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 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.
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.
