Cushings, Addisons and Acromegaly

Cushings, Addisons and AcromegalyDr Edward Hutchison FY1 (Geriatrics)Phase II Objectives3.21: Investigations Request appropriately the more common tests of thyroid, adrenal and pituitary gland function, seeking advice where necessary.3.23: Adrenal gland hormones Recognise signs and symptoms of Addisons disease, confirm diagnosis and initiate immediate management of Addisonian crisis.Recognise symptoms and signs of Cushings syndrome, confirm diagnosis, participat in management of Addisons disease and Cushings syndrome.3.24: Pituitary gland hormonesRecognise the circumstances when hypopituiarism might occur, recognise possibility of hypopituitism with non-specific symptoms, investigate causes.Initiate investigation for posterior pituitary function in patients with polyuria.Recognise acromegaly, initiate investigation for acromegaly, outline to patients the possible treatments for acromegaly.AimsHPA AxisAdrenal glandsCushings syndrome/diseaseAddisonsAcromegalyHPA Axis

Hypothalamus

GnRHTRHDopamineCRHGHRHThe hypothalamus controls body temperature, hunger, important aspects of parenting behaviours, thirst, fatigue, sleep and circadian rhythms.6Pituitary

Sphenoid sinusPituitary gland communicates with the hypothalamus via the hypophyseal tract.Split into anterior and posterior.Blood supply: hypothalamo-hypophyseal portal system7ACTH adrenal glands gluco/mineralocorticoidsFSH granulosa/sertoli cells follicle growth/spermatogenesisLH theca/leydig cells oestrogen/testosterone productionPRL milk productionTSH stimulates thyroxine/triiodothyronine productionGH many effects (discussed later)8Adrenal Glands

Remember:GFR!Cortex split into glomerulosa, fasciculata and reticularis aldosterones, cortisol and androgens respectively.

Medulla secretes catecholamines under control of the sympathetic nervous system.10Functions of Cortisol?Insulin resistance/gluconeogenesisProtein catabolismImmunosuppresionCVS regulation e.g. increasing BPCNS actions e.g. increased appetite, impaired memoryIncreased bone turnoverGastric acid secretionReduced skin collagenFluid retention Right, now onto the stuff you actually want to knowCushingsdisease or syndrome?

Which is which?SyndromeDiseaseExcessive activation of glucocorticoid receptors.Excessive production of ACTH caused by a pituitary adenoma.

ClassificationACTH-dependentPituitary adenomaEctopic ACTH production e.g. small cell lung cancer, neuroendocrine tumoursIatrogenic ACTH therapyACTH-independentIatrogenic steroid therapyAdrenal adenoma/carcinomaPseudo-CushingsEtOH excessMajor depressive disorderPrimary obesityClinical featuresOver to you

SymptomsDepressionConfusionWeight gainPoor glucose control (diabetics)Weakness rising from a chair (proximal myopathy)InvestigationBedsideBloodImaging?EtOH excessNot excludedAbstinence

Overnight dexamethasone test give 1mg dexamethasone PO at midnight then measure 0900hrs cortisol. Cortisol 75% of morning indicates Cushings.Insulin tolerance test (NOT ROUTINELY PERFORMED) peak plasma cortisol >120% excludes Cushings.Inferior venous petrosal sampling catheters placed in both inferior petrosal sinuses, sampling these and peripheral blood for ACTH. ACTH in petrosal sinus >200% peripheral ACTH indicates pituitary disease, 460nmol/L at 30 minutesManagementGlucocorticoid replacementHydrocortisone BD, usually 15mg on waking/5mg around 1800hrsExcessive weight gain = over replacementEducate patient increase hydrocortisone when unwellMineralocorticoid replacementFludrocortisone 50-100g dailyTitrate according to symptoms and U&EsAddisonian CrisisFeatures:Severe shock hypotension, tachycardiaFever, abdominal pain, nausea & vomitingHyponatraemia/hyperkalaemia hypercalcaemia, hypoglycaemiaManagement:ABCDE assessmentCorrect volume depletionReplace glucocorticoidsCorrect metabolic abnormalitiesTreat underlying cause

Fludrocortisol is not needed during acute managementHyperkalaemia usually responds to fluid therapy but may need specific interventionCorrect volume depletion with 0.9% NaCl avoid when Na