Diseases Diabetes and / From Research to Practice 2 diabetes in Jordan reported an over- decreased thyroid hormone synthesis, rates, facilitating a more steady state. all prevalence rate of 12.5%, with which in turn leads to increased TSH Standard laboratory assays measure subclinical hypothyroidism at 5%.5 secretion and increased gland growth the total free and bound thyroid hor- or goiter. Gland size, however, does mone levels of T4 and T3 unless free Thyroid Anatomy and Physiology not indicate thyroid function. hormone levels are specifically A thorough understanding of the Therefore, a goiter can be present in requested. Free hormone levels are anatomy and physiology of the thy- hypothyroidism, , or helpful in evaluating thyroid function roid gland allows diabetes clinicians euthyroidism. in states of decreased or increased to understand the rationale for specif- The thyroid gland is divided into TBG. ic assessments and to rapidly identify lobules that have a distinct vascular Thyroid hormone exerts influences thyroid abnormalities. The thyroid is supply. Each lobule has 20–40 follicles, on numerous body systems, including the largest endocrine gland, weighing and follicles are the basic functioning growth and development, muscular ~ 20 g. It is shaped like a butterfly or unit of the thyroid gland. The lumen of function, sympathetic nervous system shield and is derived from the base of each follicle is filled with viscous col- function, cardiovascular system, and the tongue.6 The thyroid gland has loid identified as the glycoprotein thy- . For exam- significant blood flow; when com- roglobulin. Thyroglobulin contains the ple, thyroid hormone is necessary for pared by tissue weight, it has more molecular structure of thyroid hor- maturation and differentiation during blood flow than the kidney.7 mones and is the precursor of all thy- development. Children with hypothy- roid .9 Thyroperoxidase roidism show bone maturation delays Understanding the Role of the (TPO) is a membrane-bound enzyme as well as delayed or absent puberty. Thyroid found on the surface of the follicular Children with thyroid deficiency have Thyroid physiology is based on a reg- cell. It is necessary to catalyze iodide stunted growth because inadequate ulatory feedback system typically into an active intermediate, an impor- thyroid hormone secretion lowers found in endocrine systems.7 The tant step in thyroid hormone . Thyroid hormone hypothalamus secretes thyrotropin- synthesis.7 Thyroglobulin and TPO also plays an important role in lung releasing hormone (TRH), which antibodies are useful thyroid laborato- maturation.7 stimulates the anterior pituitary gland ry test evaluations that can identify are necessary to secrete thyrotropin or TSH. TSH potential harm to the synthesis of thy- for normal fetal and neonatal brain increases iodide uptake and oxidation roid hormone from an autoimmune development by regulating neuronal that leads to organification and cou- process. proliferation and differentiation, pling, which are necessary steps to The follicle is surrounded by a sin- myelinogenesis, neuronal outgrowth, produce the thyroid hormones T4 and gle layer of epithelial cells and and synapse formation. The critical triiodothyronine (T3). TSH also stim- enclosed by a basement membrane. time for brain development starts in ulates growth and vasculature of the The basement membrane has parofol- utero and continues to age 2. thyroid that could potentially lead to licular cells that have contact with Deficiency of thyroid hormone during a goiter if excessive. Of the thyroid follicle cells and produce calcitonin.7 this important time can lead to struc- hormone secreted, 90% is T4, and Iodine is taken up as inorganic iodide tural and physiological impairment 9% is T3.7 T3 derives from deiodina- via the “iodide trap” in the follicular resulting in brain damage or severe tion of T4; therefore, 80% of circulat- cell. This aspect of thyroid physiology neurological impairment.7 This ing T3 is from T4.7 During serious is important because the thyroid is process cannot be reversed once com- debilitating illness or , T3 the only gland that takes up iodine, pleted, which is the reasoning behind production is reduced, possibly as a which allows for scanning and treat- universal screening for congenital control mechanism to reduce the ment of the thyroid gland using hypothyroidism. metabolic rate, which may be useful radioiodine. Hypothyroidism in adults can lead during recovery. After thyroid hormones are synthe- to dullness, decreased reflexes, lethar- Thyroid hormones enter cells by sized and secreted into the , they gy, delayed cognitive function, and diffusion and carrier-mediated trans- are bound to serum carrier proteins excessive , as well as psychologi- port and bind to nuclear TSH recep- TBG, thyroxine-binding prealbumin, cal disturbances. Correcting the tors. TSH receptors are found on the and albumin. The affinity of the T3 underlying thyroid abnormality can surface of the follicular cells within receptor is much higher (~ 10 times) reverse impaired neurological func- the thyroid as well as on adipocytes, than that of T4.7 The majority of T4 tioning in adults. Hyperthyroidism in lymphocytes, fibroblasts, and gonads. (99.96%) and T3 (99.6%) are bound, adults can also result in insomnia, This is important because TSH stimu- and binding is affected by certain decreased reflex time or hypereflexia, lates adipocyte lipolysis. T4, and to a physiological or pathological states restlessness, excitability, and lack of small degree T3, circulating in the that increase or decrease TBG. focus and concentration.7 serum inhibits secretion of TSH and Estrogen increases found in pregnan- Thyroid hormones have metabolic TRH, thereby completing the feed- cy, estrogen replacement, and birth functions that serve to control the back cycle. Transport and binding of control pills increase TBG, whereas basic hormone metabolic rate. Basic thyroid hormone is carried out by thy- androgens, , and mal- hormone metabolic rate is decreased roxine-binding globulin (TBG). nutrition decrease TBG.7 in hypothyroidism and increased in Normal thyroid hormone synthesis Free or unbound thyroid hormone hyperthyroidism. Thyroid hormones requires an adequate iodine intake of enters cells and exerts a biological stimulate most metabolic pathways 150 g in adolescents and adults, 200 effect. The bound hormone serves as a and are either anabolic and catabolic. in pregnancy, and 90–120 in reservoir that buffers short-term alter- In hypothyroidism, protein synthesis 149 Diabetes Spectrum Volume 19, Number 3, 2006 is decreased, as is protein degradation, Thyroid Hormone Effects on Diabetes individuals. The American Assoc- which results in decreased percentage The effect on carbohydrate metabo- iation of Clinical Endocrino-logists of protein body weight. Alternatively, lism can potentially lead to disruptions (AACE) recommends a screening TSH hyperthyroidism increases protein in diabetes control. Although the glu- in women of childbearing age before synthesis and degradation, resulting in cose level does not always change, pregnancy or during the first wasting.7 Thyroid hormones are there can be an abnormal response to trimester.10 lipolytic as well as lipogenic. tolerance testing in hyperthy- In 2005 AACE, ATA, and the However, there is usually more degra- roidism because glucose rises faster Endocrine Society (TES) published a dation compared to synthesis. In than normal.7 Additionally, excessive consensus statement regarding screen- hypothyroidism, there is decreased fat thyroid hormones increase the rate of ing for subclinical thyroid dysfunc- synthesis and degradation, leading to digestive tract absorption and thyroid tion.11 The authors of the consensus increased body fat and elevated lipids. hormone levels and therefore increase statement recommended the measure- In hyperthyroidism there is increased resistance and insulin degrada- ment of anti-TPO antibodies in evalu- fat synthesis and degradation, result- tion. ating patients with subclinical ing in decreased lipids. In hyperthyroidism, syn- hypothyroidism because those who Thyroid hormones exert a direct thesis and degradation increase, lead- are antibody positive have a higher effect on muscles. In hypothyroidism, ing to decreased glycogen levels.3 risk of developing overt thyroid dis- this can lead to myopathies, muscle Glucose absorption is increased, as ease.11 For patients with type 1 dia- stiffness with associated discomfort well as utilization and production. betes, it is recommended to test for and slowness of movements, Peripheral tissues have increased anti-TPO antibodies at diagnosis. If increased muscle mass (mechanism rates of glucose uptake that can lead anti-TPO antibodies are present, it is unknown), and impaired muscle to the aforementioned exaggerated recommended that clinicians perform , leading to glycogen glucose peak during a timed glucose annual TSH screening. In type 2 dia- accumulation.7 In hyperthyroidism, test. Insulin requirements are betes, it is recommended that clini- myalgias can also occur as well as increased, and, if not addressed ade- cians measure TSH at diagnosis of muscle weakness, muscle wasting, quately, control can decompensate, diabetes and every 5 years thereafter.2 and muscle , particularly in the leading to diabetic . proximal muscles in the legs, making Additionally, in patients with unde- Case Studies it difficult to climb. tected diabetes, hyperthyroidism can Within the cardiovascular system, unmask diabetes because glucose lev- Case Presentation 1 thyroid hormones increase heart rate, els can be abnormally elevated M.J. is a 70-year-old woman with myocardial contractility, and cardiac because of increased insulin resis- type 2 diabetes. She is evaluated in an output by increased sinus node stimu- tance.3 Increased dosages of diabetes outpatient endocrine clinic. She was lation and direct effects on the medications may be necessary in diagnosed with diabetes recently and myocardium.7 In hyperthyroidism, those already treated, until thyroid has not completed a comprehensive excess thyroid hormone produces function is stabilized and resultant diabetes education program. Her fast- myocardial hypertrophy. Thyroid hor- glucose stabilization occurs. ing blood glucose levels are 110–115 mones act as positive inotropes as In hypothyroidism, liver secretion mg/dl, and she does not check 2-hour well as positive chronotropes indepen- of glycogen decreases, but so does postmeal blood glucose readings. She dent of circulating . degradation, leading to increased lev- has no known macrovascular or Resultant electrocardiogram changes els of glycogen. Absorption of glucose microvascular complications. show left ventricular hypertrophy. from the gastrointestinal tract is She comes to clinic with complaints Stoke volume, heart rate, and mean slowed, and glucose utilization is of fatigue and . She is tak- systolic ejection velocity increase with slowed in the peripheral tissues. The ing glimiperide, 4-mg tablet twice decreased peripheral resistance availability of gluconeogenic substrate daily. It is interesting to note that the because of increased production of is decreased. Additionally, the insulin initial presented vasodilators, with evidence of warm, half-life is prolonged, insulin levels are and the routine screening results are moist skin and increased pulse pres- lower, and insulin secretion is consistent with the metabolic syn- sure. reduced, which may lead to reduced drome or diabetes. Unless the clinician The opposite occurs in hypothy- insulin requirements. If exogenous screened for thyroid disease, the roidism. Peripheral resistance is nor- insulin is not decreased, abnormalities could be attributed to mal or slightly increased by decreased may occur. It is likely that glucose lev- the usual course of type 2 diabetes. secretion of vasodilators, resulting in els will stabilize during hypothy- M.J.’s physical exam is normal cutaneous vasoconstriction evidenced roidism treatment. But when thyroid except that she has a 45-g goiter. Her by cold, dry skin. The ECG in function is normalized, this may lead laboratory results are: hypothyroidism shows inverted T to higher blood glucose levels and • TSH: 5.6 IU/ml (normal 0.29–3.0) waves and low P, QRS, and T wave adverse effects on glycemic control. • T4: 5.5 ug/dl (normal: 4.5–12.5) amplitudes. Excess thyroid hormone • Positive for anti-TPO antibodies resembles increased sympathetic ner- Screening Recommendations (normal: negative) vous system activity by increased The American Thyroid Association • Total : 220 mg/dl (nor- beta-adrenergic stimulation, leading (ATA) recommends testing thyroid mal 130–200) to increased heart rate, , and function in all adults beginning at age • HDL cholesterol: 34 mg/dl (normal excessive sweating.7 This stimulation 35 and reassessing thyroid function 30–80) could interfere with diabetic patients’ every 5 years. More frequent testing is • : 158 mg/dl (normal ability to recognize hypoglycemia. indicated in high-risk or symptomatic 35–160) 150 Diabetes Spectrum Volume 19, Number 3, 2006 • LDL cholesterol: 140 mg/dl (nor- er for female subjects, and is higher in symptoms within 6–8 weeks after ini- Coexisting Diseases Diabetes and / From Research to Practice mal ≤ 70) whites and Mexican Americans than tiating therapy. It is 15 • Hemoglobin A1c (A1C): 6.8% (nor- in African Americans. Anti-TPO important that she closely monitor her mal 4.0–6.3) antibodies may be positive before clin- blood glucose levels because improved M.J. has dyslipidemia and an ele- ical disease occurs and therefore may thyroid function may increase her glu- vated glucose average, as evidenced by be an indicator of early thyroid dis- cose, leading to more . her A1C elevation. She has a goiter, ease. Although still controversial, She may need additional diabetes TSH elevation with a normal T4, and treatment of subclinical hypothy- medication intervention. she tested positive for anti-TPO anti- roidism is indicated in patients who bodies, indicating subclinical hypothy- are elderly, have elevated cholesterol, Case Presentation 2 roidism. have TSH > 10 mU/l, and have other L.M. is a 38-year-old man with type 1 Treatment goals include initiating symptoms of hypothyroidism.16 diabetes who uses an . levothyroxine therapy, completing The goal of thyroid replacement He presents with , short- diabetes education, and improving therapy is to render the patient ness of breath, decreased exercise tol- glycemic control. The lipid levels will euthyroid without over- or underre- erance, fatigue, muscle weakness, likely decrease with levothyroxine placement, with a TSH goal between double vision, blisters on lower legs, therapy. However, because diabetes is 0.3 and 3.0 IU/ml unless thyroid can- , hyperglycemia, mood a risk equivalent for cardiovascular cer is present.17 Levothyroxine is a swings, /nervousness, heat disease (CVD), a cholesterol-lowering narrow therapeutic index drug, intolerance, and increased frequency agent such as a is also indicated. which means that there is a “narrow of bowel movements. Physical exami- The statin can be initiated before toxic to theurapeutic ratio with sig- nation reveals: determining the effect of thyroid hor- nificant clinical consequences of • Skin: moist and warm, blisters with mone replacement on her lipid levels excessive or inadequate treatment” an orange peel appearance on both because the purpose of the statin is that could impact bone, pregnancy, lower legs cardiovascular prevention. or heart.18 Within the past several • Head/eyes/ears/nose/throat: bilater- years, several generic levothyroxine al proptosis, stare, lid lag, scleral Discussion products have come to the market, injection, double vision with eye The Rotterdam Study (n = 1,149) and the U.S. Food and Drug motility, thyroid 60+ g and firm showed that subclinical hypothy- Administration (FDA) has deemed • Heart: tachycardia, heart rate 106 roidism may be a risk factor for them to be bioequivalent to some bpm, regular rhythm without mur- CVD.12 Participants were female and branded preparations. The major mur > 55 years of age. Subclinical hypothy- thyroid organizations (AACE, TES, • Lungs: clear to ausculatation and roidism was defined as a TSH > 4.0 and the ATA), have voiced concern percussion mU/L with a normal free T4 level. about the methodology the FDA used • Lower extremities: pretibial myx- Subclinical hypothyroidism was a to determine bioequivalence and rec- emdema in lower legs strong risk factor for atherosclerosis ommended that levothyroxine not be • Neurological exam: hyperreflexia and (MI) in substituted for other preparations.19 elderly women.12 Subclinical hypothy- The organizations’ joint position Laboratory results included: roidism was found to be a greater risk statement recommends that patients • T4: 22.0 ug/dl (normal 4.5–12.5) for MI in postmenopausal women be maintained on the same brand of • TSH: < 0.01 IU/ml (normal 0.29– than hyperlipidemia, diabetes, previ- levothyroxine that they have been tak- 3.0) ous smoking, or hypertension. ing and, in the event they are switched • Thyroid-stimulating immunglobu- Additional studies have looked at the to another brand or generic product, lin: 300% (normal < 130%) benefits of treating subclinical measure a serum TSH in 6 weeks and • Blood glucose: 345 mg/dl (normal hypothyroidism, and the results make adjustments as indicated. < 100) showed that treatment to lower TSH Patients should be educated about • A1C: 9.2% (normal 4.0–6.3) resulted in lower total and LDL cho- using the same brand of medication Imaging revealed a 77% uptake in 4 lesterol levels.13 Alternatively, long- during treatment and, when picking hours (normal 4–12%) and bone den- term data from the Whickham cohort up medications at the pharmacy, be sity T scores of 1.1 for spine and published in 1996 found no higher told to indicate that the brand of thy- 2.1 for hip. rate of from CVD in subjects roid medication should not be Treatment strategies include - with subclinical hypothyroidism com- changed without first checking with blocker therapy, an increase in pared with euthyroid subjects, con- their provider. insulin, and oral steroids for the eyes, tributing to the controversy surround- The initial dose of levothyroxine as well as discussion of options— ing treatment of subclinical hypothy- therapy is determined by the underly- including radioiodine therapy, roidism.14 ing cause of the disease, severity of surgery, or anti-thyroid therapy—and The National Health and Nutrition dysfunction, and health and age of the provision of education. Examination Survey evaluated men, person being treated. This is highly women, and children from 1988 to individualized; however, the adage in Discussion 1994 and measured TSH and antithy- the elderly or those with underlying There is an autoimmune link (HLA roid antibody levels to evaluate the CVD is to start low (typically 25 g markers) between type 1 diabetes and status of thyroid functioning, using daily) and go slow with drug Graves’ disease. The prevalence of population data.15 The study found titration.2 Graves’ disease with type 1 diabetes that the prevalence of antithyroid The woman in this case study is has been reported to be 2.7% in men antibodies increases with age, is high- likely to see improvement in her and 2–19% in women.20 Patients 151 Diabetes Spectrum Volume 19, Number 3, 2006 should be monitored closely to evalu- with TSH ≥ 6 mU/l and 8.1% in 3Ober K: Polyendocrine syndromes. In Medical ate their response to thyroid therapy women with TSH ≥ 10 mU/l com- Management of Diabetes Mellitus. Leahy J, Clark N, Cafalu W, Eds. New York, Marcel as well as their diabetes control. As pared with 0.9% in women with TSH Dekker, 2000, p. 699–717 Graves’ disease stabilizes, insulin < 6 mU/l.21 In the first trimester, preg- requirements may decrease. It may be nant women are the sole source of 4Chubb SA, Davis WA, Inman Z, Davis TM: Prevalence and progression of subclinical beneficial to place the patient in this thyroid hormones for their developing hypothyroidism in women with type 2 diabetes: case study on a glucose sensor because fetuses. the Fremantle Diabetes Study. Clin Endocrinol the glucose levels will be elevated ini- It is important to screen women of (Oxf) 62:480–486, 2005 tially, and higher doses of insulin will childbearing age and those in the first 5Radaideh AR, Nusier MK, Amari FL, Bateiha be needed. Once successful treatment trimester of pregnancy for hypothy- AE, El-Khateeb, MS, Naser AS, Ajlouni KM: is completed, close monitoring will roidism to optimize thyroid function. Thyroid dysfunction in patients with type 2 dia- also be necessary to avoid hypo- History of another autoimmune disor- betes mellitus in Jordan. Saudi Med J glycemia when insulin requirements der or a family history of thyroid dis- 25:1046–50, 2004 decrease. ease increases the possibility of 6Capen CC: Anatomy. In Werner and Ingbar’s hypothyroidism, which underlines the The Thyroid. 7th ed. Braverman LE, Utiger RD, Case Presentation 3 need for screening. For patients newly Eds. Philadelphia, Lippincott-Raven, 1996, p.19–38 R.D. is an 18-year-old woman with diagnosed with thyroid disease, type 2 diabetes diagnosed 5 years ago. levothyroxine therapy should be initiat- 7Porterfield SP: The thyroid gland. In Endocrine Since her diagnosis, she has lost 50 lb ed as soon as possible and at a dose as Physiology. St. Louis, Mo., Mosby, 1997, p. 57–81 through a diet and exercise program. close as possible to the anticipated She is normoglycemic. Coexisting requirement. Dosage increases may be 8Delange FM, Ermans A: Iodine deficiency. In health problems include polycystic seen as high as 50% because of increas- Werner and Ingbar’s The Thyroid. 7th ed. Braverman LE, Utiger RD, Eds. Philadelphia, ovarian disease and vitiligo. Family es in thyroid hormone binding globulin Lippincott-Raven, 1996, p. 296–316 history is significant for thyroid dis- in women already diagnosed with thy- 9 ease. She was taking until roid disease before pregnancy.22 Wartoski L: The thyroid gland. In Principles and Practice of and Metabolism. a recent positive pregnancy test. Additional considerations include 3rd ed. Becker KL, Ed. Philadelphia, Lippincott The patient complains of fatigue, the effects of diabetes on pregnancy. Williams & Wilkins, p. 308–471 , constipation, and feeling cold. In early pregnancy, patients with dia- 10U.S. Preventive Service Task Force: Screening Her weight loss plateaued several betes can be affected by pregnancy- for thyroid disease: recommendation statement. months ago, and now her weight is related hormones that cause increased Ann Intern Med 140:125–127:2004 slowly increasing. insulin secretion, decreased insulin 11Hossein GR, Tuttle M, Baskin HJ, Fish LH, Physical examination is unremark- requirements, and decreased glucose Singer PA, McDermot MT: Suclinical thyroid able except a 30-g thyroid. produced by the liver, which can lead dysfunction: a joint statement on management Laboratory results include: to hypoglycemia.23 During the third from the American Association of Clinical • A1C: 6.2% (normal <4.0-6.3) trimester, the opposite occurs. Endocrinologists, the American Thyroid Association, and the Endocrine Society. J Clin • Free T4: 0.6 ug/dl (normal 0.9–1.9) Estrogen and can cause signif- Endocrinol Metab 90:581–585:2005 • TSH: 13.4 IU/ml (normal 0.29–3.0) icant , therefore • Positive for anti-TPO antibody potentially causing hyperglycemia. 12Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman CM: Subclinical hypothy- (normal: negative) Close monitoring of blood glucose roidism is an independent risk factor for athero- during pregnancy allows for medica- sclerosis and myocardial infarction in elderly A referral to a dietitian is recom- tion, diet, and exercise alterations to women: the Rotterdam Study. Ann Intern Med mended to evaluate adequate calorie optimize diabetes control while nor- 132:270–278:2000 intake for diabetes, pregnancy, and malizing thyroid function. 13Huber G, Mitrache M, Guglielmetti M, Huber appropriate weight gain. Swift initia- P, Staub J-J: Predictors of overt hypothyroidism tion of levothyroxine therapy is indi- Summary and natural course: a long-term follow-up study cated because the patient is hypothy- The prevalence of thyroid disease is in impending thyroid failure. Presented at the ATA Annual Meeting, 1997. Colorado Springs, roid and pregnant. Initial symptoms higher in diabetes because of the Colo. should improve within 4–6 weeks increased age of diabetic patients as 14 unless they are secondary to the preg- well as an autoimmune link. Untreat- Cooper D: Subclinical hypothyroidism. N Engl J Med 345:260–265, 2001 nancy rather than hypothyroidism. ed or inadequately treated thyroid The 1990 Haddow Pregnancy disease can negatively impact dia- 15Hollowell JG, Staihling NW, Flanders WD, Study (n = 92) showed that euthyroid betes control. Pregnancy is a chal- Hannon WH, Gunter EW, Spencer CA, Braverman LE: Serum TSH, T4, and thyroid children of hypothyroid mothers had lenging state associated with diabetes antibodies in the population (1988 adverse results and hypothyroid chil- and can be complicated by the effects to 1994): National Health and Nutrition dren from hypothyroid mothers had of untreated or undertreated thyroid Examination Survey (NHANES III). J Clin fetal brain and IQ abnormalities.21 disease. Endocrinol Metab 87:489–499:2002 Euthyroid women with positive 16Ayala AR, Danese MD, Ladenson P: When to antithyroid antibodies had higher treat mild hypothyroidism. Endocrinol Metab rates of miscarriage, women with References Clin North Am 29:399–415:2000 higher TSH levels had a more than 17 1Carnaris GJ, Manowitz NR, Mayor G, American Association of Clinical threefold increase in risk of very pre- Ridgway EC: The Colorado Thyroid Disease Endocrinologists: Clinical practice guidelines for term delivery, and those with positive Prevalence Study. Arch intern Med the evaluation and treatment of hyperthyroidism 160:526–534, 2000 and hypothyroidism November/December 2002. antithyroid antibodies had a twofold Endocrine Pract 8:457–469:2002 increase in preterm delivery. The rate 2 Wu P: Thyroid disease and diabetes. Clinical 18 of fetal death was 3.8% in women Diabetes 18:38–39:2000 Blakesly V, Awni W, Locke C, Ludden T, 152 Diabetes Spectrum Volume 19, Number 3, 2006 Granneman G, Braverman L: Are bioequivalence Williams JR, Knight GJ, Gagnon J, O’Heir CE, requirement in the late first trimester of diabetic Coexisting Diseases Diabetes and / From Research to Practice studies of levothyroxine socium formulations in Mitchell ML, Hermos RJ, Waisbren SE, Faix JD, pregnancy. Diabetes Care 24:1130–1136:2001 euthyroid volunteers reliable? Thyroid Klein RZ: Maternal thyroid deficiency during 14:191–200:2004 pregnancy and subsequent neuropsychological

19 development of the child. N Engl J Med Jennal L. Johnson, MS, RNC, FNP, AACE, TES and ATA joint position statement 341:549–555:1999 of the use and interchangeability of thyroxine BC-ADM, CDE, is an endocrinology products [article online]. Available from 22Emerson C: Thyroid disease during and after nurse practitioner at Endocrinology http://www.aace.com/pub/pdf/guidelines/AACE- pregnancy. In Werner and Ingbar’s The Thyroid. Associates in Phoenix, Ariz. TES-ATA-ThyroxineProducts.pdf 7th ed. Braverman LE, Utiger RD, Eds.

20 Philadelphia, Lippincott-Raven, 1996, p. Vanderpump MP, Tunbridge WM: The epi- 1021–1031 Note of disclosure: Ms. Johnson has demiology of thyroid disease. In: Werner and received honoraria for speaking Ingbar’s The Thyroid. 9th ed. Braverman LE, 23Jovanovic L, Knopp R, Brown Z, Conley M, engagements from Abbott Utiger RD, Eds. Philadelphia, Pa., Lippencott Park E, Mills J, Metzger B, Aarons J, Holmes L, Williams & Wilkins, 2005, p. 474–482 Simpson J, the National Institute of Child Health Laboratories, which manufactures products for the treatment of thyroid 21 and Human Development Diabetes in Early Haddow JE, Palomaki GE, Allan WC, Pregnancy Study Group: Declining insulin disease.

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