Mkindi

2. ADRENAL INSUFFICIENCY
• Picha ya HPA na Reserve ya drenal gland

3. ADRENAL INSUFFICIENCY..
Etiology:
Primary = adrenocortical disease = Addison’s disease
1.Autoimmune: isolated or in assoc w/ APS
2.Infection: TB, CMV, histoplasmosis, paracoccidioidomycosis,syphillis
3.Vascular: hemorrhage (usually in setting of sepsis Eg:Warerhouse-
Friderichson), adrenal vein thrombosis, HIT, trauma
4.Metastatic disease: (90% of adrenals must be destroyed to cause
insufficiency)
5.Deposition diseases: hemochromatosis, amyloidosis, sarcoidosis
6.Drugs: azole antifungals, etomidate (even after single dose),
rifampin, anticonvulsants
Nelson syndrome

4. ADRENAL INSUFFICIENCY..
Secondary = pituitary failure of ACTH secretion
• But aldosterone intact b/c RAA axis
• Any cause of primary or secondary hypopituitarism
-Hypophysitis
• Glucocorticoid therapy (can occur after ≤2 wk of
“suppressive doses”; dose effect variable; even <10 mg of
prednisone daily chronically can be suppressive
• Megestrol (a progestin with some glucocorticoid activity)

5. ADRENAL INSUFFICIENCY
Tertiary causes:
• Refers to causes that relate to hypothalamic
abnormalities that reduce corticotropin-releasing
hormone (CRH) secretion.
– Abrupt cessation of high-dose glucocorticoid
therapy
– Correction (cure) of hypercortisolism (Cushing's
syndrome)

6. ADRENAL INSUFFICIENCY-Symptoms
• Primary or secondary: weakness and fatigability (99%),
anorexia (99%), orthostatic hypotension (90%), nausea
(86%), vomiting (75%), hyponatremia (88%)
• Primary only (extra s/s due to lack of aldosterone and
↑ ACTH): marked orthostatic hypotension (because
volume depleted), salt craving, hyperpigmentation
(seen in creases, mucous membranes, pressure areas,
nipples), hyperkalemia
• Secondary only: ± other manifestations of
hypopituitarism

7. ADRENAL INSUFFICIENCY-Diagnostic studies
• Early a.m. serum cortisol: <3 µg/dL virtually diagnostic; ≥18 µg/dL generally
consistent with intact adrenal function
• Standard (250 µg) cosyntropin stimulation test (testing ability of ACTH → ↑
cortisol)
• Normal = 60-min (or 30-min) post-ACTH cortisol ≥18 µg/dL
• Abnormal in primary b/c adrenal gland diseased and unable to give adequate
output
• Abnormal in chronic secondary b/c adrenals atrophied and unable to respond
(very rarely, may be normal in acute pituitary injury b/c adrenals still able to
respond→ use early a.m. cortisol instead)
• All glucocorticoids (incl creams, inh. & drops) affect test. Must know exposure to
interpret.

9. ADRENAL INSUFFICIENCY-Diagnostic studies
cont..
• Other tests : renin, aldosterone, insulin-induced hypoglycemia
(measure serum cortisol response)
• Metyrapone (blocks cortisol synthesis and therefore stimulates
ACTH, measure plasma 11-deoxycortisol and urinary 17-
hydroxycorticosteroid levels)
• ACTH: ↑ in 1°, ↓ or low-normal in 2°
• Imaging studies to consider pituitary MRI to detect anatomical
abnormalities
• Adrenal CT: small, noncalcified adrenals in autoimmune, enlarged in
metastatic disease, hemorrhage, infection or deposition (although
they may be normal-appearing)

10. ADRENAL INSUFFICIENCY-Treatment
• Acute insufficiency: volume resusc. w/ normal saline +
hydrocortisone IV
• Chronic insufficiency:
(1) prednisone ~4–5 mg PO qam or hydrocortisone
15–25 mg PO qd (⅔ a.m., ⅓ early p.m.)
(2) fludrocortisone (not needed in 2° adrenal
insufficiency) 0.05–0.2 mg PO qam
(3) backup dexamethasone 4-mg IM prefilled
syringe given to Pt for emergency situations

11. ADRENAL CRISIS IN ADRENAL
INSUFFICIENCY
• Precipitants: bilateral adrenal hemorrhage or
infarction, pituitary infarction, pre-existing
adrenal insufficiency + serious infection or GI
illness
• Presentation: shock + anorexia, N/V, abd pain,
weakness, fatigue, confusion, coma, fever Lab
findings: hyponatremia, hyperkalemia (1°)
• Rx: hydrocortisone 50–100 mg IV q8 + IVF; do not
delay for dx tests

12. HYPERCORTISOLISM
• Cushing’s syndrome = cortisol excess.
• Cushing’s disease = Cushing’s syndrome 2° to
pituitary ACTH hypersecretion.

13. Etiologies
• Most commonly iatrogenic caused by exogenous glucocorticoids
• Cushing’s disease (60–70%): ACTH-secreting pituitary adenoma (usually microadenoma) or
hyperplasia
• Adrenal tumor (15–25%): adenoma or (rarely) carcinoma
• Ectopic ACTH (5–10%): SCLC, carcinoid, islet cell tumors, medullary thyroid cancer,pheo
Clinical manifestations
 Nonspecific: glucose intolerance or DM, HTN, obesity, oligo- or amenorrhea, osteoporosis
 More specific: central obesity w/ extremity wasting, dorsocervical fat pads, spont. Bruising
 Most specific: proximal myopathy, rounded facies, facial plethora, wide purple striae
– Other: depression, insomnia, psychosis, impaired cognition, hypokalemia, acne, hirsutism,
 hyperpigmentation (if ↑ ACTH), fungal skin infxns, nephrolithiasis, polyuria

15. Treatment
• Surgical: resection of pituitary adenoma, adrenal
tumor or ectopic ACTH-secreting tumor,
-Or bilat surgical adrenalectomy if unable to
control source of ACTH
• Medical: cabergoline, pasireotide, mitotane,
ketoconazole, or metyrapone to ↓ cortisol,
and/or mifepristone to block cortisol action at
glucocorticoid receptor; frequently used
as bridge to surgery or when surgery
contraindicated

16. Treatment-Cont…
• Radiation: can do pituitary XRT, but not
effective immediately (takes 6 mo to 2 y)
• Glucocorticoid replacement therapy × 6–36
mo after TSS (lifelong glucocorticoid +
Mineralocorticoid replacement if medical
or surgical adrenalectomy)

17. HYPERALDOSTERENOSIMS
• Primary (adrenal disorders, renin-independent increase in aldosterone; JCEM 2015;100:1)
• adrenal hyperplasia (60–70%), adenoma (Conn’s syndrome, 30–40%), carcinoma
• glucocorticoid-remediable aldosteronism (GRA; ACTH-dep. rearranged promoter)
• Secondary (extra-adrenal disorders, ↑ aldosterone is renin-dependent)
• Primary reninism: renin-secreting tumor (rare)
• Secondary reninism: renovascular disease: RAS, malignant hypertension; edematous
• states w/ ↓ effective arterial volume: CHF, cirrhosis, nephrotic syndrome;
• hypovolemia, diuretics, T2D, Bartter’s (defective Na/K/2Cl transporter ≈ receiving
• loop diuretic), Gitelman’s (defective renal Na/Cl transporter ≈ receiving thiazide
• diuretic)
• Nonaldosterone mineralocorticoid excess mimics hyperaldosteronism
• 11β-HSD defic. (→ lack of inactivation of cortisol, which binds to mineralocorticoid
• recept.)
• Black licorice (glycyrrhizic acid inhibits 11β-HSD), extreme hypercortisolism
• (overwhelming 11β-HSD), exogenous mineralocorticoids
• Liddle’s syndrome (constitutively activated/overexpressed distal tubular renal Na
• channel)

18. Clinical Manifestations
• Mild-to-moderate HTN (11% of Pts w/ HTN
refractory to 3 drugs; Lancet
• 2008;371:1921) headache, muscle weakness,
polyuria, polydipsia; no peripheral edema
• because of “escape” from Na retention;
malignant HTN is rare
• Classically hypokalemia (but often normal),
metabolic alkalosis, mild hypernatremia

19. HYPERALDOSTERENISM-Diagnosis
• 5–10% of Pts w/ HTN; ∴ screen if HTN + hypoK, adrenal mass, refractory/early
onset
• HTN
• Screening: aldo (>15–20 ng/dL) and plasma aldo:renin ratio (>20 if 1°) obtain 8
a.m.
• paired values (off spironolactone & eplerenone for 6 wk); Se & Sp >85%
• ACEI/ARB, diuretics, CCB can ↑ renin activity → ↓ PAC/PRA ratio and βBs may ↑
• PAC/PRA ratio;∴ avoid. α-blockers generally best to control HTN during dx testing.
• Confirm with sodium suppression test (fail to suppress aldo after sodium load) oral
salt
• load (+ KCl) × 3 d, ✔ 24-h urine (⊕ if urinary aldo >12 μg/d while urinary Na >200
• mEq/d) or 2L NS over 4 h, measure plasma aldo at end of infusion (⊕ if aldo >5
ng/dL)

21. HYPERALDOSTERONISM-Treatment
• Adenoma → adrenalectomy vs. medical Rx w/
spironolactone or eplerenone
• Hyperplasia → spironolactone or eplerenone;
GRA → glucocorticoids ± spironolactone
• Carcinoma → adrenalectomy

22. PHAEOCHROMOCYTOMA
• Neuroendocrine neoplasm leads to inappropriate and paroxysmal release of
adrenergic
• agents including epinephrine, norephinephrine, and rarely dopamine
• Pressure (hypertension, paroxysmal in 50%, severe & resistant to Rx, occ
orthostatic)
• Pain (headache, chest pain)
• Palpitations (tachycardia, tremor, wt loss, fever)
• Perspiration (profuse)
• Pallor (vasoconstrictive spell)
• Paroxysms can be triggered by meds (eg, β-blockers) abdominal manipulation
• Associated with MEN2A/2B, von Hippel Lindau, NF1, familial paraganglioma
(mutations
• in succinate dehydrogenase gene B, C and D) or TMEM127 mutations
• Up to 40% of pheos/paragangliomas thought to have underlying genetic etiology;
genetic
• testing frequently recommended

23. Phaeochromocytoma-Dx Studies
• 24° urinary fractionated metanephrines: 85–97% Se, 69–95% Sp. Screening test of
choice
• if low-risk (b/c false ⊕ with severe illness, renal failure, OSA, labetalol due to assay
• interference, acetaminophen, TCAs, medications containing sympathomimetics).
• Plasma-free metanephrines: 89–100% Se, 79–97% Sp (JAMA 2002;287:1427).
Screening test of
• choice if high risk, but ↑ rate of false ⊕ in low-prevalence population. False ⊕
rate lower
• if patient supine for 30 min (estimated 2.8× ↑ false ⊕ if seated).
• Adrenal CT generally better than MRI; PET for known metastatic disease or to
localize
• nonadrenal mass but usually easy to find; consider MIBG scintigraphy if CT/MRI ⊖
• Consider genetic testing if bilateral disease, young Pt, ⊕ FHx, extra-adrenal

24. Phaeochromocytoma-Treatment
• α-blockade first (usually phenoxybenzamine) ±
β-blockade (often propranolol) → surgery
• Preoperative volume expansion is critical due
to possible hypotension after tumor excision

25. ADRENAL INCIDENTALOMAS
• 4% of Pts undergoing abdominal CT scan have
incidentally discovered adrenal mass;
• prevalence ↑ with age
Differential diagnosis
• Nonfunctioning mass: adenoma, cysts, abscesses,
granuloma, hemorrhage, lipoma,
• myelolipoma, primary or metastatic malignancy
• Functioning mass: pheochromocytoma, adenoma
(cortisol, aldosterone, sex hormones),
• nonclassical CAH, other endocrine tumor, carcinoma

26. Hormonal Work Up
• Rule out subclinical Cushing’s syndrome in all Pts
using 1 mg overnight DST (Sp 91%).
• Abnormal results require confirmatory testing.
• Rule out hyperaldosteronism if hypertensive w/
plasma aldo & renin (see above)
• Rule out pheochromocytoma in ALL Pts (b/c of
morbidity unRx’d pheo) using 24-h urine
• fractionated metanephrines or plasma-free
metanephrines

27. Malignancy Work Up
• CT and MRI characteristics may suggest adenoma vs. carcinoma
• Benign features: unenhanced CT <10 Hounsfield units or CT contrast-
medium washout
• >50% at 10 min; size <4 cm; smooth margins, homogenous and hypodense
• appearance; can follow such incidentalomas w/ periodic scans
• Suspicious features: size >6 cm or ↑ size on repeat scan; irregular margins,
• heterogeneous, dense or vascular appearance; h/o malignancy or young
age. Such
• incidentalomas warrant resection or repeat scan at short interval.
• Rule out metastatic cancer (and infection) in Pts w/ h/o cancer; ~50% of
adrenal
• incidentalomas are malignant

28. Follow-up
• If hormonal workup ⊖ and appearance
benign, yearly fxnal testing for 4 y w/ follow-
up
• imaging at 6, 12, & 24 mo reasonable
approach, but controversial

29. “In learning you will teach and in teaching
you will learn”-Phill Collins