ADRENAL GLANDS DISORDERSRPh. Dr. Sana MukhtarClinical Pharmacy - 702

LEARNING OBJECTIVESDefine the different disorders of adrenal gland.Discuss these disorders with its etiology, features.Enlist the diagnostic techniques for these disorders.Make a therapeutic plan.

Adrenal cortex

ADRENAL DYSFUNCTION

Decrease functionAdrenal insufficiencyEg Addison disease Increase functionCushing syndromeHyperaldosteronismPheochromocytoma .

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CUSHINGS SYNDROME

CLINICAL PRESENTATION Central obesityFace , trunk , neck, abdomen involvementMoon face with plethoraPeripheral obesity and fat accumulationBuffalo humpMyopathies or muscular weaknessStriae along lower abdomen, red to purple colourHypertension Exophthalmus CHFOsteopenia & osteoporosis

Glucose intolerancePsychiatric changesGonadal dysfunction with amenorrheaMalaiseHirsutiesStriae, acne, skin-thinning, bruisingPolyuria, nocturiadecreased libido and impotence in males

Cushing's syndrome

Frequency of signs and symptoms in Cushings syndrome

Sign or symptomOccurrence %Sign or symptomOccurrence %Central obesity94Easy bruisability60Hypertension82Osteoporosis60Glucose intolerance80Personality changes55Hirsutism75Acne50Amenorrhea or impotency75Edema50Purple striae65Headache40Plethoric faces60Poor wound healing40

DIAGNOSISHypercortisolism 24 hour urinary free cortisol test UFCNight time salivary cortisol test (>0.25 g/dl )Low dose dexamethasone suppression test.Plasma ACTH , CRH test.CT scans MRI

THERAPEUTIC PLANDepends on etiology.Symptoms resolve over several weeks to months with rational therapy.Iatrogenic dose tapering.Transphenoidal adenectomy.ACTH production decreases temporarily after surgery.Glucocorticoid replacement therapy for 3 12 months.Pituitary irradiation.Ectopic ACTH secreting tumors , adrenal adenomas surgery / radiation / chemotherapy

Cushing's syndrome SURGERY

RADIATION

CHEMOTHERAPY

CORTISOL-INHIBITING DRUGS

PHARMACOTHERAPYSteroidogenic inhibitorsNeuromodulators of ACTH secretionGlucocorticoid receptor antagonist.

STEROIDOGENIC INHIBITORSKetoconazoleInhibits 11 deoxycortisol to cortisolInhibit ACTH secretion.Highly effective in lowering cortisol.200 mg PO OD - increased to 600 800 mg ODInteractions with many drugs.Antacids, histamine 2 antagonist, sucralfate, isoniazzid , rifampin.Drug levels are required in certain conditions.ADR- gynocomastia, GI upset , elevated reversible transaminase level

Metyrapone Blocks final step inhibit 11 hydroxylase.Used when ketoconazole has limited useUsed in combination.Initial dose 250 mg upto 2 gm/dayACTH increased due to drop of cortisol.Increase in androgen and mineralocorticoids HTN, acne, hirsutism.

AminoglutethimideInhibits conversion of cholesterol to pregnelone.Short term effects due to compensatory rise in ACTH.Effects are long lasting when given in combination.

Combination therapy with metyrapone & aminoglutethemideBeneficial when used in combination.Promising results in lowering cortisol.

ADRENOLYTIC AGENTSMitotaneInhibits 11 hydroxylation in adrenal cortex.Reduced synthesis of cortisol.Cell degeneration of all zones except glomerulosa in acute therapy .

NEUROMODULATORSNot very efficacious when used alone.Combination therapy is sometimes effective.Cyproheptadine Lower ACTH secretionFor non surgical patients.Relapse can occur.BromocriptineValproic acidOctreotide Roseglitazone

GLUCOCORTICOID RECEPTOR BLOCKERMifepristone Progesterone , androgen glucocorticoid receptor blockerInhibits Dexamethsone suppressionIncreases endogenous cortisol & ACTH

Pre treatmentPost treatment

ADRENAL INSUFFICIENCY

ADDISONS DISEASEAdrenal insufficiencyAutoimmune mediated destruction of adrenal cortex.Primary and secondary adrenal insufficiency.

PRIMARYdestruction of adrenal cortex - autoimmune disorders - chronic infection

SECONDARYLack of ACTH - drugs - tumors and infections of pituitary gland

CORTISOLALDOSTERONECORTISOL

CLINICAL FEATURESWeight loss Muscle weaknessFatigueHyperpigmentation of skinAlopecia . vitiligohypotension HyponatremiaSalt craving HypoglycemiaElevated creatinineElevated ESRhyperkalemia

DIAGNOSISBasal serum cortisol < 3 g/dlCosyntropin stimulation test (>19 g/dl ruled out)Metyrapone test (plasma cortisol

PHARMACOTHERAPYDexamethasone - 0.5 mg odHydrocortisone 15 mg Cortisone 20 mgPrednisone 2.5 - 5 mg Follow up in 6 8 weeksFludricortisone acetate 0.05 mg po od For hyperkalemia deoxycorticosterone trimethylacetate in oilStress related dose adjustment 5 10 mg hydrocort.Alternative therapy licorice may be harmful

ADDISONIAN CRISISACUTE ADRENAL INSUFFICIENCY Sudden penetrating pain in lower back , abdomen or legs

Severe vomiting diarrhea with dehydration

Hypotension

Loss of consciousness

ADDISONIAN CRISIS

Establish IV access.Serum electrolytes, glucose, cortisol, ACTHRapidly infuse 2 3 l N/S or 5% dextrose.Inject hydrocortisone 100 mg IV Q6h.Taper the dose over next 2 3 days if patient stable.Start fludricortisone 0.1 mg daily Pregnancy continue the usual glucocorticoid and mineralocorticoids , some women need high doses in third trimester.Unable to take orally dexamethasone IM daily1 2 mg deoxycorticosterone 25 mg IV hydrocort Q6h Adequate saline hydrationDuring labor increase the doseFor hospitalized severly ill patients hydrocort 100 mg IV Q8h then taper

REFERENCESDipiro clinical practiceHerfindal clinical pharmacy and therapeutic.Roger walkerDavidson clinical medicine

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