Endocrinology Flashcards
endocrine abnormality and features of acromegaly
excess growth hormone secondary to pituitary adenoma
rare - caused by ectopic GHRH/GH production by tumours
Features
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
investigations and results in acromegaly
serum IGF-1 - raised
also used to monitor disease
OGTT - confirms diagnosis
no suppression of GH (should be <2)
pituitary MRI may demonstrate tumour
management of acromegaly
trans-sphenoidal surgery - first line tx
if inoperable/surgery unsuccessful may need medication
somatostatin analogue e.g., octreotide - inhibits GH
pegvisomant - GH recdeptor antagonist
dopamine agonist - bromocriptine
definition and features of addison’s disease
AI destruction of adrenal glands causing hypoadrenalism - reduced cortisol and aldosterone
features
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
non-addisonian causes of hypoadrenalism
primary causes
tuberculosis
metastases (e.g. bronchial carcinoma)
meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
HIV
antiphospholipid syndrome
secondary causes
pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
investigation findings in addison’s disease
ACTH stimulation test - short synacthen test
Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM
9am serum cortisol may also be useful
> 500 nmol/l makes Addison’s very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l should prompt a ACTH stimulation test to be performed
managing addison’s disease
glucocorticoid and mineralocorticoid replacement therapy
hydrocortisone: usually given in 2 or 3 divided doses. Patients typically require 20-30 mg per day, with the majority given in the first half of the day - double in intercurrent illness
fludrocortisone - stays the same in illness
hydrocortisone for injection for adrenal crisis
causes of an addisonian crisis
sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
steroid withdrawal
management of an addisonian crisis
hydrocortisone 100 mg im or iv
1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
cause and features of
bartter’s syndrome
inherited AR cause of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle - similar to taking massive dose of furosemide
usually presents in childhood, e.g. Failure to thrive
polyuria, polydipsia
hypokalaemia
normotension
weakness
use and moa of carbimazole
management of thyrotoxicosis - 6w high dose until pt euthyroid
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
may cause agranulocytosis
crosses placenta but may be used in low doses in pregnancy
relationship between magnesium and calcium
magnesium required for PTH secretion and its action on target tissues - may result in hypocalcaemia and cause poor response to calcium/VD supplementation
types of congenital adrenal hyperplasia
AR disorders affecting steroid biosynthesis - resulting low cortisol causes high ACTH secretion, stimulating adrenal androgen production
21-hydroxylase deficiency (90%)
11-beta hydroxylase deficiency (5%)
17-hydroxylase deficiency (very rare)
usually screened for, ACTH stimulation testing used to confirm diagnosis
features of 21-hydroxylase deficiency
virilisation of female genitalia
precocious puberty in males
60-70% of patients have a salt-losing crisis at 1-3 wks of age
11-beta hydroxylase deficiency features
virilisation of female genitalia
precocious puberty in males
hypertension
hypokalaemia
features of congenital hypothyroidism
screened for with heel-prick at 5-7 days
Features
prolonged neonatal jaundice
delayed mental & physical milestones
short stature
puffy face, macroglossia
hypotonia
If not diagnosed and treated within the first four weeks it causes irreversible cognitive impairment
17-hydroxylase deficiency features
non-virilising in females
inter-sex in boys
hypertension
types corticosteroid drugs
high mineralocorticoid activity - fludrocortisone
high mineralocorticoid - hydrocortisone
glucocorticoid - prednisolone
v high glucocorticoid - dexamethasone, betamethasone
S/E of glucocorticoids
endocrine - impaired glucose regulation, weight gain, hirsuitism, hyperlipidaemia
cushing syndrome
MSK - osteoporosis, prox myopathy, AVN femoral neck
immunosuppression
psychiatric - insomnia, mania
GI - peptic ulcers, acute pancreatitis
ophthalmic - glaucoma, cataracts
growth suppression
neutrophilia
mineralocorticoid S/E
fluid retention
hypertension
causes of cushing syndrome
ACTH dependent causes - cushing disease (80%) - pituitary tumour screning ACTH causing adrenal hyperplasia
ectopic ACTH production from SCLC
ACTH independent causes - exogenous, more common
iatrogenic: steroids
adrenal adenoma (5-10%)
adrenal carcinoma (rare)
Carney complex: syndrome including cardiac myxoma
micronodular adrenal dysplasia (very rare)
what is pseudo-cushings and how to differentiate
mimics Cushing’s
often due to alcohol excess or severe depression
causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
insulin stress test may be used to differentiate
tests to confirm cushingss syndrome
hypokalaemic metabolic alkalosis and impaired glucose tolerance
overnight (low-dose) dexamethasone suppression test - most sensitive test, first-line to test for Cushing’s syndrome - morning cortisol spike notsuppressed
24 hr urinary free cortisol
two measurements are required
bedtime salivary cortisol
two measurements are required
how is high dose dexamethasone suppression test used
cortisol and ACTH suppressed - cushings disease
cortisol and ACTH not suppressed - ectopic ACTH
cortisol not suppressed, ACTH suppressed - cushings syndrome due to other cause
features of DKA
abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
acetone-smelling breath (‘pear drops’ smell)
antibodies present in T1DM
Antibodies to glutamic acid decarboxylase (anti-GAD) (80%)
Islet cell antibodies (ICA, against cytoplasmic proteins in the beta cell) (70-80%)
Insulin autoantibodies (IAA) - presence reduces with age
Insulinoma-associated-2 autoantibodies (IA-2A)
typical features of T1DM patient
young, acute onset, recent weight loss, DKA features, ketonuria common
ketosis
rapid weight loss
age of onset below 50 years
BMI below 25 kg/m²
personal and/or family history of autoimmune disease
diagnostic criteria for diabetes
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
HbA1c figures for diabetes diagnosis
a HbA1c of greater than or equal to 48 mmol/mol (6.5%)
a HbAlc value of less than 48 mmol/mol (6.5%) does not exclude diabetes
if asymptomatic - repeat test to confirm diagnosis
misleading HbA1c results can be caused by increased red cell turnover
definition of impaired fasting glucose and impaired glucose tolerance
impaired fasting glucose = >6.1, <7
impaired glucose tolerance - fasting glucose <7, OGTT 2h > 7.8, <11.1
managing type 1 diabetes (pharmacological and monitoring)
insulin - due to absolute deficiency, SC
basal-bolus insulin - multiple daily injection
twice-daily insulin detemir
rapid acting insulin analogues before meals
add metformin if BMI >25
HbA1c measurement every 3-6m - target <48
self monitoring glucose 4x/day
blood glucose targets - 5-7 on waking, 4-7 before meals
managing type 2 diabetes
oral metformin
+ SGLT2 - if CVD
sulfonylureas (gliclazide) - stimulate pancreatic b cells to secrete insulin
gliptins (DPP4 inhibitors) - inhibits glucagon secretion
pioglitazone (thiazolidinediones) - promote adipogenesis
HbA1c measurement every 3-6m - target <48
GLP 1 drugs
exenatide - GLP1 mimic - increase insulin secretion, inhibit glucagon secretion - weight loss
sitagliptin - DPP4 inhibitors - increase incretin levels by reducing breakdown -
sick day rules for type 1 diabetes
if on insulin - do not stop due to risk of diabetic ketoacidosis
frequent checking of blood glucose
maintain normal meal pattern and drinkk >3L fluid
sick day rules for type 2 diabetes
temporarily stop some oral hypoglycaemics during acute illness
restart medication once person feeling better and drinking for 24-48h
metformin - stop if risk of dehydration (reduce risk of lactic acidosis_
sulfonylurea - increase risk of hypo
SGLT-2 inhibitors - check for ketones and stop treatment if unwill/risk of dehydration
GLP-1 receptor agonists - stop if risk of dehydration
monitor blood glucose more frequently
causes of diabetic foot disease
neuropathy: resulting in loss of protective sensation (e.g. not noticing a stone in the shoe), Charcot’s arthropathy, dry skin
peripheral arterial disease: diabetes is a risk factor for both macro and microvascular ischaemia
how does diabetic foot disease present
neuropathy: loss of sensation
ischaemia: absent foot pulses, reduced ankle-brachial pressure index (ABPI), intermittent claudication
complications: calluses, ulceration, Charcot’s arthropathy, cellulitis, osteomyelitis, gangren
what happens during diabetic ketoacidosis
uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies
causes: infection, missed insulin doses and myocardial infarction.
Features
abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath (‘pear drops’ smell)
diagnostic criteria for diabetic ketoacidosis
Key points
glucose > 11 mmol/l or known diabetes mellitus
pH < 7.3
bicarbonate < 15 mmol/l
ketones > 3 mmol/l or urine ketones ++ on dipstick
managing diabetic ketoacidosis
fluid replacement - DKA pt usually deplete 5-8l
use isotonic saline
insulin - 0.1unit/kg/hr
once blood glucose <14mmol/l start 10% dextrose at 125ml/hr
usually K+ is high - should fall following insulin tx - may cause hypokalaemia thus may need to add replacement K+ 20mmol/hr
features of diabetic neuropathy
peripheral - sensory loss, not motor loss - glove and stocking, lower legs affected first due to the length of the sensory neurons supplying this area, may be painful
mx - amitriptyline, duloxetine, gabapentin, pregabalin
gastrointestinal autonomic neuropathy - gastroparesis, bloating, vomiting, chronic diarrhoea, GORD
mx - metoclopramide, domperidone
features of androgen insensitivity syndrome
46 XY
X-linked recessive condition. Defect in androgen receptor results in end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype.
Rudimentary vagina and testes present but no uterus. Testosterone, oestrogen and LH levels are elevated
features of 5-a reductase deficiency
46 XY
Autosomal recessive condition. Results in the inability of males to convert testosterone to dihydrotestosterone (DHT).
Individuals have ambiguous genitalia in the newborn period. Hypospadias is common. Virilization at puberty.
features of female pseudohermaphroditism
46XX
Individual has ovaries but external genitalia are male (virilized) or ambiguous. May be secondary to congenital adrenal hyperplasia
features of male pseudohermaphroditism
46XY
Individual has testes but external genitalia are female or ambiguous. may be secondary to androgen insensitivity syndrome
features of true hermaphroditism
46XX or 47XXY
Very rare, both ovarian and testicular tissue are present
DVLA rules for diabetes mellitus
insulin users cannot hold HGV licence
DVLA rules
no severe hypoglycaemic event in prev 12m
full hypoglycaemic awareness
adequate condition control with regular blood glucose monitoring
undertand risks of hypoglycaemia
causes of inaccurate HbA1c interpretation
The level of HbA1c is dependent on:
red blood cell lifespan
average blood glucose concentration
lower than expected HbA1c
Sickle-cell anaemia
GP6D deficiency
Hereditary spherocytosis
Haemodialysis
higher than expected HbA1c
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
features of graves disease
most common cause of thyrotoxicosis
usually seen in F 30-50y
thyrotoxicosis
eye signs (30% of patients) - exophthalmos, ophthalmoplegia
pretibial myxoedema
thyroid acropachy, a triad of: digital clubbing, soft tissue swelling of the hands and feet, periosteal new bone formation
investigation findings in graves disease
TSH receptor stimulating antibodies (90%)
anti-thyroid peroxidase antibodies (75%)
thyroid scintigraphy
diffuse, homogenous, increased uptake of radioactive iodine
management of graves disease
propranolol - blocks adrenergic effects
carbimazole - start at 40mg and reduce to maintain euthyroidism - continue for 12-18m
radioiodine treatment - for patients who relapse
C/I - pregnancy for 4-6m, <16y
post-radioiodine, patients may become hypothyroid
indications for growth hormone therapy
GH given SC, discontinue if poor response in 1st year of therapy
proven growth hormone deficiency
Turner’s syndrome
Prader-Willi syndrome
chronic renal insufficiency before puberty
features of hashimoto’s thyroiditis
chronic autoimmune thyroiditis - autoimmune disorder assx with hypothyroidism, with transient thyrotoxicosis in acute phase
Features
features of hypothyroidism
goitre: firm, non-tender
anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies
assx with other autoimmune conditions e.g. coeliac disease, type 1 diabetes mellitus, vitiligo and MALT lymphoma
causes of hypercalcaemia
Primary hyperparathyroidism
malignancy
sarcoid
VD intoxication
acromegaly
thyrotoxicosis
causes and definition of hyperosmolar hyperglycaemic state
medical emergency with significant mortality
hyperglycaemia → ↑ serum osmolality → osmotic diuresis → severe volume depletion and electrolyte deficiencies
presents in elderly with T2DM
precipitated by intercurrent illness, dementia, sedative drugs
features of hyperosmolar hyperglycaemic state
comes on over days with more extreme dehydration and metabolic disturbances
consequences of volume loss
clinical signs of dehydration
polyuria
polydipsia
systemic
lethargy
nausea and vomiting
neurological
altered level of consciousness
focal neurological deficits
haematological
hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)
diagnostic markers for HHS
hypovolaemia
marked hyperglycaemia (>30 mmol/L)
significantly raised serum osmolarity (> 320 mosmol/kg)
can be calculated by: 2 * Na+ + glucose + urea
no significant hyperketonaemia (<3 mmol/L)
no significant acidosis (bicarbonate > 15 mmol/l or pH > 7.3 – acidosis can occur due to lactic acidosis or renal impairment)
management of HHS
fluid replacement - fluid loss of 100-220ml/kg - give normal saline 0.5-1L/.hour
monitor K+
insulin - dont give until blood glucose stops falling with IV fluids
VTE prophylaxis due to hyperviscosity
causes of hypoglycaemia (non diabetes)
insulinoma - increased ratio of proinsulin to insulin
self-administration of insulin/sulphonylureas
liver failure
Addison’s disease
alcohol - exaggerates insulin secretion
physiological response to hypoglycaemia
hormonal response - reduced insulin secretion, increased glucagon secretion
sympathoadrenal response - increased catecholamine-mediated (adrenergic) and acetycholine-mediated (cholinergic) neurotransmission in peripheral ANS and CNS
features of hypoglycaemia
BM <3.3 mmol/L - autonomic symptoms due to release of glucagon and adrenaline
Sweating
Shaking
Hunger
Anxiety
Nausea
blood conc <2.8mmol/L - causes neuroglycopenic symptoms due to inadequate glucose supply to brain
Weakness
Vision changes
Confusion
Dizziness
management of hypoglycaemia
if alert (out or in hospital)
oral glucose 10-20g - liquid, gel or tablet form, glucogel, dextrogel
unconscious or unable to swallow - SC or IM glucagon
IV 20% glucose in large vein
definition and features of primary hypoparathyroidism
reduced PTH secretion (e.g., secondary to thyroid to surgery) causing low calcium and phosphate
tx - alfacalcidiol
symptoms of hypoparathyroidism
tetany: muscle twitching, cramping and spasm
perioral paraesthesia
Trousseau’s sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
Chvostek’s sign: tapping over parotid causes facial muscles to twitch
if chronic: depression, cataracts
ECG: prolonged QT interval
definition and features of pseudoparathyroidism
target cells insensitive to PTH
Associated with low IQ, short stature, shortened 4th and 5th metacarpals
low calcium, high phosphate, high PTH
diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH
hypoparathyroidism - raise cAMP and phosphate
pseudoparathyroidism only cAMP rises or doesnt rise
features of pseudopseudohypoparathyroidism
similar phenotype to pseudohypoparathyroidism but normal biochemistry
causes of hypothyroidism
hashimoto’s thyroiditis - most common cause, AI disease
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
causes of secondary hypothyroidism
From pituitary failure
Other associated conditions
Down’s syndrome
Turner’s syndrome
coeliac disease
features of hypothyroidism
general - weight gain, lethargy, cold intolerance
skin - dry, cold, yellow skin, non-pitting oedema, dry coarse scalp hair
GI - constipation
gynaecological - menorrhagia
neurological - reduced deep tendon reflexes, carpal tunnel
doses of levothyroxine therapy
cardiac disease or >50y - start on 25mcg OD
normal patients - 50-100mcg OD
after changing thyroxine - do TFTs after 8-12w
goal - to normalise TSH level
dose in pregnancy - increase by 25-50mcg
side effects of thyroxine therapy
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
atrial fibrillation
Interactions
iron, calcium carbonate
absorption of levothyroxine reduced, give at least 4 hours apart
function of insulin
Secreted in response to hyperglycaemia
Glucose utilisation and glycogen synthesis
Inhibits lipolysis
Reduces muscle protein loss
Increases cellular uptake of potassium (via stimulation of Na+/K+ ATPase pump)
when is the insulin stress test used
used in investigation of hypopituitarism
IV insulin given, GH and cortisol levels measured
with normal pituitary function GH and cortisol should rise
types of insulin therapy
Rapid-acting insulin analogues - bolus dose (novorapid, humalog)
Short-acting insulins - bolus dose - actrapid (soluble)
Long-acting insulins - levemir OD/BD, lantus OD
premixed intermediate acting with rapid acting - novomix
side effects of insulin therapy
hypoglycaemia - give insulin treated pt glucagon kit
Lipodystrophy - atrophy or lumps of SC fat
features of an insulinoma
a neuroendocrine tumour deriving mainly from pancreatic islets of Langerhans - most common pancreatic endocrine tumour
hypoglycaemia sx, rapid weight gain
high insulin
high proinsulin:insulin ratio
high c peptide
investigation and management of insulinoma
Diagnosis
supervised, prolonged fasting (up to 72 hours)
CT pancreas
Management
surgery
diazoxide and somatostatin if patients are not candidates for surgery
definition of kallman syndrome
cause of delayed puberty secondary to hypogonadotropic hypogonadism (failure of GnRH secreting neurons to migrate to hypothalamus)
X linked recessive trait
features of kallman syndrome
‘delayed puberty’
hypogonadism, cryptorchidism
anosmia
sex hormone levels are low
LH, FSH levels are inappropriately low/normal
normal/tall
management of kallman syndrome
testosterone supplementation
gonadotrophin supplementation may result in sperm production if fertility is desired later in life
features of klinefelter’s syndrome
47 XXY
Features
often taller than average
lack of secondary sexual characteristics
small, firm testes
infertile
gynaecomastia - increased incidence of breast cancer
elevated gonadotrophin levels but low testosterone
diagnosed by karyotype
definition of liddle’s syndrome
rare autosomal dominant condition
causes hypertension and hypokalaemia alkalosis
caused by increased sodium reabsorption
moa of meglitinides
increase pancreatic insulin secretion
often used for patients with an erratic lifestyle
adverse effects include weight gain and hypoglycaemia (less so than sulfonylureas)
definition of MODY
monogenic diabetes
autosomal dominant inheritance pattern
onset <25y
impairment in insulin secretion with minimal or no defects in insulin action
not driven by lifestyle factors
features of MODY
mild non-ketotic hyperglycemia, detected incidentally
normal weight
MODY should be suspected in individuals with persistent, asymptomatic hyperglycemia detected before the age of 25, without the typical features of Type 1 or Type 2 diabetes.
features of MEN type 1
pituitary
parathyroid - hyperparathyroidism due to parathyroid hyperplasia
pancreas - insulinoma, gastrinoma
MEN1 gene
features of MEN type IIa
parathyroid
medullary thyroid cancer
phaeochromocytoma
RET oncogene
features of MEN type IIB
medullary thyroid cancer
phaeochromocytoma
marfanoid body habitus
RET oncogene
features of myxoedema coma
confusion and hypothermia
treatment of myxoedema coma
IV thyroid replacement
IV fluid
IV corticosteroids (until the possibility of coexisting adrenal insufficiency has been excluded)
electrolyte imbalance correction
sometimes rewarming
definition of neuroblastoma
7-8% of childhood malignancies
the tumour arises from neural crest tissue of the adrenal medulla (the most common site) and sympathetic nervous system
median onset 20m
features of neuroblastoma
abdominal mass
pallor, weight loss
bone pain, limp
hepatomegaly
paraplegia
proptosis
investigation findings in neuroblastoma
raised urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels
calcification may be seen on abdominal x-ray
biopsy
medical management of obesity
orlistat - pancreatic lipase inhibitor
adverse effects - faecal urgency/incontinence and flatulence
used if BMI >28 with risk factors or >30
liraglutide - GLP1 mimetic used when BMI >35
hormone profile of primary hyperparathyroidism
high Ca
low PO4
normal/high PTH
Urine calcium : creatinine clearance ratio > 0.01
causes of primary hyperparathyroidism
due to solitary adenoma (80%), multifocal disease occurs in 10-15% and parathyroid carcinoma in 1% or less
hormone profile of secondary hyperparathyroidism
high PTH, low or normal Ca, high PO4, low VD
cause of secondary hyperparathyroidism
Parathyroid gland hyperplasia occurs as a result of low calcium, almost always in a setting of chronic renal failure
may develop bone disease, osteitis fibrosa cystica and soft tissue calcifications
causes of tertiary hyperparathyroidism
result of ongoing hyperplasia of the parathyroid glands after correction of underlying renal disorder, hyperplasia of all 4 glands is usually the cause
features: Metastatic calcification
Bone pain and / or fracture
Nephrolithiasis
Pancreatitis
hormone profile of tertiary hyperparathyroidism
normal or high Ca
high PTH
low/normal PO4
low/normal VD
high ALP
Indications for surgery in secondary (renal) hyperparathyroidism
Bone pain
Persistent pruritus
Soft tissue calcifications
definition of phaeochromocytoma
a rare catecholamine secreting tumour
10% familial, may be associated with MEN type II, neurofibromatosis and von Hippel-Lindau syndrome
bilateral in 10%
malignant in 10%
extra-adrenal in 10%
features of phaeochromocytoma
episodic sx
hypertension (around 90% of cases, may be sustained)
headaches
palpitations
sweating
anxiety
investigations and management of phaeochromocytoma
24 hr urinary collection of metanephrines
alpha blocker e.g. phenoxybenzamine
then beta blocker e.g. propranolol
definition and classification of pituitary adenoma
a benign tumour of the pituitary gland - common
usually incidental findings
classified according to:
size (a microadenoma is <1cm and a macroadenoma is ≥1cm)
hormonal status (a secretory/functioning adenoma produces an excess of a particular hormone and a non-secretory/functioning adenoma does not produce a hormone to excess)
prolactinoma - most common type
can be non-secreting
how do pituitary adenomas cause symptoms
excess of a hormone e.g., cushings
depletion of a hormone - compression of normal functioning pituitary gland
stretching of dura within/around pituitary fossa causing headaches
compression of optic chiasm
investigations needed for pituitary adenoma
a pituitary blood profile (including GH, prolactin, ACTH, FSH, LSH and TFTs)
formal visual field testing
MRI brain with contrast
some thyroid problems in pregnancy
increase in TBG in pregnancy causes an increase in total thyroxine but doesnt affect free thyroxine level
Untreated thyrotoxicosis increases the risk of fetal loss, maternal heart failure and premature labour
graves disease - most common cause of thyrotoxicosis in pregnancy
propylthiouracil
managing hypothyroidism in pregnancy
thyroxine is safe during pregnancy
serum thyroid-stimulating hormone measured in each trimester and 6-8 weeks post-partum
women require an increased dose of thyroxine during pregnancy
by up to 50% as early as 4-6 weeks of pregnancy
breastfeeding is safe whilst on thyroxine
definition and causes of primary hyperaldosteronism
most common cause - bilateral idiopathic adrenal hyperplasia (60-70%)
adrenal adenoma: 20-30% of cases
unilateral hyperplasia
familial hyperaldosteronism
adrenal carcinoma
features of primary hyperaldosteronism
hypertension
hypokalaemia e.g. muscle weakness
metabolic alkalosis
investigation findings in primary hyperaldosteronism
plasma aldosterone/renin ratio - shows high aldosterone levels and low renin levels
high-resolution CT abdomen and adrenal vein sampling - differentiates between unilateral and bilateral causes of excess
management of primary hyperaldosteronism
adrenal adenoma: surgery (laparoscopic adrenalectomy)
bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
function of prolactin
Stimulates breast development (both initially and further hyperplasia during pregnancy)
Stimulates milk production
decreases GnRH pulsatility at the hypothalamic level
regulation of prolactin
constant inhibition by dopamine
Increases secretion
thyrotropin releasing hormone
pregnancy
oestrogen
breastfeeding
sleep
stress
drugs e.g. metoclopramide, antipsychotics
Decreases secretion
dopamine
dopaminergic agonists
regulation of calcium by PTH
calcium levels in the blood fall, which is detected by the parathyroid gland
chief cells secrete PTH into the blood
calcium is released from bone and reabsorbed from the renal tubules, causing its level to rise
increased calcium levels are detected by the parathyroid gland, which decreases PTH secretion
definition and clinical findings of riedel’s thyroiditis
rare cause of hypothyroidism - dense fibrous tissue replacing the normal thyroid parenchyma
hard, fixed, painless goitre
seen in middle-aged women
associated with retroperitoneal fibrosis
moa of SGLT2 inhibitors and examples
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
canagliflozin, dapagliflozin and empagliflozin.
side effects of SGLT2 inhibitors
urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored
Patients taking SGLT-2 drugs often lose weight, which can be beneficial in type 2 diabetes mellitus.
definition of sick euthyroid syndrome
everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the >normal range (inappropriately normal given the low thyroxine and T3).
phases in subacute thyroiditis
occurs post-viral infection, presents with hyperthyroidism
phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR
phase 2 (1-3 weeks): euthyroid
phase 3 (weeks - months): hypothyroidism
phase 4: thyroid structure and function goes back to normal
investigation findings and management of subacute thyroiditis
Investigations
thyroid scintigraphy: globally reduced uptake of iodine-131
Management
usually self-limiting - most patients do not require treatment
thyroid pain may respond to aspirin or other NSAIDs
in more severe cases steroids are used, particularly if hypothyroidism develops
definition of subclinical hyperthyroidism
normal serum free thyroxine and triiodothyronine levels
thyroid stimulating hormone (TSH) below normal range (usually < 0.1 mu/l)
causes of subclinical hyperthyroidism
multinodular goitre, particularly in elderly females
excessive thyroxine may give a similar biochemical picture
management of subclinical hyperthyroidism
TSH levels often revert to normal - therefore levels must be persistently low to warrant intervention
a reasonable treatment option is a therapeutic trial of low-dose antithyroid agents for approximately 6 months in an effort to induce a remission
definition of subclinical hypoothyroidism
TSH raised but T3, T4 normal
no obvious symptoms
risk of progressing to overt hypothyroidism is 2-5% per year (higher in men)
risk increased by the presence of thyroid autoantibodies
management of subclinical hypoothyroidism
TSH >10 and free thyroxine in range 2 time 3 months apart - offer levothyroxine
TSH 5.5-10 and free thyroxine in range 2 time 3 months apart - <65y offer 6m trial of levothyroxine OR if sx of hypothyroidism
if >80y - watch and wait
if asymptomatic people, observe and repeat thyroid function in 6 months
function of sulfonylureas
oral hypoglycaemic drugs which increase pancreatic insulin secretion
S/E - hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide)
weight gain
function of thiazolidinediones
agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance
Adverse effects
weight gain
liver impairment: monitor LFTs
fluid retention
types of thyroid cancer
papillary - 70% - young F
follicular
medullary
anaplastic
lymphoma
management of thyroid cancer
total thyroidectomy
followed by radioiodine (I-131) to kill residual cells
yearly thyroglobulin levels to detect early recurrent disease
causes of thyroid eye disease
autoimmune response against an autoantigen, possibly the TSH receptor → retro-orbital inflammation - glycosaminoglycan and collagen deposition in the muscles
smoking - big risk factor
features of thyroid eye disease
the patient may be eu-, hypo- or hyperthyroid at the time of presentation
exophthalmos
conjunctival oedema
optic disc swelling
ophthalmoplegia
inability to close the eyelids may lead to sore, dry eyes. If severe and untreated patients can be at risk of exposure keratopathy
causes of thyroid nodule
Multinodular goitre
Thyroid adenoma
Hashimoto’s thyroiditis
Cysts (colloid, simple, or hemorrhagic)
carcinoma
clinical features of thyroid storm
fever > 38.5ºC
tachycardia
confusion and agitation
nausea and vomiting
hypertension
heart failure
abnormal liver function test
TSH down, T4 and T3 up
thyroid autoantibodies
management of thyroid storm
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 - e.g. 4mg IV qds - blocks the conversion of T4 to T3
causes of thyrotoxicosis
Graves’ disease
toxic nodular goitre
acute phase of subacute (de Quervain’s) thyroiditis
acute phase of post-partum thyroiditis
acute phase of Hashimoto’s thyroiditis (later results in hypothyroidism)
amiodarone therapy
contrast
features of thyrotoxicosis
General
Weight loss
‘Manic’, restlessness
Heat intolerance
Cardiac
palpitations, tachycardia
high-output cardiac failure may occur in elderly patients, a reversible cardiomyopathy can rarely develop
Skin
Increased sweating
Pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli
Thyroid acropachy: clubbing
Gastrointestinal
Diarrhoea
Gynaecological
Oligomenorrhea
Neurological
Anxiety
Tremor
definition of toxic multinodular goitre
a thyroid gland that contains a number of autonomously functioning thyroid nodules resulting in hyperthyroidism
nuclear scintigraphy reveals patchy uptake
treatment - radioiodine therapy
results of the water deprivation test
psychogenic polydipsia - urine osm start lowish, no change
cranial DI - urine osm start low, end high
neph DI - urine osm start low, end low
