Endocrine disease in pregnancy. Thyroid disease during pregnancy. Gestational trophoblastic neoplasia. Oxford Medicine Online

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1 Oxford Medicine Online You are looking at 1-10 of 68 items for: heart disease in pregnancy MED00250 oxford_textbooks Endocrine disease in pregnancy C. Nelson and S. Germain DOI: /med/ This chapter describes the causes, symptoms and clinical management strategies of endocrine disease in pregnancy, beginning with thyroid and parathyroid disease, then diabetes mellitus, pre-existing diabetes, gestational diabetes, adrenal diabetes and pituitary disease. Thyroid disease during pregnancy John H. Lazarus, L.D. Kuvera, and E. Premawardhana DOI: /med/ Thyroid disorders are common. The prevalence of hyperthyroidism is around 5/1000 in women and overt hypothyroidism about 3/1000 in women. Subclinical hypothyroidism has a prevalence in women of childbearing age in iodine-sufficient areas of between 4% and 8%. As these conditions are generally much more common in females, it is to be expected that they will appear during pregnancy. Developments in our understanding of thyroid physiology (1) and immunology (2) in pregnancy, as well as improvements in thyroid function testing (3), have highlighted the importance of recognizing and providing appropriate therapy to women with gestational thyroid disorders. Before considering the clinical entities occurring during and after pregnancy it is useful to briefly review thyroid physiology and immunology in relation to pregnancy. Gestational trophoblastic neoplasia Philip Savage and Michael J. Seckl DOI: /med/ Arising from the cells of conception, gestational trophoblastic disease (GTD) forms a spectrum of disorders from the premalignant complete and partial hydatidiform moles through to the malignant invasive mole, choriocarcinoma and very rare placental site Page 1 of 5

2 trophoblastic tumours (PSTT). The latter three conditions are also collectively known as gestational trophoblastic neoplasia (GTN) and, although uncommon, are important to recognize as this enables life-saving therapy to be commenced. About 10% of molar pregnancies fail to die out after uterine evacuation and transform into malignant GTN that require additional chemotherapy (1). These cases are usually recognized early and therefore rarely prove difficult to treat, with cure rates approaching 100% reported in most modern series (2). However, GTN can also develop after any type of pregnancy including miscarriages, term deliveries, and medical abortions. Such patients are often not suspected of having GTN and may present late with widespread disease associated with a wide variety of medical, surgical, and gynaecological problems (3). The prompt diagnosis and early effective treatment of these women is aided by an awareness and understanding of these rare, but highly curable malignancies and good team-working between physicians, gynaecologists, pathologists, and oncologists Diabetes management in pregnancy David R. McCance DOI: /med/ Although the outlook for the woman with diabetes has greatly improved since the discovery of insulin, the goal of the St. Vincent Declaration (1989) that the outcome of diabetic pregnancy should approximate that of nondiabetic pregnancy has still not been realized. In the mid 1990s, a number of regional UK centres reported a four-fold to ten-fold increase in congenital malformations and three- to five-fold increase in perinatal mortality, compared with the background population. A general increase in the prevalence of type 2 diabetes is being translated into the pregnancy context and outcomes appear similar to those of type 1 diabetes. The problem of pregnancy planning and other key demographic and pregnancy-related features were highlighted in a major UK Confidential Enquiry into Maternal and Child Health (CEMACH) during , which has provided a largely unrivalled source of reference (1). While the relevance of overt hyperglycaemia to maternal and perinatal outcomes is now clearly established, the significance of minor degrees of hyperglycaemia for maternal/fetal outcome has been the subject of much controversy and dogma. The lack of a robust evidence base is reflected in the lack of consensus among published guidelines (2). Despite these limitations, the outcome of pregnancy for most women with diabetes is good, and this undoubtedly reflects improved obstetric surveillance and better management of maternal hyperglycaemia over the last several decades. The aim is, through education and maternal empowerment, to optimize blood glucose control both before and during pregnancy, so that pregnancy may proceed as normally as possible and result in the birth of a normal baby at near term. The last few years have seen the publication of a number of landmark observational studies and randomized trials (3 8), which have the potential to alter the diagnostic and therapeutic landscape considerably. Some guidance for the management of diabetes in pregnancy has recently been published (9, 10). Page 2 of 5

3 Clinical assessment of the thyroid patient Peter Laurberg and Inge Bülow Pedersen DOI: /med/ Thyroid disorders are common, especially in older people where 10 20% may have structural abnormalities of the thyroid glan and/or thyroid function tests outside the reference range (1). Evaluation of thyroid function, size, and structure is therefore an important part of any complete history and physical examination of a patient. Management of Graves hyperthyroidism Jacques Orgiazzi and Claire Bournaud DOI: /med/ The treatment strategy for the hyperthyroidism of Graves disease remains a matter of controversy for several reasons. Treatment modalities available so far are symptomatic rather than pathophysiological, patients are heterogeneous in the severity and prognosis of the disease, and, in many patients, the disease is lifelong. Even symptomatic treatment should be adapted to the severity of the disease, both in terms of intensity of hyperthyroidism and degree of immunological derangement, an elusive goal so far. Current treatment modalities are medical/conservative with antithyroid drugs, often marred by relapse, and radical/destructive with radio-iodine or surgery with subsequent hypothyroidism. Being controversial, the selection of the treatment strategy also requires the patient s informed cooperation. Finally, another peculiarity of the management of Graves disease is the frequent requirement of a multidisciplinary approach. This chapter will discuss general and specific therapeutic approaches of hyperthyroid Graves disease. Subclinical hypothyroidism Jayne A. Franklyn DOI: /med/ Subclinical hypothyroidism is defined biochemically as the association of a raised serum thyroid-stimulating hormone (TSH) concentration with normal circulating concentrations of free thyroxine (T4) and free triiodothyronine (T3). The term subclinical hypothyroidism implies that patients should be asymptomatic, although symptoms are difficult to assess, especially in patients in whom thyroid function tests have been checked because of nonspecific complaints such as tiredness. An expert panel has recently classified individuals with subclinical hypothyroidism into two groups (1): (1) those with mildly elevated serum Page 3 of 5

4 TSH (typically TSH in the range mu/l) and (2) those with more marked TSH elevation (serum TSH >10.0 mu/l). Hyperprolactinaemic anovulation Julian R. E. Davis DOI: /med/ Prolactin is a polypeptide hormone, named from its well-known effects to promote lactation. It is essential for successful reproduction in man and mammals, although it is known to have a wide variety of nonreproductive effects whose clinical significance remains uncertain. Hyperprolactinaemia, reflecting sustained overproduction of lactin by the pituitary, is relatively common in the population. The commonest cause is the use of drugs that have dopamine D2 receptor antagonist activity (e.g. antipsychotic agents such as phenothiazines), pregnancy and lactation are the commonest physiological causes, and short-term acute stress, such as the anxiety provoked by blood sampling, is also a frequent cause of transient rises in serum prolactin that may be misinterpreted and necessitate a second confirmatory blood sample. Pathological pituitary causes of hyperprolactinaemia may reflect a functioning pituitary prolactinoma, but in many cases no adenoma is detectable on scanning, in which case the condition is termed idiopathic or nontumoral hyperprolactinaemia. The typical clinical features that suggest hyperprolactinaemia are those of galactorrhoea and oligo-/amenorrhoea. Weight gain has been reported in hyperprolactinaemic women, as has insulin resistance. Serum prolactin levels are readily measured by most clinical biochemistry laboratories, and prolactin levels should be measured on more than one occasion, with persistent unexplained hyperprolactinaemia requiring evaluation. Patients with hyperprolactinaemia may require treatment for various reasons, including restoration of ovulatory function, maintenance of adequate oestrogenization, suppression of galactorrhoea, or reduction in size of a mass lesion. Depending on the presentation and underlying cause, there are several treatment options; the main current treatment option is dopamine agonist therapy, surgery and (rarely) radiotherapy are also used in the treatment of prolactinomas. Antithyroid drug treatment for thyrotoxicosis Anthony Toft DOI: /med/ The most effective and commonly used antithyroid drugs are the thionamides, including carbimazole and its active metabolite methimazole (not available in the UK). These act by inhibiting the synthesis of thyroid hormones, principally by interfering with the iodination of tyrosine by serving as preferential substrates for the iodinating intermediate of thyroid peroxidase. Oxidized iodine is thus diverted from potential iodination sites Page 4 of 5

5 in thyroglobulin. The iodinated antithyroid drugs are desulfurated and further oxidized to inactive metabolites. There is also some evidence for an immunosuppressive action which is of doubtful clinical significance as most patients relapse after drug withdrawal. Another thionamide, propylthiouracil, is, in addition, a potent inhibitor of type 1 outer ring deiodinase and acutely inhibits thyroxine (T4) to triiodothyronine (T3) conversion, but there is no good evidence to suggest that this effect is of any clinical relevance. Propylthiouracil tends to be reserved for those patients who have developed an adverse reaction to carbimazole or methimazole. Clinical assessment and systemic manifestations of thyrotoxicosis Claudio Marcocci, Filomena Cetani, and Aldo Pinchera DOI: /med/ The term thyrotoxicosis refers to the clinical syndrome that results when the serum concentrations of free thyroxine, free triiodothyronine, or both, are high. The term hyperthyroidism is used to mean sustained increases in thyroid hormone biosynthesis and secretion by the thyroid gland; Graves disease is the most common example of this. Occasionally, thyrotoxicosis may be due to other causes such as destructive thyroiditis, excessive ingestion of thyroid hormones, or excessive secretion of thyroid hormones from ectopic sites; in these cases there is no overproduction of hormone by thyrocytes and, strictly speaking, no hyperthyroidism. The various causes of thyrotoxicosis are listed in Chapter The clinical features depend on the severity and the duration of the disease, the age of the patient, the presence or absence of extrathyroidal manifestations, and the specific disorder producing the thyrotoxicosis. Older patients have fewer symptoms and signs of sympathetic activation, such as tremor, hyperactivity, and anxiety, and more symptoms and signs of cardiovascular dysfunction, such as atrial fibrillation and dyspnoea. Rarely a patient with apathetic hyperthyroidism will lack almost all of the usual clinical manifestations of thyrotoxicosis (1). Almost all organ systems in the body are affected by thyroid hormone excess, and the high levels of circulating thyroid hormones are responsible for most of the systemic effects observed in these patients (Table ). However, some of the signs and symptoms prominent in Graves disease reflect extrathyroidal immunological processes rather than the excessive levels of thyroid hormones produced by the thyroid gland (Table ). Page 5 of 5