Endocrine disease in pregnancy, including diabetes mellitus, thyroid and adrenal disease

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Chapter 19 Endocrine disease in pregnancy, including diabetes mellitus, thyroid and adrenal disease

Jenny Myers and Dan Mallaber



Diabetes mellitus (DM) is a common and growing problem, affecting approximately 650,000 pregnancies in England and Wales each year (representing 2–5% of the obstetric population). Women with diabetes have an increased risk of both fetal and maternal complications, and of requiring anaesthetic intervention. Close monitoring and treatment during pregnancy, and careful anaesthetic management during labour and delivery, can reduce these risks and improve outcomes for both mother and baby.


DM is a multisystem disorder of carbohydrate metabolism, which can result from a number of distinct pathophysiological processes. Around 7.5% of pregnancies complicated by diabetes are due to type 1 and 5% due to type 2 diabetes. Gestational diabetes (GDM) accounts for the remaining 87.5%.

Type 1

Type 1 DM is attributable to an absolute lack of insulin production and secretion by the pancreatic β cells of the Islets of Langerhans. It is primarily an autoimmune disorder, although genetic and environmental factors also play a role. It accounts for around 10% of all DM. There is an association with other autoimmune conditions, including hypothyroidism.

Type 2

Type 2 DM is caused by a combination of both relative lack of insulin secretion and insulin resistance in target tissues. It accounts for 90% of all DM cases and is primarily associated with obesity. As such, its prevalence in both obstetric and non-obstetric populations is increasing and this is particularly so amongst several ethnic groups (including people of African, black Caribbean, South Asian, Middle Eastern and Chinese family origin).

Gestational diabetes mellitus

Gestational diabetes (GDM) is defined as glucose intolerance, which is first identified during pregnancy. Insulin resistance is known to increase progressively during the second and third trimesters of pregnancy due to an increase in counter-regulatory hormones (including placental lactogen, placental growth hormone, cortisol and progesterone). GDM may therefore be thought of as a preclinical state of glucose intolerance unmasked by the physiological changes in pregnancy. For most mothers glucose levels return to normal, but there is an increased risk of subsequent type 2 diabetes in women diagnosed with GDM.

Diagnosis and screening

The diagnosis of type 1 DM is usually made in adolescence or early adulthood. It is confirmed by a fasting glucose greater than 7 mmol/L, random glucose greater than 11.1 mmol/L or greater than 11.1 mmol/L 2 hours following a 75 g oral glucose tolerance test, and accompanying classical symptoms such as thirst, weight loss, fatigue and polyuria.

Patients with type 2 DM are rarely symptomatic and the diagnosis is usually made during routine screening. The threshold values are the same as for type 1 DM. A glycated haemoglobin (HbA1c) level of greater than 48 mmol/mol is also considered strongly suggestive of DM.

Diagnosis of GDM can be more challenging because of the changes in carbohydrate metabolism that occur normally during pregnancy, and the lack of international consensus on the diagnostic criteria. Universal screening is not currently recommended and screening is currently targeted at women who have risk factors for GDM (see Table 19.1). It is worth noting, however, that one or more of these risk factors is found in 30–50% of the pregnant population in the UK. Screening of high-risk patients currently takes place at between 16 and 18 weeks’ gestation for those with previous GDM, and 24–28 weeks for those with other risk factors.

Table 19.1 Risk factors for GDM

Previous GDM
BMI > 30 kg/m2
Previous large baby (>4.5 kg or >95th centile on customized chart)
Parent, brother or sister with diabetes
Family origin (South Asian, Black Caribbean, Middle Eastern)

Screening criteria taken from NICE guidelines 2008


The treatment of women with diabetes begins before pregnancy and includes optimization of glycaemic control and cessation of medications contraindicated in pregnancy (e.g. angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), statins) with conversion to alternative antihypertensive medication if required (calcium-channel blockers, β-blockers). High-dose folate (5 mg daily) is recommended preconceptually to reduce the risk of congenital abnormalities, particularly neural tube defects. Early pregnancy assessment of women with pre-existing diabetes should include an assessment of renal function (creatinine and urine protein:creatinine ratio) and referral for retinopathy screening, which should be conducted each trimester. Recent NICE guidelines also recommend low-dose aspirin (75 mg daily) from 12 weeks’ gestation to reduce the risk of pre-eclampsia, which is more common in women with diabetes. Low-molecular-weight heparin should be considered in women at increased risk of thrombosis (BMI >40 kg/m2 and diabetic nephropathy with >3 g proteinuria).

For women with DM, rigorous glycaemic control and close monitoring during pregnancy is associated with improved outcomes for both the woman and her baby. Preconception care and advice should be offered to all women with pre-existing DM. Women with HbA1C >85 mmol/mol should be advised to avoid pregnancy until glycaemic control is improved.

Women with type I diabetes are ideally managed in a joint antenatal diabetes clinic, combining obstetric, diabetic and specialist midwifery care. If safely achievable, then fasting blood glucose levels should be kept between 3.5 and 5.9 mmol/L and 1-hour postprandial blood glucose levels below 7.8 mmol/L during pregnancy. Women should be warned of the significant risk of hypoglycaemia, which may be complicated by reduced hypoglycaemia symptom awareness. Glucagon kits should be made available and insulin therapy adjusted if hypoglycaemia is occurring frequently. Increasingly women with type 1 diabetes are being offered continuous sub-cutaneous insulin infusion (CSII) therapy. To date there is little evidence that use of pumps improves pregnancy outcomes, but it may reduce the frequency of hypoglycaemic episodes. Insulin requirements increase in pregnancy, but may decline in the last few weeks of pregnancy and during labour. Insulin doses should be reduced by approximately 50% following delivery or adjusted to the prepregnancy regime.

Women with type 2 diabetes who have previously been treated with oral hypoglycaemic agents (e.g. metformin, glibenclamide) are usually advised to continue these during their pregnancy, although many women require additional insulin treatment to achieve the rigorous glycaemic control required in pregnancy.

Women with GDM are often able to achieve adequate glycaemic control with dietary adjustments, but 20–30% will require treatment with either metformin or insulin.


Maternal complications


Diabetic ketoacidosis (DKA) occurs mainly in patients with Type I DM and is due to either failure to administer sufficient insulin or to the development of a new source of insulin resistance (e.g. infection, trauma, stress). Emesis, steroid and β-blocker use are also important triggers during pregnancy. The lack of insulin favours lipolysis, the β-oxidation of free fatty acids and the formation of acetoacetate. These biochemical events result in metabolic acidosis, hyperglycaemia and an osmotic diuresis. Signs and symptoms of DKA include tachycardia, tachypnoea, hypotension, nausea and vomiting.

The incidence of DKA in pregnancy is between 1% and 2% and occurs most commonly in the second and third trimesters. As with the non-obstetric population, the management of DKA in pregnant patients involves rehydration, control of glucose with an intravenous sliding scale insulin regime and removal/treatment of any precipitating factors. All pregnant patients with DKA should be cared for in a level 2 critical-care facility with input from both medical and obstetric teams.

The hyperosmolar hyperglycaemic state (HHS) occurs predominantly in patients with type 2 DM and is characterized by very high blood glucose levels (frequently >40 mmol/L) without accompanying ketosis. It is rare in pregnancy.

Hypoglycaemia poses a significant risk for pregnant women, occurring in up to two-thirds of patients with pre-existing type 1 DM – a rate up to 15 times higher than in the non-pregnant population. It is most common before 20 weeks’ gestation. The intensification of treatment to achieve tight glycaemic control and impairment of the counter-regulatory hormonal responses that accompany insulin therapy are the main causes. Symptoms of hypoglycaemia are non-specific and include abdominal pain, vomiting, weakness, dizziness and drowsiness. These may be absent or reduced in pregnant women who are at an increased risk of hypoglycaemic unawareness. Hypoglycaemia is much less common in women with type 2 DM or GDM.


The prevalence of chronic complications generally correlates to the duration of DM and the adequacy of glycaemic control. Atherosclerotic macrovascular complications include disease of the coronary, cerebral and peripheral vasculature. Although rare, myocardial infarction is a potential risk and suspected cardiovascular disease should be thoroughly investigated.

Microvascular complications include diabetic retinopathy and nephropathy. Pregnancy may accelerate the rate of progression of both retinopathy and nephropathy.

Diabetic neuropathy can lead to autonomic cardiovascular dysfunction and gastroparesis. This may be difficult to assess, but in the non-pregnant diabetic patient, prolongation of the QT interval on the ECG correlates with the severity of autonomic dysfunction.

The diabetic stiff joint syndrome (also known as diabetic scleroderma) occurs in patients with long-standing type I DM and is associated with short stature, joint contractures and tight skin.


Rates of gestational hypertension, pre-eclampsia, fetal macrosomia, preterm delivery, induction of labour and caesarean section are all higher in diabetic obstetric patients. Recent studies have suggested that the risk of pre-eclampsia and gestational hypertension can be reduced by optimal glycaemic control during pregnancy.

Pre-existing DM, but not GDM, is associated with a 36% risk of preterm labour and delivery – approximately two to three times the non-diabetic rate. The incidence of early fetal loss, miscarriage and still birth is also higher.

Fetal macrosomia (birth weight >4 kg) complicates up to 50% pregnancies in women with pre-existing diabetes. There is a corresponding increase in the risk of birth trauma and shoulder dystocia. The high rates of macrosomia, along with other obstetric complications such as pre-eclampsia, mean that up to two-thirds of women with diabetes will be delivered by caesarean section. Shoulder dystocia is also more common in women with both pre-existing and gestational diabetes. Warning signs such as slow progress in labour, particularly in the second stage, should be heeded with early recourse to operative delivery where significant fetal macrosomia is suspected.

Neonatal hypoglycaemia is more common, occurring in 5% and 12% of cases of pre-existing DM and GDM, respectively. An increase in fetal insulin production in response to sustained intrauterine fetal hyperglycaemia is thought to be the cause.

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Jan 28, 2017 | Posted by in ANESTHESIA | Comments Off on Endocrine disease in pregnancy, including diabetes mellitus, thyroid and adrenal disease
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