ENDOCRINOLOGY Flashcards
(172 cards)
1
Q
what is acromegaly?
A
excess GH secretion
2
Q
what are the complications associated with acromegaly?
A
- cardiomyopathy, arrhythmia, valvular, and ischaemic heart disease
- Hypertension
- Sleep apnoea
- Diabetes.
- Pre-cancerous polyps and colorectal cancer
- Bilateral carpal tunnel syndrome
3
Q
what are the clinical features of acromegaly?
A
- Coarse facial appearance including frontal bossing, enlarged nose, prognathism, separation of teeth, and macroglossia.
- Increase in size of hands, the patient may complain that their wedding ring no longer fits.
- Increase in size of feet, the patient may complain that their shoes no longer fit.
- Excessive sweating.
- Joint pain and dysfunction.
- Snoring.
- Alteration in sexual functioning.
- Fatigue.
- Features of pituitary tumour include headache and bitemporal hemianopia.
4
Q
how is acromegaly diagnosed?
A
- elevated serum IGF-1
- OGTT with no suppression of GH
- pituitary adenoma on MRI
5
Q
how is acromegaly managed?
A
- trans-sphenoidal tumour resection
- octreotide
- carbergoline if mixed GH/prolactin secretion
- pegvisomant
6
Q
what is Addison’s disease?
A
primary adrenal insufficiency
7
Q
what are the clinical features of Addison’s disease?
A
- Fatigue.
- Anorexia.
- Weight loss.
- Hyper-pigmentation in primary adrenal insufficiency (A lack of ACTH production means a lack of melanocyte stimulating hormone)
- Salt craving.
- History of other autoimmune disease such as pernicious anaemia and coeliac disease.
- History of worsening hypothyroidism symptoms when levothyroxine is started.
8
Q
what are the clinical features of Addison’s adrenal crisis?
A
- Hypotension.
- Hypovolaemic shock.
- Acute abdominal pain.
- Fever.
- Vomiting.
9
Q
how is Addison’s disease diagnosed?
A
ACTH stimulation test: no change in serum cortisol
10
Q
how is Addison’s disease managed?
A
- Offer glucocorticoid replacement therapy (hydrocortisone 20 mg daily in 3 divided doses).
- Offer mineralocorticoid replacement therapy (fludrocortisone 0.2 mg orally once daily).
- Offer androgen replacement (dehydroepiandrosterone) for women with decreased libido.
11
Q
how is an adrenal crisis managed?
A
- Administer intravenous hydrocortisone (100 mg every 6-8 hours for 1-3 days).
- Administer 1 litre of 0.9% saline over 60 minutes if there is hypotension and dehydration.
- Administer 5% dextrose if there is hypoglycaemia.
12
Q
how should the dose of glucocorticoid and mineralocorticoid be altered on a sick day in Addison’s?
A
- double glucocorticoid
- mineralocorticoid stay the same
13
Q
how is congenital adrenal hyperplasia inherited?
A
-autosomal recessive
14
Q
what are the clinical features of a salt wasting crisis in congenital adrenal hyperplasia?
A
- Hypotension.
- tachycardia.
- Vomiting.
- Poor feeding.
- Failure to thrive.
- Progression to adrenal crisis.
15
Q
what are the features of congenital adrenal hyperplasia in non-salt wasting patients?
A
- Virilisation of female genitalia such as enlarged clitoris, fused labia, and a urogenital sinus.
- Small testes and hyper pigmentation of scrotum in male.
- Hirsutism.
- Precocious puberty.
- Short stature.
- Irregular menses.
- Infertility.
- Male-pattern baldness.
16
Q
how is congenital adrenal hyperplasia diagnosed?
A
- Measure serum 17-hydroxyprogesterone levels: Elevated for age.
- Perform a rapid ACTH stimulation test to establish the diagnosis: 17-hydroxyprogesterone levels remain high.
17
Q
what is seen on blood gas in a salt wasting crisis?
A
- Hyponatraemia
- Hyperkalaemia
- Metabolic acidosis in a salt wasting crisis and hypoglycaemia.
18
Q
how is congenital adrenal hyperplasia managed?
A
lifelong hydrocortisone and fludrocortisone
19
Q
what are the clinical features of a craniopharyngioma?
A
- Acute loss of vision, such as a bitemporal hemianopia affecting the lower quadrant.
- Growth failure.
- Difficulty concentrating.
- Macrocephaly (hydrocephalus).
- Amenorrhoea.
- Erectile dysfunction.
- Headache.
- Galactorrhoea.
20
Q
how is a craniopharyngioma managed?
A
- Perform surgical biopsy and resection.
- Offer endocrine replacement therapy.
21
Q
what are the causes of Cushing’s syndrome?
A
- exogenous corticosteroids
- An ACTH secreting pituitary adenoma, this is known as Cushing’s disease.
- An ACTH secreting small cell lung cancer.
- A cortisol secreting adrenal adenoma, this causes low ACTH via negative feedback.
22
Q
what are the complications of cushing’s syndrome?
A
- Cardiovascular disease.
- Hypertension.
- Diabetes mellitus.
- Osteoporosis.
- Nephrolithiasis.
- Nelson’s syndrome after bilateral adrenalectomy.
23
Q
what are the symptoms of cushing’s syndrome?
A
- Central weight gain.
- Amenorrhoea.
- Poor libido.
- Hirsutism and acne.
24
Q
what are the signs of Cushing’s syndrome?
A
- Facial plethora and supraclavicular fullness.
- Thin skin.
- Easy bruising.
- Striae.
- Proximal myopathy.
25
how is Cushing's diagnosed?
- Perform 1 mg overnight dexamethasone suppression test: Raised morning cortisol.
- Perform 24-hour urinary free cortisol: Elevated.
- Measure serum ACTH: Raised in Cushing’s disease or ectopic ACTH secretion; Low with adrenal adenoma.
26
How is Cushing's syndrome managed?
- Offer medical therapy (metyrapone or ketoconazole) prior to surgery
- Perform trans-sphenoidal pituitary adenomectomy as the first line management of Cushing’s disease.
- Perform surgical resection of a bronchial tumour if there is ectopic ACTH secretion.
- Perform unilateral adrenalectomy if there is a unilateral adrenal adenoma or carcinoma, with adjunct chemotherapy for patients with adrenal carcinoma.
27
what are the causes of cranial diabetes insipidus?
- Trans-sphenoidal pituitary surgery usually for a pituitary adenoma.
- Craniopharyngioma or pituitary stalk lesions.
- Autoimmune disorders such as Hashimoto’s thyroiditis and type 1 diabetes.
- Subarachnoid haemorrhage and traumatic brain injury.
- Wolfram’s syndrome (DIDMOAD), a syndrome comprising diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, due to mutations in the WFS1 gene.
28
what are the causes of nephrogenic diabetes insipidus?
- Medications such as lithium, gentamicin and rifampicin.
- Systemic disease including chronic kidney disease, renal amyloidosis, and hypercalcaemia.
- Inherited as a sex-lined recessive disease.
29
what are the clinical features of diabetes insipidus?
- Polyuria.
- Polydipsia.
- Nocturia.
- Dilute urine.
- Signs of volume depletion e.g. dry mucus membranes, reduced skin turbot, tachycardia, and postural hypotension.
- Features of hypernatraemia such as irritability, restlessness, lethargy, muscle twitching.
30
how is diabetes insipidus diagnosed?
- urine osmolality <300mmol/kg
- elevated serum osmolality
- elevated sodium and low potassium
- urine osmolality <300mmol/kg following water deprivation test
- ADH simulation test: urine osmolality greater than 750mmol/kg in cranial, no increase in nephrogenic
31
how is cranial diabetes insipidus managed?
-desmopressin
32
how is nephrogenic diabetes insipidus managed?
- Offer a thiazide diuretic (hydrochlorothiazide).
- Recommend adequate fluid intake.
- Correct underlying cause for nephrogenic diabetes insipidus, including discontinuing an offending drugs (lithium or gentamicin), treating underlying kidney disease, and correcting electrolyte disturbances.
33
what is the triad of diabetic ketoacidosis?
- hyperglycaemia
- hyperketonaemia
- metabolic acidosis.
34
what are the clinical features of DKA?
- Known diabetes.
- Features of diabetes such as polyuria, polydypsia, weight loss.
- Nausea and vomiting.
- Abdominal pain.
- Hyperventilation (Kussmaul respiration).
- Dehydration suggested by dry mucus membranes, decreased skin turgor, slow capillary refill, tachycardia with a weak pulse, hypotension.
- Reduced consciousness.
- Acetone smell on breath.
35
What is seen on blood gas in DKA?
- Metabolic acidosis with raised anion gap
| - Bicarbonate less than 15 mmol/L.
36
how is DKA managed?
- Fluids
| - IV insulin with glucose and potassium
37
what are the risk factors for diabetic nephropathy?
- Poorly controlled diabetes and sustained hyperglycaemia.
- Uncontrolled hypertension.
- Family history of hypertension or kidney disease.
- Obesity.
- Smoking.
38
what are the clinical features of diabetic nephropathy?
- Oedema which may be severe and generalised (anasarca).
- Fatigue.
- Anorexia.
- Nausea and vomiting.
- Altered taste.
- Hiccups supervene.
39
how is diabetic nephropathy diagnosed?
- proteinuria
- Elevated albumin:creatinine ration
- reduced eGFR
40
how is diabetic nephropathy managed?
- good glycemic control
- ACE inhibitor or ARB
- CCB or thiazide as an add on
- statin
41
how is diabetic neuropathy managed?
- Offer a choice of duloxetine, gabapentin, pregabalin or amitriptyline, as initial treatment for neuropathic plan.
- Refer to pain management clinic in resistant painful neuropathy.
- Offer midodrine for postural hypotension.
- Offer alternating use of erythromycin and metoclorpanide for gastroparesis.
- Offer metronidazole for diabetic diarrhoea.
- Offer catheterisation a parasympathomimetic (bethanechol) for bladder dysfunction.
- Offer a PDE5 inhibitor (sildenafil) for erectile dysfunction.
42
what are the clinical features of diabetic foot disease?
- Foot ulcer.
- Foot pain.
- Foot erythema.
- Oedema of the foot, ankle or calf.
- Absent pedal pulses
- Malaise and anorexia.
43
how should an infected diabetic foot ulcer be managed?
- Offer flucloxacillin for a mild diabetic foot infection (erythema must be less than 2 cm around the ulcer).
- Offer intravenous clindamycin for moderate (erythema is more 2 cm around the ulcer) or severe (signs of systemic inflammatory response syndrome) foot infection.
- Perform amputation in areas of irreversible gangrene.
44
how is diabetic retinopathy managed?
- observation for non-proliferative diabetic nephropathy.
- Perform urgent pan-retinal photocoagulation for proliferative diabetic nephropathy.
- Perform vitrectomy for proliferative diabetic nephropathy that is not amenable to pan-retinal photocoagulation
45
which drugs causes gynaecomastia?
- phenytoin
- oestrogens
- spironolactone
- cimetidine
- digoxin
- marijuana
- goserelin
46
what are the causes of hypercalaemia?
- malignancy
- Primary multiple endocrine neoplasia
- Familial hypocalciuric hypercalcaemia
- Granulomatous disease (TB and sarcoidosis).
- Drugs (lithium and thiazides).
- Vitamins (vitamin A and D)
- hyperparathyroidism
47
what are the clinical features of hypercalcaemia?
- Confusion.
- Fatigue.
- Constipation.
- Loss of appetite.
- Nausea.
- Polyuria.
- Polydypsia.
- Poor skin turgor.
- Bone pain.
48
how is hypercalcaemia managed?
- Administer intravenous normal saline as the first line treatment when serum calcium exceeds 3.0 mmol/L.
- Administer an intravenous bisphosphonate (zoledronic acid or pamidronate disodium).
- Offer calcitonin while awaiting the effect of bisphosphonate as it has a more rapid correction of hypercalcaemia.
- Offer a loop diuretic (furosemide) to manage fluid overload.
49
what factors precipitate hyperosmolar hyperglycaemic state?
- infection
- stroke
- MI
- trauma
- hyperthyroidism
- acromegaly
- thiazide diuretics
- beta blockers
50
what are the clinical features of hyperosmolar hyperglycaemic state?
- Altered mental status.
- Weakness.
- Classical features of diabetes including polyuria, polydypsia and weight loss.
- Features of dehydration including dry mucus membranes, poor skin turgor, tachycardia and hypotension.
- Seizures.
51
how is hyperosmolar hyperglycaemic state managed?
- Administer 0.9% NaCl at a rate of 15 to 12 ml/kg/hour.
- Administer a vasopressor (noradrenaline) if hypotension persists after forced hydration.
- Start insulin therapy (insulin neutral) with a bolus of 0.1 units/kg unless the potassium is less than 3.3 mmol/L, in which case it must be delayed and potassium chloride should be given.
52
what are the clinical features of hyperparathyroidism?
- Fatigue.
- Poor sleep.
- Myalgia.
- Anxiety.
- Depression.
- Polydypsia.
- Polyuria.
- Memory loss.
- Bone pain.
- Constipation.
- Muscle cramps.
- Paraesthesia.
- Renal colic.
- Abdominal pain.
- Features of chronic kidney disease.
- Features of malabsorption syndrome.
53
how is hyperparathyroidism diagnosed?
- hypercalcaemia with normal or elevated PTH
| - elevated ALP and phosphate
54
how is primary hyperparathyroidism?
- parathyroidectomy
- Consider a calcimimetic (cinacalcet) for patients in whom surgery is unsuccessful, is unsuitable or has been declined.
- Consider a bisphosphonate (alendronate) to reduce fracture risk in patients who have an increased fracture risk.
55
how is secondary hyperparathyroidism managed?
- Recommend safe sun exposure for patients who have had a lack of sunlight exposure.
- Optimise management of underlying disease, such as Crohn’s disease or Coeliac disease.
- Recommend dietary phosphate restriction and offer a phosphate binder (sevelamer) for patients with CKD stage 3 or 4.
- Offer vitamin D sterol (calcitriol) or parathyroidectomy for patients with CKD stage 5.
56
what are the causes of hyperthyroidism?
- Graves' disease
- toxic multinodular goitre
- toxic adenoma
- molar pregnancy
- amiodarone
- struma ovarii
- de quervain's thyroiditis
57
what is graves' eye disease?
- exophthalmos (anterior bulging of the eyes)
- upper eyelid retraction
- lid lag
- erythema
- oedema of the extraocular muscles, typically the inferior rectus, producing diplopia.
58
what is graves' dermopathy?
- accumulation of mucopolysaccharides in the deep dermis of the skin
- peau d’orange (orange peel) appearance of the skin over the anterior aspect of the lower legs.
59
what is graves' acropachy?
- clubbing
- swollen fingers
- periosteal knee bone
60
what are the clinical features of hyperthyroidism?
- Heat intolerance.
- Sweating.
- Weight loss despite increased appetite.
- Palpitations.
- Fast, fine tremor.
- Hyperreflexia.
- Orbitopathy (exophthalmos, diplopia, lid retraction, lid lag, erythema, oedema).
- Warm, moist hands.
- Compression symptoms including dysphagia, breathlessness, hoarse voice.
- Irritability and agitation.
- Cardiac flow murmur.
- Muscle weakness, fatigue, and exercise intolerance.
- Muscle wasting.
- Reduced libido.
- Gynaecomastia in men.
- Amenorrhoea and oligomennorhoea.
- Painful goitre in de Quervain’s thyroiditis.
61
how is hyperthyroidism diagnosed?
- Measure serum TSH: Reduced in primary hyperthyroidism; Elevated in secondary hyperthyroidism.
- Measure free T3 and T4 if serum TSH is abnormal: Elevated, except in subclinical disease.
- Measure total T3/T4 or free T3/T4 ratio: Elevated in Graves’ disease and not in thyroiditis.
62
how is Graves' disease managed?
- radioactive iodine
- antithyroid drugs (carbimazole, propylthiouracil)
- Offer total thyroidectomy for adults with Graves’ disease if there are concerns about compression, thyroid malignancy is suspected, or first line treatments are unsuitable.
63
how is Graves' disease managed in children?
- antithyroid drugs are first line treatment
| - should be continued for at least 2 years.
64
how is a toxic nodular goitre treated?
- Offer radioactive iodine as first line treatment for adults with toxic multinodular goitre.
- Offer total thyroidectomy or life-long antithyroid drugs
65
how is thyroid crisis managed?
- Offer high dose carbimazole, intravenous hydrocortisone, iodine (Lugol solution), and oral propranolol.
- Offer cholestyramine to reduce the enterohepatic circulation of thyroid hormones.
66
what are the causes of primary hypogonadism in men?
- Klinefelter’s syndrome.
- Kallman’s syndrome.
- Orchitis related to mumps or an autoimmune disease.
- Drugs such as cyclophosphamide and chlorambucil.
- Testicular trauma or torsion.
67
what are the causes of secondary hypogonadism in men?
- Hyperprolactinaemia, as prolactin suppresses GnRH.
- Pituitary adenoma and craniopharyngioma.
- Infiltrative diseases such as haemochromatosis, sarcoidosis, and histiocytosis.
- Head trauma or surgery.
68
what are the clinical features of hypogonadism in men?
- Decreased libido.
- Loss of spontaneous morning erections.
- Erectile dysfunction.
- Gynaecomastia.
- Infertility.
- Micropenis and small testes.
- Delayed puberty.
69
how is primary hypogonadism diagnosed in men?
- reduced testosterone
| - elevated FSH and LH
70
how is secondary hypogonadism diagnosed in men?
- reduced testosterone
| - decrease FSH and LH
71
how is primary hypogonadism managed in men?
-testosterone replacement
72
what are the causes of hypoparathyroidism?
- Removal or damage to the parathyroid glands during thyroidectomy.
- Congenital deficiency including DiGeorge syndrome.
- Hypomagnesaemia associated with chronic alcoholism, malnutrition, diarrhoea and malabsorption.
- Idiopathic autoimmune hypoparathyroidism.
- Reidel’s thyroiditis.
73
what are the clinical features of hypoparathyroidism?
- Muscle spasm (tetany).
- Trousseau’s sign, a carpopedal spasm induced by ischaemia secondary to the inflation of a sphygmomanometer cuff.
- Chvostek’s sign, gentle tapping over the facial nerve causes twitching of the ipsilateral facial muscles)
- Convulsions.
- Paraesthesia.
- Anxiety
- Cataracts.
- Brittle nails.
74
what are the clinical features of pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism?
- Short stature.
- Short metacarpals.
- Intellectual impairment.
75
how is hypocalcaemia managed?
- Offer intravenous calcium gluconate for severe hypocalcaemia.
- Offer intravenous magnesium sulfate for hypomagnesaemia.
76
what are the causes of panhypopituitarism?
- neoplasia
- sheehan's syndrome
- lymphocytic hypophysitis
- sarcoidosis
- TB
- langerhans cell histiocytosis
- kallman's syndrome
- TBI
- radiotherapy
- chronic opiate use
77
what are the clinical features of panhypopituitarism?
- Features of GH deficiency occur early and include failure to thrive or short stature.
- Features of GnRH deficiency occur early and include delayed puberty, infertility, amenorrhoea, erectile dysfunction, and reduced libido, breast atrophy, hot flushes,
- Features of TSH deficiency include: Weight gain, cold intolerance, constipation, dry skin.
- Features of ACTH deficiency include: Hypoglycaemia, hypotension, nausea, vomiting, fatigue, weakness, dizziness.
- Headaches.
- Visual field defects.
- Ophthalmoplegia.
- Galactorrhoea.
78
how is panhypopituitarism managed?
- Administer oral hydrocortisone to replace ACTH deficiency.
- Offer oral levothyroxine after full adrenal replacement if there is TSH deficiency.
- For females with GnRH deficiency:
- --Offer transdermal oestradiol for if pregnancy is not desired.
- --Offer gonadotrophin if pregnancy is desired.
- Offer gonadotrophin for men with GnRH deficiency.
- Offer recombinant growth hormone (somatropin) for patients with GH deficiency.
- Offer desmopressin for patients with ADH deficiency.
79
what are the causes of hypothyroidism?
- autoimmune thyroiditis
- iodine deficiency
- thyroidectomy/RAI
- De quervain's thyroiditis
- pendreds syndrome
- postpartum
- thyroid infiltration
- reidel's thyroiditis
80
what are the cases of secondary hypothyroidism?
- Pituitary adenomas or gliomas.
- Pituitary surgery, radiotherapy, or trauma.
- Pituitary infarction.
- Sheehan’s syndrome, a postpartum pituitary necrosis due to postpartum haemorrhage. It is supplied by the portal venous system.
- Infiltrative disorders such as amyloidosis, sarcoidosis, haemochromatosis, tuberculosis.
- Drugs such as dopamine and glucocorticoids.
81
what are the clinical features of primary hypothyroidism?
- Cold intolerance.
- Hoarse voice.
- Weight gain.
- Constipation.
- Fatigue and lethargy.
- Menorrhagia.
- Infertility and subfertility.
- Dry skin and hair loss.
- Eyelid and facial oedema.
- Thick tongue.
82
what are the clinical features of secondary hypothyroidism?
- Recurrent headache.
- Diplopia.
- Visual field defects.
- Atrophic breasts.
- Galactorrhoea.
- Amenorrhoea.
- Erectile dysfunction.
- Loss of body hair.
- Cushing’s syndrome.
- Acromegaly
83
what are the clinical features of myxoedema coma?
- Lethargy.
- Bradycardia.
- Hypothermia.
- Seizures and coma
84
how is hypothyroidism diagnosed?
- Measure serum TSH as the initial investigation:
- --Elevated in primary hypothyroidism;
- --Low in secondary hypothyroidism;
- --Elevated with poor compliance to thyroxine;
- --Low with steroid therapy.
- Measure free T3 and T4 if serum TSH is abnormal:
- --Reduced in primary and secondary hypothyroidism
- --Normal in subclinical hypothyroidism
- --Normal with poor compliance to thyroxine
- --Normal with steroid therapy.
85
how is primary hypothyroidism managed?
-Offer oral levothyroxine (1.6 micrograms/kg/day) in all symptomatic patients.
86
how is myxoedema coma managed?
- Emergency admission.
- Intravenous levothyronine 5–20 micrograms every 12 hours.
- Oxygen.
- Intravenous hydrocortisone 100 mg 8-hourly.
- Glucose infusion to prevent hypoglycaemia.
- Gradual rewarming.
- Monitoring of cardiac output and pressures.
87
what are the causes of congenital hypothyroidism?
- maldescent of the thyroid
- athyrosis
- dyshormonogensis
- iodine deficiency
88
what is the klinefelters karyotype?
47, XXY
89
what are the clinical features of klinefelters?
- Taller than average.
- Lack of secondary sexual characteristics.
- Small and firm testes.
- Infertile.
- Gynaecomastia.
90
what are the clinical features of kallman's syndrome?
- Lack of smell (anosmia).
- Delayed puberty.
- Rarely cleft lip and palate.
91
what is the karyotype in turners syndrome?
45,X karyotype.
92
what are the clinical features of turner's syndrome?
- Lymphoedema of the hands and feet
- Spoon shaped nails
- Wide carrying angle
- Short stature.
- Amenorrhoea
- Webbed neck.
- High arched palate.
- Low-set ears.
- Wide-spaced nipples.
- Delayed puberty
- Coarctation of the aorta.
- Bicuspid aortic valve (aortic stenosis).
93
how is turners syndrome treated?
- Growth hormone therapy
- Oestrogen replacement for development of secondary sexual characteristics at the time of puberty (but infertility persists).
94
what are the clinical features of fragile x syndrome?
- Moderate to severe learning difficulty (IQ 20-80)
- Macrocephaly
- Macro-orchidism
- Long face
- Large everted ears
- Prominent mandible
- Broad forehead
- Mitral valve prolapse
- Joint laxity
- Scoliosis
- Autism
- Hyperactivity
95
what are the clinical features of MEN1?
- Bitemporal hemianopia affecting the upper quadrant.
- Galactorrhoea.
- Erectile dysfunction.
- Gynaecomastia.
- Amenorrhoea.
- Infertility.
- Hot flushes.
- Weight gain.
- Constipation.
- Headache.
- Renal colic.
- Polyuria and polydipsia.
- Over-sized hands and feet.
- GI bleeding.
- Epigastric pain.
- Dyspepsia.
96
what are the clinical features of MEN2?
- Headache.
- Palpitations.
- Diaphoresis.
- Renal colic.
- Polyuria and polydipsia.
- Palpable thyroid nodule.
97
how should suspected MEN1 be investigated?
- Measure serum prolactin and IGF-1: Raised.
- Measure serum parathyroid hormone and calcium: Raised.
- Measure serum gastrin: Raised.
98
how should suspected MEN2 be investigated?
- Measure serum parathyroid hormone and calcium: Raised.
- Perform 24-hour urinary collection of metanephrines: Raised.
- Perform a thyroid biopsy: Medullary thyroid cancer.
- Measure serum calcitonin: Elevated.
99
how is MEN1 managed?
- Offer intravenous saline and zoledronic acid for hypercalcaemia associated with hyperparathyroidism.
- Offer omeprazole for gastrinoma / Zollinger-Ellison syndrome.
- Offer octreotide for pancreatic islet cell tumours.
- Offer trans-sphenoidal surgery and adjunct hormonal replacement for pituitary adenomas.
100
how is MEN2 managed?
- Offer intravenous saline and zoledronic acid for hypercalcaemia associated with hyperparathyroidism.
- Perform total thyroidectomy for medullary carcinoma.
- Offer alpha and beta blockade and unilateral adrenalectomy for phaeochromocytoma.
101
what are the clinical features of phaechromocytoma?
- Resistant hypertension.
- Hypertension that presents at young age.
- Classic triad of symptoms:
- --Headache.
- --Palpitations.
- --Diaphoresis
- Pallor.
- Orthostatic hypotension.
102
how is phaechromocytoma diagnosed?
- Perform 24-hour urinary collection of metanephrines: Elevated.
- Measure serum free metanephrines: Elevated.
103
how is phaechromocytoma managed?
- alpha blocker (phenoxybenzamine)
- beta blocker (propranolol)
- surgical excision of the entire adrenal gland
- long-term alpha and beta blockade if the patient is not a surgical candidate
- chemo if malignant
104
what are the causes of primary hyperaldosteronism?
- Bilateral adrenal hyperplasia is the most common cause of primary hyperaldosteronism.
- Adrenal adenomas (Conn’s syndrome) are less common, and are sub-classified according to whether they are angiotensin unresponsive or angiotensin responsive.
105
what are the clinical features of primary hyperaldosteronism?
- Hypertension.
- Nocturia.
- Polyuria.
- Lethargy.
- Classical but rare features include muscle cramps, weakness, and paraesthesia.
106
how is primary hyperaldosteronism diagnosed?
- serum aldosterone/renin ratio: Elevated in primary hyperaldosteronism (high aldosterone and low renin
- fludrocortisone suppression test (fails to suppress aldosterone)
- adrenal villous sampling for localisation
107
how is primary hyperaldosteronism managed?
- aldosterone antagonist (amiloride or spironolactone)
- Perform unilateral laparoscopic adrenalectomy for a unilateral adrenal adenoma.
- Offer glucocorticoids (dexamethasone) to control hypertension in patients with familial hyperaldosteronism.
- Bilateral adrenalectomy is only considered for patients with marked bilateral and severe adrenal adenoma. I
108
what are the causes of SIADH?
- Drugs such as antidepressants (citalopram), antiepileptics (carbamazepine), and sulfonylureas (glipizide).
- Pulmonary processes including pulmonary infections and lung cancers, especially small cell lung cancer.
- Subarachnoid haemorrhage.
109
what are the clinical features of SIADH?
- Nausea and vomiting.
- Headache.
- Altered mental status.
- Coma.
- Absence of hypovolaemia or hypervolaemia.
110
how is SIADH diagnosed?
- hyponatraemia
- reduced serum osmolality
- elevated urine osmolality
- elevated urine sodium
111
how is SIADH managed?
- For severe neurological symptoms: Administer 3% saline with adjunct furosemide.
- For mild to moderate symptoms (nausea and vomiting): Commence fluid restriction of 1 to 1.5 litres per day.
- For persistent chronic SIADH offer a V2 antagonist (tolvaptan) in patients who are intolerant to fluid restriction.
112
what are the clinical features of thyroid carcinoma?
- Typically asymptomatic.
- Palpable thyroid nodule.
- Hoarseness due paralysis of ipsilateral vocal cord.
- Dyspnoea.
- Dysphagia.
- Tracheal deviation.
- Cervical lymphadenopathy.
- Features of carcinoid disease: Diarrhoea, flushing, palpitations (Medullary carcinoma).
- Rapid neck enlargement (lymphoma).
- Uncontrolled hypertension (MEN syndrome 2).
- Features of advanced disease: Fatigue; Night sweats; Weight loss; Back pain.
113
how is thyroid carcinoma managed?
- Offer total thyroidectomy and radioiodine and levothyroxine as first line management for papillary, follicular and medullary carcinoma.
- Offer a tyrosine kinase inhibitor (sorafenib, lenvatinib, vandetanib) for metastatic disease where the patient can manage the toxicity.
114
what are the clinical features of type 1 diabetes?
- Polyuria.
- Polydipsia.
- Weight loss.
- Generalised weakness.
- Blurred vision.
- tiredness
- Features of DKA include such as vomiting, tachypnoea, abdominal pain, coma.
115
how is type 1 diabetes diagnosed in children?
- Random plasma glucose greater than 11 mmol/L in symptomatic patients.
- Both a random plasma glucose greater than 11 mmol/L and a fasting plasma glucose greater than 6.9 mmol/L in asymptotic patients.
- A HbA1c greater than 48 mmol/mol.
116
how is type 1 diabetes diagnosed in adults?
-Diagnose type 1 diabetes on clinical grounds in adults presenting with hyperglycaemia (random plasma glucose greater than 11 mmol/L)
117
how is type 1 diabetes managed in children?
- education programme
- multiple daily injection basal-bolus insulin regimens
- Use an intermediate acting insulin (isophane insulin) for basal dosing, once daily before bed.
- Use a short acting insulin (insulin aspart) for bolus dosing before meals.
- continuous insulin pumps
118
what are the sick day rules for a child with type 1 diabetes?
- Never stop or omit insulin.
- Check blood glucose more frequently, for example every 1-2 hours including through the night.
- Check for blood ketone levels regularly, for example every 3-4 hours including through the night, and sometimes every 1-2 hours depending on results.
- Maintain normal meal patterns here possible if appetite is reduced.
- Maintain adequate fluid intake (3L) to prevent dehydration.
- Seek urgent medical advice if they are violently sick, drowsy, or unable to keep fluid down
119
how is type 1 diabetes managed in adults?
- education
- self-monitoring
- coeliac serology
- DAFNE
- Offer multiple daily injection basal–bolus insulin regimens:
- --Use a long acting insulin (insulin detemir) for basal dosing, once daily before bed.
- --Use a short acting insulin (insulin aspart) for bolus dosing before meals.
120
what are the symptoms of hypoglycaemia?
- sweating
- tremor
- pounding heartbeat.
- pallor
- sweating
121
how is mild hypoglycaemia managed?
-Prompt consumption of 10-20 g of fast acting carbohydrates preferably in liquid form (fizzy drink, Lucozade).
122
how is hypoglycaemia managed if the patient is unconscious?
- Administer intramuscular glucagon immediately.
- Arrange emergency transfer to hospital (999) if intramuscular glucagon is not available, or there is no response to intramuscular glucagon.
- Administer intravenous glucose 50% followed by a saline flush (as glucose scleroses veins).
123
what are the risk factors for developing type 2 diabetes?
- Obesity and inactivity.
- Family history.
- Ethnicity (more common in BAME people).
- History of gestational diabetes.
- Poor dietary habits (low fibres, high GI diet).
- Drug treatments such as statins, corticosteroids and combined treatment with a thiazide diuretic plus a beta blocker.
- Polycystic ovarian syndrome.
- Metabolic syndrome.
- Low birth weight for gestational age.
124
what are the clinical features of type 2 diabetes?
- Asymptomatic.
- History of candidal infections of the vagina, penis, and skin folds.
- History of urinary tract infections.
- Fatigue.
- Blurred vision.
- Acanthosis nigricans.
125
how is type 2 diabetes diagnosed?
- HbA1c >48mmol/mol on two occasions
- fasting glucose >6.9mmol/l
- random plasma glucose >11mmol/l
126
how is type 2 diabetes managed?
- education with diet and lifestyle advice
- metformin
- if metformin contraindicated, give sitagliptin, pioglitazone, gliclazide or dapagliflozin first line
- dual therapy if mono therapy fails (HbA1c >58) and triple therapy if this fails
- if high weight add exenatide (GLP-1)
- insulin
127
what is pre-diabetes?
- fasting plasma glucose level is 5.6 - 6.9
| - HbA1c is 42 - 47 mmol/mol.
128
when is pioglitazone contraindicated?
- history of bladder cancer
| - heart failure
129
what are the clinical features of achondroplasia?
- At birth or within the first year of life, with disparity between large skull, normal length trunk and short arms and legs.
- The chest is usually very narrow.
- Fingertips may only come down to the iliac crest.
- Shortness is particularly evident in the proximal segments of limbs.
- Limbs appear very broad with deep creases and trident-like hands with short fingers.
- There is often increased joint laxity.
- Skull shows a bulging vault, small face and a flat nasal bridge or 'scooped out' glabella.
- Spine shows marked lumbar lordosis.
- Frontal bossing, depressed nasal bridge.
130
how is achondroplasia diagnosed?
- based on the typical clinical and X-ray features of:
- --metaphyseal irregularity
- --flaring in the long bones
- --late-appearing irregular epiphyses.
- --pelvis is narrow in anteroposterior diameter
- --deep sacroiliac notches
- --short iliac wings.
- --spine shows progressive narrowing of the interpedicular distance from top to bottom (reverse of normal).
-prenatally on USS or plasma analysis for the FGFR3 mutation
131
what is precocious puberty?
secondary sexual characteristics appear before 8 years of age in girls and 9 years in boys.
132
what are the causes of gonadotrophin dependent precocious puberty?
-Idiopathic
- Brain neoplasms
- Cranial radiotherapy.
- Neurodisability conditions such as hydrocephalus, cerebral palsy, post-infection such as meningitis or encephalitis
- Post-traumatic head injury.
- Gain-of-function mutations in GPR54, a G protein-coupled receptor that is a ligand for kisspeptin, can cause GDPP
- Midline forebrain abnormalities such as holoprosencephaly or septo-optic dysplasia.
- Association with child adoption and sexual abuse.
133
what are the causes of gonadotrophin independent precocious puberty?
- Ovarian causes: follicular cysts of the ovary, granulosa cell tumours, Leydig cell tumours, and gonadoblastoma.
- Testicular causes: Leydig cell tumours and a defect of luteinising hormone (LH) receptor function (testotoxicosis or familial GIPP).
- Adrenal causes: Congenital adrenal hyperplasia (CAH) in males results in GIPP. Other adrenal causes include Cushing's syndrome and an adrenal virilising tumour.
- McCune-Albright syndrome (MAS).
- Exposure to exogenous hormones such as the contraceptive pill or testosterone gels
- Human chorionic gonadotrophin-secreting germ cell tumours
134
what are the clinical features of precocious puberty?
- More common in females
- Presence of risk factors
- Breast development
- Pubic/axillary hair
- Acne
- Body odour
- Menarche
- Increased growth velocity and tall stature
- Signs of McCune-Albright Syndrome
- testes >4ml in males
135
how is precocious puberty diagnosed?
- Perform a bone age estimate with a left hand/wrist x-ray: advanced
- Measure basal serum FSH and LH: Low in gonadotrophin-independent cases; elevated in gonadotrophin dependent cases
- Measure serum testosterone: Elevated in males; may be elevated in females with CAH
- Measure serum oestrogen: elevated in females
- Perform an LHRH stimulation test: elevated LH and FSH in gonadotrophin dependent cases; suppressed LH and FSH in gonadotrophin independent cases
136
how is gonadotrophin dependent precocious puberty managed?
- Treat the underlying cause
- Consider GnRH agonist to suppress puberty (leuprorelin or goserelin)
- Consider growth hormone treatment in patients with poor growth as a result of GnRH treatment
137
how is gonadotrophin independent precocious puberty managed?
- In cases of McCune-Albright Syndrome or testotoxicosis:
- --Give ketoconazole to inhibit steroid synthesis
- --Provide supportive care for McCune-Albright
- --Give GnRH agonist to suppress puberty
- In CAH:
- --Optimise management with hydrocortisone to prevent rapid virilisation and give GnRH agonist to prevent puberty
138
what is delayed puberty and what is the most common cause?
- Defined as the lack of any pubertal signs by the age of 13 years in girls and 14 years in boys.
- constitutional delay in growth and puberty
139
what are the clinical features of delayed puberty?
- Boys: testes <3ml
- Girls: absent breast development and absence of menarche
- Absent growth spurt
- Absent pubic/axillary hair
- Anosmia in Kallman’s syndrome
- Short stature
- Dysmorphic features of chromosomal abnormalities
140
how is delayed puberty diagnosed?
- Perform a bone age measurement with a non-dominant wrist x-ray: delayed bone age
- Measure basal FSH and LH: low in hypogonadotrophic hypogonadism; elevated in hypergonadotrophic hypogonadism
141
how is constitutional delay in growth and puberty managed?
- In boys:
- --Observe and monitor
- --Give a short course of oxandrolone or testosterone cypionate in boys with abnormal psychosocial adjustment
- In girls:
- --Observe and monitor
- --Give a short course of oestradiol in girls with abnormal psychosocial adjustment
142
how are organic causes of delayed puberty managed?
- In boys, induce puberty with testosterone cypionate
- In girls, induce puberty with oestradiol and cyclical progesterone
- If Turner’s syndrome, give growth hormone replacement
143
how is persistent hypogonadism post puberty managed?
- In boys, give testosterone supplementation, and testicular implants for cosmesis
- In girls, give oestradiol and progesterone, and breast implants for cosmesis
144
when should MODY be suspected?
- non-obese
- young patients
- family history of diabetes in 2 or more successive generations
145
what are the adverse effects of insulin?
- Hypoglycaemia which can lead to coma and death
| - Lipohypertrophy if injection sites are not rotated.
146
in which patients should insulin be used cautiously?
-renal impairment.
147
with which drugs does insulin interact?
-Corticosteroids increase insulin requirements
148
what are the adverse effects of metformin?
- GI upset including nausea and vomiting
- Lactic acidosis is a fatal rare side effect characterised by vomiting, difficulty breathing and muscle cramps.
- diarrhoea
149
in which patients should metformin be used cautiously?
- Avoid in severe renal impairment (metformin accumulation)
- Avoid in severe tissue hypoxia (increased lactate production)
- Caution in hepatic impairment (reduced lactate metabolism).
150
with which drugs does metformin interact?
-Increased risk of renal impairment with IV contrast media, ACE inhibitors, NSAIDS, diuretics.
151
what are the adverse effects of gliclazide?
- GI upset including nausea and vomiting
- Hypoglycaemia
- Hypersensitivity reactions including cholestatic jaundice, rash, fever and agranulocytosis.
152
in which patients should gliclazide be used cautiously?
- Caution in patients with hepatic impairment
- Caution in patients with malnutrition
- Caution in patients with adrenal or pituitary insufficiency.
153
with which drugs does gliclazide interact?
- Increased risk of hypoglycaemia with metformin, thiazolidinediones and insulin
- Reduced efficacy with drugs that elevate blood glucose including prednisolone and diuretics.
154
what are the adverse effects of pioglitazone?
- GI upset such as nausea and vomiting
- Neurological effects such as headache, dizziness and altered vision
- Oedema and cardiac failure when prescribed with insulin
- Increased risk of bladder cancer and bone fractures
- Liver toxicity.
155
in which patients should pioglitazone be used cautiously?
- Avoid in heart failure
- Avoid in bladder cancer
- Caution in people with risk factors for bladder cancer
- Caution in cardiovascular disease
- Caution in elderly patients
- Caution in hepatic impairment.
156
what are the adverse effects of sitagliptin?
- GI disturbances
- Nasopharyngitis
- Pancreatitis
- Hypoglycaemia (owing to reduced stomach emptying by GIP, with reduced glucose absorption into blood).
157
in which patients should sitagliptin be used cautiously?
- Avoid in DKA
- Caution with hepatic impairment
- Caution with renal impairment;
- Caution with heart failure
- Caution in the elderly.
158
with which drugs does sitagliptin interact?
- Increased plasma concentration of digoxin
| - Enhanced hypoglycaemic effect with other anti-diabetic drug.
159
what are the adverse effects of exenatide?
- GI disturbances
- Severe pancreatitis (haemorrhagic or necrotising)
- Hypoglycaemia
- Antibody formation.
160
in which patients should exenatide be used cautiously?
- Avoid in DKA
- Avoid in gastroparesis
- Caution in the elderly
- Caution with renal impairment.
161
with which drugs does exenatide interact?
- Increased anticoagulant effect of warfarin
| - Increased hypoglycaemic effect with other anti-diabetic drugs.
162
what are the adverse effects of corticosteroids?
- Increased risk of infection
- Increased risk of diabetes mellitus and osteoporosis
- Increased muscle weakness
- Easy bruising
- Peptic ulceration
- Mood and behavioural changes
- Hypertension
- Adrenal atrophy
- Addisonian crisis if withdrawn immediately.
163
in which patients should corticosteroids be used cautiously?
- Caution with infection
| - Caution in children.
164
with which drugs do corticosteroids interact?
- Increased risk of peptic ulceration and Gi bleeding with NSAIDs
- Increased risk of hypokalaemia with β2-agonists and diuretics
- Reduced efficacy with phenytoin, carbamazepine, rifampicin; Reduced response to vaccines.
165
what are the adverse effects of bisphosphonates?
- Oesophagitis
- Hypocalcaemia
- Osteonecrosis of jaw
- Atrial fibrillation
- Atypical femoral fractures.
166
in which patients should bisphosphonates be used cautiously?
- Avoid in severe renal impairment
- Avoid in hypocalcaemia
- Avoid in patients with active upper gastrointestinal disorders
- Caution in smokers and patients with major dental disease due to risk of ONJ.
167
with which drugs do bisphosphonates interact?
Reduced absorption with calcium salts, antacids and iron salts.
168
what are the adverse effects of carbimazole?
- Minor side effects include rash, arthritis, jaundice and headache
- Serious side effects include agranulocytosis and neutropenia.
169
in which patients should carbimazole be used cautiously?
- Avoid in severe blood disorders
- Avoid block and replace regimen in pregnancy as it crosses the placenta
- Caution in hepatic impairment
- Discontinue with neutropenia.
170
what are the adverse effects of thyroxine?
- GI features such as diarrhoea
- Cardiac features such as arrhythmia and palpitations
- Neurological features such as tremor and insomnia.
171
in which patients should thyroxine be used cautiously?
- Caution in patients with coronary artery disease
- Caution in hypopituitarism, in which Addisonian crisis may occur if corticosteroid therapy is not initiated prior to treatment.
172
with which drugs does thyroxine interact?
- Reduced absorption with antacids, calcium or iron salts
- Reduced metabolism with phenytoin or carbamazepine
- Increased anticoagulant effects of warfarin.
