Diseases of thyroid & parathyroid glands (1 of 2)

Diseases of thyroid & parathyroid glands (1 of 2)

Thyroid diseases Thyrotoxicosis Hypothyroidism Thyroiditis Graves disease Goiters Neoplasms Chronic Lymphocytic (Hashimoto) Thyroiditis Subacute Granulomatous (de Quervain) Thyroiditis Subacute Lymphocytic Thyroiditis Riedel thyroiditis adenoma Hyperfunctioning (toxic) carcinoma 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 The most common cause of thyrotoxicosis Graves Disease the most common cause of hyperthyroidism Primary Toxic (hyperfunctional) multinodular goiter Toxic (hyperfunctional) adenoma Secondary (central) rare from TSH-secreting pituitary adenoma in thyroiditis 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) 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 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

Clinical scenarios The thyroid function test (TFT) Low T4 and high TSH = 1ry hypothyroidism *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 Normal T4 and high TSH = subclinical 1ry hypothyroidism Low T4 and low TSH = central hypothyroidism If we want to choose 1 test, TSH is the best 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

Approach to thyrotoxicosis patient The examples and scenarios mentioned here are not all examples, but they are enough at this level *If central hyperthyroidism, do pituitary MRI 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 overuptake (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 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 Graves disease Multinodular goiter Toxic adenoma Thyrotoxicosis with low 24-h RAI uptake Factitious Subacute (painless) thyroiditis 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 Secondary (pituitary or hypothalamic failure) rare Congenital Primary Autoimmune Iatrogenic This label means: can cause enlargement (goiter) = Goitrous hypothyroidism Thyroid dysgenesis (problem in thyroid tissue development) Genetic Dyshormonogenetic goiter (problem in thyroid hormone production) rare but the most common cause of congenital hypothyroidism in the U.S. Hashimoto thyroiditis The most common cause in countries where iodine is supplemented in dietary salt products Endemic deficiency of dietary iodine a common cause of hypothyroidism in infants and children worldwide As a side effect -lithium -iodides -p-aminosalicylic acid Ablation Surgical ablation Ablation by radioiodine therapy Ablation by external radiation

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

Thyroiditis Chronic Lymphocytic (Hashimoto) Thyroiditis -mainly 45-65 years, but any age -Females more -CD8, IFN-gamma, other cytokines, macrophages, anti-thyroglobulin, antithyroid 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 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 Subacute Lymphocytic (Painless) Thyroiditis -Sometimes after delivery (postpartum thyroiditis) -Autoimmune (antithyroid antibodies 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 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) *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 Pseudopapillae (no fibrovascular cores) 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 )