Adrenal Cortical Hyperfunction Khaled Alswat, MD, CCD, FACPAssistance Professor of MedicineTaif University

Background

2008 McGill Molson Medical Informatics

BackgroundCortical Zone Hormone

Glomerulosa

Fasciculata

Reticularis

BackgroundCortical Zone Hormone

Glomerulosa Aldosterone (Mineralocorticoids )

Fasciculata Cortisol (Glucocorticoids)

Reticularis Androgen (DHEA-S) and Estradiol

G F RAldo co an

Hyperaldosteronism

Jerome W. ConnSeptember 24, 1907 — June 11, 1981

• Litynski reported the 1st case, but Conn was the first to well characterize the disorder in 1956 and refers specifically to Primary Hyperaldosteronism (PH) secondary to an adrenal adenoma.

Background

How did Dr.Conn define the disease?

Aldosterone • What is the normal function of the Aldosterone hormone?

• What regulate the hormone secretion?

• Polyuria and polydepsia - nephrogenic Diabetes insipidus (Low K)

• Headach hypertension.

• Muscle weakness: not typically prominent unless K <2.5 meq/L.

• Hypokalemia paralytic ileus and cardiac arrest.

• Hypomagnesemia and possible hypoCa tetany.

• HyperNa.

• Metabolic alkalosis.

Clinical Features

Primary Hyperaldosteronism (Conn’s disease)

High Aldosterone + suppressed Renin

Secondary Hyperaldosteronism

High Aldosterone + High Renin

Laboratory Evaluation Basic chemistry

Most patients has insulin resistance and at increase risk of developing type 2 diabetes so evaluation of fasting blood glucose and 75 g oral glucose tolerance test may needed.

Plasma renin and aldosterone at 8am is the Screening test

Sodium (oral or IV ) load followed by measurement of aldosterone is the confirmatory test

Lab Abnormality

Na HyperNa

K HypoK

Magnesium HypoMg

• Hypertensive patients with stage 2 (>160-179/100-109 mm Hg).

• Drug-resistant hypertension >140/90 on three anti-HTN med’s.

• Hypertension and spontaneous or diuretic-induced hypokalemia.

• Hypertension with adrenal incidentaloma.

• Hypertension and a family history of early-onset hypertension or cerebrovascular accident at a young age (<40 yr).

• All hypertensive first-degree relatives of patients with PA.

Who Should we Screen

Lack of peripheral edema is pathgnomic for primary

hyperaldosteronism (Conn’s Disease),called

aldosterone escape phenomena

Confirm the positive result with the salt loading (IV or oral)

Approach Recommendations • Disease suspected by the symptoms.

• Do basic chemistry.

• Do the screening test (If positive proceed to the next step)

• Do the confirmatory test(If positive proceed to the next step)

• Do imaging study to localize the disease.

Either CT or MRI of the Adrenal gland are helpful to localize the disease.

Causes& Treatment of Primary hyperaldosteronism

Type Age Adrenal lesion location

Treatment

Adenoma Young <40 yr Unilateral Surgical resection

Hyperplasia Old>40 yr Bilateral Medical Rx with mineralocorticoid receptor (MR) antagonist as spironolactone.

Cushing Syndrome

Hirsutism and moon face Note:wide, dark(purple stria).

Work up• What is the appropriate work up to diagnose this patient?

24 hr urine free cortisolMidnight salivary cortisol1mg overnight dexamethasone suppression test

If cortisol elevated (urine, plasma or salivary), then check ACTH

If ACTH undetectable (below reference range), then Cushing syndrome is the diagnosis, so exclude exogenous steroid intake and adrenal adenoma.

If ACTH normal or high then Cushing disease is the diagnosis, so proceed with pituitary MRI. Rarely ectopic ACTH give similar presentation/lab to Cushing disease.

X 3

Treatment • For Cushing disease (pituitary origin) trans-sphenoidal surgery.

• If surgery failed then medical treatment like ketoconazole and patient will need external pituitary radiation.

• If all failed then consider bilateral adrenalectomy.

• For Cushing syndrome ,treat the underling cause (adrenal ,ectopic etc),surgical resection is the 1st option and medical treatment is as Cushing disease.