Endocrine Flashcards
What is the difference between primary and secondary adrenal insufficiency?
Primary: destruction of adrenal cortex and reduction in adrenal hormone output
Secondary: inadequate pituitary or hypothalamic stimulation of the adrenal glands
Which parts of the adrenal gland produce aldosterone, catecholamines, and glucocorticoids?
Aldosterone: zona glomerulosa
Catecholamines: Medulla
Glucocorticoids: zona fasciculata
Other than autoimmune destruction of the adrenal gland (Addison’s disease), give three other causes of primary adrenal insufficiency.
Invasion (neoplastic, sarcoidosis)
Trauma/infarction
CAH
What are three causes of secondary adrenal insufficiency?
Exogenous steroids and antipsychotics suppress the hypothalamic-pituitary axis
Cranial irradiation
How does Addison’s disease present in its chronic form?
Tall, tanned, tired, lean
Fatigue and weight loss Nausea and vomiting Craving for salt Brown hyperpigmentation Muscle cramps and dizziness (hypotension)
What is the biochemistry seen in a patient with Addison’s disease?
Low sodium
High potassium
High calcium
Low cortisol, high ACTH, high renin, low aldosterone
How is Addison’s disease diagnosed?
ACTH stimulation (Synacthen) test Adrenal autoantibodies CT adrenals
What is the treatment of Addison’s disease?
Hydrocortisone TD
Fludrocortisone OD
Monitor symptoms, BP, Na, K, and signs of over-replacement
What occurs in treatment of primary adrenal insufficiency if hypothyroidism is present?
Precipitation of adrenal crisis if glucocorticoid is replaced before treatment of hypothyroidism
What is the most common presentation of Addison’s disease in children?
Hypogylcaemia
What are three precipitants of adrenal crises?
Stress inc pregnancy
Illness
Abrupt withdrawal of steroids
How does adrenal crisis present?
Dehydration
Hypovolaemic shock
Confusion
Abdo pain, fever, n+v
What is the management of an adrenal crisis?
Immediate IV/IM hydrocortisone at a stress dose (100mg adult)
0.9% saline
IV hydrocortisone in 5% glucose
Continuous cardiac and electrolyte monitoring
Cushing’s Syndrome can be ACTH dependent, or ACTH independent - give a few examples of each.
ACTH dependent: Cushing’s disease, ectopic ACTH-producing tumours
ACTH-independent: unilateral adrenal adenoma, adrenal carcinoma, McCune Albright syndrome, Excess glucocorticoid administration
What is the cause of Cushing’s disease?
Excessive ACTH released from pituitary
What are the most important signs of Cushing’s disease?
Truncal obesity and buffalo hump Proximal muscle wasting Moon facies Reduced libido Hypertension Osteoporosis Skin: atrophy, purple striae, easy bruising, hirsuitism, acne, pigmentation Oligomenorrhoea
How is Cushing’s syndrome and the cause diagnosed?
Syndrome: 24h urinary free cortisol, overnight dexamethasone suppression test, 48h low dose dexamethasone suppression test, sleeping midnight serum cortisol
The cause: raised plasma ACTH, serum K and bicarb, high dose dexamethasone suppression test, Corticotropin-releasing hormone (CRH) test, bilateral inferior petrosal sinus sampling, MRI pituitary/CT adrenals after it has been proved biochemically
How is a pituitary tumour removed?
Trans-sphenoidal microsurgeyr
Which drugs can normalise cortisol levels in patients who are waiting or unfit for surgery?
Ketoconazole and metryrapone
What is the pathophysiology of primary hyperaldosteronism?
Excessive aldosterone acts on the distal renal tubule, promoting sodium retention, which results in water retention, and volume expansion.
Excretion of potassium, resulting in hypokalaemia
What are three causes of primary hyperaldosteronism?
Adrenal adenoma (Conn's syndrome) Bilateral adrenal hyperplasia Familial hyperaldosteronism GRA
What are three causes of secondary hyperaldosteronism?
Excessive renin in the circulation stimulates adrenals to produce aldosterone
Diuretics, CCF, hepatic failure, renal artery stenosis
How may hyperaldosteronism present?
Routine - hypertension
Polyuria and polydipsia
Headaches and lethargy
How is hyperaldosteronism diagnosed?
- Uncontrolled hypertension, hypokalaemia, and hypernatraemia
- Low renin
- High aldosterone
- Refer to specialists - selective adrenal venous sampling
What is the treatment of Conn’s syndrome?
Spironalactone prior to laparoscopic adrenalectomy
Define hypoglycaemia.
Blood glucose<3.0mmol/L
Hospitalised patients <4.0mmol/L
What are three risk factors for hypoglycaemia?
Tight glycaemic control
Impaired awareness
Injection into lipohypertrophy sites
How does hypoglycaemia present?
Sweating, shakiness, dizziness, nausea
Coma
What is the management of hypoglycaemia in the conscious adult?
Glucose 10-20g PO (can be glucogel)
Can repeat 1-3 times
What is the management of hypoglycaemia in the unconscious adult?
IV 75-80ml 20% glucose
If at home, 1mg IM/SC glucagon
Why is a longer acting carbohydrate given after glucose in hypoglycaemic patients?
Restores liver glycogen
What is the management of hypoglycaemic coma?
IV mannitol and dexamethasone
IV glucose
What is a side effect of glucagon for hypoglycaemia?
Causes more insulin to be released - potential for secondary rebound hypoglycaemia.
Which tumours are seen in MEN Type 1 syndrome?
Pituitary prolactinomas/adenomas
Parathyroid tumours
Endocrine gastroenteropancreatic tract tumours
Cutaneous tumours
Which tumours are seen in MEN Type 2 syndrome?
Medullary thyroid cancer
Hyperparathyroidism
Phaechromocytoma
What are three risk factors for phaechromocytoma?
MEN Type 2 (bilateral)
VHL disease
NFT Type 1
How do phaechromocytomas present?
Headache, profuse sweating, palpitations, tremor
How is phaechromocytoma diagnosed?
24 hour urinary metanephrines
What molecule do non-functional pancreatic endocrine tumours secrete?
Pancreatic polypeptide
Name three pancreatic endocrine tumours.
Insulinoma
Gastrinoma
Glucagonoma
What is secondary hyperparathyroidism?
Hyperplastic PTH glands and increased secretion of parathyroid hormone in response to chronic hypocalcaemia, which is from kidney, liver, or bowel disease.
What are the causes of primary hyperparathyroidism?
Single parathyroid adenoma (85%)
4-gland hyperplasia
Parathyroid carcinoma
MEN syndromes
How does hyperparathyroidism present?
Asymptomatic, incidental finding
Osteoporosis and pathological fractures
Hypercalcaemia
What is seen on bloods in hyperparathyroidism?
High corrected calcium
High PTH
Low phosphate
Low vitamin D
What is the management of mild, asymptomatic hyperparathyroidism?
Surveillance
Check creatinine and calcium bi-annually
3-site DEXA every 1-2 years
What is the treatment of symptomatic hyperparathyroidism?
Parathyroidectomy
OR
HRT and raloxifene
What are three complications of parathyroidectomy?
Recurrent laryngeal nerve injury
Hypocalcaemia
Haematoma
What is seen on bloods in secondary hyperparathyroidism?
Calcium: low/normal
PTH: high
Phosphate: high in renal disease, low in vitamin D deficiency
What is the management of CKD-related secondary hyperparathyroidism?
Calcium supplementation
Phosphate restriction/phosphate binders
Parathyroidectomy
What is the pathophysiology of tertiary hyperparathyroidism?
The PTH glands become autonomous, producing excessive PTH even after the cause of hypocalcaemia has been corrected. This results in hypercalcaemia and hyperphosphataemia.
What are the causes of hypoparathyroidism?
Anterior neck surgery
DiGeorge syndrome
Transient in the neonatal period
How is hypoparathyroidism diagnosed?
S+S of hypocalcaemia
Bloods:
Low calcium, high phosphate, low PTH, normal ALP
How does acute pituitary failure present?
Severe headache from stretching of the dura mater in the sella
Vomiting
Diplopia, bitemporal superior quadrantic field defect
Thermal dysregulation
How is acute pituitary failure managed?
Deficiency of all hormones, urgent MRI
Resuscitation and stabilisation
IV hydrocortisone
Urgent transsphenoidal decompression
Where do pituitary tumours invade?
Dura mater
Cranial bone
Sphenoid sinus
What are the presentations of:
1) ACTH-secreting tumours
2) GH-secreting tumours
3) Prolactinomas
4) Non-secreting tumours
5) Thyrotropinoma
1) Cushing’s disease
2) Gigantism in children, acromegaly in adults
3) Women - galactorrhoea, infertility, oligomenorrhoea. Men - hypogonadism, infertility, erectile dysfunction
4) Visual loss
5) Hyperthyroidism
How are pituitary tumours diagnosed?
Pituitary function tests
Lateral skull X-Ray
MRI
Detail pituitary function tests.
Anterior: GnRH stimulation, TRH stimulation, insulin tolerance test for GH and ACTH
Posterior: prolactin levels
In response to TSH, the thyroid produces thyroxine (T4) and triiodothyronine (T3). What happens to T4?
It is inactive, so needs to be converted to T3 in the liver and kidney
Apart from Graves’ disease, give three other causes of hyperthyroidism.
Toxic multinodular goitre
Toxic adenoma
Thyroid carcinoma
What are three risk factors for hyperthyroidism?
Smoking
Family history
High iodine intake
What are the symptoms of hyperthyroidism?
SWEATING
Sweating Weight loss Emotionally labile Appetite increase Tremor/tachycardia/AF Intolerance to heat/irregular periods Nervousness Goitre/GI problems (diarrhoea)
Patients also have proximal myopathy, eye disease, and brisk reflexes
What are the symptoms of thyrotoxicosis?
Severe hyperthyroid symptoms
Hyperthermia
Mental disturbance
Arrhythmias
What extra signs are seen in Graves’ disease?
Pretibial myxedema
Thyroid acropachy
Exophthalmos, opthalmoplegia
How is Graves’ disease diagnosed?
Low TSH
High T4; if normal then High T3
anti-TPO antibodies or anti-thyroglobulin antibodies
131-I labelled thyroid scan
What is the treatment of Graves’ disease?
Carbimazole Propanolol Nitrazepam night sedation Subtotal thyroidectomy once euthyroid Radioactive iodine is CI in young adults as it leads to hypothyroidism after some time
Which hyperthyroid treatments are contraindicated in pregnancy and breastfeeding?
Carbimazole (use propylthiuracil)
Radio-iodine (subtotal thyroidectomy)
What is seen in secondary hyperthyroidism?
Pituitary releases too much TSH
High TSH, high T3, high T4
What are three causes of hypothyroidism?
Iodine deficiency
Hashimoto’s/atrophic thyroiditis
Amiodarone/lithium
What are the symptoms of hypothyroidism?
MOM’S SO TIRED
Memory loss and poor concentration Obesity Malar flush/menorrhagia Slowness inc. constipation Skin and hair dryness Onset gradual Tiredness Intolerance to cold Raised BP Energy levels fall Depression/delayed relaxation of reflexes
How is control of hypothyroidism monitored long term?
TSH
Why can gastroparesis occur in diabetics?
Neuropathy of the vagus nerve
What is the initial management of prolactinomas?
Dopamine agonists e.g. bromocriptine
What are the causes of raised prolactin?
The Ps:
Pregnancy Prolactinoma Physiological PCOS Primary hypothyroidism Phenothiazines, metoclopramide, domperidone
When is C-peptide used?
To distinguish type 1 diabetes from other types of diabetes:
Low in type 1
Normal or high in type
Name five symptoms of hypothyroid myxedema.
Expressionless dull face Pale cool doughy skin Cardiomegaly Megacolon Encephalopathy
How is type 2 diabetes controlled?
HbA1c>48mmol/L or 6.5%
OR
Fasting blood glucose>7mmol/L or random>11.1mmol/L
One sample needed if symptomatic, two if not.
What are the indications of self monitoring of blood glucose in type 2 diabetes?
Pregnancy
Patient on insulin
Hypoglycaemic episodes
What is the management of type 2 diabetes?
- Metformin
- Metformin AND [DPP-4 inhibitor, pioglitazone, or sulfonylurea]
- Metformin AND sulfonylurea AND [DPP-4 inhibitor or pioglitazone]
OR insulin - Metformin AND sulfonylurea AND GLP-1
OR insulin
How does metformin work?
Opposes insulin resistance, decreases lipids and CV risk
What are the side effects and contraindications of metformin?
Lactic acidosis, diarrhoea (try modified release)
CI: raised creatinine/eGFR<45
Name two sulfonylureas.
Gliclazide
Glibenclamide
How do sulfonylureas work?
Stimulate insulin release by binding to beta cell receptors
Stimulate the glycolytic pathway in the liver and inhibit the production of glucose
What are the main side effects of sulfonylureas?
Weight gain
Prolonged/severe hypoglycaemia
What type of drug is pioglitazone?
Thiazolidinediones
How do DPP-4 inhibitors such as sitagliptin work?
Increase insulin secretion and lower glucagon secretion
How do GLP-1 mimetics such as exenatide and liraglutide work?
Increase insulin secretion, lower glucagon secretion, slow gastric emptying
Prevent weight gain
Define hyperosmolar hyperglycaemic state (HHS)
Hypovolaemia
Hyperglycaemia >30mmol/L
Without significant hyperketonaemia (<3mmol/L) or acidosis (pH.7.3)
What may precipitate HHS?
Infection
Stroke/MI
Poor diabetic control
How does HHS present?
Weakness, cramps, confusion
Focal neurological features
N+V may occur
What osmolality is seen in HHS and how is it calculated??
> 320mosmol/kg
2Na + glucose + urea
What other investigations are important in HHS?
High Na+ and K+ U&Es for pre-renal AKI Glycosuria and normal ketonuria Blood and urine cultures CK and troponins
How is HHS managed?
IV 0.9% saline
IV insulin 0.05IU/kg/hour
What is type 1 diabetes?
Autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency.
How does type 1 diabetes present?
Weight loss
Polydipsia and polyuria
Dehydration
Ketonuria and hyperventilation
How is type 1 diabetes diagnosed, in terms of abnormal plasma glucoses, OGTT, and HbA1c?
Random >11.1mmol/L
Fasting >7mmol/L
OGTT >11.1mmol/L
HbA1c >48mmol/mol or >6.5%
What is some general advice given to type 1 diabetic new diagnoses?
Carry a source of glucose
Train a parent on administering glucagon
Sick day supply box
Do not stop insulin if ill
What levels of plasma glucose should be aimed for in type 1 diabetics?
On waking: 5-7mmol/L
Before meals: 4-7mmol/L
Describe the basal bolus insulin regimen given to type 1 diabetic patients.
Bedtime: long acting insulin
Mealtimes: rapid or short acting insulin
What is continuous subcutaneous insulin infusion?
Insulin pump
Indwelling catheter worn underneath patient’s clothing
Patient activates pre-meal boluses
In which patients is an insulin pump useful for?
Poor glycaemic control
Recurrent hypoglycaemia
Young people
Name three rapid acting insulins and why they are more useful than short acting insulins (Humulin).
Insulin aspart, glulisine, and lispro
Even faster onset of action so can be injected very shortly before or even after a meal
Name two long acting insulins.
Insulin glargine (Lantus) Insulin determir
Name three things that may precipitate DKA.
Infection
Steroid treatment
Discontinuation of insulin
Name three signs of DKA.
Acetone smell to breath
Kussmaul respiration (respiratory compensation of acidosis)
Dehydration
What is the criteria for DKA?
Ketonaemia >3mmol/L OR ketonuria >2+
Blood glucose >11mmol/L OR known DM
Venous pH <7.3, OR bicarbonate <15mmol/L
What plasma osmolality and anion gap is seen in DKA?
> 290mOsm/kg
Anion gap >13mmol/L
What is the management of DKA?
Resuscitation with ABCDE approach, obtain large bore IV access
IV 0.9% normal saline bolus followed by maintenance
watch potassium
Fixed rate IV insulin at 0.1IU/kg/hour
In DKA, once plasma glucose <12mmol/L, replace normal saline with what and why?
5% dextrose
Prevents rapid-over correction and hypoglycaemia
Name three complications of DKA.
Cerebral oedema
Iatrogenic hypokalaemia and hypoglycaemia
Cardiac dysrhythmia
Give a cause of a non-tender and a tender goitre and what they present with.
Tender: De Quervain’s thyroiditis. Hyperthyroidism
Non-tender: Hashimoto’s thyroiditis: hypothyroidism
Which autoantibodies are seen in Graves’ disease?
TSH receptor stimulating antibodies
What is seen on blood tests in sick euthyroid syndrome?
Normal-low TSH, low T3, low T4
What is the most common type of MODY (maturity onset diabetes of the young), and what are the characteristics?
MODY 3 - Hepatic nuclear factor 1-alpha (HNF 1-a)
Strong FH, misdiagnosed as type 1, but negative autoantibodies at diagnosis
Hepatic neoplasms
What is the 2nd most common type of MODY and what are the characteristics?
MODY 2 - glucokinase
Blood glucose levels are reset higher e.g. 6-8mmol/L. Usually diet managed except in pregnancy
What is the treatment of a thyroid storm?
Propylthiouracil
Iodine
Hydrocortisone (inhibits T3–>T4)
Propanolol
What is the acid base balance seen in DKA?
Metabolic acidosis
Respiratory alkalosis to compensate
What is the cause of acromegaly?
Growth hormone secreting pituitary adenoma
How is acromegaly diagnosed?
Measure IGF-1 levels
If high, give oral glucose load and GH will fail to suppress
Give eight symptoms of acromegaly.
Headache Sweating Macroglossia Increased size of hands and feet Hypertension Diabetes Carpal tunnel Bitemporal hemianopia
How is acromegaly treated?
Transsphenoidal hypophysectomy
Pituitary radiotherapy
Somatostatin analogue e.g. octreotide
Dopamine agonist e.g. cabergoline
