MED: Endocrinology Flashcards
What is acromegaly?
Disorder caused by excessive secretion of growth hormone (GH)
What is the cause of acromegaly?
Pituitary adenoma in over 95% of cases
A minority of cases are caused by ectopic GHRH or GH production by tumours e.g. pancreatic.
What are the clinical features of acromegaly?
- coarse facial appearance
- spade-like hands
- increase in shoe size
- large tongue, prognathism, interdental spaces
- excessive sweating and oily skin: caused by sweat gland hypertrophy
- features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia
- raised prolactin in 1/3 of cases → galactorrhoea
- 6% of patients have MEN-1
What are the investigations for acromegaly?
First line: Serum IGF-1 levels
If raised:
Second line: OGTT
- In normal patients GH is suppressed to <2mu/L with hyperglycaemia
- In acromegaly there is no suppression of GH
A pituitary MRI may demonstrate a pituitary tumour
What is the management of acromegaly?
Trans-sphenoidal surgery:
- First-line in majority of patients
Dopamine agonists:
- E.g. bromocriptine
- Now superseded by somatostatin analogues
- Effective only in a minority of patients
Somatostatin analogues:
- Directly inhibits release of GH
- E.g. octreotide
- May be used as an adjunct to surgery
Pegvisomant:
- GH receptor antagonist
- Once daily s/c administration
- Very effective - decreases IGF-1 levels in 90% of patients to normal
- Doesn’t reduce tumour volume therefore surgery still needed if mass effect
External irradiation is sometimes used for older patients or following failed surgical/medical treatment
What are the complications of acromegaly?
- hypertension
- diabetes (>10%)
- cardiomyopathy
- colorectal cancer
What is Addison’s disease?
// Primary adrenal insufficiency
Disorder characterized by inadequate production of cortisol and aldosterone by the adrenal cortex
What are the causes of Addison’s disease?
- Autoimmune destruction of adrenal cortex - most common cause (70-90%)
- Infections* - TB, fungal infections, HIV, and CMV
- Genetic disorders - CAH, APS-1
- Metastatic infiltration - lung, breast, or melanoma can metastasize to adrenals
- Adrenal haemorrhage - trauma, anticoagulation, sepsis
- Medications - prolonged use of glucocorticoids or drugs that inhibit steroidogenesis (e.g., ketoconazole) can suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to adrenal atrophy and insufficiency
What does the adrenal insufficiency in Addison’s cause?
Cortisol deficiency:
- Cortisol is crucial for maintaining glucose homeostasis, immune function, and stress response. - Reduced cortisol production results in hypoglycemia, increased susceptibility to infections, and an inadequate response to stressors.
Aldosterone deficiency:
- Aldosterone is responsible for regulating sodium and potassium balance.
- Insufficient aldosterone production leads to hyponatremia, hyperkalemia, and volume depletion, causing orthostatic hypotension and impaired renal function.
Adrenal androgens deficiency:
- Although their role is less prominent, adrenal androgens are involved in secondary sexual characteristics and libido.
- A deficiency may result in reduced body hair and decreased libido.
Increased ACHT: (loss of neg feedback)
- Elevated ACTH levels result in melanocyte-stimulating hormone (MSH) production, causing the characteristic hyperpigmentation
What are the clinical features of Addison’s disease?
- lethargy, weakness
- anorexia, nausea & vomiting, weight loss, ‘salt-craving’
- hyperpigmentation (especially palmar creases)
- vitiligo
- loss of pubic hair in women
- hypotension,
- hypoglycaemia
- hyponatraemia and hyperkalaemia may be seen
- crisis: collapse, shock, pyrexia
What are the investigations for Addison’s?
ACTH stimulation test (short Synacthen test):
- Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM
- Normal response = rise in blood cortisol levels
- Addison’s = little or no increase in cortisol levels
If ACTH stimulation test not readily available (e.g. in primary care):
9 am serum cortisol:
- > 500 nmol/l = Addison’s very unlikely
- <100 nmol/l = definitely abnormal
- 100-500 nmol/l = perform ACTH stimulation
Adrenal autoantibodies:
- Presence of 21-hydroxylase autoantibodies supports autoimmune adrenalitis as underlying cause
Associated electrolyte abnormalities:
- hyperkalaemia
- hyponatraemia
- hypoglycaemia
- metabolic acidosis
What is the management of Addison’s?
Glucocorticoid and mineralocorticoid replacement therapy:
- hydrocortisone
- fludrocortisone
Patient education:
- emphasise the importance of not missing glucocorticoid doses
- consider MedicAlert bracelets and steroid cards
- patients should be provided with hydrocortisone for injection with needles and syringes to treat an adrenal crisis
- discuss how to adjust the glucocorticoid dose during an intercurrent illness (see below)
Management of intercurrent illness:
- glucocorticoid dose should be doubled, with fludrocortisone dose staying the same
What is an adrenal crisis?
An acute life-threatening condition characterized by severe hypotension, hypoglycemia, and altered mental status.
Immediate treatment with IV hydrocortisone, fluids, and electrolyte correction is crucial.
What is Cushing’s disease?
Disorder caused by the overproduction of cortisol hormone by the adrenal glands
What are the causes of Cushing’s disease?
Most commonly caused by a benign pituitary tumour that secretes ACTH, which stimulates the adrenal glands to produce cortisol
What are the clinical features of Cushing’s disease?
- Central Obesity and Weight Gain - moon facies, buffalo hump
- Abdominal striae, typically purple or violaceous in colour
- Proximal myopathy affecting the hip and shoulder girdles, leading to difficulty in rising from a seated position or climbing stairs
- Osteopenia and osteoporosis with an increased risk of fractures
- Avascular necrosis of the femoral head
- Hirsutism due to increased adrenal androgens
- Acne vulgaris and seborrheic dermatitis
- Thin skin with easy bruising and poor wound healing
- Glucose intolerance or overt type 2 diabetes mellitus
- Menstrual irregularities (oligomenorrhea or amenorrhea) in females
- Decreased libido and erectile dysfunction in males
- Depression, anxiety, irritability, emotional lability, and cognitive deficits such as impaired memory or concentration
- Sleep disturbances including insomnia or hypersomnia
- Hypertension
- Increased risk of VTE
- In children, growth retardation may occur due to cortisol-mediated suppression of GH secretion
- Precocious puberty may be observed in some cases
What is the management of Cushing’s syndrome?
Treatment options include surgical removal of the pituitary tumour, radiation therapy, and medication to control cortisol levels.
What is the management of Graves’ disease?
ß-blockers:
- For rapid control of symptoms
- E.g. propranolol.
Radioactive iodine:
- First-line definitive treatment
- Patients often become hypothyroid, thus may require replacement therapy.
Antithyroid drugs:
- Offer a 12-18 month course as first-line definitive treatment if it is likely to achieve remission, or if radioactive iodine and surgery are unsuitable.
- Examples include carbimazole (first-line) and propylthiouracil.
Surgery:
- Total thyroidectomy offered as first-line definitive treatment if concerns about compression or malignancy, or radioactive iodine and antithyroid drugs unsuitable.
- Consider if antithyroid drugs have been tried but hyperthyroidism persisted or relapsed.
- Patients become hypothyroid, thus require replacement therapy.
What are important exceptions to using radioactive iodine first-line?
- Pregnancy
- Attempts to conceive within the next 4-6 months
- Presence of active eye disease
- Concerns about compression or malignancy.
What is a thyroid storm?
Thyroid storm is a rare but life-threatening complication of thyrotoxicosis.
What are the clinical features of a thyroid storm?
- fever > 38.5ºC
- tachycardia
- confusion and agitation
- nausea and vomiting
- hypertension
- heart failure
- abnormal liver function test - jaundice may be seen clinically
What is the management of a thyroid storm?
treated with beta-blockade, anti-thyroid drugs, and steroids
- symptomatic treatment e.g. paracetamol
- treatment of underlying precipitating event
- beta-blockers: typically IV propranolol
- anti-thyroid drugs: e.g. methimazole or propylthiouracil
- Lugol’s iodine
- dexamethasone
What are some causes of hypoglycaemia?
Diabetes:
- Excess insulin - most commonly from exogenous, injectable insulin - taken too much // used same amount whilst not eating enough or skipping a meal or snack.
- Sulfonylureas (e.g. gliclazide) - esp when starting or increasing dose.
- Viral illness, drunk alcohol, exercised more than usual or have just started or changed dosage of a new medication.
Non-diabetic causes:
- Iatrogenic: indomethacin, pentamidine, quinine, sulfonamide, IGF-1 and lithium.
- Alcohol consumption is the most common non-iatrogenic cause of hypoglycaemia
Rarer causes:
- Hypopituitarism and Addison’s disease
- Insulinoma - neuroendocrine tumour of the pancreas which causes unregulated secretion of insulin
What are the investigations for hypoglycaemia?
- Serum insulin: elevated in insulinoma.
- Serum C-peptide: elevated in insulinoma or sulfonylurea use.
- Serum cortisol: reduced in adrenal insufficiency or hypopituitarism.
- TSH, U&E, LFTs: abnormalities help identify secondary causes of hypoglycaemia such as hypothyroidism, chronic liver disease or kidney disease.
What are the investigations for an insulinoma?
48 to 72-hour fast with serial blood glucose, serum proinsulin, C-peptide and insulin levels
What is the management of hypoglycaemia?
If the patient is alert, a quick-acting carbohydrate may be given (GlucoGel or Dextrogel).
If the patient is unconscious or unable to swallow, SC or IM glucagon may be given.
Alternatively, IV 20% glucose solution may be given through a large vein
What are the causes of hypoparathyroidism?
- Damage or inadvertent removal of the parathyroid glands during thyroid or neck surgery - most common
- Autoimmune disorders
- Congenital absence or dysfunction of the parathyroid glands
- Certain genetic disorders like DiGeorge syndrome.
- Rarely - magnesium deficiency or damage to the glands from radiation therapy
What are the clinical features of hypoparathyroidism?
Hypocalcaemia: > Neuromuscular irritability
- Mild numbness or tingling of the extremities and around the mouth
- Muscle cramps
- Fatigue
- Tetany
- Carpopedal spasm
- Laryngospasm
- Seizures
Physical signs:
- Chvostek’s sign (twitching of the facial muscles in response to tapping over the facial nerve)
- Trousseau’s sign (carpopedal spasm induced by occluding the brachial artery with a blood pressure cuff).
Long-standing hypocalcaemia can also lead to extrapyramidal symptoms, cataracts, and calcification of the basal ganglia
What are the investigations for hypoparathyroidism?
Bloods:
- Low serum calcium
- Low or inappropriately normal PTH levels in the presence of hyperphosphatemia
- Elevated magnesium
- Urinary calcium excretion may be low
ECG:
- Prolonged QT interval due to hypocalcaemia.
Radiographs:
- May reveal intracranial calcifications or changes in bone density.
What is the management of hypoparathyroidism?
Oral calcium supplements and active vitamin D analogues, such as calcitriol or alfacalcidol.
Patients should also be advised on dietary modifications, including a high-calcium, low-phosphorus diet.
What are the causes of primary hypothyroidism?
- Hashimoto’s thyroiditis (autoimmune) - most common cause
- Subacute thyroiditis (de Quervain’s)
- Riedel thyroiditis
- After thyroidectomy or radioiodine treatment
- Drug therapy (e.g. lithium, amiodarone or anti-thyroid drugs such as carbimazole)
- Dietary iodine deficiency
What are causes of secondary hypothyroidism?
From pituitary failure
Other associated conditions:
Down’s syndrome
Turner’s syndrome
coeliac disease
What is the management of hypothyroidism?
Levothyroxine:
- BNF recommends that for patients with cardiac disease, severe hypothyroidism or patients over 50 > initial starting dose should be 25mcg od with dose slowly titrated.
- Other patients should be started on a dose of 50-100mcg od
- Following a change in thyroxine dose TFTs should be checked after 8-12 weeks
- Women with established hypothyroidism who become pregnant should have their dose increased ‘by at least 25-50 micrograms levothyroxine’*
What is Conn’s Syndrome?
Primary hyperaldosteronism
What are the causes of primary hyperaldosteroism?
- bilateral idiopathic adrenal hyperplasia - most common
- adrenal adenoma
- unilateral hyperplasia
- familial hyperaldosteronism
- adrenal carcinoma
What are the clinical features of Conn’s?
- hypertension
- hypokalaemia - e.g. muscle weakness
- metabolic alkalosis
What are the investigations for Conn’s?
Plasma aldosterone/renin ratio:
- first-line
- high aldosterone levels alongside low renin levels
High-resolution CT abdomen:
- used to differentiate between unilateral and bilateral sources of aldosterone excess
Adrenal vein sampling:
- if CT is normal adrenal venous sampling (AVS) can be used to distinguish between unilateral adenoma and bilateral hyperplasia
What is the management of Conn’s?
- adrenal adenoma: surgery (laparoscopic adrenalectomy)
- bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
Describe HbA1c targets for people with diabetes
HbA1c should be checked every 3-6 months until stable, then 6 monthly
Describe first line management in Type 2 Diabetes
Metformin:
- Titrated up slowly to minimise the possibility of gastrointestinal upset
- If standard-release metformin not tolerated then modified-release metformin should be trialled
SGLT-2 inhibitors:
Should also be given in addition to metformin if any of the following apply:
- high risk of developing cardiovascular disease (CVD, e.g. QRISK ≥ 10%)
- established CVD
- chronic heart failure
- patient develops CVD (e.g. is diagnosed with ischaemic heart disease), a QRISK ≥ 10% or chronic heart failure
metformin should be established and titrated up before introducing the SGLT-2 inhibitor
If metformin is contraindicated:
if the patient has a risk of CVD, established CVD or chronic heart failure:
- SGLT-2 monotherapy
if the patient doesn’t have a risk of CVD, established CVD or chronic heart failure:
- DPP‑4 inhibitor or pioglitazone or a sulfonylurea
- SGLT-2 may be used if certain NICE criteria are met
diagnosis?
Cushing’s DISEASE
Cushing’s disease is the result of the pituitary source of ACTH. There is a suppression of cortisol levels following a high dose of dexamethasone, resulting in appropriate negative feedback through the Hypothalamic-Pituitary-Adrenal (HPA) axis, suppressing both ACTH and cortisol.
