pato

HYPERTHYROIDISM

Definitions and Epidemiology

  • Hyperthyroidism: A clinical and biochemical syndrome that results from the excessive production of thyroid hormones by the thyroid gland. This condition is characterized by:
      - Increased circulating T3 and T4 values.
      - Suppression of TSH (Thyroid Stimulating Hormone).
      - Associated metabolic, cardiovascular, neurological, and systemic effects.

  • Thyrotoxicosis: A clinical and biological syndrome caused by an excess of thyroid hormones at the tissue level, irrespective of the cause or origin, characterized by:
      - Increased levels of circulating T3 and T4.
      - Suppressed TSH.
      - Resulting in similar systemic effects as hyperthyroidism.

Epidemiology

  • Affects approximately 2-5% of all women at some point.

  • Gender ratio is approximately 5:1 (female:male).

  • Most cases manifest between ages 20 and 40.

  • Causes: Approximately 99% of cases arise from intrinsic thyroid diseases; pituitary causes are rare.

Causes of Hyperthyroidism

Common Causes

  1. Basedow-Graves Disease: An autoimmune disorder leading to hyperfunction of the thyroid.

  2. Toxic Multinodular Goiter: Hyperactivity of multiple nodules in the thyroid.

  3. Solitary Toxic Nodule: Hyperactivity of a single nodule within the thyroid.

Rare Causes

  1. Acute thyroiditis: Caused by viral or autoimmune factors, post-radiation, or postpartum events.

  2. Gestational and Neonatal Thyrotoxicosis: Occurring during pregnancy or in newborns.

  3. Exogenous Iodine Administration: Excess iodine intake contributing to thyroid hormone overproduction.

  4. Medically Induced Conditions: Such as those caused by amiodarone or immunotherapy.

  5. TSH-secreting Pituitary Tumors: Rare tumors that secrete TSH, promoting thyroid hormone production.

  6. Metastatic Differentiated Thyroid Carcinoma: Thyroid cancer that produces hormones.

  7. HCG-Producing Tumors: Tumors that secrete human chorionic gonadotropin, mimicking TSH effects.

  8. Hyperfunctioning Ovarian Teratoma: Specifically struma ovarii, a teratoma that produces thyroid hormones.

Basedow-Graves' Disease

  • Definition: An autoimmune condition characterized by hyperactivity of the thyroid gland due to the production of anti-TSH receptor autoantibodies (TRAb), which activate the TSH receptor leading to increased hormone production.

  • Clinical manifestations may include:
      - Thyrotoxicosis.
      - Ophthalmopathy (Exophthalmia): A distinguishing feature of Graves' disease.
      - Goiter: Enlargement of the thyroid.
      - Dermopathy (Pretibial Mixedema): Rare manifestation of skin thickening in the pretibial area.

Etiopathogenesis

  • Key role of antibodies against TSH receptors (TRAb) which can stimulate thyroid hormone synthesis and secretion as well as cell proliferation.

  • Presence of both stimulating and blocking antibodies can result in varied clinical presentations depending on their ratio.

  • Anti-TPO Antibodies: Increased levels may also be present, reflecting autoimmune activity.

  • Association with specific HLA haplotypes (HLA-B8, DR3, DR2).

  • Precipitating Factors: Include excess iodine, psychological stress, smoking, estrogens during the postpartum period, and specific viral or bacterial infections associated with production of TSH-like antibodies.

Pathophysiological Mechanism of Thyrotoxicosis

  • Defect in Suppressor T Lymphocytes (Ts): Leads to stimulation of helper T lymphocytes (Th) that induce B lymphocytes to produce TRAb antibodies (IgG).

  • TRAb binds to TSH receptors in the thyroid, mimicking TSH, which stimulates the synthesis and secretion of thyroid hormones, and leads to increases in free hormone levels (FT4 and FT3).

  • Suppression of TSH secretion due to feedback inhibition from high levels of thyroid hormones.

Pathophysiological Mechanism of Graves Ophthalmopathy

  • Results from local autoimmune reactions involving:
      - Cellular Immunity: Cytotoxic T lymphocytes release proinflammatory cytokines.
      - Humoral Immunity: Antibodies target fibroblasts and orbital muscles.

  • Increased expression of TSH receptors on retro-orbital fibroblasts and ocular muscles leading to inflammation.

  • Proliferation of connective tissue and edema results in exophthalmos and ocular muscle infiltration, potentially causing diplopia.

Classification of Graves Ophthalmopathy (EUGOGO)

  1. Easy Form:
       - Eyelid retraction < 2 mm.
       - Mild exophthalmia.
       - No significant disruptions to daily life.
       - Intermittent diplopia.

  2. Moderate-Severe Form:
       - Eyelid retraction ≥ 2 mm.
       - Moderate exophthalmia.
       - Constant diplopia.
       - Significant impact on quality of life.

  3. Severe Form:
       - Compressive optic neuropathy.
       - Severe corneal ulcers.
       - Decreased visual acuity; considered a medical emergency.

Clinical Signs and Symptoms of Hyperthyroidism

  • General Signs:
      - Weight loss with preserved/increased appetite.
      - Heat intolerance.
      - Profuse sweating.

  • Cardiovascular Signs:
      - Heart rhythm disorders (e.g., sinus tachycardia leading to atrial fibrillation).
      - Palpitations.
      - Increased cardiac output and systolic hypertension.

  • Neuromuscular Signs:
      - Tremors, hyperkinesia, muscle weakness.

  • Digestive Signs:
      - Increased appetite (polifagia), accelerated intestinal transit resulting in diarrhea and vomiting.

  • Cutaneous Signs:
      - Warm, moist skin.
      - Graves dermopathy.
      - Pruritus; goiter; exophthalmos.

  • Psychiatric Signs:
      - Anxiety, irritability, tachypsychia, tachylalia, memory and cognitive impairment.

Diagnostic Criteria for Hyperthyroidism

  • Hormonal Dosage: TSH < 0.05 mU/L, high levels of fT3 and fT4, high levels of TRAb, possibly high anti-TPO antibodies.

  • Thyroid Scintigraphy: Indicates increased thyroid volume (generally diffuse).

  • Ultrasound: Shows enlargement of the thyroid, hypoechoic areas, and increased vascularization.

  • CT or MRI: To assess for infiltration of ocular muscles and retrobulbar edema.

  • Ophthalmological Exam: Including assessments of visual acuity and intraocular pressure.

Differential Diagnosis

  • Must differentiate Graves' disease from other hyperthyroid conditions, particularly in patients with substantial weight loss.

  • Possible considerations include malabsorption syndromes, tuberculosis, gastritis, gastroduodenal ulcers, and paraneoplastic syndromes.

Complications of Hyperthyroidism

Acute Complications

  • Tachyarrhythmias: Potentially leading to heart failure.

  • Thyrotoxic Crisis (Thyroid Storm): A life-threatening condition caused by severe hyperthyroidism triggered by mental stress or infections, characterized by:
      - Hyperpyrexia, severe tachycardia, extreme agitation, delirium, vomiting, and diarrhea.

Chronic Complications

  • Osteoporosis: Due to sustained high thyroid hormone levels affecting bone metabolism.

  • Cardiomyopathy: Resulting from long-term strain on the heart due to hyperthyroidism.

Treatment of Hyperthyroidism

  • Medical Treatment:
      - Synthetic antithyroid medications (e.g., Carbimazole, PTU – propylthiouracil, Tiamazole) effective for relieving symptoms of thyrotoxicosis.
      - Beta-blockers (e.g., Propranolol) to alleviate symptoms related to heightened beta-adrenergic activity.

  • Radioiodotherapy: Utilizing I-131 to reduce thyroid function.

  • Surgical Treatment: Thyroidectomy indicated in certain cases.

HYPOTHYROIDISM

Introduction

  • Definition: Hypothyroidism is marked by reduced production of thyroid hormones, typically primary in nature due to thyroid disorders, but also potentially secondary due to hypothalamic-pituitary damage affecting TSH actions.

Classification

  • Primary Thyroid Disease:
      - Acquired:
        - Autoimmune conditions: Hashimoto's thyroiditis, postpartum thyroiditis.
        - Iodine deficiency, medications (e.g., Amiodarone, Lithium), and infectious thyroiditis.
      - Congenital: Includes thyroid agenesis or ectopic thyroid (lingual).

  • Secondary Hypothyroidism: Related to pituitary or hypothalamic dysfunctions, such as:
      - Pituitary Disorders: Isolated TSH deficiency due to hypopituitarism.
      - Post-surgical or post-radiation: Resulting in loss of pituitary function.
      - Peripheral Resistance: Conditions where target tissues fail to respond to thyroid hormones.

General Pathophysiological Mechanism

  • Thyroid Hormone Deficiency: Leads to decreased metabolism and the accumulation of glycosaminoglycans (GAGs), particularly hyaluronic acid, in interstitial tissues, increasing capillary permeability to albumin.

Pathophysiological Mechanism of Hashimoto Thyroiditis

  1. Activation of self-reactive CD4+ T helper lymphocytes against thyroid antigens.

  2. Antigen-presenting cells process and present Thyroperoxidase (TPO) and Thyroglobulin (Tg) activating Th1 lymphocytes which produce pro-inflammatory cytokines (IFN-γ, IL-2, TNF-α).

  3. B lymphocyte activation leads to the production of anti-TPO antibodies.

  4. Destruction of thyroid tissue occurs via:
       - Cell-mediated cytotoxicity: By CD8+ lymphocytes.
       - Antibody-mediated cytotoxicity: Via complement activation and macrophages.
       - Chronic Inflammation: Contributing to cell destruction.

  5. Results in TSH elevation with normal FT4 levels (subclinical hypothyroidism), progressing to elevated TSH and low FT4 levels (clinical hypothyroidism).

Clinical Signs and Symptoms

  • Cardiovascular System:
      - Reduced cardiac output due to decreased heart rate and myocardial contractility.
      - Cardiomegaly owing to interstitial edema.
      - ECG changes including low voltage and signs of coronary artery disease.

  • Respiratory System:
      - Conditions such as rhinitis and bronchial infections; sleep apnea associated with macroglossia.

  • Digestive System:
      - Symptoms include constipation and decreased gastric secretion, leading to slight weight gain from reduced metabolic rates.

  • Urogenital System:
      - Amenorrhea/oligomenorrhea and decreased glomerular filtration rate (GFR) leading to reduced diuresis and hyponatremia.

  • Nervous System:
      - Mental slowness, lethargy, drowsiness, reflex abolition, potential hearing loss, syncope, or even coma.

Diagnosis

  • Hormonal Dosage: Low levels of fT3 and fT4, elevated TSH levels, and presence of anti-TPO antibodies indicating Hashimoto's Disease.

  • Biochemical Examinations: May reveal hyponatremia, hypoglycemia, anemia, and increased LDL cholesterol levels.

  • Thyroid Ultrasound: Used to assess nodules and characteristics suggesting hypothyroidism; provides differentiation between primary and central hypothyroidism.

Differential Diagnosis

  • Conditions to consider in adults include:
      - Nephrotic syndrome and renal failure (due to edema presence).
      - Heart failure and depressive syndromes.
      - Acromegaly at onset; differentiate primary from secondary forms via imaging studies of the pituitary region.

Complications

  • Untreated hypothyroidism leads to progressive deterioration in metabolic functions.

  • With appropriate management, the prognosis can be favorable. Notably, if coronary artery disease arises from untreated hypothyroidism, coronary artery bypass grafting may be necessary prior to initiating replacement therapies due to increased myocardial oxygen demand post-treatment.

Treatment

  • Replacement Therapy: Both for adults and children, utilizing levothyroxine (LT4) as the preferred option. Dosage adjustments occur at 4-6 week intervals based on TSH levels.

  • Monitoring continues semi-annually with TSH and fT4 testing.

MYXEDEMATOUS COMA

Definition

  • Myxedematous coma represents the most severe complication of hypothyroidism, albeit rare. It predominantly affects elderly individuals and is associated with triggers such as trauma or gastrointestinal bleeding.

  • Clinical manifestations include myxedema evolving to numbness, hypothermia, extreme weakness, profound lethargy, progressing to coma stages along with bradycardia, severe heart failure, pericardial effusion, hypoglycemia, and hypoventilation.

Laboratory Findings

  • Very high TSH levels are typically found in primary hypothyroidism.

  • Accompanying high serum cholesterol, hypoglycemia, and hyponatremia are often noted.