Endocrinology II - HPA axis Flashcards
Thyroid gland (3)
Largest endocrine gland
Develops from 1st and 2nd pharyngeal pouches near base of the tongue
4 parathyroid glands are distinct and secrete parathyroid hormone
What are the structure and function of follicles in the thyroid?
Follicles filled with secretory substance - colloid
Colloid made up of thyroglobulin and iodine, contains thyroid hormones
Secretes 4 hormones:
- Thyroxine (T4)
- Triiodothyronine (T3)
- Reverse T3 (rT3)
- Calcitonin (parafollicular cells)
What are the effects of thyroid hormone on the heart?
Promote normal cardiac output
Maintain heart rate and stroke volume
What are the effects of thyroid hormones on the bones?
Maintain normal growth and maturation
What are the effects of thyroid hormones on the brain?
Increase synapsis
Increase myelination
Increase dendrites
What are the effects of thyroid hormones on the integumentary system?
Proliferation of skin cells
Hair and nail growth
Skin hydration
What are the effects of thyroid hormone on the GIT?
Promote normal GIT motility and secretions
What are the effects thyroid hormones have generally/metabolically?
Increase oxygen usage
Lipolysis
Heat production
Glycolysis
LDL uptake
Increase BMR
What is the HPT axis?
Hypothalamus is stimulated, releases TRH
TRH stimulates the pituitary gland causes release of TSH
TSH stimulates the thyroid gland to release T3, T4 which is sent to target tissues
What is hyperthyroidism? Prevelance?
Overactive thyroid gland, producing excess amount of thyroid hormone
Affects 1-2% of the population
What is thyrotoxicytosis?
Wider term that includes any condition in which the body has an excess of thyroid hormones
What is primary hyperthyroidism?
One or more of the parathyroid glands produces too much thyroid hormones
Results in high T3/T4, lower TSH
What is secondary hyperthyroidism?
Due to pathology of hypothalamus or pituitary gland, the pituitary gland produces excess TSH
Results in high TSH and high T3/T4
What are the different causes of primary hyperthyroidism?
- Grave’s disease
- Toxic adenoma
- Toxic multinodular goiter
- Thyroid cancer
- Drugs (iodine excess)
What are the causes of secondary hyperthyroidism?
- Pituitary adenoma
- Gestational thyrotoxicosis
What are the symptoms of hyperthyroidism? What is a way of remembering it?
SWEATING acronym
Sweating
Weight loss
Emotional lability
Appetite increased
Tremor/tachycardia
Intolerance of heat/irregular menstruation/Irritability
Nervousness
Goiter/GI problems
What is Grave’s disease? incidence? (4)
Autoimmune disease of thyroid
Most common cause of hyperthyroidism
Caused by increased levels of thyroid stimulating immunoglobulins
Most common incidence 20-40 yrs
What are the symptoms of Grave’s disease?
Thyroid eye disease/Graves ophthalmology
Thyroid acropachy - clubbing/swelling of the digits
Dermopathy - thickening of skin on lower tibia, and oedema on pretibial portion of leg
What is the pathophysiology of Graves’ ophthalmology? Incidence
TRAb - TSH receptor antibodies binds to TSH receptor antigen > T cell cytokines > fibroblasts GAG deposition
Affects 50% of Graves’ patients
More common in smokers
What are the symptoms to Graves’ ophthalmology mneumonic?
NO SPECS
No symptoms
Only ocular irritation
Soft tissue involvement
Proptosis
Extraocular muscle involvement
Corneal exposure and ulceration
Sight loss
What is the treatment of Graves ophthalmology?
Lubrication - artificial tears
Selenium
IV methylprednisolone
Orbital radiotherapy
Surgery
Toxic multinodular goitre/Plummers disease (prevalence, symptoms)
Second most common cause of hyperthyroidism
Middle aged/elderly
Iodine deficiency
Ophthalmology extremely rare
Large nodular goitre - may be retrosternal
May be present for years
Toxic adenoma (age, cause)
Patients are younger than with toxic multinodular goiter
Functioning nodule secreting T3 and T4
Infiltrative ophthalmology never present
Almost always benign
How may different blood results give different diagnoses?
Decreased TSH and normal T3 and T4 = subclinical hyperthyroidism
Decreased TSH and increased T3 and T4 = Primary hyperthyroidism
Increased TSH and increased T3 and T4 = secondary hyperthyroidism
What thyroid autoantibodies may be present in autoimmune conditions of the thyroid - Graves’ disease?
Thyroid stimulating hormone receptor antibodies (TSHR-Ab)
Thyroid stimulating immunoglobulin (TSI)
Thyroid peroxidase antibodies (TPO)
What is thyroid storm/thyrotoxic crisis? How common, mortality?
Acute, life threatening complication of hyperthyroidism
Rare but 8-25% mortality with treatment
What are the symptoms and risk factors of thyroid storm?
Symptoms:
- CNS - restlessness, delirium, psychosis, coma
- Fever - >38C
- Tachycardia - 130+, atrial fibrillation
- Chronic heart failure (Pulmonary oedema, cardiogenic shock)
- GIT - nausea, vomiting, diarrhoea
Risk factors:
- Acute infection
- Recent surgery
- Withdrawal of anti-thyroid drugs
What is hypothyroidism? prevalence?
Common endocrine condition caused by deficiency in thyroid hormone
10x more common in females
1-4 per 100 in UK
What are the types of hypothyroidism?
Primary: when thyroid gland does not release enough thyroid hormones
Secondary: when pituitary gland does not release enough TSH
Tertiary: when hypothalamus does not release enough TRH
What are the causes of primary and secondary hypothyroidism?
Primary:
- Hashimoto’s thyroiditis
- Thyroidectomy
- Iodine deficiency
- Drugs
Secondary:
- Hypopituitarism
- Congenital
How may primary and secondary hypothyroidism present in plasma levels?
Primary: low T3 and T4, low TSH
Secondary: low T3 and T4, high TSH
What are the symptoms of hypothyroidism? Mneumonic (11)
MOM’S SO TIRED
Memory loss
Obesity
Malar flush/menorrhagia
Slowness - mentally and physically
Skin and hair dryness
Onset gradual
Tiredness
Intolerance to cold
Raised BP
Energy levels fall
Depression/Delayed relaxation of reflexes
What is the treatment for hypothyroidism?
Replacement of thyroxine
Levothyroxine - synthetic T4 - for primary hypothyroidism
Dose titrated up and down by 25 mcg. TSH checked every 2-3 months, then annually once stable
What is myxoedema coma? Symptoms, management?
Rare life threatening condition in patients with long standing severe untreated hypothyroidism
Hypoglycemia, hypothermia, hyponatremia, hypoxia, hypercarbia bradycardic, cognitive decline
IV levothyroxine. Electrolyte imbalances and hypothermia addressed
Adrenal glands - anatomy and embryological development
Paired gland on the superior pole of the kidneys
Capsule, parenchyma - cortex and medulla
Embryonic development:
- Cortex - develops from mesoderm
- Medulla - from neural crest cells
What are the regions of the adrenal cortex and medulla and what do they release?
ADRENAL CORTEX
Zona glomerulosa: aldosterone
Zona fasciculata: mainly glucocorticoid (cortisol), some androgens
Zona reticularis: mainly androgens, some glucocorticoids
ADRFENAL MEDULLA: release catecholamine - epinephrine and norepinephrine
What is the function of aldosterone (mineralcorticoid)?
Increases renal Na+ reabsorption, K+ secretion, and H+ secretion
What is the function of cortisol (glucocorticoid)?
Stimulate gluconeogenesis, inhibit inflammatory response, suppress immune response, enhance vascular responsiveness to catecholamines
What is the role of androgens (testosterone and estrogen)?
Bone density
Puberty
Sexual function
What is the HPA axis?
Hypothalamus is stimulated to release CRH
CRH stimulates the anterior pituitary gland to release ACTH
ACTH stimulates the adrenal cortex to release CORT
CORT plays into the negative feedback loop , acts on hypothalamus and anterior pituitary gland, reduce hormone secretion
What can cause abnormal secretion of cortisol?
Cushing’s syndrome (set of symptoms):
ectopic ACTH secretion, adrenal cortisol excess, exogenous steroids, pituitary steroids, pituitary ACTH excess
Cushing’s disease (when syndrome is caused by ACTH producing pituitary gland: pituitary ACTH excess
What are the symptoms of cushing syndrome? mneumonic
MOON FACIES
Menstrual disorders/moon facies
Osteopenia/osteoperosis
Obesity - central distribution of fat
Neurosis - depression/psychosis
Face - acne, hirsutism
Altered muscle physiology
supra-Clavicular and dorso-Cervical fat pads
Infection
Elevated BP
Skin - bruise easily
What are the investigations and treatment of cushing syndrome?
24 hour urine cortisol or low dose dexamethasone suppression
> abnormal > Cushing’s > Decreased = adrenal tumour, increased = pituitary/ectopic
Medical treatment - adrenal enzyme inhibitor (metyrapone/ketoconazole/mitotane)
Surgical treatment - trans sphenoidal surgery, bilateral adrenalectomy, radiotherapy
Addison’s disease - what is it, prevalance
Commonly caused by autoimmune destruction of whole adrenal cortex
More common in women
Common between 30-50 yrs age
Addison’s disease - symptoms and treatment
Loss of glucocorticoids> hypoglycaemia, anorexia, weight loss, nausea and vomiting, weakness
Mineralocorticoids >hyperkalaemia, metabolic acidosis, hypotension
Adrenal androgens > decreased pubic and axillary hair and decreased libido
Treatment: replace missing hormones
What is secondary adrenal insufficiency? and symptoms
Disorder of the pituitary gland. Decrease level of ACTH which lead to decrease production of glucocorticoids and androgens from adrenal gland although adrenal glands are not damaged
Symptoms same as addison’s:
- Loss of glucocorticoids: Hypoglycemia, anorexia, weight loss, nausea and weight loss
- Loss of mineralcorticoids: Hyperkalaemia, metabolic acidosis, hypotension
- Loss of adrenal androgens: Decreased pubic and axillary hair decreased libido
- no hyperpigmentation, less likely to have severe dehydration
What are the causes of secondary pituitary gland?
- Benign pituitary tumours
- Inflammation
- Previous pituitary surgery
- Suddenly stopping chronic corticosteroid use
