Hypothyroidism


Article Author:
Nikita Patil
Anis Rehman


Article Editor:
Ishwarlal Jialal


Editors In Chief:
Ann Anderson Berry
Mark Hudak
Sumesh Parat


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
9/2/2019 10:00:22 PM

Introduction

Hypothyroidism results from low levels of thyroid hormone with varied etiology and manifestations. The drug of choice for the treatment of hypothyroidism is levothyroxine. Untreated hypothyroidism increases morbidity and mortality. This article reviews etiology, clinical presentation, diagnosis, and management of hypothyroidism.

Etiology

The most common etiology is iodine deficiency in iodine-deficient geographic areas worldwide. Autoimmune thyroid diseases are the leading cause of hypothyroidism in the United States and the iodine-sufficient regions. Etiology can be influenced locally by iodine fortification and emergence of new iodine-deficient areas.[1]

Other common causes of hypothyroidism are drugs such as amiodarone and lithium,[1] thyroid radioactive iodine therapy or thyroid surgery, radiotherapy to head or neck area, and central hypothyroidism from neoplastic, infiltrative, inflammatory, or iatrogenic disorders of the pituitary or hypothalamus.[2]

Epidemiology

The NHANESIII (National Health and Nutrition Examination Survey) study found the prevalence of overt hypothyroidism among US adults (12 years of age and older) to be 0.3% and subclinical hypothyroidism 4.3%. Female gender and increasing age were associated with higher thyroid-stimulating hormone (TSH) and prevalence of antithyroid antibodies.[3]

Pathophysiology

The hypothalamus secretes thyrotropin-releasing hormone (TRH) that stimulates the pituitary gland to produce thyroid-stimulating hormone (TSH). Thyroid-stimulating hormone stimulates the thyroid gland to produce and secrete mainly T4 while T3 is produced mainly by conversion of T4 to T3. Levels of T3 and T4, in turn, exert a negative feedback on the production of TRH and TSH. Alteration in structure and function of any of these organs or pathways can result in hypothyroidism.

Histopathology

Predominant T-cell lymphocytic infiltration is seen in autoimmune thyroid disease.[2] Co-existing or associated malignancy such as papillary thyroid cancer can also be seen.[4]

History and Physical

It is important to maintain a high index of suspicion for hypothyroidism since the signs and symptoms can be mild and nonspecific and different symptoms may be present in different patients.

Inquire about dry skin, voice changes, hair loss, constipation, fatigue, muscle cramps, cold intolerance, sleep disturbances, menstrual cycle abnormalities, weight gain, galactorrhea.[2] Also obtain a complete medical, surgical, medication and family history.

History of adverse pregnancy and neonatal outcomes should also be sought.[5]

Symptoms of depression, anxiety, psychosis, cognitive impairments such as memory loss can be present.[6] Rarely patients can present with ascites,[7] rhabdomyolysis, and pericardial effusion.[8]

Patients can also present with carpal tunnel syndrome, sleep apnea, hyponatremia, Hypercholesterolemia, congestive heart failure, and prolonged QT interval.[2]

A physical examination may reveal an enlarged thyroid gland, the presence of nodules, prolonged ankle reflex relaxation time, hoarse voice, and skin and hair changes.[2]

Evaluation

Serum TSH level is used to screen for primary hypothyroidism in most patients. In overt hypothyroidism, TSH levels are elevated, and free T4 levels are low. In subclinical hypothyroidism, TSH levels are elevated, and free T4 levels are normal.[2]

Central hypothyroidism is of pituitary or hypothalamic origin. TSH produced can be biologically inactive and can affect the levels of bioactive TSH, hence diagnosis of central hypothyroidism should be based on free T4 rather than TSH.[2]

Labs should include evaluation for autoimmune thyroid diseases with levels of anti-thyroid antibodies: the thyroid peroxidase antibodies and anti-thyroglobulin antibodies. Particularly in patients with thyroid nodules, fine-needle aspiration biopsy should be considered.[2]

Patients with subclinical hypothyroidism and thyroid peroxidase antibody positivity have a greater risk of developing overt hypothyroidism[2] and should be followed up periodically with clinical evaluation and lab tests for the same.

T3 levels are not a reliable or recommended test. Hospitalized patients should undergo TSH testing only when thyroid dysfunction is suspected.[2]

On labs, hyperlipidemia, elevated serum CK, elevated hepatic enzymes, anemia can be present.[2]

BUN, creatinine, and uric acid levels can also be elevated.[9]

Treatment / Management

Hypothyroidism is mainly treated with levothyroxine monotherapy.[10]

Thyroid replacement treatment can exacerbate co-existing adrenal insufficiency. Patients with known or suspected adrenal insufficiency should be tested and treated for the adrenal insufficiency while awaiting results.[2] Adrenal insufficiency can also be associated with subclinical hypothyroidism that is reversible with treatment of adrenal insufficiency.[11] In patients who have confirmed adrenal insufficiency consider a reassessment of thyroid tests following adequate treatment of adrenal insufficiency.

Replacement levothyroxine dose is 1.6 mcg/kg per day, should be taken 60 minutes before a meal and at least 3 hours post-meal which makes before breakfast or at bedtime the practical times for most patients. Maintaining a consistent formulation or brand of levothyroxine is important.[10]

When switching to the intravenous (IV) form, reduce the dose to 70% of the oral dose. Malabsorption syndromes, medications such as sucralfate, calcium preparations, and bile acid sequestrants can interfere with the absorption of levothyroxine.[2]

Based on the 2012 Clinical Practice Guidelines for Hypothyroidism in Adults by American Association of Clinical Endocrinologists and the American Thyroid Association, therapy should be monitored and titrated based on TSH measurements. Serum free T4 can also be used. Labs should be drawn every 4 to 8 weeks until target levels are achieved after starting the treatment, after any dose changes, changes in formulation or brand of levothyroxine,[2] after starting or stopping of any medications that may affect levels. If stable, then monitoring interval can be extended to 6 months, and if stable then, further monitoring can be extended to 12 months or can be done at shorter intervals on a case-to-case basis along with clinical evaluation.[2] Central hypothyroidism should be monitored based on free T4 rather than TSH.[2]

For elderly patients and patients with cardiac diseases, starting at a lower dose and titrating slowly is recommended.[10] Patients with cardiac disease should be monitored for the development of any symptoms of angina.[2] Monitor for side effects of treatment such as atrial fibrillation and osteoporosis.[10]

Effective treatment should achieve a clinical improvement of signs and symptoms, along with an improved sense of patient well-being and normal TSH (or free T4 levels as applicable).[12]

A comprehensive differential diagnosis workup is recommended for unresolved symptoms in the presence of biochemical euthyroidism. There is a lack of strong evidence supporting the routine inclusion of triiodothyronine (T3) preparations with levothyroxine in the treatment of hypothyroidism.[13]

If symptoms persist despite normalization of TSH/free T4 levels, then consultation with an endocrinologist should also be considered.

Differential Diagnosis

Differential diagnosis is based on signs and symptoms; for example, fatigue can point to iron deficiency anemia, sleep apnea, depression, and rheumatological diseases.[13]

Complications

Myxedema coma is a presentation of severe hypothyroidism and is an endocrine emergency. Early recognition and prompt treatment in the intensive care unit (ICU) is essential, and even then, mortality reaches 25% to 60%.[14]

Myxedema crisis should be suspected in patients that have encephalopathy, hypothermia, seizures, severe hyponatremia, hypoglycemia, cardiogenic shock and arrhythmias, respiratory failure, and manifestations of fluid retention.[14] A combination of a few or all of these manifestations and other symptoms of mild to severe hypothyroidism as stated above can be present.

Factors leading to an increased risk of myxedema crisis include inadequate doses of thyroid hormone, interruption in treatment, undiagnosed hypothyroidism, or presence of acute illness such as sepsis [14] perhaps due to increased metabolic demands.

Supportive treatment should be provided in the intensive care unit with fluid and electrolyte management, ventilator support, vasopressors, treatment of coexisting acute illness, and hypothermia.[14]

Thyroid replacement treatment is with intravenous hydrocortisone at stress doses followed by intravenous levothyroxine then switched to oral levothyroxine after clinical improvement. If effective, this should result in cardiopulmonary and cognitive improvement.[10] There should also be an associated improvement in laboratory derangements including a down trending of TSH which should be measured every 1 to 2 days during the initial treatment period. Intravenous liothyronine (T3) can be considered until initial improvement.[10]

Endocrinology consultation should be considered.

Enhancing Healthcare Team Outcomes

Hypothyroidism affects multiple organ systems across all age groups and affects patient well-being and ability to function on a daily basis. Treatment is with levothyroxine monotherapy (Grade A, Best Evidence Level 1).[2]

Effective treatment calls for a team-based and patient-centered approach. When patient symptoms are not adequately controlled an endocrinology consult should be obtained.

Endocrinology consultation is also recommended in complex scenarios such as preconception, pregnancy, congenital and pediatric hypothyroidism, failure of treatment, co-existing cardiac or other endocrine disorders, difficulty in interpretation of thyroid test results, drug-induced hypothyroidism.[2] Other specialists that may be needed are a psychiatrist, obstetrician-gynecologist, pediatrician, cardiologist, and intensivist.

It is helpful to work closely with a pharmacist to determine medication and food interactions, the effect of changes in levothyroxine formulations, to investigate the causes for the requirement of unusually high doses of levothyroxine or fluctuating TSH levels. Prompt notification of unusually high levels of TSH by laboratory personnel, close monitoring of vital signs and mental status by nurses can facilitate early treatment and better outcomes, especially in the inpatient setting such as in myxedema coma. Rapid response teams can be effectively utilized when hypothyroidism causes hemodynamic instability.


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Hypothyroidism - Questions

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A 65-year-old female presents for evaluation of fatigue. Her fatigue is accompanied by difficulty concentrating, depression, cold intolerance, and weight gain. She does not understand why she is depressed as she recently got a job promotion, and her relationships at home are stable. She denies any psychiatric medical history. Bloodwork reveals a thyroid stimulating hormone (TSH) of 6 mU/I. Which of the following symptoms is most likely to be present in this patient?



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What does thyroid hormone deficiency cause in adults?



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What diagnosis is associated with the Sign of Hertoghe?



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Cystic fibrosis, and what other common endocrine disorder, correlate with elevated levels of sweat chloride?



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Dysphonia may associate with which endocrine disorder?



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A 17-year old female complains of significant weight gain despite decreased appetite. She also complains of fatigue, depression, hair loss, cold intolerance, and skin changes on the legs. Which of the following would be expected on a physical exam?



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What is the best test to diagnose hypothyroidism?



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A female is diagnosed with hypothyroidism and started on levothyroxine 25 mcg/day. Six weeks later, her symptoms have improved. Thyroid stimulating hormone is 10.1 mU/mL (0.27 to 4.2). What is appropriate for this patient?



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A patient on levothyroxine for hypothyroidism has had normal thyroid stimulating hormone levels for years. She read on the internet that a combination product with T4 and T3 might help with her obesity and fatigue. Which of the following would be the most appropriate in the management of this patient?



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Thinning of the outer third of the eye brow is most likely seen in a patient with which condition?



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In hypothyroidism, which of the following deep tendon reflexes will most likely appear very sluggish on examination?



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A patient is taking 0.1 mg of levothyroxine per day. What instructions does the patient need regarding this medication?



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Which of the following instructions should be included when discharging a client with a prescription for levothyroxine 0.1 mg by mouth daily?



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In preparing to administer a patient's dosage of levothyroxine, a practitioner notices that the patient's heart rate is 146 beats per minute. What is the appropriate management for this patient?



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A patient is receiving the thyroid hormone replacement levothyroxine and has been scheduled for an I-131 uptake study. When must the patient discontinue the levothyroxine?



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Which of the following is true about levothyroxine replacement therapy?



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Which of the following should be included in instructions to a pregnant female who is on thyroid replacement?



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Which is not a risk factor for hypothyroidism?



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Xerosis is often seen in patients with which of the following conditions?



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Which of the following hormones is important to evaluate in a 70-year-old female with hair loss?



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Which of the following is NOT a neurologic manifestation of hypothyroidism?



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What is the most likely diagnosis in a patient with low T4 and TSH?



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What is the most common cause of hypothyroidism in geriatric patients?



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A 37-year-old female presents complaining of fatigue and constipation. Her menses have become irregular. Which additional symptom is she least likely to have?



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Hypothyroidism rarely presents with which of the following?



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Hypothyroidism is unlikely to present with which symptom?



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Which laboratory result is suggestive of secondary hypothyroidism?



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How soon is maximal effect of levothyroxine treatment expected to be achieved?



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Which of the following is used to treat hypothyroidism?



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A 68-year-old male complains of poor concentration, lethargy, and inattentiveness. He feels like the Central Intelligence Agency is watching him. Exam shows ataxia, proximal muscle weakness, edema, pale and coarse skin, macroglossia, and delayed relaxation of deep tendon reflexes. Which of the following is the most likely diagnosis?



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A 59-year-old patient has new onset hypothyroidism. Which of the following is least important as part of the teaching plan?



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What is the most common etiology of hypothyroidism in those over 65 years in the U.S.?



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Which of the following is not a symptom or sign of hypothyroidism in children?



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Which of the following can be secondary to hypothyroidism?



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A patient is diagnosed with carpal tunnel syndrome. She also has complaints of fatigue, muscle soreness, and weight gain. What is the most likely cause of her symptoms?



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What is the most common cause of hypothyroidism worldwide?



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Select the true statement about hypothyroidism.



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Which is true regarding autoimmune hypothyroidism?



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A female has fatigue, dry skin, bradycardia, 1+/4 pitting pedal edema, and hair loss. Select the correct screening test



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What percentage of women develop transient thyroid problems postpartum?



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Which of the following is the best test to evaluate for hypothyroidism?



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A 50-year-old female reports a weight increase but denies an increase in eating or appetite. She also feels tired and complains of being cold when others are not. She feels depressed in regards to mood as well. Other physical symptoms that she describes include constipation and dry, brittle hair. Which of the following should be ordered next?



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Which of the following is the most common cause of a decreased T4 and a markedly elevated TSH with newborn laboratory screening?



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What is the probable diagnosis of a patient that exhibits a low radioiodine uptake on exam?



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Which of the following are symptoms associated with central hypothyroidism?



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Which disease process is commonly associated with coarse hair?



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What is the most common cause of hypothyroidism in the world?



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Which statement is most accurate regarding thyroid hormone replacement therapy for hypothyroidism?



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A female patient with hypothyroidism will most likely present with?



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Which statement is most accurate regarding myxedema coma?



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What is the most likely diagnosis for a 35-year-old female with weight gain, fatigue, cold intolerance, and slow reflexes?



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A 43 year old woman complains from having very little energy, always feels cold, is constipated and gained a great deal of weight in short time. The provider suspected that she has hypothyroidism. Her lab work revealed low T4 and high TSH. The patient is receiving hormone replacement therapy in the form of synthetic T4. Which of the following hormones is measured to adjust the dosage of T4?



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In a patient with hypothyroidism, what symptoms commonly are present? Select all that apply.



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A provider is reviewing a patient's laboratory findings who has been diagnosed with untreated primary hypothyroidism. Which of the following is most likely to be elevated in this patient?



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Hypothyroidism - References

References

Current evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapy., Hennessey JV,Espaillat R,, International journal of clinical practice, 2018 Feb     [PubMed]
Global epidemiology of hyperthyroidism and hypothyroidism., Taylor PN,Albrecht D,Scholz A,Gutierrez-Buey G,Lazarus JH,Dayan CM,Okosieme OE,, Nature reviews. Endocrinology, 2018 May     [PubMed]
Hollowell JG,Staehling NW,Flanders WD,Hannon WH,Gunter EW,Spencer CA,Braverman LE, Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). The Journal of clinical endocrinology and metabolism. 2002 Feb     [PubMed]
Mathew V,Misgar RA,Ghosh S,Mukhopadhyay P,Roychowdhury P,Pandit K,Mukhopadhyay S,Chowdhury S, Myxedema coma: a new look into an old crisis. Journal of thyroid research. 2011     [PubMed]
Saini V,Yadav A,Arora MK,Arora S,Singh R,Bhattacharjee J, Correlation of creatinine with TSH levels in overt hypothyroidism - a requirement for monitoring of renal function in hypothyroid patients? Clinical biochemistry. 2012 Feb     [PubMed]
Jonklaas J,Bianco AC,Bauer AJ,Burman KD,Cappola AR,Celi FS,Cooper DS,Kim BW,Peeters RP,Rosenthal MS,Sawka AM, Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid : official journal of the American Thyroid Association. 2014 Dec     [PubMed]
Garber JR,Cobin RH,Gharib H,Hennessey JV,Klein I,Mechanick JI,Pessah-Pollack R,Singer PA,Woeber KA, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid : official journal of the American Thyroid Association. 2012 Dec     [PubMed]
Anand A,Singh KR,Kushwaha JK,Hussain N,Sonkar AA, Papillary Thyroid Cancer and Hashimoto's Thyroiditis: An Association Less Understood. Indian journal of surgical oncology. 2014 Sep     [PubMed]
Abdullatif HD,Ashraf AP, Reversible subclinical hypothyroidism in the presence of adrenal insufficiency. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2006 Sep-Oct     [PubMed]
Hou J,Yu P,Zhu H,Pan H,Li N,Yang H,Jiang Y,Wang L,Wang B,Wang Y,You L,Chen S, The impact of maternal hypothyroidism during pregnancy on neonatal outcomes: a systematic review and meta-analysis. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2016     [PubMed]
Samuels MH, Psychiatric and cognitive manifestations of hypothyroidism. Current opinion in endocrinology, diabetes, and obesity. 2014 Oct     [PubMed]
Khalid S,Asad-Ur-Rahman F,Abbass A,Gordon D,Abusaada K, Myxedema Ascites: A Rare Presentation of Uncontrolled Hypothyroidism. Cureus. 2016 Dec 5     [PubMed]
Zare-Khormizi MR,Rahmanian M,Pourrajab F,Akbarnia S, Massive pericardial effusion and rhabdomyolysis secondary to untreated severe hypothyroidism: the first report. Acta clinica Belgica. 2014 Oct     [PubMed]
Guglielmi R,Frasoldati A,Zini M,Grimaldi F,Gharib H,Garber JR,Papini E, ITALIAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS STATEMENT-REPLACEMENT THERAPY FOR PRIMARY HYPOTHYROIDISM: A BRIEF GUIDE FOR CLINICAL PRACTICE. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2016 Nov     [PubMed]

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