diseases of ADRENAL CORTEX and surgical management

### Lecture on Diseases of the Adrenal Cortex

#### Introduction:
The adrenal cortex, the outer layer of the adrenal glands, plays a pivotal role in maintaining various physiological functions by producing corticosteroids, mineralocorticoids, and androgens. Disorders of the adrenal cortex can lead to significant clinical syndromes, which are essential for a final year MBBS student to understand, given their complexity and impact on homeostasis.

#### Adrenal Cortex Anatomy and Hormone Production:
The adrenal cortex is divided into three zones:
- **Zona Glomerulosa**: Produces mineralocorticoids, primarily aldosterone, which regulates sodium and potassium balance.
- **Zona Fasciculata**: Produces glucocorticoids, mainly cortisol, which is crucial for stress response, metabolism, and immune regulation.
- **Zona Reticularis**: Produces androgens, which play a role in the development of secondary sexual characteristics.

#### Disorders of the Adrenal Cortex:
1. **Hyperfunctioning Disorders:**
- **Cushing’s Syndrome**: Caused by excessive cortisol production, Cushing's syndrome presents with features such as central obesity, moon face, muscle weakness, hypertension, and glucose intolerance. It can result from an adrenal adenoma, ectopic ACTH production, or prolonged corticosteroid therapy.
- **Primary Hyperaldosteronism (Conn’s Syndrome)**: Characterized by excessive aldosterone production, leading to hypertension, hypokalemia, and metabolic alkalosis. It’s often due to an adrenal adenoma or bilateral adrenal hyperplasia.
- **Congenital Adrenal Hyperplasia (CAH)**: A group of inherited disorders affecting cortisol synthesis, leading to overproduction of androgens. CAH can result in virilization, precocious puberty, or ambiguous genitalia, depending on the specific enzyme deficiency.

2. **Hypofunctioning Disorders:**
- **Addison’s Disease**: A primary adrenal insufficiency caused by autoimmune destruction of the adrenal cortex, leading to insufficient production of cortisol and aldosterone. Clinical features include fatigue, weight loss, hypotension, hyperpigmentation, and electrolyte imbalances.
- **Secondary Adrenal Insufficiency**: Due to inadequate ACTH production from the pituitary, often secondary to chronic glucocorticoid therapy, leading to a similar but milder presentation compared to Addison’s disease.

3. **Adrenal Tumors:**
- **Adrenocortical Adenoma**: Often benign and non-functioning but can cause hypersecretion of hormones leading to syndromes such as Cushing's or Conn's.
- **Adrenocortical Carcinoma**: A rare and aggressive malignancy that may present with symptoms of hormone excess or be discovered incidentally.

1. (Adrenal Gland lecture 1 of 2)
Prof. Ahmad Uzair Qureshi [email protected]

5. Extra-adrenal paraganglia
•Paraganglia are neuroendocrine cells associated with the autonomic nervous system.
•Adrenal (medulla) or extra-adrenal -four subgroups:
•1 Sympathetic: the largest cluster is the organ of Zucker kandl, which is located at the aortic bifurcation or close
to the origin of the inferior mesenteric artery.
•2 Chemoreceptor: including aortic and carotid bodies that assist in the regulation of respiration.
•3 Visceral–autonomic: in the urinary bladder and peripheral blood vessels.
•4 Intravagal: situated within or adjacent to the vagal trunk.
•Neoplasms of extra-adrenal paraganglia are called paragangliomas (PGLs). Tumoursof chemoreceptors are
usually referred to as chemodectomas(see Chapter 52) and those from parasympathetic ganglia are termed
glomus tumours.

6. •Aldosterone
•SodiumretentionandPotassiumexcretion
•Therenin–angiotensinsystemandserumpotassium
concentration.
•Renalbloodflow(haemorrhage,dehydration,salt
depletion,orthostasis,renalarterystenosis)or
hyponatraemiaincreasesreninsecretion,resultingin
sodiumretention,potassiumexcretionandanincreased
plasmavolume.

7. •Cortisol
•ACTH, (Anteriorpituitarygland)
•CRHHypothalamus
•Increasesgluconeogenesisandlipolysis,
•Decreasesperipheralglucoseutilization,inhibits
immunologicalresponseand,intime,reducesmuscularmass.
•Itafectsfatdistribution,woundhealingandbonemineralisation;
•italsoaltersmood(causingeuphoriaor,rarely,depression)andbraincortical
activityandalertness.

8. •Adrenal androgen
dehydroepiandrosterone (DHEA)
•about20%oftotalmaleactivity
•undercontrolofACTH.

9. •Adrenaline (epinephrine; 80%) +
noradrenaline (norepinephrine;
20%) and dopamine.
•Only medulla express
phenylethanolamine-N-methyltransferase
(PNMT), which catalysesthe conversion
of noradrenaline to adrenaline.

11. INCIDENTALOM
A

13. Adrenal Mass size > 1cm
C
B
AImaging
Size
Metabolic
workup
< 4cm
Benign
Silent
1) Cortisol <1.8 ʮg/dl
2) Aldosterone <15ng/dl
3) MetaNeph <4x

14. Adrenal Mass size > 1cm
C
B
AImaging
Size
Metabolic
workup
< 4cm
Silent
Indeterminate

15. Adrenal Mass size > 1cm
C
B
AImaging
Size
Metabolic
workup
< 4cm
Silent
Indeterminate

16. Adrenal Mass size > 1cm
C
B
AImaging
Size
Metabolic
workup
Benign
Silent
> 4cm

17. Adrenal Mass size > 1cm
C
B
AImaging
Size
Metabolic
workup
< 4cm
Benign
Automonous
Cortisol
Secretion

18. Adrenal Mass size > 1cm
C
B
AImaging
Size
Metabolic
workup
< 4cm
Benign
Silent
Indeterminate
> 4cm
Automonous
Cortisol Secretion

21. DISORDERS
OF
CORTEX

22. Conn’s Syndrome
( Primary Hyperaldosteronism)
High
BLOOD
PRESSURE
LOW
Potassium
High ALDOSTERONE Levels

23. BOX 106.2 Indications for Primary Aldosterone
Screening
Hypertension with
hypokalemia
Resistant
hypertension
(three or more oral
agents including a
diuretic)
Adrenal
incidentaloma with
hypertension
Hypertension with
sleep apnea

24. BOX 106.2 Indications for Primary Aldosterone
Screening
Early-onset
hypertension (<20
years) or stroke (<50
years)
Severe hypertension
(150/100) measured
on 3 different days
Whenever
considering
secondary causes of
hypertension (i.e.,
pheochromocytoma
or renovascular
disease)
Unexplained
hypokalemia
(spontaneous or
diuretic induced)

25. Aldosterone Producing
Tumours
•Canary
Tumours

29. Aldosterone
Producing
Adenoma
Unilateral
Hyperplasia
Ovarian
Aldosterone
producing CA
Adenocarcinom
a
Surgically corrected hyper
aldosteronism

36. Cushing Syndrome/Disease
•Excess ACTH secretion (termed pituitary dependent;
Cushing’s disease) 80%
•Ectopic ACTH secretion non-pituitary tumour10%,
•Exogenous corticosteroid therapy
•Autonomous secretion of endogenous glucocorticoids
from cortical tumours of the adrenal glands (pituitary
independent; Cushing’s syndrome).

37. Left untreated,
Hypercortisolism leads to a
fivefold increase in the risk of
death from cardiovascular
disease.

38. The Principal aim
•Determine and treat the underlying
cause,
•While avoiding, if possible, long-
term hormonal deficiency or
dependence on medication.

39. The typical patient
•A facial plethora, a buffalo hump and a
moon face in combination with
hypertension,diabetes,centralobesity
and proximal muscle-wasting, traditionally
referred to as the‘lemononsticks’
appearance

40. Adrenal Adenoma – Commonest cause
•Hypercortisolism leads to suppressed
ACTH,
•Atrophy of fasciculata and reticularis, not
glomerulosa, in the residual or opposite
adrenal gland.

42. Two out of Four needed for diagnosis
•Late-night Salivary Cortisol (Two Measurements):
Raised Levels Signify A Loss Of Diurnal Rhythm;

43. Two out of Four needed for diagnosis
•Late-night Salivary Cortisol (Two Measurements):
Raised Levels Signify A Loss Of Diurnal Rhythm;
•24-hour UFC Excretion (Two Measurements): 3X
Signifies Overspill Into The Urine;

44. Two out of Four needed for diagnosis
•Late-night Salivary Cortisol (Two Measurements):
Raised Levels Signify A Loss Of Diurnal Rhythm;
•24-hour UFC Excretion (Two Measurements): 3X
Signifies Overspill Into The Urine;
•Overnight 1-mg Dst (Dexamethasone Suppression
Test): Non-suppressed Morning Cortisol >50
Nmol/L;

45. Raised Serum ACTH
Pituitary-
dependent
Disease;
Suppressed ACTH
Adrenal Origin
Disease
<5 Pg/Ml).

46. Raised Serum ACTH
Pituitary MRI
Inferior
petrosal sinus
sampling

47. Raised Serum ACTH
Pituitary MRI
Inferior
petrosal sinus
samplingBoth Negative

48. Raised Serum ACTH
Pituitary MRI
Inferior
petrosal sinus
samplingBoth Negative Ectopic ACTH

49. Raised Serum ACTH
Pituitary MRI
Inferior
petrosal sinus
samplingBoth Negative Ectopic ACTH
CT CAP
68
Ga-SSTR
PET-CT

50. Suppressed Serum ACTH
MRI
Abdomen
CT
abdomen
Hypodense (<10HU)

51. Medical Management
•Metyrapone orketoconazoletherapyreduces steroid
synthesis and secretion
•Intravenousetomidateinfusion(even at non-hypnotic doses)
can reduce serum cortisol levels to normal within 24 hours,
providing a suitable window for surgery.
• This requires monitoring in an intensive care unit setting.

52. Surgical Management
•ACTH-producing pituitary tumours -transsphenoidalresectionand/or
radiotherapy.
•ResectionofectopicACTH-secretingtumours will also correct
hypercortisolism.
•Patients who have undergone failed pituitary surgery or those with an
unresectable or unlocalised ectopic ACTH-secreting tumour may
requirebilateraladrenalectomyto control hormone excess.

53. •Unilateral adenoma should be treated by minimally invasive
adrenalectomy
•Bilateral adrenalectomy should be employed in severe Cushing’s and
equally enlarged adrenals.
•In asymmetric disease, excision of the larger gland may be curative with
a low risk of recurrence.
•In cases of subclinical Cushing’s syndrome and a unilateral adenoma,
unilateral adrenalectomy is indicated if the tumour is >4 cm or <4 cm
with features of the metabolic syndrome.
Surgical Management

54. Preoperative management
RISKS
Venous
thromboembolism,
Cardiac events,
INFECTION &
DM
Poor wound
healing

55. Preoperative management
Mech &
Therapeutic
Prophylaxis
Cardiac events,
INFECTION
Poor wound
healing

56. Preoperative management
Mech &
Therapeutic
Prophylaxis
Cardiac events,
Pre-op AntiBx
Poor wound
healing

57. Preoperative management
Mech &
Therapeutic
Prophylaxis
Intra-op
Hydrocortisone
100-150mg
Pre-op AntiBx
Good Glycemic
Control

58. Postoperative management.
After unilateral adrenalectomy
•Contralateral gland will be suppressed 15–25 mg daily of
hydrocortisone.
•In total, 15 mg/h is required parenterally for the first 12
hours
•Followed by a daily dose of 100 mg for 3 days,
•Gradually reduced thereafter.
•A synacthen test is used to confirm adequate adrenal
function

59. Nelson’s syndrome
• 10% of patients with Cushing’s disease who undergo a bilateral
adrenalectomy after failed pituitary surgery,
•The pituitary adenoma causes Nelson’s syndrome
•Continued ACTH secretion at high levels, resulting in
hyperpigmentation due to uncontrolled secretion of pro-
opiomelanocortin (POMC).
•POMC is cleaved to produce ACTH and melanocyte-stimulating
hormone, excess of the latter resulting in hyperpigmentation.