This is a mechanism of disease map for thyrotoxicosis, which encompasses hyperthyroidism. We discuss the various etiologies and manifestations of these conditions.

ERRATA:
The laboratory obtained TSH levels in Graves disease are usually LOWER than normal. I meant to elicit that the activity through the TSH pathway is increased in Graves disease, since there is errant production of antibodies, thyroidstimulating immunoglobulins (TSI), that have a similar effect to TSH. The depiction of Graves disease on final slide might be incorrect and misleading.

ADDITIONAL TAGS:
GoF mutations in TSHr gene
Subacute lymphocytic thyroiditis:
lymphocytic infiltration
Thyrotoxicosis / Hyperthyroidism
Etiologies
Core concepts
Neoplasia / mutation
Inflammation / cell damage
Iatrogenic
Microbial pathogenesis
Cardiovascular pathology
Biochemistry
Hormone dysregulation
Pharmacology / toxicity
Immune system dysfunction
Flow gradients physiology
Musculoskeletal pathology
Nutrient deficiency
Signs / symptoms
Labs / tests / imaging results
Manifestations
Thyrotoxicosis:
High level of circulating thyroid hormone (T3, T4)
→ hypermetabolism
Hyperthyroidism:
Overproduction of thyroid hormones (T3 / T4) by the thyroid gland
Definitions
thyroiditis
Subacute granulomatous thyroiditis (de Quervain): multinucleated giant cells, granuloma and fibrosis
Viral infections: mumps, coxsackie, influenza, echovirus, adenovirus
αinterferon, lithium, amiodarone, IL2, TK inhibitors, iodine (contrast)
Druginduced thyroiditis
Postpartum thyroiditis
T1DM
TPO Ab
RAIA, external beam RT
PTH surgery
Radiation thyroiditis
Palpation thyroiditis
xerostomia
Excessive exogenous intake of thyroid hormone
Ectopic (extrathyroidal) hormone production
Struma ovarii
Metastatic follicular thyroid carcinoma
hyperfunctioning gland
Graves disease: TSHr IgG
↑ TSH
Infectious: Y enterocolitica, B burgdorferi
Pregnancy
Pituitary thyrotropic adenoma
TSHr mutation → autonomous functioning nodules
Chronic iodine def → ↓T3,T4 → ↑TRH → persistent ↑TSH → nodular hyperplasia
Toxic multi nodular goiter
Multiple palpable nodules
Painless
Toxic adenoma:
Solitary hot nodule
Hydatidiform mole
Choriocarcinoma
↑ βhCG
Increased cutaneous blood flow
Excessive sweating
Heat intolerance
Increased appetite
Weight loss
Glycosaminoglycan deposition
Infiltrative dermopathy (pretibial myxedema)
Adrenergic overactivity
Spasming of the smooth muscle of the levator palpebrae superioris
TSH autoAb in orbital cavity → bind TSHr → lymphocytic infiltration → inflammation, cytokines → stimulates fibroblasts to secrete GAGs (hyaluronic acid) → osmotically pulls water into space
Graves ophthalmopathy
Lid lag
Diffuse, smooth goiter
Tachycardia
Palpitations
Heart failure
Hypertension
Pedal edema
Exertional dyspnea
Hyperreflexia, tremulousness (fine tremor)
T3 stimulates osteoclastic bone resorption
Osteopathy +/ fractures
↑ Serum sex hormonebinding globulin (SHBG) levels
↓ testosterone PLUS
↑ extragonadal conversion of testosterone→estradiol
↓ serum free (unbound) estradiol
Oligo/amenorrhoea, anovulatory infertility, dysfunctional uterine bleeding
Gynecomastia, decreased libido, infertility, erectile dysfunction
Neuropsych: anxiety, emotional instability, depression, restlessness, insomnia