Untitled Quiz

Endocrine Pathophysiology Introduction

• Focuses on hypothalamic disruptions, posterior and anterior pituitary disorders, and parathyroid dysfunction.
• Briefly reviews hormone synthesis, release, transport, and receptor interactions.
• Emphasizes the delicate balance between hormone levels and their impact on the body.

Hormone Receptors

• Bind to specific hormones, initiating cellular responses.
• Located on cell membranes, in the cytoplasm, or in the nucleus.
• Mediate hormone effects via various mechanisms (e.g., changes in gene expression).
• Their number and sensitivity can be regulated, affecting hormone action.

Hypothalamic Disruptions

• Can affect hormone release from the pituitary gland.
• Include disruptions in the synthesis or release of releasing & inhibiting hormones.
• May result in anterior pituitary dysfunction (hypopituitarism or hyperpituitarism).
• Can lead to abnormalities in posterior pituitary function (DI or SIADH).

Posterior Lobe Diabetes Insipidus (DI)

• Characterized by insufficient ADH (vasopressin) leading to excessive urination.

ADH (Vasopressin)

• Controls water reabsorption in the kidneys.
• Increases the permeability of the collecting ducts to water.
• Regulates blood pressure.
• Synthesized in the hypothalamus, stored & released by the posterior pituitary.
• Deficiency leads to DI; excess leads to SIADH (Syndrome of Inappropriate Antidiuretic Hormone).

Neurogenic (Central) DI

• Results from decreased ADH secretion due to hypothalamic or pituitary damage.
• Can be caused by tumors, trauma, infections, or autoimmune diseases.
• Characterized by polyuria, polydipsia, and hypernatremia.
• Diagnosis involves water deprivation test, ADH stimulation test.
• Treatment includes ADH replacement therapy (desmopressin).

Nephrogenic DI

• Caused by kidney's inability to respond to ADH.
• Results from mutations in the ADH receptor or disruptions in downstream signaling.
• Can have genetic or acquired causes (e.g., electrolyte imbalances, medications).
• Treatment focuses on managing fluid intake and addressing the underlying cause.

Pseudo DI

• Characterized by excessive water loss due to non-hormonal factors.
• Common causes include excessive sweating, polyuria from other medical problems.
• Treated by addressing the underlying condition causing polyuria.

Pathophysiology of DI

• ADH deficiency leads to decreased water reabsorption in the kidneys.
• This causes increased urine output and potentially dehydration and hypernatremia.
• The body tries to compensate by increasing water intake (polydipsia).

Clinical Manifestations of DI

• Polyuria (excessive urination).
• Polydipsia (excessive thirst).
• Nocturia (frequent nighttime urination).
• Dehydration, hypernatremia.
• Symptoms vary depending on the severity and underlying cause.

Evaluation of DI

• Measures urine volume, osmolality, and electrolytes.
• Water deprivation test assesses ADH response.
• ADH stimulation test distinguishes between central and nephrogenic types.

Treatment of DI

• Desmopressin (ADH replacement) for central DI.
• Amiloride/HCTZ (diuretics) and low sodium diet for nephrogenic DI.
• Hydration strategies to maintain fluid balance.

Posterior Lobe SIADH (Syndrome of Inappropriate Antidiuretic Hormone)

• Characterized by excessive ADH secretion leading to fluid retention and hyponatremia.

Causes of SIADH

• Can be caused by tumors (lung cancer), CNS disorders, infections, medications, or certain conditions (e.g., pneumonia).
• Ectopic ADH production is a common cause.
• Lung cancer is a significant cause of SIADH.

Pathophysiology of SIADH

• Excess ADH leads to increased water reabsorption in the kidneys.
• This causes fluid retention (dilutional hyponatremia).
• Reduced urine volume and increased sodium excretion..

Clinical Manifestations of SIADH

• Hyponatremia (low serum sodium).
• Nausea, vomiting, headache.
• Neurological symptoms (confusion, seizures).
• Weight gain.

Diagnosis of SIADH

• Measures serum sodium, osmolality, urine sodium, and urine osmolality.
• Water load is avoided; hypertonic saline may be required.

Treatment of SIADH

• Fluid restriction is crucial.
• Demeclocycline (inhibits ADH action).
• Hypertonic saline may be needed in severe cases..
• Tolvaptan (ADH receptor antagonist).

Anterior Pituitary Hypopituitarism

• Characterized by deficient hormone production from the anterior pituitary gland.

Pituitary Failure

• Can result from tumors, trauma, infections, infarcts, or autoimmune diseases.
• Deficiency in multiple hormones is common, including:
  • Growth hormone (GH) deficiency.
  • Thyroid-stimulating hormone (TSH) deficiency.
  • Adrenocorticotropic hormone (ACTH) deficiency.
  • Gonadotropin deficiency (FSH & LH).
  • Prolactin deficiency.
• Can cause a variety of symptoms depending on which hormones are deficient.

Pathophysiology of Hypopituitarism

• Decreased production of anterior pituitary hormones affects target organs.
• Leads to hormone deficiencies and downstream consequences.

Clinical Manifestations of Hypopituitarism

• Vary depending on the affected hormones.
• Include fatigue, weight loss, decreased libido, menstrual irregularities, cold intolerance, etc.

Evaluation & Treatment of Hypopituitarism

• Assesses hormone levels (e.g., GH, TSH, ACTH, FSH/LH, prolactin).
• Imaging of the pituitary (CT or MRI).
• Treatment involves hormone replacement therapy.

Anterior Lobe Growth Hormone (GH)

• Essential for growth and development.
• Regulates metabolism and cellular processes.

GH Secretion

• Regulated by the hypothalamus (GHRH and somatostatin).
• Pulsatile secretion, mostly during sleep.
• Influences liver production of IGF-1 (Insulin-like Growth Factor 1).

GH Actions

• Stimulates growth of bones, muscles, & organs.
• Increases protein synthesis.
• Affects metabolism of carbohydrates, lipids, & minerals.

Acromegaly

• Results from Excess GH (IGF-1) production.

Excess GH (IGF-1) Production

• Primarily caused by pituitary adenomas.
• Leads to overgrowth of bones, soft tissues, and organs.
• Can result in various complications (cardiovascular, metabolic).

Pathophysiology of Acromegaly

• Excess GHRH or GH-secreting pituitary adenoma increases GH & IGF-1 levels.
• Results in excessive growth & various metabolic effects.

Clinical Manifestations of Acromegaly (Adults)

• Enlarged hands, feet, and facial features.
• Joint pain & arthralgias.
• Headaches.
• Sleep apnea.
• Glucose intolerance & type 2 diabetes.
• Hypertension.
• Increased risk of certain cancers.

Evaluation of Acromegaly

• Measures IGF-1 level & GH after oral glucose tolerance test.
• Pituitary MRI identifies pituitary adenomas.

Treatment of Acromegaly

• Transsphenoidal surgery (removal of adenoma).
• Somatostatin analogs (octreotide, lanreotide).
• Dopamine agonists (cabergoline, bromocriptine).
• Pegvisomant (GH receptor antagonist).

Anterior Lobe Prolactin Excess

• Hyperprolactinemia.

Prolactin Regulation

• Primarily inhibited by dopamine.
• Stimulated by TRH (thyrotropin-releasing hormone).
• Also affected by other hormones and substances.
• Release of prolactin is triggered by suckling.

Prolactin Excess

• Most often caused by pituitary adenomas (prolactinomas).
• Can result from other causes (e.g., hypothyroidism, medications).
• Hyperprolactinemia can lead to galactorrhea (breast milk production), menstrual irregularities, infertility, decreased libido.

Pathophysiology of Prolactin Excess

• Prolactinomas secrete excessive prolactin interfering with other hormone regulation.
• Affects gonadal function due to increased prolactin suppressing GnRH.

Clinical Manifestations of Prolactin Excess

• Galactorrhea (milk production).
• Menstrual irregularities or amenorrhea.
• Infertility.
• Decreased libido.
• Osteoporosis (in women).

Evaluation & Treatment of Prolactin Excess

• Measures serum prolactin levels.
• Pituitary MRI to identify adenomas.
• Treatment includes dopamine agonists (cabergoline, bromocriptine), sometimes surgery.

Parathyroid Dysfunction

• Involving either hypoparathyroidism or hyperparathyroidism.

PTH Secretion

• Primarily regulated by serum calcium levels.
• Low calcium stimulates PTH release, raising serum calcium.
• High calcium inhibits PTH release, lowering serum calcium.

Function of Parathyroid Hormone (PTH)

• Maintains serum calcium homeostasis.
• Increases calcium resorption from bone.
• Increases calcium absorption in the gut.
• Increases calcium reabsorption in the kidneys.

Hypoparathyroidism

• Characterized by deficient PTH leading to low serum calcium.

Causes of Hypoparathyroidism

• Surgical removal or damage to parathyroid glands.
• Autoimmune disorders.
• Genetic mutations.
• Other rare causes.

Pathophysiology of Hypoparathyroidism

• Decreased PTH leads to decreased resorption of calcium from bone, less absorption in gut.
• Less calcium reabsorption by the kidneys.

Clinical Manifestations of Hypoparathyroidism

• Hypocalcemia (low blood calcium).
• Tetany (muscle spasms).
• Seizures.
• Cardiac arrhythmias.

Evaluation of Hypoparathyroidism

• Measures serum calcium, PTH, and phosphorus levels.
• ECG assesses cardiac function.

Treatment of Hypoparathyroidism

• Calcium & vitamin D supplementation.
• Phosphate binders.
• Bisphosphonates.
• Calcitriol or other Vitamin D analogs.

Hyperparathyroidism

• Characterized by excess PTH secretion leading to high serum calcium levels.

Primary Hyperparathyroidism

• Usually caused by a parathyroid adenoma.
• Less often caused by hyperplasia or carcinoma.
• Excess PTH leads to increased bone resorption, which causes calcium to leak from bones.

Secondary Hyperparathyroidism

• Results from chronic hypocalcemia (e.g., CKD, vitamin D deficiency).
• Body secretes excess PTH in an attempt to raise blood calcium levels.

Tertiary/Pseudo Hyperparathyroidism

• Involves long-standing secondary hyperparathyroidism where the parathyroid glands become autonomous.
• PTH levels remain elevated even after correction of hypocalcemia.
• Continued high PTH levels can cause increased bone resorption, causing bone and kidney damage.

Clinical Manifestations of Primary Hyperparathyroidism

• Refer to the table provided in the original text for a detailed breakdown by organ system. The table categorizes symptoms by organ system (GU, GI, M/S) and explains the underlying physiological mechanism.