Pituitary, thyroid, adrenals, enzymes and metabolic disorders - PowerPoint Presentation

1. Pituitary, thyroid, adrenals, enzymes and metabolic disordersChem Path 2Dr Vlad Makeev

2. The purpose of this talk Give you an overview of the important topics regarding to some (not all) of chemical pathologyRevise some basic physiology relevant to the above Emphasise the concept of a structured approach to examination answers Hopefully make you feel more comfortable with pathology in generalThis talk will not:Provide intense details on all pathology pertaining to a particular topic Provide you with every bit of information you need to get a distinction Cover the minutiae

3. Outline2 sections with questions at the end of each sectionSection 1ThyroidPituitarySection 2AdrenalsDiabetesMetabolic disorders

4. Learning objectivesAnterior pituitary hormones: recall the six anterior pituitary hormones and explain the hypothalamic factors responsible for their controlPlasma protein function: summarise the functions of commonly measured plasma proteins and explain factors that contribute to their concentrationCori cycle: explain the Cori cycleInsulin: explain the synthesis, storage, secretion and physiological actions of insulin incl. the role of c-peptide, and homeostatic mechanisms of controlGlucose homeostasis: explain the factors regulating blood glucose incl. counter-regulatory mechanismsPorphyrine metabolism: summarise the principles of porphyrine metabolismAdrenal physiology: summarise adrenal function, histology, microanatomy and zonationCholesterol and lipoprotein metabolism: summarise cholesterol and lipoprotein metabolism and explain the link between lipid disturbance and cardiovascular diseaseRenal physiology: define glomerular filtration rate (GFR) and compare different methods of GFR assessmentRenal physiology: explain why serum creatinine alone is a poor marker of absolute kidney function, and why a normal serum creatinine does not mean that renal function is normalThyroid physiology: summarise thyroid physiologyEnergy metabolism: summarise energy metabolism incl. protein, lipid and carbohydrate metabolismPurine metabolism: summarise the basics of purine metabolismEnzymes: summarise the roles of enzymes in body metabolism and recognise the effect of organ-specific/biochemical disease on plasma levels of enzymes and subsequent outcomesTherapeutic drug monitoring: interpret the factors affecting serum levels for a given dose (pharmacokinetics) and those factors affecting response to a drug at its active site (pharmacodynamics)Therapeutic drug monitoring: explain the concept of a therapeutic range and demonstrate awareness of its limitationsTherapeutic drug monitoring: list examples of drugs which require measurement of levels, for therapeutic and toxic reasons e.g. anticonvulsants, lithium, digoxin and theophyllineMetabolic disorders and screening: recognise how prevalence, predictive values, sensitivity and specificity relate to disease and diagnostic tests of diseaseMetabolic disorders and Screening: demonstrate awareness of current UK screening for inherited metabolic disorders and future prospects incl. Phenylketonuria (PKU)

5. ThyroidThyroxine is important for:Regulating basal metabolic ratePotentiating responses to catecholamines

6. HypothyroidismAetiologyAutoimmunePrimary atrophic (no goitre)Hashimoto’s (goitre and anti-TPO/TG)OtherIodine deficiencySurgery/radioactive ablationDrugs: amiodarone, lithium, carbimazoleSymptoms/SignsWeight gainCold intoleranceDepressionDry skinHair loss FatigueConstipationBradycardia

7. HypothyroidismInvestigations:Bloods including TSH and T4Addition of other hormone panels if indicated Imaging is in the form of central if ?secondary disease ManagementOral levothyroxineTitrate to normal TSH with 6 weekly check ups until stableEnsure no signs of over-replacement - palpitations Higher doses may be needed in pregnancy, nephrotic syndromeI.V LiothyronineOnly for Myxoedema coma

8. Additional thyroid statesSick euthyroidPre-hypothyroidPituitary gland can compensateHigh TSH, normal T3/4If positive anti TPO Ig then higher risk of hypothyroidism laterSubclinical hypothyroidismSevere illnessBody tries to shut down metabolismTo conserve energyLow T3 and T4Initially high TSH, then low TSHHave similar TFTsOnly way to differentiate is based on clinical picture

9. HyperthyroidismAetiologyAutoimmune - Graves’De Quervain’sNeoplasm - Thyroid adenomaDrug induced - AmiodaroneToxic multinodular goitrePostpartum Symptoms / Signs: Weight lossIrritabilityHeat intolerancePalpitationsIncreased appetiteGoitreGraves specificPretibial myxoedema, graves’ orbitopathy Investigations:Bedside - ECG (?AF)Bloods - U+Es, TFTs, antibodies Anti-TSHR)Basic imagingUSSAdvanced imagingThyroid uptake scan (radiolabelled iodine)

10. Hyperthyroidism ManagementConservativeSmoking cessation MedicalCarbimazole or PropylthiouracilTitrate or block & replaceTx Usually for 18 monthsBeta-blockersLugol’s iodine Radio-iodineSurgicalHemi/Total thyroidectomyMust be euthyroid before surgery

11. Pituitary massPituitary adenomaMacroadenoma >1cmUsually non-functionalOccasionally can be associated with hyperprolactinaemiaMicroadenomaMore likely to be functionalGH or Prolactin secretingLead to Acromegaly Symptoms:Bitemporal hemianopiaProlactin related:Galactorrhoea,Gynaecomastia,Oligo/amenorrhoea, loss of libido, Impotence. Somatotrophin relatedAcromegaly - Soft tissue growth (Hands, feet, tongue), Organomegaly, Symptoms of heart failure, hypertension, DiabetesCarpal tunnel

12. Pituitary massInvestigation:ImagingAcromegalyGlucose tolerance test Measurement of GHPlasma IGF-1ProlactinomaSerum prolactin levels (>6000)Management:MedicalOctreotide (Somatostatin analogue)Cabergoline or bromocriptine (Dopamine agonist)Pegvisomant (GH Receptor antagonist)RadiotherapySurgicalTrans-sphenoidal debulkingMonitoringSerum GH / Prolactin levelsBowels (acromegaly)

13. Thyroid tumoursCommonest: papillaryThen: follicularGood prognosis5% medullaryC-cells that produce calcitoninLinked to MEN2 (see histo)Lymphoma Risk in Hashimoto’sAnaplasticElderly, undifferentiatedPoor prognosisPapillary & FollicularSurgery +/- radio-iodineReplace thyroxine to completely suppress TSHMonitor thyroglobulin levels13Klatt, E., Robbins, S. and Cotran, R. (2015). Robbins and Cotran atlas of pathology. Philadelphia: Elsevier/Saunders.Psammoma body

14. The (anterior) Pituitary14Laycock and Meeran 2012

15. HypopituitarismAetiology:MalignancyPituitary adenoma*CraniopharyngiomaWeird & WonderfulInfectionTBSyphilisInfiltrationSarcoidLymphoma IatrogenicSurgical / Traumatic / radiationInfarct Sheehan’s or ApoplexyTertiary (rare!) Symptoms/signs:GenericLethargyWeight gainHypotensionHair loss MyalgiaSex hormonesImpotence (men)Loss of libido Oligo/amenorrhoea ACTHAddisonian crisisTSHMyxoedema coma

16. CPFT: combined pituitary function testGive a patient GnRH, TRH and insulinMeasure levels of pituitary hormones every 30 mins for 2hGHCortisolTSHLHFSHProlactinVarious normal rangesCheck to see if an adequate responseFSH/LH only applicable after pubertyPoor response can indicate hypopituitarism16NB: Acromegaly needs an oral glucose tolerance test to diagnoseMeasurement of IGF-1 is sensitive but not specific

17. HypopituitarismInvestigationScreening9am cortisol / salivary cortisolTFTsSerum testosterone/oestrogenCombined pituitary function testAdminister LHRH + TRH + Induce hypoglycaemia Measure LH, FSH, TSH, ACTH and growth hormone for 2 hours at half hourly incrementsImaging CT/MRI ManagementReplacement of end hormones - much cheaper and easier to controlHydrocortisone No need for fludrocortisoneThyroxineOestrogen / Testosterone Cause specific Adenoma Next sectionInfiltrationSteroids InfectionAntibiotics as needed

18. Halfway questions and break22/02/202218MentimeterCode4272 1861Feedback link:https://forms.office.com/r/VYYRE1Wxmt

19. AnswersA woman has diarrhoea, sweating, fever and palpitations for the last week. Bloods show low TSH and high thyroxine. She does not have good uptake on technetium scan. Which blood marker is monitored to check for recurrence of papillary thyroid carcinoma post resection?What antibodies are tested for in the laboratory diagnosis of Hashimoto's thyroiditis?Which medication is used for hyperthyroidism?De Quervain’sThyroglobulinAnti TG and TPOCarbimazole22/02/202219

20. AnswersCommonest cause of hypothyroidism in the UK?Commonest thyroid cancer?Hashimoto’sPapillary (memory aid: papillary = popular)22/02/202220

21. 22/02/202221

22. AdrenalsThe adrenal gland is divided into zones which provide different steroid hormones:Glomerulosa - Mineralocorticoids (Aldosterone)Fasciculata - Glucocorticoids (Cortisol)Reticularis - Sex hormonesMedulla – Catecholamines“the closer to the middle, the sweeter it gets”

23. Addison’sAetiology:PrimaryIatrogenic AutoimmuneTB InfarctMalignancySecondaryPituitary Signs/Symptoms:Postural symptoms Weight loss, anorexiaFatigueVomiting, salt cravingSkin/Mucosal pigmentation (*)*Schmidt’s Syndrome

24. 24Investigations:9am Cortisol (>350 excludes addisons)Electrolytes (Hyponatraemia, Hyperkalaemia). Serum ACTHCheck glucoseSynacthen test Synthetic ACTH administered IV/IMCortisol readings at 0, 30, 60Only rises in secondary diseaseManagementHydrocortisoneSick day rulesFludrocortisone

25. Cushing’sAetiologyPrimaryAdrenal malignancySecondaryPituitary adenoma Ectopic/Paraneoplastic ACTH (SCC Lung Ca) IatrogenicInvestigationsDexamethasone suppressionLow dose - confirms Cushing’s syndromeHigh dose - Helps to determine Cushing’s syndrome from disease ImagingCT CAP / AdrenalsMRI pituitary ManagementPrimaryAdrenalectomy +/- steroid replacement*Nelson’s syndrome Pituitary adenoma MxEctopic - Cancer Mx Ketoconazole / Metyrapone / Mifepristone

26. Conn’sAetiologyAdrenal hyperplasiaAdrenal adenoma / carcinomaSymptoms/SignsTreatment resistant hypertensionHypokalaemiaHypernatraemia InvestigationsBloods - electrolytes, plasma aldosterone:renin ratio (raised) Adrenal vein samplingImaging Treatment:Aldosterone antagonistsSurgery

27. Conn’s and PhaeosConn’s syndromePulses of hypertension, arrhythmias, sweatsMeasure 24h urine catecholaminesFormerly vanillylmandelic acid (VMA)Adrenal medulla tumour : adrenalinePeripheral neural tumour : noradrenalinePhaeochromocytomaAdrenal hyperplasia or tumourHypertensionHigh sodium, low potassiumMeasure aldosterone:renin ratioHigh in Conn’s syndromeTreat with spironolactone and possibly adrenalectomy27

28. PhaeochromocytomaAssociated with:MEN-2(A/B)NF-1VHLSymptoms/Signs:Episodes of “impending doom”/Panic Resistant hypertensionInvestigationsUrinary/Plasma nor/metanephrinesFalse positives - TCAs, CCBs, Beta-blockersImagingManagementAlpha blockadePhenoxybenzamine Beta blockadeSurgery

29. 3 x P2 x P1 x M1 x P3 x MWikipedia

30. DiabetesFeatureType I Type IIHabitusLeanObesePlasma insulinLowVariableB cell function AbsentPresentB cell antibodiesPresent [ICA, IAA, GADA, IA-2A]AbsentFamily historyAbsent [usually]Present [usually]Ketosis prone YesNoWeight lossYesNoPrevalence0.25%4-7%HLA associationsDR-3 or 4NoneEthnicities Europeans Asian, AfricanAgeYoung / Adolescent (can be old – LADA)Middle age (Can be and is increasing in young)OnsetAcuteGradual

31. DiagnosisDiagnosis = symptomatic + one of the above test being positiveBe wary in using HbA1cPre-diabetesDiabetesFasting blood glucose6.1-6.9>7OGTT7.8-11>11.1HbA1c42-47>48 (6.5%)Random BM7.8 - 11>11.1

32. ManagementType 1ConservativeLifestyle advice (alcohol)Diabetes nurse reviewDietary adviceMedicalInsulinBasal bolus Insulin pumpBiphasic OD/BDMetformin if BMI >25SurgicalSPK (Single pancreas kidney transplant)Type 2Conservative Diet + Lifestyle adviceExercise MedicalMetforminAdd one of:SulphonylureaDPP-4 agonistsSGLT-2 inhibitorsAdd GLP-1 antagonist or two of aboveInsulinSurgicalBariatric surgery

33. Hyperglycaemic hyperosmolar state (HHS) Predominantly type II diabeticsInsulin resistance causing persistent hyperglycaemia Osmotic diuresis results Takes days to fully developPresents as:Confusion Clinically very dehydrated (Patients lose up 10-20% of body weight in water)Investigations:Raised serum osmolality (>320) Glucose >30NO ketones / acidosisTreatment:IV Fluids Aim +3-6L/24h NaCl +/- KCl MonitoringElectrolytes (Na, K)Beware of rapidly over-correcting hypernatraemiaBMs + KetonesBMs should fall at around 5mM/hNeurological statusInsulin (0.05u/kg FRII)Only needed if Ketones rising or if BMs no longer falling with just fluids

34. DKAPredominantly type I diabeticsA state of absolute insulin deficiency regardless of whatever insulin is present in the body Body thinks it’s starving despite hyperglycaemiaUnregulated ketosis results with subsequent acidosisResults in polyuria, dehdyration and circulatory shockSigns / SymptomsConfusionAbdominal painVomitingConfusion / drowsinessKussmaul breathingCausesInfectionSurgeryAlcoholMissed insulinTrauma

35. DKAInvestigations:Ketones >3pH <7.3BM >15Find the cause:FBC, blood Cultures, CXR, Urine culture/dip, Find the damageU/Es, A/VBG, ECG Treatment:FluidsDeficit + Maintenance/24hrRapid initial administration then taperPotassium (If K+ <5.5)Intravenous Insulin (0.1u/kg)Continue normal s/c insulin!10% DextroseWhen BM <15 MonitoringCatheter Accurate urine output neededAt least 0.5ml/kg/hr Hourly Ketones + BMKetones should drop by 0.5/hHourly VBGK+ and bicarbonateKeep potassium >4ResolutionKetones <3pH > 7.3Stop FRII when back E+D and has had normal insulin 1h ago

36. Porphyria

37. MentimeterCode: 3768 4640

38. Practice QuestionA 55 year old patient presents with low blood pressure, increased pigmentation of skin creases, low glucose, low sodium and high potassiumWhat is the best investigation to order to confirm the likely diagnosis?38

39. Practice QuestionA patient presents with new-onset type 2 diabetes, an enlarged jaw and forehead and carpal-tunnel syndrome. Which investigation would be most useful to diagnose the likely cause?Short SynACTHen testCombined pituitary function testMeasurement of plasma [growth hormone]Low-dose dexamethasone suppression testOral glucose tolerance test39

40. Both mother and grandmother had medullary thyroid carcinoma, and have tested positive for MEN2. What [biomarker/protein] would be raised in the blood to confirm medullary thyroid cancer?

41. A 24-year-old female is brought into the emergency department with a 3-day history of abdominal pain, vomiting, polyuria and reduced eating and drinking.She has T1DM and usually takes both long and short acting insulin.pH 7.32Ketones 5BM 20Along with an appropriate fluid regime what other management should be started?

42. Feedback link:https://forms.office.com/r/VYYRE1WxmtThank you very much!