Topic Two: Endocrine Function - Thyroid & Adrenal Dysfunction Flashcards
What is released from the thyroid gland and why?
Thyroid hormones such as thyroxine T4 and the more active tri-iodothyronine (T3) are released from the thyroid gland in response to thyroid stimulating hormone. (TSH)
Where is TSH released from?
Thyrotrophs in the anterior pituitary in response to thyrotropin releasing hormone (released by hypothalamic cells)
What is thyroid also known for releasing?
Calcitonin - Key hormone for calcium regulation
What does thyroid bind to?
Thyroid-binding globulin (TBG)
Simply, how are thyroid hormones synthesised?
Thyroid hormone is produced by attaching iodine to the tyrosine amino acids in the thyroglobulin protein.
When modified, iodinated tyrosine residues are then cut out of the protein to produce mature thyroid hormone
Describe simple differences between hyper and hypo states RE Thyroid gland.
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What is a goitre?
An enlarged thyroid.
When can goitre occur?
Hyperthyroid, Hypothyroid and Euthyroid states
Goitres can be nodular or diffuse
Enlargement is proportional to degree of dysfunction.
What are some symptoms of a result of hypo-metabolic state?
- fatigue and low energy levels
- depression
- slow heart rate
- unexplained weight gain (despite reduced appetite)
- intolerance to cold temperatures
- fatigued and aching muscles
- dry, coarse skin
- puffy face (sometimes called myxoedema) & tongue enlargement
- hair loss (brittle hair)
- constipation & flatulence
- problems with concentration & memory
- goitre (enlarged thyroid gland).
- heavier menstrual bleeding, abnormal ovulatory cycles
How does lack of iodine affect the onset of hypothyroidism?
Lack of iodine in diet can cause hypothyroidism so food (salt) contains supplements. Dietary insufficiency still a problem in developing countries – usually inland, mountainous areas or areas with high rainfall.
What is congenital hypothyroidism?
This type of hypothyroidism develops in utero or shortly after birth during the neonatal period.
It is usually the thyroid gland itself that is affected.
The most common cause for thyroid dysgenesis can be due to ectopic causes such as maternal TSH autoantibodies crossing into the fetal circulation or a maternal iodine deficiency.
Congenital hypothyroidism occurs in developing countries usually because of?
Maternal hypothyroidism - due to dietary iodine deficiency.
If hypothyroidism is untreated what does it result in?
Cretinism
- Poor growth
- Mental impairment
- Swollen tongue
- Umbilical hernia
Thyroid hormone is necessary for brain development.
Causes of acquired hypothyroidism?
Iodine deficiency
Hasmimoto’s disease
What is Hashimoto’s thyroiditis?
Inflammation of the thyroid gland; autoimmune
Also called Hashimoto’s disease, chronic lymphocytic thyroiditis, autoimmune thyroiditis
What is the cause of Hasmimoto’s thyroiditis?
Ageing is a risk Genetic component (family history of autoimmune disease).
What are the complications of Hashimoto’s thyroiditis?
Goitre
Emotional (depression, reduced libido)
Heart conditions (increased LDL)
myxoedema
What is myxoedema?
- Sever form of hypothyroidism: occurs when left untreated
- swollen, puffy skin appearance
- myxoedema coma is life threatening - 80% mortality rate
- Develops due to an increased production of connective tissue components.
Symptoms of myoxedema?
- Decreased mental activity
- Hoarseness
- Increased sleep
- Cold intolerance
- Dry Skin
- Brittle hair
What are some signs of myoxedemia?
- Hypothermia
- Bradycardia
- Hypotension
- Physical features consisting of long standing hypothyroidism
- Disorders of muscular function (paralytic ileus, urinary retention, atonic bowel with faecal impaction)
What are physical features of long standing hypothyroidism?
- thick doughy appearing skin
- Periorbital oedema
- Large tongue
- Alopecia
What is treatment of hypothyroidism?
- Iodine replacement where deficient
- Oral thyroxine
What are causes of hyperthyroidism/thyrotoxicosis?
- Graves disease
- Multinodular goitre
- Adenoma
- Ingestion of excessive thyroid hormone
- Iodine containing agents (can also cause hypothyroidism)
- Thyroid storm - exaggerated manifestation of thyrotoxicosis.
Note the manifestations of hyperthyroidism resulting from a hypermetabolic state.
- Lipolysis
- Increased glucose absorption from GIT
- Increased protein breakdown: muscle fatigue, skin changes
What are some manifestations of hyperthyroidism.
- Increased sympathetic activity
- Restlessness, irritability, fine muscle tremor
- Increased heart rate/cardiac output
- Palpitation, atrial fibrillation or tachycardia
- Weight loss despite increased appetite
- Heat intolerance and excessive bleeding
- Exophthalmos (bulging of the eye)
What is Graves disease?
An autoimmune disease.
- Stimulation of the thyroid gland by thyroid stimulating antibodies that bind normal TSH receptors
- Usually very high thyroxine levels despite low TSH
What is the onset of Graves disease?
20-40years, 8 times more common in women - familial tendency.
What is a visual symptom that is usually indicative of Graves disease?
Opthalamopathy
- It occurs in 1/3 cases
- It is an enlargement and paralysis of extra orbital muscles, optic nerve damage
A manifestation of hyperthyroidism can also be nodules - lumps on an otherwise normal gland.
Describe what the lumps are like.
- usually benign (>95%) but can sometimes be cancerous
- 3x more common in women than men
- sometimes fluid filled cysts
- often asymptomatic - if there are more nodules there can be an increase in T4 (thyroxine)
- multinodular goitre can cause problems with swallowing and breathing.
What are some drugs used to treat hyperthyroidism?
- Thioamides e.g. propylthiouracil (PTU)
- Iodide
- Iopdate
The drugs that are used to treat hyperthyroidism commonly do what?
- Inhibit thyroid hormone production
- Inhibit iodination of tyrosine and thyroid hormone release, decrease size and vascularity of the thyroid
- Radioactive iodine concentrates in, damages thyroid
- Supress conversion of T4 to T3 in tissues
- beta blockers to control tachycardia and cardiac abnormalities.
What is the parathyroid?
A group of four small glands in the posterior of the thyroid
What does the parathyroid do?
- Produces parathyroid hormone PTH
- Increases blood calcium (ca2+) levels
- Works together with Calcitonin which decreases calcium levels
When PTH increases blood calcium levels - what else occurs?
- Increased resorption of bone calcium (stimulate osteoclasts cell activity)
- Reduced renal calcium excretion
- Increased Ca2+ and P absorption from the gut through stimulation of vitamin D production
What is hypoPARAthyroidism?
- A low level of parathyroid hormone
- Very rare
- Usually due to damage or removal following thyroid surgery
- leads to hypocalcaemia (interferes with muscle contraction and nerve conduction)
- Can be life threatening
- Treated with supplements of calcium and vitamin D
What is the hypocalcaemia mneomic?
Cats go numb
What is cats go numb?
Convulsions, arrhythmias, tetany and numbness in the hands and feet and around the mouth
Cats go numb - occurs why?
Due to an increased neuromuscular excitability.
Calcium normally blocks sodium channels so removing it lowers the threshold for depolarisation
Heart rate and contractility also decrease.
What are the two signs of hypocalcaemia?
Chvostek’s sign - Tapping the inferior portion of the cheek bone will produce facial spasms
Trousseau sign - Latent tetany - elicits carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic.
What is hyperparathyroidism?
- Elevation of parathyroid hormone
- Primary hyperparathyroidism = issue with the gland directly (usually associated with a benign tumour or hyperplasia
- Secondary = problem lies elsewhere (usually issues that cause low Ca2+ and hence reduced negative feedback.)
Regarding secondary hyperparathyroidism and a low Ca2+ concentration - what is this usually the result of?
- Kidney failure - resulting in reduced VIT D activation and hence low Ca2+ absorption from the gut
- Malabsorption conditions of the gut
- Low calcium in diet
What are the clinical features of hyperparathyroidism?
- Hypercalcaemia
- Hypophopshataemia
- Hypercalciuria
- Bone resorption, leading to weak bones and pathological fractures.
- Myalgia (muscle pain)
What are the symptoms of hyperparathyroidism?
- Fatigue and anaemia
- Muscle weakness and joint pain
- Constipation with nausea
- Frequent urination, sometimes bloody
- Mood change with confusion
- Kidney pain due to stones
- Hypertension
How do you treat hyperparathyroidism?
- Drug options are not conclusively effective
- Surgery to remove tumours (primary hyperthyroidism)
- 2ndary hyperthyroidism - identify and treat cause
Remind me - What hormones come from the adrenal cortex?
- Mineral corticosteroids (aldosterone) from the zona glomerulosa
- Glucocorticoids, particularly cortisol from zona fasciculata
- Sex hormones from zona reticularis (androgens and oestradiol)
Remind me - What hormones comes from the adrenal medulla?
- Adrenaline (epinephrine) - 90%
- Noradrenaline (norepinephrine) - 10%
Why are glucocorticoids released?
As part of the activation of the HOPA axis in time of stress and trauma.
Why are mineralocorticoids released?
As part of the regulation of the water balance and blood pressure.
Regarding a adrenal cortical insufficiency what is a disease that is categorised with this insufficiency?
Addison’s disease
An autoimmune disease where the adrenal cortex becomes immunogenic and is destroyed
What are manifestations regarding Addison’s disease?
- Mineralocorticoid deficiency
- Glucocorticoid deficiency
- Hyperpigmentation
Addison’s disease: Mineralocorticoid deficiency means?
- Decrease in aldosterone
- Loss of sodium
- Water loss
= Hyponatraemia, loss of ECF, decreased cardiac output, hyperkalaemia.
Low BP can cause dizzy spells on standing
Addison’s disease: Glucocorticoid deficiency means?
- Decrease in cortisol
- Decrease in gluconeogenesis
- Decrease in stress hormone
= Hypoglycaemia, fever, anorexia, nausea, vomiting, poor stress tolerance
Addison’s disease: Hyperpigmentation means?
From elevated ACTH and NSH levels because there is a lack of negative feedback
- The preprotein that makes ACTH also makes MSH (melanocyte stimulating hormone)
In regard to primary, secondary and tertiary insufficiencies what is Addisons?
A primary insufficiency - there is an issue with the gland itself.
A secondary insufficiency would mean a pituitary problem (usually hypopituitarism or surgical removal of the pituitary gland)
A tertiary insufficiency is incredibly rare, and is due to a hypothalamic defect.
Glucocorticoids are used to treat adrenal deficiency. Why?
Replaces endogenous cortisol with synthetic long acting equivalents e.g. hydrocortisone, prednisone
These vary in duration of action, half-life, salt-retention capacity and ability to penetrate lipid barriers
What are side effects of glucocorticoid use in adrenal deficiecncy?
Side effects are related to metabolic, catabolic, immunosuppressive and other actions of glucocorticoids.
Long-term glucocorticoids can lead to osteoporosis, diabetes, muscle wasting, growth inhibition in children.
Sudden cessation of long-term glucocorticoid therapy can also lead to acute adrenal insufficiency.
Mineralocorticosteriods are used to treat adrenal insufficiency. Why?
E.g. Fludrocortisone
Replace lost endogenous aldosterone
Fludrocortisone has long duration of action & significant glucocorticoid actions
What is a manifestation of excess cortisol?
Cushing’s syndrome
What are the four cause of excess cortisol?
Pituitary – excessive ACTH by a tumour of pituitary (called Cushing’s disease)
Adrenal – adrenal tumour
Ectopic Cushing – nonpituitary malignant tumour
Iatrogenic Cushing syndrome – long-term therapy with glucocorticoids
What is pseudo Cushing’s syndrome?
Similar signs and symptoms of Cushing’s syndrome, including elevated cortisol, but not due to defects in hypothalamic-pituitary axis (HPA). Causes include chronic stress, depression, polycystic ovary syndrome and excessive alcohol consumption.
What are some manifestations of excess cortisol?
- Manifestations of excess cortisol include:
- Hyperglycaemia
- gluconeogenesis and glucogenesis
- Skin thinning and bruising (purpura)
- Decreased immune response
- Altered fat metabolism
- Buffalo hump, abdominal fat deposition
- Abdominal striae
- Muscle weakness due to protein breakdown
- Bone protein loss and altered calcium metabolism may result in osteoporosis
- Sodium retention increasing blood volume, hypokalaemia and hypertension
- Hirsutism, mild acne, amenorrhoea and infertility
Emotional disturbances
What are drug treatments for adrenal gland hypersecretion?
- Receptor antagonists
- Synthesis inhibitors
- Surgical removal of the adrenal glands
What is pheochromocytoma?
- Tumour, most commonly located in adrenal medulla
8% are malignant
Produce and secrete excessive amounts of catecholamines (adrenaline & noradrenaline)
- Results in periods of hypertension and can cause hypertensive crisis
Symptoms
Headaches, nervousness, facial tremour, weakness, fatigue, weight loss, variable BP
What is the treatment for pheochromocytoma?
Treatment is surgical excision
Non-selective alpha-adrenergic antagonists (eg phenoxybenzamine) are used to control severe hypertension prior to surgery
