Toxic multinodular goiter differential diagnosis

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

Overview

Toxic multinodular goiter must be differentiated from other thyroid disorders. The most common differentials include Grave's disease, thyrotoxic phase of subacute thyroiditis and toxic adenoma.

Differentiating Toxic multinodular goiter from other Diseases

Toxic multinodular goiter may be differentiated from other thyroid disorders as follows:

Differentiation based on Functional (Nuclear) Imaging for Thyrotoxicosis

Functional (Nuclear) Imaging for Thyrotoxicosis
Diagnosis	Degree of Thyrotoxicosis	Radioactive iodine Uptake	Scintigraphy Image
Toxic multinodular goiter	+/++	Normal or +/++	Enlarged gland with multiple "hot" or "cold" nodules
Grave's disease	++++	++++	Enlarged gland with homogenous uptake
Thyrotoxic phase of subacute thyroiditis	++++	<1% at 4 or 24 hr.	Absent isotope uptake
Toxic adenoma	+/++	Normal or +/++	Dominant "hot" nodule with low or absent uptake in the surrounding normal gland.

Differentiation based on Imaging and TSH receptor antibodies

Cause of thyrotoxicosis	TSH receptor antibodies	Thyroid US	Color flow Doppler	Radioactive iodine uptake/Scan	Other features
Toxic nodular goiter	-	Multiple nodules	-	Hot nodules at thyroid scan	-
Graves' disease	+	Hypoechoic pattern	↑	↑	Ophthalmopathy, dermopathy, acropachy
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

Differentiation based on overall findings

Disease		Findings
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.
Thyroiditis	Direct chemical toxicity with inflammation	Amiodarone, sunitinib, pazopanib, axitinib, and other tyrosine kinase inhibitors may also be associated with a destructive thyroiditis.
	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.
	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.
	Acute hyperthyroidism from a levothyroxine overdose	The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.
	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.
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.

Disease	Findings
Multinodular goiter	Multinodular goiter is the multinodular enlargement of the thyroid gland. They are large nodules of more than 1 cm that produces symptoms of hyperthyroidism.
Grave's disease	Grave's disease is an autoimmune disease that affects the thyroid. It frequently results in hyperthyroidism and an enlarged thyroid. Pretibial myxedema and ophthalmopathy are some of the findings of grave's disease.
Hashimoto's disease	Hashimoto's disease is an autoimmune disease in which the thyroid gland is attacked by a variety of cell-mediated and antibody-mediated immune processes, causing primary hypothyroidism.
Medullary thyroid carcinoma	Medullary thyroid carcinoma is a form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.
Thyroid lymphoma	Thyroid lymphoma is a rare malignant tumor which manifests as rapidly enlarging neck mass causing respiratory difficulty.
De Quervain's thyroiditis	De Quervain's thyroiditis is a subacute granulomatous thyroiditis preceded by an upper respiratory tract infection.
Acute suppurative thyroiditis	Acute suppurative thyroiditis is an uncommon thyroid disorder usually caused by bacterial infection.