Thyroid Gland Anatomy and Function

Anatomy of the Thyroid Gland

• The thyroid gland's key function is to secrete thyroid hormones and calcitonin.
• The thyroid gland is composed of follicles, which serve as the functional units.

The Thyroid Produces and Secretes 2 Metabolic Hormones

• These hormones are thyroxine (T4) and triiodothyronine (T3).
• They are essential for cell homeostasis, influencing cell differentiation, growth, and metabolism.

Iodine Sources

• Iodine is a trace mineral obtained through foods like seafood, bread, and dairy products, iodized salt, or supplements.
• The recommended daily intake is at least 150 micrograms.

Production of T4 and T3

• T4 is primarily secreted by the thyroid gland, while T3 is produced through two processes:
  • 80% of circulating T3 originates from the deiodination of T4 in peripheral tissues.
  • 20% comes from direct thyroid secretion.

Carriers for Circulating Thyroid Hormones

• Over 99% of circulating T4 and T3 are bound to plasma carrier proteins:
  • Thyroxine-binding globulin (TBG) accounts for 75%.
  • Transthyretin (TTR), also known as thyroxine-binding prealbumin (TBPA) contributes 10-15%.
  • Albumin binds about 7%.
• Carrier proteins can be influenced by physiological changes, medications, and diseases.
• Only unbound (free) hormone exhibits metabolic activity and physiological effects.
  • Free hormone constitutes a small percentage of total hormone in plasma (around 0.03% T4; 0.3% T3).

Effects of Thyroid Hormone

• Thyroid hormone plays a crucial role in fetal brain and skeletal maturation.
• It increases the basal metabolic rate.
• It exerts inotropic and chronotropic effects on the heart.
• It enhances sensitivity to catecholamines.
• It stimulates gut motility.
• It increases bone turnover.
• It raises serum glucose levels and decreases serum cholesterol.

Thyroid Hormone is Critical for Normal Bone Growth and Development

• T3 is essential for skeletal maturation at the growth plate.
  • It regulates the expression of factors contributing to linear growth.
  • It participates in osteoblast differentiation and proliferation, as well as chondrocyte maturation leading to bone ossification.

Control of Thyroid Function: Hypothalamic-Pituitary-Thyroid Axis

• The hypothalamus secretes Thyroid Releasing Hormone (TRH).
• TRH stimulates the anterior pituitary to release Thyroid Stimulating Hormone (TSH).
• TSH, in turn, regulates thyroid hormone production, secretion, and growth.
• T4 and T3 exert negative feedback on TSH.

Thyroid-Stimulating Hormone (TSH)

• Regulates thyroid hormone production, secretion, and growth.
• Subject to negative feedback regulation by T4 and T3.

Thyrotoxicosis & Hyperthyroidism

• Thyrotoxicosis is a clinical syndrome characterized by high levels of circulating thyroid hormones.
• Hyperthyroidism is a condition where the thyroid gland is overactive.

Hyperthyroid Symptoms

• Weight loss despite increased appetite.
• Heat intolerance.
• Increased sweating.
• Palpitations and rapid heart rate.
• Tremor.
• Nervousness and anxiety.
• Insomnia.
• Diarrhea.
• Muscle weakness.
• Goiter (enlargement of the thyroid gland).
• Eye problems (exophthalmos, lid lag).
• Hair loss.
• Menstrual irregularities.
• Fatigue.

Hypothyroid Symptoms

• Weight gain despite decreased appetite.
• Cold intolerance.
• Constipation.
• Fatigue and lethargy.
• Muscle aches and weakness.
• Dry skin and hair.
• Bradycardia (slow heart rate).
• Depression.
• Goiter.
• Memory impairment.
• Hoarseness.
• Menstrual irregularities.

Evaluation of Thyroid Function

• Total T4 (normal: 4-12 ug/dl).
• Total T3 (normal: 80-120 ng/dl).
• Free T3 and T4 levels.
• Radioactive iodine uptake (RAI): Normal uptake (24 hours after administration) is 5-30% of the administered dose.
• Serum TSH levels.
• Thyroid ultrasound.
• Fine-needle aspiration biopsy.

Growth Hormone Physiology

• Increases blood glucose.
• Enhances protein synthesis.
• Increases free fatty acids (FFA).

Acromegaly

• Characterized by excessive growth caused by overproduction of GH.
• Usually due to a benign pituitary tumor (adenoma).

Acromegaly Clinical Picture

• Coarse facial features, including exaggerated supraorbital ridges.
• Enlarged soft tissue in the nose and lips.
• Enlarged and furrowed tongue.
• Overgrowth of the jaw bone (prognathism).
• Enlarged hands and feet.
• Coarse body hair growth with skin thickening and darkening.
• Increased sweating.
• Deep and husky voice due to thickened cartilage in the larynx.
• Joint pain.
• Cardiomegaly, hypertension, and hepatomegaly.
• Nerve compression leading to sensory disturbances and weakness in the arms and legs.
• Severe headaches.
• Irregular menstrual cycles.

Adrenal Gland Disorders

• The adrenal gland's cortex secretes cortisol, mineralocorticoids, and androgens, while the medulla secretes adrenaline (epinephrine).

Functions of Adrenocortical Hormones

• Involved in complex nutrient processing and utilization, including carbohydrates, fats, and proteins.
• Essential for the normal functioning of the circulatory system and heart.
• Regulate muscle function.
• Contribute to blood cell production.
• Maintain the skeletal system.
• Support proper brain and nerve function.
• Regulate the immune system's responses.

Cushing's Syndrome

• Excess cortisol circulating in the bloodstream.

Cushing's Syndrome Etiologies

• Iatrogenic: Steroid therapy is the most common cause.
• Pituitary adenoma (ACTH) leading to adrenal cortex hyperplasia.
• Adrenal cause:
  • Adrenal adenoma.
  • Adrenal hyperplasia.
  • Adrenal malignancy.
• Ectopic source (ACTH): Small cell carcinoma of the lung.

Cushing's Syndrome Symptoms

• Mood changes, including depression and euphoria.
• Easy bruising.
• Weakness.
• Weight gain.
• Amenorrhea.
• Back pain.

Cushing's Syndrome Signs

• Weight gain, particularly in the face ("moon face"), trunk ("truncal obesity"), upper back, and back of the neck ("buffalo hump").
• Striae rubra (purple and pink stretch marks).
• High blood pressure.
• Weak and thinning bones (osteoporosis).
• Weak muscles.
• Thin and fragile skin with bruising and slow healing tendencies.
• Potential development of diabetes.
• Increased susceptibility to infections.
• Hirsutism in women: abnormal hair growth in areas like the beard and mustache, accompanied by hair loss on the head (receding hairline).

Adrenal Gland Hypofunction

• Etiology:
  • Secondary: Pituitary insufficiency.
  • Primary: Addison's disease (primary adrenal failure).
    • Hypoplasia or destruction of the adrenal glands due to:
      • Granulomatous disease (e.g., tuberculosis, fungus).
      • Amyloidosis.
      • Hemochromatosis.
      • Tumors.
      • Autoimmune processes.

Adrenal Gland Hypofunction Symptoms

• Weakness, tiredness, and dizziness.
• Fatigue or lethargy.
• Nausea, vomiting, and weight loss.
• Diarrhea and dehydration.
• Salt craving.
• Abdominal pain.

Adrenal Gland Hypofunction Signs

• Hyperpigmentation:
  • Skin darkening, resembling tanning, on both sun-exposed and unexposed areas.
  • Pigmented buccal mucosa.
• Hypotension.
• Reduced hair growth.
• Signs of dehydration.

Parathyroid Glands

• Four small glands located in the neck at the posterior surface of the thyroid gland.
• Secrete parathyroid hormone (PTH), which maintains calcium homeostasis in the blood.

Stimuli for PTH Secretion

• Hypocalcemia (low calcium levels in the blood) is the primary stimulus.

Hyperparathyroidism

• Majority of patients are asymptomatic (50%).
• Non-specific symptoms may include weakness and fatigue.
• Symptoms related to hypercalcemia:
  • Anorexia, nausea, and vomiting.
  • Dyspepsia.
  • Constipation.
  • Increased incidence of peptic ulcers and acute pancreatitis.
  • Interstitial nephritis: Calcium deposition in the renal tubules leading to inability to concentrate urine, resulting in polyuria, polydipsia, and nocturia.
  • Increased susceptibility to renal stones (calcium oxalate and calcium phosphate stones), causing renal colic and repeated UTIs.
  • Nephrocalcinosis due to whole kidney calcification.
  • Impaired mentation, memory loss, emotional lability, depression, anosmia, drowsiness, stupor, and coma.
  • Weakness (proximal muscles), arthralgia.
  • Severe pruritus (skin calcification).
  • Joint pains.
  • Rare cases of pathological fractures.
  • Calcification at the corneo-scleral junction, leading to keratitis and corneal opacity.
  • Solitary bone resorption causing solitary cysts, brown tumors of the mandible, or subperiosteal erosion of the phalanges (osteitis fibrosa cystica).

Hyperparathyroidism Diagnosis

• Hypercalcemia (Normal Ca = 9-11 mg/100cc).
• Hypophosphatemia (Normal = 2.5-4 mg/100cc).
• Increased alkaline phosphatase.
• Increased PTH levels.
• Urinalysis and kidney X-rays.
• Bone density tests.

Hyperparathyroidism Treatment

• Medical: Management of hypercalcemia.
• Surgical removal of the affected parathyroid gland.

Hypoparathyroidism

• Failure of PTH secretion due to:
  • Surgical: Following thyroidectomy, neck exploration, or removal of neck malignancies.
  • Transient: After removal of a parathyroid adenoma.
  • Idiopathic (autoimmune).
  • Prolonged severe hypomagnesemia.
• Clinical picture:
  • Asymptomatic or manifestations of hypocalcemia.
  • Neuromuscular activity disturbances:
    • Numbness and tingling around the mouth and lips.
    • Paresthesias in the hands and feet.
    • Bronchospasm or laryngeal spasm (stridor).
  • Carpopedal spasm (spasmodic contractions of the hands and feet).

Hypoparathyroidism Diagnosis

• Decreased serum calcium levels.
• Increased phosphate levels in the absence of renal failure.
• Low PTH levels: Diagnostic of hypoparathyroidism.