Endocrinology conditions Flashcards
Embryology
Hypothalamus:
- develops from neuroectoderm of the forebrain
- GNRH, TRH, CRH, GnRH, dopamine, somatostatin
Neurohypophysis:
- evagination of ventral hypothalamus and 3rd ventricle
- vasopressin, oxytocin
Adenohypophysis:
- derived from Rathke’s pouch - ectoderm - oropharynx
- ACTH, LH, FSH, TSH, GH, PRL
Hypothalamic-pituitary axis
anterior pituitary hormones
Stimulatory hypothalamic hormones → anterior pituitary hormones |— inhibitor hypothalamic hormones
Examples:
GnRH → FSH, LH
GHRH → GH
|— somatostatin
TRH → TSH and prolactin
|— somatostatin for TSH and dopamine for both
VIP, PHI → prolactin |— dopamine
CRH → ACTH
Posterior pituitary
Arginine vasopressin - controls fluid balance
Oxytocin
Clinical presentations of pituitary tumours
Hormone hyper-secretin
Space occupying lesion:
→ headaches
→ visual loss (field defects)
Hormone deficiency states:
→ interference with surrounding normal pituitary
Tumours of the anterior pituitary can cause syndromes of hormone excess
ACTH → Cushing’s disease (pituitary problem causing excess cortisol)
TSH → secondary thyrotoxicosis
GH → acromegaly
LH/FSH → (non-functioning pituitary tumour)
PRL → prolactinoma
Pressure on optic chiasm
Pressure on the optic chiasm caused by a tumour can lead to:
→ field of vision loss - bitemporal hemianopia
Non-functioning pituitary tumours
→ majority of all pituitary tumours
→ no syndrome of hormone excess produced
→ cause symptoms due to space occupation
- headache
- visual field defects - as pressure on optic chiasm
- pituitary function - deficiency of hormones
→ treatment
- endoscopic trans-sphenoidal hypophysectomy - surgery done through the nose
→ radiotherapy
→ no effective medical therapy
Acromegaly
→ enlarged extremities
→ usual onset at age 40-60 (gigantism if pre-puberty)
→ occasionally familial in association with MEN I
→ mortality is twice that of the general population
Presents as :
- signs of GH symptoms
- pressure symptoms
- field defects
- loss of anterior pituitary function
Acromegaly symptoms
- course facial features
- soft tissue thickening
- excessive sweating
- hypertrichosis
- carpel tunnel syndrome
- headaches
- thick lips, enlarged nose
- spade like hands
- frontal bossing
- macroglossia
- prognathism and separation of teeth
- snoring and obstructive sleep apnoea syndrome
- enlargement of supraorbital ridges
- kyphosis
- goitre
- myopathy
- hypertension, diabetes mellitus, heart failure
Tests for acromegaly
Diagnosis:
→ raised insulin like growth factor 1 (IGF1) - integrated effect of growth hormone (GH) at tissue level
→ oral glucose tolerance test (GTT) with GH measurement - GH should suppress completely
→ imaging - MRI pituitary with Gadolineum contrast
Acromegaly treatment
→ endoscopic transnasal transsphenoidal surgery
→ somatostatin analogues - Octreotide, Lanreotide, Pasireotide
(somatostatin inhibits GH secretion)
→ radiotherapy
→ growth hormone receptor antagonist - pegvisomant
→ dopamine agonist therapy - bromocriptine, cabergoline - less effective
(Dopamine inhibits GH secretion)
Prolactin physiology
→ prolactin secretion is toxically inhibited by one or more prolactin inhibiting factors (PIFs)
→ dopamine is the most important of these
> originates from hypothalamic tubero-infundibular tract and reaches lactotroph via hypophyseal portal vessels
Clinical manifestations of hyperprolactinaemia
Women:
- galactorrhoea 30-80%
- menstrual irregularity
- infertility
Men:
- visual field abnormalities
- headache
- galactorrhoea (uncommon)
- impotence
- anterior pituitary malfunction
Prolactinoma
→ prolactinoma is the second most common pituitary tumour after chromophobe adenoma
→ anything that interrupts the dopamine inhibitory pathway can result in hyperprolactinaemia
→ hyperprolactinaemia is often drug induced - particularly by antipsychotic medication
Hyperprolactinaemia Treatment
→ dopamine inhibits prolactin secretion
→ prolactin suppression can shrink tumour
→ dopamine agonists - bromocriptine, cabergoline, quinagolide
→ surgery
→ radiotherapy
Causes of hypopituitarism
- pituitary tumours
- pituitary surgery
- pituitary radiotherapy
- pituitary infarction - Sheehan’s syndrome
- pituitary apoplexy
Cushing’s disease
→ too much cortisol
→ often caused by taking too many steroids or by anterior pituitary tumour
Symptoms:
- increased fat on chest and tummy but slim arms and legs
- a build-up of fat on the back of the neck ‘buffalo hump’
- red, puffy, round face
- bruises easily
- large purple stretch marks
- weakness in upper arms and thighs
- depression and mood swings
- low sex drive
Cushing’s syndrome clinical features
Due to pituitary adenoma = Cushing’s disease
Clinical features:
- ‘moon faces’
- interscapular fat
- central obesity weight gain
- proximal myopathy
- hypertension
- malaise
- psychoses
- hirsuitism and acne
- skin thinning
- oligo-or amenorrhoea
- bruising
- polyuria, nocturia
- decreased libido
- purple ‘angry’ striae
- backache / kyphosis
- renal caniculi
Cushing’s syndrome test and diagnosis
Screening:
→ 24 hour urinary free cortisol
→ overnight Dexamethasone suppression test
Confirming:
→ low dose Dexamethasone suppression
Source:
→ ACTH measurement
→ high dose dexamethasome - 50% fall in 80-90% with pituitary disease
→ CRF test - normal or exaggerated response of ACTH in Cushing’s disease
Cushing’s syndrome - tumour localisation
Tumour localisation:
Pituitary
→ MRI
→ petrosal sinus sampling +/- CRH
Adrenal
→ MRI
→ selective venous catheterisation
Ectopic
→ MRI/CT
Chushing’s syndrome - treatment
Surgical:
→ transphenoidal, adrenal
Medical:
→ adrenolytic therapies may be used in preparation for surgery (metyrapone, mitotane, ketaconazole, etomidate)
→ Chemotherapy - oat cell, carcinoid
→ Radiotherapy
Addison’s disease symptoms - Primary adrenocortical failure
Symptoms:
- weakness and fatigue
- anorexia and weight loss
- abdominal pain
- postural hypotension
- pigmentation due to ACTH hypersecretion (this makes skin look tanned)
Addison’s disease - aetiology and presentation
Addison’s disease - primary hypo-adrenalism
Aetiology:
- most cases are now autoimmune
- females twice as likely to have it
- previously TB more common
- occasionally direct tumour invasion or metastasis, AIDS
Presentation:
- lethargy, weakness, postural hypotension, weight loss, abdominal pain, nausea and vomiting
- pigmentation - at sites of trauma, buccal mucosa, axillae, groins, genitalia, skin creases, scars
Addison’s disease - biochemistry, investigation and treatment
Biochemistry:
- serum sodium normal or reduced
- serum potassium increased
- urea increased (dehydration)
- may be hypoglycaemic
Investigation:
- basal cortisol
- adrenal antibodies
- short synacthen test
Treatment:
- emergency - IV fluids, IV hydrocortisone 100mg stat, then IV hydrocortisone 50mg 6 hrly or as infusion
- replacement - hydrocortisone per oral 20mg/day in divided doses, fludrocortisone 50 to 200mg/day
Hyperthyroidism
- syndrome resulting from excess of free T4 and/or free T3
- more common in women
- hyperthyroidism indicates thyroid gland overactivity
- T3 toxicosis (raised FT3 but normal FT4) is earliest phase and is found in some cases
Causes of hyperthyroidism
Primary hyperthyroidism:
→ Graves’ disease (large majority of all cases of hyperthyroidism)
→ toxic multinodular goitre
→ toxic adenoma
Thyrotoxicosis without hyperthyroidism:
→ excessive T4 administration
→ thyroiditis - post-partum, de Quervain’s, amiodarone induced thyrotoxicosis
→ new immune therapy drugs
Clinical features of hyperthyroidism
Symptoms:
- weight loss
- increased appetite
- heat intolerance and sweating
- fatigue and weakness
- hyperactivity, irritability, insomnia, palpations
- tremor
- diarrhoea
Physical signs:
- lid lag, lid retraction
- tremor
- hyperreflexia
- tachycardia, AF (in over 50s)
- warm moist skin, hair loss, onycholysis
Hyperthyroidism - treatment
→ antithyroid drugs - carbimazole, propyl thiouracil
→ radioactive iodine therapy
→ thyroidectomy
Common causes of primary thyroid failure
- autoimmune thyroiditis
- idiopathic atrophy
- previous Rx with radioiodine or thyroidectomy
- iodine deficiency
- antithyroid drugs
- subacute and silent thyroiditis
Clinical features of primary thyroid failure
- onset may be insidious
> non-specific and vague symptoms - presenting symptoms and signs diverse
- reflect widespread action of thyroid hormones
- reflect widespread action of thyroid hormones
- in mild disease symptoms and signs are often absent
- tiredness and lethargy
- weight gain
- control intolerance
- hyperlipidaemia
- Bradycardia
- delayed relaxation of reflexes
- aches and pains
Hypothalamic-pituitary gonadal (HPG) axis
Hypothalamus → GnRH → pituitary → LH and FSH → testis → testosterone → back to hypothalamus or pituitary
Or
Hypothalamus → GnRH → pituitary → LH and FSH → ovary → oestrogen and progesterone → back to hypothalamus or pituitary
HPG dysfunction
Problems with sexual maturation/secondary characteristics:
- precocious puberty
- short stature
- delayed puberty
Men
- hypogonadism
- infertility
- erectile dysfunction
Women
- infertility
- secondary amenorrhoea
Pituitary causes
Gonadal causes
Summary of endocrinological diseases
Pituitary hyper-secretion:
- acromegaly
- Cushing’s disease
- prolactinoma
Pan-hypopituitarism
- HPA axis
(adrenal hyper-secretion - Cushing’s)
(adrenal hypo-function - Addison’s)
- HPT axis
- HPG axis
