What Is Endocrinology? The Basics Endocrinology is a branch of medicine that deals with the endocrine system, which controls the hormones in your body. An endocrinologist is a physician who specializes in the field of endocrinology. Endocrinologists diagnose and treat a wide range of conditions affecting the endocrine system, including diabetes mellitus, thyroid disorders, osteoporosis, growth hormone deficiency, infertility, cholesterol problems, hypertension (high blood pressure), obesity and more. How the Endocrine System Works The endocrine system’s glands and organs release hormones that regulate a number of vital functions of our body. These glands include the hypothalamus, pineal body, pituitary, thyroid, parathyroids, adrenals, pancreas, testes and ovaries. The hormones in your body all have specific jobs to complete. There are up to 40 different hormones circulating in your blood at any time. Once released into the bloodstream, a hormone travels throughout the body until it reaches its specific destination(s) to perform its function. These destinations, called targets, can be located either on other endocrine glands or on other organs and tissues in the body. When a hormone reaches its target, it tells that part of your body what work to do, when to do it and for how long. Hormones are often referred to as the “messengers” because they help different parts of the body communicate. Overall, they are involved in many different processes in the body, including: Blood sugar control Growth and development Metabolism (the process of getting and maintaining energy in the body) Regulation of heart rate and blood pressure Sexual development and function Reproduction Mood What Happens When the Endocrine System Does Not Work? Hormonal function is a balancing act. Too much or too little of one hormone can have an impact on the release of other hormones. If this hormonal imbalance occurs, some of your body’s systems will not work properly. These imbalances can often be corrected by the body itself. Your body has built-in mechanisms to keep track of and respond to any changes in hormone levels to bring them back to normal and restore the balance. Sometimes, however, this system goes wrong and there can be a problem that the body can’t fix itself. In this case, a primary care physician will refer you to an endocrinologist, who is an expert in treating frequently complex (and often chronic) conditions which can involve several different systems within the body. The Anatomy of the Endocrine System The endocrine system is made up of a collection of glands. Each gland has a specific function in the body, and all these glands work together to regulate vital functions of our body. Adrenal glands Located just above the kidneys, adrenal glands are responsible for the secretion of several hormones which maintain the body’s salt and water balance that in turn regulate blood pressure, help the body cope with and respond to stress, regulate body meta

2.  Endocrine system is a network of ductless glands that secrete hormones
directly into the blood.
 It is considered as the regulatory system of the body.
 Controlled by hormone synthesis rather than degradation.

3.  These are chemical signals produced by specialized cells secreted into
blood stream and carried to a target tissue.
 They act at tissues or sites different from where they are synthesized and
released.
 Play an important role in growth and development of an individual.
 Regulated by metabolic activity either by positive or negative feedback
mechanism.

4.  Sometimes they are influenced by physiologic factors such as age, as in
case of the elderly who secrete less triiodothyronine, parathyroid
hormone, aldosterone, and cortisol.
 Major functions: To maintain the constancy of chemical composition of
extracellular and intracellular fluids; and control metabolism, growth,
fertility, and responses to stress.

5.  The majority of endocrine functions are regulated through the pituitary
gland, which in turn is controlled by secretions from the hypothalamus.

6.  Positive Feedback System (PFM)
 An increase in the product results to elevation of the activity of the system
and the production rate (e.g., gonadal, thyroidal and adrenocortical
hormones).
 Negative Feedback System (NFM) – most common
 An increase in the product results to decreased activity of the system and the
production rate (e.g., luteinizing hormone)

8.  Long FM: Feedback from hormones produced in the pituitary target glands
on the hypothalamus
 Short FM: Feedback of hormones at the level of the pituitary gland
 Ultrashort FM: Feedback mechanism between the pituitary and
hypothalamus.

9.  Endocrine
 Secreted in one location and released into blood circulation
 Binds to a specific receptor to elicit physiological response
 Paracrine
 Secreted in endocrine cells and released into interstitial space
 Binds to a specific receptor in adjacent cell and affects its function.

10.  Autocrine
 Secreted in endocrine cells and sometimes released into interstitial space
 Binds to a specific receptor on cell of origin resulting to self-regulation of its function
 Juxtacrine
 Secreted in endocrine cells and remains in that same cellular space in relation to
plasma membrane.
 Acts on immediately adjacent cell by direct cell-to-cell contact
 Intracrine
 Secreted in endocrine cells and functions inside the origin of synthesis

11.  Exocrine
 Secreted in endocrine cells and released into lumen of gut, and affects their functions
 Neurocrine
 Secreted in neurons and released into extracellular space
 Binds to a receptor in nearby cell and affects its functions
 Neuroendocrine
 Secreted in neurons and released from nerve endings
 Interacts with receptors of cells at distant site

13. Properties Examples
• Water-soluble and not bound to a
carrier protein
• Synthesized and stored within the
cell in the form of secretory granules
and are cleaved as needed.
• Cannot cross the cell membrane due
to their large molecular size
• Produce their effect on the outer
surface of the cell
Glycoprotein
FSH, HCG, TSH, and Erythropoietin
Polypeptides
ACTH, ADH, PTH, GH, Angiotensin,
Calcitonin, Cholecystokinin, Gastrin,
Glucagon, Insulin, Melanocyte-
stimulating Hormone, Oxytocin,
Prolactin, and Somatostatin
Peptides and Proteins

14. Properties Examples
• Water-insoluble (hydrophobic) and
circulate bound to a carrier protein.
• Cholesterol as a common precursor
• Produced by adrenal glands, ovaries,
testes, and placenta
Aldosterone, Cortisol, Estradiol,
Progesterone, Testosterone, and
Activated vitamin D3
Steroids

15. Properties Examples
• Intermediary between steroid and
protein hormones
• Derived from an amino acid
Epinephrine, Norepinephrine,
Triiodothyronine, and Thyroxine
Amines

16. Circadian rhythms:
 biological rhythms (endogenously generated) with a period close to 24 hours
Diurnal rhythms:
 a circadian rhythm that is synchronized with the day/night cycle

17. Ultradian rhythms:
 Biological rhythms (e.g., feeding cycles) with a much shorter period (i.e., much
higher frequency) compared to a circadian rhythm
 Examples of ultradian rhythms are blood circulation, pulse, heart rate,
thermoregulation, blinking, micturition, appetite
Infradian rhythms:
 Biological rhythms with a cycle that lasts longer than 24 hours (e.g., the human
menstrual cycle)

18.  The nervous system and the endocrine system are closely
interrelated and both are involved intimately in:
 maintaining homeostasis;
 keeping the body functioning regularly;
 responding properly to environmental stimuli through the regulated secretion of
hormones, neurotransmitters, or neuromodulators.

19.  It is the portion of the brain located on the walls and floor of the
third ventricle
 It is above the pituitary gland, and is connected to the posterior
pituitary by the infundibulum.
 The link between the nervous system and the endocrine system
 The supraoptic and paraventricular nuclei produce vasopressin and
oxytocin

20.  The neurons in the anterior portion release the following hormones
(hypophyseal hormones):
 thyrotropin-releasing hormone (TRH)
 gonadotropin-releasing hormone (Gn-RH)
 somatostatin, also known as growth hormone-inhibiting hormone
(GI-IH)
 growth hormone-releasing hormone (GH-RH)
 prolactin-inhibiting factor (PIF)

21.  Open-loop negative feedback mechanism
 Pulsatility: abrupt response to a stimulus or “pulse” pattern of
hormone secretion
 Cyclicity: the nervous system regulates this pattern through
external signals

22. ENDOCRINE GLANDS
HORMONES

23. PINEAL GLAND
 It is attached to the midbrain
 Its secretions are controlled by nerve stimuli.
 It secretes melatonin that decreases the pigmentation of the skin.
 Main functions: Receives information about the state of the light-
dark cycle from the environment and conveys this information to
produce and secrete the hormone melatonin.
 Possible causes of dysfunction: Accidental and developmental
conditions (pineal tumors, craniopharyngiomas, and injuries to the
gland).

24. Melatonin
N-acetyl-5-
hydrotryptamine

25. Melatonin N-acetyl-5-
hydrotryptamine
 Synthesized within the pinealocytes from tryptophan.
 It is only secreted during the dark period of the day.
 Marker of the phase of internal circadian clock (regulates the
circadian system and sleep patterns).
 It is used in therapy for sleep disorders.
 It has cell protection and neuroprotection properties
 It may be secreted in other sites such as in the GIT, skin, retina,
bone marrow, and placenta acting in an autocrine or paracrine.

26.  Except for the pineal gland, the abovementioned sites contribute
little to circulating concentration while after pinealectomy,
melatonin levels remain undetectable.
 Plasma melatonin in adults: 60 to 70 pg/mL when measured with
high-specificity assay
 Concentration in saliva: 3x lower in plasma
 Urine: 6-sulfatoxymelatonin (aMT6s) - good marker of melatonin
secretion
 Method: Immunoassay

27.  Health Benefits from Melatonin:
 Anti-oxidant and anti-aging properties
 Potent free radical scavenger
 More effective than glutathione in reducing oxidative stress (highly
concentrated in the mitochondria)
 Factors that Influence Melatonin Plasma Level:
 False Increased: Posture (night), exercise, and caffeine
 False Decreased: Alcohol and aspirin

28. PITUITARY GLAND
HYPOPHYSIS
 It is located in a small cavity in the sphenoid bone of the skull
called the sella turcica or Turkish saddle
 It is connected by the infundibular stalk to the median eminence
of the hypothalamus
 All pituitary hormones have circadian rhythms.
 Regions of the hypophysis: Adenohypophysis and
Neurohypophysis

29. ANTERIOR PITUITARY
ADENOHYPOPHYSIS
 It is the “true endocrine gland”.
 Regulates the release and production of hormones such as
prolactin, growth hormone, gonadotropins (FSH and LH), TSH,
and ACTH
 The hormones secreted by this anterior lobe are either peptides
or glycoproteins with pulsatile pattern.

30. GROWTH
HORMONE

31. Growth Hormone
GH Somatotropin
 The most abundant of all pituitary hormones
 Controlled by GH-RH (the amount released) and somatostatin
(governs the frequency and duration of secretory pulsatility).
 Its anabolic and metabolic actions are facilitated indirectly by
somatomedin G.
 The structure is similar to prolactin and human placental
lactogen.
 Its secretion is erratic and occurs in short burst

32.  Its overall metabolic effect is to metabolize fat stores while conserving
glucose.
 It promotes bone growth with anti-insulin effect on muscles.
 Major stimulus: Deep sleep (markedly increased GH)
 Major inhibitor: Somatostatin (synthesized by the hypothalamus)
 Physiologic stimuli (increased): Stress, fasting, and high-protein diet
 Pharmacologic stimuli (increased): Sex steroids, apomorphine, and
levodopa

33.  GH suppressors: Glucocorticoids and elevated fatty acid
 Increased: Acromegaly, chronic malnutrition, renal disease, cirrhosis,
sepsis, and DM
 Decreased: GHD, obesity, and hypothyroidism
 Common method: Chemiluminescent Immunoassay
 Reference value (fasting): <10ng/mL

34. Growth Hormone Deficiency (GHD)
 It is defined as a serum GH concentration <10ng/mL with
provocation as tested by a combination of at least two separate tests
 In healthy normal individuals, 70% to 80% of GH results are below
1 ng/mL (<1µg/L), and secretory peaks typically reach 20 to 40
ng/mL (20-40 g/L). Thus, in a child with decreased growth velocity, a
low or non-detectable GH does not necessarily indicate GHD.

35.  Idiopathic GHD
 The most common cause of GH deficiency
 GHD in childhood is described as the failure of serum GH to
reach defined levels when at least two different pharmacological
stimuli are used.
 In children with pituitary dwarfism, normal proportions are
retained and there are no intellectual abnormalities.
 Pituitary Adenoma
The most common etiology in adult-onset GH deficiency.

36. Acromegaly
 It is due to overproduction of GH (>50 ng/mL or 2210 pmol/L)
 Usually observed during adulthood
 Clinical manifestations: Diffused enlargement of soft tissues and
organs throughout the body, prognathism, fontal bossing, and
spade-like hands.

37.  Specimen requirement: Preferably fasting serum
 Fasting: 8-12 hours

38. Growth Hormone Deficiency
 Screening test: Physical Activity Test (Exercise test)
 GHD: Deficient or decreased
 Non-GHD: Elevated serum GH
 If GH fails to increase after exercise, a confirmation must be made
 GH is always elevated after any form of exercise.

39.  Confirmatory test
 Gold Standard: Insulin Tolerance Test (ITT)
 Second Confirmatory Test: Arginine Stimulation Test
 Third Confirmatory Test: Glucagon Stimulation Test
 Patient Preparation in ITT: Complete rest 30 minutes before blood
collection
 Procedure: 24-hour or Night-Time Monitoring of GH
 Interpretation in ITT: Failure of GH to rise >5 ng/mL in adults and >10
ng/mL in children is confirmed GHD.
 ITT determines the integrity of hypothalamus-pituitary axis, specifically
the GH secretion.
 ITT induces hypoglycemia and provokes GH release
 Confirmation of GHD in children is made if there is no increase after a two
pharmacologic stimuli.

40. Acromegaly
 Screening Test: Serum Somatomedin C or Insulin-like Growth-
Factor-1 (IGF-1)
 IGF-1: is produced in the liver,
increased in patients with acromegaly
low in GHD
 GH stimulates the production of IGF-1
 Physiologic increase: Pregnancy and late-stage adolescence

41.  Confirmatory Test: Oral Glucose Tolerance Test (75g)
 Fasting blood is required and the baseline blood glucose and GH levels
are measured.
 Blood is collected every after 30 minutes for 2 hours
 Normal response: Suppression of GH <1 ng/mL
 Acromegaly: If GH fails to decline <1 ng/mL
 Diagnostic of Acromegaly: Failure of GH to be suppressed below 0.3
ng/mL accompanied by an elevated IGF-1
 Excludes Acromegaly: Suppression of GH below 0.3 ng/mL with normal
IGF-1
 Requires follow-up and monitoring: Suppression of GH but increased
IGF-1

42. Macromelin Acetate Stimulation Test:
 It is considered as a secondary confirmatory in GHD
 Macromelin acetate is a drug that binds to the ghrelin receptor
 Oral dose: 0.5 mg/kg
 A reproducible safe diagnostic test for adult GHD, with accuracy
comparable to that of the ITT.

43.  Glucagon stimulation test and macromelin test are reasonable
alternatives to the insulin tolerance test, whereas the arginine
test is no longer recommended by the 2019 AACE Clinical
Practice Guidelines because this test has insufficient diagnostic
accuracy and requires a very low peak GH cut-point of 0.4 ug/L
to make diagnosis

44. Somatomedin C
 Also known as the insulin growth factor-1 (IGF-1)
 Mostly produced by the liver in response to GH stimulation.
 It determines if a person is producing a normal amount of GH
 It is vital for bone and tissue development by meditating the action
of GH
 Its plasma concentration is directly proportional to GH though it is
more stable

45. Somatomedin C
 Excess GH and IGF-1: Abnormal growth of the skeleton seen in
gigantism and acromegaly
 Deficiency of IGF-1: Lack of responsiveness to GH
 Deficiencies of GH and IGF-1: Hypopituitarism or the presence of a
non-GH-producing pituitary tumor that damages hormone-
producing cell.

46. GONADOTROPINS:
FOLLICLE-
STIMULATING
HORMONES
LUTEINIZING
HORMONE

47. Gonadotropins: FSH and LH
 Important markers in the diagnosis of fertility and menstrual
cycle disorders.
 Present in the blood of both male and female across ages.
 FSH functions in growth and maturity of ovarian follicles and
estrogen secretion; also aids in spermatogenesis (male).
 LH helps Leydig cells to produce testosterone (male); necessary
for ovulation and the final follicular growth in females.

48. Gonadotropins: FSH and LH
 LH acts on thecal cells to cause the synthesis of androgens,
estrogens (estradiol and estrone), and progesterone.
 Elevation of FSH is a clue in the diagnosis of premature
menopause.
 Increase in FSH and LH after menopause is due to estrogen
 Measure ovarian reserve: FSH and anti-müllerian hormone.
 Method: Immunoassay

49. Reference Limits of Gonadotropins
Male Female
Follicle-
Stimulatin
g
Hormone
<12 months: ≤ 3.3 IU/L
≥12 months to ≤5 years: ≤ 1.9 IU/L
≥5 years to ≤10 years: ≤ 2.3 IU/L
≥10 years to ≤15 years: 0.6-6.9 IU/L
≥15 years to ≤18 years: 0.7-9.6 IU/L
>18 years: 1.2-15.8 IU/L
<12 months: 1.2-12.5 IU/L
≥12 months to ≤10 years: 0.5-6.0 IU/L
≥10 years to ≤15 years: 0.9-8.9 IU/L
≥15 years to ≤18 years: 0.7-9.6 IU/L
Premenopausal:
Follicular: 2.9-14.6 IU/L
Midcycle: 4.7-23.2 IU/L
Luteal: 1.4-8.9 IU/L
Postmenopausal: 16.0-157.0 IU/L
Luteinizing
Hormone
6-30 mU/mL
Premenopausal: >35 mU/mL
Postmenopausal: <30 mU/mL

50.  Hypogonadotropic hypogonadism (2° hypogonadism):
 Low FSH and LH
 Decrease in testicular production and synthesis of testosterone:
 Deficiency of FSH and LH
 Inadequate spermatogenesis:
 Deficiency of FSH and LH
 Polycystic ovarian disease (PCOS):
 Normal FSH and High LH (sometimes FSH is low)

51.  Male testosterone secretion rate and concentration drop beyond
50 years old while female pituitary gonadotropins, particularly
FSH, increase.
 Hypogonadotropic hypogonadism is a common cause of secondary
amenorrhea.

52. Gonadotropin-Releasing Hormone
(GnRH) Stimulation Test
 Gold standard test in identifying central precocious puberty (CPP)
and premature activation of the activation of the hypothalamic-
pituitary-gonadal axis (HGPA) in cases with clinical signs and
symptoms of early puberty.
 Purpose: To determine the cause of the onset of pubertal signs
before the age of 8 years in girls.
 Sample requirement: Multiple blood samples at different time
points to measure gonadotropin level.

53.  Standard dose: 100 µg GnRH IV bolus
 Procedure: An IV cannula was inserted and blood samples are
obtained immediately before the injection and at 15, 30, 45, 60, 90
and 120 minutes after the injection.
 Duration of the test: 90 to 120 minutes (reaching up to 24 hours)
 Marker for CPP, CDCG, and HPGA: FSH, LH, Estrogen, and
Testosterone

54.  Markers for HH: GnRH, FSH, and LH
 In CPP, added tests: LH, FSH, and estradiol (measured together with
GnRH)
 Result: A stimulated LH value ≥5 IU/L was considered diagnostic for
CPP in patients with pubertal signs.
 Stimulated LH value <5 IU/L: Classified as having puberty thelarche
(PT)

55. 1. Establish the diagnosis of CPP
2. Distinguish constitutionl delay of growth and puberty (CDGP)
from hypogonadotropic hypogonadism (HH)
3. Evaluate hypogonadotrophic hypogonadism in infancy
4. Determine accelerated pubertal progression
Indications for GnRH Stimulation Test

56.  It is also known as thyrotropin.
 It is the main stimulus for the uptake of iodide by the thyroid gland.
 It acts to increase the number and size of follicular cells.
 It stimulates thyroid hormone synthesis.
 It is composed of 2 mono-covalently linked to a and B subunits has the
same amino acid sequences of LH, FSH, and HCG, while the B-subunit
directs the receptors for binding to express its hormonal activities
 Blood levels may contribute in the evaluation of infertility.
 Reference range: 0.5- 5 µU/mL (0.5- 5 µU/L)
Thyroid-Stimulating Hormone (TSH)

57. Thyroid-Stimulating Hormone Assay
TSH Assay Detection Limit Clinical Significance Remarks
First Generation
(RIA)
1.0 mIU/L
Diagnosis of primary
hypothyroidism
Requires TRH stimulation test to
detect hyperthyroidism
Second Generation
(Immunometric)
0.1 mIU/L Diagnosis hyperthyroidism
Without TRH stimulation test to
identify hyperthyroidism
Third Generation
(ICMA)
0.01 mIU/L
Most useful test for the
assessment of thyroid function
Differentiates
hyperthyroidism from
euthyroidism
Determines abnormality in
thyroid hormone synthesis
Most commonly used method
Preferred method for monitoring
and adjusting THRT
Detects subclinical thyroid
disease
Few false negative result
compared to second generation.
Fourth Generation
(LiCA Smart)
0.0004 mIU/L For research purpose
Not used in disease diagnosis
Detects TSH levels <0.01 mIU/L

58. ADRENOCORTICOTROPI
C HORMONE
(ACTH)

59. Adrenocorticotropic Hormone
(ACTH)
 It is a single-chain peptide without disulfide bonds.
 It is produced in response to low serum cortisol - regulator of adrenal
androgen synthesis.
 Deficiency in ACTH will lead to atrophy of the zona fasciculata and
zona reticularis (layers of the adrenal cortex)
 Highest level is between 6:00 AM to 8:00 AM, while the lowest level is
between 6:00 PM to 11:00 PM
 Sample requirement : Blood sample is best collected between 8:00AM -
10:00 AM

60. Adrenocorticotropic Hormone
(ACTH)
 Blood collection tube: Sample should not be allowed to have contact
with glass because ACTH adhere to glass surface resulting to decreased
levels, hence plastic tubes are utilized.
 Sample precaution: Blood should be collected into pre-chilled
polystyrene (plastic) EDTA tubes to prevent degradation of ACTH.
 Method: Two-site Immunoradiometric or Immunochemiluminometric
 Increased: Cushing's disease, Addison's disease, ectopic tumors, and
after protein-rich meals
 Reference range: 9-52 pg/mL (2-12 pmol/L) between 7 AM to 10 AM
 ACTH is reported to be stable in EDTA plasma at 4°C for only 18hours
compared with 19 other hormones that are stable for >120 hours.

61. PROLACTIN (PRL)

62. Prolactin (PRL)
 It is pituitary lactogenic hormone, a stress hormone, and a direct
effector hormone.
 It is secreted in a circadian rhythm with secreted pulsatile feedback.
 Its action is controlled by the inhibitory action of dopamine produced by
the hypothalamus.
 It functions in the initiation and maintenance of lactation.
 Together with estrogen and progesterone, it promotes breast tissue
development.
 It is clinically significant when the serum concentration is elevated.

63. Prolactin (PRL)
 It is a supplemental test in erectile dysfunction.
 It is influenced by hook effect (prozone effect).
 Unique characteristic among the anterior pituitary hormones: Tonic
inhibition
 Major circulating form of PRL: Non-glycosylated monomer
 Major inhibitor: Dopamine (secreted by the hypothalamus)
 Method: Immunoassay
 Increased: Amenorrhea, galactorrhea, infertility, acromegaly, renal
failure, polycystic ovary syndrome, cirrhosis, and primary and secondary
hypothyroidism

64. Prolactin (PRL)
 Very high PRL (>200 ng/mL): Pituitary adenoma (prolactinoma can
result in anovulation)
 Consequence of prolactin excess: Hypogonadism
 High PRL: Low FSH, LH, and testosterone; low sperm count
 Pituitary necrosis or infarction: PRL deficiency
 Reference range: Male = 1-20 ng/mL (1-20 µg/L)
Female = 1-25 ng/mL (1-25 µg/L)
 Prolactin serum level >250 µg/L: Pituitary tumor (prolactinoma can
result in anovulation

65.  Highest serum level (during sleep):
 4:00 am and 8:00 am; 8:00 pm and 10:00 pm
 Physiologic stimuli (increased):
 Exercise, sleep, stress, pospandrial pain, coitus, pregnancy, nipple stimulation or
nursing.
 Pharmacologic (increased):
 Intake of verapamil, phenothiazines, olanzapine, Prozac, cimetidine, and opiate

66.  Sample Collection:
 Blood should be collected 3 to 4 hours after the individual has awakened.
 Sample requirement:
 Fasting serum; ideally three (3) samples should be obtained at 20- to 30-minute
intervals because of physiologic stimuli
 Procedure for the three samples:
 It can be measured separately and their results averaged, or an equal aliquot
from each sample can be pooled into one final sample that is the analyzed.

67. POSTERIOR PITUITARY
(Neurohypophysis)
 This portion of the pituitary is capable of releasing hormones, but not
capable of producing.
 The hormones released by neurohypophysis are synthesized in the
magnicellular neurons of the supraoptic (ADH) and paraventricular
(oxytocin) of the hypothalamus, and stored in the nerve terminals that
end in the posterior pituitary gland.
 The release of the hormones occurs in response to serum osmolality or by
suckling.
 Hormones produced by the neurohypohysis are controlled by the central
nervous system (CNS).

68. OXYTOCIN

69. Oxytocin
 a nonapeptide and very similar in composition to ADH.
 secreted in association with a carrier protein.
 It stimulates contraction of the gravid uterus at term - "Fergusson
reflex.“
 released in response to neural stimulation of receptors in the birth
canal and uterus, and of touch receptors in the breast.
 It plays a role in hemostasis at the placental site following delivery.

70. Oxytocin
 It stimulates muscle contraction during delivery and lactation - with
bursts of oxytocin secretion occurring with anticipation of nursing or on
hearing a baby cry.
 Synthetic preparations: To increase weak uterine contractions during
parturition and to aid in lactation
 Pathologic conditions associated with oxytocin excess of deficiency are
rare and are limited to case reports. Its function in males remains
unknown

71. ARGININE
VASOPRESSIN

72. Arginine Vasopressin (AVP)
 It is formerly known as the anti-diuretic hormone (ADH).
 It is a nonapeptide that acts on the distal convoluted and collecting
tubules of the kidneys.
 It decreases the production of urine by promoting reabsorption of water
by the renal tubules thereby maintains water homeostasis.
 It regulates the total concentration of blood through water balance
(osmotic homeostasis).
 It increase blood pressure - decrease in blood volume or blood pressure
will likewise stimulate AVP release.

73. Arginine Vasopressin (AVP)
 It makes the renal collecting tubule permeable to water.
 It is a potent pressor agent and affects blood clotting by promoting
factor VII release from hepatocytes and factor VIII (von Willebrand
factor) release from the endothelium.
 Major function: Maintains osmotic homeostasis by regulating water
balance
 Sample: Serum or EDTA plasma
 Method: Immunoassay
 Reference range: 0.5-2 pg/µL

74.  Principal regulator of AVP secretion: Increased plasma osmolality
 Physiologic stimuli to AVP secretion: Nausea, cytokine, hypercarbia,
pregnancy, hypoglycemia, and nicotine.
 Physiologic stimuli to AVP release: Dehydration (emesis), physical and
emotional stress due to major surgery
 Suppress AVP release: Low plasma osmolality
 Inhibitors of AVP release: Ethanol, cortisol, lithium, and demeclocycline
 Defect in AVP regulation: Malignancies, pulmonary disease, CNS
disorders, and fungal infection.

75.  Secretion of AVP is directly related to the concentration of the plasma
osmolality.
 AVP secretion is maximally stimulated at a serum osmolality >295
mOsm/kg and suppressed when the osmolality is <284 mOsm/kg.
 A rise in plasma osmolality shrinks the hypothalamic osmoreceptor cells
stimulating the thirst center in the cerebral cortex, thereby promoting AVP
synthesis in the supraoptic and paraventricular nuclei.
 Conversely, a decline in effective osmolality causes swelling of the
osmoreceptor cells, resulting in inhibition of AVP production.

76.  Types of AVP receptors:
 V1 receptors = responsible for the increase in vasomotor tone with metabolic
effects
 V2 receptors = associated with antidiuresis
 V3 receptors = stimulates ACTH secretion
 Antidiuretic effect of ADH:
 Facilitated by the protein aquaporin-2 on the collecting duct membrane to
make the tubule permeable to water.

78. Diabetes Insipidus
 It is characterized by the deficiency of AVP which results in severe
polyuria (≥2.5 liters of urine/day).
 Hallmark of DI: Hypotonic urine
 Serum osmolality: Increased (>295 mOsm/kg)
 Urine osmolality: Decreased (<300 mOsm/kg)
 Serum Sodium: Increased (<145 mmol/L)
 Clinical picture: Normoglycemia, polyuria with low specific gravity,
polydipsia (secondary polydipsia), and polyphagia (occasional).

79.  defined as excretion of a urinary volume
 >150 mL/kg/24 hours at birth
 >100-110 mL/kg/24 hours up to the age of 2 years
 >50 mL/kg/24 hours in older children and adults.
 a urine sample with an osmolality of <300 mOsm/kg.

80.  True Diabetes Insipidus
 Hypothalamic/Neurogenic/Cranial/Central DI
 It is characterized by either a complete absence of or low plasma
AVP receptors.
 It results from damage to the hypothalamus or even the
neurohypophysis which is responsible for the release of AVP.
 It may also be caused by genetic abnormalities or mutations
affecting the hypothalamus or pituitary gland, and medications.
 Other causes: Head trauma, infectious diseases, anemia, alcoholism,
and drugs.

81.  Nephrogenic Diabetes Insipidus
 It is seen as having normal plasma or elevated AVP but abnormally
functioning AVP receptors (renal resistance to AVP action).
 It is due to kidney failure (due to renal disease) to respond to
normal or elevated AVP plasma concentration.
 Nephrogenic DI is either congenital (X-linked receptor defect) or
acquired (medications).
 It may also be caused by using prohibited drugs such as
propoxyphene (darvon).
 Other causes: Electrolyte imbalance, multiple myeloma, and
sarcoidosis.

82.  Primary Polydipsia
 Psychogenic Polydipsia/Dipsogenic DI
 It is also known as the compulsive water drinking disorder without a
stimulus.
 It may be due to a faulty thirst hypothalamic mechanism

83.  Primary Polydipsia
 The AVP secretion is normal, however, excess water intake without an
underlying stimulus causes the loss of the concentrating ability of the
kidneys with increased urine volume.
 Although primary polydipsia is not a true DI state, long-standing
primary polydipsia can give rise to a DI-like picture on laboratory
evaluation.
 Serum osmolality and Sodium: Normal or low level

84.  Gestational Diabetes Insipidus
 It develops due to the excessive activity of the placental cysteine
aminopeptidase (PCAP) or placental vasopressinase.
 It results from the degradation of the AVP by PCAP during pregnancy.
 It is usually observed in the last trimester of pregnancy and remitting
spontaneously 4 to 6 weeks post-partum.

85.  Gestational Diabetes Insipidus
 Other factors may also contribute to gestational DI such as the
increase in the secretion of other hormones during pregnancy that are
against the action of PCAP.
 AVP secretion is normal but there is overactivity of the PCAP leading
to catalysis of the hormone.
 PCAP is expressed by placental trophoblasts.

86.  Water Deprivation Test/Dehydration Test
 Gold standard
 It measures the serum and urine osmolality.
 Patient Preparation: At least 8 hours no fluid intake or until 5% of the
body mas has been lost; avoid smoking and caffeine intake that might
affect AVP release or urine output.
 Baseline test: Serum and urine osmolality, serum Sodium (include
serum AVP or copeptin together with the WDT, if available)

87.  Water Deprivation Test/Dehydration Test
 Procedure: Patient weight, pulse rate, BP should be taken hourly;
serum osmolality is measured every 4 hours and urine volume and
osmolality every 2 hours; test is conducted usually for 8 hours.
 Option: WDT may also be performed in the morning, starting 8 am.
 Precaution: When the serum osmolality increases to >305 mOsm/kg, it
is highly suggestive of DI, and the WDT should be discontinued; if the
body is 3% or less, the WDT may be stopped.

88.  Sign of DI: >295 mOsm/kg
 Highly suggestive of DI: Serum osmolality >305 mOsm/kg
 Excludes DI: Urine osmolality 800-1200 mOsm/kg
 After 8 to 12 hours without fluid intake, urine osmolality does not
rise above 300 mOsm/kg, it is diabetes insipidus.
 Plasma osmolality of about 285 mOsm/kg usually act as a trigger
for thirst.

89.  AVP and Copeptin: Differentiates neurogenic DI and primary
polydipsia from nephrogenic DI
 Desmopressin: Differentiates neurogenic from nephrogenic DI
 3% HSI with Copeptin: Differentiates neurogenic DI from primary
polydipsia.
*HSI – hypertonic saline infusion

90. Types of DI Water Deprivation Test
Plasma
AVP
Plasma
Copeptin
HIS with
Copeptin
Standard Test
(Urine Osm)
With
Demospressin
Neurogenic DI <300 mOsm/kg >800 mOsm/kg Low Low ≤4.9 pmol/L
Nephrogenic DI <300 mOsm/kg <300 mOsm/kg High High
Primary
Polydipsia
300-800 mOsm/kg Low Low
Gestational DI
WDT is normally not recommended during pregnancy because it may lead to
significant dehydration.
Desmopressin drug (for treatment) may be prescribed with a caution.
Pituitary MRI is requested to exclude lesions in the hypothalamic-pituitary
region.
Baseline test reveals: Low UOsm with upper limit serum osmolality and
Sodium.

91.  It is a 39-amino-acid C-terminal segment of pre-pro-arginine vaspressin.
 It is secreted in response to the same stimuli as AVP and in equimolar
amounts to AVP.
 Its high ex-vivo stability and ease of measurement make it an excellent
surrogate for AVP.
 Clinical significance: Marker for Diabetes Insipidus
 Increased: Acute illness, Myocardial infarction, and Stroke

92.  Copeptin with arginine infusion stimulation has been shown to
differentiate between DI and PP (aside from copeptin and HSI).
 Diagnostic of Nephrogenic DI: Baseline copeptin level of >21.4 pmol/L
(without pre-thirsting).
 Reference range: 1.0-13.8 pmol/L (McPherson and Pincus, 2022)
4.0-4.4 pmol/L (Balanescu et al., 2011)

93. Desmopressin test is performed together
with the WDT after the 8-hour
dehydration or NPO.
2 µg desmopressin is administered IV or
IM then urine and serum/plasma
samples are obtained hourly for 1 to 2
hours after injection.

94.  It is seen with continuous production of ADH in the absence of stimuli.
 Increased ADH or copeptin concentrations are often associated with
SIADH.
 Causes: CNS disease, cancer, tuberculosis, pneumonia, medications, and
nicotine.
 Diagnostic feature: Euvolemic hypoosmolar hyponatremia associated
with hyperosmolar urine.
 Urine volume: Decreased
 Serum Sodium: Decreased (<135 mmol/L)
Syndrome of Inappropriate ADH
Secretion

95.  Urine Sodium: Normal or Increased (>20 mmol/L)
 Serum osmolality: Decreased (<275 mOsm/kg)
 Urine osmolality: Normal or Increased (>800 mOsm/kg)
 Diagnostic test: Water Loading Test (WLT)
 Confirm SIADH based on WLT:
 Failure to excrete ≥80% of the administered water load within 4 hours and to
suppress the UOsm to <100 mOsm/kg.
Syndrome of Inappropriate ADH
Secretion