Endocrine

N324 Pathophysiology: Endocrine Pathologies Part I

Learning Objectives

  • Identify the locations of the endocrine glands.

  • Describe the common characteristics and functions of hormones.

  • Describe the functions of hormones secreted by various glands: anterior and posterior pituitary, pancreas, thyroid, parathyroid, and adrenal glands.

  • Compare positive and negative feedback mechanisms in hormone control.

  • Describe and differentiate types of diabetes mellitus (DM) and metabolic syndrome.

  • Compare and contrast common disorders of the major endocrine glands.

Endocrine vs Exocrine Glands

  • Endocrine glands:   - Release hormones (chemical substances) directly into the bloodstream or tissues of the body.

  • Exocrine glands:   - Release enzymes through ducts to another organ within the body or outside the body.

Overview of the Endocrine System

  • Key Function: Maintaining homeostasis (balance).   - Fluid and electrolyte balance.   - Temperature and metabolism regulation.   - Nutritional and elimination processes.   - Reproductive and central nervous system development in the fetus.   - Stimulating growth and development during childhood and adolescence.   - Facilitating sexual reproduction.   - Responding to emergency demands (illness, injury, stressors).

Location of Major Glands of the Endocrine System

  • Hypothalamus

  • Pituitary gland (anterior and posterior)

  • Pineal gland (not mentioned in recent pages)

  • Thyroid

  • Parathyroid

  • Adrenals

  • Pancreas (islets of Langerhans)

  • Testes (male) and Ovaries (female)

Hormones

  • Definition: Hormones are chemical substances that act as messenger molecules throughout the body.   - Synthesized in one body part and act on other parts to regulate cellular and organ functions.   - Example: Insulin produced by beta cells in the pancreas.

  • Mechanism of Action:   - Hormone binding to its receptor is analogous to a "lock and key fit." Target cells respond only to specific hormones.   - Most hormones are secreted directly into the bloodstream by endocrine glands.   - Factors such as drugs, diet, lifestyle, and pathological conditions can increase or decrease hormone secretion.   - After action upon target cells, hormones are metabolized by the liver and excreted by the kidneys.

Hormones vs Neurotransmitters vs Neurohormones

  • Neurotransmitters:   - Move mainly from neuron to neuron via synaptic spaces.

  • Hormones:   - Move throughout the bloodstream.

  • Neurohormones:   - Some substances function as both, being transported via blood and synaptic spaces.

Hypothalamus

  • Location: Above the pituitary gland.

  • Function: Monitors hormone, nutrient, and ion levels; connects nervous and endocrine systems via neurosecretory neurons.

  • Action: Hypothalamic hormones regulate hormones from the pituitary gland (hypothalamic-pituitary axis).

  • Key Hypothalamic Hormones:   - Corticotropin Releasing Hormone (CRH)   - Thyrotropin Releasing Hormone (TRH)   - Gonadotropin Releasing Hormone (GnRH)   - Somatostatin (suppresses release of growth hormone (GH) and Thyroid Stimulating Hormone (TSH)).

Pituitary Gland

  • Location: Under the hypothalamus at the base of the brain.

  • Structure: Divided into anterior and posterior pituitary.   - Anterior Pituitary: Regulated by hypothalamus via releasing and inhibiting hormones. It secretes six major hormones known as tropic hormones (that control other glands).   - Posterior Pituitary: Primarily secretes oxytocin and Antidiuretic Hormone (ADH).

Anterior Pituitary Hormones

  • Thyroid-Stimulating Hormone (TSH) / Thyrotropin:   - Stimulates thyroid gland to release T4 (thyroxine), which is converted into T3 (Triiodothyronine), controlling metabolism across all cells.

  • Adrenocorticotropin (ACTH):   - Stimulates adrenal cortex to produce glucocorticoids.

  • Prolactin (PRL / Lactogenic hormone):   - Stimulates mammary glands for breast milk production.

  • Growth Hormone (GH):   - Stimulates growth of muscles and bones; responsible for protein synthesis and cell growth.

  • Gonadotropins:   - Follicle Stimulating Hormone (FSH):     - In women: Stimulates growth of ovarian follicles and ovulation.     - In men: Stimulates sperm production.   - Luteinizing Hormone (LH):     - In females: Stimulates ovulation and production of estrogen and progesterone.     - In males: Stimulates testosterone secretion and development of testes.

Posterior Pituitary Hormones

  • ADH:   - Stimulates kidney tubules to reabsorb water; released in response to hypovolemia (low blood volume) and increased plasma osmolality. Reduces urine output.

  • Oxytocin:   - Involved in childbirth and lactation; stimulates uterine contractions and milk ejection; related to social bonding. Higher levels are found in females. Lower levels found in individuals with Autism Spectrum Disorders.   

Adrenal Glands

  • Location: On top of each kidney, consisting of two parts: adrenal cortex and adrenal medulla.

  • Adrenal Cortex Functions:   - Cortisol: Increases blood glucose level and assists the body in coping with long-term stressors.   - Aldosterone: Regulates sodium and potassium levels, affecting blood pressure and fluid balance.   - Sex Hormones: Includes androgens and estrogens.

  • Adrenal Medulla Functions:   - Releases epinephrine and norepinephrine as part of the fight or flight response (acute stress).

Disorders of the Pituitary Gland

  • Pituitary Tumors (Adenomas):   - Most common cause of disorders.   - Likely benign and usually do not spread but can cause pressure on nearby structures.

  • Panhypopituitarism:   - Rare condition with deficient hormone production from the anterior pituitary.   - Causes include congenital defects or tumors.

  • Thyroid and Adrenal Disorders:

  • Hyperpituitarism:   - Gigantism (prior to puberty) and acromegaly (post puberty) due to excess growth hormone.   - Cushing's Disease/Syndrome (excessive ACTH leading to increased cortisol).   

Diabetes Mellitus (DM)

  • Overview: Three types: Type 1, Type 2, and Gestational.   - Type 1 DM: Autoimmune destruction of beta cells leading to absolute insulin insufficiency. Symptoms include classic 3 P's: polyuria, polydipsia, polyphagia.   - Type 2 DM: Insulin resistance; characterized by high blood sugar, often managed with lifestyle changes and medications initially, potentially requiring insulin later.   - Gestational DM: Develops during pregnancy; may require insulin if diet management is insufficient.   

Metabolic Syndrome

  • Not a form of diabetes but increases the risk of developing Type 2 DM and cardiovascular disease.

  • Characterized by a cluster of at least three conditions: obesity, high blood pressure, elevated blood sugar, and abnormal cholesterol levels.

Acute Complications of DM

  • Acute Hypoglycemia: Severe low glucose levels (<70 mg/dL), can be life-threatening. Symptoms include confusion, seizures, unconsciousness.

  • Acute Hyperglycemia: Glucose above 180 mg/dL, with symptoms of the 3 P's along with fatigue and blurred vision.

  • Diabetic Ketoacidosis (DKA): Presented with significant elevation in blood glucose with metabolic acidosis, requires immediate treatment.

Case Studies

  1. Case Study 1:    - Symptoms: Polydipsia, polyuria, hypotension; history of pituitary tumor removal.    - Suspected Condition: Possible diabetes insipidus due to ADH deficiency.

  2. Case Study 2:    - Symptoms: Extreme fatigue, weight gain, puffy face, dry skin, muscle cramps.    - Suspected Condition: Hypothyroidism, possibly associated with low thyroid hormone levels.

  3. Case Study 3:    - Symptoms: Chronic fatigue, increased thirst, constant hunger, frequent urination, history of gestational diabetes.    - Suspected Condition: Likely Type 2 Diabetes Mellitus due to insulin resistance.

Hormones Mentioned

  • Insulin, Estrogen, Progesterone, Oxytocin, testosterone, Cortisol, Glucagon, Antidiuretic Hormone (ADH).

Study Guide:

What do endocrine glands do? Release hormones into the blood stream or tissues of the body.

What do exocrine glands do? Release enzymes through ducts to another organ within the body or even outside the body.

Key function of the endocrine system? Maintain homeostasis.

Locations of major glands in endocrine system:

    hypothalamus: Acts to increase or decrease hormones from the pituitary gland.

  • CRH Corticotropin

  • TRH Thyrotropin

  • GnRH Gonadotropin

  • Somatostatin (Suppresses release of GH and TSH)

    pituitary gland (anterior and posterior): Master gland

  • Anterior has 6 major hormones

    • TSH acts on thyroid gland

    • Adrenocorticoids stimulate adrenal cortex.

    • Prolactin promotes milk production in lactating women and plays a role in reproductive health.

    • Growth hormone stimulates growth, cell reproduction, and cell regeneration in humans and many other animals, making it crucial for normal physical development.

    • Gonadotropins

      • Follicle stimulating hormone: growth of ovarian follicle and sperm production

      • Luteinizing hormone: Stimulate ovulation, produce estrogen, secrete testosterone.

  • Posterior has 2 hormones known as tropic hormones: Oxytocin and ADH. Extension of hypothalamus.

    • ADH stimulates kidney tubules in nephrons to reabsorbs water. Retain water and reduce amount of urine.

    • Oxytocin: Love, sex, childbirth/

    pancreas

    thyroid: Think metabolism.

    parathyroid

    adrenals

What connects the hypothalamus and pituitary gland? Hypophyseal stalk

What are hormones? chemical substances that act like messenger molecules in the body. Target cells only respond to their specific hormone. After action on the target cells, the hormone is metabolized by liver and excreted by kidneys to prevent an accumulative effect.

What is the difference between neurotransmitters and hormones?

    Neurotransmitters move from neuron to neuron

    Hormones move through the blood stream.

    Neurohormones are transported both ways.

What does insulin do in the body? It helps transport glucose from the blood stream into the cells to provide energy.

    Why do we need it? To regulate blood sugar levels and prevent hyperglycemia, which can lead to serious health complications.

    Where does it come from? Insulin is produced by beta cells in the pancreas. These cells are located in the islets of Langerhans, which are clusters of cells within the pancreas that regulate blood sugar levels by secreting insulin and other hormones.

    Insulin cannot be taken by mouth.

Diabetic Ketoacidosis: a serious complication of diabetes resulting from insufficient insulin levels, leading to the body breaking down fat for energy and producing ketones, which can cause the blood to become acidic.

Acute problems of DM I and II Hypoglycemia kills quick

Acute problems of DM I and II Hyperglycemia kills slowly.

Clinical manifestations of DM is polyuria, polydipsia, and polyphagia.

Neuropathy: Pain/paresthesia of feet and or hands.

Why does IV insulin drop potassium levels? Big dose of insulin moves glucose from blood stream into cells, and it also moves K out of blood stream and back into cells.

Diabetes means increased urine.

When insulin is decreased, blood levels of glucose, potassium, and ketones are all elevated.

Complications of corticosteroid use is a decrease in serotonin levels, so you become moody. It also decreases immune system’s ability to fight infections. It makes you hungry and leads to weight gain. Increased gastric acid can lead to GI bleeding. It increases insomnia.

Out of hyperglycemia, hypoglycemia, thyrotoxicosis, myxedema, Addison crisis, and pheochromocytoma attack, what would you treat first? Hypoglycemia would be treated first, if blood glucose falls below 30 it can lead to death.

What is a sign of DKA and needs to be treated quickly?

Why do you have increased urine output with DM? Excess glucose ends up in urine and pulls more water which results in more urine.

If your body makes too much cortisol, what can it result in? Cushing syndrome

Panhypopituitarism: absent production of all or most of anterior pituitary gland hormones.

What hormone is affected in hypoparathyroidism? The hormone affected in hypoparathyroidism is parathyroid hormone (PTH), which regulates calcium and phosphate balance in the body. Hypoparathyroidism can lead to low levels of calcium in the blood (hypocalcemia), resulting in symptoms such as muscle cramps, tingling in the fingertips, and in severe cases, seizures.

Why does diabetic ketoacidosis happen? Diabetic ketoacidosis occurs when the body cannot produce enough insulin, leading to high levels of ketones in the blood as fat is broken down for energy instead of glucose. This can happen in individuals with type 1 diabetes who have undiagnosed or poorly controlled diabetes, as well as in type 2 diabetes patients during times of stress, illness, or when the body becomes resistant to insulin.

What is type 1 DM? Insulin production problem. Diagnosed first in children usually. Beta cell destructions lead to insulin not being produced and the treatment is lifelong insulin injections.

What is Type 2 DM? Insulin resistance problem at first but can later lead to insulin production stopping. Overworked beta cells may lead to decreased insulin production.

Who is least likely to be at risk for developing Type II DM? Caucasians and Eastern Europeans.

What are the risk factors for Type II DM? Genetics, obesity, race, advancing age (45), history of gestational diabetes.

What hormone is affects with Cushing syndrome? Cortisol, the body makes too much, or you take too many corticosteroids.

What are the clinical manifestations of Cushing Syndrome? Truncal obesity, moon face, buffalo hump, thin arms and legs, acne, thinning and balding of the hair on head, facial hair and irregular mensural cycle in women, hyperglycemia, and osteoporosis.

What are the complications of DM? hypoglycemia, hyperglycemia, HTN, cardiovascular disease, diabetic retinopathy, renal failure, pregnancy complications, diabetic neuropathy, increased susceptibility to infections, delayed healing, and sexual dysfunction.

    Acute hypoglycemia which kills you fast and is a result of low glucose (less than 70). The most common cause is mismatch insulin, food intake, and physical activity. Early signs include, hunger, irritability, pale sweat skin, tremors, anxiety, and fatigue. The person needs to eat/drink something with sugar in it. Glucose under 50 can affect the brain and under 30 can kill you.

    Acute hyperglycemia kills slower and is a result of glucose above 180. It needs treatment but it is not as life threatening.

    DKA is a glucose over 250 and blood pH less than 7.3. Results in Kussmauls respirations, fruity breath, confusion, ketones in urine, and possibly coma.

What are the clinical manifestations of hyperthyroidism? HTN, increased, anxiety, intolerance to heat, recent weight loss without diet, insomnia.

What hormone is affected with hypothyroidism and hyperthyroidism? Both conditions primarily affect the production of thyroid hormones, specifically thyroxine (T4) and triiodothyronine (T3). In hypothyroidism, there is a deficiency of these hormones, while in hyperthyroidism, there is an excess.

What are the clinical manifestations of hypoparathyroidism? Cold intolerance, unexplained weight gain without diet changes, fatigue.

What hormone is affected with Addison disease? Adrenal glands and lowers cortisol and aldosterone.

What is the CM of Addison disease? Weight loss, low BP, muscle weakness, salt craving, hyperpigmentation over the joints.

What is a medical emergency of Addison disease? Addison crisis which presents with severe weakness, low BP, N/V, and diarrhea.

What are the clinical manifestations of SIADH? Too much ADH, person has little to no urine output. Decreased sodium, edema in legs, fluid in lungs, loss of consciousness, seizures, rain swelling (cerebral edema), and death.

What causes SIADH? Pituitary tumors, TBI.

What is the CM of DI? Low ADH with increased urine up to 20X normal.

How do you treat DI? Give fluids and vasopressin (ADH)

What is the pathology of Pheochromocytoma? Rare tumor and the tumor excrete increased epinephrine and norepinephrine and leads to pheochromocytoma crisis (HTN, tachycardia, and hyperglycemia)

What hormone is affected with hyperparathyroidism? Hyperparathyroidism typically involves an increase in parathyroid hormone (PTH), which leads to elevated calcium levels in the blood by promoting calcium release from bones, increased intestinal absorption of calcium, and reduced renal excretion of calcium.

What is the CM of hyperparathyroidism? Caused from release of too much calcium from bones into the blood stream and causes osteoporosis, pathological fractures, renal calculi, abdominal pain, N/V, constipation, and anorexia.

What hormone is affected with hypoparathyroidism? Hypoparathyroidism typically involves a decrease in parathyroid hormone (PTH), which results in lower calcium levels in the blood, leading to symptoms such as muscle cramps, tetany, and increased neuromuscular excitability.

What is the CM of Hypoparathyroidism? Common manifestations (CM) of hypoparathyroidism include symptoms related to low calcium levels, such as muscle spasms or cramps, tingling in the fingertips and around the mouth, fatigue, anxiety, and in severe cases, seizures or cardiac issues due to prolonged low calcium levels.

What is gigantism? Excessive growth hormone before puberty resulting in excessively tall stature.

What is acromegaly? Growth hormone after puberty resulting in increased bone size of the face, hands, and feet.

What happens with diminished growth hormone? Delayed growth and development, small in size but may be proportionate.

How can you treat someone with diminished growth hormone? Treat by giving growth hormone

What increases when insulin is decreased? Glucose, potassium, and ketones are elevated.