Adrenal - Clinical Flashcards
What are the layers of the adrenal gland?
Cortex (GFR)
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
Medulla
What is secreted by the zona glomerulosa?
Mineralocorticoids - Aldosterone
What is secreted by the zona fasciculata in the adrenal cortex?
Glucocorticoids
What is secreted by the zona reticularis?
Sex hormones
What is secreted by the medulla of the adrenal glands?
Adrenaline/Noradrenaline
What is cushing’s syndrome?
The term used to describe the clinical state of increased free circulating glucocorticoid. It occurs most often following the therapeutic administration of synthetic steroids or ACTH (see below).
What groups are the causes of cushing’s syndrome divided into?
- ACTH dependent
- ACTH independent
What are causes of ACTH dependent cushing’s syndrome?
- Pituitary dependent (Cushing’s Disease)
- Ectopic ACTH production Tumours
- ACTH administration
What are non-ACTH dependent causes of Cushing’s Syndrome?
- Adrenal Adenoma’s
- Adrenal CArcinoma’s
- Glucocorticoid administration
- Alcohol induced pseudo-Cushing’s syndrome
What are ectopic causes of excess ACTH production?
- SCLC
- Carcinoid tumours
What are features of an ectopic source of ACTH production in someone with Cushing’s Syndrome?
- Pigmentation
- Hypokalaemic metabolic alkalosis
- Weight loss
- Hyperglycaemia
Classical features of Cushing’s are often absent
What is Cushing’s Disease?
Bilateral adrenal hyperplasia caused by an ACTH-secreting pituitary adenoma (ususally microadenoma)
What are symptoms of Cushing’s syndrome?
- Weight gain
- Depression
- Insomnia
- Irritability
- Psychosis
- Proximal weakness
- Amenorrhoea
- Hirsutism
- Poor Libido
- Polyuria/Polydipsia
- Erectile dysfunction
What are signs of Cushing’s Syndrome?
- Moon Face
- Plethora
- Acne
- Hirsutism
- Thin Skin
- Bruising
- Poor Wound healing/Skin infections
- Ostoporosis/Pathological Fractures
- Buffalo Hump
- Central Obesity
- Striae/Pigmentation
- Oedema
- Proximal myopathy
- Glycosuria
Why do individuals with Cushing’s Syndrome get abdominal striae?
There is an increase in hormones thought to have a catabolic effect on fibroblasts (essential to form the collagen and elastin needed to keep skin taut), leading to dermal and epidermal tearing
What else can cause a Cushingoid appearence apart from adrenal/pituitary causes?
Alcohol - pseudo-Cushing’s syndrome
What causes of cushings syndrome cause hyperpigmentation?
ACTH-dependent causes.
Why do you get bruising in Cushing’s syndrome?
Loss of subcutaneous connective tissue, due to the catabolic effects of glucocorticoids, exposes underlying vessels prone to rupture. It is a similar mechanism to that of striae.
Why do individuals with Ectopic ACTH secretion get hypokalaemia?
Due to the mineralocorticoid activity of cortisol
Why can Hirsutism occur in Cushing’s syndrome?
The mechanism is not clear. Excess ACTH has been shown to cause hyperstimulation of the zona fasciculata and zona glomerulosa, producing cortisol, androgens and potentially hirsutism.
What is the mechanism behind pigmentation seen in Cushing’s Syndrome?
In Cushing’s disease, where ACTH is secreted by pituitary tumours, ‘tanning’ may occur by stimulation of melanocytes in a similar process to Addison’s disease.
Why can those with Cushing’s be plethoric?
In Cushing’s Disease, excess cortisol causes degradation and atrophy of the epidermis and underlying connective tissue. This leads to apparent thinning of the skin and the appearance of facial plethora
Why can those with Cushing’s Syndrome experience poluria?
Excess glucocorticoids have been shown to inhibit osmosis-stimulated ADH secretion as well as directly enhancing free water clearance, thus producing polyuria.
Hyperglycaemia causing osmotic diuresis is rarely the cause of polyuria in Cushing’s syndrome.
Why can proximal myopathy occur in Cushing’s Syndrome?
The catabolic effects of glucocorticoids break down proteins in the muscle fibres, causing weakness. Additional factors induced by excess steroids include hypokalaemia, depressed protein synthesis, decreased sarcolemmal activity and increased myosin degeneration.
What investigations would you do if you suspected Cushing’s Syndrome?
Stepwise Process
- First line - overnight dex suppression test + 24hr urinary free cortisol
- 2nd line - 48 hr Low Dose Dex supression Test + Urine Free Cortisol
- Localise - Plasma ACTH levels
- ACTH high - High Dose Dex test
- ACTH low - Pituitary MR/CT; BIPSS; CT chest
Other investigations
- U+E’s
What is involved in the overnight dexamethasone suppression test?
Patient takes 1mg of dexamethasone at 23:00, plasma cortisol measured next morning at 09:00. Normal test result <50 nmol/L, whereas no suppression indicates Cushing’s
What is involved in a 48 hr low-dose dexamethasone suppression test?
0.5mg 6 hourly for 2 days. Plasma cortisol measurements taken on day 0 and day 2. If failed suppression of cortisol after 2 days - Cushing’s syndrome present.
What is involved in a high-dose dexamethasone suppression test?
2mg dexamethasone 6 hrly over 48 hrs. Cortisol measurements on day 0 and day 2. This test is used to distinguish between pituitary suppression and no pituitary suppression
What does failure to suppress cortisol on high-dose dexamethasone suppression test mean?
Failure of significant plasma cortisol suppression suggests an ectopic source of ACTH or an adrenal tumour.
What do low/undetectable ACTH levels suggest in someone presenting with suspected Cushing’s syndrome?
Two or more occasions are a reliable indicator of non-ACTH-dependent disease.
What cause of cushing’s syndrome can cause impaired glucose tolerance and hypokalemia?
Ectopic ACTH
When measuring plasma ACTH in someone with cushings syndrome, what does a low value indicate?
Adrenal tumour likely
How would you treat an iatrogenic cushing syndrome?
Stop therapy
How would you teeat someone with Cushing’s Disease?
Surgery
- Trans-sphenoidal removal of pituitary adenoma
- Bilateral adrenalectomy - if no pituitary source
How would you manage someone with an adrenal carcinoma?
Adrenalectomy + adjuvant radiotherapy
How would you treat someone with cushing’s syndrome that had an Ectopic source?
Surgery - if no widespread mets
Symptom management - if reasonable
- Metyrapone or ketoconazole - beneficial for symptoms
- Bilateral adrenalectomy
What is Conn’s syndrome?
Primary hyperaldosteronism
Adrenal adenomas (Conn’s syndrome) originally accounted for 60% of cases of primary hyperaldosteronism but represented a rare cause of hypertension. Bilateral adrenal hyperplasia also falls under the umbrella of conn’s syndrome
What is the pathophysiology of primary hyperaldosteronism?
Primary hyperaldosteronism is a disorder of the adrenal cortex characterized by excess aldosterone production, leading to:
- Sodium retention
- Potassium loss
- Combination of hypokalaemia and hypertension
What distinguishes primary hyperaldosteronism from secondary hyperaldosteronism?
Secondary hyperaldosteronism arises when there is excess renin (and hence angiotensin II) stimulation of the zona glomerulosa. Primary hyperaldosteronism is a disorder of the adrenal cortex overproducing aldosterone, leading to suppressed renin levels
What are causes of secondary hyperaldosteronism?
Hypertensive
- Malignant hypertension
- Renal artery stenosis
Normotensive
- Congestive cardiac failure
- Cirrhosis
- Diuretics
What are features of primary hyperaldosteronism?
Often asymptomatic
- Hypertension
-
Features of Hypokalaemia - not frequently present
- Muscle weakness
- Polyuria
- Paraesthesia
- Nocturia
- Tetany
What are causes of primary hyperaldosteronism?
- Adrenal adenoma
- Bilateral adrenal hyperplasia