Endocrine Flashcards
What is Acromegaly and what is a genetic association to it
This is increase GH secretion from a pituitary tumour (or rarely an ectopic NET) leading to increased IGF-1 causing bone and soft-tissue growth
MEN-1 association in 5%
What are the signs and symptoms of Acromegaly
Tumour mass (4)
- Headache
- Visual fields defects
- CN Palsies
- Pituitary stalk compression
Prolactin secretion (5)
- Low libido
- Infertility
- Galactorrhea
- ED
- Amen/Oligomen
Excess IGF-1
- Skin & Soft-tissue: Oily, Sweaty, Thick skin + Skin tags + Carpal tunnel
- Resp: Snoring + Sleep Apnoea + Upper airway obstruction
- Osteo: Arthropathy + Osteoarthritis + Vertebral fractures
- CV: HTN + HF + Arrhythmias + Hypertrophic
- Met: DM
- Organomegaly: Thyroid + Prostate
- Other: Hypercalciuria
What are the investigations indicated in Acromegaly
- Oral Glucose Tolerance Test (OGTT): 75g oral load causes GH >1microgram/L
- Serum IGF-1: Elevated
- MRI Pituitary
- Visual fields: Bitemporal Hemianopia
What is the treatment for Acromegaly
Resectable 1st - Transphenoidal surgery 2nd - SS - Octreotide A - Dopamine agonist - Cabergoline 3rd - Growth hormone receptor antagonist - Pegvisomant 4th - Radiotherapy
Non-resectable
The same without Transphenoidal surgery
What are possible complications of Acromegaly
- Cardiac complications + HTN
- Sleep apnoea + Carpal tunnel
- Osteoarticular + DM
- Precancerous polyps + Hypopituitarism
What are the classifications of Adrenal insufficiency and what are their respective causes
1o - Addison’s - High ACTH
- 80% Autoimmune in UK
- TB worldwide most common cause
- Adrenal mets
- Lymphoma
- HIV
- Adrenal haemorrhage
- Congenital adrenal hyperplasia
2o - Low ACTH
- Iatrogenic - Withdrawal of steroids that have caused suppression of the pit-adrenal axis
- Hyperthalamic-pituitary disease
What sex is mostly affected by Adrenal insufficiency
Women 90%
What are the symptoms of Adrenal insufficiency
- Fatigue + Weakness (Most common PC)
- Muscle weakness + Myalgia + Arthralgia
- Anorexia + Weight loss
- N&V + Constipation + Abdominal pain
Salt cravings
Dizziness
What are signs of Adrenal insufficiency
- Mucosal/cutaneous hyperpigmentation in sights of continuous friction: Palms, Knuckles, Elbows, Scars, Inside mouth - Not in 2o
- Postural hypotension - Decreased mineralocorticoid activity
- Hx Autoimmunity - Vitiligo + Hashimoto’s + Pernicious anaemia
- Axillary and pubic hair loss in women
What are the signs of an adrenal crisis
Shock = Low BP + High HR
Fever
Coma
What are appropriate investigations in Adrenal insufficiency and the associated investigator findings
- Morning Cortisol (9am) - <83nmols/L
- Short ACTH stimulation test (Synacthen test) - 250micrograms of ACTH given - Cortisol <497nmols/L
- Serum ACTH - High in 1o; Low in 2o (Aldosterone will also be lower in 1o)
Other
- U+Es: Hyperkalaemia, Hyponatraemia, Uraemia
- FBC: Eosinophilia
- CT Adrenal
- CXR
Outline treatment for Adrenal insufficiency
Crisis
IV Hydrocortisone + Normal Saline + 5% Dextrose
Stable
Glucocorticoid + Mineralcorticoid (Prednisolone + Fludrocortisone)
- Stress dosing
DHEA - Androgen replacement in women with reduced libido
What the complications of Adrenal insufficiency
2o Cushing’s
Osteopenia/Osteoporosis
Treatment related hypertension
What are the causes of Primary hyperaldosteronism
This is excess production of aldosterone leading to low K+ and HTN
80% are due to adenomas in the zona glomerulosa - Conn’s -
Other causes include: (3)
- Bilateral adrenal hyperplasia (BAH)
- Glucocorticoid remediated aldosteronism (GRA)
- Adrenal carcinoma
What are the signs and symptoms of Primary hyperaldosteronism
Patients are usually asymptomatic
- Hypokalaemia - Weakness + lethargy
- HTN (Due to increased Na and water retention)
- Metabolic alkalosis
- Polyuria + Polydipsia
- Headaches
Normal or elevated Na
What are the appropriate investigations in Primary hyperaldosteronism and the relative findings
U+Es - Hypokalaemia, possible Hypernatraemia Renin - Low Aldosterone - Elevated Aldosterone/Renin Ratio - >20 in plasma Adrenal venous sampling CT Adrenals ECG - Arrhythmias
Lying/Standing Aldosterone/Renin Ratio
Increase by 30% in BAH. No increase in Conn’s
What are the treatment’s for Primary hyperaldosteronism
Conn’s
Laproscopic adrenalectomy with pre and postoperative spironolactone (Aldosterone antagonist)
BAH
Amiloride/Spironolactone
GRA
Dexamethasone
2 - Spironolactone
What are the complications of Primary hyperaldosteronism
HF AF MI Stroke Hyperkalaemia Impaired renal function
What are the classifications of Cushing’s syndrome and what are their respective causes
Cushing’s syndrome is excess cortisol production
High ACTH - Ectopic no suppression with high dose
- Cushing’s disease (Most common endogenous cause of Cushing’s syndrome) - Pituitary adenoma
- Ectopic ACTH production - Small cell lung cancer and carcinoid tumours - Atypical presentations
Low ACTH
- Iatrogenic oral steroids (Most common cause of Cushing’s syndrome)
- Adrenal adenoma/carcinoma
- Adrenal nodular hyperplasia
What are the atypical presentations of Cushing’s syndrome when it is caused by ectopic ACTH production
Symptoms of high ACTH from Addison’s
- Pigmentation
Symptoms of high mineralocorticoid from Conn’s
- Hypokalaemia
- Metabolic alkalosis
Weight loss due to Carcinoma
High dose dexamethasone will still not suppress ectopic ACTH production
What are the signs and symptoms of Cushing’s syndrome
Excess cortisol
- Obesity + Supraclavicular fat pad + Interscapular hump (Buffalo hump)
- Facial fullness + Plethora
- Proximal myopathy
- Bruising
- Red striae
- Fractures - Osteoporosis
Hyperglycaemia
- Diabetes
- HTN
- Increased risk of CVD
- Increased infections
- Poor wound healing
- Amenorrhea
- Psychiatric
What are the appropriate investigations in Cushing’s syndrome and the relative findings
1st Line
- Overnight dexamethasone suppression test (1mg) -> 8am cortisol - >50nmols/L
- 24hr Urinary free cortisol >50micrograms/24hrs
Then
- 48hr 2mg dexamethasone supression test >50nmols/L
- 12am Cortisol salivary or blood during sleep - Elevated
Localisation
- Plasma ACTH - High in Adrenal problems; Low in Pituitary or Ectopic
- Inferior petrosal sinus sampling - Central/peripheral ACTH ratio over 2 indicative of Cushing’s disease
- High dose dexamethasone - Ectopic will not suppress - No longer really done
Imaging
MRI Pituitary
CT Adrenals
CXR
Outline treatment for Cushing’s syndrome
Cushing’s disease
- Transphenoidal surgery
- Pre-op - Metyrapone/Ketoconazole/Mifepristone
- Post-op - Pituitary hormone replacement + Corticosteroid replacement
Ectopic
- Resection of tumour
- Medical therapy - Metyrapone/Ketoconazole/Mifepristone
Unilateral adrenal mass
- Mass resection
- Pre op - Metyrapone/Ketoconazole/Mifepristone
Bilateral adrenal disease
- Bilateral resection
- Permanent corticosteroid replacement
What is Diabetes insipidus
This is impaired ADH secretion (Cranial - 2o) or lack of response to ADH being secreted (Nephrogenic - 1o) leading to production of a large amount (>3L/day) of hypoosmolar (dilute) urine.
What are the causes of cranial Diabetes insipidus
Acquired
- Idiopathic
- Tumours
- Surgery
- Head injury
- Granulomata
- Infections
- Vascular disorders
- Post-radiotherapy
Congenital
- DIDMOAD - Autosomal recessive - DI, DM, Optic Atrophy and Deafness
- Autosomal dominant mutations of vasopressin gene
What are the causes of nephrogenic Diabetes insipidus
Acquired
- Idiopathic
- Hypokalaemia
- Hypercalcaemia
- Chronic kidney disease
- Other metabolic derangments
- Drugs - Lithium, Orlistat, Ofloxacin
- Renal tubular acidosis
- Pregnancy
- Post-obstructive uropathy
Congenital
- X-linked mutation in V2 ADH receptor gene
- Autosomal recessive defect in AQP2 gene
- Sporadic nephrogenic DI with general learning disability and intracerebral calcification (V rare)
What are the signs & symptoms of Diabetes insipidus
Polyuria
Polydipsia
Nocturia
Dehydration + Potential palpable bladder
What are the appropriate investigations in Diabetes insipidus and the relative findings
Urine Osmolality - <300 Serum Osmolality - Normal or elevated Serum Na - Normal or elevated Serum K - Normal or low Serum Ca - Normal or elevated Urine dipstick - -ve for glycosuria 24hr Urine collection - >3L/24hrs
Water deprivation - 8hrs of water deprivation or until 3% of body weight is lost - Only performed if not hypernatraemic - Both types of DI will show that urine osmolality will be below 700 after the test (Some patients not show optimal concentration of urine because they have primary polydipsia)
To distinguish between the 2 types of DI:
Desmopressin stimulation test
Central/Cranial DI will respond
Nephrogenic DI will not
What are the treatments for Diabetes insipidus
Hypernatraemia - Important complication
Fluids - 0.45% Normal Saline, 5% Dextrose
Central/Cranial
Desmpression
Nephrogenic
Maintain adequate intake of water
+ Treat underlying cause
What is SIADH
This is when there is hyponatraemia (<125) and low plasma osmolality (<260) with concentrated urine (>100; urine Na >20) in the absence of hypovolaemia, oedema or diuretics
Primary cause is due to ADH secretion even though the plasma is concentrated (Low osmolality)
<50% of severe hyponatraemia is caused by SIADH (It is over diagnosed)
What are causes of SIADH
Brain (6)
- Haemorrhage/thrombosis
- Meningitis
- Abscess
- Trauma
- Tumour
- Guillain-‐Barre syndrome
Lung (3)
- Pneumonia
- TB
- Other: Abscess, Aspergillosis, Small cell carcinoma
Tumours (4) - Small cell lung caner - Lymphoma - Leukaemia - Others: Pancreatic cancer, prostate cancer, mesothelioma, sarcoma, thymoma
Drugs (4)
- Vincristine
- Opiates
- Carbamazepine
- Chlorpropamide
Metabolic (2)
- Porphyria
- Alcohol withdrawal
What are the signs and symptoms of Hyponatraemia
Mild: Usually Asymptomatic
Moderate: Headache, N&V, Claudication, Irritability
Severe: Confusion, Drowsiness, Convulsions, Coma
What are the appropriate investigations in SIADH and the relative findings
Diagnosis: Plasma osmolality - Low Urine osmolality - High Plasma Na - Low Urine Na - High Absence of hypovolaemia, oedema or diuretics
Things to check:
- Creatinine - Renal function
- Glucose, Protein, Lipids - Rule out pseudohyponatraemia (When sodium is reported as low due to high lipids or protein)
- T4 and TSH - Hypothyroidism
- Synacthen test - Adrenal insufficiency
How is SIADH treated
- Treat the underlying cause
- Fluid restriction
- Vasopressin receptor antagonists - Vaptans (tolvaptan)
Severe - Slow IV hypertonic saline and furosemide with close monitoring
What are the possible complication of SIADH
Convulsions
Coma
Death - <110
Central pontine myelinolysis - Occurs with rapid correction of hyponatraemia
- Quadriparesis
- Respiratory arrest
- Fits
What are the causes of Hypothyroidism
1o - 95%
Acquired:
- Hashimoto’s thyroiditis: Goitre due to lymphocytic and plasma cell infiltration. Potential initial state of hyperthyroid
- Primary atrophic hypothyroidism - Diffuse lymphocytic infiltration of the thyroid, leading to atrophy, hence no goitre
- Iodine deficiency - World wide main cause
- Post-thyroidectomy or radio iodine treatment
- Drugs induced: Amiodarone, lithium, iodine
Congenital:
- Thyroid dysgenesis
2o - 5%
Pit-Hypo disease
What are the signs and symptoms of Hypothyroidism
Weakness + Lethargy Cold sensitivity Constipation Weight gain Depression Menstraul irregularity Myalgia Dry and coarse skin Facial oedema Thick tongue Bradycardia Deep voice Goitre Delayed tendon relaxation Diastolic hypertension with or without narrow pulse pressure
How is Hypothyroidism investigated
TFTs - 1o High TSH, Low T4,
Lipids - Hyperlipidaemia and cholsterolaemia
FBC - Macrocytosis
How is Hypothyroidism treated
Levothyroxine - Rule out Addisons first - Check TSH after 4 weeks
Myxoedema coma = IV T4/T3
- Oxygen
- Rewarming
- Rehydration
- IV hydrocortisone
- Treat underlying cause
What is Thyroiditis and what are its causes
Thyroiditis is inflammation of the thyroid
Hashimoto’s thyroiditis is an autoimmune condition that is the most common cause of hypothyroidism in the UK.
Other types include:
- de Quervan’s thyroiditis
- Postpartum thyroiditis
- Drug-induced thyroiditis
- Acute or infectious thyroiditis
- Riedel’s thyroiditis
In Hashimoto’s there is lymphocyte infiltration of the thyroid causing the formation of a goitre
What are the signs and symptoms of Thyroiditis
Symptoms of hypothyroidism
- Bradycardia
- Constipation
- Lethargy
- Weakness
- Weight gain
- Los of appetite
- Hair loss
- Low mood
- Menstrual irregularities
- Cold intolerance
- Dry skin
Goitre formation leads to:
- Dyspnoea
- Dysphagia
- Tenderness
What are the appropriate investigations for Thyroiditis
- Serum TSH - High
- Antibodies - Anti-TPO Abs + Anti-thyroglobulin Abs
- Thyroid US
- Radionuclide isotope scanning
- Histology - Diffuse lymphocytic and plasma cell infiltration with formation of lymphoid follicles
How is Thyroiditis treated
Pharmacological
Levothyroxine - Titre based on patients need
Surgical
If there is a large goitre that is impeding on the surrounding structures
What are possible complications of Thyroiditis
2o Hyperthyroid
Hyperlipidaemia
Myxoedema coma
Hashimoto’s encephalopathy
What are the different types of Prolactinoma
Micro-adenoma - <1cm
Macro-adenoma - >1cm
Giant Pituitary adenoma - >4cm
Malignant Prolactinoma (Rare)
Association to MEN-1 syndrome
There is a risk of tumour enlargement in pregnancy
What are the signs and symptoms of Prolactinoma
Women
- Amen/Oligomen
- Galactorrhea
- Osteoporosis
- Low libido
- Hirsuitism
- Infertility
Men
- ED
- Reduced beard growth
- Low libido
Tumour size
- Headache
- Visual field defects
- CN palsies
- Pituitary stalk compression
What are appropriate investigations for Prolactinoma
Serum prolactin - Elevated
Visual fields - Bitemporal hemianopia
MRI Pituitary - Prolactinoma
TFTs - High TRH can cause hyperprolactinaemia
Outline the treatment of Prolactinomas
Men
Dopamine agonist
Transphenoidal surgery
Sellar radiotherapy
Women Dopamine agonist Combined oral contraceptive (If not desiring pregnancy) Transphenoidal surgery Sellar radiotherapy
What are possible complications of Prolactinomas
Osteoporosis
ED
Infertility
What is Hypopituitarism
This is partial or complete reduction in secretion of 1 or more anterior pituitary hormone
Panhypothyroidism is deficiency in all pituitary hormones
What are the causes of Hypopituitarism
- Pituitary masses
- Pituitary trauma - Radiation, surgery, fracture
- Hypothalamic dysfunction - Anorexia, Kallman’s, starvation, over-exercise
- Infiltrative disease - Sarcoidosis, Haemochromatosis, Langerhans’ cell histiocytosis
- Vascular - Pituitary apoplexy, Sheehan’s syndrome
- Infection
- Genetic mutation - Pit-1 and PROP-1 genes
What are the signs and symptoms of Hypopituitarism
Depends on the hormone affected
GH
- Short stature in children
- Low mood + Fatigue + Reduced exercise capacity and strength + Increased fat in adults
LH or FSH
- Delayed puberty, Decreased libido, Loss of 2o sexual hair
- Females: Breast atrophy + Amen/Oligomen + Painful sex, Infertility
- Males: Testicular atrophy + Gynaecomastia, Impotence
ACTH - Adrenal insufficiency
TSH - Hypothyroidism
Prolactin - Not clinically noticed
Apoplexy:
Headache
Visual loss
CN palsies
What are appropriate investigations for Hypopituitarism
PFTs 9am Cortisol + ACTH - Both low LH + FSH - Both low Testosterone - Low Oestrogen - Low IGF-1 - Low Prolactin - Slightly elevated Free T4 and TSH level - Low High serum and urine osmolality Low sodium
Insulin induced hypoglycaemic - GH and Cortisol will show no increase
MRI Pituitary
Visual field testing
How is Hypopituitarism treated
Hormone replacement:
- Hydrocortisone
- Levothyroxine
- Testosterone in males
- Oestrogen with/without progesterone in females
- Growth hormone - Somatropin
- Desmopressin
