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Endocrinology > Adrenal > Flashcards

Adrenal Flashcards

1
Q

What is the origin of the adrenal cortex and the 3 layers of the adrenal cortex

A
  • Mesothelial origin, derived from the mesoderm

From outside to inside:

  • Zona glomerulosa, aldosterone/mineralocorticoid
  • Zona fasciculata, glucocorticoids
  • Zona reticularis, androgens
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2
Q

Synthesis of adrenal steroids.

A

Synthesis of all steroid hormones begin with the common precursor, cholesterol which is converted into pregnenolone via cholesterol desmolase. LDL&raquo_space; HDL

  • The rate-limiting process in steroidogenesis is the transport of free cholesterol through the cytosol to the inner mitochondrial membrane, the site of the cholesterol side-chain cleavage enzyme (CYP11A1) that catalyzes the first step in steroidogenesis
    Steroid Acute Regulatory Protein (StAR) stimulates the transport of cholesterol from the cytosol into the mitochondria for first step first of the common pathway to yield pregnenolone
  • Progesterone is the substrate for mineralocorticoid synthesis.
  • Adrenal hormone Receptors are intracellular; cytoplasmic

Adrenal hormones are lipophilic

  • CYP enzymes are P450 enzymes (membrane bound; encoded by single gene)
  • CYP enzymes in aldosterone and cortisol production are not found in the gonads; hence preferential production of androgens
  • Hydroxysteroid dehydrogenases enzymes (membrane bound; encoded by multiple genes)
  • 17βHSDs is NOT found in the adrenal gland

Steroidogenesis is similar in adrenal cortex, ovary, testes, but adrenal androgens are not important in males; and are only important in prepubertal females as it regulates hair growth (adrenarche)

Cortisol and aldosterone have similar structure; cortisol has ten times more glucocorticoid activity as aldosterone, and only one fourth of mineralocorticoid activity as aldosterone

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3
Q

What is the origin of the adrenal medulla

A
  • Derived from the neural crests
  • Consists of chromaffin cells which secrete catecholamines (norepinephrine, epinephrine, dopamine)
  • Tumours of chromaffin cells = pheochromocytoma
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4
Q

21-hydroxylase (CYP21A2) deficiency leads to what?

A

Reduction in aldosterone and cortisol production

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5
Q

Electrolyte abnormalities in adrenal insufficiency

A

Hyperkalaemia
Normal anion gap Metabolic acidosis
Hyponatremia
Hypotension

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6
Q

What are the subtypes of adrenal insufficiency?

A
  • Primary: adrenal
  • Secondary: pituitary
    Causes: pituitary adenoma, pituitary resection, sheehan’s syndrome
  • Tertiary: hypothalamus
    Causes: withdrawal of long term steroids, lesions in hypothalamus
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7
Q

Main causes of primary adrenal insufficiency (Addison’s disease)

A
  • Autoimmune adrenal failure - associated with other autoimmune endocrinopathies, autoimmune polyglandular syndrome, commonly APS2 in adults (APS2>APS1)
  • TB
  • Fungi: histoplasmosis
  • Metastatic disease, lymphomas
  • Granulomas
  • Adrenal haemorrhage
  • Congenital adrenal hyperplasia - autosomal recessive, 95% cases involve gene for 21-hydroxylase (overproduction of androgen is the hallmark)
  • meningococcal septicaemia (Waterhouse-Friderichsen syndrome) causing bleeding into the adrenal gland
  • HIV
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8
Q

Clinical features of adrenal insufficiency.

A
  • In primary adrenal insufficiency, patients develop hyperpigmentation (due to high ACTH) and hyperkalaemia (due to hypoaldosteronism) due to mineralcorticoid deficiency.
  • this is not present in secondary and tertiary adrenal insuficiency
  • Hypoaldosteronism: hypotension, hyponatremia, hyperkalaemia, normal anion gap metabolic acidosis
  • Hypocortisolism: fatigue/lethargy, gastrointestinal complaints like nausea/vomiting/diarrhoea, orthostatic hypotension, hypoglycaemia
  • Hypoandrogenism: loss of libido, loss of axillary and pubic hair, decreased DHEA-S
  • Elevated ACTH: hyperpigmentation due to increased MSH
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9
Q

Investigations for adrenal insufficiency.

A

FBC: anaemia, eosinophilia, hypoglycaemia, normal anion gap metabolic acidosis.

EUC: Hyponatremia + hyperkalemia (only in primary adrenal insufficiency due to mineralocorticoid/aldosterone deficiency)

(1) Fasting cortisol: low (first step)
(a) Fasting ACTH:
- High: primary AI
Low: secondary / tertiary - central AI

  • Aldosterone: Low (primary), Renin: High (primary)
  • Hypoandrogenism: low DHEA-s (only relevant in patients without testes for whom the adrenal glands are one of the main sources of androgens)
  • Short synacthen test: gold standard for diagnosis of primary adrenal insufficiency
    250 μg IV synacthen; measure cortisol at 30 and 60 minutes; Cortisol >500 = normal
  • OCP and Glucocorticoids such as prednisolone and methylprednisolone must be withheld for 48 hours prior
  • No increase in serum cortisol after stimulation: primary
  • Increase in serum cortisol after stimulation: secondary/tertiary

To distinguish between secondary and tertiary: CRH stimulation test

  • Secondary: CRH –> no increase in ACTH –> no increase in cortisol
  • Tertiary: CRH –> increase in ACTH –> increase in cortisol

Tailor further investigations as per differentials
Primary:
- Adrenal autoantibodies (21 hydroxylase ab)
- If positive: screen for autoimmune polyendocrine syndromes, eg: calcium, PTH, diabetes (anti-GAD, islet cell), pernicious anaemia (anti-parietal, anti IF), thyroid (TSH, TPO)
- If autoantibody negative, measure plasma concentration of very long chain fatty acids (VLCFAs) - elevated in nearly all males with adrenoleukodystrophy (X-linked condition ; neurological symptoms and erectile dysfunction and adrenal insufficiency)
-If VLCFA negative, consider CT adrenal gland + testing for infections

Secondary +tertiary: Pituitary hormone profile + MRI pituitary

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10
Q

Treatment for adrenal insufficiency

A
  • Glucocorticoids: hydrocortisone, prednisone, dexamethasone
    Requires 12.5-25mg of equivalent hydrocortisone daily.
  • Mineralocorticoids: fludrocortisone (SE can cause worsening of pre-existing HF, oedema, hypokalaemia) - only used for primary, not required for secondary.
  • Androgens: DHEA (controversial)
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11
Q

What are symptoms specific to primary adrenal insufficiency?

A
  • Hypoaldosteronism characterised clinically by hypotension, salt craving
  • Lab tests show: hyponatremia, hyperkalaemia, normal anion gap metabolic acidosis
  • Also have elevated ACTH causing hyperpigmentation due to increased MSH
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12
Q

Autoimmune adrenal disease is the most common cause of primary adrenal insufficiency. What is autoimmune adrenal disease associated with?

A
  • Associated with polyglandular autoimmune syndrome type II > type I
  • anti-21-hydroxylase ab
  • Also associated with ovarian failure (primary hypogonadism), Type I diabetes (DQ8 HLA allele), hypoparathyroidism, hypothyroidism

Type 1: (APS-1, Whitaker syndrome, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, or APECED)
• Less common than APS-2 (1:100,000)
• Autosomal recessive inheritance; no HLA association
• Caused by a mutation in the autoimmune regulator gene (AIRE)
• Age of onset: usually in childhood
• Associated endocrine deficiencies (two or more of the following should be present)
○ Most commonly
§ Primary adrenal insufficiency
§ Hypoparathyroidism
§ Chronic mucocutaneous candidiasis
§ Ectodermal dystrophy of skin, nails, and dental enamel
○ Less commonly: hypogonadism, pernicious anemia, alopecia, vitiligo, hepatitis

Type 2 (APS-2, Schmidt syndrome): defined by the occurrence of primary adrenal insufficiency with thyroid autoimmune disease and/or type 1 diabetes mellitus
• More common than APS-1 (1.4 - 2:100,000)
• Associated with HLA‑DR3 and/or HLA‑DR4 haplotypes
• Age of onset: usually in adulthood
• Main manifestation: primary adrenal insufficiency
○ Associated endocrine deficiencies (one or more of the following may be present)
§ Most commonly
□ Thyroid autoimmune disease (e.g., Hashimoto thyroiditis)
□ Type 1 diabetes mellitus
Less commonly: celiac disease, pernicious anemia, alopecia areata, vitiligo

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13
Q

What is congenital adrenal hyperplasia characterised by?

A

Autosomal recessive defects in enzymes that are responsible for the production of cortisol. All forms of CAH are characterized by low levels of cortisol, high levels of ACTH, and adrenal hyperplasia. Also characterised by hypoglycaemia and hyperpigmentation.
3 subtypes: 21B hydroxylase (95%), 11B hydroxylase (5%), 17a hydroxylase (rare).

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14
Q

Clinical features of congenital adrenal hyperplasia?

A
  • The exact clinical manifestations depend on the enzyme defect. The most common form of CAH is caused by a deficiency of 21β-hydroxylase causing overproduction of androgens - manifests with hypotension, ambiguous genitalia, virilization (in the female genotype), and/or precocious puberty (when puberty occurs at young age) (in both males and females).
  • CAH treatment involves lifelong glucocorticoid and fludrocortisone replacement therapy.
  • Certain rare forms of CAH (e.g., 11β-hydroxylase and 17α-hydroxylase deficiencies) manifest with symptoms of mineralocorticoid excess (e.g., hypertension) and therefore require spironolactone (aldosterone receptor inhibitor) in addition to glucocorticoid replacement.
  • Complications of CAH include severe hypoglycemia, adrenal insufficiency, and failure to thrive
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15
Q

What is the difference between hirsutism and virilization?

A

Hirsutism is the medical term that refers to the presence of excessive terminal (coarse) hair in androgen-sensitive areas of the female body (upper lip, chin, chest, back, abdomen, arms, and thighs). Virilization is more extensive than hirsutism with additional evidence of masculinization - deepening of voice, clitoromegaly, temporal hair loss

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16
Q

What is deoxycorticosterone?

A

Deoxycorticosterone (DOC) are steroid hormones synthesized in the zona fasciculata (ZF) and zona glomerulosa (ZG) of the adrenal gland and is a precursor for the synthesis of cortisol and aldosterone

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17
Q

In congenital adrenal hyperplasia, which hormones are affected?

A

All subtypes have low cortisol, high ACTH and low aldosterone.
- 21B hydroxylase deficiency: low deoxycorticosterone
(DOC) = low mineralocorticoid/glucocorticoid, increased androgens (have virilization), hypotension

  • 11B hydroxylase deficiency: high DOC (increased mineralocorticoid, reduced glucocorticoid), high androgens, hypertension
  • 17a hydroxylase: high DOC (increased mineralocorticoid, reduced glucocorticoid), low androgens, hypertension

1 DOC: if the deficient enzyme starts with 1 (11B, 17-), there is increased DOC
AND 1: if the deficient ends with 1 (21, 11B), androgens are increased.

Increased in DOC leads to hypertension.

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18
Q

Which gene codes for 21B- hydroxylase

A

CYP21A2 gene

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19
Q

How is 21B hydroxylase deficiency screened for?

A

Screening is conducted by measuring 17-hydroxyprogeterone for newborn

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20
Q

Deficiency of the adrenal enzyme 21B hydroxylase causes what enzyme and endocrine findings?

A

Endocrine:

  • Low cortisol, high ACTH, low aldosterone
  • Low DOC (Hypotension) and high androgens

Enzymes

  • Hyponatremia
  • Hyperkalaemia
  • Metabolic acidosis

11B hydroxylase and 17a hydroxylase is the opposite

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21
Q

Treatment for congenital adrenal hyperplasia

A
  • All patients receive glucocorticoid therapy
  • 21B hydroxylase: also need fludrocortisone (aldosterone substitute)
  • 11B hydroxylase and 17a hydroxylase: spironolactone
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22
Q

Features of primary hyperaldosteronism (Conn)

A
  • Normally secondary to adrenal hyperplasia (bilateral) or adrenal adenoma (unilateral)
  • Refractory Hypertension (due to increased sodium reabsorption and water retention)
  • Hypokalaemia (due to increased urinary potassium secretion)
  • Metabolic alkalosis
  • High aldosterone, low renin
  • Aldosterone: renin ratio high >20
  • High urine aldosterone excretion

**Plasma aldosterone concentration to plasma renin activity ratio
(PAC/PRA) ratio above 20 with LOW RENIN strongly predictive

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23
Q

Features of secondary hyperaldosteronism

A 
Secondary hyperaldosteronism is caused by reduced renal blood flow which stimulates the RAAS system to increase aldosterone. 
Causes:
- Obstructive renal artery disease
- Renovascular hypertension 
- Diuretic use 
- Renin secreting tumour
- Coarctation of the aorta 
- Oedematous disorders: heart failure, cirrhosis with ascites, nephrotic syndrome

High renin, high aldosterone
Aldosterone: renin < 10

24
Q

Treatment for primary hyperaldosteronism.

A
  • Bilateral adrenal hyperplasia: spironolactone (first line) or eplerenone as it is less likely to cause side effects like gynecomastia and menstrual irregularities due to greater mineralocorticoid receptor sensitivity , amiloride (2nd line)
  • Surgical (unilateral): adrenalectomy
25
Q

Investigations for primary hyperaldosteronism.

What is the confirmatory test for primary hyperaldosteronism?

A

(Step 1)
Screen: Aldosterone: renin ratio
Plasma aldosterone concentration to plasma renin activity ratio
(PAC/PRA) ratio above 20 with LOW RENIN strongly predictive

(Step 2)
Confirmation: oral salt loading, saline suppression test, fludrocortisone suppression test.
- Oral sodium loading test: patient has high sodium intake for 3 days and then 24 hour urine aldosterone collected. Primary hyperaldosteronism if urinary aldosterone > 12mcg
Note: normally high salt would inhibit renin and thus no aldosterone produced. In normal people, urinary + plasma aldosterone should fall

Saline infusion test, doesn’t inhibit aldosterone and it continues to be high

(Step 3)
Distinguish between unilateral adenoma vs bilateral adrenal hyperplasia
- Adrenal venous sampling
- Postural test

  • Adrenal Ct scan
  • Adrenal vein sampling to differentiate adenoma (treatment surgical)
    vs hyperplasia (medical treatment) may be needed
26
Q

What is the gold standard to different between unilateral aldosterone overproduction from bilateral aldosterone overproduction?

A

Do CT and then Adrenal venous sampling

Allows the measurement of the aldosterone to cortisol ratio of each vein

27
Q

Causes of primary hyperaldosteronism

A
  • Normally secondary to adrenal hyperplasia (bilateral) or adrenal adenoma (unilateral)

Less common causes

  • Aldosterone secreting adrenal carcinoma (>4cm in size)
  • Familial hyperaldosteronism - have family hx and/or family hx of early stroke
  • Ectopic aldosterone production occurring outside the adrenal gland, eg: aldosterone producing tumour in kidney/s ovaries
28
Q

What medications can increase renin levels.

A

ACEi/ARB
Aldosterone receptor antagonist
Potassium wasting diuretic (thiazide)

29
Q

Cause of cushing’s syndrome

A
  • Exogenous administration of glucocorticoids (factitious cushing) - most common cause
  • Pseudocushing (high cortisol but asymptomatic) secondary to alcoholism, major depressive disorder
  • Primary hypercortisolism (ACTH independent 20% of cases) - adrenal adenoma, adrenal carcinoma

Secondary Hypercortisolism
(ACTH dependent 80% of cases):
- Hypersecretion of ACTH by pituitary adenoma = cushing disease
- Ectopic production of ACTH (ACTH dependent): small cell lung cancer which normally associated with hypokalaemia

30
Q

Clinical Features of cushing’s

A

Skin

  • Striae
  • Hirsutism
  • Thin, easily bruisable skin with ecchymoses
  • In secondary hypercortisolism, can cause hyperpigmentation

Neurological: lethargy, depression, sleep disturbance, psychosis

MSK: osteoporosis, avascular necrosis of femoral head, muscle atrophy/weakness. Proximal myopathy and weakness.

Endocrine/metabolic: insulin resistance, dyslipidaemia, weight gain with central obesity, moon facies, buffalo hump, decreased libido

Reproductive: decreased libido, amenorrhoea (due to cortisol mediated gonadotrophin releasing hormone suppression)
Other features:
Secondary HTN: amplify catecholamines on blood vessels and cross react with mineralocorticoid receptors to cause increase in BP by retaining fluid.
Immunosuppression
Cataracts
Peptic ulcer disease

31
Q

Side effects of corticosteroids.

A 
CUSHINGOID 
Cataracts
Ulcers
Striae/skin thinning 
Hypertension/hirsuitism/hyperglyacemia
Infections 
Necrosis (of the femoral head) 
Glucose elevation 
Osteoporosis/obesity
Immunosuppression 
Depression/diabetes
32
Q

How do patients with secondary hypercortisolism due to ectopic ACTH often present?

A

May present with rapid onset hypertension and hypokalaemia without other typical features of Cushing syndrome.

33
Q

Investigations for cushing’s

A

General lab findings

  • Hypernatremia, hypokalaemia, metabolic alkalosis
  • Hyperglycaemia
  • Hyperlipidaemia
  • Leukocytosis

ACTH: low (independent) in primary hypercortisolism (adrenal adenoma/carcinoma)
ACTH: normal/elevated: secondary hypercortisolism (ACTH dependent)

Note: cortisol is normally low in the morning

(Step 1) - Screening:
- Elevated 24 hour urinary cortisol - x3 upper limit of normal
- Elevated morning serum cortisol following low dose dex suppression.
Overnight low dexamethasone test and then measuring early morning serum cortisol
Dexamethasone: being a powerful glucocorticoid suppresses ACTH. In cushing’s syndrome , despite receiving dexamethasone, ACTH and cortisol levels remain high.
- Elevated midnight salivary cortisol.
- Elevated midnight serum cortisol
These need to be done at least twice to ensure reproductivity of results.

(Step 2)
If the above is positive, you check ACTH levels.
Low ACTH (independent): adrenal adenoma/carcinoma
High ACTH (dependent): pituitary adenoma or ectopic ACTH producing tumour.

(Step 3)
Confirmation:
If high ACTH (ACTH dependent) then confirmation is via high dose dexamethasone or
CRH stimulation
- Pituitary adenoma (cushing’s disease): ACTH is suppressed with high dose dex and ACTH/cortisol increases with CRH –> Cranial CT/MRI –> surgery
- Ectopic ACTH producing tumour: ACTH level remain high with high dose dex and there is no change in ACTH/cortisol with CRH –> CTCAP looking for malignancy (SCLC, RCC, carcinoid)
Note: ectopic ACTH producing tumours DO NOT respond to high dose dexamethasone

Imaging: MRI of pituitary, CT adrenal, CTAP

Petrosal sinus sampling of ACTH to differentiate between pituitary and ectopic ACTH secretion.

Insulin stress test to differentiate between Cushing and pseudocushing

CT/MRI abdomen: primary hypercortisolism
CT/MRI if cushing disease - pituitary adenoma. If no findings then bilateral sampling of the inferior petrosal sinus to measure ACTH levels.

Ectopic ACTH-secreting tumours: CT, MRI, positron emission tomography [PET] or octreotide scintigraphy

34
Q

What is the difference between cushing syndrome and cushing disease

A

Cushing syndrome: any cause of hypercortisolism
Cushing disease: is due to pituitary ACTH producing tumour - secondary hypercortisolism that results from excessive production of ACTH by pituitary adenoma.

35
Q

What are causes of pseudocushing.

A 
stress
depression 
alcohol withdrawal
poorly controlled diabetes
pregnency
obesity  
PCOS
infection 
anorexia nervosa
36
Q

Treatment for cushing syndrome

A
  • Reduce endogenous steroids
  • Surgical intervention
    After surgical intervention, patients may develop adrenal insufficiency and require lifelong glucocorticoid therapy.
  • Medications to suppress cortisol synthesis: Ketoconazole, metyrapone, mitotane
    SE: hepatoxicity, gynaecomastia
  • Bilateral adrenalectomy is done as last resort, requires life long steroid replacement, 10% risk of nelson syndrome (ACTH producing pituitary tumour not always prevented by radiotherapy)

Nelson: bilateral adrenalectomy in patients with a previously undiscovered pituitary adenoma.

37
Q

What is nelson syndrome

A

Post adrenalectomy syndrome.
Bilateral adrenalectomy –> no endogenous cortisol production –> no negative feedback from cortisol on hypothalamus –> increase CRH production –> uncontrolled enlargement of pre-existing ACTH secreting pituitary adenoma –> increased ACTH and MSH –> symptoms of pituitary adenoma and increase MSH

Clinical features: headache, bitemporal hemianopia (mass effect), cutaneous hyperpigmentation

High beta MSH + ACTH
Pituitary adenoma on MRI
Surgery + pituitary radiation therapy

38
Q

How do you differentiate cushing disease from pituitary adenoma and ectopic ACTH production?

A

If high ACTH (ACTH dependent)
Confirmation is via high dose dexamethasone or
CRH stimulation
- Pituitary adenoma (cushing’s disease): ACTH is suppressed with high dose dex and ACTH/cortisol increases with CRH –> Cranial CT/MRI –> surgery
- Ectopic ACTH producing tumour: ACTH level remain high with high dose dex and there is no change in ACTH/cortisol with CRH –> CTCAP looking for malignancy (SCLC, RCC, carcinoid)

Petrosal sinus sampling of ACTH may be required to differentiate between pituitary and ectopic ACTH secretion.

39
Q

What is the alpha subunit?

A

Common subunit to LH, FSH and TSH

Often produced in excess by chromophobe adenomas and TSH secreting adenomas.

40
Q

What is the pituitary panel?

A 
LH, FSH, testosterone, oestradiol
TSH, FT4
Prolactin
Morning cortisol
IGF-1
Alpha subunit if pituitary tumour present
41
Q

What is the size of pituitary microadenomas and macroadenomas.

A

Microadenoma < 10mm

Macroadenoma > 10mm

42
Q

Free cortisol is part of the circadian rhythm

A
  • Peaks in the morning
  • Drops in the evening
  • Maintains BP - increase sensitivity of peripheral blood vessels to catecholamines
  • Dampen inflammatory and immune response - reduce production and release of inflammatory mediators like prostaglandins and interleukins
43
Q

When should the low dose dexamethasone test not be performed?

A

Should not be performed when cortisol binding globulin (CBG) is likely to be abnormal, eg: malnutrition, cirrhosis, nephrotic syndrome and OCP.

44
Q

Comparison between adrenal adenoma and carcinoma

A

Hounsfield, is a quantitative scale for describing radiodensity.

Adrenal adenoma

  • Diameter <4cm
  • Homogenous enhancement
  • Round clear margins
  • CT: <10 hounsfield units
  • Not highly vascular
  • Necrosis, haemorrhage, calcifications: rare
  • Growth: slow

Adrenocortical Carcinoma

  • Diameter >4cm
  • Heterogenous enhancement
  • Irregular margins
  • Calcifications, necrosis
  • CT: >10 Hounsfield units (usually >25)
45
Q

Characteristics of pheochromocytoma .

A
  • Tumour of adrenal medulla arising from the chromaffin cells which are derived from the neural crest
  • 90% in adrenal medulla
  • 10% can from extra-adrenal sympathetic or parasympathetic paraganglia.
    • The most common location for extraadrenal sympathetic paragangliomas is the abdomen, whereas parasympathetic paragangliomas are usually found in the head and neck.
    • Pheochromocytomas and extra-adrenal sympathetic paragangliomas almost always secrete catecholamines (norepinephrine, epinephrine, dopamine); however, head and neck parasympathetic paragangliomas almost never do.
46
Q

What are the hereditary conditions associated with pheochromocytoma.

A
  • Multiple endocrine neoplasia (MEN2a, 2b)
    MEN2A: medullary thyroid cancer, pheochromocytoma, parathyroid hyperplasia (RET exon 11)
    MEN2B: medullary thyroid cancer, pheochromocytoma, oral/intestinal neuromas, marfanoid habitus (RET exon 16)
  • Neurofibromatosis type 1: cutaneous neurofibromas, cafe au lait spots, lisch nodules ( pigmented hamartomatous nodular aggregate of dendritic melanocytes affecting the iris), peripheral nerve sheath tumour, breast cancer
  • Von Hippel Lindau disease (VHL): renal cell carcinoma, hemangioblastoma, angiomatosis, pheochromocytoma

NOTE: More likely to be bilateral or recurrent in familial cases

47
Q

Clinical features of pheochromocytoma

A

Triad of episodic headache, sweating and tachycardia

  • Episodic HTN
  • Episodic headaches, sweating, tachycardia
  • Diaphoresis, tachycardia, heart palpitations
  • Weight loss
  • Hyperglycaemia
  • Pallor

Hypertensive crisis can be triggered by palpation of the tumour on abdo exam

48
Q

Investigations for pheochromocytoma

A
  • Initial: plasma free metanephrines
  • Confirmatory: 24 hour urine metanephrines and cetacholamines
  • Genetic testing
  • 24 hour ambulatory BP monitoring
  • Adrenal/abdominal CT or MRI
  • Sctinigraphy MIBG if CT/MRI negative
49
Q

Treatment for pheochromocytoma

A
  • Requires pre-operative blood pressure management to prevent life threatening cardiovascular complications related to massive release of catecholamines during surgery.
  • Give PHEnoxybenzamine (irreversible alpha blocker, blocks alpha-1 and alpha-2)
  • B-Adrenoceptor blockers (metoprolol or propranolol) are added later to treat reflex tachycardia, but should never be started before adequate a.-blockade has been achieved due to the risk of hypertensive crisis from unopposed a-receptor stimulation
  • Laparoscopic tumour resection

Requires annual metanephrine measurement

For malignant pheochromocytoma: MIBG therapy.

Starting beta blocks before alpha blockers is contraindicated. Beta blockers cancel out the vasodilatory effect of peripheral beta 2 potentially leading to unopposed alpha adenoceptor stimulation, causing vasocontriction and ultimately hypertensive crisis

50
Q

What is MEN 1 associated with?

A

Autosomal dominant
Parathyroid: hyperparathyroidism due to parathyroid hyerplasia
Pituitary
Pancreas: insulinoma, gastrinoma (leading to recurrent peptic ulceration)

Other: carcinoid, adrenocortical adenoma

51
Q

Characteristics of adrenal crisis

A
  • Adrenal crisis resulting from bilateral adrenal hemorrhage can occur with
    the antiphospholipid syndrome, disseminated intravascular
    coagulation, or systemic anticoagulation.
  • Adrenal crisis may occur when onset of adrenal failure is abrupt (bilateral adrenal hemorrhage) or when increased stress occurs in the setting of chronic adrenal failure.
  • Manifestations of adrenal crisis include shock, hypotension,
    fever, nausea, vomiting, abdominal pain, tachycardia, and even death.
  • Aldosterone is critical to the maintenance of intravascular
    volume and blood pressure, while cortisol contributes
    to augmentation of blood pressure mostly during times of
    increased physical stress
  • Aldosterone deficiency is the major impetus for the development of hypotension and shock in patients with untreated primary adrenal failure. - Adrenal crisis is rare in the
    setting of secondary cortisol deficiency because the reninangiotensin- aldosterone pathway is intact.

Tx: IV hydrocortisone 100mg, IV fluid resus
Hydrocort continued at 100-200mg/day in divided doses (every 6-8 hours)

52
Q

Which cancers metastasise to the adrenals?

A

Lymphoma
Carcinoma
Melanoma

53
Q

What are the causes of drug related adrenal insufficiency/addisons?

A

Cortisol synthesis inhibitors

  • Rifampicin
  • Fluconazole,
  • Phenytoin,
  • Ketoconazole
54
Q

What is the dynamic test for mineralocorticoid (aldosterone) excess (primary hyperaldosteronism)

A

Dynamic test (least to most invasive)

  • Saline suppression test
  • Fludrocortisone suppression test
  • Oral sodium loading test
  • Adrenal vein sampling

Medications that interfere include: spironolactone, eplerenone
Potassium wasting diuretice
ACEi/ARB
Dihydropyridine CCB, beta blockers

Non interfering anti HTN: verapamil, hydralazine, prazosin

55
Q

Investigation for primary and secondary adrenal insufficiency

A

Primary: short synacten test
Secondary:
- insulin tolerance test gold standard for diagnosing secondary adrenal insufficiency
Normal: insulin –> hypoglycaemia (strong stimulator for ACTH and cortisol secretion) –> stress induced increase in plasma ACTH –> increased cortisol
in secondary adrenal insufficiency: no rise in ACTH or cortisol levels

  • CRH stimulation test
    Secondary adrenal insufficiency: CRH –> no increase in ACTH –> no increase in cortisol
56
Q 
Metoprolol is avoided as the first-line antihypertensive in patients with phaeochromocytoma because it antagonises the effects of which adrenoceptor?
A. Alpha-1.
B. Alpha-2.
C. Beta-1.
D. Beta-2.
E. Beta-3
A

D. Beta-2.

Endocrinology (10 decks)

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