Introduction Flashcards
3 Classes of Hormones
- Peptide & 2. Monoamine
- Peptide: Insulin, ACTH, TRH
- Monoamine: Epinephrine, Serotonin
- Cell membrane receptors
- activate 2nd messenger membrane channel - Hydrophobic: Steroids, Vitamin D3, T3
- Have nuclear receptor
- Activate transcription factor
- transport in blood via plasma binding protein
Tropic vs. Target Hormones
Trophic hormones: control levels of Target Hormones
- e.g., Hypothalamic-Pituitary Axis
- Often under negative feedback by the target hormones
- May stimulate or suppress target hormones
Hormone Measurement & Variability
Measurement techniques:
- Bioassay
- Immunoassay
- Chemical Assay
Peptide Hormones:
- variability in isoforms
- Bioactivity: improper peptide sequence may affect ability to bind to receptor
vs.
- Immunoactivity: variability in how antibodies interact with particular isoform
Etiologies of Hormone Deficiency
- Gland destruction (autoimmune, infarction, trauma, etc) - Abnormal gland development - Bioinactive hormone » Abnormal synthesis » Abnormal prohormone processing
Stimulation Testing
- Useful for evaluating HORMONE DEFICIENCY
- goal is to provide a physiologic or pharmacologic stimulus to hormone secretion and measure the hormone response
Example:
Pituitary function:
- Hypoglycemia normally stimulates cortisol
and growth hormone secretion (both restore blood glucose to normal)
- Could administer insulin to induce hypoglycemia; normal response would stimulate cortisol & GH
Adrenal Function:
- Aldosterone normally increases in response
to acute volume depletion induced by diuretic
- Cortisol normally increases in response to
synthetic ACTH (cosyntropin)
Hormone Excess Classification & Diagnosis
Classification
» Target gland autonomy (Primary)
» Tropic hormone autonomy (Secondary)
» Ectopic hormone production
Diagnosis » Characteristic clinical syndrome » Elevated target hormone level » Target hormone does not suppress » Tropic hormone low (primary autonomy) » Tropic hormone “normal” or high (secondary autonomy or ectopic)
Suppression Test
- useful for evaluating AUTONOMOUS HORMONE PRODUCTION
- perform maneuvers that should normally suppress hormone secretion and we measure the response
Hormone Resistance Classification & Diagnosis
Classification
- Receptor defect
- Post receptor defect
- Endogenous receptor blocker
Diagnosis
» Variable clinical syndrome with features
consistent with hormone deficiency
» Target hormone level normal or elevated
» Diminished or absent response to
exogenous hormone
Testicular Feminization in 46XY:
- Male levels of testosterone, but abnormal testosterone receptors –> female body habitus
Severe insulin resistance type B:
» Anti-insulin receptor antibodies present
» Hyperglycemia despite high insulin level
Target Cell Activation Classification & Diagnosis
Classification
» Receptor-activating mutation
» Post-receptor autonomy
» Endogenous hormone agonist
Diagnosis
» Clinical syndrome consistent with hormone
excess
» Hormone level low
McCune Albright Syndrome
- Clinical features: pseudoprecocious puberty, Cushing syndrome, thyrotoxicosis, café au spots, fibrous dysplasia of bone, etc.
» Pituitary tropic hormones (ACTH, TSH, LH, FSH) are low
» Due to Gs constitutive activating mutations
Humoral hypercalcemia of malignancy
- Hypercalcemia
» Parathyroid hormone (PTH) low
» “PTH-related” peptide present