Endocrine System Disorders

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

A growth hormone producing adenoma in adulthood leads to acromegaly.

The dental symptoms of acromegaly include:

• enlargement of mandible (prognathism due to active growth in the condylar centre)

• frontal bossing

• enlarged crenated tongue

• marked interdental spacing

• increased thickness in the jaw bones, lips and nose

• deepening and hoarseness of the individual's voice

• osteoporosis

• hypercementosis

• thickened cranium with exaggerated muscle and ridge attachments with an enalrged sella turcica

Treatment

• Octreotide is an analogue of somatostatin and has been associated with a decrease in growth hormone size and and levels

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

Synthetic versions of the drugs are collectively referred to as corticosteroids. They are metabolised in the liver and excreted in the urine. These include:

• orally active prednisolone; acute exacerbations of asthma, rheumatoid arthritis, inflammatory bowel disease and as immunosuppressant after transplants. Half life of 36 - 72 hours.

• endogenous hydrocortisone: emergency treatment of anaphylaxis and severe asthma, Addison's disease, along with fludrocortisone. Half life of 8 - 12 hours.

• cyclesonide, budesonide and fluticasone to treat some symptoms of asthma

• dexamethasone: treat cerebral oedema in patients with brain tumours

• beclomethasone, betamethasone

The side effects from taking glucocorticoids include:

• Diabetes mellitus

• Muscle wasting (proximal myopathy)

• Hypertension

• Adrenal suppression

• Bruising

• Thinning of skin

• Possibility of developing Cushing Syndrome

Topical application

• Oral candidiasis

• Dysphonia

• Sore throat

• Effects can be minimised using a spacer device

• acne, rosacea and eprioral dermatitis

• growth suppression with oral GCS

• infections, tuberculosis, fungal disease or cellulitis

• adrenal atrophy up to 36 months after stopping therapy. In this case, it is important to take hydrocortisone.

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

Auto-immune mediated atrophy of the adrenal cortex results in reduced cortisol, aldosterone and adrenal androgens. The disease can be life - threatening particularly at times of stress. Low cortisol results in hypersecretion of ACTH and hyperpigmentation.

Treatment

• saline and intravenous glucocorticoid.

• intravenous high dose glucocorticoid has adequate mineralocorticoid activity.

• Synacthen stimulation test

Congenital Adrenal Hyperplasia - Primary adrenal insufficiency

The enzyme 21 hydroxylase or 11 beta - hydroxylase is deficient and it helps to make cortisol and corticosterone. This deficiency decreases the levels of cortisol. This may also impair levels of aldosterone causing salt wasting and life threatening. This reduces normal feedback, leading to uncontrolled ACTH secretion, causing adrenal hyperplasia, and stimulating the synthesis of adrenal androgens. Hence, there is masculination in female patients and hyperpigmemtatopm.

Congenital adrenal hyperplasia is a complex clinical example of adrenal insufficiency where glucocorticoid is permanently deficient, mineralocorticoid is variably deficient and may lessen with age (and where there is also an excess of adrenal androgen).

Treatment

• saline and intravenous glucocorticoid.

• intravenous high dose glucocorticoid has adequate mineralocorticoid activity.

• Synacthen stimulation test

• Lifelong glucocorticoid and mineralocorticoid therapy is required, at a minimum of twice per day dose and the glucocorticoid needs to be adjusted with physical and/or psychological stress.

• Adults require approximately 37.5 mg of cortisone acetate (30 mg of hydrocortisone acetate daily) and 100 to 200 ug of fludrocortisone.

Adrenal crisis

Due to insufficient endogenous hydrocorticoids in stressed patients. Infections, minor or major surgery, trauma and emotional upset are all sufficient to precipitate such a crisis and are all encountered in the dental surgery. Steroid crisis may arise in any situation when corticosteroid levels are suppressed and when the adrenal cortex is unable to respond to immediate stresses. For example, interruption of the hypothalamic-pituitary axis or destruction of the adrenal glands results in reduced steroid levels, putting the patient at risk of steroid crisis. Alternatively, if systemic corticosteroids are taken by the patient, there is often atrophy of the adrenal cortex and a consequent inability to respond to stress by secreting hydro-corticosteroid. In both instances, it is necessary to increase the patient's dose of corticosteroids in anticipation of response to the stresses of dental disease and treatment. Even a brief course of corticosteroids may result in some degree of adrenal insufficiency which may only become manifest when the patient is stressed in the dental chair. For example, had the patient in this problem suffered an acute oral infection requiring extraction, the dentist would have had to increase the patient's dose of prednisolone, or perhaps manage a steroid crisis in the chair. Whether adrenal suppression develops as a result of exogenous glucocorticoid administration depends on three variables: the dose of the glucocorticoid administered, the duration of administration, and the schedule of administration. Patients may be on steroid therapy for a number of medical reasons ie transplant immunosuppresion, treatment of cancer/lymphoreticular tumours, autoimmune conditions which may not be evident, judging from their external appearance. The current standard of practice is to increase the dose of cortisol in the context of ‘stress’ either actual or anticipated. The dose of cortisol is doubled for the duration of the stress and returned to replacement levels immediately after the stress ceases.

Treatment

• Acute glucocorticoid deficiency is treated with large doses of cortisol given intravenously, 100mg every 6 hours, coupled with emergency support of blood pressure plus volume expansion and pressors when indicated.

• Oral and facial pigmentation. Some of the features of adrenocortical insufficiency are pigmentation of the mucosa and the skin, weakness, low blood pressure and anorexia with consequent effects on dental management. One of the early signs is the skin pigmentation which can be easily recognized by dentists. Further investigation for adrenal insufficiency may avoid the incidence of steroid crisis during surgical procedures. If there is intraoral pigmentation, it is normally seen on the gingiva, lips or buccal mucosa.

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

Thyroid cancers can arise from thyroid epithelial cells (follicular cells), thyroid C-cells, or lymphocytes within the thyroid.

Follicular cell origin

Papillary thyroid cancer

Follicular thyroid cancer

Anaplastic thyroid cancer

C-cell origin: medullary thyroid cancer

Thyroid lymphocytes cause lymphoma

TSH secreting pituitary adenoma: causes secondary hyperthyroidism (high or normal TSH, high T4)

Nonsecretory pituitary adenoma: causes secondary hypothyroidism (normal or high TSH, low T4)

Primary myxoedema

In primary myxoedema, thyroid blocking auto-antibodies are directed to thyroid stimulating hormone receptor. This results in decreased thyroid hormone production and causes a state of hypothyroidism. Hence, the medical symptoms include:

• atrophic thyroiditis

• weight gain despite decreased appetite

• cold intolerance and abnormal sensitivity

• sluggishness, fatigue and weakness and depression

• constipation

• hair and skin becomes dry

• slow pulse

• yellowing of the skin on the palms

• disordered respiration in severe cases leading to sleep apnoea

• puffiness of the face, hands and supraclavicular fossae due to glycosaminoglycans in the subcutaneous tissues

• characteristic osedema of facial tissues around the yes, tongue and gingival papillae

• painful muscles

• delay in reflexes

• irregular menstrual cycles

The oral symptoms of hypothyroidism include

• delay in tooth eruption

• protruding big tongue or macroglossia

• enamel hypoplasia in both dentitions, being less intense in the permeanent dentition

• anterior open bite

• micrognathia

• thick lips

• dysguesia

• mouth breathing

Treatment

This is treated with thyroxine beginning with a small dose. This is usually in the elderly or those with ischaemic heart disease and severely affected patients and particularly any with sleep apnoea. The adequacy is monitored by TSH concentrations, allowing at least 4 weeks for the concentration to become stable at a particular dosage of T4.

Hashimoto's Thyroiditis

There are activated T cells which cause an underactive thyroid.

The symptoms of Hashimoto's Thyroiditis match that of primary hypothyroidism, including:

• low titres of T4, high titres of TSH

• high titre antibodies to thyroid peroxidase

• weight gain despite decreased appetite

• cold intolerance and abnormal sensitivity

• sluggishness, fatigue and weakness and depression

• constipation

• hair and skin becomes dry

• slow pulse

• yellowing of the skin on the palms

• disordered respiration in severe cases leading to sleep apnoea

• puffiness of the face, hands and supraclavicular fossae due to glycosaminoglycans in the subcutaneous tissues

• painful muscles

• delay in reflexes

• irregular menstrual cycles

Treatment

If thyrotoxicosis is left untreated for too long, this can lead to cardiovascular diseases, palpitations and increasing dyspnoea.

This is treated with thyroxine beginning with a small dose. This is usually in the elderly or those with ischaemic heart disease and severely affected patients and particularly any with sleep apnoea. The adequacy is monitored by TSH concentrations, allowing at least 4 weeks for the concentration to become stable at a particular dosage of T4.

Dental considerations

• dental anaesthestics with the adrenaline component is contraindicated as it may potentiate the already high levels of catcholamines circulating int he blood. This is minimised by aspiration prior to inejction

• propylthiouracil and methimazole, which are medications used to treat thyroid disease, may cause bilateral swelling of the salivary glands and decreased taste sensation. they may also affect the bone marrowm causing agranulocytosis and a decrease in white blood cells. There may also be thrombocytopenia causing a disturbance in paltelet aggregation and excessive bleeding from surgical procedure

Hypothyroidism

The medical symptoms of hypothyroidism include:

• variable levels of T4, high levels of TSH

• weight gain despite decreased appetite

• cold intolerance and abnormal sensitivity

• sluggishness, fatigue and weakness and depression

• constipation

• hair and skin becomes dry

• wide set eyes (hypertelorism)

• slow pulse

• yellowing of the skin on the palms

• disordered respiration in severe cases leading to sleep apnoea

• puffiness of the face, hands and supraclavicular fossae due to glycosaminoglycans in the subcutaneous tissues

• painful muscles

• delay in reflexes

• irregular menstrual cycles

• memory loss

The oral symptoms of hypothyroidism include

• delay in tooth eruption

• protruding big tongue or macroglossia

• enamel hypoplasia in both dentitions, being less intense in the permeanent dentition

• anterior open bite

• micrognathia

• thick lips

• dysguesia

• mouth breathing

Treatment

This is treated with thyroxine beginning with a small dose. This is usually in the elderly or those with ischaemic heart disease and severely affected patients and particularly any with sleep apnoea. The adequacy is monitored by TSH concentrations, allowing at least 4 weeks for the concentration to become stable at a particular dosage of T4.

Graves' Disease

Graves' Disease involves thyroid stimulating auto-antibodies, directed to thyroid hormone receptors. This causes the overproduction of thyroid hormones. Due to this this being a direct problem with the thyroid. Hence, it is a form of a primary hyperthyroidism. There is higher T4 levels and lower TSH.

The medical symptoms of Grave's disease match hyperthyroidism, including:

• weight loss usually accompanied with an excessive appetite

• heat intolerance accompanied by excessive sweating and increased heat production

• sluggishness and fatigue due to energy wasting

• diarrhoea and an increase in bowel frequency

• tachycardia due to vasodilation and sensitivity to catecholamines

• anxiety and irritability

• muscle weakness and wasting

• proximal myopathy

• hyper-reflexia

• light menstruation

The medical symptoms of Grave's Disease can also include:

• diffuse toxic goitre or thyroid enlargement

• exophthalamas or proprtosis

• pretibial myxoedema: skin thickening in the pretibial position

• lid retraction where the sclera is visible above the iris

• lid lag where the descent of the upper eyelid lags behind the iris

• diffuse goitre that may have a bruit due to increased vascularity

Treatment

Graves' disease go into remission after 12 - 18 months therapy.

The treatment is to administer radio-iodine (I-131). This may cause hypothyroidism and is contraindicated in pregnancy,

Simple goitre

Due to dietary iodine deficiency, the thyroid cannot make sufficient thyroxin and triiodothyronine hormones. As a result, the anterior pituitary secretes thyroid stimulating hormone and causes the thyroid to increase in size. This causes the neck to appear larger and is known as goitre.

There are several grades of goitre:

• Grade 0: no goitre visible or palpable

• Grade 1a: goitre detectable only by palpation and not visible when neck fully extended

• Grade 1b: goitre palpable and is visible when the neck is fully extended

• Grade 2: goitre is visible with neck in normal position

• Grade 3: very large goitre recognisable from a considerable distance

A goitre can be described as either diffuse or nodular.

Thyrotoxicosis/ Hyperthyroidism

The medical symptoms of hyperthyroidism include:

• variable levels of T4, low TSH

• weight loss usually accompanied with an excessive appetite

• heat intolerance accompanied by excessive sweating and increased heat production

• sluggishness and fatigue due to energy wasting

• diarrhoea and an increase in bowel frequency

• tachycardia due to vasodilation and sensitivity to catecholamines

• anxiety and irritability

• muscle weakness and wasting

• proximal myopathy

• hyper-reflexia

• light menstruation

The oral manifestations of patients with hyperthyroidism include:

• accelerated dental eruption in children

• maxillary or madndibular osteoporosis

• enlargement of extraglandular thyroid tissue (mainly in the lateral posteror tongue)

• increased susceptibility to caries

• periodontal disease

• burning mouth syndrome

• development of connective tissue disorders such as Sjorgen's syndrome or systemic lupus erythematosus

Treatment

If the cause of thyrotoxicosis is excess thyroxine intake, the treatment is to decrease the levels of thyroxine.

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

This is indicated using blood glucose levels lower than 3.9mmol/L, or 70mg/dL blood sugar levels. Causes include:

• physical activity with insufficient food

• continuous consumption of alcohol (which inhibits gluconeogenesis) without food, delayed or missed meals

• errors in insulin dose or inappropriate insulin regimens

Manifestation of symptoms appearing at ~3.0 mmol/L and cognitive dysfunction at ~2.7 mmol/L. Symptoms include confusion, blurry vision and light-headed ness. These symptoms include tremor, tachycardia, palpitations, sweating, weakness and awareness of hypoglycaemia. Self-diagnosis and treatment of hypoglycaemia usually occur at this stage. It is considered more dangerous than hyperglycaemia in a dental setting as it can lead to headache, altered mental status, visual disturbances, neurological deficit and seizures.

Management

• adequately treated with ingestion of 15 to 20 G of oral glucose (eg. 6-7 jelly beans OR 150 mls normal Coke) followed by some complex carbohydrate (eg.a slice of bread OR a piece of fruit).

• When severe hypoglycaemia occurs where the patient is unconscious or unable to swallow, treatment is with either an intravenous injection of glucose (50%), or an intramuscular injection of glucagon, followed by ingestion of complex carbohydrate as soon as the patient regains consciousness. After an episode of severe hypoglycaemia has been treated, blood glucose level may rebound to a very high level afterwards. In this situation, it is important not to treat the hyperglycaemia too aggressively with insulin in the first 24-48 hours, or hypoglycaemia may return and may also perpetuate the vicious cycle of hypoglycaemia–failure in counterregulation–more hypoglycaemia

Acute Dangers of Diabetes: Hyperglycaemia

This is defined as blood glucose levels above 126mg/dL or 7.8mmol/L. Symptoms include dizziness and sweating. Dangers include seizures.

Short acting insulin: solution of insuline before each meal

*greatest risk 2 -3 hours after injecting insulin

Intermediate acting insulin: isophane or NPT bound to protamine

* greatest risk 4 to 10 hours after injecting insulin

Very long acting insulin: determir binds to albumin, glargine

Metformin/ biguanides: increased glucose uptake into cells

alpha-glucosidase inhibitors: reduce glucose for absorption, such as acarbose

Sulfonuyrleas: potentiate glucose stimulated insulin release, risk of hypoglycaemia, stimulate weight gain and appetite

Repaglinide: stimulate the same receptor as sulphonylurias

DPP-IV: breaks down GLP-1 and GIP, incretins that stimulate insulin dependent glucose release from pancreas

Glitazones: reduce insulin resistance by acting on peroxisome proliferator receptors

SGLT-2 inhibitors: prevent reabsorption of glucose by proximal renal tubule

Acute Dangers of Diabetes: Diabetic keto-acidosis

In more serious cases, diabetics break done fat for energy causing a hyperglycaemia state and also high ketones in their blood. This is called diabetic keto-acidosis. Keto-acidosis attack can be detected using fruity breath. People with blood glucose higher than 240mg/dL should check their urine for the presence of ketones.

Dental Management of Diabetes

Signs of Poorly Controlled Diabetes

HbA1c tests indicate the overall levels of control over blood glucose levels over the past 2 - 3months.

HbA1c levels above 10% suggest poorly controlled diabetes.

HbA1c levels below 8% suggest well controlled diabetes.

• Recommend early morning appointments as the levels of cortisol are higher in the morning and this helps to prevent a hypoglycaemic attack.

• Tetracycline can reduce collagen breakdown and is believed to help with healing. Hence, it is often applied topically in combination with root planing and scaling.

• For patients using short/ long acting insulin therapy, it is important to avoid appointments whereby it coincides with peak insulin activity.

• Check the patient's blood sugar levels before the appointment.

• Have a glucometer to monitor for low blood sugar levels before the appointment. Blood sugar levels should be between 70mg/dL and 100mg/dL (3.9 - 5.6mmol/L)

• If the patient has low blood sugar, have sugary snacks such as fruit juices, skim milk and biscuits ready at the dental clinic in case of hypoglycaemia. Ask the patient that they have had enough food before the meal. For many diabetic patients, avoid using orange juices which are high in potassium, as this can incur more damage to their kidneys. Consider alternative juice options such as apple juice and cranberry juice.

• Note implant placement in patients with uncontrolled diabetes has an unpredictable prognosis and is mostly avoided

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)