Diseases of thyroid & parathyroid glands

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Thyroid diseases

Thyrotoxicosis Hypothyroidism Thyroiditis Goiters Neoplasms

adenoma

carcinoma

Hyperfunctioning (toxic)

Nontoxic

Chronic Lymphocytic (Hashimoto) Thyroiditis

Subacute Granulomatous(de Quervain) Thyroiditis

Subacute Lymphocytic Thyroiditis

Riedel thyroiditis

Graves disease

Thyrotoxicosis

Increased production from thyroid gland (hyperthyroidism) Exogenous Release of preformed hormones from destroyed gland

in thyroiditis

The most common cause of thyrotoxicosis

GravesDisease…the mostcommon causeof hyperthyroidism

Toxic(hyperfunctional)multinodular goiter

Toxic(hyperfunctional) adenoma

Primary Secondary (central)…rare…from TSH-secreting pituitary adenoma

*A hypermetabolic state due to increased T3 & thyroxine (T4) in the blood

1- Granulomatous (de Quervain) thyroiditis (painful)2- Subacute lymphocytic thyroiditis (painless)

*Thyrotoxicosis also can occur in Hashimoto thyroiditis(Hashitoxicosis)

Clinical manifestations of thyrotoxicosis• Soft, warm & flushed skin…due to peripheral vasodilation to increase heat loss

• Heat intolerance and excessive sweating

• Weight loss in spite of normal or even increased appetite

• Rapid transit time (hypermotility) of the gut… diarrhea and fat malabsorption (steatorrhea)

• Palpitations and tachycardia…due to increased cardiac contractility & increased tissues oxygen requirements…may cause high cardiac output heart failure

• Nervousness, tremor and irritability

• Proximal muscle weakness (thyroid myopathy)

• Ocular changes (wide, staring gaze and lid lag)

• Thyroid ophthalmopathy: (wide, staring gaze and lid lag) + exophthalmos (proptosis)… in Graves disease

• Apathetic hyperthyroidism…in older adults…typical thyrotoxicosis features are blunted and only present with exaggerated heart disease or weight loss

In cases of infection, surgery, cessation of anti-thyroid medication, or any form

of stress…a thyroid storm may occur…especially in Graves…risk of fatal arrhythmia

Clinical scenarios

• Low T4 and high TSH = 1ry hypothyroidism

• Normal T4 and high TSH = subclinical 1ry hypothyroidism

• Low T4 and low TSH = central hypothyroidism

• Low T4 and normal or mildly elevated TSH = also central hypothyroidism

• High T4 and low TSH = non-central hyperthyroidism

• Normal T4 and low TSH check T3 (if high: T3 thyrotoxicosis), if T3 is not high subclinical non-central hyperthyroidism

• High T4 and high TSH = central hyperthyroidism

• High T4 and normal or mildly decreased TSH = also central hyperthyroidism

*We measure free T4 & free T3...these have the feedback on TSH*T3 is stronger than T4 in activating receptors…T4 is converted to T3 peripherally *Minor change in T3/T4 will cause a large change in TSH level *Most of the time we take free T4 & TSH and analyze their levels for the diagnosis

If we want to choose 1 test,TSH is the best

The thyroid function test (TFT)

Approach to thyrotoxicosis patient • Thyroid scan is different from thyroid uptake

• In thyroid scan we use a radioactive iodine or technetium and see the distribution of its uptake in the gland…it shows if a nodule is over-uptaking (a toxic adenoma for example) or homogenous over-uptake (Graves disease for example)

• In thyroid uptake, we give the iodine or technetium and just count the percentage of uptake to know if high- or low uptake*If central hyperthyroidism, do pituitary MRI

*If non-central hyperthyroidism:…do uptake…if the uptake is high, do scan, it may be Graves (in scan: homogenous) or toxic adenoma (in scan: 1 spot) or toxic multinodular goiter (in scan: multiple spots)…if the uptake is low, measure thyroglobulin, if it is high: thyroiditis (because thyroglobulin increases also with cell destruction), if it is low or normal: it may be factitious (exogenous)

The examples and scenarios mentioned here are not all examples, but they are enough at this level

Thyrotoxicosis with high 24-h RAI uptake

Thyrotoxicosis with low 24-h RAI uptake

Graves disease Factitious

Multinodular goiter Subacute (painless) thyroiditis

Toxic adenoma Granulomatous (painful) thyroiditis

Secretion from strumaovarii (ovarian teratoma containing mostly thyroid tissue)

Iodine-induced hyperthyroidismRAI: Radioactive iodine

Like using iodinated contrasts for imaging

Hypothyroidism

Secondary (pituitary or hypothalamic failure)…rare

Primary

CongenitalAutoimmune

Iatrogenic

Surgical ablation

Ablation by radioiodine therapy

Ablation by external radiation

AblationAs a side effect

Genetic

Thyroid dysgenesis(problem in thyroid tissue development)

Dyshormonogenetic goiter(problem in thyroid hormone production)

rare but the most common cause of congenital hypothyroidism in the U.S.

Endemic deficiency of dietary iodine

a common cause of hypothyroidism in infants and children worldwide

Hashimoto thyroiditis

The most common cause in countries where iodine is supplemented in dietary salt products

This label means: can cause enlargement (goiter) =Goitrous hypothyroidism

-lithium -iodides -p-aminosalicylicacid

Clinical manifestations of hypothyroidism• Cretinism in infancy or early childhood and myxedema in older children and adults

*Glycosaminoglycans with associated water are the cause of myxedematousfluid accumulation

-Protruding tongue-Growth retardation with short limbs-Coarse dry skin-Lack of hair and teeth-Mental deficiency-Pot belly-Often umbilical hernia-Hypotonia

Rubin, Raphael, David S. Strayer, and Emanuel Rubin, eds. Rubin's pathology: clinicopathologic foundations of medicine. Lippincott Williams & Wilkins

Thyroiditis

Chronic Lymphocytic (Hashimoto) Thyroiditis-mainly 45-65 years, but any age-Females more-CD8, IFN-gamma, other cytokines, macrophages, anti-thyroglobulin, anti-thyroid peroxidase-Goiter with too many lymphocytes including germinal centers with destruction of follicles, Hurthle (oxyphil) cell change and fibrosis…may end with atrophy-CTLA-4 mutations

Subacute Granulomatous(de Quervain) Thyroiditis-30-50 years-Females more-Viral infection-induced…not autoimmune-A majority of patients have ahistory of an upper-respiratory infection shortly before theonset of thyroiditis-painful-usually self-limited-destroyed follicles, extravasatedcolloid with exuberant granulomatous reaction

Subacute Lymphocytic(Painless) Thyroiditis-Sometimes after delivery(postpartum thyroiditis)-Autoimmune (antithyroidantibodies in majority of patients)-middle-aged women-usually self-limited

Riedel Thyroiditis-extensive fibrosis involving the thyroid and contiguous neck structures-an IgG4-related disease

The manifestations range from thyrotoxicosis to euthyroidstate to hypothyroidism

Patients with Hashimoto thyroiditis often have other autoimmune diseases and are at increased risk for the development of B-cell non-Hodgkin lymphomas in thyroid

Elsevier. Kumar et al. Robbins and Cotran pathologic basis of diseases 9th

Graves disease

Diffuse goiter + thyrotoxicosis + (in 40%) infiltrative ophthalmopathy (exophthalmos) + (in a minority of patients) infiltrative dermopathy (pretibial myxedema)

*20-40 years*Women more*1.5% to 2% of women in theUnited States…not uncommon*Genetic predisposition*HLA-DR3, CTLA-4 & PTPN22*Elevated antibodies:-TSI (thyroid-stimulating immunoglobulin)…an IgG…specific & in all patients-Thyroid growth-stimulating immunoglobulins-TSH-binding inhibitor immunoglobulins*Exophthalmos is caused by retroorbitalInflammation & increased retroorbital connective tissue/glycosaminoglycans, muscle & fat*Associated with other autoimmune diseases

Hypertrophy & hyperplasia of follicular epithelial cells

Pseudopapillae (no fibrovascular cores)

Lymphocytic infiltrate with germinal centers is common…not shown

Elsevier. Kumar et al. Robbins and Cotran pathologic basis of diseases 9th

Elsevier. Kumar et al. Robbins basic pathology 10th…modified

Goiter• Regarding the previously mentioned goitrous diseases (other than Graves):

…Early in goiter development, TSH-induced hypertrophy and hyperplasia of thyroid follicular cells usually result in diffuse, symmetric enlargement of the gland (diffuse goiter)

…Virtually all long-standing diffuse goiters convert into multinodular goiters

Clinical manifestations:-Cosmetic problem of a large neck mass-It may cause airway obstruction or dysphagia-It may cause compression of large vessels in the neck and upper thorax (so-called “superior vena cava syndrome”)