The endocrine system describes the system which makes the chemical messengers named hormones.
Hypothalamus
The hypothalamus has releasing and inhibiting hormones. These regulate the production of hormones in the anterior pituitary.
gonadotrophin releasing hormone (GNRH)
corticotrophic releasing hormone/ corticoliberin (CRH)
Pituitary gland
Pituitary gland tumours
Pituitary gland tumours occur in 6 - 23% of subjects in unselected autopsy series.
CT or MRI studies demonstrate a lesion of 3mm or more in 20% of normal glands.
Pituitary gland tumours rarely metastasise but may be locally invasive. These include G protein adenomas, Ras and PKC mutations in the rare pituitary adenomas. Tumour suppressor gene inactivation may be responsible for some pituitary tumorigensis, with Menin gene mutations identified in pituitary tumours.
This can lead to headache from stretching of the dura mater, or with very large tumours, CSF obstruction and hydrocephalus. There might be visual field disturbances from optic nerve compression, classically a bitemporal hemianopia; third, fourth and sixth cranial nerve palsies.
Hypopituitarism arises from the destruction of the normal pituitary tissue by the tumour, or iatrogenically as consequences of its treatment.
Microadenomas
Microadenomas are less than 1cm in diameter.
Treatment
Pituitary microadenomas may not require specific therapy, as they are asymptomatic or causing minimal symptoms. For these patients, periodic neurologic, neuroendocrinologic and neuro-opthalmologic follow- up are appropritated.
Macroadenomas
Macroadenomas are greater than 1cm in diameter.
Pituitary adenomas are rate in children.
Treatment
Pituitary macro-adenomas include surgery, radiation therapy and medical therapy.
All pituitary tumours can be changed with trans-sphenoidal surgery or medical therapy. Radiation therapy can be delivered by conventional external beam techniques, stereotactic radio-surgery techniques or more recently by isotope labelled radio-pharmaceuticals.
Anterior pituitary gland
Growth hormone (GH)
Growth hormone producing adenoma makes up about 13% of pituitary gland tumours and results in hyper-secretion of growth hormone.
Gigantism
Growth hormone producing adenoma during childhood leads to gigantism:
gigantism, with excessive longitudinal growth and facial bone overgrowth
headache
visual disturbances
osteoporosis
hypercementosis
thickened cranium with exaggerated muscle and ridge attachments with an enalrged sella turcica
diabetes mellitus may accompany hyperpituitarism
Treatment
Octreotide is an analogue of somatostatin and has been associated with a decrease in growth hormone size and and levels
Acromegaly
Luteinizing hormone (LH)
Thyroid stimulating hormone (TSH)
Thyrotrope adenoma (1%)
The medical symptoms of thyrotrope adenomas include:
precocious puberty
thyrotoxicosis
Adrenocorticotropic hormone/ corticotropin (ACTH)
This is a polypeptide hormone which stimulates the production and secretion of corticosteroids and gonadocorticoids in the adrenal cortex.
Beta - endorphin
Prolactin (PRL)
Prolactinoma (27%)
The medical symptoms of prolactinomas include:
galactorrhea, menstrual irregularity or infertility in women
no significant physiological role in men
Treatment
Cabergoline, a dopamine agonist, inhibits the synthesis and release of prolactin, and reduces the level of serum prolactin
Follicular stimulating hormone (FSH)
Gonadotrope adenoma
(9%)
Posterior pituitary gland
Oxytocin
Antidiuretic hormone (ADH)
Antidiuretic hormone, otherwise known as vasopressin, controls water absorption by the kidney, via V2 receptors that leads to increased cAMP, which increases water channels (aquaporin) in apical membrane and the dilation of spaces between cells. The result is increased water flow back into the bloodstream and extracellular fluid.
Secondly, the V1 receptors leads to increased DAG / IP3 and rise in calcium inside vascular smooth muscle cells, causing increased peripheral resistance. At normal physiological concentrations this is buffered by effect of vasopressin to lower heart rate, so blood pressure is not affected.
Diabetes Insipidus
Diabetes insipidus refers to the frequent urination and tasteless urine. This is caused by the destruction of cell bodies in hypothalamus or mutation in vasopressin gene.
The medical symptoms include:
polyuria
polydipsia
If thirst mechanism is distrupted, this leads to circulatory collapse and fatal.
Treatment
Administer nasal vasopressin.
Pineal gland
Melatonin is secreted by the pineal gland which regulates the biological day/ night and seasonal cycles. When the pineal gland is sympathetically innervated, it is usuallt at night in the absence of light and caused by neurons originating in the suprachiasmatic nuclei of the anterior hippocampus, which receives information from the retina.
Melatonin can be measured in the blood and saliva. Its primary metaboliste, 6 - sulphatoxymelatonin, is excreted in the urine. Given its sensitivity to light, its levels are usually measured in dim conditions. The onset of melatonin lasts around the same time as the nightly increase in sleepiness and sleep propensity. The administration of melatonin increases sleepiness levels.
Circadian Disruption
Circadian disruption occurs due to disruption in night shift workers and trans-meridian travellers, and contributes signIficantly to jet lag.
This is also commonly found in people who have blindness, or patients with delayed or advanced sleep phases.
Treatment
Melatonin administration in conjunction with bright light exposure achieves maximum effect for circadian disruption disorders.
Adrenal glands
The adrenal glands are paired triangular glands embedded in fat located near the upper portion of each kidney.
Each gland is divided into an outer cortex and an inner medulla, developed from the embryonic mesoderm and neural crest respectively. Whilst the medulla may be removed, the cortex is essential to life. Blood supply is provided by the adrenal arteries.
Adrenal cortex
The adrenal cortex can be further divided into three zones. Each zone uses lipid droplets here to make steroids.
1) Zona glomerulosa
Constituting 15% if the cortical volume, these are in ovoid clusters. These produce mineralocorticoid hormones for sodium and potassium homeostasis and water balance. This is called aldosterone, conserving sodium ions and water in the body.
This is regulated by the renin - angiotensin system. When salt is low, the renal juxtaglomerular apparatus releases protease renin, converting circulating angiotensinogen made in the liver to angiotensin - I. Angiotensin - I is then converted into angiotensin II by the peptidase angiotensin converting enzyme (ACE). This activates aldosterone sythesis and release.
2) Zona fasiculata
Making up 80% of the bulk of the cells, these are arranged in long straight cords.
Glucocorticoids include cortisol (hydrocortisone), corticosterone and cortisone.
They increase glucose levels. In muscle, it causes protein catabolism (chiefly glutamine and alanine) to release amino acids into the blood stream by upregulating a protein called ubquitin which marks proteins for degradation in proteasomes. It also prevents re-uptake of glucose, thus reducing sensitivity of muscle to insulin. This effect is antagonised by insulin, insulin-growth-1 and testosterone. It causes the breakdown of lipid stores into adipose tissue to release free fatty acids and glycerol. They also increase gluoconeogenesis so more glucose is released from the liver into the bloodstream. It also suppresses glucose oxidation. Some amino acids are used to make enzymes in the pathway. Cortisol acts to redistribute fuel reserves from peripheral sites, especially from muscle and peripheral fat stores, by promoting hormone sensitive - lipase activity at these sites. They turn into very low density lipoproteins in the the liver, which are later incorporated as triacylglycerols in fat cells at central fat stores. Hence, cortisol also increases hepatic glycogen levels. Amino groups, which are released in hepatocytes, as toxic ammonium ions, turn into urea and are excreted by the kidneys.
They also depress immune and inflammatory responses. This works by binding to intracellular steroid receptors, forming GCS-receptor complexes binding to particular nucleotide sequences such as glucocorticoid response elements (GRE), which then subsequently initiates or represses the transcription of mRNA encoding particular proteins, such as those involved in anti-inflammation. The GCS receptor complex may also bind to transcription factors for pro-inflammatory cytokines, preventing mRNA of cytokines being produced.
Some mineralocorticoid activity causing sodium retention, potassium and calcium loss. However, this is regulated by a special enzyme in the kidney called 11 beta - hydroxy steroid dehydrogenase, which converts cortisol into the inactive cortisone.
They also increase vascular reactivity to agents like noradrenaline.
Under normal conditions, cortisol is involved in growth and development and diurnal variations in metabolism. Under stressful conditions, cortisol exerts regulatory control to prevent injury. When hypothalamic CRH (corticotrophic releasing hormone) is released, ACTH (adrenocorticotropic hormone) levels rise from the anterior pituitary , this causes the levels of cortisol to also rise. Binding of ACTH to the cell membrane activates adenylate cyclase and this increases second messenger cyclic AMP inside the cell, which in turn activates protein kinase A and this ultimately leads to the conversion of cholesterol (stored
in the cells in lipid droplets) to pregnenolone by P450 side chain cleavage enzyme that sits on the mitochondrial inner membrane. Pregnenolone is the precursor for all steroid hormones and in these cells is converted after several steps involving other P450 enzymes to cortisol. cortisol levels are too high, CRH (corticotrophic releasing hormone) exerts negative feedback on the adrenal glands to lower its levels. Cortisol levels tend to be the highest in the morning, and reach their lowest levels just before sleep onset.
Circadian Disruption
Circadian disruption occurs due to disruption in night shift workers and trans-meridian travellers, and contributes significantly to jet lag.
This is also commonly found in people who have blindness. Patients with delayed or advanced sleep phases tend to have elevated levels with cortisol which contribule to decreased sleep levels.
Treatment
Melatonin administration in conjunction with bright light exposure achieves maximum effect for circadian disruption disorders.
Side Effects from Corticosteroids
3) Zona reticularis: Making up 5% of the bulk volume, they assume a net like structure. These primarily secrete gonadocorticoids, or weak androgens like dehyroepiandrosterone and androstenedione. When hypothalamic CRH (corticotrophic releasing hormone) is released, ACTH (adrenocorticotropic hormone) levels rise from the anterior pituitary, this causes androgens to rise.
Adrenal insufficiency
Adrenal Insufficiency
Primary
where the two adrenal glands are damaged, destroyed or absent
destroyed or damaged due to bilateral haemorrhage or removal will result in abrupt onset of symptoms
onset may be slow and insidious due to necrosis or infiltration (malignancy, amyloidosis, sarcoidosis, infection )
taking synthetic inhibitors of cortisol such as ketoconazole and metyrapone
first presentation may be life threatening, precipitated by intercurrent infection.
Patients are hyperpigmented due to increased ACTH drive, and sodium deficiency with postural hypotension
Secondary
when pituitary ACTH is deficient or absent
as a result of tumour, other destructive lesions and radiotherapy to the hypothalamic-pituitary area
pale, because they have lost ACTH
symptoms of electrolyte disturbance-hypotension, nausea etc are less prominent
Generally only glucocorticoid replacement is required, at full replacement dose
Patients need written instructions and education on increasing glucocorticoid dosage in times of stress. Theyshould also have one dose of parenteral glucocorticoid for self administration if persistent vomiting occurs and medical help is not immediately available
Tertiary
when hypothalamic CRH is deficient or absent
In the latter two types of insufficiency mineralocorticoid lack is only partial because the major control of adrenal mineralocorticoid production is via the renin-angiotensin system. Adrenal insufficiency can further be defined by whether it is permanent (a destructive lesion) or temporary (exogenous steroid suppression) and by whether it is complete or partial. The latter is important if partial progresses to complete as replacement therapy may require adjustment.
Addison's Disease - Primary adrenal insufficiency
Congenital Adrenal Hyperplasia - Primary adrenal insufficiency
Adrenal crisis
Adrenal Hyperactivity
Cushing's disease / Hypercortisolemia - Secondary Adrenal Hyperfunction
Corticotrope adenoma makes up 10% of all pituitary gland tumours. It causes hypersecretion of ACTH. This then causes hyper-secretion of cortisol. This is responsible for a range medical conditions, such as:
skin hyperpigmentation due to ACTH elevation
moon face and obesity due to cortisol redistributing fat into the visceral region
striae
acne
muscle wasting (myopathy) due to high cortisol levels
reduced inspiratory muscle stength and reduced strength of hip flexor muscles. These are the fast twitch Type IIB fibres.
Dental implications
decreased collagen synthesis and depression of protein metabolism
extraction sockets or surgical wounded take longer to heal and potential for alveolar osteitis
susceptibility to infection (intraorally, usually candidiasis)
sometimes diabetes mellitus, which increase the risk of serious dental disease
Treatment
Ketoconazole, an anti-fungal agent which inhibits adrenal stereoidogenesis
Adrenal medulla
Organised into ovoid clusters, there are cytoplasmic granules that contain the catecholamines epinephrine and norepinephrine. The amino acid tyrosine is converted to DOPA by the enzyme tyrosine hydroxylase, then to dopamine, then noradrenaline, and the to adrenaline. These increase energy consumption through increased metabolism and blood glucose, and increased blood pressure (vasoconstriction). They are secreted in response to sympathetic innervation to stressful situations.
Actions of the catecholamines on adrenoceptors include:
decreased insulin secretion from beta pancreatic islet cells
platelet aggregation
decreased release of noradranaline from sympathetic terminals
inhibit adenyl cyclase and decrease intracellular cyclic AM, increases intracellular Ca2+ concentration by several mechanism, causing activation of phospholipase C
Actions of the catecholamines on betareceptors include
increased forces of contraction of the myocardium
increased A-V node of conduction
juxtaglomerular cells in the kidney to increase renin secretion
smooth muscle relaxation in the blood vessels, bronchi, gut and genitourinary systems
glycogenolysis in skeletal muscle and liver also stimulared
induces lypolysis in adipose tissue
activate specific G proteins that result in the stimulation of adenylate cyclase, converts ATP to second messenger cAMP
Hence, catecholamines are used as pharmacological agents to elevated blood pressure in hypotension secondary to shock from any cause. To mediate the symptoms of thyrotoxicosis, as in the beta adreno-ceptor blockage.
Phaeochromocytoma
This is a relatively uncommon tumour which in 90% of cases arise in the adrenal medulla. The cells secrete adrenaline and/ or noradrenaline.
The medical signs and symptoms include:
throbbing
headache
fear and anxiety
tenseness
tremour, palpitations
sweating
weakness
dizziness
Parathyroid
There are four small masses of epithelial tissue on the posterior surface of the thyroid glands called parathyroid glands. The parathyroid secretes parathyroid hormone which act to increase calcium levels in the blood.
Hypoparathyroidism
Insufficient secretion of parathyroid hormone leads to increased nerve excitability. The low blood calcium levels trigger spontaneous and continuous nerve impulses, which then lead to muscle contractions.
Thyroid
T3 and T4 stimulates metabolism.
Calcitonin decreases blood calcium level.
The thyroid is a highly vascularised, two lobed organ on either side of the trachea connected by an isthmus in the neck. It consists of follicles which require iodine to produce hormones - 95% thyroxine (T4) and 5% triiodothyronine (T3) hormones containing iodine. Patients with normal levels of hormones are called euthyroid. The majority of T3 in the body is formed by the conversion of T4 to T3. T4 also has a longer half life. T4 levels are also directly stimulated by the levels of TSH secreted from the pituitary gland. If T4 levels become high, there is negative feedback and normally less TSH secretion.
Patients with high levels are called hyperthyroid while patients with low levels are called hypothyroid. Production is regulated by a negative feedback mechanism involving the hypothalamus, adeno-hypophysis and circulating hormone.
The thyroid also contains para-follicular cells to secrete calcitonin which decreases the levels of calcium in the blood for it to return to normal.
Thyroid cancers
Primary myxoedema
Hashimoto's Thyroiditis
Hypothyroidism
Graves' Disease
Simple goitre
Thyrotoxicosis/ Hyperthyroidism
Thymus
The thymus produces thymosin and leads to immuno-competency in T lymphocytes.
Pancreas & Pancreatic Disorders
The pancreas is a long, soft organ that lies transversely along the posterior abdominal wall, posterior to the stomach, and extends from the region of the duodenum to the spleen. This gland has an exocrine portion that secretes digestive enzymes that are carried through a duct to the duodenum. The endocrine portion consists of the pancreatic islets, which secrete glucagons and insulin.
Alpha cells secrete glucagon increases blood glucose levels. Beta cells secrete insulin lowers blood glucose levels. Beta cells contain large numbers of vesicles (also called secretory granules) which are packed full of insulin. On arrival of a suitable stimulus, these granules move to the cell membrane and deliver their cargo of insulin. The major stimulus for insulin secretion is a blood glucose concentration of greater than 5 mM but secretion is modulated by other nutrients, hormones, and even neural stimuli.
Insulin is initially synthesised as a large polypeptide called pre proinsulin. Immediately after synthesis in the rough endoplasmic reticulum, a 23 amino acid signal sequence is removed to leave a single polypeptide called proinsulin. Proinsulin is the A-and B-chains of insulin joined by a 35 amino acid polypeptide called C-peptide. Just after packaging into the secretory granules, the proinsulin is hydrolysed by peptidases to give mature insulin and free C-peptide. Non-diabetic individuals thus secrete C-peptide along with insulin.
Diabetes Mellitus
Diabetes mellitus is a condition characterised by high blood glucose levels. There are two types of diabetes. Type 1 Diabetes: Commonly known as juvenile diabetes, the average onset is between 13 - 14 years. More males than females are affected. This is caused by the pancreas being unable to secret insulin. The body makes antibodies against the pancreatic beta cells. Type 2 Diabetes: Commonly referred to as a lifestyle disease, this is caused by high fat diets and lack of physical activity. The average onset is usually between 45 to 64. More males than females are affected.
Acute Dangers of Diabetes: Hypoglycaemia
Acute Dangers of Diabetes: Hyperglycaemia
Acute Dangers of Diabetes: Diabetic keto-acidosis
Dental Management of Diabetes
Gonads
Androgens (males) and oestrogens (females) support the development of gametes and secondary sex characteristics. These hormones are steroids which come from choesterol, and then made into intermediates pregnenolone and progesterone.
Testes
Leydig cells synthesise testosterone in the testis. This is normally stimulated by luteinising hormone (LH) secreted by the anterior pituitary under the influence of hypothalamic gonadotrophin releasing hormone (GNRH). Some estradiol is produced in men by aromatase present in fat cells but not in the testes.
Ovary
The ovarian follicular cells are the major sites of estradiol production in non-pregnant, pre-menopausal women. Its synthesis is promoted by follicle stimulating hormone (FSH) from the anterior pituitary gland and under the influence of hypothalamic gonadotrophin releasing hormone (GNRH). After ovulation, the corpus luteum synthesises and releases progesterone under stimulation by LH.
Placenta
During pregnancy, the cytotrophoblasts and syncytiotrophoblasts of the placenta secrete estadiol and progesterone under the control of placental (human) chorionic gonadotropin (HCG)
コメント