Endocrinology (Adrenal) Flashcards
cushings disease vs cushings syndrome
Cushings syndrome is a set of sign and symptoms due to prolonged exposure to glucocorticoids which may be endogenous or exogenous
Cushings disease is where a pituitary tumour secretes excess adrenocorticotropic hormone (ACTH) leading to the increased release of cortisol - leads to cushings syndrome
most common causes of exogenous cushings
most common causes of exogenous glucocorticoids
e.g. taking corticosteroids for too long
most common causes of endogenous cushings
ACTH-secreting pituitary adenomas are the most common endogenous cause of Cushing’s syndrome
ACTH-dependent cushings
These are endogenous causes that lead to inappropriately raised ACTH levels resulting in excess glucocorticoid production. They may be:
- Cushing’s disease – ACTH-secreting pituitary adenoma
- Ectopic ACTH-secreting tumours (e.g. small cell lung cancer)
ACTH-independent
These are endogenous causes that lead to excess glucocorticoid production despite having low or normal ACTH levels. They may be:
- Exogenous glucocorticoids
- A unilateral adrenal adenoma
- An adrenal carcinoma
presentation of cushings syndrome
- Moon face
- Truncal obesity
- Red face
- Buffalo hump
- Purple striae
- High glucose
- Acne
- Ostoeporosis
- Depression
- Easy burising
- Muscle weakness (proximal)
- irregular periods or amenorrhoea
- Hirsutism
Pituitary tumour: bitemporal hemianopia
Pseudo-Cushing’s syndrome
- Often due to alcohol excess, severe depression/anxiety, obesity, or poorly-controlled diabetes mellitus
- Avoidance of alcohol results in normal cortisol levels after a few days
investigations for cushings
Specific
- Overnight dexamethasone supression test
- 24-hour urinary free cortisol
Others
- FBC
- UEs - hypokalaemic metabolic alkalosis
- Blood glucose -raised
Imaging
- pituitary MRI
Dexamethasone suppression tests
Administering dexamethasone should lead to decreased cortisol secretion due to negative feedback on the hypothalamus and pituitary gland. This negative feedback should lead to reduced cortisol-releasing hormone (CRH) from the hypothalamus and ACTH from the pituitary, leading to low cortisol levels.
The dexamethasone suppression tests are based on this principle and help to localise where the problem is.
how many types of Dexamethasone suppression tests
2
- Low dose dexamethasone suppression test
- High dise dexamethasone suppression test
Low-dose dexamethasone suppression test
- Cortisol suppressed (low) – normal
- Cortisol not suppressed (high/normal) – Cushing’s syndrome
High-dose dexamethasone suppression test:
- This is done if the low-dose test shows Cushing’s syndrome may be present
- Cortisol suppressed and ACTH suppressed – Cushing’s disease
- Cortisol not suppressed but ACTH suppressed – adrenal adenoma
- Cortisol not suppressed and ACTH not suppressed – ectopic ACTH
Cortisol suppressed and ACTH suppressed
Cushings disease - pit adenoma
Cortisol not suppressed but ACTH suppressed
adrenal adenoma
Cortisol not suppressed and ACTH not suppressed
ectopic ACTH
management of cushings
1st-line: manage underlying cause, examples are:
- Cushing’s disease: transsphenoidal pituitary adenomectomy
- Ectopic ACTH: manage cause (e.g. chemotherapy/radiotherapy/surgery for cancer)
complications of cushings
- Diabetes mellitus
- Metabolic syndrome
- Hypertension
- Obesity
- Hyperlipidaemia
- Thrombophilia
Adrenal insufficiency
is characterised by insufficient steroid hormone production from the adrenal glands. There are usually reduced amounts of glucocorticoids (cortisol) and/or mineralocorticoids (aldosterone), which are both types of steroid hormones.
types of adrenal insufficiency
Primary
Secondary
Tertiary
Primary adrenal insufficiency (Addison’s disease):
- The problem is within the adrenal cortex itself leading to impaired steroid hormone synthesis and secretion
Secondary adrenal insufficiency:
The problem is with the pituitary gland and there is inadequate adrenocorticotropic hormone (ACTH) release, leading to impaired steroid hormone synthesis and secretion
Tertiary adrenal insufficiency:
The problem is with the hypothalamus and there is inadequate corticotropin-releasing hormone (CRH) release, leading to impaired steroid hormone synthesis and secretion
causes pf primary adrenal insufficiency
- Addison’s disease – around 80% of cases
- Trauma
- Tuberculosis
- HIV
- Congenital adrenal hyperplasia
pathophysiology of addisons
This describes the autoimmune destruction of the adrenal glands
Causes of secondary adrenal insufficiency
- Pituitary tumours – some can lead to hypopituitarism
- Trauma
- Radiotherapy
- Neoplasia
presentation of adrenal insufficiency
- Fatigue
- Weight loss
- Loss of appetite
- Hyperpigmentation:
- Craving salt
- Vague abdominal pain:
- Nausea and vomiting
- Loss of pubic hair:
- Orthostatic hypotension:
- Presenting in an Adrenal crisis
why hyperpigmentation in adrenal insufficiency
- Due to excess ACTH stimulating melanocytes
- Usually in palmar creases and buccal mucosa
adrenal insufficiency: loss of pubic hair
Loss of pubic hair:
Due to decreased androgen synthesis
adrenal insufficiency: orthostatic hypotension
Due to mineralocorticoid deficiency leading to fluid and electrolyte imbalances
investigations for adrenal insufficiency
Specific
- Morning serum cortisol
- ACTH stimulation test
General
- FBC
- glucose- may be low
- UEs - low sodium, high potassium and calcium
- ABG- metabolic acidosis
Morning serum cortisol and adrenal insuffiency
- usually between 8-9 am where cortisol levels peak
- A value of 100-500nmol/L warrants an ACTH stimulation test
ACTH stimulation test (also known as the short Synacthen test) and adrenal insufficiency
diagnostic test:
- Synthetic ACTH is given and plasma cortisol is measured before and 30 minutes after.
- Serum cortisol is usually <500 nmol/L and fails to rise
management of Addisons disease
replacement hydrocortisone + fludrocortisone
* Hydrocortisone is usually divided into 3 doses, with the highest dose in the morning
Addisonian crisis
life-threatening condition associated with an acute deficiency in steroid hormones, namely the glucocorticoid cortisol and, to a lesser extent, the mineralocorticoid aldosterone. It requires immediate emergency treatment.
causes of addisonian crisis
- Infections e.g. pneumonia, I illness
- Abrupt steroid withdrawal
- Physiological stress/pain
- Dehydration
- Emotional distress
- ## HYpoglycaemia
presentation of addisonian crisis
It is important to remember that adrenal crises can happen in people without Addison’s disease (e.g. those who suddenly stop taking long-term corticosteroids). Features may be:
- Haemodynamic instability – hypotension and tachycardia
- Malaise
- Fatigue
- Vague abdominal pain – acutely worsening, this suggests an adrenal crisis
- Low-grade fever
- Muscle pains and cramps
- Confusion
- Dehydration
- Loss of consciousness
management of addisonian crisis
- IM or IV hydrocortisone + IV rehydration with normal saline + treat underlying cause
- The doses of hydrocortisone used in an adrenal crisis are enough to exert mineralocorticoid effects, so fludrocortisone is not necessary.
*
avoidance of addisonian crisis
- Sick day rules- taking more steroids on sick days
- Steroids must not be stopped suddenly if they have been used for >2 weeks
- Perioperative ‘stress doses’ of steroids may be given to mitigate the risk of adrenal crises arising
Phaeochromocytoma (PCC)
- is a catecholamine-secreting tumour of the adrenal medulla composed of phaeochromocytes (chromaffin cells).
- The catecholamines are adrenaline, noradrenaline, and dopamine.
The classical features of a phaeochromocytoma
are episodes of:
* headaches
* sweating
* palpitations
* anxiety
* extreme hypertension.
* Excess catecholamine production can lead to potentially life-threatening hypertension or arrhythmia.
PCC risk factors
Risk Factors
- Family history
- MEN2
- VHL
- NF1
investigations for PCC
24-hour urinary metanephrines:
Elevated
management of PCC
First: stabilisation
- Alpha blocker and then beta blocker
Second: after stabilisation surgical resection of tumour
why alpha before beta blocker
- An alpha-blocker (e.g. phenoxybenzamine) is given before a beta-blocker before surgery
- Excess catecholamines can decrease blood volume, so alpha-blocker use allows for blood re-expansion. This reduces the risk of hypotension during surgery
- Starting a beta blocker first can lead to unopposed alpha stimulation which can precipitate a hypertensive crisis
Hyperaldosteronism
is characterised by excess levels of aldosterone and is the most common cause of curable secondary hypertension.
types of hyperaldosteorism
primary
secondary
primary hyperaldosteronism
- Most commonly due to bilateral idiopathic adrenal hyperplasia
- Secretion is independent of the renin-angiotensin-aldosterone system (RAAS)
Secondary hyperaldosteronism
Due to high renin levels, often due to renal artery stenosis, heart failure, liver failure, nephrotic syndrome, and diuretic use
Conn’s syndrome
is a form of primary hyperaldosteronism due to an adrenal adenoma. It was previously thought to be the most common cause, but recent studies demonstrate that bilateral idiopathic adrenal hyperplasia makes up most cases.
Renin-angiotensin-aldosterone system (RAAS)
The renin-angiotensin-aldosterone system (RAAS) system is a hormone system that regulates blood pressure, along with fluid and electrolytes. Reduced blood flow to the juxtaglomerular cells in the kidneys leads to the secretion of renin (an enzyme) into the circulation. The liver releases angiotensinogen, which is cleaved by renin to form angiotensin I. Angiotensin I is converted into angiotensin II by angiotensin-converting enzyme (ACE) predominantly in the lungs.
Angiotensin II leads to the following:
- Vasoconstriction of vascular smooth muscle – increases blood pressure
- Acts at the hypothalamus to stimulate ADH release and stimulates thirst
- Acts on the renal tubules to increase Na+ and Cl- reabsorption, water retention, and K+ excretion
- Acts on the adrenal gland cortex to release aldosterone
effect of aldosterone
Mineralocorticoids affect electrolyte and fluid balance, and aldosterone is the main endogenous mineralocorticoid. In summary:
- it retains sodium ions
- increases the excretion of potassium ions.
Pathophysiology of hypertension: Since the sodium ions are retained, water follows, increasing the water content in the body. As there is a larger volume of fluid in the circulation, the blood pressure increases.
presentation of hyperaldosteronism
Hyperaldosteronism should be considered in a patient with difficult-to-treat hypertension. Many patients may be asymptomatic. Features can be:
- Hypertension – the main feature
- Alkalosis – bicarbonate is elevated
Features of hypokalaemia:
- Polyuria
- Lethargy
- Tetany
- Muscle weakness
- Headaches
how to tell the difference betwen primary and secondnary hyperaldosteronism
Primary hyperaldosteronism
Plasma aldosterone/renin ratio is elevated
Secondary hyperaldosteronism
Plasma aldosterone/renin ratio is reduced
investigations for hyperaldosteronism
specific
- Aldosterone/renin ratio
- Adrenal CT - looking for hyperplasia
- Adrenal venous sampling
general
- UEs- hypokalaemia
Adrenal venous sampling (AVS) and hyperaldosteronism
Performed if the CT is normal. It can help to distinguish between bilateral idiopathic adrenal hyperplasia and an adrenal adenoma
Aldosterone/renin ratio:
- If raised: primary hyperaldosteronism is the likely diagnosis (as there is more aldosterone than renin)
- If reduced: secondary hyperaldosteronism is the likely diagnosis (e.g. due to renal artery stenosis as there is more renin than aldosterone)
Management
Primary hyperaldosteronism
- If bilateral adrenal hyperplasia: aldosterone antagonist is 1st-line (e.g. spironolactone/eplerenone)
- If an adrenal adenoma is present: consider surgery
management of Secondary hyperaldosteronism
1st-line: manage underlying cause (e.g. renal artery stenosis)
Congenital adrenal hyperplasia (CAH)
describes a group of autosomal recessive conditions characterised by impaired cortisol synthesis.
The most common form is due to a deficiency in 21-hydroxylase, which consists of cortisol deficiency, and androgen excess with or without aldosterone deficiency.
deficiency in 21-hydroxylase causes
cortisol deficiency, and androgen excess with or without aldosterone deficiency.
i.e. because cortisol cant be made from its precursor more androgen is produced
In summary, 21-hydroxylase is necessary for the synthesis of glucocorticoids and aldosterone from progesterone. A deficiency in 21-hydroxylase leads to a surplus of progesterone which is converted to extra testosterone to reduce its levels. This leads to an increased level of androgens, and a cortisol and aldosterone deficiency
presentation of CAH in girls
The severity of CAH depends on the degree of 21-hydroxylase deficiency. In severe cases, it can lead to salt loss (hyponatraemia and hyperkalaemia). Features in girls may be:
1) Features of virilisation (development of male physical traits) due to increased androgens:
- Ambiguous genitalia
- Male-pattern hair growth
2)Early puberty and early menarche
3) Adolescents/young adults may have oligo-/amenorrhoea
presentation of CAH in boys
1) Subtle hyperpigmentation:
- Due to increased ACTH secretion secondary to reduced cortisol
2) Salt-loss crises often happen within the first 2 weeks of life and are characterised by:
- Lethargy
- Dehydration
- Shock
- Hyponatraemia
- Hyperkalaemia
investigations for CAH
U&Es:
* May show hyponatraemia and hyperkalaemia due to adrenal insufficiency
Serum 17–hydroxyprogesterone:
* Raised in 21-hydroxylase deficiency
Pelvic ultrasound:
* To assess pelvic organs in cases of ambiguous genitalia (e.g. looking for the absence of a uterus)
Karyotyping:
Establishing patient’s chromosomal sex if they have ambiguous genitalia
managemet of CAH
Treatment involves glucocorticoids and fludrocortisone to account for the adrenal insufficiency
