Hypothyroidism resident survival guide

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Hypothyroidism Resident Survival Guide Microchapters
Overview
Causes
Diagnosis
Treatment
Do's
Don'ts

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

Synonyms and keywords: Approach to hypothyroidism, Hypothyroidism work-up, Hypothyroidism management

Overview

Hypothyroidism is a clinical state where there is a reduced production or action of thyroid hormones - Thyroxine (T4) and Triiodothyronine (T3). It is classified based on the location of pathology into primary hypothyroidism, secondary hypothyroidism and tertiary hypothyroidism. The most common cause worldwide is Iodine deficiency. In iodine sufficient areas the most common cause is autoimmune thyroiditis. Risk factors for the development of hypothyroidism include female sex, iodine deficiency, selenium deficiency, presence of other autoimmune conditions. Clinical presentation depends on the degree and rapidity of hormone depletion. Patients can be asymptomatic or present with symptoms like cold intolerance, fatigue, weight gain, constipation, depression, neck mass. The diagnosis of hypothyroidism is made with the help of biochemical tests measuring TSH and Thyroxine (FT4) levels. Treatment of this condition is with Levothyroxine supplementation. [1]

Causes


Hypothyroidism can be classified based on the location of the pathology or based on etiology as shown in the table below.[2][3][4][5][6]

Life Threatening Causes

Common Causes

Causes of hypothyroidism
Primary hypothyroidism Central hypothyroidism

( Secondary and Tertiary )

Congenital hypothyroidism
Autoimmune Drug induced Iatrogenic Transient Hypothyroidism Infiltrative disorders Genetic causes Iatrogenic Tumors Vascular Infiltrative Infectious Miscellaneous
  • TRH deficiency
  • Isolated CeH
  • Inactive TSH
  • Inactive TRH receptor


Diagnosis

Shown below is an algorithm summarizing the diagnosis of hypothyroidism: [7][8][9][10][11]


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signs and Symptoms of hypothyroidism are present.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TSH, free T4 (FT4)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TSH >5.5mU/L
 
 
 
 
 
 
 
 
TSH 0.5-5mU/L
 
 
 
 
 
 
 
 
 
TSH<0.5mU/L
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FT4 Low
 
 
FT4 Normal
 
 
 
FT4 Elevated
 
 
FT4 Low
 
 
 
 
 
 
 
 
 
FT4 Low
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TPOAb
(Thyroid peroxidase antibody)
 
 
Subclinical hypothyroidism
 
 
 
1. T4 to T3 conversion defect
(5' deiodinase deficiency, amiodarone use),
2. Thyroid hormone resistance
 
 
1. Central hypothyroidism,
2. T3 replacement therapy
 
 
 
 
 
 
 
 
 
1. Following excess levothyroxine withdrawal,
2. "Post hyperthyroid" hypothyroidism
( I131 or surgery),
3. T3 replacement therapy,
4.Central hypothyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Central hypothyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Autoimmune thyroid disease
(Hashimotos disease)
 
1. Euthyroid sick syndrome
2. External radiation
3. Drug induced
4. Iodine deficiency
5. Congenital hypothyroidism
6. Seronegative autoimmune thyroid disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brain MRI
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abnormal
 
Normal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pituitary or Hypothlamus lesion
 
Congenital TRH, TSH deficiency,
Infiltrative diseases
 
 
 
 

Treatment

Shown below is an algorithm summarizing the treatment of Primary hypothyroidism. [12][13]

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary hypothyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TSH > 5.5mU/L,
FT4 Low
 
 
 
 
 
 
 
 
TSH = 5.5 - 10 mU/L,
FT4 Normal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Start Levothyroxine
 
 
 
 
 
 
 
 
Symptoms of hypothyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Measure TSH after 4-6 weeks
 
 
 
Present
 
 
 
 
 
 
 
Absent
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Goal TSH = 0.4-4mU/L
Adjust levothyroxine dose if goal TSH not reached
 
 
 
Levothyroxine trial for 3-6 months.
 
 
 
 
 
 
 
 
TPoAB
(Thyroid Peroxidase) Antibodies
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptoms of hypothyroidism
 
 
 
 
 
 
Positive
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Resolved
 
Unresolved
 
 
 
 
Follow up with annual TSH
 
Follow up with TSH every 3 years
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lifelong levothyroxine therapy
 
 
 
 
 
 
 
 
 
 

Shown below is an algorithm summarizing the treatment of Central hypothyroidism. [14]


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Central hypothyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TSH<0.5mU/L
0r 0.5-5.5mu/L, FT4 Low
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adrenal insufficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MRI Brain
 
 
 
 
 
 
 
 
 
 
 
Give glucocorticoids for 1-2 weeks to prevent adrenal crisis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor
 
 
 
 
 
 
 
 
 
 
 
Levothyroxine
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Present
 
Absent
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider Surgery
 
Levothyroxine
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reassess by measuring FT4
Goal FT4 is
upper limit of normal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Do's

Don'ts

References

  1. Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM; et al. (2018). "Global epidemiology of hyperthyroidism and hypothyroidism". Nat Rev Endocrinol. 14 (5): 301–316. doi:10.1038/nrendo.2018.18. PMID 29569622.
  2. Rizzo LFL, Mana DL, Serra HA (2017). "Drug-induced hypothyroidism". Medicina (B Aires). 77 (5): 394–404. PMID 29044016.
  3. Falhammar H, Juhlin CC, Barner C, Catrina SB, Karefylakis C, Calissendorff J (2018). "Riedel's thyroiditis: clinical presentation, treatment and outcomes". Endocrine. 60 (1): 185–192. doi:10.1007/s12020-018-1526-3. PMC 5845586. PMID 29380231.
  4. Gupta V, Lee M (2011). "Central hypothyroidism". Indian J Endocrinol Metab. 15 (Suppl 2): S99–S106. doi:10.4103/2230-8210.83337. PMC 3169862. PMID 21966662.
  5. Vural Ç, Paksoy N, Gök ND, Yazal K (2015). "Subacute granulomatous (De Quervain's) thyroiditis: Fine-needle aspiration cytology and ultrasonographic characteristics of 21 cases". Cytojournal. 12: 9. doi:10.4103/1742-6413.157479. PMC 4453108. PMID 26085833.
  6. Kumar PG, Anand SS, Sood V, Kotwal N (2005). "Thyroid dyshormonogenesis". Indian Pediatr. 42 (12): 1233–5. PMID 16424561.
  7. Ladenson PW, Singer PA, Ain KB, Bagchi N, Bigos ST, Levy EG; et al. (2000). "American Thyroid Association guidelines for detection of thyroid dysfunction". Arch Intern Med. 160 (11): 1573–5. doi:10.1001/archinte.160.11.1573. PMID 10847249.
  8. Walsh JP, Bremner AP, Feddema P, Leedman PJ, Brown SJ, O'Leary P (2010). "Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques". J Clin Endocrinol Metab. 95 (3): 1095–104. doi:10.1210/jc.2009-1977. PMID 20097710   20097710  Check |pmid= value (help).
  9. Fitzgerald SP, Bean NG, Falhammar H, Tuke J (2020). "Clinical Parameters Are More Likely to Be Associated with Thyroid Hormone Levels than with Thyrotropin Levels: A Systematic Review and Meta-analysis". Thyroid. doi:10.1089/thy.2019.0535. PMID 32349628    32349628   Check |pmid= value (help).
  10. Peeters RP (2017). "Subclinical Hypothyroidism". N Engl J Med. 376 (26): 2556–2565. doi:10.1056/NEJMcp1611144. PMID 28657873.
  11. Persani L, Brabant G, Dattani M, Bonomi M, Feldt-Rasmussen U, Fliers E; et al. (2018). "2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism". Eur Thyroid J. 7 (5): 225–237. doi:10.1159/000491388. PMC 6198777. PMID 30374425.
  12. Okosieme O, Gilbert J, Abraham P, Boelaert K, Dayan C, Gurnell M; et al. (2016). "Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee". Clin Endocrinol (Oxf). 84 (6): 799–808. doi:10.1111/cen.12824. PMID 26010808.
  13. Chakera AJ, Pearce SH, Vaidya B (2012). "Treatment for primary hypothyroidism: current approaches and future possibilities". Drug Des Devel Ther. 6: 1–11. doi:10.2147/DDDT.S12894. PMC 3267517. PMID 22291465.
  14. Persani L (2012). "Clinical review: Central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges". J Clin Endocrinol Metab. 97 (9): 3068–78. doi:10.1210/jc.2012-1616. PMID 22851492.
  15. 15.0 15.1 Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/10.4158/EP12280.GL Check |pmid= value (help).