Adrenal Cortical Hyperfunction

Khaled Alswat, MD, CCD, FACP Assistance Professor of Medicine Taif University

Background

2008 McGill Molson Medical Informatics

Background
Cortical Zone
Glomerulosa
Fasciculata Reticularis Hormone

Background
Cortical Zone
Glomerulosa
Fasciculata Reticularis Hormone

Aldosterone (Mineralocorticoids )
Cortisol (Glucocorticoids) Androgen (DHEA-S) and Estradiol

G Aldo

F co

R an

Hyperaldosteronism

Jerome W. Conn September 24, 1907 June 11, 1981

Background
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.

How did Dr.Conn define the disease?

Aldosterone
What is the normal function of the Aldosterone hormone?

What regulate the hormone secretion?

Clinical Features
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.

Primary Hyperaldosteronism (Conns disease)

High Aldosterone + suppressed Renin

Secondary Hyperaldosteronism

High Aldosterone + High Renin

Laboratory Evaluation
Basic chemistry
Lab
Na K Magnesium

Abnormality
HyperNa HypoK HypoMg

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

Who Should we Screen

Hypertensive patients with stage 2 (>160-179/100-109 mm Hg). Drug-resistant hypertension >140/90 on three anti-HTN meds. Hypertension and spontaneous or diuretic-induced hypokalemia. Hypertension with adrenal incidentaloma.
Lack of peripheral edema is pathgnomic for primary hyperaldosteronism Hypertension and a family history of early-onset hypertension or (Conns Disease),called cerebrovascular accident at a young age (<40 yr).aldosterone escape phenomena

All hypertensive first-degree relatives of patients with PA.

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 Adenoma Hyperplasia Age Young <40 yr Old>40 yr Adrenal lesion location Unilateral Bilateral Treatment Surgical resection 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 cortisol X3 Midnight salivary cortisol 1mg 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.

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.