disorders of adrenal

1. ADRENOCORTIAL
INSUFFICIENCY

2. Primary
Hypoadrenalism
• Primary adrenal
diseases
Secondary
Hypoadrenalism
• Decreased
stimulation of
adrenals by ACTH

3. Physiology
 The HPA axis is critical for life and is a major part
of our homeostatic regulatory system.
 The output --> the endogenous glucocorticoid -
cortisol

4.  powerful anti-inflammatory functions both at a
whole-cell and at a transcriptional level.
 induce apoptosis of T lymphocytes, neutrophils,
basophils and eosinophils.
 regulate multiple proinflammatory genes encoding
cytokines, chemokines and inflammatory enzymes
associated with repression of AP1 and nuclear factor-
κB (NF-κB) transcription.
 inhibit antigen presentation, MHC II expression and
antibodies, and favour TH 1 vs TH 2 responses.
 influence cytotoxic effects via cell death and oxidative
stress,
 role in metabolic regulation through glucose
utilization and ATP production and interact with the
major neurotransmitters and many secondary
neuropeptidergic systems.
 modulate emotion and cognition, with key examples
being learning ability, performance, emotional
perception and mood

5.  The hypothalamic–pituitary–adrenal (HPA) axis is
a key system that synchronizes the stress
response with circadian regulatory processes.
 Regulation of the HPA axis is very dynamic with
both ultradian and circadian oscillations.
 Acute stress--> High ACTH --> High cortisol with
pulsatility maintained--> ACTH decreases --
> Adrenal ACTH increases
 In chronic stress, hypothalamic activation of the
pituitary changes from CRH-dominant to arginine
vasopressin-dominant, and cortisol levels remain
raised due at least in part to decreased cortisol
metabolism.
 Chronic elevation and non-physiological patterns
of cortisol result in poor cognitive, metabolic and
immune function.

6. Physiology

7. Patterns of Adrenocortical
insufficiency
 Three major patterns
 1) Primary Acute Adrenocortical Insufficiency
 2) Primary Chronic Adrenocortical Insufficiency
 3) Secondary Acute Adrenocortical Insufficiency

8. Primary Acute Adrenocortical Insufficiency
 Occurs in a variety of clinical settings

9. Acute Adrenal Insufficiency
 presence of hypotension that is refractory to
therapy with volume expansion and inotropes
 Supraventricular tachycardia, reduced stroke
volume, and decreased peripheral resistance are
usual
 Unexplained abdominal or loin pain, vomiting,
fever, and altered mental state, or in non stable
patients after hemorrhagic shock
 Consider bilateral adrenal hemorrhage or adrenal
vein thrombosis

11. Pathogenesis
 Primary adrenal insufficiency (Addison’s disease) is
caused by disordered adrenal function.
A low cortisol production rate and a high plasma
ACTH concentration
 Secondary adrenal insufficiency is caused by
disordered function of the hypothalamus and
pituitary gland  a low cortisol production rate and
a normal or low plasma ACTH concentration
 incidence of 4 to 6 in a population of a million

12.  Glucocorticoid modulates ACTH secretion,
maintains cardiac contractility, modulates vascular
response to the β-adrenoceptor agonists, and is
involved in hepatic glucose metabolism
 Glucocorticoid deficiency (if the hypothalamo-
pituitary unit is normal) is clinically manifested as
ACTH-mediated hyperpigmentation (stimulates
melanocortin-1 receptors on cutaneous
melanocytes)
 palmar creases, scars, knuckles, and oral mucosa),
 Hypotension characterized by tachycardia, reduced
stroke volume, decreased peripheral vascular
resistance, and (in some cases) hypoglycemia.

13.  Mineralocorticoid modulates the renal handling of
sodium, potassium, and hydrogen ions
 promoting sodium retention at the expense of
potassium and hydrogen excretion
 Isosmotic dehydration, leading to hyponatremia,
hyperkalemia, and metabolic acidosis

14.  In secondary adrenal insufficiency, the isolated
effects of glucocorticoid insufficiency lead to
hypotension and hyponatremia.
 Hyponatremia occurs secondary (at least in part)
to antidiuretic hormone (ADH)-mediated water
retention, with normal potassium and hydrogen
ion concentrations.
 ACTH hyperpigmentation is absent in secondary
adrenal insufficiency.

17. Autoimmune Adrenal
Insufficiency
 80% to 90% of patients with primary adrenal
insufficiency have autoimmune adrenalitis
 Isolated (50%)
 as part of an autoimmune polyendocrine Syndrome
 21-hydroxylase antibodies are present in more than
90% of recent-onset patients
 Cumulative risk of developing autoimmune Addison’s
disease in the presence of 21-hydroxylase
antibodies was 48.5%.
 (This cumulative risk was higher in children than in
adults (100% vs. 31.9%), and a male preponderance
was noted.)
 Antibodies against scc and 17 alpha

21. CUSHING SYNDROME

22.  Elevated plasma cortisol levels
 Endogenous
 Exogenous( iatrogenic )


23. CAUSES

24. Clinical Picture

25. ADRENAL NEOPLASMS

26. Adrenocortical Adenoma
 Usually incidental finding
 Mostly clinically silent
 Mostly well circumscribed, nodular lesion

27. Adrenocortical Adenoma
 Usually incidental
finding
 Mostly clinically silent
 Mostly well
circumscribed,
nodular lesion.
 Cut-section: yellow to
yellow brown

28. Adrenocortical Adenoma
 Microscopy:
 Cells simillar to
normal adrenal cortex.
Nuclei small , minimal
pleomorphism
vaculated
eosinophillic
cytoplasm

29. Adrenocortical Carcinoma
 Rare neoplasms
 Can occur at any age
 Usually functional
associated with virilism
or other clinical
manifestations of
hyperadrenalism
 Mostly large,invasive
lesions, efface the
native adrenal.
 Cut-section; varigated
with areas of necrosis ,
hmg and cystic change

30. Adrenocortical Carcinoma
 Microscopy;
 Composed of well
differentiated to
bizzare cells
 Mets to regional and
periaortic nodes
 Distant mets

31. Pheochromocytoma
 Paraganglioma of adrenal medulla composed of
chromaffin cells that produce catecholamines
 Mostly sporadic but often associated with genetic
syndromes in 30-40% of cases
 Malignant in approx 10% of cases

32. Etiology
 30% are hereditary and associted with
 Von- Hippel –Lindau syndrome
 MEN Type 2
 NF-1
 Familial Paraganglioma
 Suspect heriditary when
 Family history or symptoms
 Bilateral tumors
 Presentation < 40 years
 Paraganglioma + Pheochromocytoma

33. Clinical Presentation
 Classic triad of Episodic headaches, sweating
and tachycardia in 30%
 Palpitations , anxiety, postural hypotension and
paroxysmal hypertension
 10-30% present with adrenal incidentaloma

34. Diagnosis
 Clinical suspicion with lab testing and imaging
 Confirmed on HPE

35. GROSS
 Well circumscribed
and unencapsulated
 Solid,white to red-
brown haemorrhagic
cut surface
 4-6cm in size

36. Miocroscopy
 Nested, trabecular or
solid arrangement
outlined by
sustenticular cells.
 Cells large ,
polygonal, uniform or
vacuolated
 Round to oval nucleus
fine to granular
cytoplasm