Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (98 page)

•
Nonaldosterone mineralocorticoid excess
mimics hyperaldosteronism

11β-HSD deficiency (→ lack of inactivation of cortisol, which binds to nonselective mineralocorticoid receptor)

Black licorice (glycyrrhizinic acid inhibits 11β-HSD), extreme hypercortisolism (overwhelming 11β-HSD), exogenous mineralocorticoids

Liddle’s syndrome (constitutively activated/overexpressed distal tubular renal Na channel)

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

Diagnostic studies

• 5–10% of Pts w/ HTN; ∴ screen if HTN + hypokalemia, adrenal mass or refractory 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. ɑ-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 aldo >12 µg/d while Na >200 mEq/d)
or
2L NS over 4 h, measure aldo at end of infusion (
if aldo >5 ng/dL)

Figure 7-4 
Approach to suspected hyperaldosteronism

Treatment

• Adenoma → adrenalectomy vs. medical Rx w/ spironolactone or eplerenone

• Carcinoma → adrenalectomy

• Hyperplasia → spironolactone or eplerenone; GRA → glucocorticoids ± spironolactone

ADRENAL INSUFFICIENCY

Etiologies

•
Primary
= adrenocortical disease =
Addison’s disease

autoimmune
: isolated or in assoc w/ PGA syndromes (see table on page 7-2)

infection
: TB, CMV, histoplasmosis

vascular
: hemorrhage (usually in setting of sepsis), thrombosis, HIT and trauma

metastatic disease
: (90% of adrenals must be destroyed to cause insufficiency)

deposition diseases
: hemochromatosis, amyloidosis, sarcoidosis

drugs
: ketoconazole, etomidate (even after single dose), rifampin, anticonvulsants

•
Secondary
= pituitary failure of ACTH secretion (but aldosterone
intact
b/c RAA axis) any cause of primary or secondary hypopituitarism (see “Pituitary Disorders”)

glucocorticoid therapy (can occur after ≥2 wk of “suppressive doses”; dose effect variable; <10 mg prednisone daily chronically can be suppressive)

megestrol (a progestin with some glucocorticoid activity)

Clinical manifestations
(
NEJM
1996;335:1206)
•
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 (see “Pituitary Disorders”)
Diagnostic studies
(
Annals
2003;139:194)
• Early a.m. serum cortisol: <3 µg/dL virtually diagnostic; ≥18 µg/dL rules it out (except in severe septic shock—see below) • Standard (250 µg)
cosyntropin stimulation test
(testing ability of ACTH → ↑ cortisol)

normal = 60-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 secondary
b/c adrenals still able to respond; early a.m. cortisol can be used rather than post-stim value in these cases)

• Other tests to evaluate HPA axis (w/ guidance by endocrinologist): insulin-induced

hypoglycemia (measure serum cortisol response); metyrapone (blocks cortisol synthesis

and therefore stimulates ACTH, measure plasma 11-deoxycortisol and urinary

17-hydroxycorticosteroid levels)

• Other lab abnormalities: hypoglycemia, eosinophilia, lymphocytosis, ± neutropenia • 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)

Adrenal insufficiency & critical illness
(
NEJM
2003;348:727;  
JAMA
2009;301:2362)
• ↑ circulating cortisol despite ↓ ACTH due to ↓ clearance and possibly stimulation by cytokines; ∴ dx of adrenal insufficiency problematic (
NEJM
2013;368:1477) • Nonetheless, reasonable to perform ACTH stim ASAP in hypotensive Pt suspected to have absolute adrenal insuffic.

• Initiate corticosteroids early: use dexamethasone 2–4 mg IV q6h + fludrocortisone 50 µg daily prior to ACTH stim; change to hydrocortisone 50–100 mg IV q6–8h once test completed.

• Rx of
relative adrenal insufficiency
controversial (see “Sepsis”)
Treatment

•
Acute
insufficiency: volume resuscitation w/ normal saline +
hydrocortisone IV
as above •
Chronic
insufficiency

Hydrocortisone: 20–30 mg PO qd (2⁄3 a.m. 1⁄3 early p.m.) or prednisone ~5 mg PO qam

Fludrocortisone (
not
needed in 2° adrenal insufficiency): 0.05–0.1 mg PO qam

backup dexamethasone 4-mg IM prefilled syringe given to Pt for emergency situations

PHEOCHROMOCYTOMA

Clinical manifestations (five Ps)

•
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)

• “Rule of 10”: 10% extra-adrenal (known as paraganglioma), 10% in children,

10% multiple or bilateral, 10% recur (↑ in paraganglioma), 10% malignant (↑ in

paraganglioma), 10% familial, 10% incidentaloma

• Emotional stress does not trigger paroxysms, but abdominal manipulation can trigger

catecholamine release; some reports of IV contrast causing paroxysms

• Associated with MEN2A/2B, von Hippel Lindau, neurofibromatosis type 1, familial

paraganglioma (mutations in succinate dehydrogenase gene B, C and D)

Diagnostic studies

• 24° urinary fractionated metanephrines & catechols: 90% Se, 98% Sp (
JCEM
2003;88:553). Screening test of choice if low-risk (as false
with severe illness, renal failure, OSA, labetalol due to assay interference, TCAs, medications containing sympathomimetics).

• Plasma free metanephrines: 99% Se, 89% Sp (
JAMA
2002;287:1427). Screening test of choice if high risk, but ↑ rate of false
in low-preval. population.