Lecture 5: Prolactin and GH

Question 1

Regulation of MAIN pit hormones
What does the hypothalamis release and then pit and then target organ

Answer 1

CRH (Corticotrophin releasing hormone) to Pit releasing ACTH to adrenal gland = Cortisol

TRH (Thyrotrophin releasing hormone) to pit (TSH) to thyroid = T3 and T4

GHRH (GH releasing hormone) to pit (GH) to liver (IGF-1)

GnRH (Gonadotrophin (LH, FSH) releasing hormone to pit (LH, FSH) to ovaries and testes (progestrone or testerone inhibin)

Dopamine to pit (PRL) to mammary glands (inhibit lacation)

Somatosatin - inhibit TSH
Vasopressin - inhibit ACTH

Question 2

Common cause of pituitary disorders

Answer 2

Adenoma or carcinoma which may overproduce one or more pituitary hormones, or the tumour may press on the normal pituitary cells, causing underproduction of one or more pituitary hormones.

Question 3

Prolactin-secreting adenomas are divided into 2 groups:

Answer 3

Microadenomas (more common in premenopausal women), which are smaller than 10 mm 2)

Macroadenomas (more common in men and postmenopausal women), which are 10 mm or larger.

Question 4

Examples of disorders that result from underproduction of pituitary hormones include

Answer 4

Central diabetes insipidus:Vasopressin

Hypopituitarism: Multiple hormones

Question 5

Prolactin purpose and secretion is controlled by… and feedback system used…

Answer 5

An anterior pituitary tropic hormone which has its principle physiological action in initiation and maintenance of lactation.

Prolactin secretion is controlled primarily by inhibition from the hypothalamus and it is not subject to negative feedback directly or indirectly

Question 6

Prolactin Regulation:
What inhibits prolactin and process of this
What stimulates prolactin

Answer 6

Dopamineserves as the major prolactin-inhibiting factor or brake on prolactin secretion.

Dopamine is secreted into portal blood by hypothalamic neurons, binds to receptors on lactotrophs, and inhibits both the synthesis and secretion of prolactin.

Prolactin secretion is positively regulated bythyroid-releasing hormone,gonadotropin-releasing hormoneand vasoactive intestinal polypeptide.

Question 7

Excess prolactin effects:

Answer 7

1.Low sex hormones
2.infertility
3.osteoporosis (low estrogen no longer can caused increased osteoclast death, thus more osetoclasts removing bone)

Question 8

Hyperprolactinaemia effects in Male

Answer 8

Highbloodprolactinconcentration interferes with the function of the testicles, the production of testosterone and sperm production.

Question 9

Hyperprolactinaemia in Male pathophyisology

Answer 9

Prolactininhibits pulsatile GnRH secretion and consequently inhibits the pulsatile release of FSH, LH and testosterone.

This results in marked effects on spermatogenesis ranging from alteration in sperm quality to complete spermatogenic arrest.
As a result, the patient may present with secondaryhypogonadismor male infertility.

Question 10

High prolactin and gynecomastia in males

Answer 10

Imbalance between estrogen action relative to androgen action at the breast tissue level appears to be the main etiology of gynecomastia.

The balance between free testosterone and estrogen is also affected by serum levels of sex hormone—binding globulin, which is the proposed mechanism of gynecomastia

Defined as benign proliferation of male breast glandular tissue, due to increased estrogen activity, decreased testosterone activity, or the use of numerous medications.

Question 11

Hyperprolactineamia in Females and effects

Answer 11

Raised levels of prolactin can result in suppression of luteinising hormone secretion and inhibition of ovulation and thus be associated with infertility.

This usually manifests with oligomenorrhoea or amenorrhoea, and diagnosis in such cases is straightforward.

Another common symptom is “galactorrhoea”, which is the occurrence of a milky discharge from the breast in a woman who has not recently been pregnant.
Due to persistent high prolactin levels stimulating the mammary gland for milk production.

Question 12

What is Macroprolactinoma and why does it not form symptoms

Answer 12

increase in serum prolactin without symptoms

Serum prolactin molecules can polymerize and subsequently bind to IgG.

This form of prolactin is unable to bind to prolactin receptors and exhibits no systemic response.

Question 13

Complication of Macroprolactinomas

Answer 13

Macroprolactinomas may press against nearby parts of the pituitary gland and the brain causing vision problems, when the tumour presses on the optic nerves or optic chiasm, the part of the brain where the two optic nerves cross over each other
headaches
low levels of other pituitary hormones, such asthyroid hormonesandcortisol

Question 14

Diagnosis of hyperprolactenaemia flowchart

Answer 14

Lecture Slide

Question 15

Growth hormone (GH) function and information

Answer 15

Promotes growth: skeleton, muscles, viscera
Effects mediated by somatomedins
Released at night during growth
Variety of metabolic effects
Anabolic, positive nitrogen balance
Anti-insulin

Question 16

GH stimulated and inhibited by..

Answer 16

Stimulated by GHRH, stress, exercise, Low glucosem grehlin
Inhibited by somatostatin

Question 17

Regulation of Growth Hormone

Answer 17

Somatostatin(SS) inhibits growth hormone release in response to GHRH and to other stimulatory factors such as low blood glucose concentration.

Ghrelinis a peptide hormone secreted from the stomach.
Ghrelinbinds to receptors on somatotrophs and stimulates secretion of growth hormone.

Question 18

3 Metabolic actions of Growth Hormone

Answer 18

Increase rate of protein synthesis in most of cells

Increase mobilization of fatty acids for energy production

Decrease rate of glucose utilization throughout body

Question 19

GH Effect on Protein Metabolism

Answer 19

1.Increase rate A.A. uptake by cells

2.Increase protein synthesis by Ribosome

3.Increase RNA synthesis

4.Decrease catabolism of protein and Amino- acids

Question 20

GH effect on fat metabolism

Answer 20

1. Enhancement of fat utilization for energy

2.Increase circulating Free fatty acids

3.FFA being source of energy during hypoglycaemia

4.Ketogenic Effect: due to production of large quantities of Acetoacetic acid

Question 21

GH Effect on Carbohydrate Metabolism

Answer 21

1.Decrease in carbohydrate utilization

2.Decrease in glucose uptake by tissues such as skeletal muscles and fat

3.Increase glucose production by liver: Gluconeogenesis

4.Inhibition of Glycolysis

5.Increase in glycogen stores

Question 22

What is the mediator of GH?
and the role/function of it?
How is it stimulated?

Answer 22

IGF-1 (insulin like growth factor 1)

necessary for normal human development.

IGF-1 is synthesised mainly by the liver but also locally in many tissues.

Activation of the growth hormone receptor stimulates the synthesis and secretion of IGF-1

IGF-1 circulates in the blood at high concentrations and acts as a mitogen, stimulating DNA, RNA and protein synthesis.

Question 23

What does excess GH secretion cause and description

*when do they occur?

Answer 23

1. Giantismis the result of excessive growth hormone secretion that begins in young children or adolescents then shows in adults. It is a very rare disorder, usually resulting from a tumour of somatotrophs.

2.Acromegalyresults from excessive secretion of growth hormone in adults, usually the result of benign pituitary tumours. The onset of this disorder is typically insidious, occurring over several years.

Question 24

Acromegaly pathophysiology
What is Acromegaly?

Answer 24

Is a disorder of disproportionate skeletal, tissue, and organ growth.

Characterized by: hypersecretion of GH, which is caused by the existence of a secreting pituitary tumour

In rare instances, elevated GH levels are caused by extra pituitary disorders.

Hypersecretion of GH in turn causes subsequent hepatic stimulation of IGF-1 leading to enlarge physical features.

Peripheral neuropathies occur commonly because of compression of nerves by adjacent fibrous tissue

Question 25

Gigantism pathophysiology

Answer 25

Like Acromegaly however begins in childhood BUT OCCURS in adulthood.

caused by an adenoma, a tumour of the pituitary gland. Gigantism occurs in patients who had excessive growth hormone in childhood.

Question 26

GH excess and Glucose Metabolism

Answer 26

GH excess affects insulin sensitivity and gluconeogenesis and can alter pancreatic β-cell function, leading to a derangement of glucose metabolism in a considerable percentage of acromegaly patients.

Induces hyperglycaemia by increasing endogenous glucose production and decreasing peripheral glucose disposal in muscle.

Trigger for GH release is low glucose

Question 27

Diagnosis of excess GH

Answer 27

1.Basal plasma GH level: High

2.Plasma Prolactin level: High

3.Glucose tolerance suppression test: 75 grams of glucose to be given orally, GH and blood glucose level to be measured 2 hourly

Normal: Suppression of GH by hyperglycaemia
Acromegaly or gigantism: No suppression

4.Visual field defects: Due to pressure by pituitary adenoma
5.CT scan skull

Question 28

Growth Hormone deficiency (GHD) causes and condition it causes

Answer 28

1. From birth (congenital), resulting from genetic mutations or from structural defects in the brain.

2.Acquired later in life as a result of trauma, infection, radiation therapy, or tumour growth within the brain.

3.No known or diagnosable cause (idiopathic).

Causes dwarfism

Question 29

Dwarfism characteristic symptoms and signs

Answer 29

Disease of cartilage and endochondral bone growth

Cartilage-hair hypoplasiais a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities; fine, sparse hair (hypotrichosis), immune deficiency

growth retardation, short stature, delay of lengthening of the bones of the extremities, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension,

Question 30

Dwarfism auto dominant or recessive

Answer 30

An autosomal dominant disorder

Question 31

GH deficiency and glucose

Answer 31

Fasting hypoglycaemia and marked insulin sensitivity have sometimes been observed in GHD children due to diminished hepatic output through decreased gluconeogenesis or abnormal glucose mobilisation

Question 32

Diagnosis of GH deficiency

Answer 32

1.Low IGF-1 can indicate GH deficiency

2. GH stimulation test
   Testis performed by administering the amino acid arginine in a vein to raiseGHlevels.
   Thetestmeasures the ability of the pituitary to secretegrowth hormonein response to the arginine.

Question 33

IGF- Z score normal range

Answer 33

-2 to +2

Question 34

Flowchart for likely, unlikely and idiopathic GHD

Answer 34

Lecture Slide

Likely
Height: < or = -2SD
Growth Rate: < -1.5
IGF-1 Z score: < - 2

Unlikely
Height: Less than or = -2SD
Growth Rate: Less than or = to -1 SD or greater than -1.5
IGF-1 Z score: -1 to 2

Idiopathic
Height: Less than or = -2SD
Growth Rate: > -1
IGF-1 Z score: > -1

Question 35

What is Primary, secondary and severe primary IGF-1 in terms of IGF-1 and GH levels

Answer 35

Primary IGFDmay happen when IGF-1 levels are low, even though growth hormone levels are normal or even high
Secondary IGFDhappens in children whose IGF-1 levels are low; this may be due to their bodies’ inability to produce enough growth hormone, poor nutrition, thyroid problems or other factors
Severe primary IGFDis a type of primary IGFD in which IGF-1 levels are exceptionally low, despite sufficient or high growth hormone levels