Adrenal dysfunction

Basic anatomy Suprarenal triangular glands Parts- outer cortex & inner medulla Cortex- 3 layers- G.F.R. Zona glomerulosa- mineralocorticoids- aldosterone Zona fasciculata- glucocorticoids- cortisol Zona reticularis- androgens- DHEA & DHEAS Medulla- produces epinephrine & norepinephrine

Basic physiology Cortisol- Secretion regulated by stress & ACTH-negative feedback Free cortisol is active fraction Regulates intermediary metabolism of nutrients

to increase blood glucose Promotes anti-inflammatory & fluid retention Aldosterone- Secretion regulated by renin-angiotensin system, K, ACTH Regulates extracellular volume & K, acting on DCT of kidney Androgen- Regulates male secondary sexual characteristics

Adrenal dysfunction Hyperadrenalism- Cushing’s Primary hyperaldosteronism Pheochromocytoma Virilization

Hypoadrenalism- Addison’s, crisis

Cushing syndrome Causes- Exogenous steroids ACTH hypersecretion by pituitary adenoma- Cushing disease Excessive adrenal production- hyperplasia/tumor Paraneoplastic- SCLC, carcinoid, pancreatic carcinoma Consequences- Central obesity- moon face, buffalo hump, supraclavicular fat pad,

protuberant abdomen, thin extremities Hyperpigmentation- points towards extra-adrenal tumor HT, IGT, osteoporosis, acne, purple striae, easy bruisability Virilization, amenorrhea Impaired wound healing, opportunistic infection Neurosispsychosis

Investigation Leukocytosis with neutrophilia, IGT, hypokalemia Screening- low-dose dexamethasone suppression test-

1 mg at night8 a.m. serum cortisol Confirm hypercortisolism- Midnight serum/salivary cortisol 24-hr urine for free cortisol & creatinine- absolute/ratio High-dose dexamethasone suppression test-

0.5 mg q 6 hrs x 48 hrs urine/plasma cortisol- normal suppression-Cushing disease; non-suppression- adrenal tumor/ectopic ACTH

Establish etiology- ACTH- serum or inferior petrosal sinus MRI for pituitary adenoma CT abdomen for adrenal pathology ± CT chest for SCLC In-111 octreotide scanning- to detect occult tumors

Treatment Pituitary adenoma- trans-sphenoidal

resection/stereotactic radiosurgery Adrenal tumor- surgery Ectopic ACTH secreting tumor- surgery Metyrapone, ketoconazole, ?rosiglitazone-

decrease hypercortisolism All fails- B/L adrenalectomy with replacement

Complication- Nelson syndrome- pituitary adenoma following B/L adrenalectomy

Primary aldosteronism A cause of secondary HT Due to aldosterone producing adrenal adenoma

-Conn syndrome or hyperplasia/carcinoma Causes polyuria/polydipsia, muscle weakness,

diastolic HT, hypokalemia Ix- Hypokalemia ± hypernatremia Low plasma renin or high aldosterone:renin ratio Inability to suppress aldosterone, despite salt-loading CT abdomen- to localize adrenal pathology Rx- spironolactone, surgery

Pheochromocytoma Tumors of adrenal medulla, causing 2° HT

due to secretion of catecholamines Rule of 10-

10% without HT, extra-adrenal, B/L, familial, malignant

May be part of MEN- 2A- + medullary ca. thyroid + hyperparathyroidism 2B- + MCT + multiple mucosal neuroma s/s- Headache, sweating, palpitation, anxiety, tremors HT- sustained or paroxysmal, postural tachycardia/hypotension May precipitate HTive crisis or arrythmias

Management Ix- 24-hour urinary

metanephrine/catecholamine:creatinine ratio CT or MRI or PET/CT fusion In-111 octreotide or I-123 mIBG scanning Rx- Control of BP- CCB, α-blockers Preoperative- α-blockers + nifedipine + propranolol Laparoscopic removal of tumor

Hirsuitism & Virilization Defects in females, due to increased male

hormones- adrenal or extra-adrenal Hirsuitism- male-pattern excessive terminal

hair growth in women Virilization- increased muscularity, male-

pattern baldness, deepening of voice, clitoromegaly in women

Causes- Idiopathic/familial PCOS, 21-hydroxylase deficiency/defect, ovarian tumors Drugs- minoxidil, cyclosporin, phenytoin, anabolic steroids

Clinical s/s- Excess hair, acne, irregular menses, defeminization Pelvic/genital examination Ix- Serum free testosterone- for ovarian tumor Serum DHEAS- for adrenal source of androgen LH:FSH ratio > 2- in PCOS US or CT- abdomen & pelvis- for localization Rx- Drugs- spironolactone, finasteride, flutamide, OCP PCOS- metformin, +infertility- clomiphene Local treatment for excess hair

Addison disease Primary chronic deficiency of

adrenocortical hormones Causes- Tuberculosis, fungal infection, infections in AIDS-

CMV Autoimmune, congenital adrenal hyperplasia Consequences- Fatigability, weight loss, nausea/vomiting, irritability Skin/mucosal pigmentation, hypotension Reduced body hair, specially in women

Management Ix- Increased lymphocytes & eosinophils, low Na, high K Low plasma cortisol & DHEA, raised ACTH Rapid ACTH stimulation test- inadequate cortisol rise CT scan of abdomen- for adrenal size & pathology Rx- Prednisone, 5+2.5 mg/day- normalises DLC Fludrocortisone- mineralocorticoid replacement Ample salt intake & treat underlying infection

Other adrenal hypofunction Secondary- Due to pituitary dysfunction, NO hyperpigmentation Aldosterone deficiency not as common or severe Ix-Low cortisol & low ACTH Rx- glucocorticoid replacement Acute- crisis- Cause- sepsis, B/L hemorrhage, rapid steroid withdrawl Manifestation- vomiting, abdominal pain, confusion, shock Na low, K high Rx- rehydration, IV hydrocortisone, Abx