Hormone Pathways: Adrenal Insufficiency, Thyroid, and Diabetes
Corticotropin-Releasing Hormone (CRH) – Adrenocorticotropic Hormone (ACTH) – Cortisol Pathway
Adrenal Insufficiency (Cortisol Hyposecretion)
Because cortisol is needed to permit cardiovascular action of epinephrine, and decreased aldosterone secretion increases sodium/water loss, this can lead to hypotension.
Because cortisol promotes the release of glucose into the bloodstream, this can lead to hypoglycemia.
Primary Adrenal Insufficiency (Addison’s Disease): Loss of adrenal cortisol function due to autoimmune destruction of cells of the adrenal gland leads to decreased aldosterone secretion, causing an imbalance of water/sodium, which exacerbates hypotension.
Secondary Adrenal Insufficiency: Pituitary disease leads to decreased ACTH secretion, resulting in decreased ACTH in plasma and decreased cortisol (only).
Cortisol Hypersecretion
Cushing’s Syndrome: Excess cortisol in the blood (due to a primary defect like a cortisol-secreting tumor of the adrenal gland or a secondary defect like an ACTH-secreting tumor of the pituitary gland) such that increased blood levels of cortisol promote uncontrolled catabolism of bone, muscle, skin, and other organs, leading to osteoporosis, muscle weakness, hyperglycemia, immunosuppression, hypertension, and obesity.
Thyroid-Releasing Hormone (TRH) – Thyroid-Stimulating Hormone (TSH) – Triiodothyronine (T3), Thyroxine (T4) Pathway
Hypothyroidism (Hashimoto’s Disease): Autoimmune destruction of the thyroid gland, through negative feedback, increases TRH, increases TSH, and decreases T3 and T4. Increased TSH causes goiter (enlargement of the thyroid). Decreased T3 causes decreased metabolic rate/consumption of calories/heat production, resulting in weight gain and cold intolerance.
Hyperthyroidism (Grave’s Disease): Autoimmune disorder where autoantibodies agonize TSH receptors, through negative feedback, decreases TRH, decreases TSH, and increases T3 and T4. Increasing T3 increases metabolic rate and heart rate, resulting in increased nervousness and anxiety due to sympathetic input to autonomically innervated cells of the heart.
Central Diabetes Insipidus
Release of vasopressin/antidiuretic hormone from the posterior pituitary is dysfunctional, leading to decreased vasopressin concentration in plasma. This results in decreased insertion of aquaporin 2 channels into the luminal membrane of the tubular epithelial cells in the collecting duct, decreasing water reabsorption and increasing water excretion via urine, leading to dehydration. This causes a decrease in ECF volume, plasma volume, blood volume, and pressure, ultimately decreasing MAP.
Angiotensin-Converting Enzyme Inhibitors (Anti-Hypertensive Drug)
ACE inhibitors block the pathway that converts angiotensin I to angiotensin II, decreasing angiotensin II. This leads to a decrease in vasoconstriction, decreasing TPR and MAP.
A decrease in angiotensin II also decreases aldosterone secretion from the adrenal cortex, leading to decreased sodium and water reabsorption and increased water excretion, decreasing ECF volume, plasma volume, blood volume, and pressure, ultimately decreasing MAP.
Patient with Excessive Cortisol Secretion
A patient with excessive cortisol secretion is treated with dexamethasone but is not responsive to this drug therapy. Is this individual likely to be suffering from Cushing’s Disease?
Cortisol is released from ACTH and the adrenal cortex. Since the individual appears to be unresponsive to dexamethasone, the cause must be from a primary defect like a tumor, which is Cushing’s Syndrome. Therefore, the individual is unlikely to be suffering from the secondary defect that is Cushing’s Disease.