Sandbox: TMNG

Jump to navigation Jump to search


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

Pathophysiology

  • Toxic Multinodular Goiter (TMNG) is the result of hyperfunctioning thyroid follicles that are producing excess of thyroid hormones.
  • TMNG develops on top of hypertrophied thyroid from prolonged (due to iodine deficiency or any cause of primary hypothyroidism). Low T3 and T4 levels cause prolonged TSH stimulation which causes hypertrophy of the thyroid gland and the development of focal or diffuse hyperplasia.
  • Some of the nodules might develop hyperplasia and autonomous activity while others might degenerate, bleed and calcify.
  • After the gland has undergone global activation and hyperplasia. Thyrotoxicity develops due to focal epithelial cell proliferation and thyroxine secretion.
  • Hyperplastic gland is more likely to develop toxic goiter due to the following factors:
  • With high proliferation rate in the hyperplastic gland, there might be transcription errors that go unchecked. This gives rise to a variety of mutations including mutations leading to activation of cAMP such as TSH-R and Gsα mutations.
  • The process of synthesis of thyroxines involves the production of H2O2 and other free radicals, increasing the chance of developing mutations.
  • A thyroid gland under the stress of over proliferation (in response to a state of hypothyroidism and excessive TSH stimulation) has increased growth factor expression. After resolution of the stimulus, the proliferating follicles continue to produce thyroxines even after the TSH stimulus ceases. Moreover, cells having the mutations will continue to produce cells having the same mutations.

Historical perspective

  • Goiter was first seen in the inhabitants of Alps. They documented that consuming sea weeds caused improvement of the condition (which is supports the theory that the goiter was due Iodine deficiency).[1]
  • Goiter was described in Ancient Greece also and was called “Broncholcele”. This was 200 years before the discovery of thyroid gland.[2]
  • In 1850, Consuming Iodine as a preventive measure from goiter was suggested and this was the basis of providing Iodine in the meals provided to the students.
  • In 1884, thyroidectomies were tried successfully for treatment of goiter.[3]
  • In a 2000 thyroidectomies performed by Kocher in the 19th century, the mortality rate was reported as 5%.

Classification

  • A "diffuse goitre" is a goitre that has spread through all of the thyroid. It can be
  • Simple goitre"
  • multinodular goitre").
  • "Toxic goitre" refers to goitre with hyperthyroidism. These most commonly due to Graves disease, but can be caused by inflammation or a multinodular goitre.
  • "Nontoxic goitre" (associated with normal or low thyroid levels) refers to all other types (such as that caused by lithium or certain other autoimmune diseases).

Causes

Differentiating toxic nodular goiter from other diseases

Toxic multinodular goiter must be differentiated from other diseases that cause hyperthyroidism and neck mass such as Graves' disease and thyroiditis

Cause of thyrotoxicosis TSH receptor Antibodies Thyroid US Color flow Doppler Radioactive iodine uptake/Scan Other features
Graves' disease + Hypoechoic pattern Ophthalmopathy, dermopathy, acropachy
Toxic nodular goiter - Multiple nodules - Hot nodules at thyroid scan -
Toxic adenoma - Single nodule - Hot nodule -
Subacute thyroiditis - Heterogeneous hypoechoic areas Reduced/absent flow Neck pain, fever, and
elevated inflammatory index
Painless thyroiditis - Hypoechoic pattern Reduced/absent flow -
Amiodarone induced thyroiditis-Type 1 - Diffuse or nodular goiter ↓/Normal/↑ ↓ but higher than in Type 2 High urinary iodine
Amiodarone induced thyroiditis-Type 2 - Normal Absent ↓/absent High urinary iodine
Central hyperthyroidism - Diffuse or nodular goiter Normal/↑ Inappropriately normal or high TSH
Trophoblastic disease - Diffuse or nodular goiter Normal/↑ -
Factitious thyrotoxicosis - Variable Reduced/absent flow ↓ serum thyroglobulin
Struma ovarii - Variable Reduced/absent flow Abdominal RAIU

Prominent features in the different causes of hyperthyroidism

Disease Findings
Thyroiditis Direct chemical toxicity with inflammation Amiodarone, sunitinib, pazopanib, axitinib, and other tyrosine kinase inhibitors may also be associated with a destructive thyroiditis.[4][5]
Radiation thyroiditis Patients treated with radioiodine may develop thyroid pain and tenderness 5 to 10 days later, due to radiation-induced injury and necrosis of thyroid follicular cells and associated inflammation.
Drugs that interfere with the immune system Interferon-alfa is a well-known cause of thyroid abnormality. It mostly leads to the development of de novo antithyroid antibodies.[6]
Lithium Patients treated with lithium are at a high risk of developing painless thyroiditis and Graves' disease.
Palpation thyroiditis Manipulation of the thyroid gland during thyroid biopsy or neck surgery and vigorous palpation during the physical examination may cause transient hyperthyroidism.
Exogenous and ectopic hyperthyroidism Factitious ingestion of thyroid hormone The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.[7]
Acute hyperthyroidism from a levothyroxine overdose The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.[8]
Struma ovarii Functioning thyroid tissue is present in an ovarian neoplasm.
Functional thyroid cancer metastases Large bony metastases from widely metastatic follicular thyroid cancer cause symptomatic hyperthyroidism.
Hashitoxicosis It is an autoimmune thyroid disease that initially presents with hyperthyroidism and a high radioiodine uptake caused by TSH-receptor antibodies similar to Graves' disease. It is then followed by the development of hypothyroidism due to the infiltration of the thyroid gland with lymphocytes and the resultant autoimmune-mediated destruction of thyroid tissue, similar to chronic lymphocytic thyroiditis.[9]
Toxic adenoma and toxic multinodular goiter Toxic adenoma and toxic multinodular goiter are results of focal/diffuse hyperplasia of thyroid follicular cells independent of TSH regulation. Findings of single or multiple nodules are seen on physical examination or thyroid scan.[10]
Iodine-induced hyperthyroidism It is uncommon but can develop after an iodine load, such as administration of contrast agents used for angiography or computed tomography (CT), or iodine-rich drugs such as amiodarone.
Trophoblastic disease and germ cell tumors Thyroid-stimulating hormone and HCG have a common alpha-subunit and a beta-subunit with considerable homology. As a result, HCG has weak thyroid-stimulating activity and high titer HCG may mimic hyperthyroidism.[11]

References

  1. Ghosh N, Chattopadhyay D, Mukhopadhyay S, Addya S, Chatterjee GC (1988). "Cellular defence mechanism under the influence of lanthanum intoxication in chick bone marrow". Indian J. Exp. Biol. 26 (5): 374–6. PMID 3169859.
  2. Ahn J (2008). "[Historical perspectives of the treatment of thyroid disease]". Uisahak (in Korean). 17 (1): 99–110. PMID 19008657.
  3. Hennessey JV (2015). "HISTORICAL AND CURRENT PERSPECTIVE IN THE USE OF THYROID EXTRACTS FOR THE TREATMENT OF HYPOTHYROIDISM". Endocr Pract. 21 (10): 1161–70. doi:10.4158/EP14477.RA. PMID 26121440.
  4. Lambert M, Unger J, De Nayer P, Brohet C, Gangji D (1990). "Amiodarone-induced thyrotoxicosis suggestive of thyroid damage". J. Endocrinol. Invest. 13 (6): 527–30. PMID 2258582.
  5. Ahmadieh H, Salti I (2013). "Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment". Biomed Res Int. 2013: 725410. doi:10.1155/2013/725410. PMC 3824811. PMID 24282820.
  6. Vialettes B, Guillerand MA, Viens P, Stoppa AM, Baume D, Sauvan R, Pasquier J, San Marco M, Olive D, Maraninchi D (1993). "Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies". Acta Endocrinol. 129 (1): 31–8. PMID 8351956.
  7. Cohen JH, Ingbar SH, Braverman LE (1989). "Thyrotoxicosis due to ingestion of excess thyroid hormone". Endocr. Rev. 10 (2): 113–24. doi:10.1210/edrv-10-2-113. PMID 2666114.
  8. Jha S, Waghdhare S, Reddi R, Bhattacharya P (2012). "Thyroid storm due to inappropriate administration of a compounded thyroid hormone preparation successfully treated with plasmapheresis". Thyroid. 22 (12): 1283–6. doi:10.1089/thy.2011.0353. PMID 23067331.
  9. Fatourechi V, McConahey WM, Woolner LB (1971). "Hyperthyroidism associated with histologic Hashimoto's thyroiditis". Mayo Clin. Proc. 46 (10): 682–9. PMID 5171000.
  10. Laurberg P, Pedersen KM, Vestergaard H, Sigurdsson G (1991). "High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland". J. Intern. Med. 229 (5): 415–20. PMID 2040867.
  11. Oosting SF, de Haas EC, Links TP, de Bruin D, Sluiter WJ, de Jong IJ, Hoekstra HJ, Sleijfer DT, Gietema JA (2010). "Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non-seminomatous germ-cell tumors". Ann. Oncol. 21 (1): 104–8. doi:10.1093/annonc/mdp265. PMID 19605510.