(BQ) Part 2 book Oxford handbook of endocrinology and diabetes presents the following contents: Endocrinology in pregnancy, calcium and bone metabolism, paediatric endocrinology, neuroendocrine disorders, inherited endocrine syndromes and MEN, endocrine surgery,... and other contents.
Chapter 5 Endocrinology in pregnancy Thyroid and parathyroid disorders 426 Maternal hyperthyroidism 428 Maternal hypothyroidism 431 Post-partum thyroid dysfunction 432 Thyroid cancer in pregnancy 433 Parathyroid disorders 434 Pituitary disorders 436 Prolactinoma in pregnancy 437 Management of prolactinoma 438 Cushing’s syndrome 439 Management of Cushing’s syndrome 440 Acromegaly 441 Non-functioning pituitary tumours 441 Hypopituitarism in pregnancy 442 Adrenal disorders 444 Addison’s disease in pregnancy 445 Congenital adrenal hyperplasia 446 Phaeochromocytoma 447 Management of phaeochromocytoma 448 425 426 Chapter 5 Endocrinology in pregnancy Thyroid and parathyroid disorders Normal physiology Effect of pregnancy on thyroid function • Iodine stores Fall due to i renal clearance and transplacental transfer to fetus • Thyroid size Increase in thyroid volume by 10–20% due to hCG stimulation and relative iodine deficiency • Thyroglobulin Rise corresponds to rise in thyroid size • Thyroid-binding globulin (TBG) Twofold i in concentration as a result of reduced hepatic clearance, and i synthesis stimulated by oestrogen Concentration plateaus at 20 weeks’ gestation and falls again post-partum • Total T4 and T3.i concentrations, corresponding to rise in TBG • Free T4 and T3 There may be a small rise in concentration in first trimester due to hCG stimulation, then fall into normal range During second and third trimester, FT4 concentration is often just below the normal reference range • Thyroid-stimulating hormone (TSH) Within normal limits in pregnancy However, suppressed in 13.5% in first trimester, 4.5% in second trimester, and 1.2% in third trimester due to hCG thyrotropic effect +ve correlation between free T4 and hCG levels, and –ve correlation between TSH and hCG levels in first half of pregnancy Upper limit of normal range is higher in pregnancy • Thyrotropin-releasing hormone (TRH) Normal • TSH receptor antibodies When present in high concentrations in maternal serum, may cross the placenta Antibody titre decreases with progression of pregnancy Fetal thyroid function • TRH and TSH synthesis occurs by 8–10 weeks’ gestation, and thyroid hormone synthesis occurs by 10–12 weeks’ gestation • TSH, total and freeT4 and T3, and TBG concentrations increase progressively throughout gestation • Maternal TSH does not cross the placenta, and although TRH crosses the placenta, it does not regulate fetal thyroid function Iodine crosses the placenta, and excessive quantities may induce fetal hypothyroidism Maternal T4 and T3 cross the placenta in small quantities and are important for fetal brain development in the first half of gestation Thyroid and parathyroid disorders 427 428 Chapter 5 Endocrinology in pregnancy Maternal hyperthyroidism (b see Thyrotoxicosis in pregnancy, p. 44.) Incidence • Affects 0.2% of pregnant women • Most are diagnosed before pregnancy or in the first trimester of pregnancy • In women with Graves’s disease in remission, exacerbation may occur in first trimester of pregnancy Graves’s disease • The commonest scenario is pregnancy in a patient with pre-existing Graves’s disease on treatment, as fertility is low in patients with untreated thyrotoxicosis Newly diagnosed Graves’s disease in pregnancy is unusual • Aggravation of disease in first trimester, with amelioration in second half of pregnancy because of a decrease in maternal immunological activity at that time • Symptoms of thyrotoxicosis are difficult to differentiate from normal pregnancy The most sensitive symptoms are weight loss and tachycardia Goitre is found in most patients Management • Risks of uncontrolled hyperthyroidism to mother: heart failure/ arrhythmias • Antithyroid drugs (ATDs) are the treatment of choice but cross the placenta • Propylthiouracil (PTU) should be used in the first trimester in case of teratogenic effects of carbimazole (check liver function monthly) Thereafter, carbimazole is recommended • Carbimazole use in pregnancy was discouraged, as it was thought to be associated with aplasia cutis, a rare scalp defect, though recent studies have shown no increase in rate Studies have shown that carbimazole may be associated with choanal and oesophageal atresia, but the maternal hyperthyroidism may be a factor in this • Propylthiouracil may rarely be associated with hepatocellular inflammation, which, in severe cases, can lead to liver failure and death A recent study also showed that PTU was associated with low birthweight infants • A short course of 40mg of propranolol tds can be used initially for 2–3 weeks while antithyroid drugs take affect • Most patients will be on a maintenance dose of ATD A high dose of ATD may be necessary initially to achieve euthyroidism as quickly as possible (carbimazole 20–40mg/day or propylthiouracil 200–400mg/ day) in newly diagnosed patients, then use the minimal dose of ATD to maintain euthyroidism • Do not use block and replace regime as higher doses of ATDs required, and there is minimal transplacental transfer of T4, thereby risking fetal hypothyroidism • Monitor TFTs every 4–6 weeks Maternal hyperthyroidism • Aim to keep FT4 at upper limit of normal and TSH low normal (2.85mmol/L), then parathyroidectomy can be arranged in the second or early third trimester Hypoparathyroidism • Pregnancy increases the demand for vitamin D. Therefore, replacement doses will need to be increased in pregnancy • Maternal levels of corrected calcium and vitamin D should be checked monthly • Untreated hypoparathyroidism leads to miscarriage, fetal hypocalcaemia, and neonatal rickets ... Clinical features • Failure of lactation • Involution of breasts • Fatigue, lethargy, and dizziness • Amenorrhoea • Loss of axillary and pubic hair • Symptoms of hypothyroidism • Diabetes insipidus is rare... weeks post-partum in non-lactating women • Serum LH and FSH Undetectable levels in pregnancy and blunted response to GnRH because of –ve feedback inhibition from high levels of sex hormones and PRL... Table 5.1) 439 440 Chapter 5 Endocrinology in pregnancy Management of Cushing’s syndrome • First trimester: • Offer termination of pregnancy and instigate treatment, particularly if adrenal carcinoma