128 - Endocrine Flashcards
What are the 4 ways signals are sent in the endocrine system?
Autocrine (to same cell)
Paracrine (to neighbours)
Endocrine (via bloodstream)
Neurohormones (from synapses, via bloodstream)
What are the 4 types of hormone?
Peptide
Amino acid/amine
Steroid
Fatty acid derivatives
How are peptide hormones produced?
Encoded by a gene, preprohormone gets made, modified in the ER, then turned into a prohormone in the golgi, then processed into the active hormone and packaged into secretory vesicles.
Which hormone type is water soluble?
Peptide hormones, amino acid derivatives
Which hormone type is lipid soluble?
Steroid hormones
What makes up amine hormones?
Derived from thyroside
What makes up steroid hormones?
Derived from cholesterol
What subtypes of steroid hormones are there?
Glucocorticoids - cortisol
Mineralocorticoids - Aldosterone
Sex steroids - testosterone, Oestrogen, Progesterone
What makes up fatty acid derivatives?
Polyunsaturated fatty acids
- eg. Eicosanoids - prostaglandins
What is the mechanism of action of water soluble hormones?
They can’t cross cell membrane, so bind to a specific receptor, use a secondary internal messenger which alters cell function and exerts the physiological effects needed.
What is the mechanism of action of Lipid soluble hormones?
They can diffuse through the cell membrane, bind to nuclear receptors directly, form an activated hormone receptor complex which causes specific protein production and exerts the physiological effects needed.
What is chronotropic control?
Endogenous neuronal rhythmicity - causes diurnal rhythms and sleep wake cycles..
Describe the hypothalamic-pituitary-adrenal axis
Hypothalmus produces CRF, acts on anterior pituitary - produces ACTH - acts on adrenal cortex - produces cortisol.
(cortisol has negative feedback against hypothalamus and pituitary)
What effect does cortisol have on the body?
Stress response
Increase blood glucose
Reduce the immune system
Reduce protein synthesis
What disease is caused by excess cortisol production?
Cushing’s syndrome
What are the causes of Cushing’s syndrome?
Iatrogenic (give to much cortisol)
Primary Cushing’s - Excess cortisol production, eg. adrenal tumour
Secondary Cushing’s - Excess ACTH causing increased cortisol production, eg. pituitary tumour, cushing’s disease.
What re the features of Cushing’s / excess cortisol?
Moon face Central adiposity Hirsutism Depression High blood sugar High BP Fatigue Immunosuppression Leg oedema If cause is high ACTH - skin pigmentation.
What investigations would you do if you suspected Cushing’s?
24hr urinary cortisol levels - high
ACTH levels - low=primary disease, high=secondary disease
Dexamethasone suppression test - give low dose at midnight, should suppress cortisol production in the morning. In Cushing’s it doesn’t.
What can be given to treat Cushing’s?
Metyrapone - inhibit synthesis of cortisol
Look into removing tumour if cause?
What is adrenal insufficiency?
Insufficient production of cortisol
= Addison’s disease
What can cause adrenal insufficiency?
Sudden withdrawal of long term steroids
Addison’s - primary adrenal insufficiency, can be autoimmune of TB.
What are the features of adrenal insufficiency?
Pigmentation (as compensatory high ACTH) Malaise Nausea Vomiting Low blood glucose hypotension Weight loss
What is an addisonial crisis?
Often the first presentation of addison’s
Causes collapse, very low BP, Low blood sugar.
Can be fatal
What investigations would you do if you suspected adrenal insufficiency?
ACTH infusion - you would see an inadequate cortisol response
Measure blood - high basal ACTH, high K+, low Na+, low blood glucose
What is the treatment for addison’s?
Hydrocortisone and Fludrocortisone
Apart from disruption of cortisol production, what other pathologies relating to the adrenal glands occur?
Pheochromocytoma - excess catecholamine production
Conn’s syndrome - excess Aldosterone
Congenital adrenal hyperplasia - disruption in cortisol, androgens and insufficient aldosterone
What occurs in pheochromocytoma?
Excess catecholamines due to adrenal or extra-adrenal cause - eg. tumour. Intermittent or sustained hypertension Sweating Tachycardia Headaches
What test could you do, and how would you treat pheochromocytoma?
24 hr urine test - high levels
Treat - alpha and beta blockers, high salt diet, surgery?
What is conn’s syndrome referred to as?
Endocrine hypertension. Primary hyperaldosteronism
What are the features of Conn’s syndrome?
High Bp (often in young people with unexpectedly high Bp)
low K+
Metabolic alkalosis
Why would you request a CT scan with someone with Conn’s syndrome?
To look for tumour - likely cause is adrenal adenoma.
Describe congenital adrenal hyperplasia
Usually a 21 hydroxylase deficiency - required in the cortisol production chain, also linked in to aldosterone production and androgen production.
In children causes low aldosterone - causes salt wasting,
and inaproriate levels of androgen in utero, causing pseudohemaphodism, short stature, hirsutism
In adults - increased androgen. Impaired fertility
What test would confirm a diagnosis of congenital adrenal hyperplasia?
Raised 17α OH progesterone before and after synacthen - build up as needs 21 hydroxlase to progress further, which is lacking in the condition.
How would you treat congenital adrenal hyperplasia?
Hormone replacement therapy
corrective surgery for sexual characteristics
Describe how calcium and parathyroid hormone interact.
Low calcium stimulated parathyroids to produce PTH which causes:
- Bone resorption - increasing calcium
- Stimulates the kidneys to increase calcium reabsorption
- Allows the kidneys to convert Vit D into the active 1,25 hydroxy vit D3 - which causes increased absorption int he gut.
What are the three types of hyperparathyroidism?
Primary - increased PTH produced due to adenoma/hypertrophy of the parathyroid gland itself
Secondary- increased PTH produced due to hypocalcemia - compensatory
Tertiary - Chronic hypocalcemia causing autonomous high PTH
What are the features of hyperparathyroidism?
Often asymptomatic
Picked up incidentally
If hypercalcemia - Stones, groans, abdo moans and psychiatric overtones.
How do you test for hyperparathyroidism - how do you distinguish between the 3 types?
24 hour urine levels + blood tests
Primary - High PTH. High Ca. High Ca in urine. Low PO4
Secondary - High PTH. Normal Ca. High PO4
Tertiary - High PTH. High Ca. Low PO4
Someone with metastatic cancer is seen who has signs of hypercalcamia - what would you suspect they have?
Malignant hypercalcaemia. Malignancy causes increased bone resorption, increasing calcium in the blood.
What can cause hypoparathyroidism?
Post surgery or radiotherapy to glands
Hypomagnesamia - causes release of stored calcium in cells (in sarcoplasmic reticulum), so there is high Ca which inhibits release of PTH
What are the features of hypoparathyroidism?
Neuromuscular excitability
Tingling
Epileptic
ECG abnormalities
What is Pseudohypoparathyroidism?
Resistance to PTH.
eg. Albright’s hereditary dystrophy
Despite a high PTH there is low Ca.
Can give Vit D to help Ca absorption
What is osteomalacia?
Low Vit D causes reduced Ca uptake. Despite High PTH there isn’t enough - bone problems
What is the endocrine axis of gonadal hormones?
Hypothalamus produces GnRH, stimulates the anterior pituitary to produce LH and FSH
In girls: LH stimulates follicles to priduce testosterone which is converted rapidly into oestrogen and inhibin is produced which has negative feedback on hypothalmus and pituitary. FSH stimulates oestrogen conversion.
In Males: LH stimulates lydig cells to produce testosterone.
FSH stimulates sertolli cells to mature sperm.
What occurs in male hypogonadism?
Primary eg. Klinfeller’s. - impaired sperm production, androgen deficiency.
Secondary eg. delayed puberty, obesity, drugs.
- Low testosterone, inappropriately low/normal FSH and LH levels.
What are the features of male hypogonadism?
Small or absent testes. Gynaecomastia. Infertility. Reduced hair. Eunuchoid body proportions.
What test can confirm hypogonadism?
9am blood test - will show reduced testosterone yet high LH and FSH.
What is Foetal androgen deficiency?
Embryological lw testosterone levels/resistance.
Male chromosomes, but born phenotypically female. Primary amenorrhea.
Treat? Orchidectomy and give oestrogen replacement therapy - grow up as girls.
What is precocious puberty and how is it treated?
Rare in boys, mostly girls.
Premature puberty - raised LH and FSH compared to what is should be for their bone age.
Treat - give LHRH which downregulates the LH/FSH produced.
What causes premature ovarian failure?
Idiopathic
Post Chemo
What are the signs of premature ovarian failure?
Hypergonadotrophic amenorrhoea under the age of 40.
High FSH levels
Treat: give oestrogen replacement therapy
What does androgen excess in females cause?
Ovarian dysfunction
hirsutism
Acne
What are the causes of androgen excess in females?
PCOS
Ovarian tumour
What can be used to treat PCOS?
Metformin (diabetes drug) helps control cysts
Oestrogen therapy
Fertility help
Describe the hypothalamic-pituitary-thyroid axis
Hypothalmus produces TRH whcih stimulates anterior pituitary to produce TSH which causes thyroid to produce T3 and T4. T4 is then converted to T3 in peripheral tissues.
T3 causes increase in metabolism, growth and development. It increases the catecholamine effect.
Production of T3 and T4 is iodine dependant.
What are the features of primary hypothyroidism?
Low T3 and T4 production. Weight gain Low metabolic rate Sensitive to cold Sluggishness Poor memory
Test shows low T4 despite high TSH.
What is given to treat hypothyroidism?
Thyroxine
What are the features of hyperthyroidism?
eg. Graves diesease High metabolic rate Weight loss Sensitivity to heat Hyperactivity Palpitations
What would hormone levels be like in hyperthyroidism?
High free T4, high T3, suppressed TSH if overt
What treatment is available for hyperparathyroidism?
Carbimazole (reduces T3 and T4 production)
Radioactive iodine
Surgery
What is a goitre?
Enlarged thyroid - looks like swelling on the neck
