Physiology

Endocrine disorders are abnormal states that arise from either hormone excess or deficiency. Understanding what constitutes a normal hormonal balance is crucial for identifying and interpreting abnormal states

Normal Endocrine Function

• Hormone Synthesis and Secretion
  • Synthesis: Hormones are synthesized in endocrine glands through various biochemical pathways, often involving enzymatic reactions and precursor molecules
  • Secretion: Hormone secretion is regulated by feedback mechanisms, neural signals, and hormonal signals to maintain homeostasis
• Hormone Transport
  • Protein Binding: Many hormones are transported in the bloodstream bound to carrier proteins, which protect them from degradation and prolong their half-life
  • Free Hormone: Only the free (unbound) hormone is biologically active and can interact with target tissues
• Hormone Action
  • Receptor Binding: Hormones bind to specific receptors on target cells, initiating intracellular signaling cascades
  • Signal Transduction: These cascades alter cellular function, gene expression, and protein synthesis to produce physiological effects
• Hormone Metabolism and Excretion
  • Metabolism: Hormones are metabolized in the liver, kidneys, and other tissues to inactive forms
  • Excretion: Metabolites are excreted in the urine or bile
• Feedback Mechanisms
  • Negative Feedback: Hormone levels are tightly regulated by negative feedback loops, where the hormone’s effects inhibit its own secretion
  • Positive Feedback: In some cases, hormones can stimulate their own secretion, leading to a surge in hormone levels (e.g., during ovulation)

Abnormal Endocrine Function

• Hormone Excess
  • Causes: Tumors, autoimmune disorders, ectopic hormone production
  • Effects: Exaggerated physiological responses, metabolic imbalances, organ damage
• Hormone Deficiency
  • Causes: Autoimmune destruction, surgical removal, genetic defects, infections
  • Effects: Impaired physiological responses, metabolic abnormalities, developmental issues
• Receptor Abnormalities
  • Receptor Resistance: Target tissues fail to respond normally to hormones due to receptor defects or post-receptor signaling abnormalities
  • Receptor Mutations: Genetic mutations can alter receptor structure and function, leading to hormone resistance or constitutive activation
• Ectopic Hormone Production
  • Non-Endocrine Tumors: Some tumors can produce hormones that are not normally secreted by that tissue, leading to hormonal imbalances
  • Paraneoplastic Syndromes: These syndromes can cause a wide range of endocrine and metabolic abnormalities

Specific Endocrine Disorders

0.0.1 Pituitary Disorders

• Hyperpituitarism (Hormone Excess)
  • Acromegaly: Excess growth hormone (GH) leads to enlarged hands, feet, and facial features
  • Cushing’s Disease: Excess adrenocorticotropic hormone (ACTH) leads to excess cortisol production, causing weight gain, hypertension, and muscle weakness
  • Hyperprolactinemia: Excess prolactin leads to galactorrhea (milk production) and amenorrhea (absence of menstruation) in women, and hypogonadism in men
• Hypopituitarism (Hormone Deficiency)
  • Growth Hormone Deficiency: Leads to growth retardation in children and metabolic abnormalities in adults
  • Adrenal Insufficiency: Deficiency of ACTH leads to decreased cortisol production, causing fatigue, weight loss, and hypotension
  • Hypothyroidism: Deficiency of thyroid-stimulating hormone (TSH) leads to decreased thyroid hormone production, causing fatigue, weight gain, and cold intolerance
  • Hypogonadism: Deficiency of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) leads to decreased sex hormone production, causing infertility and sexual dysfunction

0.0.2 Thyroid Disorders

• Hyperthyroidism (Hormone Excess)
  • Graves’ Disease: Autoimmune disorder that stimulates the thyroid gland, leading to excess thyroid hormone production
  • Toxic Nodular Goiter: Overactive thyroid nodules produce excess thyroid hormone
  • Symptoms: Weight loss, anxiety, heat intolerance, palpitations, and exophthalmos (bulging eyes)
• Hypothyroidism (Hormone Deficiency)
  • Hashimoto’s Thyroiditis: Autoimmune destruction of the thyroid gland, leading to decreased thyroid hormone production
  • Iodine Deficiency: Inadequate iodine intake impairs thyroid hormone synthesis
  • Symptoms: Fatigue, weight gain, cold intolerance, constipation, and dry skin

0.0.3 Adrenal Disorders

• Hypercortisolism (Cushing’s Syndrome) (Hormone Excess)
  • Cushing’s Disease: Pituitary tumor that overproduces ACTH, leading to excess cortisol production
  • Adrenal Tumors: Tumors of the adrenal gland that produce excess cortisol
  • Exogenous Steroids: Prolonged use of corticosteroids
  • Symptoms: Weight gain, moon face, buffalo hump, hypertension, muscle weakness, and skin changes
• Adrenal Insufficiency (Hormone Deficiency)
  • Addison’s Disease: Autoimmune destruction of the adrenal glands, leading to decreased cortisol and aldosterone production
  • Secondary Adrenal Insufficiency: Pituitary or hypothalamic disorders that decrease ACTH production
  • Symptoms: Fatigue, weight loss, hypotension, hyperpigmentation (in Addison’s disease), and electrolyte imbalances
• Hyperaldosteronism (Hormone Excess)
  • Primary Hyperaldosteronism (Conn’s Syndrome): Adrenal tumor that produces excess aldosterone
  • Secondary Hyperaldosteronism: Increased renin production due to kidney disease or other conditions
  • Symptoms: Hypertension, hypokalemia, and muscle weakness
• Pheochromocytoma (Hormone Excess)
  • Tumor of the adrenal medulla that produces excess catecholamines (epinephrine and norepinephrine)
  • Symptoms: Hypertension, palpitations, sweating, anxiety, and headaches

0.0.4 Pancreatic Endocrine Disorders

• Diabetes Mellitus (Hormone Deficiency/Resistance)
  • Type 1 Diabetes: Autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency
  • Type 2 Diabetes: Insulin resistance and progressive beta-cell dysfunction
  • Symptoms: Polyuria, polydipsia, polyphagia, weight loss, and hyperglycemia
• Insulinoma (Hormone Excess)
  • Tumor of the pancreatic beta cells that produces excess insulin, leading to hypoglycemia
  • Symptoms: Hypoglycemia, sweating, palpitations, anxiety, and confusion

0.0.5 Parathyroid Disorders

• Hyperparathyroidism (Hormone Excess)
  • Primary Hyperparathyroidism: Parathyroid adenoma or hyperplasia that produces excess parathyroid hormone (PTH), leading to hypercalcemia
  • Secondary Hyperparathyroidism: Increased PTH production due to chronic kidney disease or vitamin D deficiency
  • Symptoms: Hypercalcemia, kidney stones, bone pain, and muscle weakness
• Hypoparathyroidism (Hormone Deficiency)
  • Surgical removal or autoimmune destruction of the parathyroid glands, leading to hypocalcemia
  • Symptoms: Hypocalcemia, muscle cramps, tetany, and seizures

0.0.6 Gonadal Disorders

• Hypogonadism (Hormone Deficiency)
  • Primary Hypogonadism: Gonadal failure due to genetic disorders, autoimmune destruction, or radiation exposure
  • Secondary Hypogonadism: Pituitary or hypothalamic disorders that decrease LH and FSH production
  • Symptoms: Infertility, sexual dysfunction, decreased muscle mass, and osteoporosis
• Polycystic Ovary Syndrome (PCOS)
  • Hormonal disorder characterized by hyperandrogenism, irregular menstruation, and polycystic ovaries
  • Symptoms: Hirsutism (excess hair growth), acne, infertility, and metabolic syndrome

Summary Table of Normal and Abnormal States

Endocrine Gland:	Hormone:	Normal State:	Hormone Excess:	Hormone Deficiency:
Pituitary	GH	Normal growth and metabolism	Acromegaly	Growth hormone deficiency
	ACTH	Normal cortisol production	Cushing’s disease	Adrenal insufficiency
	TSH	Normal thyroid hormone production	Rare, can cause hyperthyroidism	Hypothyroidism
	Prolactin	Normal lactation	Hyperprolactinemia	Rare
Thyroid	T3/T4	Normal metabolism	Hyperthyroidism (Graves’ disease)	Hypothyroidism (Hashimoto’s)
Adrenal Cortex	Cortisol	Normal stress response, metabolism	Cushing’s syndrome	Addison’s disease (adrenal insuff.)
	Aldosterone	Normal blood pressure, electrolyte balance	Hyperaldosteronism (Conn’s)	Adrenal insufficiency
Adrenal Medulla	Epinephrine/Norepi.	Normal “fight or flight” response	Pheochromocytoma	Rare
Pancreas	Insulin	Normal glucose metabolism	Insulinoma	Diabetes mellitus (Type 1 & 2)
Parathyroid	PTH	Normal calcium homeostasis	Hyperparathyroidism	Hypoparathyroidism
Gonads	Estrogen/Testosterone	Normal sexual development/function	Precocious puberty, hormone-producing tumors	Hypogonadism

Key Terms

• Homeostasis: The maintenance of stable internal conditions
• Negative Feedback: A regulatory mechanism where the output inhibits its own production
• Positive Feedback: A regulatory mechanism where the output stimulates its own production
• Hormone Receptor: A protein on a target cell that binds to a hormone
• Signal Transduction: The process by which a hormone-receptor interaction triggers intracellular events
• Hypersecretion: Excessive hormone production
• Hyposecretion: Insufficient hormone production
• Hormone Resistance: A condition where target tissues fail to respond normally to a hormone
• Ectopic Hormone Production: Hormone production by non-endocrine tissues
• Autoimmune Disorder: A condition where the immune system attacks the body’s own tissues
• Tumor: An abnormal mass of tissue
• Hyperplasia: An increase in the number of cells in a tissue or organ
• Atrophy: A decrease in the size of a tissue or organ
• Metabolic Syndrome: A cluster of conditions that increase the risk of heart disease, stroke, and diabetes
• Polycystic Ovary Syndrome (PCOS): A hormonal disorder characterized by hyperandrogenism, irregular menstruation, and polycystic ovaries
• Hypertension: High blood pressure
• Hypotension: Low blood pressure
• Hypercalcemia: Elevated blood calcium levels
• Hypocalcemia: Reduced blood calcium levels
• Hyperkalemia: Elevated blood potassium levels
• Hypokalemia: Reduced blood potassium levels
• Hirsutism: Excess hair growth in women
• Virilization: Development of male characteristics in women
• Gynecomastia: Enlargement of breast tissue in men
• Galactorrhea: Spontaneous milk production
• Amenorrhea: Absence of menstruation
• Infertility: Inability to conceive
• Osteoporosis: Reduced bone density, increasing the risk of fractures
• Lethargy: A state of fatigue or drowsiness
• Goiter: Enlargement of the thyroid gland
• Exophthalmos: Bulging eyes, typically associated with hyperthyroidism