Week 5 Flashcards
The Pituitary Gland
Small outgrowth of the forebrain
Size of half a pea
Two functional parts
Adenohypophysis (anterior pituitary)
Neurohypophysis (posterior pituitary)
Blood and nerve supply pituitary gland
Hypothalamus
• Hypothalamic neurons release hormones directly into capillary plexus
Anterior pituitary • Blood supply from median eminence of hypothalamus – portal system • Hormones from hypothalamus to pituitary • Sympathetic/parasympathetic nerves
Posterior pituitary
• Supraoptic and paraventricular nuclei
in hypothalamus
Hypothalamus releasing hormones
CRH: Corticotrophin releasing hormone (ACTH)
TRH: Thyrotropin releasing hormone
GHRH: GH releasing hormone
Somatostatin: GH inhibition
GnRH: Gonadotrophin (LH, FSH) releasing hormone
Dopamine: Prolactin inhibition
Vasopressin: ACTH release
Pituitary Stimulating Hormones
The anterior pituitary produces six major
hormones:
(1) prolactin (PRL)
(2) growth hormone (GH)
(3) adrenocorticotropic hormone (ACTH)
(4) luteinizing hormone (LH)
(5) follicle-stimulating hormone (FSH)
(6) thyroid-stimulating hormone (TSH)
Pituitary Disorder Introduction
Can malfunction in several ways, usually as a
result of developing a noncancerous tumour
(adenoma)
Prolactin-secreting adenomas are divided into 2 groups:
Microadenomas (more common in premenopausal women), which are smaller than 10 mm)
Macroadenomas (more common in men and postmenopausal women), which are 10 mm or larger.
Pituitary Malfunction
Disorders that result from overproduction of pituitary hormones include
Acromegaly or gigantism: Growth hormone
Cushing disease: Adrenocorticotropic hormone ( ACTH),
Galactorrhea (the secretion of breast milk
by men or by women when not pregnant): Prolactin
Erectile dysfunction: Prolactin
Infertility (particularly in women):
Prolactin
Disorders that result from underproduction of
pituitary hormones include
Central diabetes insipidus: Vasopressin
Hypopituitarism: Multiple hormones
Prolactin secretion
Prolactin secretion is controlled primarily by inhibition from the hypothalamus and it is not subject to negative feedback directly or indirectly by peripheral hormones.
Prolactin Regulation
Dopamine serves 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. In addition to tonic inhibition by dopamine, prolactin secretion is positively regulated by several hormones, including thyroid-releasing hormone, gonadotropin-releasing hormone and vasoactive intestinal polypeptide.
Complications of high Prolactin
Excess prolactin, or hyperprolactinemia, can lower levels of sex hormones in both women and men.
Related complications can include
infertility
bone loss (osteoporosis)
Hyperprolactinaemia in Male
High blood prolactin concentration interferes with the function of the testicles, the production of testosterone (the main male sex hormone), and sperm production
Hyperprolactinaemia in Male Pathophysiology
Prolactin inhibits 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
secondary hypogonadism or male
infertility.
Furthermore, prolactin may also impact male
fertility through a direct effect on
spermatogenesis.
Hyperprolactinaemia in Male
High prolactin and gynecomastia
Defined as benign proliferation of male breast glandular tissue, is usually caused by increased estrogen activity, decreased testosterone activity, or the use of numerous medications
Imbalance between estrogen action
relative to androgen action at the
breast tissue level appears to be the
main etiology of gynecomastia
Hyperprolactineamia in Females
(high prolactin)
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.
The discharge is the result of persistent high PRL levels
stimulating the mammary gland for milk production.
Hyperprolactineamia in Females, Macroprolactinoma
Is the apparent increase in serum prolactin without
symptoms
Serum prolactin molecules can polymerize and
subsequently bind to immunoglobulin G (IgG).
This form of prolactin is unable to bind to prolactin receptors
and exhibits no systemic response.
In the asymptomatic patient with hyperprolactinemia, this
condition should be considered.
Complication of Macroprolactinoma
Vision problems, caused 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 as thyroid
hormones and cortisol
Growth hormone (GH)
Promotes growth: skeleton, muscles, viscera
Effects mediated by somatomedins
Released at night during growth
Variety of metabolic effects
Anabolic, positive nitrogen balance
Anti-insulin
Regulation of Growth Hormone
Somatostatin (SS) is a peptide produced by
several tissues in the body, including the
hypothalamus.
Somatostatin inhibits growth hormone
release in response to GHRH and to other
stimulatory factors such as low blood glucose
concentration.
Ghrelin is a peptide hormone secreted from
the stomach.
Ghrelin binds to receptors on somatotrophs
and potently stimulates secretion of growth
hormone.
Metabolic actions of Growth Hormone
Increase rate of protein synthesis in most of cells Increase mobilization of fatty acids for energy production Decrease rate of glucose utilization throughout body
Mediator of Growth hormone IGF-1
One of several growth factors necessary for normal
human development.
IGF-1 is synthesized mainly by the liver but also locally in
many tissues.
Activation of the growth hormone receptor stimulates the
synthesis and secretion of insulin-like growth factor-1 (IGF-
1), a small peptide (about 7.5 kD) structurally related to
proinsulin.
IGF-1 circulates in the blood at high concentrations and acts as a mitogen, stimulating DNA, RNA and protein synthesis.
Clinical Syndrome of GH
Giantism is the result of excessive growth hormone secretion that begins in young children or adolescents. It is a very rare disorder, usually resulting from a tumour of somatotrophs. Acromegaly results 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. Growth hormone deficiency
Acromegaly pathophysiology
Is a disorder of disproportionate skeletal, tissue,
and organ growth.
Characterized by hypersecretion of growth
hormone (GH),which is caused by the
existence of a secreting pituitary tumour in
more than 95% of acromegaly cases.
In rare instances, elevated GH levels are
caused by extra pituitary disorders.
Hypersecretion of GH in turn causes
subsequent hepatic stimulation of insulin-like
growth factor-1 (IGF-1) leading to enlarge
physical features.
Peripheral neuropathies occur commonly
because of compression of nerves by
adjacent fibrous tissue and endoneural
fibrous proliferation.
Gigantism pathophysiology
Like Acromegaly however occurs
in adulthood
GH excess and Glucose Metabolism
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.
Diagnosis of excess GH
Functional tests for GH 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 1. Acromegaly or gigantism: No suppression 2. Visual field defects: Due to pressure by pituitary adenoma 3. CT scan skull
