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Update in Endocrinology. Dr K Foster Consultant Endocrinologist Spire Gatwick Park & East Surrey Hospitals. Update in Endocrinology. Funny thyroid function tests. Early hyperparathyroidism. Vitamin D Deficiency . Cancer & Diabetes PCOS . Funny thyroid function tests.
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Update in Endocrinology Dr K Foster Consultant Endocrinologist Spire Gatwick Park & East Surrey Hospitals
Update in Endocrinology • Funny thyroid function tests. • Early hyperparathyroidism. • Vitamin D Deficiency. • Cancer & Diabetes • PCOS.
Funny thyroid function tests. • 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).
Funny Thyroid Function Tests. • TSH = 0.01mu/l, fT4 = 33.2 pmol/l. = Thyrotoxic. • Subclinical Thyrotoxicosis. TSH = < 0.3mu/l, fT4= 19.0pmol/l. Would you treat?, Repeat?,check T3 or watch?
Funny Thyroid Function Tests • 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).
Funny Thyroid Function Tests • TSH = 2.4mu/l, fT4 = 10.2pmol/l. Patient is tired & constipated. • Diagnosis? Action?
Funny Thyroid Function Tests • TSH =2.4mu/l, fT4 = 10.2pmol/l. • 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. • 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 • TSH = 56.2mu/l, fT4 = 52.6pmol/l • 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 • 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 • 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 • 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.
Surgery in Hyperparathyroidism • 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 • Follow up of cases where surgery not indicated: Serum Ca & Symptoms – 6 monthly. Serum Creatinine – yearly. Bone density – 2-3 yearly.
Sources of Vitamin D. • 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 (AlkP’ase usually raised) & myalgia. Probably • Increased risk of Diabetes T1 & T2. • CVD • Bowel & Breast Cancer • MS
Measuring Vitamin D. • 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 • 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 & Alkp’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.
Diabetes & Cancer 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 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 • 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 . • 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 • Weight loss 5% • Anovulation; Metformin. Clomiphene, FSH • Hirsutism; Cyproterone (as Dianette?) Eflornithine (Vaniqa) Local treatments.