This lecture explains the basics of pituitary function tests along with the mechanisms involved and other related aspects.
Outline of Lecture
Pituitary Function Tests
Neural Control Of Glandular Secretion
regulated secretion of hormones, neurotransmitters, or neuromodulators by specialized cells
endocrine cells and neurons are prototypical secretory cells
Secretory cells
endocrine cells secrete their contents directly into the bloodstream
paracrine cells secrete their contents into the extracellular space
autocrine secretory cells affect their own function by the local actions of their secretions
Neurosecretion
Neurons
secretory cells that send their axons throughout the nervous system to release their neurotransmitters and neuromodulators predominantly at specialized chemical synapses
Neurohumoral or neurosecretory cells
a unique subset of neurons whose axon terminals are not associated with synapses
Three types of hypothalamic neurosecretory cells
Normal anatomy of the human hypothalamic-pituitary unit in sagittal (A) and coronal planes (B)
Principal Human Hypothalamic Peptides Directly Related To Pituitary Secretion
Vasopressin
Oxytocin
Thyrotropin-Releasing Hormone
Gonadotropin-Releasing Hormone
Corticotropin-Releasing Hormone
Growth Hormone-Releasing Hormone
Somatostatin
Vasoactive Intestinal Peptide
Prolactin-Releasing-Peptide
Ghrelin
anterior pituitary
master gland derives its name from the Greek ptuo and Latin pituita, “phlegm,” reflecting its nasopharyngeal origin.
adult pituitary weighs about 600 mg (range 400-900 mg)
measures about 13 mm x 6 to 9 mm x 9 mm
situated within the bony sella turcica
five distinct hormone-secreting cell types
Corticotrophs 20% (CRH)
Thyrotrophs <10% (TRH)
Gonadotrophs 10% (GnRH)
Somatotrophs 50% (GHRH)
Lactotrophs 10-20% (PRH)
Coronal section of the sellar structures and cavernous sinus
Schematic representation of the blood supply of the hypothalamus and pituitary
Pituitary Control
Concept of feedback control
short-loop feedback control
glucocorticoids, gonadal steroids, thyroid hormone,anterior pituitary hormones
ultrashort-loop feedback control
hypophyseotropic factors
Regulatory feedback loops of the hypothalamic-pituitary-target organ axis
Assessment of endocrine function
by measuring levels of
basal circulating hormone
evoked or suppressed hormone
hormone binding proteins
hormone hypersecretion
diagnosed by suppressing glandular function
hormone hyposecretion
attempting to evoke hormone secretion by recognized stimuli
Regulation of the hypothalamic-pituitary-thyroid axis
Regulation of the hypothalamic-pituitary-adrenal axis
Regulation of the hypothalamic-pituitary-growth hormone (GH) axis
Regulation of the hypothalamic-pituitary-prolactin (PRL) axis
Regulation of the hypothalamic-pituitary-gonadal axis
Control of hypothalamic-pituitary target organ axes
Growth hormone axis
Integrated model of the GH-IGFBP-IGF axis in the growth process
Specific Investigations For Growth Hormone Deficiency
Screening dynamic function tests
Basal Growth hormone level ???
Post sleep growth hormone levels
GH levels at peak after 1 hour of deep sleep
INVESTIGATIONS
Exercise stimulation test
Basal levels before exercise
After 20 min of strenuous exercise
Normal response >20mIU/L
Levo dopa stimulation test
Dose 0.5g/1.73m2
Samples taken at 30,60,90 & 120 min
Normal response >20mIU/L
Confirmatory Investigations
Subnormal response from a single test is not diagnostic
Confirmatory dynamic function tests
Only in cases where strong indications are present
Life threatening complications may arise
presence of Medical Officer mandatory
Stimulation tests for pituitary function
Insulin tolerance test
Arginine infusion test
Clonidine stimulation test
Glucagon
Insulin Tolerance test (Gold standard)
Regular human insulin
Dose = 0.12-0.15 U/kg
Injection of insulin after sample for baseline Growth hormone levels is taken
Observation for heart rate/ blood pressure/ signs of severe hypoglycemia, blood glucose monitoring– 25% Dextrose in emergency/ induction of hypoglycemia
Samples for GH levels taken at 0,30 and 60 minutes after induction of hypoglycemia
Normal response: GH levels more than 20 mIU/L
Prolactin
Structure : four helix peptide chains
Short half-life
Circulates in different sizes :
Little PRL : Active form ( 80% )
Big PRL non active forms
Big Big PRL
Cleared by the liver and kidney
Regulation of Prolactin
Pituitary Failure
Impaired synthesis of one or more anterior pituitary hormones
heritable genetic factors
acquired anatomic insults
inflammation
vascular damage
Combined hypothalamic hormone stimulation (GnRH, TRH, CRH, and GHRH) or insulin-evoked hypoglycemia reveals blunted responses consistent with varying degrees of pituitary hormone deficiencies.
Assessment Of Anterior Pituitary Function
Adrenocorticotropic hormone
Thyroid-stimulating hormone
Prolactin
Luteinizing hormone and follicle-stimulating hormone
Growth hormone
Adrenocorticotropin
Corticotroph cells make up about 20% of functional anterior pituitary cells
These cells produce the POMC gene products including ACTH(1-39), β-lipotropin, and endorphins
Physiologic ACTH Regulation
Stress Response
Integrated Regulation of ACTH Secretion
Dynamic Testing for ACTH Reserve
Hypothalamic Testing
Insulin
Metyrapone
Pituitary Stimulation
Adrenal Stimulation
Adrenal Stimulation Test
Interpretation
Thyroid-Stimulating Hormone
Assays
third-generation assays have a functional sensitivity of 0.01-0.02 mU/L
newer fourth-generation assays portend greatly enhanced sensitivity (0.001-0.002 mU/L
Deficiency