Update in
Endocrinology
Dr K Foster
Consultant Endocrinologist
Spire Gatwick Park & East Surrey Hospitals
Update in Endocrinology
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Funny thyroid function tests.
Early hyperparathyroidism.
Vitamin D Deficiency.
Cancer & Diabetes
PCOS.
Funny thyroid function tests.
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UK Guidelines for the use of Thyroid Function
Tests. (Assn. Clin. Bioch.. Brit. Thy. Assn.,
2006).
Management of Thyroid Dysfunction during
Pregnancy….. (Endo. Soc. 2009).
The Diagnosis and Management of Primary
Hypothyroidism (RCP & al 2006).
Thyrotoxicosis
Funny Thyroid Function Tests.
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TSH = 0.01mu/l, fT4 = 33.2 pmol/l.
Thyrotoxic.
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Subclinical Thyrotoxicosis.
TSH = < 0.3mu/l, fT4= 19.0pmol/l.
Would you treat?, Repeat?,check T3 or watch?
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Hypothyroidism
Funny Thyroid Function Tests
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TSH = > 10mu/l, fT4 = <10pmol/l,
Hypothyroid and treat if markedly abnormal or
symptomatic
Borderline and subclinical hypothyroidism,
(TSH = 3.3-7, fT4 = >12).
Before lifelong treatment, repeat TFTs in
3/12, treat if symptomatic (or strongly positive
anti-thyroid antibodies).
Severe myxoedema
Funny Thyroid Function Tests
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TSH = 2.4mu/l, fT4 = 10.2pmol/l. Patient is
tired & constipated.
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Diagnosis?
Action?
Funny Thyroid Function Tests
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TSH =2.4mu/l, fT4 = 10.2pmol/l.
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Probable sick euthyroid syndrome, consider
poor compliance with T4 treatment, pituitary
disease & subacute thyroiditis.
Consider general health, repeat, possibly
check fT3 levels
Funny thyroid function tests.
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Not just funny but bizarre!
TSH = 56.2 mu/l, fT4 = 52.6pmol/l.
Patient complains of being tired.
What would you do?
Funny thyroid function tests
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TSH = 56.2mu/l, fT4 = 52.6pmol/l
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Consider interference in assay (1:500).
Check fT3 or Total T4, anti thyroid abs, use
clinical judgement and ask for another lab to
perform the assay.
TSH levels in TSH-omas are usually much
lower.
Thyroid Disease in Pregnancy
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Hypothyroid: check TFTs before planned
pregnancy, when pregnancy is diagnosed and
expect to increase dose early in pregnancy.
Aim TSH > 2 mu/l.
Thyrotoxicosis: strict control needed,
propylthiouracil preferred, anti receptor
antibodies useful in late pregnancy.
Early Hyperparathyroidism
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Consensus guidelines from the Endocrine
Society and NIH .(up dated 2009)
Surgery remains the mainstay of management
for primary HPT.
Medical treatment:
Vitamin D if low.
Biphosphonates ?
Cinacalcet possibly.
Early Hyperparathyroidism
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Surgery recommended if serum adjusted Ca >
0.25mmol/l above ULN (=2.8mmol/l).
Other Indications for surgery:
Hypercalciuria (>10.0mmol/24hr).
Age < 50 yrs.
Osteopaenia.
Serum Creatinine >100umol/l.
Not able to be followed up.
Trials in Early Hyperparathyroidism.
USA -15 yr follow up; (n=49).
Baseline serum Ca = 2.62mmol/l
5 year serum Ca = 2.67mmol/l
10 year serum Ca = 2.70mmol/l
15 year serum Ca = 2.78mmol/l
(mean serum PTH, serum Creatinine, & 24hr Ur
Calcium unchanged).
Approx 25% will progress to surgery in 5 yrs.
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Surgery in Hyperparathyroidism
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Diagnosis must be confirmed.
>95% cure with minimal mordidity.
Cheaper after 7 yrs (US).
Reduced serum & urine Ca, improved BMD and
possible improved QOL. (for higher Ca Levels)
Serum Ca & PTH are risk factors for CVD
Hypertensive HPT patients at especial risk
Glucose intolerance linked to HPT.
Early Hyperparathyroidism
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Follow up of cases where surgery not indicated:
Serum Ca & Symptoms – 6 monthly.
Serum Creatinine – yearly.
Bone density – 2-3 yearly.
Vitamin D Deficiency in Adults.
Se 25 OH Vit D
(nmol/l).
<25
25-50
Condition
Management
Risk of
osteomalacia
High dose
calciferol(10,000u od)
For 8-12 weeks.
Deficiency with
associated disease risk
Vit D supplementation
(1000 u od)
>75
Optimal
>500
Toxicity
Sources of Vitamin D.
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UK, 50% of population have insufficient levels and
16% severely deficient in Spring.
20-30 mins sun exposure at midday for a fair skinned
person in short sleeved shirt, yield 2000u, (UV B,
April –October).
Oily fish are best source, also egg yolk, margerine,liver
and wild mushrooms.
Enzyme inducing agents increase risk of deficiency.
Disease associated with Vitamin D
Deficiency.
Osteomalacia (Alk P’ase usually raised) &
myalgia.
Probably
 Increased risk of Diabetes T1 & T2.
 CVD
 Bowel & Breast Cancer
 MS
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Measuring Vitamin D.
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Routine results are for 25 - 0H cholecalciferol,
½ life 2-3 weeks.Moderately light stable
Active calcitriol (1,25 - OH cholecalciferol has
short ½ life, is light instable and is related to
serum PTH and does not reflect true Vitamin D
status.
Ergocalciferol refers to related plant sterols.
Treating Vitamin D Deficiency
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Osteomalacia – 10,000u ergocalciferol daily (may
be difficult to obtain), or cholecalciferol (special
order) 20,000u capsules 3 per week, or
Ergocalciferol 100,000u im, (rpt 3/12 & 612).
Insufficiency – 1000u daily as calcium and
vitamin D tablets, but tolerability is a problem
and is Ca desireable? Consider propriety vit D.
Alfacalcidol & Cacitriol preferred for renal
failure and hypoparathyroidism.
Monitor Serum Ca & Alk p’ase.
Diabetes & Cancer
T2 DM associated with increased risk of cancer,
especially pancreas, breast & colon.
 This may be multifactorial;
Obesity
Metabolic Syndrome
Raised blood Tg, insulin & IGF1 levels
Lower with metformin than SU or Insulin.
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Diabetes & Cancer
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2009, 4 Registry based studies confirm higher risk.
Germany: Dose dependent risk for insulin, increased
risk for glargine v human insulin.
UK Health Information Network, confirmed higher
risk SU & insulin. Metformin cut risk for pancreatic &
colon cancer.
Scotland; Increased breast cancer with glargine versus
glargine plus other insulins.
Sweden; Also more breast cancer on glargine alone.
Diabetes & Cancer
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Do registry review trials have a selection bias?
Detimer; no increased risk.
Sitagliptin; in animals increased pancreatic duct
cell turnover prevented by metformin.
Liraglutide; in rodents increased thyroid c cell
tumours, not so far in man.
Medical aspects of PCOS
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2003 Consensus; Diagnosis made on the basis of
2 of these criteria:
Polycystic ovaries on imaging,
Oligo-ovulation, anovulation,
Clinical / biochemical evidence of androgen
excess.
(serum testosterone usually <5mmol/l)
Medical aspects of PCOS .
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Investigations may depend on presentation, but
may include:
U/S
Serum LH, FSH, Oestradiol, testosterone.
Possibly TFTS, 17OH Progesterone,
prolactin.
Consider BP, blood glucose.
Medical management of PCOS
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Weight loss 5%
Anovulation; Metformin.
Clomiphene, FSH
Hirsutism; Cyproterone (as Dianette?)
Eflornithine (Vaniqa)
Local treatments.