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Pituitary Function Tests

This lecture explains the basics of pituitary function tests along with the mechanisms involved and other related aspects.

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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

 

 

 

 

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