Thyroid Study Notes Introduction - the thyroid begins as a patch on the back of the tongue (at the foramen cecum) and it descends into the necks - occasionally some or all of the gland ends up in the mediastinum instead, explaining the occasional retrosternal goiter - when the thyroid is active or just overstimulated, the cells will become taller and thyroglobulin will be reabsorbed - when the thyroid is inactive, the cells flatten down and the amount of colloid increases - any enlarged thyroid is a goiter Hyperthyroidism - categories - primary hyperthyroidism means the thyroid gland is over functioning becasue of some problem other than excess hTSH - secondary hyperthyroidism means the gland is hyper-functioning because it is being over-stimulated by too much hTSH, reflecting a primary problem in the hTSH-producing organ - tertiary hyperthyroidism means there is too much hTSH because there is too much TRH - signs and symptoms - hypermetabolism - weight loss, muscel atrophy, heat intolerance, and increased appetite; food is being burned for heat tather than ATP - increased mentation - may be mistaken for Alzheimer's in the elderly - enhanced epinephrine effect - tremulousness and anxiety - lid lag - a delay in downward movement of the upper eyelid as the pt looks down - atrial fibrillation - osteoporosis - LDL cholesterol goes dowm - thyroid storm - most dreaded problem - development of extreme hypermetabolism, leading to coma and death, when the pt is subjected to some other major physiologic stress - causes of hyperthyroidism - Grave's disease - hyperactive multinodular goiter / hyperactive adenoma - Jod-Basedow - well-differentiated thyroid cancer - DeQuervain's with rapid release of thyroglobulin - excess hTSH - excess TRH Cretinism - hyperthyroidism, presenting first in infancy or childhood - these people remain like small children both mentally and physically throughout their lives - if a mother is severely iodine deficient, the child will be severely retarded, deaf and spastic - less-severely affected children fail to thrive and remain stunted, they are likely to show any or all of the problems of adult myxedema - unless the cause is absence of thyroid hormone receptors, cretinism should never develop - epidemic cretinism - the result of endemic dietary deficiencies in iodine - sporadic cretinism - the result of some link in development or metabolism - causes - failure of the gland to form, problem with thyroxine synthesis, non-functioning thyroid hormone receptors, autoimmune thyroiditis, or radiation damage to the gland - you need to treat these kids aggressively with thyroid supplements Acquired Hypothyroidism - categories - primary hypothyroidism means the thyroid gland is under-functioning because of some problem other than insufficient hTSH - secondary hypothyroidism means the gland is hypo-functioning because it is being under-stimulated by too little hTSH, reflecting a primary problem in the pituitary gland - tertiary hypothyroidism means there is too little hTSH because there is too little TRH - signs and symptoms - slowing of mind and body - this progresses to myxedema coma and death - myxedema properly refers to accumulation of hydrophilic ground substance throughout the connective tissues of the body; this leads to coarsening of the facial features, enlargement of the tongue, puffiness around the eyes, and deepening and croaking of the voice - LDL cholesterol rises strikingly - cardiac dysfunction leads to low heart rate and loss of cardiac strength - constipation is common - dry skin and coarse, brittle hair - yellowish discoloration of the skin - cold intolerance - delayed deep tendon reflexes - causes later on in life - iatrogenic lack of thyroid tissue - excess iodine - iodine deficiency - subsisting largely on dietary goitrogen - Hashimoto's autoimmune thyroiditis or severe lymphatic thyroiditis - DeQuervain's - secondary hyporthyroidism - tertiary hypothyroidism Birth Defects - thyroglossal duct cysts are bits of the old thyroglossal duct; the cysts may be lined by thyroid and/or squamous epithelium, always with some lymphoid tissue - in some folks, the thyroid gland just never develops; unless the hormone is replaced, these people will become cretins Hashimoto's Thyroiditis - a common, chronic, progressive thyroid disease - pts are likely to have a gotier; most are euthyroid, many are hypothyroid, and a few are at least temporarily hyperthyroid - if biopsy it, you will see 1) lots of lymphocytes in the thyroid gland; 2) germinal centers; 3) plasma cells; 4) Hurthle cells - the thyroids express HLA-DR antigens on their follicular cells, and this might get the process going - these people have increased rates of autoimmune addisonism, pernicious anemia, Sjogren's, vitiligo, and type I diabetes Non-Hashimoto Lymphocytic Thyroiditis - abundant lymphocytes in the thyroid gland, but without germinal centers, plasma cells, or Hurthle cells; this is extremely common, especially in older pts and women - there may be a small goiter, and there may be transplant hyperthyroidism - the pathologist suspects the histopathology covers several diagnostic entities, including the ill-defined primary autoimmune myxedema, often seen in Down's Dequervain's Subacute Granulomatous Thyroiditis - infections involving the thyroid gland are extremely uncommon, with the outstanding exception of Dequervain's, a common, usually missed, usually mild disease - the thyroid follicles cells die off in patches, almost certainly the result of some virus or other - known culprits include mumps, coxsackie, EBV, ECHO, and adenovirus - the gland becomes large and painful - most pts are young adult women, but nobody is immune; major problem is usually pain - occasionally, enough thyroglobulin may be broken down to produce transient hyperthyroidism, or enough of the gland may be destroyed to produce hyperthyroidism - in weeks to months, things settle down and the disease goes away by itself Riedel's - a rare process in which fibroblasts proliferate and lay down collagen - most pts are older women, who present with a rock-hard neck mass - Riedel's does not respect the thyroid capsule, or anything else - it mimics an invasive sarcoma - enough of the gland may be destroyed to produce hypothyroidism - the disease usually stops before the pt asphyxiates Grve's Disease - this is a common problem caused by autoantibodies directed against the hTSH receptor; the receptor mistakes them for TSH - pts also usually exhibit opthalmopathy (proptosis/exopthalmous) - this is caused by a different autoantibody, and supposedly happens because thyroid microsomes, against which the Graves; pt makes antibodies, are mimics for some eye muscel antigen - to complete the triad, pts often exhibit myxedema-like nodules confinedto the anterior aspects of the lower extremities - Graves' is usually the cause of diffuse toxic goiter Diffuse Nontoxic Goiter - diffuse enlargement of the thyroid gland was historically due to epidemic goiter, caused by lack of iodine in the diet - this was often exacerbated goitrogens in the diet - Jod-Basedow phenomenon - when an iodine deficient pt is treated with a large amount of iodine, acute hyperthyroidism and even hyperthyroid crisis can supervene - a small diffuse goiter is almost the rule rather than the exception around menarche - in a multinodular goiter, there a re many nodules, most composed of follicles more or filled with colloid, others representing sites of old hemorrhage and fibrosis - carcinoma very seldom arises in multinodular goiter, and most cold nodules removed from thyroid glands turn out simply to be sleepy nodules from multinodular goiters Thyroid Adenomas - the vast majority of dominant thyroid nodules are either benign adenomas or just big nodules in a multinodular goiter - thyroid adenomas are composed of thyroid follicles; they are harmless or might produce excess T3 or T4 - thyroid adenomas have virtually no tendency to turn malignant Papillary Adenocarcinoma (orphan Annie's tumor) - this is a common, multifocal cancer common in adults, and not known in children - irridiating the thyroid gland gives an increased rate of papillary carcinoma; the increased risk from radioactive iodine therapy of Grave's is very small - any reasonably well-differentiated thyroid tumor with Orphan Annie nuclei will act like a papillary carcinoma of the thyroid - another finding is psammoma bodies - except for a few uncommon subtypes, these lesions are noted for being non-aggressive - often first diagnosed as a metastasis in a cervical node, survival is the rule - it prefers the lymphatic route - can kill people, typically by asphyxiation - also the breeding ground for anaplastic carcinoma of the thyroid - Orphan Annie's tumor reminds us of papillary carcinoma of the thyroid - primarily affects younger women - tends to stay around for years without getting any bigger - is usually well-behaved and seldom kills people - its nuclei exhibit marginated chromatin, producing the Orphan Annie's eye appearance - relative frequency of detected thyroid carcinomas: - papillary 65% - the large majority will not die of it - follicular 25% - around 75% will eventually die of it; it may be more than 5 years - medullary 5% - 50% 5-year mortality if sporadic, much better if you picked it up early as part of a workup - anaplastic 5% - almost all will die of it in short order Follicular Adenocarcinoma - this is a more aggressive thyroid carcinoma which generally makes follicles - often, maliganncy is established by demonstrating that a thyroid nodule contains groups of cells invading vessels - there are no good fibrovascular pappillae, Orphan Annie nuclei, or psammoma bodies - the tumor cells often take up radioactive iodine, which is useful both in scanning for metastases and for treating them - the tumor may be moderately hTSh dependent, and thyroid hormone administration may suppress them temporarily - this tumor tends to metastasize to lungs and bone Medullary Adenocarcinoma - this is cancer of C-cells - its stroma is almost always laced liberally with calcitonin pleated into amyloid - caused at least in part by loss of both copies of the MEN-II anti-oncogene on chromosome 10 - as befits cancer of C-cells, the tumor makes calcitonin; tetany may result Anaplastic Adenocarcinoma - very, very ugly, both histologically and clinically; we believe that most of these tumors arise in a previous papillary or follicular carcinoma - primary thyroid lymphoma is an uncommon B-cell neoplasm arising usually in Hashimoto's; look malignant lymphocytes inside the follicles Atrophy of the Thyroid - may have ingested I131 - other causes could be burned-out Hashimoto's or Dequervain's Thyroid Testing - serum T4 will give you total bound plus unbound - serum T3RU gives you a value inversely proportional to the number of unbound sites on the serum thyroid hormone carrying proteins - multiply T4 by T3RU to get thyroxine index, a measure of biologically active hormone