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A2 ME3031 ENDO DM > 03: Clinical Lectures 2 > Flashcards

03: Clinical Lectures 2 Flashcards

1
Q

Classify the steroid hormones according to their main physiological effects and the endocrine gland cell types that secrete them.

A

MINERALCORTICOIDS (zona medullarosa) = ALDOSTERONE
*salt balance = water balance

GLUCOCORTICOIDS (zona fasciculata) = CORTISOL
*energy balance

SEX STEROIDS (zona reticularis) = TESTOSTERONE
* sex

MEDULLA (extension of sympathetic system) = Norepinephrine and epinephrine
*stress response

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2
Q

Outline schematically the main pathways and cellular compartments involved in the synthesis of steroid hormones; and indicate the main agents and points of control.

A

CHOLESTEROL
=> PROGESTERONE

  • > CORTICOSTERONE > ALDOSTERONE
  • > CORTISOL
    (21-hydroxylase)

CHOLESTEROL
=> PROGESTERONE + DHEA => ANDROSTENEDIONE
> ESTRONE
> ANDROSTENEDIONE > TESTOSTERONE > estradiol
> DHT

  • different enzymes found in different adrenal zones in order to make different enzymes
    e. g. aldosterone enzymes found in zona glomerulosa
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3
Q

Outline diagrammatically the structure of the (compound) adrenal gland, indicating its zonation, vascularisation and innervation.

A

thoracic splanchnic nerve

The adrenal medulla is driven by the sympathetic nervous system via preganglionic fibers originating in the thoracic spinal cord, from vertebrae T5–T11

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4
Q

Justify the view that the adrenal cortex is essential for survival of the individual while the adrenal medulla is not.

A

Adrenal cortex produces hormones that controls sex (androgens, estrogens), salt balance in the blood (aldosterone), and sugar balance (cortisol). The adrenal medulla produces hormones involved in the fight-or-flight response (catecholamines, or adrenaline type hormones such as epinephrine and norepinephrine).

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5
Q

Describe the normal circadian basal rhythm in plasma total cortisol concentration & levels in pathology

A

high @ morning, lowest at midnight, ACTH mirrors levels

very high ACTH plasma = ectopic ACTH
very low ACTH = non-ACTH-dependent = adrenal gland
CUSHINGS (pituitary) = overlap between ectopic ACTH therefore ACTH measurement not enough to dx

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6
Q

Define the terms: plasma protein bound cortisol; plasma free cortisol.

A

95% of plasma cortisol bound to CORTISOL BINDING GLOBULIN

bind to receptors found in all nucleated cells

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7
Q

State the likely effect upon the plasma glucose concentration of administering cortisol to a normal subject; and list the target sites and processes underlying that effect.

A

Under stressful conditions, cortisol provides the body with glucose by tapping into protein stores via gluconeogenesis in the liver

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8
Q

Discuss the clinical features and biochemical diagnosis of the hyperfunction syndromes of the adrenal cortex and medulla (Cushing’s syndrome)

A

causes:

1º HYPERALDOSTERONISM:
*unilateral adenoma, bilaeral hyperplasoa

  • CUSHINGS: adrenal gland = XS cortisol androgens
  • tissue breakdown, sodium retention, insulin antagonism = DM, immune system suppression
    => central obesity, HT, glucose intolerance, Hirsutism, Striae

• ACTH-dependent = pit. tumour (cushing’s disease), ectopic ACTH secretion (lung carcinoid) = ⇧ACTH = XS cortisol.
or CRH secreting tumour = ⇧ACTH
• ACTH-independent = adrenal tumour (adenoma/carcinoma); corticosteroid therapy = 1º issue @ adrenal gland level

1) SCREENING: overnight dex test + 24hr free cortisol in urine
2) 24hr free urine cortisol rpt. + low dose dex test
3) ACTH monitoring @ morning-midnight
4) High dose dex test (pit or not pit.)
5) MRI sella, CT adrenal, BIPSS, CT chest

> Sx of tumour
ADRENAL HORMONE SYNTH INHIB (Ketoconazole etc.)
Destroy adrenocortical cells (Mitotane)
RT
Bilateral adrenalectomy

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9
Q

Describe the clinical features, diagnosis and management of adrenal hypofunction (Addison’s disease).

A

causes: adrenal dysgenesis, adrenal destruction, impaired steroidogenesis

1º ADRENAL INSUFFICIENCY

  • Addison’s: AuImm, Invasion, Infiltration, Iatrogenic, Infarction
  • +ve adrenal autoantibodies, lymphocytic infiltrate
  • no cortisol prod > ⇧CRH (hypothal) > ⇧ACTH & ⇧MSH (due to common POMC precursor) = PIGMENTATION
  • Decreased BV = postural hypotension

ADRENAL ENZYME DEFECTS
- congenital adrenal hyperplasia (21-hydroxylase deficiency)

• Low Na High K
• CORTISOL LEVELS CHECK
• SYNACTHEN TEST + BASAL ACTH: basline cortisol and ACT > synthetic ACTH (tetracosactrin) > measure over time,
= 450nmol+ over normal
= 1º adrenal insufficiency = no response
= 2º adrenal insufficiency = no CRH thus trophic diminished = stunted cortisol production
• followed by PLASMA ACTH measurements
• followed by Adrenal Antibodies + other autoimmune antibodies monitoring

+ long chain fatty acids (men) for adrenoleukodystrophy

> STEROIDS (if too unwell for SYNACTHEN)
daily: GLUCOCORTICOID (steroids) in divided doses to mimic diurnal variation (HC)
Mineralocorticoid replacement (fludrocortisone) which bind to ALDOSTERONE receptors; monitored for dose adjustment

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10
Q

Discuss the importance of glucocorticoids in acute stress (guidelines for the management of patients on replacement steroids).

A
  • HYPOADRENAL PATIENTS / REPLACEMENT STEROIDS require doubling steroid doses in order to react to stresses
  • Patients receiving long-term treatment and take exogenous steroids: endogenous steroid prod affected thus replacement steroids required.
  • minor short lived illness or stress = 2x
  • major illness/operation = 100mg HC iv
  • patient education to safetynet, partners and carers taught to inject IM HC w/ sever vom and diarrhoea
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11
Q

Outline inborn errors of the adrenal glands (congenital adrenal hyperplasia).

A

21-hydroxylase defect = aldosterone and cortisol def.
*salt and glucose balance disruption

  • excessive adrenal androgen production
  • hyperplasia d/t nil cortisol to negative feedback ACTH and CRH = continuous adrenal cortex stimulation
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12
Q

Screening tests for Cushings

A

24hr urinary free cortisol = 14-135nmol/24hr (normal)

Overnight Dex. suppression test = <50nmol/l @ 0900 (normal)

  • normal: cortisol drops
  • Pituitary dependent = drops after some time (day 4) d/t high dose eliciting neg feedback
  • Ectopic ACTH = cortisol levels remain high and not suppressed,
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13
Q

Discuss the clinical features and biochemical diagnosis of the hyperfunction syndromes of the adrenal cortex and medulla (Conn’s syndrome)

A

Xs ALDOSTERONE d/t adenoma or bilateral hyperplasia: normally stimulated by Angio.II (powerful vasoconstrictor) = water retention and HT

d/t
ALDOSTERONE-PRODUCING TUMOUR = renal tubules ⇧water retention etc. = ⇩renin = ⇩Angio.II =
⇧aldosterone:renin ratio

1) measure aldosterone:renin ratio, ratio >20 1º hyperaldosteronism
2) plasma renin activity (PRA) & plasma aldosterone concentration (PAC)
3) 24hr urine aldosterone w/ salt loading
4) CT adrenal, plasma 18-hydroxycorticosterone
5) adrenal venous sampling

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14
Q

Discuss the clinical features and biochemical diagnosis of the hyperfunction syndromes of the adrenal cortex and medulla (Phaeochromocytoma)

A

PHEOCROMOCYTOMA: neuroendocrine tumour in adrenal medulla = XS catecholmaines
= ⇧HR = ⇧CO = ⇧BP
= Diabetogenic d/t adrenergic effect on glucose metabolism

  • HT (especially young HT) & paroxysmal attacks: headache, sweating, palpitations, tremor, pallor, anxiety,
  • TUMOUR-ASSOCIATED
  • HYPERGLYCAEMIC; fight or flight stress.
  • MEN II (multiple endocrine neoplasia): phaecrom.
  • Von Hippel-Landau
  • MEN III

1) 24hr urine for metanephrines & plasma metanephrines
2) discontinue any contributing medications
3) Adrenal CT/MRI
4) Radionecleotide scan: selective uptake and localisation of lesion

+genetic testing w/ family hx > tumour evaluation (expression studies)

> Sx risk of crisis release of hormone release
thus
• alpha-adrenergic blockade > THEN beta blocker (lols)

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15
Q

Adrenal Mass Dx Algorithm

A

1) endocrine workup: free metanephrine plasma/urine, dex test, ALD:PRA
= Sx if functional and secretory
2) CT or MRI (non-functional, need to id malignant or benign)
3) surveillance or surgery

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16
Q

Congenital adrenal Hyperplasia

A

21-hydroxylase def.

Xs of precursors and shunted pathway to TESTOSTERONE

*lack of cortisol = no neg feedback = ⇧ACTH = adrenal hyperplasia

  • neonatal salt loss crisis
  • ambiguous genitalia (girls)
  • hirsutism (women)
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17
Q

Calcium distirbution & adjustment

A

dietary calcium forms salts and thus majorly excreted

BONE calcium reservoir
PLASMA calcium: 45% of plasma calcium is free/ionised and bio active
* total calcium needs to be adjusted
* albumin levels; binds to calcium thus dictate active calcium levels

  • 2.20-2.6mmol/l
  • ADJUST BY 0.1mmol/L FOR EACH 5G/L reduction in albumin from 40g/l

e.g. albumin of 30g/l = 0.2mmol INCREASE d/t to LOSS in albumin = above normal range

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18
Q

Parathyroid Glands

A

CHIEF CELLS: PTH

OXYPHIL CELLS: larger and less abundant;

*calcium-sensing receptors indicate and dictate PTH levels depending on plasma calcium

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19
Q

Vitamin D Metabolism

A

Inactive vitamin D (25-hydroxylase vitamin d) synthesised from precursors (obtained from sun metabolism @ skin or diet)

Activated (1,25) in kidney, controlled by PTH

acts on gut and serum calcium

  • inactive vitamin D is circulating form, long 1/2L
  • patients with renal impairment or chronic kidney disease REQUIRE ACTIVATED VITAMIN D
    >ALFACALCIDOL or CALCITRIOL prescribed (hydroxylated derivatives)
20
Q

hypocalcaemia: signs, causes, dx, mgmt

A

tetany + cardiac features (acute)
paraesthesia, twitching and spasm
*CHOVSTEK’S SIGN
*TROSSEAU’S SIGN

ectopic calcification, parkinsonism, dementia (chronic)

  • vit d deficiency (common)
  • Mg2+ deficiency interfere with PTH (GI Pt., diarrhoea, alcohol abuse, omperazole)
  • Cytotox drugs
  • genetic disorders
  • Bisphosphonates, calcitonin

1) Confirm adjusted calcium levels
2) PTH levels
3) Mg (⇩PTH) or Urea and Creatinine (⇧PTH)
4) Vitamin D
* ⇩phosphates & ⇧PTH in Vtamin D def.
* ⇧phosphates in hypoparathyroidism

combination of treatments (mild) >1.9mmol
> oral calcium tablets
> vitamin D
> Mg2+ replacement
> remove offending meds

severe <1.9mmol/L
MEDICAL EMERGENCY
> IV Calcium gluconate + ECg monitoring
> solve underlying cause

21
Q

hypoparathyroidism

A

inappt. low PTH in presence of hypocalcaemia

* common surgical cause, followed by autoimmune

22
Q

pseudohypoparathyroidism

A

presents in childhood, obesity, short stature, shortening of metacarpals

*hypocalcaemia + ⇧PTH

23
Q

ACUTE HYPERCALCAEMIA

A

<3.0mmol - MILD. OFTEN ASYMPTOMATIC, URGENT CORRECTION
3-3.5mmol - MOD. TOLERATED, SYMPTOMATIC, PROMPT TREATMENT
>3.5mmol - URGENT CORRECT, RISK OF COMA

24
Q

HYPERCALCAEMIA

A

1º Hyperparathyroidism, or non-parathyroid MALIGNANCY,
*drug induced (thiazide diuretics, Vit D & calcium supplements)
?hyperthyroidism
?milk alkali syndrome, antacid

  • polyuria, polydipsia, renal stones, anorexia, N&V, constipation
  • neuro: poor concentration, brain fog, confusion
  • cvd: shortening QT, bradycardia

1) PTH
2) Calcium, albumin

(1)
> Rehydration
> IV bisphosphonates (zolendronic acid) - will take a few days, repeated.

(2)
> GLUCOCORTICOIDS - lymphoma, granulomatous disease
> CALCITONIN - poor biphosphonate response
> CALCIMIMETICS
> PARATHYROIDECTOMY

25
Q

Testing for Hypercalcaemia

A 
Calcium & *PTH*
Glucose, TFTs
PO4
Serum ACE - sarcoidosis
CXR = secretory malignancies

?medication

26
Q

1º Hyperparathyroidism: Present., Causes, Investigations, Tx

A

Asympt. Associated w/ irradiation = parathyroid adenoma and gland hyperplasia. F > M

1) PTH
UE: renal function
2) USS - localise and aid Sx
3) SESTAMIBI: nuclear trace.

65+ 4D-CT, high dose

> Surgery for <65yo, >0.25mmol over recommended, osteoporosis on DEXA, eGFR <60
!hypocalcaemia (temporary)

> Fluid intake & Vit D replacement
Cinacalcet mimics calcium receptor action = ⇩PTH

27
Q

FHH

A

Familial Hypocalciuric Hypercalcaemia, AD
= ⇩urinary calcium

•normal/elevated PTH

28
Q

Multiple Endocrine Neoplasia

A

MEN, AD = 1º Hyperparathyroidism, pancreatic

*family history & genetic testing!

29
Q

Discuss the concept of neoplasms of the endocrine system as being functional (ie, secreting hormones) and non-functional (ie, non-secretory)

A

*adenomas, carcinoma etc.

FUNCTIONAL

  • secretes hormones
  • Thyroid Medullary carcinoma

NON-FUNCTIONAL

  • non-secretory
  • follicular adenoma: most non-functioning, encapsulated tumour, small microfollicles

*Endocrine organs have high reserve capacity and can be extensively damaged/reduced in volume before disease manifests

30
Q

Discuss the concept of neoplasms being benign and malignant, in the context of the endocrine system.

A

Benign
Often circumscribed, localised, cannot invade, don’t usually transform

Malignant
Synonymous with cancer, invades, metastasises, if untreated, will often prove fatal

31
Q

Discuss the presentation, investigation and management of thyroid cancer.

A

a

32
Q

Hashimoto’s Thyroiditis

A

F > M, adults

AuIm attack of thyroid epithelial cells
= lymphocytic infiltrate + circulating AuAb(thyroglobulin & thyroid perox.)

  • wt gain, bradycardia, dry skin, constip, intolerance to cold, slowed speech
  • HISTO: HURTHLE CELL CHANGE (dmg); intense infiltrate
33
Q

Goitre

A

Enlarged thyroid

MULTI-NOD

  • I2 def, goitrogens = impaired T3, T4 = ⇧TSH = hypertrophy and hyperplasia of thyroid epithelium
  • simple => multinodular
  • HISTO: ⇧follicles - crowded, distended colloid, fibrotic change
  • Toxic nodule may develop

DOMINANT NODULE in MULTI-NOD

CYST

FOLLICULAR ADENOMA

CARCINOMA: family hx, chronic inflamm, radiation, obesity

  • Differentiated Thyroid carcinoma
  • Papillary carcinoma
34
Q

Thyroid Nodule Investigations

A

TFT

USS

FNA - cytology

35
Q

Follicular carcinoma

A

Invasive, solitary, mets: blood, bone with RAS mutation

F>M, 10% thyroid malignancy

36
Q

Papillary carcinoma

A

Radiation, BRAF mutation, <50yrs

  • lymphatic spread, good prognosis
  • HISTO: empty nuclei, papillary projections, psammoma bodies (calcium deposits)
37
Q

Thyroid Medullary carcinoma

A

malignant chief cells,
CALCITONIN+ - promotes bony absorption of calcium and prevents bone resorption
ACTH+
sporadic, MEN2A, 2B

> Sx
Radioactive Iodine
RT
ChemoT

38
Q

2º Hyperparathyroidism

A

Response to ⇩Ca2+ d/t renal failure

39
Q

Pituitary Adenoma: hyperfunction & hypofunction

A

common cause: pituitary adenoma, with carcinomas are rare

  • 35-60y/o, sporadic
  • soft well-circumscribed lesion
  • functionning: hormone excess: prolactinoma (galactorrhoea, menstrual disorders), GH++, ACTH++ (cushings disease)
  • acromegaly,
  • moon face, buffalo hump, bruise easily
  • non-functionning: not as much common
  • MASS PRESSURE EFFECT: ⇧ICP, visual field abn.,
  • compression damage = hypopituitrism (75% loss); alt. Trauma, infection (TB, sarcoidosis), Post-partum ischaemic necrosis: Sheehan’s Syndrome
40
Q

Adrenal Glands & Masses

A

Mass lesion: late effect

Hyperplasia, atrophy, mass of the glands

41
Q

Masses: Adrenal Cortical Hyperfunction Syndromes

A

HYPERCORTISOLISM = CUSHINGS SYNDROME
exo iatrogenic vs endogenous ACTH (pit adenoma vs adrenal adenoma)

HYPERALDOSTERONISM = CONN’S SYNDROME
bilateral idiopathic hyperplasia, or functionning adrenal adenoma

ADRENOGENITAL SYNDROMES
functionning adrenal tumour, congenital adrenal hyperplasia

42
Q

Adrenal Insufficiency

A

WATERHOUSE FRIDERICHSEN: acute meningococcal septicaemia = destruction

ADDISON’S DISEASE: chronic autoimmune nature or: infection, replacement, atrophy (therapy)

43
Q

Adrenocortical Tumours

A

ADENOMA: functionnal = hyperadrenal syndromes + atrophy of adjacent cortex

CARCINOMA: rarer

  • functional: virilising
  • invades via adrenal vein = lung breast

Adrenal Medullary Tumour - PHAEOCHROMOCYTOMA: medulla neuroendocrine cells, catecholamine+++, bilateral, inherited

44
Q

MEN

A

multiple endocrine neoplasia: inherited, hyperplasia, younger age

MEN1 WERMER SYNDROME: parathyroid hyperplasia and adenomas, pit. adenoma = prolactinoma

MEN2A SIPPLE SYNDROME: parathyroid hyperplasia, phaeochromocytoma

MEN2B: neuroma of skin, mucosal neuroma

45
Q

Outline the main mechanisms and long-term pathological complications of diabetes mellitus.

A

DM1:

  • HLA mut = autoimmune attack via T cells = beta cell destruction
  • environmental triggers
  • molecular mimicry: the activation of auto-aggressive T cells in T1D as the result of a virus carrying an epitope that strongly resembles certain structures on the beta cells, and which consequently induces a cross-reactive autoimmune response

DM2:

  • ⇩tissue sens to insulin (resistance) + inability to secrete sig. levels of insulin
  • gene variant factor affecting insulin secretion (pancreas)

1) ⇧⇧visceral fat = ⇧FFA
2) ⇩insulin receptor sens.
3) ⇧⇧Pancreas demand to mobilise glucose into cells
=> PERIPHERAL HYPERINSULINAEMIA
4) Genes: Poor beta cell high end function
=> INSULIN SECRETION CANNOT COUNTERACT THE INSULIN RESISTANCE CAUSED BY CENTRAL ADIPOSITY

46
Q

Be able to describe the pathogenesis, appearances, and consequences of diabetic macro and micro vascular disease

A

*MI commonest cause of death (LT complciation)

MACROVASCULAR
- acceleration of atherosclerosis; glc attachment to LDL preventing liver uptake = HYPERLIPIDAEMIA

MICROVASCULAR - ARTERIOLES
- buildup of molecules in subendothelial space resulting in basal lamina thickening
- buildup of albumin and collagens
= HYALINE CHANGE: widespread narrowing arteriole = ischaemia

  • kidney, peripheral tissue, retina, arterioles supplying nerves
  • AMPUTATION
  • END STAGE RENAL DISEASE
  • BLINDNESS

MICROVASCULAR - CAPILLARIES
⇧connective tissue around capillaries creating lesions
- GLYCOSYLATION of proteins (reversible) > Advanced Glycosylation End-products (irreversible)
- Glycosylated collagen binds albumin in subendothelial space
- AGE protein cross-linking,

A2 ME3031 ENDO DM (11 decks)

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