Autoimmune polyendocrine syndrome medical therapy: Difference between revisions

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{{Autoimmune polyendocrine syndrome}}
{{Autoimmune polyendocrine syndrome}}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}}{{Akshun}}


==Overview==
==Overview==
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
Medical [[therapy]] for autoimmune polyendocrine syndrome (APS) depends upon the sub-type and the [[organ system]] involved. In APS, the focus is to treat the presenting [[Disorder (medicine)|disorder]] which can either be [[mucocutaneous]] [[candidiasis]], [[hypoparathyroidism]], [[adrenal insufficiency]] or [[autoimmune thyroiditis]]. The goal of treatment is to correct [[hormone]] deficiencies, prevent [[complications]], and reduce [[morbidity]]. Treatment includes monitoring of [[glandular]] functions for early detection of glandular failure, lifelong [[hormone replacement therapy]] for established [[glandular]] failure, and [[familial]] [[Screening (medicine)|screening]].
 
OR
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
 
OR
 
The majority of cases of [disease name] are self-limited and require only supportive care.
 
OR
 
[Disease name] is a medical emergency and requires prompt treatment.
 
OR
 
The mainstay of treatment for [disease name] is [therapy].
 
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
 
OR
 
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
 
OR
 
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].


==Medical Therapy==
==Medical Therapy==
Medical therapy for autoimmune polyendocrine syndrome (APS) depends upon the subtype and the organ system involved.
Medical [[therapy]] for autoimmune polyendocrine syndrome (APS) depends upon the sub-type and the [[organ system]] involved.
*In APS type 1 focus is to treat the presenting disorder which can either be mucocutaneous candidiasis, hypoparathyroidism or adrenal insufficiency.  
*In APS the focus is to treat the presenting [[Disorder (medicine)|disorder]] which can either be [[mucocutaneous]] [[candidiasis]], [[hypoparathyroidism]], [[adrenal insufficiency]] or [[autoimmune thyroiditis]].
*Patient education is an important aspect of treatment in APS. Patient with APS who present with mucocutaneous candidiasis may take upto 5-10 years to develop hypoparathyroidism and another 10 years to show manifestations of adrenal insufficiency. Therefore, patients with family history of APS or an early age onset of APS should be advised to undergo regular surveillance.
*[[Patient]] [[education]] is an important part of treatment in APS. Patients with APS who present with [[mucocutaneous]] [[candidiasis]] may take upto 5-10 years to develop [[hypoparathyroidism]] and another 10 years to show manifestations of [[adrenal insufficiency]]. Therefore, [[patients]] with [[family history]] of APS or an early age onset of APS should be advised to undergo regular surveillance.
* Treatment of APS 1 includes:
**Mucocutaneous candidiasis: Treat with oral fluconazole (200 mg/day PO) and ketoconazole(200-400 mg/day PO)
 
 
*APS type 1: Chronic mucocutaneous candidiasis is commonly present in patients with APS type 1 and should be aggressively treated to prevent developmeent of epithelial carcinoma.
In addition the medical therapy should be aimed at the autoimmune disorder present.<ref name="pmid16704638">{{cite journal |vauthors=Collins SM, Dominguez M, Ilmarinen T, Costigan C, Irvine AD |title=Dermatological manifestations of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome |journal=Br. J. Dermatol. |volume=154 |issue=6 |pages=1088–93 |year=2006 |pmid=16704638 |doi=10.1111/j.1365-2133.2006.07166.x |url=}}</ref>
 
'''Type I:''' Treatments focus on the three major clinical features, including [[fluconazole]] and [[ketoconazole]], [[calcium]] and [[vitamin D]], and [[steroid]]. The prognosis of autoimmune polyendocrine syndrome type I is variable, depending on how organs are affected and the severity of the disease.
 
'''Type II:''' Treatment involves drug therapy.  Drugs for such signs mentioned above are the main treatment opinion, including replacement therapy with [[hydrocortisone]] and [[fludrocortisone]], antithyroid medications, [[insulin]], and medicines on other manifestations. Prognosis of autoimmune polyendocrine syndrome type II depends on whether endocrine end-organ failures occur or not.


'''Type III:''' Compared with type I and II, autoimmune polyendocrine syndrome type III does not involve the adrenal cortex. Studies demonstrate that autoimmunity, environmental factors and genetic factors are involved in the cause of autoimmune polyendocrine syndrome type III. The goals of treatment of autoimmune polyendocrine syndrome type III are to correct hormone deficiencies, prevent complications, and reduce morbidity. Treatments include monitoring of glandular functions for early detection of glandular failure, lifelong hormone replacement therapy for established glandular failure, and familial screening.
* Treatment of APS  includes:<ref name="pmid26938200">{{cite journal |vauthors=Bilezikian JP, Brandi ML, Cusano NE, Mannstadt M, Rejnmark L, Rizzoli R, Rubin MR, Winer KK, Liberman UA, Potts JT |title=Management of Hypoparathyroidism: Present and Future |journal=J. Clin. Endocrinol. Metab. |volume=101 |issue=6 |pages=2313–24 |year=2016 |pmid=26938200 |pmc=5393596 |doi=10.1210/jc.2015-3910 |url=}}</ref><ref name="pmid27810905">{{cite journal |vauthors=Gan EH, Pearce SH |title=MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison's disease |journal=Eur. J. Endocrinol. |volume=176 |issue=3 |pages=R123–R135 |year=2017 |pmid=27810905 |doi=10.1530/EJE-16-0581 |url=}}</ref><ref name="pmid25138826">{{cite journal |vauthors=Inder WJ, Meyer C, Hunt PJ |title=Management of hypertension and heart failure in patients with Addison's disease |journal=Clin. Endocrinol. (Oxf) |volume=82 |issue=6 |pages=789–92 |year=2015 |pmid=25138826 |doi=10.1111/cen.12592 |url=}}</ref><ref name="pmid24766944">{{cite journal |vauthors=Tucci V, Sokari T |title=The clinical manifestations, diagnosis, and treatment of adrenal emergencies |journal=Emerg. Med. Clin. North Am. |volume=32 |issue=2 |pages=465–84 |year=2014 |pmid=24766944 |doi=10.1016/j.emc.2014.01.006 |url=}}</ref><ref name="pmid24755997">{{cite journal |vauthors=Napier C, Pearce SH |title=Current and emerging therapies for Addison's disease |journal=Curr Opin Endocrinol Diabetes Obes |volume=21 |issue=3 |pages=147–53 |year=2014 |pmid=24755997 |doi=10.1097/MED.0000000000000067 |url=}}</ref><ref name="pmid24031090">{{cite journal |vauthors=Grossman A, Johannsson G, Quinkler M, Zelissen P |title=Therapy of endocrine disease: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe |journal=Eur. J. Endocrinol. |volume=169 |issue=6 |pages=R165–75 |year=2013 |pmid=24031090 |pmc=3805018 |doi=10.1530/EJE-13-0450 |url=}}</ref><ref name="pmid23177474">{{cite journal |vauthors=Napier C, Pearce SH |title=Autoimmune Addison's disease |journal=Presse Med |volume=41 |issue=12 P 2 |pages=e626–35 |year=2012 |pmid=23177474 |doi=10.1016/j.lpm.2012.09.010 |url=}}</ref><ref name="pmid22907517">{{cite journal |vauthors=Quinkler M |title=[Addison's disease] |language=German |journal=Med Klin Intensivmed Notfmed |volume=107 |issue=6 |pages=454–9 |year=2012 |pmid=22907517 |doi=10.1007/s00063-012-0112-3 |url=}}</ref><ref name="pmid24434360">{{cite journal |vauthors=Caturegli P, De Remigis A, Rose NR |title=Hashimoto thyroiditis: clinical and diagnostic criteria |journal=Autoimmun Rev |volume=13 |issue=4-5 |pages=391–7 |year=2014 |pmid=24434360 |doi=10.1016/j.autrev.2014.01.007 |url=}}</ref><ref name="pmid25266247">{{cite journal |vauthors=Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, Cooper DS, Kim BW, Peeters RP, Rosenthal MS, Sawka AM |title=Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement |journal=Thyroid |volume=24 |issue=12 |pages=1670–751 |year=2014 |pmid=25266247 |pmc=4267409 |doi=10.1089/thy.2014.0028 |url=}}</ref>
 
**'''Mucocutaneous candidiasis''':
==Medical Therapy==
***Preferred regimen (1): [[Fluconazole]] 800 mg (12 mg/kg) on day 1, then 400 mg daily (6 mg/kg/day) for 14 days after first negative [[blood culture]] and resolution of [[Signs and Symptoms|signs/symptoms]]
*Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
***Alternative regimen (1): [[Ketoconazole]] 200-400 mg/day [[Oral|PO]] may increase to 400 mg once daily if response is insufficient. Continue until active [[fungal infection]] is resolved; some [[infections]] may require a treatment duration of up to 6 months.
*Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
**'''Hypoparathyroidism''': Conventional therapy for [[hypoparathyroidism]]:
*Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
*** Oral [[calcium]]: Preferred regimen (1): [[Calcium carbonate]] (40% [[elemental calcium]]) (better absorption with meals)
*Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
***:* Alternative regimen (1): [[Calcium citrate]] (21% [[elemental calcium]]) (more effective in patients with [[achlorhydria]] and [[Proton pump inhibitor|proton pump inhibitors]]' use, worsening [[constipation]])
===Disease Name===
***[[Vitamin D]] supplementation
***:* Preferred regimen (1): [[Calcitriol]] 0.25 to 2 μg q24h (>.75 μg administered in divided doses)
***:* Preferred regimen (2): [[Cholecalciferol]] (parent vitamin D3)
***:* Preferred regimen (3): [[Ergocalciferol]] (parent vitamin D2)
***:* Alternative regimen (1): 1α-Hydroxyvitamin D ([[alfacalcidol]]) (used outside the United States)
***:* Alternative regimen (2): [[Dihydrotachysterol]] (used outside the United States)
***::Note(1): Serum [[calcium]] ([[Hypoparathyroidism laboratory findings|corrected for albumin]]), [[phosphorus]], and [[creatinine]] concentrations should be measured weekly to monthly during dose adjustments, and twice annually once a stable regimen has been reached.  
***::Note(2): 24-hour [[urinary]] [[calcium]] and [[creatinine]] should be considered during dose adjustments and should be measured twice annually on a stable regimen to evaluate for [[renal]] toxicity.
**'''Adrenal insufficiency (Addison's disease)''':
***[[Glucocorticosteroid]]: Preferred regimen (1): [[Cortisone]] 10 to 37.5 mg q12h [[Orally ingested|orally]] given in 2 divided [[doses]] with two-thirds of the total [[dose]] given in the morning  and one third in the afternoon
***:*Preferred regimen (2): [[Hydrocortisone]] : 15-30 mg/day orally given in 2 divided [[doses]] with two-thirds of the total [[dose]] given in the morning and one third in the afternoon
***:*Preferred regimen (3): [[Dexamethasone]] : 0.25 to 0.75 mg orally once daily
***:*Preferred regimen (4): [[Prednisone]] : 2.5 to 5 mg orally once daily
***[[Mineralocorticoids|Mineralocorticosteroid]]: Preferred regimen (1): [[Fludrocortisone]] : 0.1 to 0.2 mg orally once daily
***Patients of [[Addison's disease]] with mild-to-moderate [[Stress (medicine)|stress]]:
***:*Alternative regimen (1): [[Cortisone]]  50-100 mg/day [[Orally ingested|orally]] given in 2 divided [[doses]] with two-thirds of the total [[dose]] given in the morning (around 8 a.m.) and one third in the afternoon (noon to 4 p.m.) for 3 days
***:*Alternative regimen (2): [[Hydrocortisone]] 30-90 mg/day [[Orally ingested|orally]] given in 2 divided [[doses]] with two-thirds of the total [[dose]] given in the morning (around 8 a.m.) and one third in the afternoon (noon to 4 p.m.) for 3 days
***:*Alternative regimen (3): [[Dexamethasone]] 0.50 to 2.25 mg [[Orally ingested|orally]] once daily for 3 days
***:*Alternative regimen (4): [[Prednisone]]  5-15 mg [[Orally ingested|orally]] once daily for 3 days
***Patients of [[Addison's disease]] with severe [[Stress (medicine)|stress]]:
***:*Alternative regimen (5): [[Hydrocortisone]] sodium succinate 100 mg [[intravenously]] every 6-8 hours
**'''Autoimmune thyroiditis''':
***:*Preferred regimen (1) [[Levothyroxine (oral)|Synthetic levothyroxine]] (L-[[T4]]) 1.6–1.8 μg/kg of body weight per day orally.


* '''1 Stage 1 - Name of stage'''
* '''For complete [[therapy]] for [[hypopituitarism]] please [[Hypopituitarism medical therapy|click here.]]'''
** 1.1 '''Specific Organ system involved 1'''
*** 1.1.1 '''Adult'''
**** Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)''' 
**** Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
**** Preferred regimen (3): [[drug name]] 500 mg q12h for 14-21 days
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
**** Alternative regimen (3): [[drug name]] 500 mg PO q6h for 14–21 days
*** 1.1.2 '''Pediatric'''
**** 1.1.2.1 (Specific population e.g. '''children < 8 years of age''')
***** Preferred regimen (1): [[drug name]] 50 mg/kg PO per day q8h (maximum, 500 mg per dose) 
***** Preferred regimen (2): [[drug name]] 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
***** Alternative regimen (1): [[drug name]]10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
****1.1.2.2 (Specific population e.g. ''''''children < 8 years of age'''''')
***** Preferred regimen (1): [[drug name]] 4 mg/kg/day PO q12h（maximum, 100 mg per dose）
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose) 
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
** 2.1 '''Specific Organ system involved 2'''
*** 2.1.1 '''Adult'''
**** Preferred regimen (1): [[drug name]] 500 mg PO q8h
*** 2.1.2  '''Pediatric'''
**** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h (maximum, 500 mg per dose)


* 2 '''Stage 2 - Name of stage'''
* '''For complete [[therapy]] for [[diabetes mellitus type 1]] please [[diabetes mellitus type 1 medical therapy|click here.]]'''
** 2.1 '''Specific Organ system involved 1 '''
**: '''Note (1):'''
**: '''Note (2)''':
**: '''Note (3):'''
*** 2.1.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.1.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) ''''''(Contraindications/specific instructions)''''''
**** Oral regimen
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
** 2.2  '<nowiki/>'''''Other Organ system involved 2''''''
**: '''Note (1):'''
**: '''Note (2)''':
**: '''Note (3):'''
*** 2.2.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.2.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
**** Oral regimen
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)


==References==
==References==

Latest revision as of 20:00, 30 October 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Overview

Medical therapy for autoimmune polyendocrine syndrome (APS) depends upon the sub-type and the organ system involved. In APS, the focus is to treat the presenting disorder which can either be mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency or autoimmune thyroiditis. The goal of treatment is to correct hormone deficiencies, prevent complications, and reduce morbidity. Treatment includes monitoring of glandular functions for early detection of glandular failure, lifelong hormone replacement therapy for established glandular failure, and familial screening.

Medical Therapy

Medical therapy for autoimmune polyendocrine syndrome (APS) depends upon the sub-type and the organ system involved.

References

  1. ↑ Bilezikian JP, Brandi ML, Cusano NE, Mannstadt M, Rejnmark L, Rizzoli R, Rubin MR, Winer KK, Liberman UA, Potts JT (2016). "Management of Hypoparathyroidism: Present and Future". J. Clin. Endocrinol. Metab. 101 (6): 2313–24. doi:10.1210/jc.2015-3910. PMC 5393596. PMID 26938200.
  2. ↑ Gan EH, Pearce SH (2017). "MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison's disease". Eur. J. Endocrinol. 176 (3): R123–R135. doi:10.1530/EJE-16-0581. PMID 27810905.
  3. ↑ Inder WJ, Meyer C, Hunt PJ (2015). "Management of hypertension and heart failure in patients with Addison's disease". Clin. Endocrinol. (Oxf). 82 (6): 789–92. doi:10.1111/cen.12592. PMID 25138826.
  4. ↑ Tucci V, Sokari T (2014). "The clinical manifestations, diagnosis, and treatment of adrenal emergencies". Emerg. Med. Clin. North Am. 32 (2): 465–84. doi:10.1016/j.emc.2014.01.006. PMID 24766944.
  5. ↑ Napier C, Pearce SH (2014). "Current and emerging therapies for Addison's disease". Curr Opin Endocrinol Diabetes Obes. 21 (3): 147–53. doi:10.1097/MED.0000000000000067. PMID 24755997.
  6. ↑ Grossman A, Johannsson G, Quinkler M, Zelissen P (2013). "Therapy of endocrine disease: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe". Eur. J. Endocrinol. 169 (6): R165–75. doi:10.1530/EJE-13-0450. PMC 3805018. PMID 24031090.
  7. ↑ Napier C, Pearce SH (2012). "Autoimmune Addison's disease". Presse Med. 41 (12 P 2): e626–35. doi:10.1016/j.lpm.2012.09.010. PMID 23177474.
  8. ↑ Quinkler M (2012). "[Addison's disease]". Med Klin Intensivmed Notfmed (in German). 107 (6): 454–9. doi:10.1007/s00063-012-0112-3. PMID 22907517.
  9. ↑ Caturegli P, De Remigis A, Rose NR (2014). "Hashimoto thyroiditis: clinical and diagnostic criteria". Autoimmun Rev. 13 (4–5): 391–7. doi:10.1016/j.autrev.2014.01.007. PMID 24434360.
  10. ↑ Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, Cooper DS, Kim BW, Peeters RP, Rosenthal MS, Sawka AM (2014). "Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement". Thyroid. 24 (12): 1670–751. doi:10.1089/thy.2014.0028. PMC 4267409. PMID 25266247.

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