Basics Endocrinology Flashcards
What is Addison’s?
- autoimmune destruction adrenal glands
- most common cause hypoadrenalism
- reduced cortisol and aldosterone
- hyponatraemia, hyperkalaemia, hyperpigmentation, vitiligo, hypoglycaemia, hypotension, salt craving, weight gain etc.
How do you investigate Addison’s?
- ACTH stimulation test
- plasma cortisol 30 min before and after 250 ug IM synacthen
- electrolyte abnormalities
How do you manage an Addisonian crisis?
- hydrocortisone 100mg IM or IV
- 1 litre normal saline or dextrose if hypoglycaemic
- continue hydrocortisone 6 hourly until stable
Management of Addison’s
glucocorticoid and mineralocorticoid replacement therapy (hydrocortisone and fludrocortisone)
What is Acromegaly?
- excess GH
- 95% secondary due to pituitary adenoma
- coarse facial features, prognathism, interdental spaces, increase shoe size, sweat gland hypertrophy, features of primary tumour
How do you investigate acromegaly?
- GH vary so not diagnostic
- serum IGF-1 levels first line
- OGTT can help to confirm
- Pituitary MRI
How do you manage acromegaly?
-transphenoidal surgery if not: -somatostatin analogue e.g. octreotide -GH receptor antagonist e.g. pegvisomant -dopamine agonist e.g. bromocriptine
What is Bartter’ syndrome?
- autosomal recessive severe hypokalaemia due to defective chloride absorption at NKCC2 in ascending loop of Henle
- normotensive
- failure to thrive in childhood, polyuria, polydipsia, hypokalaemia, normotension and weakness
What are the causes of congenital adrenal hyperplasia?
- autosomal recessive disorders
- high ACTH in response to low cortisol
- 21-hydroxylase deficiency
- 11-beta-hydroxylase deficiency
- 17-hydroxylase deficiency
What investigations for Cushing’s
- hypokalaemic metabolic alkalosis
- impaired glucose tolerance
- ectopic ACTH leads to hypokalaemia
- insulin stress test to distinguish pseudo
- confirm with overnight dexamethasone suppression test and 24 hour urinary free cortisol
Explain the difference in results between normal, Cushing’s syndrome, disease and ectopic ACTH with low dose dexamethasone, high-dose and ACTH levels:
- normal: decrease, decrease, no change
- syndrome: no change, no change, decrease
- disease: no change, decrease, increase
- ectopic ACTH: no change, no change, increase
What is Liddle’s syndrome?
- rare autosomal dominant cause of hypertension
- hypokalaemic alkalosis
- disordered increased sodium reabsorption
- treat with amiloride or triamterene
MEN type I
-parathyroid
-pituitary
-pancreas
(adrenal and thyroid)
MEN1 gene
MEN type II
-medullary thyroid cancer
-parathyroid
-phaeochromocytoma
RET oncogene
MEN type III
-medullary thyroid cancer
-phaeochromocytome
-marfanoid body, habits, neuromas
RET oncogene
What is a myxoedema coma and how do you treat it?
- decompensated hypothyroidism
- confusion and hypothermia
- IV thyroid replacement, IV fluids, IV corticosteroids, electrolyte imbalance correction
What is a phaeochromocytoma?
- rare catecholamine secreting tumour
- 10% familial: MEN type II, neurofibromatosis, von Hippel-Lindau
- causes hypertension, episodic headaches, palpitations, sweating and anxiety
How do you test for phaeochromocytoma?
- 24hr urinary collection of metanephrines
- replaced 24hr collection of catecholamines
How do you treat phaeochromocytoma?
- surgery
- before surgery, stabilise with alpha blocker (phenoxybenzamine) and beta blocker (propranolol)
What are some typical symptoms of pituitary adenomas?
- symptoms due to excess or depletion of hormone
- stretching of dura causing headaches
- compression of optic chasm causing bitemporal hemianopia
What are the investigations for pituitary adenomas?
- pituitary blood profile: HG, prolactin, ACTH, FH, LSH, TFTs
- formal visual field testing
- MRI brain with contrast
How can you treat pituitary adenomas?
- hormonal therapy (bromocriptine)
- surgery if progression in size
- radiotherapy
What are the features of primary hyperaldosteronism and what is it caused by?
- adrenal adenoma, bilateral idiopathic adrenal hyperplasia and adrenal carcinoma
- hypertension, hypokalaemia, alkalosis
What are the investigations for primary hyperaldosteronism?
- plasma aldosterone/renin (increased aldosterone, decreased renin due to negative feedback)
- adrenal venous sampling
- CT abdomen
Treatment of hyperaldosteronism?
- adrenal adenoma: surgery
- bilateral arden-cortical hyperplasia: aldosterone antagonist e.g. spironolactone
Carbimazole ADR
- agranulocytosis (sore throat, fever)
- crosses placenta so lower dose in pregnancy
What type of activity do different corticosteroids have?
- fludrocortisone: very high mineralocorticoid, low glucocorticoid
- hydrocortisone: high mineralocorticoid, glucocorticoid
- prednisolone: high glucocorticoid, low mineralocorticoid
- betmethasone, dexamethasone: very high glucocorticoid, minimal mineralocorticoid
Glucocorticoid ADR
- endocrine: dysregulated glucose, hirsutism, hyperlipidaemia, increased appetite and weight gain
- Cushing’s
- MSK: osteoporosis, proximal myopathy, avascular necrosis
- immunosuppression
- psychiatric
- peptic ulcers, pancreatitis
- opthalmic: glaucome, cataracts
- decreased growth children
- neutrophilia
- ICHTN
Mineralocorticoid ADR
- fluid retention
- HTN
Growth hormone ADR
- headache
- ICHTN
- fluid retention
How does insulin stress test work and what are the contraindications?
- to investigate hypopituitarism
- IV insulin and measure cortisol and GH which should rise normally
- CONTRA: ischaemic heart disease, epilepsy, adrenal insufficiency
Features of insulinoma, diagnosis and treatment:
- hypoglycaemia early in morning and before meal
- weight gain, increased insulin, increased proinsulin:insulin and increased c-peptide
- investigate with CT abdomen and prolonged fasting 72 hours
- treat surgically or with diazoxide and somatostatin
Meglitinides (MOA, examples and ADR)
- increases pancreatic insulin secretion similarly to sulfonylureas (good for erratic lifestyle)
- e.g. nateglinide, repaglinide
- ADR: weight gain, hypoglycaemia
Orlistat (MOA, ADR)
- pancreatic lipase inhibitor for obesity
- for >=28 with risk factors or 30kg/m2 BMI
- ADR: faecal incontinence/urgency and flatulence
SGLT-2 inhibitors (examples, ADR)
-dapagliflozin, empagliflozin, canagliflozin
ADR:
-urinary and genital infections (Fournier’s)
-increased risk lower limb amputations
-normoglycaemic ketoacidosis
-weight loss
Sulfonylureas (MOA, ADR)
-binds to ATP independent K+ channel on pancreatic beta cells
-increases insulin secretion
ADR:
-weight gain
-hypoglycaemic
-hyponatraemia
-bone marrow suppression
-hepatotoxicity
-peripheral neuropathy
-AVOID in pregnancy and breast feeding
Thiazolidinediones (MOA, ADR)
-agonists of PPAR gamma receptor and decreased peripheral insulin resistance ADR: -weight gain -liver impairement -bladder cancer -increased risk fractures -fluid retention (contra in HF)
Androgen insensitivity syndrome
- x-linked recessive condition
- defect in androgen receptor so end organ resistance to testosterone
- male genotype and female phenotype (no uterus)
- testosterone, oestrogen and LH elevated
5-alpha reductase deficiency
- autosomal recessive
- inability to convert testosterone to dihydrotestosterone
- ambiguous genitalia in newborn, hypospadias and virilisation at puberty
Kallmann’s syndrome
- cause of delayed puberty secondary to hypogonadotrophic hypogonadism
- inherited x-linked recessive
- failure of GnRH secreting neurones to migrate to hypothalamus
- anosmia, decreased sex hormones, LH and FSH, normal or above average height, cleft lip/palate and visual/hearing defects
Klinefelter’s syndrome
- XXY
- taller
- lack of secondary sexual characteristics
- small, firm testes
- infertile
- gynaecomastia
- GnRH increased and testosterone decreased
