Endocrine Flashcards
Thyroid Symptoms
Thyrotoxicosis = weight loss, restless, heat intolerance, palp, arrhythmias, sweating, diarrhoea, oligomenorrhea, anxiety, tremor
Hypo = weight gain, tired, cold intolerance, dry skin, non-pitting oedema, dry coarse hair, lose lateral eyebrows, constipation, v deep reflexes, carpal tunnel, menorrhagia
Hypothyroid: Causes
Hashimoto’s Thyroiditis
Most common, AI destruction of thyroid, 10F:M
Link - coeliac, T1DM, Addison’s, pernicious anaemia
= firm non-tender goitre, MALT lymphoma
Inv - anti TPO, anti thyroglobulin
Iodine Def
Most common cause in developing world
Subacute Thyroiditis (De Quervain’s)
Hypothyroid post-viral infection
= painful goitre, hyper/ eu/ hypothyroid, self-limiting
Inv - ^ESR, global reduction of iodine uptake
Riedel’s Thyroiditis
Parenchyma replaced by dense fibrous tissue
= hard fixed painless goitre, middle-age F, retroperitoneal fibrosis
Others - post-radioiodine, post-partum, lithium, carbimazole, amiodarone, 2nd to Down’s, Turner’s, coeliac
Hyperthyroid: Causes
Graves Disease
Most common, TSH Ab mimic TSH, 40yr F
= exophthalmos, eye pain, pretibial myxedema, thyroid acropachy (digital clubbing, periosteal bone formation and soft tissue swelling)
Inv - TSH receptor stim Ab, anti-TPO, scintigraphy (diffuse homogenous and ^uptake)
-> propranolol for symptoms, may start carbimazole while waiting for referral
Toxic Multinodular Goitre
Autonomously functioning nodules secrete hormones
Inv - scint (patchy uptake)
-> radioiodine therapy
Amiodarone (stop)
Subclinical Thyroid
Hyper: low TSH, normal T3/4, observe/ try antithyroid for 6m
Hypo: high TSH, normal T3/4, treatment based on TSH level
> 10 (2x 3mths apart) - consider levothyroxine
5.5-10 - consider if <65yrs + symptoms, if no symptoms repeat TFTs in 6 months
Thyroid Function Tests Interpretation
. TSH Free T4
Primary Hyper - Low High
Secondary Hyper - High High
Sick euthyroid - Low Low
Subclinical Hyper - Low Normal
Subclinical Hypo - High Normal
Thyroxine incompliance - High Normal
Steroids - Low Normal
Sick euthyroid: very ill, back to normal when they recover
Thyroid Storm and Myxoedema coma
Storm
Rare, life-threatening comp of (established) thyrotoxicosis
Causes - infection, surgery, trauma, acute iodine load
= fever, tachy, ^BP, n+v, confusion, HF, jaundice
-> IV propranolol, anti thyroid drugs, maybe Dex (blocks conversion of T4-T3)
Myxedema Coma
Emergency, severe hypothyroid
= confused, hypothermia, coma
-> IV thyroid replace, IV fluids, IV steroids (until excl. adrenal insufficiency)
Thyroid Cancers
Rarely secrete hormones (euthyroid)
Types
Papillary: 70%, excellent prognosis, ^young F, spread to cervical nodes
Follicular: 20%, solitary nodule, vascular invasion
Medullary: cancer of parafollicular (C) cells, secrete calcitonin, MEN-2
Anaplastic: poor response to treatment, pressure symptoms, local invasion, elderly F
Lymphoma: link to Hashimoto’s
Inv - refer unexplained neck lump, US, biopsy
-> total thyroidectomy, radioiodine kills residual cells, yearly thyroglobulin for recurrence
SIADH
Hyponatremia 2nd to excessive water retention (dilutional), inappropriate release of ADH
Causes - small cell lung cancer, stroke, SAH, subdural, meningitis, TB, sulfonylureas, SSRIs, TCAs, vincristine, carbamazepine, cyclophosphamide
Inv - low plasma osmolality, high urine osmolality (^Na)
-> fluid restriction, ADH antagonists, slow correction of Na (central pontine myelinolysis)
Cushing’s Syndrome
Group of symptoms 2nd to excess cortisol in the body
ACTH-dependent
- Cushing’s disease (80%, pit adenoma secretes ACTH causing adrenal hyperplasia)
- ectopic ACTH (small cell lung cancer)
ACTH-independent
- steroids
- adrenal adenoma (Conn), adrenal carcinoma (rare)
- Carney complex (cardiac myxoma)
Inv - ABG (v K alkalosis), IGT, Dexamethasone Suppression
Overnight: morning cortisol spike not suppressed in Cushing’s
High-dose: cortisol and ACTH suppressed in Disease, only ACTH suppressed in Adrenal Adenoma, neither in Ectopic
Pseudocushings
Causes - alcohol excess or severe depression
Inv - false positive on dex suppression, insulin stress test to differentiate (GH and cortisol should rise after IV insulin)
Water Deprivation Test
For patients with polydipsia
Stop drinking, empty bladder -> hourly urine and plasma osmolality
Starting plasma, final urine, post desmopressin
Psychogenic - Low, >400, >400
Cranial DI - high, <300, >600
Nephrogenic - high, <300, <300
Hyponatremia
Hypovolemic
Causes - renal failure, thiazide/ loop diuretics, Addison’s
Euvolemic
causes - SIADH, hypothyroidism
Hypervolemic
Causes - HF, liver cirrhosis, nephrotic syndrome, PP
Also, burns, d+v, sweating
= headache, lethargy, n+v, dizzy, confused, muscle cramps, seizure, coma, resp arrest
Comp - cerebral oedema, brain herniation
Hyponatremia: Management
Mild <135, Moderate <130, Severe <120
-> Chronic >48hrs
Hypo - normal saline
Euvolemic - fluid restrict
Hyper - fluid restrict
-> Acute with symptoms
Hypertonic saline (3% NaCl) in HDU
Comp - osmotic demyelination syndrome (CPM, raise by 4-6 in 24hrs only)
Primary Hyperaldosteronism
Causes - bilateral idiopathic adrenal hyperplasia, Conn’s syndrome (adrenal adenoma)
= HTN + low K (muscle weakness), met alkalosis
Inv - high aldosterone: low renin, high res CT abdo and adrenal vein sampling (? uni/bilateral)
-> surgery for adenoma, spironolactone for hyperplasia
Congenital Adrenal Hyperplasia
AR, excessive androgens production 2nd to deficiency of 21-hydroxylase (11-beta/ 17)
= virilize female infant, early puberty in boys
DKA
Uncontrolled lipolysis, excess free fatty acids converted to ketones
= abdo pain, polyuria, polydipsia, deep hyperventilation (Kussmaul), pear drop breath
Inv - glucose > 11, pH 7.3, bicarb <15, ketones >3
-> Isotonic saline, + insulin infusion at (0.1u/kg/hour), + 10% dextrose infusion when glucose <14 (125ml/hr), may add K
Continue long acting insulin but stop short acting
DKA resolution = pH >7.3, ketones <0.6, bicarb >15
Endocrine review if not by 24hrs
Watch out for cerebral oedema post-resus (^young)
Metabolic Acidosis
Classified based on the anion gap (positive - negative ions)
Normal (10-18)
= GI bicarb loss (diarrhea, fistula), Addison’s, RTA, acetazolamide
Raised
= high lactate (shock, sepsis, hypoxia, metformin), ketones (DKA, alcoholic KA - glucose is normal), urate (renal failure), salicylate/ methanol poisoning
Primary Hyperparathyroism
Causes - 85% solitary adenoma, hyperplasia, multiple adenoma, carcinoma
Link - MEN1/2
= 80% asymp, otherwise high calcium (bones, stones, abdo groans and psychic moans)
Inv - norm or ^PTH, ^Ca, v phosphate, skull XR (pepper pot)
-> parathyroidectomy, conservative using calcium mimetic (cinacalcet)
Acromegaly
Excess growth hormone due to pituitary adenoma (95%) or ectopic GH (drug, pancreatic tumour), 6% have MEN1
= coarse facial features, spade hands, big feet, large tongue, prognathism, interdental spaces, sweaty, oily skin, galactorrhea
*bitemporal Hemianopia and headaches in pit tumour
Inv - serum IGF-1, serial GH and OGTT (usually high glucose suppresses GH), pit MRI
Comp - HTN, DM, cardiomyopathy, CRC
Acromegaly Management
-> trans-sphenoidal surgery, drug if not
Ocreotide: somatostatin analogue, inhibits GH release
Pegvisomant: GH receptor antagonist, no effect on size
Bromocriptine: dopamine agonists
Addison’s Disease
Autoimmune destruction of the adrenal glands
Other causes of hypoadrenalism - TB, mets, Waterhouse-Friedrichsen, HIV, APL syndrome
= hyperpigmentation (primary only), vitiligo, lethargy, n+v, weight loss, salt craving, hypotension, v pubic hair
Inv - ^K, v Na, v glucose, met acidosis, ACTH stimulation test (measure cortisol 30min before and after giving synacthen, should x2), 9am serum cortisol (>100)
-> hydrocortisone (most in first half of day, double if ill), fludrocortisone, hydro injection kit for crisis
Diabetes: Key Facts
C-peptide low in T1, normal in T2
Diagnosis
Fasting glucose 7.0+ or random glucose/ 2hr GTT 11.1+
If no symptoms need two separate occasions
T1 - 80% anti-GAD/ islet cell Ab, insulin auto-Ab
T2 - HbA1c >48 (not useful in T1)
Pre-Diabetes:
IFG: fasting glucose 6.1-6.9
IGT: fasting <7 + OGTT 7.8-11.1
HGV license - no hypo in 12m, good control, understand risks
Other types of DM
MODY: inherited genetic disorders affecting insulin production
= young with T2 symptoms, FHx
-> sensitive to sulfonylureas
LADA: autoimmune, later in life
Others incl. chronic panc, haemochromatosis, steroids
Management of T1 DM
Monitor HbA1c every 3-6 months (target <48)
Monitor BG 4x a day (target 5-7 on waking, 4-7 before meals)
MDI basal bolus preferred (BD detemir + analogue)
Add metformin if BMI 25+
T2DM: Targets
Targets:
Lifestyle +/- metformin - 48
Drugs that may cause hypo - 53
Only add second drug if 58+
BP - same as normal (ACEi 1st, ARB if black)
Satin - if Q risk >10% (atorvastatin 20mg)
Check HbA1c 6mthly
T2DM: Management
- Metformin (titrate up before adding next)
If contra use SGLT2, DPP4, pio or sulf - +SGLT2 if Q risk 10%, CVD or HF
HbA1c >58
3. + DPP4 or pio or sulf or SGLT2
- metformin + sulf + DPP4/ pio/ SGLT2, or insulin
- switch one of triple for GLP1 mimetic
DM sick day rules
May stop oral hypoglycaemic in acute illness
Stop metformin and GLP1 if becoming dehydrated
Do not stop insulin (risk of DKA), check BG 1-2hrly
Sex development disorders
Androgen Insensitivity (46XY)
X linked recessive, end organ resistance to testosterone
= male with female genotype
5-a Reductase Deficiency (46XY)
AR, inability to convert T to DHT
= ambiguous genitalia in newborn, hypospadias, virilised at puberty
Kallman’s
X linked recessive, hypogonadotropic hypogonadism, failure of GnRH-secreting neurons to migrate to hypothalamus
= anosmia, boy with delayed puberty, low sex hormones, low/norm FSH + LH
Klinefelter’s (47 XXY)
= tall, small firm testes, lack 2nd sexual characteristics, gynecomastia, low testosterone, high gonadotrophins
Gynaecomastia
Abnormal amount of breast tissue in M, ^oes:androgen ratio
Causes - puberty, low T (Kallman, Klinefelter), testicular failure (mumps), seminoma, hyperthyroidism
Drugs incl. spironolactone, digoxin, cimetidine, cannabis, finasteride, goserelin
Hypercalcaemia
Causes - primary hyperparathyroidism, cancer (PTHrP from squamous cell lung ca, bone mets, myeloma)
Rarely sarcoid, Vit D OD, acromegaly, thyrotoxicosis, thiazide, dehydration, Addison’s
= bones, stones, abdo pain, psychic groans, corneal calcification, v QT, HTN
-> normal saline (4-6L per 24hours), bisphosphonates (days to work)
Hypoparathyroidism
Decreased PTH secretion, v Ca and ^PO4
Causes - thyroid surgery
= symptoms of low Ca
-> Alfacalcidiol
Pseudo: target cells are insensitive to PTH (^PTH, v Ca)
= low IQ, short stature, short metacarpals
Pseudopseudo - normal biochem
Hypocalcaemia
Causes - low Mg, acute pancreatitis, hypoparathyroid, low vit D (OM), CKD
= tetany, perioral paraesthesia, Trousseau (carpal spasm with BP cuff), Chvostek (tap parotid face twitch), ^QT
-> IV calcium gluconate if severe, monitor ECG
Multiple Endocrine Neoplasia
AD, inherited endocrine disorder
1 - Parathyroid, Pituitary, Pancreas
*present with Ca
RET oncogene
2a - Medullary thyroid, Parathyroid, Phaeochromocytoma
2b - Medullary thyroid, Marfanoid body habitus, Phaeochromocytoma, Neuromas
Phaeochromocytoma
Rare, catecholamine secreting tumour
RF - FHx, MEN2, NF, VHL
Bilateral in 10%, malignant in 10%, extra adrenal in 10% (aortic bifurcation)
= HTN, headaches, palpitations, sweating, anxiety
Inv - 24hr urinary metanephrine collection
-> stabilise on alpha blocker then beta blocker before surgery
Hyperparathyroidism: Labs
Primary - high/ normal PTH, high Ca, low PO4
Secondary (CKD) - high PTH, low/ normal Ca, high PO4, low Vit D
Tertiary - high PTH, high/ normal Ca, low/ normal PO4, low vit D, high ALP
Causes of high prolactin
Prolactinoma
Pregnancy
Oestrogen
Stress
Acromegaly
PCOS
Hypothryoid (TRH stimulates prolactin release)
Metoclopramide, domperidone
Phenothiazines
Haloperidol
SSRIs
Prolactinoma
Pituitary adenoma, may secrete hormone
= impotence, v libido, galactorrhea, amenorrhea, infertility, osteoporosis, bitemporal hemianopia or upper temporal quadrantanopia
Inv - MRI (micro <1cm)
-> dopamine agonists for symptoms, surgery if not
Insulinoma
Neuroendocrine tumour, pancreatic islet of langerhan cells, 10% cancerous
RF - 50% MEN-1
= hypoglycemia, rapid weight gain
Inv - ^insulin, ^proinsulin:insulin, ^c-peptide (doesn’t reduce when given insulin), supervised fasting, CT pancreas
Hypokalaemia
Causes - d+v, diuretics, Cushing’s, hyperaldosteronism, RTA, acetazolamide, Mg deficiency
= weak, U waves, small T, long PR, depressed ST
-> max rate 10mmol/hr (>20 need cardiac monitoring)
Central Pontine Demyelinosis
Low sodium in the blood, water moves from areas of low (blood) to high solutes (brain), brain swells
With time, brain cells lose sodium to balance this
(chronic hyponatraemia only)
When sodium is corrected too rapidly, water moves quickly from brain to blood
Dehydrated astrocytes and oligodendrocytes undergo apoptosis → demyelination
C-Peptide
C peptide cleaves proinsulin into insulin
If the level is raised, it indicates that a lot of this process is occurring.
? OD due to exogenous insulin (normal c-peptide) or sulfonylureas (inc endogenous production of insulin so ^c-peptide)
Hba1c
Falsely High = iron def, splenectomy, b12 lack, alcoholism
Falsely Low = sickle cell, G6PD, spherocytosis, haemodialysis
Hormonal Axis Physiology
Ant Pituitary - all but ADH and Oxytocin.
Thyroid - Hypothalamus releases TRH. Ant pituitary releases TSH. Thyroid releases T4. (neg feedback on hypothalamus).
Adrenal - Hypothalamus releases CRH. Ant pit releases ACTH. Adrenals release cortisol. Cortisol causes inhibition of bone and immune system. Inc alrtness and glucose.
GH - GHRH released from hypothalamus. GH from pituitary. IGF from liver.
Parathyroid - PTH released when low calcium and also low Mg / high phosphate. Inc osteoclast activity, calcium reabsoprtion kidney and activation of Vit D.
Symptoms of Cushing’s
= moon face, central obesity, thin limbs, easy bruising, insomnia, HTN, cardiac hypertrophy, ^glucose, OP
Levothyroxine interaction
Iron and calcium carbonate = decreased absorption of levothyroxine
-> given 4hrs apart
HHS
Hyperosmolar Hyperglycaemic state, emergency, ^T2 elderly, high mort
Hyperglycaemia + osmotic diuresis in the absence of ketones
= days, polyuria, polydipsia, n+v, confusion, dehydration, ^HR, v BP, stroke, MI
-> IV fluids , insulin when glucose stops falling, VTE prophylaxis
