Thyrotoxicosis clinical disorder due to excessive thyroid hormone action; more common in women

sometimes secondary to Hyperthyroidism sustained in thyroid hormone synthesis and release from thyroid gland
Etiology

(1) Thyrotoxicosis Associated with Hyperthyroidism (i.e., normal or high radioactive iodine uptake (RAIU)) TSH Production through pituitary tumor (thyrotroph adenoma) or thyrotroph resistance to T4 feedback Thyroid Stimulation Graves disease (TSH-R antibodies), trophoblast tumor (chorionic gonadotropin) Intrinsic Thyroid Autonomy toxic adenoma (benign tumor); toxic multinodular goiter, thyroid cancer (2) Thyrotoxicosis NOT Associated with Hyperthyroidism (i.e., low radioactive iodine uptake (RAIU)) Inflammatory disease silent thyroiditis, subacute thyroiditis (release of preformed hormones) Extrathyroidal source of hormone exogenous hormone (meds, food), ectopic thyroid tissue (struma ovarii)
Pathophysiology

(1) Overall increase of oxidative processes and thermogenesis (2) Increasing of metabolic activities in most tisues (3) Increase in adrenergic receptors in heart leading to inotropic and chronotropic effects
Clinical Manifestations

General: Heat intolerance, diaphoresis ( thermogenesis and cutaneous vasodilation), weight loss ( catabolic state, protein
degradation), weakness

Skin: Warm and moist, hyperhydrosis Eyes: Tremor eyes: stare, lid lag, lid retraction (increased sympathetic tone) Cardio: Palpitations ( heart rate, stroke volume, and thus cardiac output). Hyperdynamic circualtion ( peripheral resistance,
widened pulse pressure). Arrythmias

GI: Hypermotility fat malabsorption, hyperdefecation Pulmonary: Dyspnea (weak respiratory muscles), pulmonary compliance, vital capacity Neuropsych: Nervousness, anxiety, emotional lability, poor ability to concentrate, memory loss, insomnia, hyperkinesia (inability to
sit)

Neuromuscular: Proximal weakness and myopathy (protein degradation) Musculoskeletal: Hyperactive deep tendon reflexes, pathological fractures Repro: menstrual blood flow, libido, gynecomastia in males Labs: Negative nitrogen balance (protein degradation), serum lipids
Diagnosis

Measurement of thyroid hormone levels T4 x RT3U = Free T4 index Assessment of the hypothalamic-pituitary-thyroid axis High Sensitivity TSH (usually suppressed), TRH test
algorithms:

Start with low Free T4, confirm with high TSH start high TSH, confirm with low Free T4 Radioactive Iodine Uptake (RAIU)
Treatment

Radioactive Iodine (I-131) induces cell death; amelioration of symptoms take 6 months Antithyroid drugs (propylthiouracil, methimazole) blocks thyroid peroxidase and peripheral conversion T4 T3 Surgery removal of thyroid gland Symptomatic Therapty e.g., -blockers (propranolol)
Conditions Leading to Thyrotoxicosis due to Thyroid Overproduction of T4 and T3

Graves Disease women age 20-40, HLA-DR3, association with autoimmune disorders. 3 manifestations: (1) Thyrotoxicosis and GoiterThyroid Stimulating IgG (TSI) activate TSH receptor thyroid growth, vasularity,

secretion

(2) Optholmopathy infiltration of mononuclear cells, mucopolysaccharides; edema and fibrosis in orbital tissues
(extraocular muscles, orbital fat, lacrimal glands, interstitial connective tissue) leads to proptosis (3) Dermopathy: (1% of patients) Pretibial Myxedema accumulation of acid mucopolysaccharides and lymphocytes

Toxic multinodular Goiter (Plummers disease) age > 50; thyrotoxicosis from longstanding multinodular goiter Histology autonomous thyroid hyperplasia within individual follicles followed by continued replication and growth Toxic Adenoma benign tumor of the thyroid gland secretes thyroid hormone without TSH stimulation
typically presents as "Hot Nodule" single palpable nodule with intense iodine uptake

Jod-Basedow Phenomenoniodine-induced thyrotoxicosis production of T4 by autonomous thyroid with excess iodine this is the only thyrotixicosis with high T4 production and low RAIU (radioactive isotope is diluted out with stable iodine) Subacute Thyroiditis (DeQyervains, granulomatous thyroiditis) after a viral illness; self-limited, complete recovery painful giant cell inflammation/destruction of follicular epithelium with discharge of preformed hormone into circulation Painless Thyroiditis postpartum women; high titers of antimicrosomal antibodies (against intrathyroidal peroxidase) painless inflammation of thyroid still results in discharge of preformed thyroid hormone from damaged follicles