Endocrine Flashcards
Pituitary Gland basics:
A-Location, Sections & corresponding hormones secreted?
B-Disorders of the hormone axis?
• Pituitary Gland
o Location:
Below hypothalamus, near optic chiasm
• Significance: Pituitary tumours can cause bitemporal hemianopia
o Sections: Anterior • TSH • ACTH • GH • FSH • LH • Prolactin Posterior • ADH • Oxytocin
o Disorders of the hormone axis:
Primary: End organ (e.g. thyroid, adrenals)
Secondary: Pituitary
Tertiary: Hypothalamus
Hyperprolactinaemia:
Physiology of prolactin?
Causes?
• Physiology of prolactin:
o TRH inhibits dopamine (therefore, stimulate prolactin release)
o Dopamine inhibits prolactin
o Prolactin inhibits GnRH
• Cause
o Physiological
Pregnancy (sometimes), post-pregnancy/breast feeding (always)
Stress
o Endocrine causes: Prolactinoma Hypothyroidism: causes elevation in TRH= inc. in prolactin. Cushing’s (↑stress) PCOS
o Drugs:
Gut motility (metoclopramide, domperidone) – dopamine antagonists
Typical antipsychotics (Haloperidol)
phenothiazines
Hyperprolactinaemia:
Presentation, Ix & Mx?
• Presentation:
o Men: Erectile dysfunction, Hypogonadism
o Women: Amenorrhea/oligomenorrhea, galactorrhea
o Bitemporal hemianopia
• Ix:
o First:
TFTs, Prolactin level
MRI Pituitary (look for prolactinoma) <1cm=Microadenoma, if >1cm= macroadenoma.
*prolactinomas can be secretory or non-secretory.
• Rx for prolactinoma:
o First: Dopamine agonists (bromocriptine, cabergoline) usually x3yr
o If refractory: Surgery (Trans- sphenoidal surgery)
Adenoma
disorders:
Acromegaly:
Terminology associated, physiology & causes?
• Terminology:
o Gigantism ↑GH affecting children PRIOR to fusion of epiphysis; giants (>7ft tall)
o Acromegaly ↑GH affecting adults, no growth of height (other changes though)
• Physiology: GH stimulates IGF-1 (produced in liver; stimulates growth)
• Cause:
o Functioning/ secretory Macroadenoma (75%; >1cm)
Acromegaly:
Features, Ix & Mx?
- Features: ABCDEF of GH (arthralgia/arthritis, ↑BP, CarpTun, DM, Enlarged organs, Field defects)
- Ix:
o Initial test: Insulin-like Growth Factors (IGFs) (↑↑ in acromegaly)
o Best test/gold standard: OGTT w/ GH measurements
o Further Rx: MRI Pituitary
• Rx:
o First line: Surgery
Diabetes Insipidus:
What is it? Causes?
Diabetes Insipidus: ADH deficiency (neurogenic/central) or unresponsiveness (nephrogenic)
• Cause:
o Cranial/Neurogenic (partial or complete lack of ADH) – any pathological process in brain
o Nephrogenic (lack of response from renal tubules) lithium, ↑Ca, ↓K+, idiopathic
Diabetes Insipidus: Symptoms, Diagnosis & Mx?
• Symptoms: Polyuria (dilute), polydipsia, nocturia
• Diagnosis:
o Step 1 – Water deprivation test
Still pees lots = DI (+dilute)
o Step 2 – Vasopressin challenge
Steps:
• Give vasopressin
o If urine concentrates (↑50% conc) Neurogenic/Central
o If urine does not concentrate (<50%) Nephrogenic
• Treat:
o Neurogenic/Central DI: Desmopressin (intranasally)
o Nephrogenic DI: High dose desmopressin
Thyroid gland basics:
Function & Ix’s of all thyroid diseases:
• Thyroid gland
o 99% of iodine in body goes to thyroid gland Produces T4 (mainly), some T3
INVESTIGATING ALL THYROID DISEASE
• STEP 1 TFTs:
o TSH low, T4 high: Primary hyperthyroidism
o TSH high, T4 low: Primary hypothyroidism
o TSH high/norm, T4 high : Secondary hyperthyroid
o TSH low/norm, T4 low: Secondary hypothyroidism (NB: normal TSH is INAPPROPRIATE)
- STEP 2 Autoantibodies – Anti-TSH Receptor (Graves’), Anti-Thyroid Peroxidase (Hashimoto’s)
- STEP 3 Radioactive Iodine Test (for hyperthyroidism)
Hyperthyroidism: Features?
• Features: THYRODISM o Tremor o Hair loss, heart rate up o Yawning o Restlessness o Oligomenorrhea/amenorrhea o Intolerance to heat o Diarrhoea o Increased appetite o Sweating o Muscle wasting/weight loss
Hyperthyroidism: causes?
o Grave’s (most common) 30-50yr old
Symptoms: ↑thyroid symptoms, small goitre, eye disease (specific to Grave’s; 40%)
Graves eye disease Only present in 40%
• Exophthalmos (very important sign)
- Ophthalmoplegia (very important sign)
- Lig lag (poor sign) When patients moves eye from up to down, can temporarily see sclera above the iris (NOT down to up)
- Lid retraction
- Conjunctival oedema/chemosis
- Multinodular goitre (2nd most common overall, most common in >50 [NB: Graves <50]
- Single/hot nodule (single hot nodule on RIU)
• Subacute/De Quervain’s thyroiditis ↓Radioiodine uptake, resolves on own in 2wks
o Cause: Recent viral infection
o Stages: 1) Hyperthyroid, 2) Hypothyroid, 3) Euthyroid (recovery)
o Features: Hyperthyroid symptoms, Thyroid pain + fever, NO eye symptoms
• Drugs (amiodarone, Li+)
Ix of hyperthyroidism?
Diagnose:
First:
• TFTs ↓TSH, ↑FT4/FT3
• Anti-TSH receptor antibody (95% sens. graves)
Second: Radioiodine Uptake (only need if atypical) Diffuse excess uptake
Mx of hyperthyroidism?
TREATING HYPERTHYROIDISM
• First: Treat symptoms (e.g. in hyperthyroid – give propanalol)
• Second – anti-thyroid therapy:
o Carbimazole, methimazole, propylthiouracil
• Third – definitive therapy:
o Radio-iodine ablation (I131 – radioactive form)
o Surgery
Hypothyroidism features & causes?
Hypothyroidism
• Features:
o Tired, cold intolerance, weight gain, constipation, hoarse voice, menorrhagia, slowing/depression
• Causes:
o Hashimoto’s thyroiditis (most common in North America)
Definition: Thyroid destruction via autoantibodies
Epidemiology: Women 90%, men 10%
o Iatrogenic
o Drugs Lithium, Amiodorone
o Subacute thyroiditis
De Quervain’s (viral, not autoimmune) Hypothyroid phase – give steroids
o Iodine deficiency (uncommon w/ iodine supplement, but most common worldwide)
Hypothyroidism: Dx & Mx?
• Diagnosis:
o First: TFTs
o Second:
Anti-thyroid peroxidase (TPO) (95% Hashimoto’s)
• Treat: Lifelong Thyroxine (T4)
Hyperparathyroidism
• Epidemiology &
Types?
Hyperparathyroidism
• Epidemiology: 3rd most common endocrine disorder
• Types: o Primary: Single adenoma (80%) 15%: hyperplasia 4%: multiple adenoma 1%: carcinoma
Hyperparathyroidism: features, Dx & Mx?
• Features:
Polyuria, polydipsia, HTN.
o “Stones, Bones, Abdo groans, Thrones, Psych moans + Malignant undertones”
Renal stones
Pathological fractures & bone pain
Abdo pain, N&V
Polyuria
Depression, anxiety , confusion, coma, insomnia
• Diagnosis:
o Primary: ↑PTH + ↑Calcium + ↓Phosphate
o Then: Sestamibi/technitium scan Hot PTH nodule(s) – 90% = single
• Treat:
o First: Treat hypercalcaemia (see below), or
o Second: Surgery – parathyroidectomy
calcimimetic agents such as cinacalcet- for secondary hyperparathyroidism.
Hypercalcemia Mx?
• Any calcium >3 is an EMERGENCY o Acutely: First: • IV Fluids • Furosemide o NB: evidence does not support, but USEFUL if volume overloaded as can continue to give saline!
If refractory after 24hr: IV Bisphosphonates
Cushing’s disease: features
o Features:
Fat Moon face, Buffalo hump (+ supraclavicular fat pads), Central obesity, Striae
Blood Hyperglycaemia (30%), HTN (50%)
Bone Osteoporosis (inevitable if untreated)
METABOLIC SYNDROME (central obesity, raised triglyc, reduced HDL, raised BP, raised fasting plasma glucose) + OSTEOPOROSIS – big subsequent co-morbidity
Cushing’s causes?
o Causes:
Cushing’s Disease: Pituitary adenoma – NB: Cushing’s disease is the most common cause of high cortisol!
Cushing’s Syndrome: • Iatrogenic/exogenous • Adrenal adenoma (10%) • Adrenal carcinoma (10%) • Adrenal hyperplasia w/o pituitary tumour (E.g. CAH; very rare)
Cushing’s Dx?
o Diagnose:
Is it Cushing’s (i.e. disease or syndrome)?
• First: Overnight Dexamethasone Suppression Test (Low Dose) 48hr
A condition of high cortisol (Cushing’s disease OR syndrome) has now been diagnosed, but must determine the source (pituitary, adrenal, ectopic)
• Where is it coming from?
o First: ACTH Level (at 9am and midnight)
If low: Adrenal neoplasia/hyperplasia (or exogenous)
- CT/MRI adrenals
- Rx: Adrenalectomy
If high: Pituitary adenoma
- MRI pituitary
- Rx: Trans-sphenoidal surgery
Adrenal Insufficiency: Definition & causes?
Definition: inability of the adrenal glands to produce Glucocorticoids +/- mineralocorticoids.
Primary Adrenal insufficiency (loss of the gland function):
1- Drugs which lower adrenal hormone: Long-term steroids (most common cause of adrenal insufficiency), ketoconazole, metyrapone
2- Autoimmune (Addison’s; common [>80% of non-drug adrenal insufficieny])
o Progressive destruction of adrenal gland due to cytotoxic T-lymphocytes.
o Biochemical deficiencies only occur once 90% of gland destroyed.
3-Other: Waterhouse-Friderichsen: acute primary insufficiency due to adrenal hemorrhage. TB: in developing countries.
Secondary-pituitary failure: It SPARES the mucosa/skin + NO hypokalaemia.
Tertiary: Hypothalamic failure. Similar to secondary.
*The above are all chronic, but acute adrenal insufficiency is called Adrenal/Addisonian crises! Its when people have the chronic causes but get triggered by surgery, illness, infection, massive haemorrhage.
Adrenal insuffiency: Features? (chronic & acute)
o Features: Difficult to diagnose
Fatigue, weakness, N+V, GI disturbances.
Hypotension, Hypoglycemia
Hyperpigmentation (from ↑ACTH, i.e. only in primary!)
• Look in buccal mucosa + palmar/digit creases.
Addison’s as above but also: vitiligo, pernicious anaemia, hashimoto thyroiditis.
*ACUTE crises: Hypoglycaemia, Hyponatraemia, hyperkalaemia, metabolic acidosis & signs of shock!
Adrenal Insuffiency: Dx?
o Diagnosis:
First: Low blood sugar, low BP
Second: Urinalysis (↑Na, ↓K) Blood (↓Na, ↑K)
Short SynACTHen Test
• Addison’s disease – Cortisol will NOT rise!!!
This tells us if there’s adrenal insuffiency. Then to find out if its primary, secondary or tertiary: perform plasma ACTH= high= Addison’s. Low=2/3 causes.
Other: screen for TFT, TB,Haemochromatosis.
Adrenal Insuffiency: Mx?
o Hydrocortisone
o Fludrocortisone
Acute: high dose IV hydrocortisone.
Pheochromocytoma: definition, features?
(phios – dusky, chromo – colour, cytoma – growth of cells)
• Definition: Adrenaline producing tumour
• Features: o EPISODIC Headache (80%) o Palpitations (70%) o Profuse sweating (60%) o Tremor o HTN (sustained in 60%, paroxysmal in 40%)
Might be associated with: MEN type II, neurofibromatosis and von Hippel-Lindau syndrome (10%)
Pheochromocytoma: Dx & Mx?
o First: Urinary metanephrines (97% sens, more specific)
o Positive Urine: MRI adrenals
• Treat: A-blocker: PHaeochromocytoma - give PHenoxybenzamine before beta-blockers otherwise hypertensive crisis
lABetalol- blocks both alpha & beta receptors if not above regimen.
Surgery: 10 days after Medical Rx
T1DM-background?
• Type 1
o Background:
No insulin production
Insulin autoantibodies can be detected as early as 6-12mo of age
Initiates with precipitating event (e.g. infection)
T1DM:
Dx & Follow up?
o Diagnosis: Use the American Diabetes Association (ADA) criteria
DIAGNOSE: Random BG ≥11.1 OR fasting BG ≥7 OR HbA1C >6.5% (48)
• If BG 6-6.9 (impaired fasting glucose): 75g OGTT (test 2hr after)
o Diabetes: BG ≥11.1
o Impaired Glucose Tolerance (IGT): BG 7.8-11
Anti-Islet cell + Anti-GAD (75% each)
T1DM: Mx?
• Treat: o First: Insulin S/C Types: • Short-acting (e.g. novorapid) o Ultra-short acting o Rapid acting • Intermediate (e.g. isophane) • Long-act (e.g. glargine, levemir)
Best regimen: 1 Long-acting OD + 1 Ultra-short acting at meal time
o Second: Insulin pump
o Third: Islet cell transplant
• Follow-Up:
o HbA1C
o Diabetic log
T2DM- Background & Dx?
• Background:
o Insulin resistance, but still producing insulin
• Diagnosis: Same as T1DM
T2DM: Mx?
• Treat:
o First: Diet + Exercise + Educate if >6.5% or 48mmol/mol (target to reduce to 6.5% or 48mmol/mol.
o Second: Metformin (biguanide)
If patient has HbA1c of >6.5% or >48mmol/mol & wants to try metformin:
Start people on lifestyle + metformin unless mild and patient NOT overweight
Lactic acidosis
Diarrhoea/N+V (reduce in severity as Rx goes on, worse at beginning of Rx)
Contraindicated if poor renal function
No risk of hypos, no risk of weight gain (in fact causes weight LOSS)
ONLY oral hypoglycaemic proven to reduce stroke + MI
Reduced mortality
The modified release variant of metformin appears to have a better gastrointestinal side effect profile and is recommended in patients experiencing those side effects as a second-line treatment. It’s given once daily rather than the immediate release which can be given TDS.
o Third – HbA1c still >6.5%: after 6 months. Increase Metformin dose to maximum tolerated dose e.g. His HbA1c is 51 mmol/mol (6.8%). You increase his metformin from 500mg bd to 500mg tds and reinforce lifestyle factors
Fourth: already on on drug but HbA1c risen to >7.5% or >53mmol/mol= add Second drug either Sulfonylurea (e.g gliclazide), Gliptins, or SGLT2 inhibitors, pioglitazone. Each has pros/cons so chosen for the right patients needs.
Sulfonylurea (e.g. gliclazide)
Weight gain
Risk of hypo so e.g. can’t be given to lorry drivers
Gliptins- DPP4 inhib when BMI <35 but probably the least effective drug and should only be used if there is no better alternative.
Sodium-glucose transport protein 2 (SGLT2) inhibitor (the ‘gliflozins’)-improve cardiovascular outcomes and reduce the admission rates for patients with heart failure - an extra benefit in this case. They do carry a small hypoglycaemia risk, but much less so than gliclazide.
Glitazone/Thiazolidenidiones (pioglitazone) usually given as last resort e.g. third drug.
Weight gain
Abnormal LFTs
Fluid retention Contraindicated in heart failure
Bladder cancer (RR 2.64)
Pathological fractures
No risk of hypos
Fifth: If this fails, NICE recommends triple therapy with either:
Metformin + gliclazide + gliptin/glifozin/pioglitazone or
Metformin + pioglitazone + glifozin or
Insulin +/- other drug (not if significantly overweight and has already struggled with hypos)
o Sixth: Incretins (GLP-1 analogue [Exenatide]
GLP-1 when BMI >35
achieve an 11 mmol/mol (1%) reduction in HbA1c AND 3% weight loss in the first 6 months in order for it to be continued.
o Last: Insulini
Complications of DM: DKA for T1DM- give definition, presentation & Diagnosis?
• Diabetic Ketoacidosis/DKA (Type 1) o Definition (Amer Diab Assoc): BG >11-13.8 pH <7.3 Ketones +
o Presentation:
Young (teens)
Abdominal pain, Vomiting, Confusion/Low GCS, SOB (Kussmaul breathing)
Polyuria
o Diagnose: Criteria as above
Blood sugar
Urine dip
VBG
DKA: Mx?
• Treat:
o First:
Fluid
Insulin
Dextrose?
Potassium?
The osmolar gradient caused by the high blood glucose in DKA results in water shift from the intracelluar fluid (ICF) to the extracellular fluid (ECF) space and contraction of cell volume. Correction with insulin and intravenous fluids can result in a rapid reduction in effective osmolarity, reversal of the fluid shift and the development of cerebral edema.“ Or simply: Insulin clears up glucose + fluid = low osmolality (ECF) = water moves from low to high osmolality in the brain (ICF) = cerebral edema
Young patients need 1:1 nursing to monitor neuro-observations, headache, irritability, visual disturbance, focal neurology etc.
It usually occurs 4-12 hours following commencement of treatment but can be present at any time.
If any suspicion, request a CT head and call senior immediately.
T2DM complication: • Hyperosmolar Hyperglycaemic State (HHS):
Give Features, Dx & Mx?
o Features:
Very high blood glucose (often >30-40)
Normal ketones (or small amount only)
Normal pH (>7.3 at least, unless combined with AKI)
Dehydrated/polyuria (massive – biggest problem)
o Diagnose: High blood sugar Normal pH Normal ketones High serum osmolality
o Treat:
IV Fluid (vigorous; 0.9% NS)
Insulin
± K+
Chronic complications of DM?
o Microvascular
Neuropathy
Nephropathy
Retinopathy
o Macrovascular MI, Stroke, PVD…
Hypoglycaemia: Definition, causes?
Hypoglycaemia*** (<3.0… however <2.5 = pathological)
• Definition: Whipple’s Triad:
o ↓glu
o Symptoms of hypoglycaemia (tachycardia, confusion, sweating…)
o Reversal with sugars
• Cause:
o Fasting/starving
o Liver failure, adrenal failure (Addison’s)
o Endogenous insulin
Insulinoma
o Exogenous insulin Factitious/Drugs:
Insulin
Sulfonylureas
Hypoglycaemia: Mx?
• Mx:
o First:
Not unwell (conscious):
• Oral sugar x3 (10-20g)
• Complex carb to prevent subsequent hypo
Unwell (unconscious): IV dextrose (100mL of 20%) – check BM 15min later, and continue as necessary
• If IV access not available: Glucagon 1mg IM/SC/IV
o Second – Ongoing Mx: 10% dextrose infusion + hourly glucose monitoring
Particularly important in sulphonylurea overdose as effects may continue
Hypoglycaemia: Features & complications?
• Features: Lethargy, confusion, seizures, stroke-like syndrome, coma
• Complication: Prolonged hypoglycemic coma
o Cause: Cerebral oedema
Hyperaldosteronism: Definition & causes?
Definition: High aldosterone secretion.
Causes:
1-Primary (Conn’s):
high Aldosterone, low renin
due to- adrenal adenoma or bilateral adrenal hyperplasia.
Secondary: high aldosterone & high renin.
Due to-Renovascular hypertension, juxtaglomerular cell tumors, oedema (cirrhosis, HF, Nephrotic disease).
Features of Hyperaldosteronism:
Hypernatraemia, Hypokalaemia, Hypertension, Metabolic alkalosis
-Lethargy, headaches, muscle cramps.
Hyperaldosteronism: Ix & Mx?
1-U&E’s for electrolytes imbalances + any renal secondary causes.
2-Aldosterone:Renin ratio- high=p Conn’s
Normal= Secondary.
*stop spironolactone & diuretics 6w before.
3-ECG 4-CT adrenals + adrenal venous sampling.
Mx:
Conn’s-
1-Adrenalectomt if adrenal adenoma.
2-Aldosterone antagonists: Spironolactone, eplerenone or amiloride if bilateral hyperplasia.
Secondary: Treat underlying cause.
T2DM: drugs, MOA, SE & CI:
Metformin (biguanide):
MOA:
increase insulin sensitivity, increase glucose uptake, reduce liver gluconeogenesis.
SE:
Lactic acidosis
Diarrhoea/N+V (reduce in severity as Rx goes on, worse at beginning of Rx)
CI:
poor renal function
Positives:
No risk of hypos, no risk of weight gain (in fact causes weight LOSS)
ONLY oral hypoglycaemic proven to reduce stroke + MI
Reduced mortality
Sulfonylurea (e.g. gliclazide)
MOA: Insulin secretors-
1- stimulate pancreas to secrete Insulin by blocking K-channel= release insulin.
SE:
Weight gain
Risk of hypo
CI:
Liver impairment
Glitazone/Thiazolidenidiones (pioglitazone) PPAR gamma agonists:
MOA: increases insulin sensitivity by reducing peripheral insulin resistance.
SE:
Weight gain
Abnormal LFTs
Fluid retention
CI: heart failure Bladder cancer (RR 2.64) Pathological fractures Positives: No risk of hypos
Incretins (GLP-1 analogue [Exenatide]:
MOA: Inhibits glucagon production in pancreas which stimulates cells of pancreas to release insulin.
SE: headaches, weight loss, pancreatitis.
DPP-4 inhibitor [Sitagliptin])
MOA: Inc. levels of GLP-1.
SGLT-2 inhibitor (sodium glucose transport protein 2) e.g. Dapagliflozin, canagliflozin, empagliflozin.
MOA: Helps kidney lower blood glucose levels (stops reabsorption of glucose back to blood).
SE: normoglycaemic ketoacidosis (CI IN T1DM!!)
Increased risk of lower-limb amputation: feet should be closely monitored
CI: frequent UTI’s & thrush infections.
o Last: Insulin
Non- hyperparathyroidism causes of hypercalcaemia
Two conditions account for 90% of cases of hypercalcaemia:
- Primary hyperparathyroidism: commonest cause in non-hospitalised patients
- Malignancy: the commonest cause in hospitalised patients. This may be due to number of processes, including; bone metastases, myeloma, PTHrP from squamous cell lung cancer
Other: sarcoidosis* vitamin D intoxication acromegaly thyrotoxicosis Milk-alkali syndrome drugs: thiazides, calcium containing antacids dehydration Addison's disease Paget's disease of the bone** TB histoplasmosis
Hashimoto’s Thyroiditis: What is the single most important blood test to assess her response to treatment (levothyroxine)?
Dose?
TSH- the therapeutic goal is ‘normalisation’ of the thyroid stimulating hormone (TSH) level.
Cardiac disease, severe hypothyroidism or patients over 50 years the initial dose = 25mcg od
Other patients initial
dose = 50-100mcg od
Hypothyroidism in pregnancy= dose increased ‘by at least 25-50 micrograms
