Endocrinology in Primary Care. HN Buch

Transcription

1 Endocrinology in Primary Care HN Buch

2 Endocrinology in Primary Care Death by Powerpoint HN Buch

3 Agenda Endocrine Condition Primary v Secondary Care Initial management Follow up Focus of Discussion Hypothyroidism Largely primary care Primary care Pitfalls in management Hyperthyroidism Secondary care Secondary care Pre-referral management Hyperparathyroidism Most need referral Many in primary care Follow up strategy Hyperprolactinaemia If true all need referral Some in primary care Check list prior to referral

4 Hypothyroidism is Easy Aetiology is either autoimmune or iatrogenic: Surgery, RAI and it does not affect the treatment Easy to diagnose High prevalence: 2% in women, 0.1% of men Well recognised clinical features Easy-to-interpret, cheap test - high TSH and low FT4/FT3 No need for imaging

5 Hypothyroidism is Easy Easy to manage Cheap treatment Single agent (T3, armour thyroid etc have no advantage) No significant interactions Treatment can be easily monitored with TSH Most patients respond well to treatment; those that do not, do not respond to much else!!

6 Hypothyroidism is Easy Start mcg; 25mcg in cardiac patients or elderly Weight based regimes offer no advantage Adjust at intervals not shorter than 6-8 weeks Aim to maintain TSH in the lower half of reference range If >200mcg is required consider Suboptimal compliance Malabsorption

7 Hypothyroidism is Easy

8 Diagnostic pitfalls Not Always Easy!

9 Case 1 34/F, recurrent hyperthyroidism Received radioiodine therapy (RAI) FT4 (10-22) FT3 ( ) TSH ( ) Pre RAI 2/12 post <0.01 <0.01 Persistent Hyperthyroidism FT4 (10-22) FT3 ( ) TSH ( ) Pre RAI 4/12 post <0.01 <0.01 Post-RAI Hypothyroidism

10 Case 1 During transition from hyperthyroidism to hypothyroidism only TSH is not enough to diagnose hypothyroidism

11 Case 2 61/male, presented with lethargy, tiredness, weakness /12 after CABG UE/LFT/Bone/FBC normal/vitamin D 19 TSH 1.1 ( ) Started on vitamin D but no improvement 3/12 later represented with reduced right eye vision Ophthalmology: optic nerve dysfunction with VF impairment MRI: larger pituitary tumour

12 Case 2 Initial 2/12 later FT4 7.2 FT3 3.6 TSH Peak Synacthen cortisol: 298 Testosterone (4.5-28) 3.1 MRI: Normal but smaller pituitary gland Diagnosis: Hypopituitarism possibly secondary to hemodynamic instability during CABG

13 Case 2 TSH is not enough to diagnose secondary hypothyroidism

14 Case 3 56/M, presented with lethargy and TSH was 7.6 Started on thyroxine 50 3/12: bumping in to people MRI showed a large pituitary tumour on MRI

15 Case 3 Full TFT: TSH: 7.6 T 4 : 31 (10-22) T 3 : 7.2 ( ) Diagnosis: TSH producing Pituitary macroadenoma

16 Case 3 High TSH is not always due to hypothyroidism Other causes Drugs TSHoma Adrenal insufficiency

17 Cases 1, 2 and 3 All patients with hypothyroidism do not have high TSH and all patients with high TSH do not have hypothyroidism

18 Cases 1, 2 and 3 Although TSH alone is sufficient for the diagnosis and treatment monitoring of primary hypothyroidism most cases, full TFT should be requested in patients Who are in transition from hyperthyroidism With clinical suspicion of pituitary pathology

19 Not Always Easy! Management challenges

20 Case 3 22, male, university student 2/12 history of lethargy, dizziness and 2 kg weight loss TSH: 80mU/L ( ); FT 4 : 8.2pmol/L (12-22) TPO 1:1000 Diagnosis: Autoimmune hypothyroidism Thyroxine 75mcg, increased to 125mcg over 3/12

21 3 months later Clinically and biochemically well replaced TSH 1.7mU/L, FT 4 16pmol/L However not feeling well Further 2kg weight loss More dizzy Haemoglobin 12.4 LFT Normal S Creatinine 0.78 Calcium 9.8 S Na 143 CXR Normal S K 5.4 ECG Normal

22 Diagnostic Test was Performed Short synacthen test (ACTH 250mcg IV) Autoimmune Polyglandular Syndrome 2 Time (min) Cortisol APS 1 APS ACTH-128 (8-60) Diagnosis Addison s disease + Primary Hypothyroidism Inheritance AR, no HLA Polygenic DR3/DR4 Age Infancy/childhood Adult Gender M=F F>M Major conditions Addison s Hypoparathy MC candidiasis (~90% each) Addison s (100%) Thyroid (70%) T1DM (50%)

23 Management Hydrocortisone PO 10mg immediately on rising, 5mg at midday, 5mg at 5pm Fludrocortisone 100mcg Thyroxine 100mcg Excellent clinical response Absence of clinical response despite achieving biochemical target should prompt a search for additional pathology especially autoimmune

24 Case 4 38, businessman Bronchial asthma on inhalers Anaemia on iron supplements for 12 months Lethargy, weight gain TSH: 38mU/L, FT 4 : 10.1pmol/L, TPO positive Thyroxine commenced

25 THYROXINE DOSE TSH (mu/l) ft4 (pmol/l) Diagnosis mcg months later TTG antibodies and D2 biopsy: Coeliac disease Gluten free diet instituted 250 <

26 If suboptimal biochemical response despite escalating thyroxine dose, consider poor adherence or absorption Absorption Diet: Ingestion after meals, soya milk, prunes, herbal remedies Gastrointestinal: Coeliac or any other cause of malabsorption Drugs: Cholestryramine, Colestipol, Lovastatin, Non-compliance

27 Case 5 27/F, hair loss, dry skin, mild weight gain (6/12) T , TSH 8.1 No treatment given More information? Any drugs Radioiodine TPO 1:126 Options Treat with thyroxine No treatment, monitor TFT TSH ( ) FT4 (10-22) FT3 ( ) Dx 4/12 12/12 24/

28 Case 5 Diagnosis: Subclinical hypothyroidism A biochemical diagnosis ( TSH, normal T 4 /T 3 ), 2-4% Possible causes Impending thyroid failure; 2% p.a. progress to hypothyroidism Drugs e.g. amiodarone Normal

29 TSH distribution curve TSH mu/l Euthyroid people

30 Treat or Not to Treat No convincing evidence of beneficial effect on Symptoms CV outcomes despite association with risk factors Treat, if the lifetime risk of overt hypothyroidism is high TSH >10 (10-15% per annum) TPO or associated AI conditions (5-10% p.a.) Post RAI >80% risk over 10 years Pregnant or pregnancy is planned Consensus guidelines, 2005, ATA & AES

31 Case 6 24/F, recently married, presents with weight gain (Endo clinic) T 4 : 10.5 (12-22), TSH 12.1 ( ), TPO + Commenced on T4 50mcg 75mcg T 4 : 17.3 (12-22), TSH 1.4 ( ) discharged to PC 6/12 TFT 6/12 later: 7/40 pregnant T 4 : 11.3 (12-22), TSH 7.4 ( ), Thyroxine increased: 75mcg 125mcg 12/40 - T 4 : 17 (12-22), TSH 3.1 ( ),

32 Case 6 Why was her management sub-optimal during the initial hospital consultation? Patient should have been advised to thyroxine dose by 25-50mcg as soon as pregnancy was confirmed Why?

33 hcg induced in maternal T4 Fails in patients with atrophic thyroid Subtle neurodevelopment deficiencies in baby in demand of maternal T4 Placenta is relatively impermeable to thyroxine Foetus is entirely dependent on maternal T4 until mid-gestation

34 Pregnancy and Hypothyroidism Maternal Foetal Optimum Management Sub-fertility Pre-eclampsia, preterm birth, higher CS rate (overt HT) Neurodevelopmental disorders with lower IQ Maintain TSH <2.5 during the period leading up to pregnancy When pregnancy is confirmed increase thyroxine by 30-50% proactively Close follow up; optimise thyroid status 4-8 weekly intervals

35 Conclusions Please manage hypothyroidism in PC but consider referral if: TFT are discordant Central (secondary) hypothyroidism is suspected Suboptimal clinical/biochemical response to T4 Patient is considering pregnancy or is pregnant Associated multiple autoimmune conditions Uncertainty in some of the patients with subclinical hypothyroidism

36 Do Not Ignore Hypothyroidism Researchers determined that the 6/12 Republican presidents over the past 50 years had an average IQ of 115.5, with President Nixon having the highest at 155. President Bush (Jr) had the lowest at 91. Why?

37 All 3 in this photo had thyroid dysfunction

38 Hyperthyroidism Well recognised clinical symptoms and signs High T4/T3 and suppressed TSH Please refer all patients No need for US or RN scan prior to referral Please initiate treatment in patients with significant clinical or biochemical hyperthyroidism

39 Pre-referral Treatment Initiation Carbimazole (CMZ) 40mg od Warn about agranulocytosis Beta-blockers as appropriate; the only treatment in patients with mild rise T4 and no symptoms If rashes Propylthiouracil 200mg BD If agranulocytosis or hepatitis not for PTU; urgent referral

40 Caveats Request urgent review Pregnant Significant thyroid eye disease Active CV/psychiatric disorder Agranulocytosis or hepatitis to CMZ Do not start treatment if No symptoms + mild rise of T3/T4 Discordant biochemical picture Tender goitre with fever and raised ESR Post RAI

41 Hyperthyroidism CMZ 40 ± -blockers 6-8/52: euthyroid Autonomous nodule(s) Graves disease (+? aetiology) Patient preference RAI Surgery Indefinite low-dose ATD Relapse (50-70%) Block/replace (6/12) Titration (18/12) Remission (30-50%)

42 Aetiology 5 min uptake= 6% 5 min uptake= 0%

43 Case 7 79/F Routine testing: T4 17.1, TSH What next? FT3 6.7 ( ) Diagnosis: T3 toxicosis; management is identical to hyperthyroidism with high T4

44 Case 7 79/F Routine testing: T4 17.1, TSH What next? FT3 5.1 ( ) Diagnosis: Sub-clinical hyperthyroidism Increases risk of AF and osteoporosis but no treatment as no convincing intervention data 6-12 monthly TFT

45 Hyperthyroidism FT4, TSH Both normal Normal FT4 & suppressed TSH High FT4 & suppressed TSH No further tests FT3 Thyrotoxicosis Normal Subclinical hyperthyroidism High T3 Thyrotoxicosis

46 Primary Hyperparathyroidism Diagnosis High calcium High PTH Much less common possibilities: Tertiary hyperparathyroidism (End-stage renal failure, long-standing severe vitamin D deficiency) Genetic conditions: hypocalciuric hypercalcaemia

47 Primary Hyperparathyroidism (PHPT) Should all patients be referred? Yes Should all patients be followed up in specialist care? No

48 PHPT: Endocrine Clinic Confirm diagnosis: repeat calcium, PTH Age H/O fractures, fracture risk (DEXA, FRAX) H/O renal stones, KUB imaging egfr Vitamin D status Needs surgery Endocrine follow-up Indications for surgery May need surgery Endocrine follow up ~2 years Does not need surgery Discharge for annual primary care follow up What needs monitoring?

49 Indications for Surgery Age <50 Calcium>2.85 Fragility fracture or vertebral fracture BMD <-2.5 Renal calculi Decline in egfr to <60 (High urinary calcium)

50 Primary Care Follow Up Surgery is not likely to be required in foreseeable future Annual calcium Ensuring adequate vitamin D replacement Re-referral If serum calcium rises to >2.80 New onset symptoms, osteoporosis, fractures and renal stones/dysfunction

51 Hyperprolactinaemia Cause Prolactin level Macroprolactinoma ,000 mu/l Microprolactinoma Other large non-functioning pituitary tumours with compression on the pituitary stalk Up to 2500 mu/l Drugs Miscellaneous: stress, PCO

52 Hyperprolactinaemia Exclude macroprolactin Repeat PRL Exclude hypothyroidism Drug history Not MRI If persistently high PRL and euthyroid refer Urgency dictated by visual symptoms

53 Macroprolactinaemia Not to be confused with macroprolactinoma Biologically inactive large molecules of PRL and IG Routinely measured in all patients with high prolactin High total PRL with normal monomeric PRL no action needed

54 Agenda Endocrine Condition Primary v Secondary Care Initial management Follow up Focus of Discussion Hypothyroidism Largely primary care Primary care Pitfalls in management Hyperthyroidism Secondary care Secondary care Pre-referral management Hyperparathyroidism Most need referral Many in primary care Follow up strategy Hyperprolactinaemia If true all need referral Some in primary care Check list prior to referral

55 Conclusions Endocrine Condition Primary v Secondary Care Initial management Follow up Conclusions Hypothyroidism Largely primary care Primary care Limitations of TSH Hyperthyroidism Secondary care Secondary care Carbimazole 40 Hyperparathyroidism Most need referral Many in primary care Surgery v observation Hyperprolactinaemia If true all need referral Some in primary care Exclude macroprolactin

56 La Fin

57 Agenda Endocrine Condition Primary v Secondary Care Focus of Discussion Hypothyroidism Managed in primary care; only a few need referral Pitfalls in management Hyperthyroidism All need referral Pre-referral management Hyperparathyroidism Prolactinomas Most need referral but many can be followed up in primary care If true hyperprolactinaemia need referral; some can be followed up in primary care Follow up strategy Check list prior to referral

58 Take Home Message Consider thyroiditis in patients with Spontaneously fluctuating thyroid status Significant thyroid dysfunction with disproportionately less symptoms Tender inflamed thyroid Appropriate setting Post partum Sub-acute thyroiditis Post-RAI

59 Subclinical hypothyroidism 27/F Aches and pains Weight gain 4 kg in 1 year No relevant PH, FH OCP FT4 15.6, TSH months later: FT4 16.1, TSH 6.6

60 Subclinical hypothyroidism Treat or not to treat

61 Subclinical hypothyroidism Causes Recent onset thyroid failure Drug induced: amiodarone, antiepileptics Hypocortisolism Heterophile antibodies Normal

62 Subclinical hypothyroidism Treat if TSH>10 TPO antibodies strongly positive Post RAI Pregnant or planning pregnancy Not for symptoms in absence of above

63 Hyperprolactinaemia Exclude macroprolactin Repeat prolactin with other relevant investigation Baseline biochemistry: UE, LFT Repeat prolactin, testosterone/oestradiol, FSH, LH, TFT Not for MRI If persistent hyperprolactinaemia with euthyroidism refer with urgency dictated by recent onset visual symptoms

64 Pre-referral Check-list Confirm persistently high levels Exclude hypothyroidism Exclude drug related causes and withdraw if possible Exclude macroprolactin

65 Isotope scan Ocassionally Technetium, simple, harmless Contraindicated during pregnancy Indications to request: Hyperthyroid patient when low uptake state is suspected Graves disease Solitary nodule Thyroiditis/factitious

66 Grave s Disease Incidence 2-3 per 1000 per year (Sex ratio 5:1) Prevalence 1.9% female, 0.16% male 90% of patients have a diffuse painless goitre Autoimmune driven conditiona Spontaneous remission in around 50% of patients after months on ATD Other manifestations of Graves disease?

67 11/10/06

68 Multi-nodular goitre Common cause of hyperthyroidism in the elderly No spontaneous remission 11/10/06 68

69 Hyperthyroidism CMZ 40 OD + -blockers 4-6/52: euthyroid Autonomous nodule(s) Patient preference Graves disease (+? aetiology) RAI Surgery Indefinite ATD Relapse (50-60%) ATD B/R 6/12 or Titration 18/12 Remission (40-50%)

70 Case 5 24 year, housewife Delivered a baby boy 5 months ago Presented to GP with 2 week history of tiredness, some weight loss, mood changes although better for last 4 days Suspected to be hyperthyroid FT4: <5 pmol/l (9-19), TSH: >100mU/L ( )

71 Case 5 Endocrine clinic: 2/52 No clinical signs of thyroid dysfunction No goitre TPO antibodies: negative FT4: 6.2 pmol/l (9-19), TSH: >100mU/L ( ) No treatment

72 Case 5 FT4 (9-19pmol/L) TSH ( mU/L) At presentation <5 >100 2/ / / /

73 Case 5 Diagnosis Post-partum thyroiditis Presenting with hypothyroidism

74 Post partum thyroiditis Incidence: 5-10% pregnancies Histopathology: Inflammation with an autoimmune basis Clinical presentation at 3-12 months post-partum Hyperthyroid Hypothyroid Euthyroid 4-8 weeks 2-3 months - Inflammation Dysfunction Recovery No hyperthyroid phase 25% No hypothyroid phase 25% Permanent hypothyroidism: 20-30% (50% after 10 years) Recurrence during subsequent pregnancies 70%

75 Management Observational policy Symptomatic treatment ( -blockers) during hyperthyroid phase (Anti-thyroid drugs are not effective) Thyroxine may be given (for ~4-6/12) to those with prolonged and symptomatic hypothyroidism

76 T4 (9-19) T3 ( ) Interpretation of Difficult TFT TSH ( ) Interpretation Not Primary HT, could be Secondary HT Sick euthyroid/drugs Not hyperthyroid, could be Assay related Drugs Normal Not Primary TT, most likely TSHoma or TH resistance Not hyperthyroid, could be Assay related Action Do not treat, please refer Do not treat, no need to refer in most cases Please refer Do no treat, please discuss/repeat T3 toxic Ignore T4 and manage as hyperthyroid Consider secondary hypothyroidism Please refer