Thyrotoxicosis

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

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

Etiology

(1) Thyrotoxicosis Associated with Hyperthyroidism (i.e., normal or high radioactive iodine uptake (RAIU))

Ý TSH Production – through pituitary tumor (thyrotroph adenoma) or thyrotroph resistance to T₄ feedback

Ý 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 b adrenergic receptors in heart – leading to Ý inotropic and chronotropic effects

Clinical Manifestations

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

Skin: Warm and moist, hyperhydrosis

Eyes: Tremor eyes: stare, lid lag, lid retraction (increased sympathetic tone)

Cardio: Palpitations (Ý heart rate, stroke volume, and thus cardiac output). Hyperdynamic circualtion (ß peripheral resistance, widened pulse pressure). Arrythmias

GI: Hypermotility Þ fat malabsorption, hyperdefecation

Pulmonary: Dyspnea (weak respiratory muscles), ß pulmonary compliance, ß 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: ß menstrual blood flow, ß libido, gynecomastia in males

Labs: Negative nitrogen balance (protein degradation), ß 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 T₄Þ T₃

Surgery – removal of thyroid gland

Symptomatic Therapty – e.g., b -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 Goiter–Thyroid Stimulating IgG (TSI) activate TSH receptorÞ Ý 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) Þ leads to proptosis

(3) Dermopathy: (1% of patients) Pretibial Myxedema – accumulation of acid mucopolysaccharides and lymphocytes

Toxic multinodular Goiter (Plummer’s 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 Phenomenon–iodine-induced thyrotoxicosis – Ý 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 (DeQyervain’s, 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