The Hypothalamic Pituitary Axis Growth Hormone And Pituitary Disorders

Question 1

Understand the relationship between the hypothalamus and the anterior pituitary gland

Answer 1

The hypothalamus and pituitary gland form a complex functional unit that serves as a link between the endocrine and nervous systems.
Anterior pituitary arises from evagination of oral ectoderm (primitive gut tissue).
Hormones synthesised in the hypothalamus are transported down axons and stored in the median eminence before release into hypophyseal portal system. These stimulate target endocrine cells in the anterior pituitary gland. The endocrine cells secrete a variety of hormones into the bloodstream to act on a distant target. The anterior pituitary hormones also affect neighbouring cells

Question 2

Understand the relationship between the hypothalamus and the posterior pituitary

Answer 2

The posterior pituitary gland is physically connected to the hypothalamus since the hypothalamus drops down through the infundibulum to form the posterior pituitary.
Posterior pituitary originates form neuroectoderm (primitive brain tissue).
Oxytocin and antidepressants hormone produced by neurosecretory cells in the supraoptic and paraventricular nuclei of the hypothalamus. These are transported down the axons to the posterior pituitary where it is stored and released into the general circulation to act on distant targets.

Question 3

Name the hormones produced by the hypothalamus and describe their roles

Answer 3

Produced in hypothalamus for release from posterior pituitary:
- Oxytocin (milk let down and uterus contractions)
- Antidiuretic hormone (regulation of body water volume)
Tropic hormones of the hypothalamus are produced in hypothalamus. Have direct effects on release of anterior pituitary hormones
- TRH (Thyrotropin releasing hormone)
- PIH (Prolactin release inhibiting hormone (dopamine
- CRH (Corticotropin releasing hormone)
- GnRH (Gonadotropin releasing hormone0
- GHRH (Growth hormone releasing hormone)
GHIH (Growth hormone inhibiting hormone

Question 4

Name the hormones produced by the anterior pituitary gland and describe their roles

Answer 4

TSH (thyroid stimulating hormone) - Secretion of thyroid hormone from thyroid gland
ACTH (Adrenocorticotropic hormone) - Secretion of hormones from adrenal cortex
LH (luteinising hormone) - Ovulation and secretion of sex hormones
FSH (Follicle stimulating hormone) - Development of eggs and sperm
PRL (Prolactin) - Mammary gland development and milk secretion
GH (Growth hormone) - Growth and energy metabolism. Stimulates IGFs

Question 5

describe the factors controlling GH secretion (long and short loop negative feedback)

Answer 5

Growth is influenced by many factors. Growth hormone is the most important endocrine regulator of postnatal growth.
The secretion of GH is influenced by many factors. The principal point of control is via the hypothalamic production of GHRH (increases GH secretion) and somatostatin (decreases GH secretion). Growth promoting effects mainly exerted (IGF) insulin-like growth factors (Somatomedins). In response to GH cells of the liver and Skeletal muscle produce and secrete IGF.
Regulation of GH secretion occurs via long loop and short loop negative feedback mechanisms.
Long loop negative feedback is mediated by IGFs which inhibit release of GHRH from hypothalamus, stimulate release of Somatostatin from hypothalamus, inhibit action of GHRH in anterior pituitary.
Short loop negative negative is mediated by GH itself via the stimulation of somatostatin release from the hypothalamus.

Question 6

Describe how GH exerts its effects on cells both directly and indirectly through Insulin like Growth factors.

Answer 6

GH acts on cells both directly through its own receptors and indelicately through the induced production of IGF-1.Only cells expressing GH receptors respond to GH. GH receptor part of the cytokine receptor. The are coupled to an enzyme called Janus kinase.

Question 7

What can deficiency and excess of growth hormone lead to

Answer 7

Growth hormone deficiency in childhood results in pituitary dwarfism. It is a proportionate type of dwarfism that can be complete or partial. Height is below 3rd percentile. Growth rate is slower then expected and there is delayed/no sexual development during teen years. Both respond to GH therapy.
Growth hormone excess results in gigantism in childhood. In adulthood leads to acromegaly.

Question 8

What are insulin like growth factors (IGFs)

Answer 8

There are 2 IGFs in mammals (IGF1 and IGF2)
- IGF2 is mainly involved in foetal growth
- IGF1 is a major growth factor in adults.
Binding proteins modulate their availability.
Actions of IGFs can be paracrine and autocrine as well as endocrine
IGFs act through IGF receptors to modulate: Cell growth (hypertrophy), Cell number (Hyperplasia), increase in rate of protein synthesis.

Question 9

Explain pituitary disorders

Answer 9

Disorders of the pituitary gland are quite rare. Can be caused by over or under secretion of pituitary hormones. Most common cause of pituitary malfunction is a tumour.
Most pituitary hormones are non functioning so that the tumour cell itself doesn’t produce any hormone.

Question 10

What is the investigation and diagnosis when it comes to pituitary disorders

Answer 10

Investigation of a suspected pituitary tumour involves:
- delineation of the anatomy, size and topographical location of the pituitary or parapituitRy mass (seen by MRI)
- assessment of any visual field defects
- assessment of endocrine function by measuring hormone levels in blood to determine where there is an abnormal hormonal excess or deficiency

Question 11

Explain hypopituitarism

Answer 11

Insufficient pituitary hormone production (hypopituitarism), is most commonly a result of a pituitary adenoma. There is typically a progressive loss of anterior pituitary function with GH and LH/FSH

Question 12

Explain hyperpituitarism

Answer 12

There are 3 main conditions caused by excess pituitary hormone production from a hypersecreting pituitary adenoma:
- Prolactin excess
- Growth hormone excess
- ACTH excess

Question 13

Describe the clinical feature of disease states resulting from malfunction of the hypothalamic pituitary axis

Question 14

Outline the endocrine test use to asses pituitary function

Answer 14

Blood tests:
Thyroid - TSH
gonadal - Testosterone and Oestradiol
Prolactin - Serum prolactin
HPA - Cortisol
GH - GH and IGF-1
Radiological assessment:
MRI

Question 15

Outline management an treatment options for pituitary disorders

Answer 15

Acromegaly treatment - Surgical removal and treatment and somatostatin analogues
Prolactinoma treatment - Dopamine agonists, bromocriptine, cabergoline