Pituitay And Thyroid Flashcards
What are the regions of the hypothalamus?
The supraoptic nucleus which produces oxytocin and vasopressin
The periventricular nucleus produces TRH and CRH for endocrine control. These hormones are released into the hypothalamus-hypophyseal portal system.
How are thyroid hormones released into circulation?
TSH which acts on the TSH receptors follicular cells of the thyroid gland to stimulate synthesis of thyroglobulin, a component of the thyroid hormones formed of tyrosine amino acid residues. Trapping of I-/iodine ions occur via the sodium-iodide co-transporter. Iodide is converted -> iodine by thyroxine peroxidase and iodine is inserted into the tyrosine amino acid chain to form the thyroid hormones:
Monoiodothyroxine + diodothyroxine= triiodothyronine (T3)
Diiodothyroxine + diiodothyroxine = tetrathyroinine (t4)
What is the action of thyroid hormones?
Thyroid hormones travel via the bloodstream, but require a transport protein thyroglobulin produced from the liver. It is lipid soluble and can directly enter cells to cause:
Increased metabolism, enhancing the effect of catecholeamines by increasing availability of beta receptors, glycogenolysis, gluconeogenesis to increase basal meta IVC rate and oxygen consumption.
It promotes basal metabolism and increases the conversion of carotene -> vitamin A and promotes GI motility.
What are the types of pituitary tumours?
-> Adenoma of the pituitary gland which rarely metastasises and are typically found incidentally, associated with visual defects of bitemporal hemianopia, headaches and hormone-related deficiencies
-> In children, cancers of the pituitary gland can be craniopharyngiomas, which is a congenital malformation that arises from the Rathke cells that are the progenitors of the anterior pituitary gland during development. These are located between anterior and the posterior pituitary gland.
What are the causes of hypopituitarism?
Adenocarcinoma, including craniopharyngiocarcinomas
Compression by overfilling of sella turcica with cerebrospinal fluid
Pituitary apoplexy, where haemorrhage of vessels in the hypophyses-portal system occurs leading to infarction, associated with Sheehan syndrome
Iatrogenic damage from radiotherapy, surgery or medications.
What is Sheehan syndrome?
Increased blood demand during pregnancy for pituitary gland combined with excessive blood loss in childbirth results in apoplexy of pituitary gland. Clinical signs include inability to breastfeed due to failure of oxytocin release from the posterior pituitary gland and secondary amenorrhea, breast atrophy and libido with dry skin and diabetes insipidus.
What is the role of growth hormone?
Growth hormone is important for the uptake of amino acids by muscle and stimulating lipolysis and stimulating GH receptors on the liver to produce IGF-1.
What is the role of IGF-1?
IGF-1 causes protein synthesis in muscles, gluconeogenesis, and increases cartilage formation and endochondral ossification in the bone.
What are the features of growth hormone deficiency?
Delayed puberty, short stature, delayed puberty, fatigue, weight gain, low cardiac output, hypoglycaemia, central obesity, atherosclerosis.
What are the features of FSH and LH deficiency/
FSH and LH deficiency results in infertility, oligorrhoea, ammenorrhoea, breast atrophy, hypogonadism, erectile dysfunction, decreased libido
How s hypopituitarism diagnosed?
Hypopituitarism is diagnosed with an insulin stress test, where insulin administration should cause hypoglycaemia and stimulates cortisol and GH release. Glucagon should also stimulate cortisol and GH release
Investigations include cortisol urine test and ACTH test, pituitary MRI, blood test to assess thyroid hormones and water deprivation test to rule out issues with desmopressin release.
How is hypopituitarism diagnosed?
Hypopituitarism is treated with removal of pituitary adenoma and hormone replacement therapy such as hydrocortisone and glucocorticoids.
What are the conditions caused by hyperpituitarism?
-> Acromegaly due to excessive growth hormone that causes enlargement of hands and feet, causing increased risk of cardiovascular disease due to insulin resistance and hyperglycaemia
-> Cushing’s disease, due to excessive release of GH which is assoicated with hyperpigmentation due to high ACTH, osteoporosis, weight gain. It causes hypokalemia, metabolic acidosis, hyperglycaemia.
-> Hyperprolactinaemia, resulting in breast enlargement, milk production, infertility, low libido, osteoporosis
-> Secondary hyperthyroidism, causing weight gain and increased. basal metabolism.
What are the investigations for hyperpituitarism?
Oral glucose tolerance test, which should cause a drop in growth hormone
24 hour serum cortisol to assess cortisol levels
Dexamethasone suppression test, where injection of corticosteroids should cause a decrease of both cortisol and ACTH
-> Suppression of just cortisol indicates ACTH secreting adenoma of the adrenal or pituitary gland
-> Neither suppressed indicates benign ACTH syndrome
What is primary aldosteronism?
Conn’s syndrome, where there is excessive production of aldosterone from the adrenal glands due to:
Bilateral adrenal hyperplasia which is the most common cause
Adrenal adenoma
Familial hyperaldosteronism, an autosomal dominant condition that is rare
What are the pathological changes caused by primary aldosteronism?
Aldosterone promotes Na+ and H20 retention and promotes loss of K+.
This causes hypokalemia WITH HYPERTENSION AND METABOLIC ALKALOSIS, hypernatremia, hypophosphataemia and fluid overload and hypertension. Symptoms include excessive thirst, fatigue, muscle cramps, and headaches.
What are the investigations for primary aldosteronism?
Investigations include aldosterone-renin ratio, which will show a high aldosterone
Adrenal vein sampling to distinguish between unilateral and bilateral hyperplasia.
Cosyntropin test to inject ACTH and determine the functioning of the adrenal gland via cortisol production
CT scan of the pituitary gland
What is the treatment for primary aldosteronism?
Spironolactone to cause K+ sparing to correct hyperkalemia and reduce hypertension
Removal of adenoma in the pituitary or adrenal glands
Restriction of dietary salt intake
What is phaechromocytoma?
Phaechromocytoma is a tumour arising from the chromaffin cells of the adrenal medulla, which results in excess catecholeamines secretion. It is associated with a triad of: -> -> episodic headache
-> palpitations
-> Prolonged vasoconstriction causing hypovolemia
-> diaphoresis (sweating)
-> tachycardia
->hyperglycaemia
-> cardiomyopathy.
Symptoms will be worsened by consuming beer, cheese or wine due to high tyramine content.
What is the treatment of phaechromocyotma?
It is treated with alpha-blockers, beta blockers and surgical resection of the tumour. Medication like metyrosine inhibits the synthesis of catecholeamines to reduce levels
What are the investigations for phaechromocytoma?
FBC, U&Es, LFTs
ECG
24 hour urine test for presence of noradrenaline metabolites
CT scan of chest and adrenal glands
What is Addison’s disease?
Addison’s disease is autoimmune mediated damage of the adrenal cortex or 21-hydroxylase which results in reduced production of catecholeamines, cortisol, aldosterone and sex hormones that can result in an adrenal crisis in times of stress like infection or surgery.
What are the features of Addison’s disease?
Addison’s disease is characterised by:
Low ADH: hyperkalemia, hyponatremia, hypotension
Low cortisol: weight loss, hypoglycaemia
Low sex hormones: in females, this is more prominent and results in amenorrhoea and infertility.
What are the features of Addison’s crisis?
Features of Addison’s crisis includes hyperkalemia, hyponatremia, low bicarbonate and hypoglycaemia. Addison’s crisis can cause hyperkalemic metabolic acidosis which causes a sudden extreme weakness in the legs, restlessness, confusion, severe hypotension and dehydration.
What are the causes of primary Addison’s disease?
Autoimmune destruction, which increases the risk of polyglandular autoimmune syndromes
Autoimmune diseases such as anti-phospholipid syndrome
Infiltration of adrenal glands from deposition in haemochromatosis, amyloidosis, sarcoidosis, lymphoma or secondary metastases
Infection from tuberculosis, syphyllis, cytomegalovirus and most importantly HIV, which causes adrenal necrosis.
Adrenal haemorrhaging from trauma or disseminated intravascular coagulation or atherosclerotic plaques
Medications
Which medications can cause primary adrenal insufficiency?
Ketaconazole is an antifungal which directly inhibits adrenal enzymes and blocks steroid production
Etomidate is an intravenous anaesthetic which blocks 11-b-hydroxylase enzyme for synthesis of testosterone.
What is Waterhouse-Friderichson syndrome?
Rupturing of vessels of the adrenal glands due to bacterial infection, typically from Neisseria meningitidis that occurs as a complication of sepsis and causes adrenal insufficiency.
What are the investigations for Addison’s disease?
FBC for aldosterone, renin and ADH levels
U&Es and LFTs
ECG
Insulin stress test, where fasting while using insulin should cause hypoglycaemia and stimulate release of cortisol
What is the cause for secondary adrenal insufficiency?
Secondary adrenal insufficiency occurs due to pituitary gland tumours which result in low ACTH.
Alternatively, excessive glucorticoids that reduces endogenous ACTH production.
Paraneoplastic syndrome from cancers
What is the clinical presentation of Adrenal insufficiency?
Chronic abdominal pain, tachycardia and low appetite
Hypotension
Nausea and vomiting
Fatigue and generalised weight loss
Hyperpigmentation only occurs in primary Addison’s disease due to excess circulating ACTH binding to melanocytes receptors, causing pigmentation in palmar creases, armpits, gingiva, lips and elbows..
What are the features of hyperthyroidism?
Hyperthyroidism is associated with increased basal metabolism, excessive sweating, weight loss, tachycardia and diarrhoea. It causes a low potassium and mild normocytic anaemia.
What is the most common cause of hyperthyroidism?
The most common cause of hyperthyroidism is Graves’ disease, an autoimmune condition associated with mutation of HLA-DR3 or HLA-B9 that causes hyperactivity against the TSH receptor to result in production of thyroid stimulating antibody, causing excessive activation and stimulation, that stimulates hypermetabolic effects.
What is a key feature of Graves’ disease?
A key feature of Graves’ disease is Opthalmos, due to inflammation from cytokines produced by cytotoxic T cells and thyroid stimulating antibody results in the growth of the extraocular muscles and the retro-orbital connective and adipose tissue and the synthesis of excess glycosaminoglycans. The GAGs draw water in and promote water trapping in the muscle, leading to swelling and oedema
What are the characteristics of Graves’ disease?
Graves’ disease can cause pretibial myexdaema, where deposits of the glycoprotein mucin occur under the skin of the legs and cause thickening.
Graves affects vision, causing double vision, light insensitivity, proptosis (bulging eyes) and Opthalmos.
What are the signs of hyperthyroidism?
Tachycardia, systolic hypertension, atrial fibrillation, oedema, raised JVP, palpable goitre, palmar erythema.
What are the triggers for Graves’ disease?
Pregnancy (mainly postpartum)
iodine excess
infections
Emotional stress
Smoking
Treatment of Graves’ disease is beta blockers, carbimazole to inhibit synthesis of thyroid hormones, radioactive iodine treatment or thyroidectomy.
What are the investigations for Graves’ disease?
FBC for TSH test, free levels of T3 and T4, prescence of TSH antibodies in the blood, ultrasound of the thyroid gland and T3/T4 ratio.
-> T3/T4 ratio greater than 20 indicates Graves’ disease.
What is the 2nd most common cause of hyperthyroidism?
Toxic multinodular goitre is the 2nd common cause for hyperthyroidism, where there are multiple goitres on the thyroid gland which autonomously produce thyroid hormones. This can be diagnosed by a high free thyroid hormone level and low TSH.
Risk factors for multi nodular goitre is iodine deficiency inducing hyperplasia of thyroid gland, smoking, family history and high levels of IGF-1 associated with acromegaly.
What is single solitary nodule?
Single solitary nodule is caused by an adenoma of the thyroid gland releasing excessive thyroid hormone, which is typically treated by thyroidectomy.
What is De Quervain’s thyroiditis?
De Quervain’s thyroidis is inflammation of the thyroid gland during typically URT infection, associated with painful thyroid gland, neck pain, swelling, dysphagia, fever, malaise and tenderness.
This results in an initial hyperthyroidism phase -> hypothyroidism phase before resolving and is self-limiting, so only supportive care is required with analgesics.
What is thyroid storm?
Thyroid storm occurs is an acute severe presentation where there is a stressor like surgery or sepsis during chronic hyperthyroidism that causes sympathetic activation and worsens hyperthyroidism, causing is tachycardia, delirium and pyrexia which is corrected with anti-arrythmia drugs and supportive fluids.
What is pituitary micro adenoma?
Pituitary micro adenoma are a subtype of pituitary adenoma which cause excessive production of hormones like TSH and usually found incidentally on MRI. It is a type of secondary hyperthyroidism which also causes Cushing’s disease, gynaecomastia and acromegaly.
What are the general causes of hyperthyroidism?
Graves
Single solitary nodule
Toxic multi nodular goitre
Pituitary micro adenoma
Initial stage of De Quervain’s thyroiditis
What is the cause of a painful enlarged thyroid?
Radiation
Trauma
Infection-> Related to De Quervain’s thyroiditis
What is the cause of painless enlarged thyroid?
Autoimmune conditions induced by
Drugs
Post-partum
What is the presentation of hyperthyroidism?
Goitre
Metabolic dysfunction, causing heat intolerance, weight loss, increased appetite
Neurological dysfunction due to greater metabolism, causing increased neuron activity with hyperactivity of behaviour and deep tendon reflexes
Tachycardia and increased contractility, which can lead to atrial fibrillation and supraventricular tachycardia and hypertension
Systemic vasodilation
Menstrual irregularies and reproductive dysfunction
Increases fibroblast and GAG proteins, leading to water retention and pre-tibial myedema associated with Graves
What is the management of hyperthyroidism?
Radioactive iodine therapy
Anti-thyroid drugs such as Carbimazole, propylthiouracial and methimazole
Thyroidectomy
Which patients should radioactive iodine therapy be avoided in?
Pregnancy patients, breastfeeding patients and those planning to conceive within the next 6 months. Those with moderate to severe Graves’ orbitopathy should not receive this
What is the use of propylthiouracial?
Propylthiouracial inhibits the action of thyroid peroxidase or the conversion of iodide- > iodine and the synthesis of new iodine hormones.
It can cause liver dysfunction and is more effective in hyperthyroidism and thyroid storm.
What is the use of methimazole?
Methimazole inhibits the action of thyroid peroxidase and the iodination of thyroglobulin, however does not interfere wih conversion of T3 -> T4 so it is less effective in thyroid storm compared to propylthiouracial.
What are the general causes of hypothyroidism?
Iodine deficiency
Thyroid destruction from autoimmune conditions
Post -party’s
Riedel’s thyoriditis
De Quervain’s thyroiditis
Pituitary macroadenoma
Sheehan’s syndrome
What is the most common autoimmune condition in hypothyroidism?
Hashimoto’s disease, where auto-antibodies like anti-thyroid peroxidase (TPO) and anti thyroxidase causes due to a mutation inHLA-DR3 and HLA-DR-4 reduce thyroid hormone production.
What is post-partum thyroiditis?
Postpartum thyroiditis is a self-limiting condition in the first 12 months after pregnancy where autoimmune destruction of the thyroid gland occurs due to anti-thyroid peroxidase antibodies that causes the release of thyroid hormones from the follicles that causes a transient hyperthyroid state which becomes hypothyroid.
Treatment depends on the phase, with propylthiouracil for hypothyroid phase or beta blockers for hyperthyroid phase.
What is Riedel’s thyroiditis?
Riedel’s thyroiditis is where IgG antibodies destroy the thyroid gland and activate fibroblasts causing fibrosis of the thyroid gland, causing compression of the recccurent laryngeal nerve, trachea and oesophagus, leading to hoarseness of voice, dysphagia and stridor or wheezing.
Riedel’s can also cause inflammation of the aorta and fibrosis of the retroperioneum.
What is the Wolf-Chaikoff effect?
Wolf-Chaikoff effect where rapid rise in high levels of iodine causes inhibiton of thyroid peroxidase function associated with:
-> Use of amiodarone
-> Radio-iodine therapy
How do pituitary macroadenoma affect the levels of thyroid hormones?
Pituitary macro adenomas compress the hypophyseal portal system that prevents the circulation of TSH into the bloodstream. This can cause compression known as mass effect, leading to headaches, optic chiasma causing bitemporal hemianopia
What are the clinical signs of hypothyroidism?
Goitre due to pituitary macroadenoma, where excessive TSH causes thyroid gland enlargement.
-> Painless vs painful goitre acts as a differential
Metabolic dysfunction with weight gain and cold intolerance
Hypothyroidism stimulates the pproduction of ADH, causing water retention and hyponatremia
Neurological dysfunction due to reduced metabolism, with reduced neuron activity and extreme fatigue and depression and hyporeflexia
Bradycardia
Reduction in hypothyroidism reduces expression of LDL, causing more fat build up in the blood and leading to Hyperlipidaemia and atherosclerosis
Constipation
Macrocytosis with large RBCs
Which conditions are hypothyroidism associated with?
Rheumatoid arthritis and type 1 diabetes
What is an emergency complication with hypothyroidism?
Stressors like surgery, hypothermia or infection can cause a myexdema coma, where there is minimal metabolism. Thyroid hormones are important for the action of the Na+/K+ pump, therefore it results in multi organ defects causing:
Hypothermia, severe bradycardia, pulmonary oedema, encephalopathy and pretibila myexdema.
What is urine osmolality?
Concentration of particles in urine, and it is an important indicator for the ability of the kidneys to concentrate urine and the action of ADH to maintain water absorption and Na+. The normal value is between 50-1200 mOsm/Kg
What does high urine osmolality mean?
Patient is dehydrated with highly concentrated urine high in solutes, indicating high ADH activity for excessive water and Na+ reabsorption due to:
-> pathology of the kidneys such as AKI
-> congestive heart failure causing fluid retention
What does low urine osmolality mean?
Patient has very diluted urine, indicating low levels of ADH activity due to:
Excess fluid intake, causing overhydration
Kidney failure or renal tubular necrosis reducing response to ADH
Diabetes insipidus or SIADH
What does serum osmolality measure?
The concentration of particles within the plasma of the circulating bloodstream, determined by the levels of sodium.
What does a high serum osmolality mean?
Serum is highly concentrated and indicates hypernatremia, due to
What does low serum osmolality indicate?
Body serum is highly diluted and there is hyponatremia due to:
What stimulates the release of ADH?
Reduction in blood volume and a rise in serum osmolality.
What is SIADH?
Syndrome of inappropriate ADH secretion, which is characterised by a euvolemic state with low serum osmolality and a high urine osmolality due to excessive ADH release.
What are the causes of SIADH?
Respiratory infection, with strong associations with pneumonia
Carcinomas small cell lung cancer, pancreatic cancer, gastric, duodenal, ureter, bladder and prostate.
CNS disorders such as stroke, meningitis and tumours
Trauma or carcinoma of the pituitary gland
Medications
Conditions such as hypothyroidism and adrenal insufficiency
Which medications cause SIADH?
CARDISH
Chemotherapeutic agents and carbamezapine
Antidepressants
Recreational drugs
Diuretics
Inhibitors of ACE and SSRIs
Sulphonylureas
Hormonal therapy with desmopressin
What is the pathophysiology of SIADH?
SIADH causes water retention which causes a low serum osmolality. The high fluid volume stretches cardiac muscles and causes the release of ANP and BNP, promotes loss of Na+ through urine, leading to a high urine osmolality. Overtime, kidneys reduce their expression of aquaporin and this causes reduced water reabsorption. SIADH patients will be in a euvolemic state with low serum osmolality and high urine osmolality, despite salt or water ingestion.
What is the clinical presentation of SIADH?
Divided into
Acute hyponatremia, with cerebral oedema causing tentorial herniation encephalopathy, seizure and stroke
Chronic hyponatremia which may be asymptomatic or present with nausea, vomiting, izziness and issues with movement
Clinical euvolemia is a requirement for diagnosis, therefore indicators of hyperkalemia from ascites/oedema or hypovolemia from dry skin/hypotension/mouth exclude SIADH
What is the management of SIADH?
-> Restriction of fluid intake and treating underlying cause
-> Hypertonic saline solution with slow administration
-> if fluid overload occurs, administer furosemide
-> Demeclocylcine and tolvaptan
How does hypothyroidism cause SIADH?
Hypothyroidism results in reduced action of the Na+/K+ ATPase pump, reducing cardiac output that causes a low circulating volume and release of ADH excessively.
How does adrenal insufficiency result in SIADH?
Cortisol is important in the negative feedback of ACTH and CRH but it also directly suppresses ADH release from the pituitary gland. Lower cortisol causes an increase in ADH release.
What is the action of demeclocycline?
Tetracycline antibiotic which impairs the binding of ADH to its receptor on . It is generally indicated for use in bacterial infection but can result in diabetes insipidus with overuse.
What is the action of tolvaptan?
It is a selective competitive vasopressin receptor 2 antagonist which is used to treat hypovolemia assoicated with SIADH and congestive heart failure.
What is diabetes insipidus?
Characterised by excessive thirst and polyuria in the abscence of hyperglycaemia and insulin resistance. It occurs due to a dysfunction in the response to ADH due to:
-> Central diabetes insipidus
-> Primary polydipsia due to excessive fluid intake such as IV fluid overload
-> Nephrogenic diabetes insipidus?
What is the cause of central diabetes insipidus?
Impairment of ADH production from the posterior pituitary gland with acute onset of polydipsia and polyuria compared to primary polydipsia due to:
-> Idiopathic is most common
-> Familial hypothalamic diabetes insipidus, an autosomal dominant condition caused by mutation of ADH gene
-> Wolfram syndrome
-> Craniopharyngiocarcinoma
-> Trauma or surgery of the brain, with lack of perfusion to the hypothalamus or pituitary gland
-> Langerhan cell histiocytosis
Diagnosis is made from fluid deprivation test to stimulate endogenous vasopressin release.
What is the cause of nephrogenic diabetes insipidus?
-> Congenital X linked mutation of the aquaporin 2 channel
-> Medications such as lithium, clozapine, demeclocyline, alcohol and phenytoin.
-> Polycystic kidney disease
-> Gestational diabetes insipidus
-> Sickle cell disease due to occlusion of vasa recta causing medullary infacts
-> Decreased protein intake
Nephrogenic diabetes insipidus is characterised by hypercalcaemia and hypokalemia.
What is Wolfram syndrome?
Autosomal recessive condition where there is childhood onset of Type 2 diabetes, characterised by optic atrophy and deafness.
What is gestational diabetes insipidus?
Complication in third trimester of diabetes, where there is excessive production of vasopressinase activity, which increases the metabolism of ADH hormone, leading to polyuria and polydipsia.
How is diabetes insipidus Diagnosed?
Urine dipstick and culture
24 hour urine output
Water deprivation test to differentiate between central and nephrogenic diabetes insipidus by administering ADH following 24 hours of zero water to assess change in urine osmolality
-> Nephrogenic diabetes insipidus will have no change
What is the treatment of central diabetes insipidus?
What is the treatment of congenital diabetes insipidus?
Monitoring of fluid balance due to loss of thirst mechanisms with a low sodium diet, use of thiazide diuretics to inhibit sodium reabsorption and the use of NSAIDs.
