Thyroiditis Subtypes & Thyrotoxicosis Differential

Destructive thyroiditis: leaking, not overproducing

Two kinds of thyrotoxicosis. Thyrotoxicosis means tissues are exposed to excess thyroid hormone from any source; hyperthyroidism is the subset in which the gland is synthesizing too much. Destructive thyroiditis causes thyrotoxicosis without hyperthyroidism: inflammation breaks open follicles, and stored colloid empties into the blood carrying preformed T4, T3 and thyroglobulin. With TSH suppressed and follicles injured, the gland traps almost no iodide, so radioactive iodine uptake (RAIU) is near zero while serum thyroglobulin is high.

The triphasic course. The thyrotoxic phase lasts only until colloid stores run out, usually a few weeks. A hypothyroid phase follows for weeks to months while TSH rises and follicles regenerate. Most patients are euthyroid again within about a year; a minority, more often in the autoimmune forms, stay permanently hypothyroid. Not every patient shows every phase.

Methimazole and propylthiouracil block synthesis that is not happening, and an inflamed gland cannot concentrate radioiodine, so neither helps. Propranolol controls tremor and tachycardia; levothyroxine is reserved for a symptomatic or prolonged hypothyroid phase.

Subacute, painless and postpartum thyroiditis

Subacute granulomatous (de Quervain) thyroiditis. This presumed post-viral disorder follows an upper respiratory infection by a few weeks, is linked to HLA-B35, and mostly affects women aged 30–50. The gland is exquisitely tender, pain radiates to the jaw or ear and may migrate from one lobe to the other, and patients have fever and malaise. ESR is markedly raised, often above 50 mm/h, and thyroid antibodies are usually absent. Microscopy shows follicle destruction with early neutrophils, then granulomas whose multinucleated giant cells surround fragments of colloid. NSAIDs treat mild pain; prednisone brings relief within a day or two in severe cases (a response that supports the diagnosis), and pain may flare if the taper is too fast. About 5–15% remain permanently hypothyroid.

Painless (silent) thyroiditis. A self-limited variant of autoimmune (Hashimoto-type) thyroiditis: the gland is nontender and normal-sized or slightly enlarged, ESR is normal, and anti-TPO antibodies are present in about half. Histology shows lymphocytic infiltration without granulomas and without the extensive fibrosis and Hürthle-cell change of established Hashimoto disease.

Postpartum thyroiditis. The same lymphocytic process arising within 12 months of delivery or miscarriage, as the immune tolerance of pregnancy rebounds. It affects about 5% of women; the thyrotoxic phase typically falls 1–4 months and the hypothyroid phase 4–8 months postpartum. Risk factors are anti-TPO positivity during pregnancy, type 1 diabetes and a previous episode. It usually recurs after later pregnancies, and many women develop permanent hypothyroidism over the following years, so TSH is checked yearly.

Postpartum Graves disease is the key mimic: it has TSH-receptor antibodies, high uptake, increased Doppler flow and a total T3:T4 ratio above 20 (ng/µg), whereas thyroiditis has low uptake, reduced flow and a lower ratio. A radioiodine scan in a nursing mother requires a temporary pause in breastfeeding.

Riedel, suppurative and drug-induced thyroiditis

Riedel thyroiditis. Dense fibrosis replaces the gland and breaks through the capsule into the strap muscles, trachea, esophagus, recurrent laryngeal nerves and sometimes the parathyroids, producing a painless, woody, fixed goiter with stridor, dysphagia or hoarseness. It is part of IgG4-related disease and clusters with retroperitoneal fibrosis, sclerosing cholangitis, type 1 autoimmune pancreatitis and orbital pseudotumor. A hard, fixed mass also suggests anaplastic carcinoma, and fine-needle samples are often inadequate, so core or open biopsy decides. Anaplastic carcinoma arises in the elderly, often in a long-standing goiter, grows rapidly, shows pleomorphic spindle and giant cells with frequent TP53 mutations, and is usually fatal within a year. Riedel is treated with glucocorticoids (tamoxifen or rituximab if refractory) plus surgery to relieve airway compression.

Acute suppurative thyroiditis. The thyroid normally resists infection thanks to its capsule, rich blood and lymphatic supply and high iodine content. Bacterial infection (Staphylococcus aureus, Streptococcus pyogenes, oropharyngeal anaerobes) causes fever and a red, fluctuant, painful neck with usually normal thyroid function. In children, recurrent left-sided episodes point to a piriform sinus fistula, a remnant of the third or fourth pharyngeal pouch, shown by barium swallow or CT and cured by excising the tract. Adults at risk are immunocompromised or have a nodule or recent needle aspiration.

Drug-induced thyroiditis. PD-1 and PD-L1 inhibitors (nivolumab, pembrolizumab, atezolizumab) cause a painless destructive thyroiditis, usually in the first months of therapy, that often ends in permanent hypothyroidism; CTLA-4 blockade (ipilimumab) more often causes hypophysitis. Interferon-α can trigger painless thyroiditis, Hashimoto hypothyroidism or Graves disease. Lithium mainly causes goiter and hypothyroidism by inhibiting hormone release but is also linked to painless thyroiditis. Amiodarone, about 37% iodine by weight, causes type 1 thyrotoxicosis (iodine-fueled synthesis in a nodular or latent Graves gland; thionamides) or type 2 (destructive thyroiditis in a normal gland; glucocorticoids).

Sorting thyrotoxicosis: uptake, thyroglobulin and hCG

The workup. A suppressed TSH with high free T4 or T3 establishes thyrotoxicosis; an unsuppressed TSH instead points to a TSH-secreting adenoma. Unless Graves disease is obvious from ophthalmopathy and a diffuse goiter, TSH-receptor antibodies or an uptake scan separate overproduction from leakage. Doppler flow and the T3:T4 ratio help when radioiodine is contraindicated, as in pregnancy.

Autonomous nodules. Toxic adenomas and the hot nodules of toxic multinodular goiter carry somatic gain-of-function mutations, most often in the TSH receptor and less often in Gsα (GNAS). Constitutive Gs–cAMP signaling drives growth and secretion without TSH. Toxic multinodular goiter (Plummer disease) favors older adults from iodine-deficient regions and lacks Graves eye and skin signs. Hot nodules are rarely malignant, and an iodine load such as CT contrast can unmask their autonomy (Jod-Basedow phenomenon).

Low-uptake causes. Exogenous levothyroxine, taken surreptitiously or for weight loss, suppresses TSH, leaving a small gland and a low thyroglobulin, the key distinction from thyroiditis; anti-thyroglobulin antibodies can falsely lower the measurement and are checked alongside. After an iodine load the expanded iodide pool dilutes the tracer. Struma ovarii, an ovarian teratoma made mostly of thyroid tissue, secretes hormone outside the neck, so tracer collects in the pelvis.

hCG-mediated thyrotoxicosis. hCG shares the α subunit of TSH, LH and FSH, and its β subunit resembles that of TSH, so very high levels weakly stimulate the TSH receptor. Gestational transient thyrotoxicosis appears near the first-trimester hCG peak, especially with hyperemesis gravidarum or twins; TSH-receptor antibodies are negative, there is no ophthalmopathy, and it fades as hCG falls. Hydatidiform mole and choriocarcinoma produce far higher hCG and can cause overt hyperthyroidism that remits once the tumor is treated.