Diseases of thyroid & parathyroid glands (1 of 2) Ali Al Khader, M.D. Faculty of Medicine Al-Balqa’ Applied University Email: ali.alkhader@bau.edu.jo

Thyroid diseases Thyrotoxicosis Hypothyroidism Thyroiditis Graves disease Goiters Neoplasms adenoma Chronic Lymphocytic (Hashimoto) Thyroiditis carcinoma Subacute Granulomatous (de Quervain) Thyroiditis Riedel thyroiditis Hyperfunctioning (toxic) Subacute Lymphocytic Thyroiditis Nontoxic

Thyrotoxicosis *A hypermetabolic state due to increased T3 & thyroxine (T4) in the blood Increased production from thyroid gland (hyperthyroidism) Exogenous Release of preformed hormones from destroyed gland in thyroiditis The most common cause of thyrotoxicosis Primary Secondary (central) …rare …from TSH-secreting pituitary adenoma Toxic (hyperfunctional) multinodular goiter 1- Granulomatous (de Quervain) thyroiditis (painful) 2- Subacute lymphocytic thyroiditis (painless) *Thyrotoxicosis also can occur in Hashimoto thyroiditis (Hashitoxicosis) Graves Disease …the most common cause of hyperthyroidism Toxic (hyperfunctional) adenoma

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

*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 Clinical scenarios The thyroid function test (TFT) 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 If we want to choose 1 test, TSH is the best

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 The examples and scenarios mentioned here are not all examples, but they are enough at this level *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) 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 struma ovarii (ovarian teratoma containing mostly thyroid tissue) Iodine-induced hyperthyroidism RAI: Radioactive iodine Like using iodinated contrasts for imaging

Hypothyroidism This label means: can cause enlargement (goiter) = Goitrous hypothyroidism Secondary (pituitary or hypothalamic failure) …rare Primary Iatrogenic Autoimmune Congenital Hashimoto thyroiditis Ablation As a side effect Genetic The most common cause in countries where iodine is supplemented in dietary salt products Surgical ablation -lithium -iodides -p-aminosalicylic acid Dyshormonogenetic goiter (problem in thyroid hormone production) Thyroid dysgenesis (problem in thyroid tissue development) Ablation by radioiodine therapy Ablation by external radiation Endemic deficiency of dietary iodine rare but the most common cause of congenital hypothyroidism in the U.S. a common cause of hypothyroidism in infants and children worldwide

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 myxedematous fluid accumulation

The manifestations range from Thyroiditis Chronic Lymphocytic (Hashimoto) Thyroiditis Subacute Granulomatous (de Quervain) Thyroiditis Subacute Lymphocytic (Painless) Thyroiditis Riedel Thyroiditis -extensive fibrosis involving the thyroid and contiguous neck structures -an IgG4-related disease -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 -30-50 years -Females more -Viral infection-induced …not autoimmune -A majority of patients have a history of an upper-respiratory infection shortly before the onset of thyroiditis -painful -usually self-limited -destroyed follicles, extravasated colloid with exuberant granulomatous reaction -Sometimes after delivery (postpartum thyroiditis) -Autoimmune (antithyroid antibodies in majority of patients) -middle-aged women -usually self-limited The manifestations range from thyrotoxicosis to euthyroid state 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

Graves disease Diffuse goiter + thyrotoxicosis + (in 40%) infiltrative ophthalmopathy (exophthalmos) + (in a minority of patients) infiltrative dermopathy (pretibial myxedema) Pseudopapillae (no fibrovascular cores) *20-40 years *Women more *1.5% to 2% of women in the United 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 retroorbital Inflammation & increased retroorbital connective tissue/glycosaminoglycans, muscle & fat *Associated with other autoimmune diseases Lymphocytic infiltrate with germinal centers is common …not shown Hypertrophy & hyperplasia of follicular epithelial cells

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”)

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