Endocrinology in Primary Care

HN Buch

Endocrinology in Primary Care

Death by Powerpoint

HN Buch

Agenda

Endocrine Condition Primary v Secondary Care

Focus of Discussion Initial management Follow up

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

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

• 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!!

Hypothyroidism is Easy

• Start 50-100mcg; 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

Hypothyroidism is Easy

Hypothyroidism is Easy

Not Always Easy!

• Diagnostic pitfalls

Case 1

• 34/F, recurrent hyperthyroidism

• Received radioiodine therapy (RAI)

Pre RAI 2/12 post

FT4 (10-22)

55

FT3 (3.5-6.5)

19

TSH (0.5-4.0)

<0.01 <0.01

Persistent Hyperthyroidism

Pre RAI 4/12 post

FT4 (10-22)

55 6

FT3 (3.5-6.5)

19 2.9

TSH (0.5-4.0)

<0.01 <0.01

Post-RAI Hypothyroidism

Case 1

During transition from hyperthyroidism to hypothyroidism

only TSH is not enough to diagnose hypothyroidism

Case 2

• 61/male, presented with lethargy, tiredness, weakness /12

after CABG

• UE/LFT/Bone/FBC normal/vitamin D 19

• TSH 1.1 (0.5-4.0)

• 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

Case 2

Initial 2/12 later

FT4 7.2

FT3 3.6

TSH 1.0 1.0

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

Case 2

TSH is not enough to diagnose secondary hypothyroidism

• 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

Case 3

Case 3

Full TFT:

• TSH: 7.6

• T4: 31 (10-22)

• T3: 7.2 (3.5-6.8)

Diagnosis:

• TSH producing Pituitary macroadenoma

Case 3

High TSH is not always due to hypothyroidism

Other causes Drugs TSHoma Adrenal insufficiency

Cases 1, 2 and 3

All patients with hypothyroidism do not have high TSH and all patients with high TSH do not have

hypothyroidism

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

Not Always Easy!

• Management challenges

• 22, male, university student

• 2/12 history of lethargy, dizziness and 2 kg weight loss

• TSH: 80mU/L (0.5-4.0); FT4: 8.2pmol/L (12-22)

• TPO 1:1000

• Diagnosis: Autoimmune hypothyroidism

• Thyroxine 75mcg, increased to 125mcg over 3/12

Case 3

3 months later

Clinically and biochemically well replaced

• TSH 1.7mU/L, FT4 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

Diagnostic Test was Performed

Short synacthen test (ACTH 250mcg IV)

Time (min) Cortisol

0 92

30 176

60 198

ACTH-128 (8-60)

Autoimmune Polyglandular Syndrome 2

Diagnosis

Addison’s disease +

Primary Hypothyroidism

APS 1 APS 2

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%)

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

• 38, businessman

• Bronchial asthma on inhalers

• Anaemia on iron supplements for 12 months

• Lethargy, weight gain

• TSH: 38mU/L, FT4: 10.1pmol/L, TPO positive

• Thyroxine commenced

Case 4

THYROXINE DOSE TSH (mU/L) fT4 (pmol/L)

Diagnosis 38 10.1

100mcg 32.7 12.5

5 months later

100 250 18.4 15.1

TTG antibodies and D2 biopsy: Coeliac disease

Gluten free diet instituted

250 <0.01 25

150 2.1 18.2

Absorption

• Diet: Ingestion after meals, soya milk, prunes, herbal remedies

• Gastrointestinal: Coeliac or any other cause of malabsorption

• Drugs: Cholestryramine, Colestipol, Lovastatin,

Non-compliance

If suboptimal biochemical response despite escalating

thyroxine dose, consider poor adherence or absorption

Case 5

• 27/F, hair loss, dry skin, mild weight gain (6/12)

• T4 15.2 , TSH 8.1

• More information ? – Any drugs

– Radioiodine

– TPO 1:126

• Options – Treat with thyroxine

– No treatment, monitor TFT

Dx 4/12 12/12 24/12

TSH (0.5-4.0)

8.1 7.8 9.0 6.9

FT4 (10-22)

15.2 15.6 16.9 17.1

FT3 (3.5-6.5)

4.3

No treatment given

Case 5

Diagnosis: Subclinical hypothyroidism

– A biochemical diagnosis (TSH, normal T4/T3),

– 2-4%

– Possible causes

• Impending thyroid failure; 2% p.a. progress to hypothyroidism

• Drugs e.g. amiodarone

• “Normal”

TSH distribution curve

TSH 0.5-4.0 mU/L

Euthyroid people

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

Case 6

24/F, recently married, presents with weight gain (Endo clinic)

• T4: 10.5 (12-22), TSH 12.1 (0.5-4.0), TPO +

Commenced on T4 50mcg 75mcg

• T4: 17.3 (12-22), TSH 1.4 (0.5-4.0) – discharged to PC 6/12 TFT

6/12 later: 7/40 pregnant

• T4: 11.3 (12-22), TSH 7.4 (0.5-4.0),

Thyroxine increased: 75mcg 125mcg

• 12/40 - T4: 17 (12-22), TSH 3.1 (0.5-4.0),

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?

Foetus is entirely dependent on

maternal T4 until mid-gestation

Placenta is relatively

impermeable to thyroxine

hCG induced in

maternal T4

in demand of

maternal T4

Fails in patients with

atrophic thyroid

Subtle neurodevelopment

deficiencies in baby

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

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

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?

All 3 in this photo had thyroid dysfunction

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

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

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

• Block/replace (6/12)

• Titration (18/12)

Remission (30-50%)

• RAI • Surgery • Indefinite

low-dose ATD

Relapse (50-70%)

Hyperthyroidism

CMZ 40 ± -blockers

Patient preference

Graves’ disease (+ ? aetiology) Autonomous nodule(s)

6-8/52: euthyroid

Aetiology

5 min uptake= 0%

5 min uptake= 6%

Case 7

• 79/F

• Routine testing: T4 17.1, TSH 0.005

• What next?

• FT3 – 6.7 (3.5-5.7)

• Diagnosis: T3 toxicosis; management is identical to hyperthyroidism with high T4

Case 7

• 79/F

• Routine testing: T4 17.1, TSH 0.005

• What next?

• FT3 – 5.1 (3.5-5.7)

• Diagnosis: Sub-clinical hyperthyroidism

• Increases risk of AF and osteoporosis but no treatment as no convincing intervention data

• 6-12 monthly TFT

FT4, TSH

Hyperthyroidism

Both normal High FT4 & suppressed TSH

FT3

Normal FT4 & suppressed TSH

No further tests

Normal Subclinical hyperthyroidism

High T3 Thyrotoxicosis

Thyrotoxicosis

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

Primary Hyperparathyroidism (PHPT)

Should all patients be referred?

Yes

Should all patients be followed up in specialist care?

No

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

May need surgery Endocrine follow

up ~2 years

Does not need surgery Discharge for annual

primary care follow up

PHPT: Endocrine Clinic

Indications for surgery

What needs monitoring?

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)

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

Hyperprolactinaemia

Cause Prolactin level

Macroprolactinoma 5000-100,000 mU/L

Microprolactinoma

Up to 2500 mU/L Other large non-functioning pituitary tumours with compression on the pituitary stalk

Drugs

Miscellaneous: stress, PCO

Hyperprolactinaemia

Exclude macroprolactin

• Repeat PRL • Exclude

hypothyroidism • Drug history

Not MRI

If persistently high PRL and euthyroid refer Urgency dictated by visual symptoms

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

Agenda

Endocrine Condition Primary v Secondary Care

Focus of Discussion Initial management Follow up

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

Conclusions

Endocrine Condition Primary v Secondary Care

Conclusions Initial management Follow up

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

La Fin

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 Most need referral but many can be followed up in primary care

Follow up strategy

Prolactinomas If “true hyperprolactinaemia” need referral; some can be followed up in primary care

Check list prior to referral

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

Subclinical hypothyroidism

• 27/F

• Aches and pains

• Weight gain 4 kg in 1 year

• No relevant PH, FH

• OCP

• FT4 15.6, TSH 6.8

• 3 months later: FT4 16.1, TSH 6.6

Subclinical hypothyroidism

• Treat or not to treat

Subclinical hypothyroidism

Causes

• Recent onset thyroid failure

• Drug induced: amiodarone, antiepileptics

• Hypocortisolism

• Heterophile antibodies

• “Normal”

Subclinical hypothyroidism

Treat if

• TSH>10

• TPO antibodies strongly positive

• Post RAI

• Pregnant or planning pregnancy

Not for symptoms in absence of above

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

Pre-referral Check-list

• Confirm persistently high levels

• Exclude hypothyroidism

• Exclude drug related causes and withdraw if possible

• Exclude macroprolactin

Isotope scan

• Technetium, simple, harmless

• Contraindicated during pregnancy

Indications to request:

• Hyperthyroid patient when low uptake state is suspected

Graves’ disease Solitary nodule Thyroiditis/factitious

Ocassionally

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 12-18 months on ATD

Other manifestations of Graves disease?

11/10/06

11/10/06 68

Multi-nodular goitre

• Common cause of hyperthyroidism in the elderly

• No spontaneous remission

ATD B/R 6/12 or

Titration 18/12

Remission (40-50%)

RAI Surgery Indefinite ATD

Relapse (50-60%)

Hyperthyroidism

CMZ 40 OD + -blockers

Patient preference

Graves’ disease

(+ ? aetiology)

Autonomous nodule(s)

4-6/52: euthyroid

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 (0.5-4.5)

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 (0.5-4.5)

• No treatment

FT4

(9-19pmol/L)

TSH

(0.5-4.5mU/L)

At presentation <5 >100

2/52 6.2 62

6/52 8.2 36

3/12 9.4 20

4/12 11.2 3.9

Case 5

Diagnosis

Post-partum thyroiditis

Presenting with hypothyroidism

Case 5

Post partum thyroiditis

• Incidence: 5-10% pregnancies

• Histopathology: Inflammation with an autoimmune basis

• Clinical presentation at 3-12 months post-partum

• Permanent hypothyroidism: 20-30% (50% after 10 years)

• Recurrence during subsequent pregnancies 70%

Hyperthyroid Hypothyroid Euthyroid

4-8 weeks 2-3 months -

Inflammation Dysfunction Recovery

No hyperthyroid phase 25%

No hypothyroid phase 25%

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

Interpretation of Difficult TFT

T4 (9-19)

T3 (3.5-5.7)

TSH (0.5-4.0)

Interpretation Action

8.2 3.6 0.19 Not Primary HT, could be Secondary HT Sick euthyroid/Drugs

Do not treat, please refer

22 5.0 0.64 Not hyperthyroid, could be Assay related Drugs Normal

Do not treat, no need to refer in most cases

24 7 3.6 Not Primary TT, most likely TSHoma or TH resistance

Please refer

16 6.3 1.2 Not hyperthyroid, could be Assay related

Do no treat, please discuss/repeat

7.0 6.8 0.01 T3 toxic Ignore T4 and manage as hyperthyroid

7.0 3.3 7 Consider secondary hypothyroidism

Please refer