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Adrenal gland disorders kinara

Feb 18, 2017


Health & Medicine

Stephen Kinara
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Presenter: KINARA S. KENYORU MED/18/11Facilitator: DR. LUSWETI

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Suprarenal glands• Paired organ each weighing 5-6 grams• pyramidal• superior pole of kidneys at the level of the T12• Enclosed by fibro elastic connective tissue


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CORTEX: Zona glomerulosa 15% Mineralocorticoids

(Aldosterone) Zona fasciculata 75% Glucocorticoids (Cortisol & corticosterone) Zona reticularis 10% Androgens (Dehydroepiandrosterone & androstenedione)

MEDULLA: Catecholamines (Epinephrine & norepinephrine)

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Regulation of adrenal gland secretion

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Increased or stimulated Gluconeogenesis Glycogen deposition Protein catabolism Fat deposition Sodium retention Potassium loss Free water clearance Uric acid production Circulating neutrophils

Decreased or inhibited Protein synthesis Host response to infection Lymphocyte transformation Delayed hypersensitivity Circulating lymphocytes Circulating eosinophils

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ADRENAL HYPOFUNCTION Reduction in output of glucocorticoids and/or

minerallocorticoids Can be:

1. Primary insufficiency – inability of adrenal glands to produce adequate hormones

2. Secondary insufficiency –inadequate pituitary or hypothalamic stimulation of the adrenal gland

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Etiology Glucocorticoid treatment Autoimmune adrenalitis Tuberculosis Meningococcal septicaemia Adrenalectomy Secondary tumor deposits Amyloidosis Haemochromatosis Histoplasmosis, tuberculosis, CMV, AIDS Adrenal haemorrhage Metabolic failure in hormone production

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Addison disease Autoimmune primary hypoaldosteronism. Most likely

due to cytotoxic T lymphocytes bt 50% have autoab eg 21OHAb, adrenal cortex autoab, steroid cell autoab, 17αOHAb

Isolated or associated with other autoimmune disease (autoimmune polyendocrine syndrome 1 & 2, primary ovarian insufficiency, Schmidt syndrome)

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Clinical presentationSkin & mucous membrane pigmentation (ACTH is melanocyte stimulating hormone - proopiomelanocortin). Scars before onset not affected Tiredness, progressive weaknessN & V, diarrhoea, weight loss, dehydration, hypotensionDizziness, orthostasisImpotence, amenorrhoeaLoss of body hair (F since adrenal major source of androgens) Myalgia, flaccid muscle paralysis from hyperkalemiaHistory of medications used

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Ix Aldosterone & cortisol low, high ACTH, high reninUECs: Low sodium , high potassiumACTH stimulation testAdrenal antibodies

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Treatment : Hydrocortisone 100 mg IV bolus, then 300 mg/day in divided doses every 8 hours or as a continuous infusion for 48 hours. When patient stable, change to oral, 50 mg every 8 hours for 6 doses, then taper to 30 - 50 mg/day.

Fludricortisone - minerallocorticoid

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Management Hormone replacement Life-long replacement therapy gluco +

minerallocorticoid• Hydrocortisone 20-30 mg daily PO e.g. 10 mg on

waking, 5 mg at12 00h, 5mg at 1800h• Prednisolone 7.5mg daily PO e.g 5mg on waking,

2.5mg at 1800h• 9α-fludrocortisone 50-300 |jg daily

Secondary adrenocortical insufficiency • Hormone replacement may also need T4• may also require more definitive treatment e.g.

surgical removal of a pituitary tumour.

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Adrenal crisis Acute adrenal insufficiency Medical emergency Acute in onset; can be fatal if not promptly recognized

and treated Clinical features :

• Severe hypovolaemia• Dehydration• Shock• Hypoglycaemia• possible mental confusion and loss of consciousness

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Causes : Precipitated by stress :infection, infarction, trauma or surgery in patients

with incipient adrenal failure/treated with glucocorticoids if dosage is not increased

Adrenal haemorrhage due to cx of anticoagulant treatment Meningococcal septicaemiaIx Plasma cortisol concentration

• <50nmol/L at 0900H → effectively diagnostic • >550nmol/L excludes the Dx

Plasma renin and aldosterone levels: low aldosterone high renin ACTH stimulation test :primary vs secondary adrenal insufficiency CRH stimulation test: hypothalamic vs pituitary plasma ACTH Metyrapone test

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ACTH stimulation test

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Adrenal crisis management Assuming normal cardiovascular functionOne litre of 0.9% saline should be given over 30-60 minutes with 100 mg of intravenous bolus hydrocortisone.Subsequent requirements are several litres of saline within 24 hours plus hydrocortisone, 100 mg i.m., 6-hourly, until the patient is clinically stable.Oral replacement medication is then started, unless unable to take oral medication, initially hydrocortisone 20 mg, 8-hourly, reducing to 20-30 mg in divided doses over a few days. Glucose if hypoglycaemic

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Congenital adrenal hyperplasia (CAH)Pathophysiology This condition results from an autosomal recessive

deficiency of an enzyme in the cortisol synthetic path ways.

6 types,most common is 21-hydroxylase deficiency which occurs in about 1/15 000 births

Due to defects on Xsom 6 near the HLA-region affecting one of the cytochrome p450 enzymes

Cortisol secretion is ↓and feedback leads to ↑ACTH secretion to maintain adequate cortisol →to adrenal hyperplasia.

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Diversion of the steroid precursors into the androgenic steroid pathways→ increased 17-hydroxyprogesterone, androstenedione and testosterone levels →virilization.

Aldosterone synthesis may be impaired with resultant salt wasting.

Other enzymes affected are:llfi-hydroxylase, 17a-hydroxylase, 3fS-hydroxysteroid dehydrogenase and a cholesterol side-chain cleavage enzyme (p450scc)

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Clinical features symptoms due 2 ↓ cortisol , & depending upon the site

of block, ↓ or ↑mineralocorticoids & androgen. If severe, presents at birth with sexual ambiguity or

adrenal failure (collapse, hypotension, hypoglycaemia), S’times with salt-losing state (hypotension,

hyponatremia). In female- clitoral hypertrophy, urogenital abnormalities

and labioscrotal fusion are common Precocious puberty with hirsutism is a later presen tation Milder cases only present in adult life, usually

accompanied by primary amenorrhoea.

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Investigations Expert advice is essential in the confirmation and

differential diagnosis of 21-hydroxylase deficiency17-Hydroxyprogesterone levels are increased.Urinary pregnanetriol excretion is increased.Basal ACTH levels are raised.

RX : Replacement of glucocorticoid activity, and mineralo-corticoid activity if deficient

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ADRENAL HYPERFUNCTION Cushing syndrome High Cortisol Hyperaldosteronism High aldestrone Pheochromocytoma High catecholamine

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Hyperaldosteronism Rare Can be: 1. Primary – hyporeninemic hyperaldosteronism. Causes : adrenal adenoma (Conn’s syndrome)60%, bilateral hypertrophy of zona glomerulosa 30%, adrenal caHypertension, renal K wasting, hypokalemic alkalosis2. Secondary – Hyperreninemic hyperaldosteronismCauses : CCF, Liver cirrhosis with ascites, nephrotic syndrome, renal artery stenosis, Na losing nephritis, renin secreting tumoursHTN, muscle weakness, paralysis, tetany, paraesthesia, polydipsia, polyuria, nocturia

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Investigations Electrolyte & BGAsHypernatremia, hypokalemia, alkalosis Plasma aldosterone:renin ratio in pmol/liter per

µg/(liter·h). Is a screening test

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Saline infusion test1.25l of 0.9% saline over 2 hrs. If aldosterone remains >240pmol/l Conn’s syndrome Plasma aldosterone morning sample pt recumbent since

waking and after 4 hrs of ambulation Urinary potassium loss > 30 mmol/day in hypokalemia. CT - adenoma vs hyperplasia MRI

RXSurgical excision for adenomaSpironolactone PO 100-400mg/day OD/BD S.E nausea, rash, gynecomastia

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Secondary hyperaldosteronism Arises when there is excess renin (and hence

angiotensin II) stimulation of the zona glomerulosa. Common causes asso. with hypertension

• accelerated hypertension • renal artery stenosis

Causes associated with normotension• congestive cardiac failure • cirrhosisExcess aldosterone production contributes to sodium


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Treatment Treatment for heart failure: Spironolactone is of value 25 mg/day has been

shown to improve survival in heart failure

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Cushing syndrome Group of symptoms occurring due to high cortisol. Cushing

disease is due to incr. ACTH production by pituitaryCauses:Exogenous/iatrogenic – intake of glucorticoids (most common)Endogenous – pituitary tumour - cushing disease 70%

nodular pituitary hyperplasiaadrenal tumour 15%ectopic ACTH tumours 15% bronchus, thymus,

pancreas, ovary

Pseudocushings is caused by alcoholism, anorexia nervosa, obesity, PCOS, severe depression thought to be due to HPA axis stimulation

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Clinical features


1. Weight gain (central) 2. Change of appearance 3. Depression,

Insomnia,Psychosis4. Amenorrhoea/

oligomenorrhoea5. Poor libido6. easy bruising7. Hair growth/acne8. Muscular weakness9. Growth arrest in children 10. Back pain 11. Polyuria/polydipsia

1. Moon face, Central obesity , Kyphosis 'Buffalo hump’(dorsal fat pad), exophthalmos (retroorbital fat)

2. Plethora3. Depression/psychosis4. Hirsuitism, Frontal balding (female)5. Thin skin,Bruising, Poor wound healing6. Pigmentation, Acne7. Striae (purple or red) 8. Skin infections- tinea versicolor9. Hypertension10.Osteoporosis, Pathological # (vertebrae and ribs)11.Oedema12.Proximal myopathy13.Glycosuria

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Ix 24 hr urinary free cortisol

Circadian rhythm 8am and 11pm (50% less) serum cortisol. Rhythm lost in cushing’s syndrome normal in pseudo cushing

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Low dose Dexamethasone suppression test0.5 mg Dexamethasone (oral) given 6 hourly for 2

days, blood for plasma cortisol collected 6 hour after last dose urine for UFC is collected before & on the 2nd day of DexaResult:UFC suppress by 50% ( < 70nmol/24h) normal plasma cortisol suppress < 140 nmol/L pseudo- Cushingno suppression of UFC & Pl. cortisol Cushing's synd

UECs hypokalemia, hypernatremia

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Investigating causeCRH testPlasma ACTHImaging : CT adrenal, MRI sella turcica, CT or MRI thorax & abdomen for ectopic ACTH tumour, radiolabeled octreotide

RXDepends on cause

Adrenal adenoma, Adrenal Carcinoma – resection, radiation

Cushing’s disease - transphenoidal hypophysectomy Drug ( block cortisol synthesis ) – metyrapone PO

750mg/day Q 6-8hrlyKetoconazole PO 200mg TDS

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Phaeochromocytoma Def: tumours of the sympathetic nervous system very rare <1/1000 cases of hypertension Rule of 10s

10% extradrenal10% familial10% malignant10% childhood onset10% bilateral

Some asso. with MEN 2 syndromes & the von Hippel-Lindau syndrome

Most tumours release both NE& adrenaline but large tumours & extra-adrenal tumours produce almost entirely NE.

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Pathology Oval groups of cells occur in clusters and stain for

chromogranin A. Of neural crest origin

Clinical features are those of catecholamine excess and are frequently

intermittent. Anxiety or panic attacks, Palpitations, Tremor,

Sweating, Headache, Flushing, Nausea and/or vomiting, Weight loss, Constipation or diarrhea, Raynaud's phenomenon, Chest or abd pain, Polyuria/nocturia.

Signs : Arrhythmias, Bradycardia, Orthostatic hypotension, Pallor or flushing, Glycosuria, Fever (Signs of hypertensive damage)

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Diagnosis: Measurement of urinary catecholamines and

metabolites. Normal levels on three 24-hour collections of

metanephrines virtually exclude the diagnosis. Resting plasma catecholamines are raised. Plasma chromogranin A (a storage vesicle protein) is

raised. Clonidine suppression and glucagon stimulation

tests may be appropriate Imaging : CT abdomen, MRI,Scanning with

[131I]metaiodobenzylguanidine (mlBG) which gives specific uptake in sites of sympathetic activity with about 90% success.

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Treatment Tumours should be removed if this is possible; 5-year

survival is about 95% when not malignant Medical pre-op and peri-op Tx is vital

Complete α & ß blockade with phenoxybenzamine (20-80 mg daily initially in divided doses)

then propranolol (120-240 mg daily), plus trans fusion of whole blood to re-expand the

contracted plasma volume. When operation is not possible, α & ß blockade can be

used long term. Radionucleotide treatment with mlBG has been attempted

with limited success over 10% recur or develop a further tumour- Catecholamine excretion measurements at least annually.

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REFERENCES Davidsons Principles and practice of medicine Current medical diagnosis and treatment Upto date http://www.endocrinology.orgUK Society of Endocrinology http://www.endo-society.orgEndocrine Society Pituitary Foundation (UK charity) Medscape