Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report.

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hyperthyroidism 4 endocrinologydiseases
hypothyroidism 54 endocrinologydiseases
lactose intolerance 3 endocrinologydiseases
obesity 1 endocrinologydiseases
osteoporosis 4 endocrinologydiseases
sunitinib 1 endocrinologydiseasesdrugs
amyloidosis 1 endocrinologydiseases

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sunitinib 34110 include phenytoin, carbamazepine, and rifampin. A number of kinase inhibitors, including imatinib and sunitinib , appear to influence thyroxine requirements through what is likely a class effect [[114]–[116]]. Moreover,
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amyloidosis 19206 malabsorption in patients with cystic fibrosis [[9], [79]–[81]]. Cystic fibrosis can be complicated by amyloidosis [[82], [83]] that can have a direct effect on the thyroid [[9], [84]]. In 2009, Morris discussed nephrotic
hyperthyroidism 5484 can indicate thyroid dysfunction. However, it is not uncommon to discover symptoms of both hypo- and hyperthyroidism in the context of diagnostic findings that are within the desired reference range specified by the current
hyperthyroidism 5705 current treatment guidelines [[18]]. Supratherapeutic doses of levothyroxine, which can induce iatrogenic hyperthyroidism , should not be used as a strategy to suppress hypothyroidism symptoms. In the panel’s experience,
hyperthyroidism 12623 knowledge of the prescribing physician. Most of the cases resulted in either mild symptoms of hypo-or hyperthyroidism and/or unexpected thyroid function tests that were outside normal limits [[43]].Drugs that treat GI
hyperthyroidism 23438 consequence of excessive replacement [[98]].While it is generally accepted that lengthy periods of hyperthyroidism affect bone mass density (BMD) and can increase the risk of osteoporosis, there is significant controversy
hypothyroidism 97 Title: Journal of Endocrinological InvestigationDiagnosis and management of treatment-refractory hypothyroidism : an expert consensus reportM. CentanniS. BenvengaI. SachmechiPublication date (epub): 7/2017Publication
hypothyroidism 1331 should take a systematic approach to managing patients whom they suspect of having treatment-refractory hypothyroidism . This may include searching for, and adjusting, occult medical conditions and/or other factors that
hypothyroidism 1995 medication adjustments and their consequences for both patients and clinicians.IntroductionPrimary hypothyroidism is considered to be refractory to oral thyroxine when there is biochemical or clinical evidence of hypothyroidism
hypothyroidism 2109 is considered to be refractory to oral thyroxine when there is biochemical or clinical evidence of hypothyroidism [serum level of thyroid-stimulating hormone (TSH) above the upper target level, usually 4.5 mU/L following
hypothyroidism 2901 (Table 1) [[3]–[8]]. This consensus paper provides current thinking on the causes of refractory hypothyroidism and recommendations for its diagnosis and management.Table 1Causes of treatment-refractory hypothyroidismDecreased
hypothyroidism 3008 hypothyroidism and recommendations for its diagnosis and management.Table 1Causes of treatment-refractory hypothyroidism Decreased bioavailability Poor adherence to, or tolerability of, drug therapy Maldigestion due to patient-related
hypothyroidism 3843 antibodies Inappropriate tablet storageTSH thyroid-stimulating hormone [[3]–[6], [8]]BackgroundRefractory hypothyroidism is a clinical condition that is increasingly recognized worldwide [[8]–[10]]. Even though its prevalence
hypothyroidism 4608 target when using levothyroxine [[11]–[14]]. Since levothyroxine is the first-line treatment for hypothyroidism [[18], [19]] and one of the most widely used drugs in the US with more than 115 million prescriptions
hypothyroidism 5168 therapy: 18, 27, 18, 15, 28%; Excessive thyroxine therapy: 14, 21, 22, 18, 14% [[11]–[15]]Refractory hypothyroidism —clinical and laboratory findingsDiagnosis of refractory hypothyroidism is both art and science. The
hypothyroidism 5241 14% [[11]–[15]]Refractory hypothyroidism—clinical and laboratory findingsDiagnosis of refractory hypothyroidism is both art and science. The traditional diagnostic tools such as laboratory tests (TSH, free (F) T4,
hypothyroidism 5767 levothyroxine, which can induce iatrogenic hyperthyroidism, should not be used as a strategy to suppress hypothyroidism symptoms. In the panel’s experience, such patients may be referred to a specialist for additional
hypothyroidism 6036 high doses of levothyroxine (>1.9 µg/kg/day) and continuing to experience persistent symptoms of hypothyroidism .TSH testingAccording to the most recent guidelines from the American Thyroid Association (ATA), “TSH
hypothyroidism 6345 reference range (0.4–4.0 mIU/L) should be considered the therapeutic target” [[18]]. Subclinical hypothyroidism is generally characterized by a serum TSH level above the upper reference limit, combined with a normal
hypothyroidism 6664 is a normal hypothalamic–pituitary–thyroid axis, and no recent or ongoing severe illness. Overt hypothyroidism is typically characterized by an elevated TSH (above 10 mIU/L) in combination with a subnormal FT4
hypothyroidism 6888 the appropriate clinical context, a subnormal serum FT4 level usually establishes the diagnosis of hypothyroidism , whether primary (elevated serum TSH) or central (normal or low serum TSH) [[22], [23]]. The primary
hypothyroidism 7023 (elevated serum TSH) or central (normal or low serum TSH) [[22], [23]]. The primary test for detecting hypothyroidism in patients with secondary hypothyroidism who are on a stable regimen of levothyroxine is a serum FT4
hypothyroidism 7065 low serum TSH) [[22], [23]]. The primary test for detecting hypothyroidism in patients with secondary hypothyroidism who are on a stable regimen of levothyroxine is a serum FT4 assessment. FT4 is also the primary measurement
hypothyroidism 7733 currently in use [[21], [24]]. FT3 measurement has somewhat limited utility, however, in the diagnosis of hypothyroidism , since FT3 values often fall in the normal range as a result of hyperstimulation of the remaining functioning
hypothyroidism 8639 found in the thyrotrophs will usually cause a substantial reduction in serum TSH in the setting of hypothyroidism , the same modest level of increase in peripheral tissues (liver, muscles, etc.) does not cause appreciable
hypothyroidism 8914 decline in serum TSH to normal levels (pituitary euthyroidism) can, in theory, still coexist with tissue hypothyroidism in one or more target tissues. Residual hypothyroid symptoms may be a consequence of insufficient hormone
hypothyroidism 9698 the so-called “normal range”, tissue T3 may decline by 70–80%, resulting in profound cellular hypothyroidism with normal serum TSH, FT4, and FT3 levels [[29]–[39]]. As a result, TSH may be a poor indicator of
hypothyroidism 10375 means of assessing thyroid function in over 80% of patients.Primary factors contributing to refractory hypothyroidism In cases where TSH levels are unable to be maintained within a desired TSH range without the use of unexpectedly
hypothyroidism 10729 patients refractory to the traditional thyroid hormone treatment.Non-pathologic causes of refractory hypothyroidism Non-compliance For many years, poor compliance with the daily dosing of levothyroxine was reputed to
hypothyroidism 11926 levothyroxine preparations at the pharmacy has been shown to contribute to sub-optimal management of hypothyroidism . In 2010, the American Association of Clinical Endocrinologists (AACE), American Thyroid Association
hypothyroidism 14404 factors need to be considered. Alexander et al. prospectively studied 20 pregnant women with treated hypothyroidism . Early in the first trimester, the investigators noted an increased levothyroxine requirement of up
hypothyroidism 14629 which peaked midway through pregnancy and remained constant until delivery [[60]]. Women with treated hypothyroidism , accordingly, may need to increase their dose of levothyroxine to prevent hypothyroidism and its attendant
hypothyroidism 14718 with treated hypothyroidism, accordingly, may need to increase their dose of levothyroxine to prevent hypothyroidism and its attendant adverse outcomes for pregnancy [[61]]. A pregnancy test should be considered for women
hypothyroidism 14899 pregnancy test should be considered for women of reproductive age suspected of having treatment-refractory hypothyroidism .The most recent ATA guidelines provide the following trimester-specific reference ranges for TSH: “The
hypothyroidism 15032 ATA guidelines provide the following trimester-specific reference ranges for TSH: “The treatment of hypothyroidism during pregnancy must be considered within the context of trimester-specific alterations in thyroid
hypothyroidism 15525 second trimester, and 0.3–3.0 mIU/L for the third trimester” [[18]].Pathologic causes of refractory hypothyroidism Concomitant GI diseases Possibly misunderstood in the past, or even confused with pseudomalabsorption
hypothyroidism 17588 deiodinase, or 5′-deiodinase) may help to explain why some patients who fail to achieve control of hypothyroidism with a background of levothyroxine therapy respond to natural desiccated thyroid or to the combined
hypothyroidism 18771 However, the benefits of that treatment remain controversial [[77], [78]].Less common causes of refractory hypothyroidism Other causes of treatment-refractory hypothyroidism are usually more difficult to identify. These include
hypothyroidism 18822 controversial [[77], [78]].Less common causes of refractory hypothyroidismOther causes of treatment-refractory hypothyroidism are usually more difficult to identify. These include dysfunction in the hypothalamic–pituitary–thyroid
hypothyroidism 19065 thyroid hormone) and Addison’s disease [[8]]. Benvenga and others have reported the occurrence of hypothyroidism due to levothyroxine malabsorption in patients with cystic fibrosis [[9], [79]–[81]]. Cystic fibrosis
hypothyroidism 19881 3.4% of patients (2/58) with non-autoimmune thyroid diseases [[88]].Unknown reasons for refractory hypothyroidism Suzuki and colleagues reported failure to identify a cause in approximately 10–20% of patients requiring
hypothyroidism 20236 [[89]]. Benvenga and Centanni have also reported rates of 10–20% for apparent idiopathic refractory hypothyroidism [[9]]. Hays described “thyroid-resistant” patients in a paper published in 1968. In that early study,
hypothyroidism 21431 also been conceived [[94], [95]]. Our specific recommendations for diagnosing and managing refractory hypothyroidism resulting from the wide range of etiologies discussed in this paper are presented below.DiscussionAs
hypothyroidism 21568 wide range of etiologies discussed in this paper are presented below.DiscussionAs noted above, primary hypothyroidism is considered to be refractory to oral thyroxine when there is biochemical or clinical evidence of hypothyroidism
hypothyroidism 21682 is considered to be refractory to oral thyroxine when there is biochemical or clinical evidence of hypothyroidism (serum level of TSH above the upper target level, usually 4.5 mU/L following a 6-week interval after
hypothyroidism 24153 (including the very real risk of heart disease) associated with elevated TSH levels or physiologic hypothyroidism [[99]]. The first-line treatment of hypothyroidism dictates that thyroxine dosing be carefully monitored
hypothyroidism 24204 associated with elevated TSH levels or physiologic hypothyroidism [[99]]. The first-line treatment of hypothyroidism dictates that thyroxine dosing be carefully monitored and adjusted as necessary to prevent ongoing bone
hypothyroidism 25904 sub-therapeutic doses of levothyroxine for long periods not only may suffer the classic symptoms of uncontrolled hypothyroidism , but may experience other significant physiologic effects. In a recent study, Piantanida et al. demonstrated
hypothyroidism 26063 physiologic effects. In a recent study, Piantanida et al. demonstrated a correlation between uncontrolled hypothyroidism and increased risk for masked hypertension (MH). Masked hypertension, or the association of normal office
hypothyroidism 26641 neuromuscular symptoms in 57 newly diagnosed hypothyroid patients. Among those patients with overt hypothyroidism , there was a significantly higher prevalence of both neuromuscular symptoms (myalgias, slowness of movement,
hypothyroidism 28375 According to the authors, levothyroxine dose and formulation changes escalate the socioeconomic burden of hypothyroidism care by both increasing healthcare costs and decreasing work productivity [[104]].Patient satisfaction
hypothyroidism 29528 hypothyroid-treating physician in the past year: +66.1% (P = .054) [[105]].Diagnosing and managing refractory hypothyroidism Key principleWhen confronted with patients in which escalating doses of thyroid replacement hormone have
hypothyroidism 29692 which escalating doses of thyroid replacement hormone have failed to control TSH levels and symptoms of hypothyroidism , clinicians should employ a systematic approach to gathering information and determining an effective
hypothyroidism 30116 levothyroxine:Confirm the diagnosis and laboratory results By laboratory definition, frank primary hypothyroidism requires low levels of thyroid hormones (free–FT4 and FT3) as well as elevated TSH. The finding of
hypothyroidism 33147 1.9 μg/kg body weight, and who have persistently elevated TSH levels and/or unresolved symptoms of hypothyroidism , should be evaluated, and, if indicated, undergo testing for malabsorption. We are recommending a diagnostic
hypothyroidism 38650 alternatives may eliminate a number of factors that contribute to levothyroxine tablet failure and refractory hypothyroidism . They may also offer options to patients who are non-compliant, have difficulty swallowing medication,
hypothyroidism 39300 replacement treatment and require unexpectedly high doses of levothyroxine or who have erratic control of hypothyroidism , alternating between over-replacement and under-replacement. In addition to clinical situations where
hypothyroidism 39898 and beverages, including coffee). Significant swings in weight may also cause treatment-refractory hypothyroidism . Switching to generic levothyroxine products has also been correlated with sub-optimal outcomes.The
hypothyroidism 40891 should take a systematic approach to managing patients whom they suspect of having treatment-refractory hypothyroidism . This may include searching for occult medical conditions, or other factors that may affect the absorption
hypothyroidism 41637 stated by Trimarchi in 2015 [[124]]. This holistic approach acknowledges that treatment-refractory hypothyroidism is a condition that exists within the context of other important factors—GI disease, concomitant drug
lactose intolerance 3375 l-thyroxineLuminal factors (e.g., food, coffee, and medications)Intramural factors (e.g., short bowel syndrome, lactose intolerance , gluten enteropathy, inflammatory bowel disease, infiltrative enteropathy, infection with Giardia)Increased
lactose intolerance 13770 conditions such as gastroesophageal reflux disease (33.8%), irritable bowel syndrome (IBS) (9.7%), lactose intolerance (7.8%), or the use of prescription and OTC medications used to treat these conditions (34%). The use
lactose intolerance 15982 tract, including: Helicobacter pylori infection, inflammatory bowel disease (IBD), celiac disease, lactose intolerance , atrophic body gastritis (ABG), gastric bypass, biliary pancreatic diversion, and gastroparesis, among
obesity 9257 conditions such as chronic emotional or physical stress, chronic illness, diabetes, insulin resistance, obesity , leptin resistance, depression, chronic fatigue syndrome, fibromyalgia, premenstrual syndrome (PMS),
osteoporosis 23514 that lengthy periods of hyperthyroidism affect bone mass density (BMD) and can increase the risk of osteoporosis , there is significant controversy as to whether the long-term use of levothyroxine at suppressive or
osteoporosis 23670 whether the long-term use of levothyroxine at suppressive or non-suppressive levels actually increases osteoporosis risk. Comprehensive, definitive research is required to establish with certainty whether suppressed
osteoporosis 23829 required to establish with certainty whether suppressed or low-normal TSH levels increase the risk of osteoporosis and/or fractures, and whether the use of supplemental T3 has any effect at all on the risk of osteoporosis.
osteoporosis 23936 osteoporosis and/or fractures, and whether the use of supplemental T3 has any effect at all on the risk of osteoporosis . The extent of such risk should also be assessed in comparison to the large number of other health risks

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