Endocrine Flashcards
Type 1 diabetes
Autoimmune disorder where insulin producing beta cells of islets of Langerhans in pancreas are destroyed by immune system leading to absolute insulin deficiency
classic triad of type 1 diabetes
weight loss, polydipsia (excessive thirst), polyuria
fatigue, blurred vision, candidal infection and sometimes DKA
type I diabetes Ix
• Fasting Glucose: 7.0 mmol/L • OGTT: 11.1 mmol/L • HbA1c: 48 mmol/L • Presence of islets autoantibodies o GAD, IA-2 and ZnT8 • C peptide – decrease after 3-5 year after diagnosis
type I diabetes Mx
carb counting, exercise, reduce drinking and stop smoking
Inuslin: basal/bolus
Insulin types
Rapid acting: Novorapid or Humalog – 5 hours: inject at start of meal or just after
Short acting: Humulin S, Actrapid – 6 hours
Intermediate acting: Humulin I (isophane), Insulatard – 12 hours
Long acting: Lantus, Levemir – 18 hours
Rapid acting analogue-intermediate mixture – Humalog Mix 25/50, Novomix30
Short acting-intermediate mixture – Humulin M3
plasma glucose levels
5-7 on waking
4-7 before meals
5-9 after meals at least 90 minutes after
Type II diabetes
Type 2 diabetes (due to a progressive loss of β-cell insulin secretion frequently on the background of insulin resistance)
Type II diabetes signs/symptoms
- Blurred vision
- Recurrent UTIs
- Tiredness
- Polyuria
- T2DM- Signs of complications- neuropathy, retinopathy and nephropathy
Pre-diabetes
Fasting: 6.1-6.9
OGTT: 7.8-11.0
HbA1c: 42-47
Diabetes management
lifestyle: exercise+diet: lose 5-10kg in a year
Monotherapy:
- Metformin + SU (intolerant of modified and standard release metformin)
combination: Met + SU or SLG2-inhibitor, DDP4 and pioglitazone
further combination: Met + SU + SLGT2, DDP4 or pioglitazone or injectable (GLP-1 agonist)
Further; Met + SU + SLGT2, DDP4 or pioglitazone or injectable (GLP-1 agonist + basal insulin )
o Once daily NPH (isophane – intermediate acting) Insulin is added to Metformin (+/- SU).
o If this is ineffective or becomes so then change to bd NPH insulin or mixed insulin (Humulin M3) or basal/bolus (e.g. Lantus and Novorapid)
BP 130/80: ACEi
Simvastatin 40mg or atrovastatin 10mg
Diabetic neuropathy
- Peripheral (stocking, absent ankle jerks, charcot joint, pes cavus, claw toes: 10g monofilament)
- autonomic
- proximal
- focal
Treated as neuropathic pain: amitriptyline, duloxetine, gabapentin or pregabalin
Diabetic nephropathy + Mx
damage to capillaries in glomeruli
- proteinuria
- diffuse scarring
- ACEi/ARB (dilation of renal efferent arterioles, decrease filtration pressure, GFR and proteinuria)
- SGL2 inhibitor
Microalbuminuria
ACR > 2.5 and >3.5 (female), PCR > 15 and negative dipstick
Proteinuria
ACR: >30 AND PCR >50 with positive dipstick
Diabetic retinopathy types
o Mild non-proliferative (Background)
o Moderate non-proliferative
o Severe non-proliferative
o Proliferative
diabetic retinopathy and maculopathy treatment
Retinopathy: (proliferative or maculopathy)
- Laser panretinal or macular grid photocoagulation
- viterectomy
Maculopathy:
1. Anti-VEGF medications
LADA
late-onset type 1 diabetes is probably quite common in patients presenting with ‘typical’ type 2 diabetes
ketosis = type 1 diabetes
DKA
Diabetic ketoacidosis (DKA) is a disordered metabolic state that usually occurs in the context of an absolute or relative insulin deficiency accompanied by an increase in the counter-regulatory hormones i.e. glucagon, adrenaline, cortisol and growth hormone.
Caused by uncontrolled lipolysis -> excess free fatty acids that are converted to ketone bodies. Dehydration, hyperglycaemia and hyperosmolar state (more electrolytes in the serum)
DKA precipitating factors
infection, missed insulin doses and MI
newly diagnosed type I diabetes
illicit and alcohol use
non-adherence to insulin
DKA diagnsis
Glucose: >11 Ketones > 3 or 5 and urine ketones (++) pH<7.3 metabolic acidosis K+ 5.5 mmol-1 Raised lactate, creatinine and amylase WCC: Median 25 Na: low Bicarbonate: <10
DKA management
- Fluid: 0.9% NaCl, glucose falls to 15, switch to dextrose
- Insulin: commence 6 units per hour IV and continue basal insulin (once per day) e.g. levemir
- Potassium: standard replacement is 40mmol/L IV fluid if K+ between 3.5 and 5 due to hypokalaemia
DKA complications
Hyperkalaemia or Hypokalaemia: Predispose to cardiac arrythmias
ARDS
Cerebral oedema
Gastric stasis
Hyperosmolar hyperglycaemic state (HHS)
Hyperosmolar hyperglycemic state is a metabolic complication of diabetes mellitus (DM) characterized by severe hyperglycemia, extreme dehydration, hyperosmolar plasma, and altered consciousness.
Osmotic diuresis, severe dehydration and electrolyte deficiency
HHS signs/symptoms
Fatigue, lethargy, Nausea and Vomiting, altered level of consciousness, headaches, papilloedema, weakness, hyperviscosity of blood -> CV events. Dehydration, hypotension, tachycardia.
HHS diagnosis
- Glucose over 50
- Hypovolaemia
- No ketonaemia
- Bicarbonate > 15
- ph >7.3
- osmolaity >320 (2xNa + urea + glucose). Normal = 275-295
HHS management
Careful fluid replacement – risk of fluid overload but try and replace/correct fluid deficit during the first 24 hours
o 3L+ve at 6 hours
o 3-6L+ve at 12 hours
Reduce glucose by 5mmol/hr and no more (prevent cerebral oedema and seizures)
Decreases osmolality 3-8 per hour
K+: 40mmol/L if K+ is between 3.5-5 due to treatment
Slower insulin or may not require (often glucose improves with fluids) e.g. 3 units/hour
Ketones > 1.0 then low dose 0.05 u/kg/hour
Sodium – avoid rapid fluctuations .g. ≤0.5mmol/l/hr and consider 0.45% Saline
Co-morbidities: screen vascular event or LMWH unless contradicted
STOP any SGLT2 inhibitors
Euglycaemic Keto-acidosis
Euglycemic diabetic ketoacidosis (EDKA) is a clinical triad comprising increased anion gap metabolic acidosis, ketonemia or ketonuria and normal blood glucose levels <200 mg/dL. This condition is a diagnostic challenge as euglycemia masquerades the underlying diabetic ketoacidosis.
Look for SGLT2i
Severe Alcohol-induced Keto-acidosis
Alcoholic ketoacidosis is a metabolic complication of alcohol use and starvation characterized by hyperketonemia and anion gap metabolic acidosis without significant hyperglycemia. Alcoholic ketoacidosis causes nausea, vomiting, and abdominal pain.
History: acomprosate
Severe Alcohol-induced Keto-acidosis Mx
- IV fluids (dextrose)
- IV pabrinex
- IV-antiemetics
Lactic acidosis
Type A: Tissue hypoxemia e.g. ischaemic bowel, cardiogenic and hypovolemic shock
Type B: associated with diabetes
Lactic acidosis management
Reduced bicarbonate Raised anion gap [(Na+ + K+) – (HCO3 + Cl-)]. Normal 10-18 Glucose variable – maybe [often] raised Absence of ketonaemia Raised phosphate
Treat underlying condition: Fluids and antibiotics
Withdraw offending medication
MODY
AD: genetic defect in B cell function
Types
• HNF-1α
• HNF-4α
• Glucokinase
MODY 2 (Glucokinase)
rate limiting step (glucokinase). Sensing defect, blood glucose threshold for inulin secretion is increased . Homeostatic point at 7 insead of 5
MODY 2 management
diet treatment
MODY 1 and 3
defects in HNF-1a, 1b and 4a.
Also regulate β cell differentiation and function
glycolytic flux, expression of GLUT2 transporters, cell growth, insulin secretion, glucose transport and metabolism
MODY 1 and 3 Mx
glicazide work on KATP channels
Neonatal diabetes
Kir6.2 mutations: constitutively activated KATP channels or an increase in KATP numbers
Transient or permanent
Neonatal diabetes Mx
SURs such as tolbutamide
Graves disease
Autoimmune disease: Antibodies bind to and activate thyrotropin receptors diffuse thyroid enlargement, increase in hormone production (T3) & react with orbital autoantigens
signs/symptoms of hyperthyroidism
Weight loss, ‘manic’, restlessness, heat intolerance, palpitations (even provoke arrhythmias), increased sweating, diarrhoea, oligomenorrhea, anxiety and tremor.
Graves disease signs/symptoms
- Exophthalmos and ophthalmoplegia
- Pretibial myxoedema
- Thyroid acropachy
- thyroid bruit
Graves diagnosis
TSH decrease and FT4/T3 increase
hypercalcaemia and ALP increase
Leukopenia
TRAb
Graves management
- Propranolol
- Carbimazole and PTU (1st trimester of pregnancy)
- Radioiodine treatment
- Thyroidectomy
- Mild eye disease (topically lubricants and steroids)
Carbimazole risk
aplasia cutis and agranulocytosis (fever, oral ulcer or oropharyngeal infection - do urgent FBC)
PTU risk
Liver failure and agranulocytosis (fever, oral ulcer or oropharyngeal infection - do urgent FBC)
Toxic multi nodular goitre
autonomously functioning thyroid nodules that secrete excess thyroid hormones
TMG signs/symptoms
Thyroid nodular and asymmetrical goitre
diagnosis TMG
FT4 increases and TSH decreases
Scintigraphy: high uptake
Thyroid USS: Exclude cancer
TRAb negative
Toxic adenoma
Solitary nodule producing T3 and T4.
Hot nodule on scintigraphy
Other causes of hyperthyroidism
- Ectopic thyroid tissue: follicular cancer (blood spread) or struma ovarii (ovarian teratoma with thyroid tissue)
Exogenous: iodine excess, contrast media and levothyroxine excess (T4 increases, T3 and thyroglobulin)
Subacute de Quervains thyroiditis: self-limiting post viral with painful goitre: associated neck tenderness, fever, viral symptoms, low isotpe scan and NSAIDs for treatment
Drug induced: amiodarone and lithium
Post-partum: In postpartum thyroiditis
Hashimotos thyroiditis
Autoimmune destruction of thyroid gland and reduced thyroid hormone production
Signs/symptoms of hypothyroidism
Weight gain, lethargy, cold intolerance, dry (anhidrosis), cold, yellowish skin. Non-pitting oedema e.g hands and face. Dry, coarse. Constipation. Menorrhagia. Decreased deep tendon reflexes and carpal tunnel syndrome
diagnosis of Hashimotos
TSH increase, FT4 decrease
MCV, CK, LDL increase
hyponatremia: decrease renal tubular water loss
hyperprolactinaemia: TRH increase leads to PRL increase
Anti-TPO antibodies
Hashimotos management
Younger patients: start levothyroxine at 50-100 μg daily. Review 12 weeks and adjust every 6 weeks by clinical state and to normalise it to suppress TSH
Elderly or IHD: start levothyroxine at 25-50 μg daily, adjusted every 4 weeks according to response. Cautiously as levothyroxine can cause angina or MI
Other causes of primary hypothyroidism
Goitrous
- iodine deficiency, drug (amiodarone, lithium) and maternal
Non-goitrous
- atrophic thyroiditis
- post ablative (radioidoine, surgery)
- Post radiotherapy
- congenital
Secondary hypothyroidism/hyperthyroidism causes
Diseases of the hypothalamus and pituitary gland (multiple!) o Infiltrative – sarcoid o Infectious o Malignant o Traumatic o Congenital o Cranial radiotherapy o Drug-induced
Subclinical hypothyroidism - when to treat
TPO positive
TSH > 10
past graves
pregnant
Subclinical hyperthyroidism
Treatment generally advised if TSH <0.1 (or if co-existing osteoporosis/fracture or AF)
Thyroid storm seen when?
hyperthyroid patients with an acute infection/illness, recent thyroid surgery, MI or radioiodine
signs/symptoms of thyroid storm
• Agitation, confusion, tachycardia, AF, D&V, goitre, thyroid bruit, acute abdomen and heart failure
Respiratory and cardiac collapse
• Hyperthermia
• Exaggerated reflexes
Thyroid storm management
Iugol’s iodine, glucocorticoids, beta blockers, PTU, fluids and monitoring
Myxoedema coma
affects elderly women with long standing but frequently unrecognized or untreated hypothyroidism
myxoedema coma diagnosis
ECG: bradycardia, low voltage complexes, varying degrees of heart block, T wave inversion, prolongation of the QT interval
Type 2 respiratory failure: hypoxia, hypercarbia, respiratory acidosis
Myxoedema coma management
Passively rewarm: aim for a slow rise in body temperature
Cardiac monitoring for arrhythmias
Close monitoring of urine output, fluid balance, central venous pressure, blood sugars, oxygenation
Broad spectrum antibiotics if infection suspected
Thyroxine cautiously and hydrocortisone
Papillary thyroid
Most common form of thyroid cancer
Cystic solitary nodule in thyroid and derived from follicular epithelium
Lymph spread more
Papillary thyroid FNA
Orphan Annie eye nuclear inclusions: clear nucleus?
Psnommona bodies
Papillary Thyroid cancer management
Thyroid lobectomy with ismuscetomy – papillary microcarcinoma (<1 cm diameter)
Sub-total thyroidectomy – nodal involvement and extrathyroidal spread
Total thyroidectomy
Nodal clearance: Central compartment clearance and lateral lymph node sampling for papillary tumours
3-6 months: WBIS. If remants, thyroid remnant ablation
sorafenib and lenvatibib: refractory
Follicular thyroid cancer
2nd commonest thyroid cancer
Single nodule with invasive growth pattern.
Haematogenous spread
Follicular thyroid cancer management
same as papillary apart from
Thyroid lobectomy with ismuscetomy – minimally invasive follicular carcinoma with capsular invasion
Sub-total thyroidectomy – distant mets and extrathyroidal spread
Medullary thyroid cancer
parafollicular C cells (neuroendocrine). Bilateral (familial) and MEN 2A and 2B
Secrete calcitonin
Total thyroidectomy
Anaplastic carcinoma
Undifferentiated and aggressive tumours
Primary parahyperthyroidism
Primary activity of the parathyroid gland through various causes
Solitary/multiple adenomas, hyperplasia of all glands, and carcinoma
Primary parahyperthyroidism
stereotypical - elderly females with unquenchable thirst and a normal or elevated
signs/symptoms of parahyperthyroidism
Bones, stones, abdominal groans and psychic moans
• Polydipsia, polyuria but dehydrated
• Peptic ulceration/constipation/pancreatitis
• Bone pain/fractures/osteopenia/osteoporosis due to bone resorption
• Renal stones
• Depression
• Hypertension
• Associations: hypertension. Multiple endocrine neoplasia: MEN I and MEN II
Primary parahyperthyroidism diagnosis
- Raised calcium
- Raised PTH
- Increased calcium excretion (urine)
- decrease serum phosphate
- Increase in ALP
- DEXA
- Sestamibi scanning
Primary parahyperthyroidism management
Mild: Increase fluid intake to prevent stones, avoid thiazides (hypercalcaemia) and high Ca2+ and Vit D intake
Rehydrate with 0.9% saline 4-6L in 24hours. Consider loop diuretics
Bisphosphonates- single dose will lower Ca over 2-3d.
surgery: adenoma or hyperplasia but needs to be end organ damage
- bone disease e.g. pepper pot skull
- gastric ulcers & renal stones
- Very high calcium (>2.85)
- Under age 50
- eGFR < 60ml/min
Secondary PTH
excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels) or Vitamin D with resultant hyperplasia of these glands or CKD
Secondary PTH diagnosis
PTH increased
Ca low
Phosphate high
Vit D low
Tertiary PTH
Tertiary hyperparathyroidism is a state of excessive secretion of parathyroid hormone (PTH) after a long period of secondary hyperparathyroidism and resulting in a high blood calcium level. It reflects development of autonomous (unregulated) parathyroid function following a period of persistent parathyroid stimulation.
Tertiary PTH diagnosis
PTH high Ca high Phosphate low Vit D normal ALP elevated
Malignant PTH diagnosis
Ca and ALP high
PTH low as PTHrp
Primary hypoparathyroidism
PTH is low due to gland failure
Autoimmune and congenital absence (DiGeorge syndrome)
Symptoms/signs
signs/symptoms of primary 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. Wrist and fingers flex
Chvostek’s sign: tapping over the parotid gland causing facial muscles to twitch
Primary hypoparathyroidism diagnosis
Reduced PTH
Reduced Calcium
Increased phosphate
Normal ALP?
Primary Hypoparathyroidism Mx
Calcium supplements >1-2g per day
Tablet: calcitriol or alfacalcidol (active metabolite of Vitamin D)
Depot injection: Cholecalciferol 300,000 units 6 monthly (vitamin D)
Emergency acute hypocalcaemia treatment
IV calcium gluconate 10 ml, 10% over 10 mins (in 50ml saline or dextrose)
Infusion (10ml 10% in 100 ml infusate, at 50 ml/h)
Pseudohypoparathyrodism
Pseudohypoparathyroidism (PHP) is a genetic disorder in which the body fails to respond to parathyroid hormone.
Pseudohypoparathyrodism signs/symptoms
Bone abnormalities (McCune Albright syndrome): Short metacarpals (esp 4th and 5th)
Round face, short stature, calcified basal ganglia
Obesity
Learning disability
Brachdactyly (4th metacarpal)
Pseudohypoparathyrodism dx
low calcium and high PTH
Pseudopseudohypoparathyrodism
• The same features as Pseudohypoparathyrodism but with normal biochemistry. Both genetic
Hypocalciuric hypercalcaemia
rare autosomal dominant condition.
It occurs as a result of mutations in the calcium-sensing receptor gene (CASR) causing decreased receptor activity. mild hypercalcemia, hypocalciuria, hypermagnesemia, hypophosphatemia
Cushing’s Disease vs Cushing’s syndrome
Cushing’s disease refers to the specific condition where a pituitary adenoma secretes excessive ACTH and causes Cushing’s syndrome.
ACTH dependent (problem arising with pituitary gland and excess of ACTH)
Pituitary adenoma (68%): Cushings Disease
Paraneoplastic Ectopic ACTH 12% (carcinoid/carcinoma)
Ectopic CRH <1%
ACTH independent (too much cortisol)
- Adrenal adenoma 10%
Adrenal carcinoma 8% - Nodular hyperplasia 1%
- Exogenous steroids e.g. asthma, rheumatoid arthritis, inflammatory bowel disease, transplants
- Chronic suppression of pituitary ACTH production and adrenal atrophy. Unable to respond to stress (illness/surgery). Need extra doses of steroid when ill/surgical procedure
Cushings syndrome signs/symptoms
- Easy bruising
- Facial plethora: fullness
- Abdominal Striae
- Proximal myopathy
- Central obesity
- Buffalo hump
- Hypertension, cardiac hypertrophy, hyperglycaemia, depression and insomnia
- Osteoporosis, easy skin bruising
- Gonadal dysfunction: oligio/amenorrhoea, hirsutism, acne
Cushings diagnosis
Establish cortisol excess: low dose dexamethasone suppression test (1mg): suppress cortisol
High dose dexamethasone (6-8mg) over 48 hours and measure ACTH:
- Pituitary adenoma: some negative feedback and cortisol is suppressed
- Adrenal adenoma: cortisol production is independent from pituitary, therefore is not suppressed however ACTH is suppressed (negative feedback)
- Ectopic ACTH: Neither cortisol or ACTH are suppressed because ACTH production is independent of hypothalamus and pituitary gland
MRI: brain and adrenal glands
CT lungs and adrenal glands for cancer
Hypokalaemia
Cushings management
Pituitary:
- Hypophysectomy and external radiotherapy
- bilateral adrenalectomy (refractory)
Adrenal
- adrenalectomy and steroid replacement
Ectopic
- remove source or the above
Addison’s Disease
primary adrenal insufficiency and hypocortisolism, is a long-term endocrine disorder in which the adrenal glands do not produce enough steroid hormones (autoimmune: adrenal cortex destroyed).
signs/symptoms of addisons
> 90% destroyed before symptomatic.
• Anorexia, weight loss
• Fatigue/lethargy
• Dizziness and low BP
• Abdominal pain, vomiting, diarrhoea
• Skin pigmentation – darkness in the palmar creases and buccal hypopigmentation
o ACTH very high and cross react with melanin receptors to cause pigmentation disease
Addisons biochem
low Na, high K+
hypoglycaemia
Addisons test
SHORT SYNACTHEN TEST
- Measure plasma cortisol before and 30 minutes after iv/im ACTH injection
- Normal: baseline >250nmol/L
- post ACTH >550nmol/L (needs to peak)
Plasma ACTH: increased
Renin/aldosterone:
increased renin, decreased aldosterone due to adrenal cortex destruction
Addison’s management
IV fluid resus
correct hypoglycaemia
Hydrocortisone (15-30mg): split into 3 doses
Fludrocortisone: aldosterone replacement
Secondary Adrenal insufficiency
Inadequate ACTH stimulating the adrenal glands resulting low cortisol release
Secondary Adrenal insufficiency causes
Pituitary/hypothalamic disease tumours e.g. Surgery/radiotherapy • Infection • Sheehan’s syndrome • Loss of blood flow • Exogenous steroid use
Secondary Adrenal insufficiency Mx
hydrocortisone replacement (fludrocortisone unnecessary)
Primary Aldosteronism
Autonomous production of aldosterone independent of its regulators (angiotensin II/potassium)
Primary Aldosteronism causes
Adrenal adenoma secreting aldosterone: Conns syndrome
Bilateral adrenal hyperplasia
Familial hyperaldosteronism type 1 and type 2
Adrenal carcinoma
Primary Aldosteronism signs/symptoms
Often asymptomatic
Weakness, cramps
Signs of hypokalaemia and hypernatremia
Polyuria and polydipsia
Hypertension
Primary Aldosteronism diagnosis
Low serum renin and high aldosterone: express as ratio
If raised: saline suppression test
- Failure of plasma aldosterone to suppress by > 50% with 2 litres of normal saline confirms PA
Adrenal CT/MRI to demonstrate adenoma
Sometimes adrenal vein sampling to confirm adenoma is true source of aldosterone excess
Conns management
Surgical: Unilateral laparoscopic adrenalectomy
cases
Medical: In bilateral adrenal hyperplasia, use MR antagonists (spironolactone or eplerenone)
Secondary Aldosteronism causes (excess renin)
Several causes for high renin levels and they occur when the BP in the kidneys is disproportionately lower than BP in the rest of the body
- Renal artery stenosis
- Renal artery obstruction
- Heart failure
Secondary Aldosteronism diagnosis and management
Serum renin will be high and high aldosterone
US, CT and MRI angiogram
Percutaneous renal artery angioplasty via femoral artery to treat renal artery stenosis
Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of rare inherited autosomal recessive disorders characterized by a deficiency of one of the enzymes needed to make specific hormones
21-hydroxylase deficiency is one of a group of disorders known as congenital adrenal hyperplasia’s that impair hormone production and disrupt sexual development.
Congenital Adrenal Hyperplasia diagnosis
Increase in androgens (ambiguous female genitilia) but deceases in aldosterone (hypotension) and cortisol
increased 17-OH progesterone
CAH management
Paediatricians o Timely recognition o Glucocorticoid replacement o Mineralocorticoid replacement in some o Surgical correction o Achieve maximal growth potential
Adult Physicians
o Control androgen excess
o Restore fertility
o Avoid steroid over-replacement
Pheochromocytoma
Tumour of the chromaffin cells in the adrenal glands in the adrenal medulla
Extra adrenal [sympathetic chain] – paraganglioma
- MEN 2, NFL and VHL
Pheochromocytoma classic triad
hypertension, headaches and sweating
Pheochromocytoma diagnosis
Hyperglycaemia – adrenaline secreting tumours
low potassium level
High haematocrit – i.e. raised Hb concentration
Mild hypercalcaemia
Lactic acidosis – in absence of shock
Urine – 2x24hour catecholamines or metanephrins (more biologically stable)
MRI, MIBG and PET scan
Pheochromocytoma management
Full α and β- blockade (α before β): if you block B first, all adrenaline goes to A and it vasoconstricts (significant) too much causing a stroke
- Phenoxybenzamine (α-blocker)
- Propranolol, atenolol or metoprolol (β-blocker)
- Fluid and/or blood replacement
Surgical: laparoscopic: need to have symptoms controlled medically first
- Adrenalectomy
- Tumour de-bulking
- Chemotherapy if malignant
- Radio-labelled MIBG
Prolactinoma
noncancerous tumour (adenoma) of the pituitary gland in your brain overproduces the hormone prolactin. The major effect is decreased levels of some sex hormones — oestrogen in women and testosterone in men.
Prolactinoma causes
Physiological: breast feeding, pregnancy, stress and sleep, drugs (dopamine antagonists, antipsychotics e.g. phenothiazines, anti-depressants e.g. TCA
Pathological: Hypothyroidism, stalk lesions (iatrogenic, road accident – stalk affect), Prolactinoma (adenoma)
Prolactinoma signs/symptoms
Female (early presentation)
• Galactorrhoea (normal milk production but at abnormal time: 30-80%)
• Menstrual irregularity
• Ammenorrhoea: body is fooled into thinking it is pregnant
• Infertility
Male (Late presentation) • Impotence • Visual field abnormal • Headache • Ant pit malfunction
Prolactinoma management
Dopamine agonists:
- Cabergoline
- Bromocriptine: three times per day oral
- Quinagolide
Surgery: Pituitary and radiotherapy alone
Acromegaly signs/symptoms
Giant (before epiphyseal fusion)
Thickened soft tissues e.g. skin, large jaw, sweaty, large hands. Prominent forehead and brow, large nose, large tongue (macroglossia), protruding jaw
Snoring/Sleep apnoea (thickened nasopharynx)
Hypertension (heart), cardiac failure (hypertrophic)
Headaches (vascular) – not pressure
Diabetes mellitus – stress hormone so releases glucose and raises BG (type 2)
Local pituitary effects: visual fields (bitemporal hemianopia), hypopituitarism
Early CV Death
Colonic polyps and colon cancer (colorectal cancer)
Acromegaly diagnosis
IGF1
OGTT: Glucose increases and GH should decrease
Acromegaly management
Surgery Medical - somatostatin analogues - dopamine agonists - GH antagonist e.g. Pegvisomant
Pan Hypopituitarism
inadequate or absent production of the anterior pituitary hormones.
GGAT: Gonadotrophins (women present first due to periods going quickly), GH, ACTH and TSH
Pan Hypopituitarism management
Thyroxine: 100-150mcg/day
Hydrocortisone: 10-25 mg/day (am/pm).
ADH: Desmospray (nasal) or desmopressin tablets
GH: GH nightly sc
HRT/Oest/prog pill for female
Testosterone for males
Cranial diabetes Insipidus/Nephrogenic Diabetes Insipidus
Cranial diabetes insipidus is a condition in which the hypothalamus does not produce enough anti-diuretic hormone.
Nephrogenic diabetes insipidus is a condition in which the kidneys fail to respond to anti-diuretic hormone
Cranial diabetes Insipidus/Nephrogenic Diabetes Insipidus signs/symptoms
Polyuria Polydipsia Dehydration Postural hypotension Hypernatremia
DI diagnosis
Ur/Serum Osmol ratio >2 then it is normal, otherwise DI
Water deprivation test
ADH given - urine osmality increases (cranial) if not, nephrogenic
Cranial DI management
Desmospray, desmopressin
Nephrogenic DI management
Correct reversible causes such as hypokalaemia, hypercalcaemia and stop offending drugs e.g. lithium
• Massive doses of ADH can sometimes help and drink lots
• Thiazides potentially
SIADH diagnosis
low plasma sodium and osmolality
High urine osmolality and sodium
SIADH management
Exclude hypothyroidism (not able to excrete enough water at kidneys: low sodium and plasma osmolarity) and Addison’s
Fluid restrict them: 1-1.5 Litres per day
Demeclocycline – old fashioned antibiotic that uncouples the aquaporin 2 receptor from vasopressin (V2) receptor
Tolvaptan: V2 receptor antagonist allow the free water excretion that is required – diuretics not good as they excrete sodium along with water and therefore there is no change in osmolality and the hyponatraemia is exacerbated. Very expensive
WHO infertility
Group I Hypothalamic pituitary failure – not producing GnRH, ovaries then don’t get FSH or LH (Hypogonadotrophic hypogonadism)
group II Hypothalamic pituitary dysfunction
Group III: Ovarian failure
Anorexia management
Pulsatile GnRH (pump): SC or IV. SC or IV. Pump worn continuously (Pulsatile administration every 60-90 mins/Mono pregnancy)
Gonadotrophin (FSH+LH) daily injections: higher multiple pregnancy rates
PCOS diagnosis
Bloods: high free androgens, high LH, impaired glucose tolerance
Diagnosis: score 2 out of three:
- chronic anovulation: Oligio/amenorrhoea
- polycystic ovaries – ultrasound
- hyperandrogenism (clinical or biochemical) e.g. acne, hirsutism
Insulin resistance - lowers SHBG: increased free testerstone
PCOS management
lifestyle: wt loss
- Clomifene citrate, add in metformin
- Gonadotrophin therapy
- Laparoscopic ovarian diathermy
Primary Hypogonadism
Testes primarily affected
Decreased testosterone = decreased -ve feedback
Anterior pituitary secretes higher amounts of LH/FSH to help testes to produce more testosterone “hypergonadotrophic hypogonadism”
Spermatogenesis is affected more than testosterone production
Primary Hypogonadism (problem with testes) Ix
Measure Total Testosterone and SHBG (between 8-11am: 9am)
FSH and LH
Karotyping
Iron studies
Primary Hypogonadism Mx
Testosterone replacement therapy
Contradictions to testosterone therapy
- Confirmed hormone responsive cancer (e.g. prostate/breast)
- Possible prostate cancer (e.g. raised PSA, suspicious prostate on PR).
- Haematocrit >50%. Stimulates bone marrow to produce RBC, will cause people to become polycythaemia – increased chance of stroke and thickened blood
- Severe sleep apnoea/heart failure
Secondary Hypogonadism (Kallmann’s syndrome)
• Hypothalamus/pituitary affected, testes capable of normal function
LH/FSH low (or inappropriately normal) despite low testosterone “hypogonadotrophic hypogonadism”
Not able to produce higher LH/FSH due low testosterone
Spermatogenesis and testosterone production are affected equally – whole testes are not being stimulated
Kallmann’s syndrome
isolated hypogonadotrophic hypogonadism”)
Genetic disorder: isolated GnRH deficiency and hyposmia/anosmia
MEN 1
AD: Mutations occur throughout MEN1 gene located chromosome 11q13
3Ps: parathyroid, pituitary and pancreatic
Leading causes of death in MEN1
malignant pancreatic neuroendocrine tumour
thymic carcinoids
MEN2
AD: RET mutations
MEN2A
MEN2A accounts for 90‐95% of MEN2 cases
MEN2A describes combination of medullary thyroid cancer in association with phaeochromocytoma and parathyroid tumours
MEN2B
MEN2B is less frequent (5¬‐10% of MEN2 cases)
MEN2B = MTC and phaeochromocytoma in association with a marfanoid habitus, mucosal neuromas, medullated corneal fibres, intestinal autonomic ganglion dysfunction
VHL
Tumours of abnormal blood vessels – angioma of the eyes
Mutation in VHL gene
Autosomal dominant
Gene mutation leads to accumulation of HIF proteins and stimulation of cellular proliferation
Range of vascular tumours
Carney Complex
autosomal dominant syndrome associated with spotty pigmentation of the skin, endocrinopathy, and endocrine and nonendocrine tumors, including the following: Myxomas of the skin, heart, breast, and other sites. Primary pigmented nodular adrenocortical disease.
Primary pigmented nodular adrenocortical disease = PPNAD
PPNAD causes the adrenal glands to produce an excess cortisol leading to the development of Cushing syndrome
McCune¬‐Albright Syndrome
disorder that affects the bones, skin, and several hormone-producing (endocrine) tissues.
