7.1 Hypothyroidism

EXPLANATION OF CONDITION

Hypothyroidism comprises a lack of thyroid hormones, thyroxine (T4) and tri-iodothyronine (T3). This may be primary (impaired functioning of thyroid tissue) or central (due to pituitary or hypothalamic disease).

T4 circulates in the blood in two forms:

Causes

The commonest causes encountered in pregnancy are autoimmune thyroiditis, with or without goitre (Hashimoto’s or atrophic thyroiditis), and a history of thyroidectomy or radioiodine treatment.

Autoimmune thyroid disease occurs in families; sometimes in association with other organ-specific autoimmune diseases, e.g. type 1 diabetes, reflecting a genetic predisposition to organ-specific autoimmunity. Auto-antibodies to thyroid peroxidase (TPO) are usually present in serum.

Symptoms

The symptoms are independent of the cause and may affect multiple systems. They include:

• Weight gain
  
• Constipation
  
• Cold intolerance
  
• Alopecia
  
• Dry skin
  
• Hoarseness
  
• Lethargy
  
• Ataxia
  
• Cognitive impairment
  
• Normochromic normocytic anaemia
  
• Menorrhagia
  
• Bradycardia¹

However, the majority of cases have few or no symptoms at diagnosis.

Signs

Slow-relaxing ankle reflexes, coarse skin, cool skin, periorbital puffiness.

Subclinical hypothyroidism is defined biochemically as a raised TSH concentration with normal free T4 (fT4) and free T3 (fT3) concentrations². This condition can resolve spontaneously, but 2.6% of antibody negative and 4.3% of antibody positive subjects become hypothyroid per year.

Investigations

Investigation consists of the measurement of circulating thyroid hormones with thyroid function tests. In primary hypothyroidism thyroid stimulating hormone (TSH) will be raised, free thyroxine (fT4) will be reduced, as will fT3, although this is not always measured. In central hypothyroidism the TSH will also be low.

TPO antibodies are usually positive in autoimmune thyroiditis. Up to 5% of women have positive antibodies in early pregnancy.

COMPLICATIONS

Myxoedema coma is a rare complication that occurs in undiagnosed or chronically untreated hypothyroidism. There is loss of consciousness with hypothermia, hypoventilation and bradycardia.

There are pregnancy associated complications:

• To mother:
  
  
  
  • Reduced fertility
    
  • Pregnancy induced hypertension
  
  
• To baby:
  
  
  
  • Low birth weight
    
  • Psychomotor retardation

NON-PREGNANCY TREATMENT AND CARE

The standard treatment is thyroid hormone replacement with oral L-thyroxine at a dose sufficient to restore TSH to the normal range – usually 50–150 micrograms once daily.

In central hypothyroidism the dose is adjusted to keep the fT4 in the normal range.

PRE-CONCEPTION ISSUES AND CARE

Women with hypothyroidism may have anovulation and may present with infertility.

Pre-conception care is especially important, as the prospective mother and future child are at risk of:

• Pregnancy induced hypertension – this is two–three times as common in overt or subclinical hypothyroidism
  
• Low birth weight – but there is no excess of congenital malformations
  
• Reduced psychomotor development – associated with hypothyroidism in early pregnancy
  
• Lower IQ in children at age 8 years – associated with untreated maternal hypothyroidism; fetal thyroid starts to produce hormones at 10–12 weeks and early fetal brain development depends on small amounts of maternal thyroid hormone that cross the placenta^3,4

Women who are known to have hypothyroidism should be informed of the above issues, but can be reassured that adequate treatment with thyroxine will reduce the risks to a minimum. They should be reminded to take their thyroxine regularly throughout the pregnancy.

A measurement of fT4 and TSH should be taken as baseline and the dose of thyroxine adjusted if necessary to ensure the woman is euthyroid at the time of conception.

Women with recently-diagnosed hypothyroidism should be advised to delay conceiving until their TSH is restored to a normal level.

Women with subclinical hypothyroidism, who are contemplating pregnancy, should be treated with thyroxine to correct the TSH concentration. As weight gain and lethargy are common problems, the BMI should be estimated (see Appendix 13.1.1) and if overweight a reducing diet advised and an exercise plan recommended.

7.2 Thyrotoxicosis

EXPLANATION OF CONDITION

Thyrotoxicosis is the clinical syndrome caused by high serum concentrations of thyroid hormones. Symptoms and signs include:

• Heat intolerance
  
• Weight loss (despite good appetite)
  
• Insomnia
  
• Agitation
  
• Tremor
  
• Retraction of the upper eyelid
  
• Sweating
  
• Tachycardia and bounding pulse
  
• Diarrhoea
  
• Oligo- or amenorrhoea

Since several of these features occur in normal pregnancy, the clinical diagnosis of thyrotoxicosis can be difficult to make in this context. The combination of raised serum free thyroxine (fT4), and low thyroid stimulating hormone (TSH) confirms the diagnosis. Occasionally the fT4 is in the normal range, but if the fT3 is raised T3 toxicosis occurs¹.

Causes

Graves’ disease: Most women with primary hyperthyroidism in pregnancy will have Graves’ disease (GD), an autoimmune condition in which thyrotoxicosis is caused by auto-antibodies to the thyroid stimulating hormone receptor (TSHR). These thyroid stimulating immunoglobulins (TSIg) mimic the effects of TSH on its receptor, but in an unregulated way. Endogenous TSH falls in response to high levels of fT3 and fT4, but production and release of these hormones continues to be stimulated by TSIgs. A smooth, symmetrical goitre (enlarged thyroid gland) is often present, over which a bruit may be heard. In some cases Graves’ disease is associated with other organ-specific autoimmune conditions, e.g. type 1 diabetes and pernicious anaemia.

Excess thyroid hormone ingestion: This may be iatrogenic (overtreatment of hypothyroidism) or factitious (taking thyroid hormone surreptitiously, perhaps to aid weight loss).

HCG-dependent hyperthyroidism: Human chorionic gonadotrophin (HCG) shows a degree of homology with TSH, and can act as a weak TSHR agonist. Conditions characterised by raised concentrations of HCG may cause hyperthyroidism. The commonest is hyperemesis gravidarum which results in transient hyperthyroidism in one-third of cases. Trophoblastic tumours such as hydatidiform mole may rarely cause thyrotoxicosis¹.

COMPLICATIONS

• Graves’ ophthalmopathy (GO) describes the range of eye symptoms and signs seen in up to 50% of patients with GD. These range from a stare due to retraction of the upper eyelid to exophthalmos of one or both eyes that may result in diplopia and even blindness due to optic nerve compression. Corneal damage can occur when the patient cannot close her eyes properly. Smoking is a risk factor for GO. The disease is thought to be due to an immune response directed against orbital antigens resembling TSHR²
  
• Graves’ dermopathy is an uncommon feature characterised by localised, usually pre-tibial, myxoedema
  
• Thyrotoxic storm is severe life-threatening thyrotoxicosis, usually precipitated by the withdrawal of antithyroid drug treatment or intercurrent illness. Features include high fever, tachycardia, drowsiness and coma³

NON-PREGNANCY TREATMENT AND CARE

Antithyroid Drugs

Carbimazole (CBZ) (methimazole in the US) and propylthiouracil (PTU) block the organification of iodine – an essential step in the manufacture of thyroid hormones. They are also weakly immunosuppressive and may induce long-term remission of GD.

Treatment is usually started at a high dose, which reduces fT4 and fT3 to normal in approximately 4 weeks. Propranolol, a non-selective beta-blocker, may be prescribed to relieve symptoms during this phase, but is not required long term. In order to avoid iatrogenic hypothyroidism it is necessary either to reduce the dose of CBZ or PTU to that required to keep the concentration of fT4 in the normal range (dose titration) or to continue with high dose CBZ or PTU in combination with L-thyroxine (block and replace). After treatment for 12–18 months with dose titration, or 6–12 months with block and replace, medication is stopped.

Remission is induced in 60% of cases. Some who relapse opt for long-term CBZ or PTU (titrated dose), others choose radioiodine treatment or surgery. Side effects include urticaria and arthralgia. Agranulocytosis (incidence 0.2–0.5%) is potentially life threatening and patients must be counselled when starting treatment¹.

Radioiodine (¹³¹I)

The thyroid gland in GD is avid for iodine and will take up ¹³¹I given orally. This radioactive isotope causes a thyroiditis that eventually destroys sufficient thyroid tissue to lower thyroid hormone levels to normal, or subnormal. Women are counselled not to conceive for 6 months following ¹³¹I treatment.

Thyroidectomy

Subtotal thyroidectomy is usually reserved for cases of GD uncontrolled by large doses of antithyroid drugs, or where there is a large goitre.

PRE-CONCEPTION ISSUES AND CARE

The woman is at risk of oligo-/amenorrhoea and consequently reduced fertility.

There are additional risks of fetal and neonatal transfer of the thyroid antibodies causing neonatal thyroid dysfunction.

Women on block and replace treatment are switched to a titrated dose of CBZ or PTU. The woman should be euthyroid by fT4 before conception. If uncontrolled by drug therapy, surgery is considered prior to cessation of contraception². Women should continue with contraception for 6 months following ¹³¹I treatment.

Aplasia cutis is a rare defect of the skin of the scalp. It has only been reported in babies born to mothers who took CBZ and not PTU in pregnancy. Some endocrinologists recommend using PTU rather than CBZ in pregnancy⁴.

7.3 Type 1 Diabetes Mellitus

EXPLANATION OF CONDITION

Type 1 diabetes mellitus (T1DM) accounts for 15–20% of all diabetes mellitus. Since it usually presents in childhood or early adulthood, it accounts for the majority of cases of pre-gestational diabetes. It is caused by autoimmune destruction of the insulin-producing β-cells of the pancreatic islets leading to insulin dependency, and there is a genetic pre-disposition to the condition.

The symptoms are of hyperglycaemia and include thirst, polydipsia, weight loss, fatigue and blurred vision. If not diagnosed at this stage, diabetic ketoacidosis may develop – a medical emergency, characterised by dehydration, and metabolic acidosis, that can lead to coma and death. Diagnostic criteria are included in Appendix 7.3.1. Most patients with T1DM would have had symptoms at presentation and a raised fasting or random venous plasma glucose..

COMPLICATIONS¹

Microvascular Complications

These are caused by chronic hyperglycaemia and are preventable if patients can achieve near normal blood glucose concentrations for much of the time.

Retinopathy

The early stages are asymptomatic, so annual photographic screening is essential. The stages progress from background (requiring no specific treatment) through pre-proliferative to proliferative retinopathy in which retinal ischaemia has stimulated new vessel formation on the optic disc or in the periphery of the retina. New vessels are prone to tear leading to vitreous haemorrhage. The fibrous stalk carrying the new vessels can cause traction retinal detachment. Each scenario can cause blindness. Laser photocoagulation is an effective treatment for pre-proliferative and proliferative retinopathy.

Nephropathy

The earliest sign is microalbuminuria (albumin : creatinine ratio >3.5 mg/mmol). Angiotensin converting enzyme inhibitors (ACEI) are indicated at this stage to reduce the risk of progression. The next stage is overt proteinuria (Albustix® positive). Renal function deteriorates and blood pressure increases. Renal failure progresses to chronic kidney disease (CKD). Some may require dialysis or transplantation.

Neuropathy

The commonest presentation is with a symmetrical sensory polyneuropathy of the feet and legs; this confers a risk of foot ulceration. Less commonly there may be diabetic mononeuropathies and autonomic neuropathy that can cause postural hypotension, gastroparesis, diarrhoea and bladder dysfunction.

Cataract Formation

Three to four times more likely in those under the age of 60 years.

NON-PREGNANCY TREATMENT AND CARE

The aims of treatment are to prevent symptomatic hyper- and hypoglycaemia, and the development of complications. Treatment is with subcutaneous insulin injections. Although insulin preparations are of standard strength, they differ considerably in the rate of onset and duration of action. Patients may take 2–5 injections per day. Injections are given with disposable syringes and needles or with pen-injectors. Some patients use a continuous subcutaneous insulin infusion (CSII) (insulin pump).

The diabetic diet is designed to achieve and maintain a healthy weight. It is high in unrefined carbohydrate (60%) and low in fat (<30%).

Patients are encouraged to monitor their own capillary glucose concentrations to help them to achieve target values. Carbohydrate counting and appropriate adjustment of the insulin dose is the cornerstone of modern diabetes management. However, not all patients achieve ideal control. Routine care includes assessment of diabetic control by measuring HbA1c, physical examination for complications, retinal photography, screening urine for microalbumin and measurement of serum creatinine.

PRE-CONCEPTION ISSUES AND CARE

Pre-pregnancy counselling is essential because of the risks of miscarriage, congenital anomalies, IUGR, pre-eclampsia, macrosomia, polyhydramnios and IUFD. This should be part of routine diabetes care wherever this is provided, but women who are considering pregnancy should have access to a multidisciplinary pregnancy preparation service.

The aim is a planned pregnancy with the woman taking high-dose folic acid (5 mg daily)² and having the best possible diabetic control at the time of conception³. Women with suboptimal diabetic control (HbA1c >53 mmol/mol) should be encouraged to use contraception while efforts are made to improve control^4,5. There should be a thorough assessment of complications, as retinopathy and nephropathy can deteriorate as a result of pregnancy, placing both mother and baby at risk.

Medication should be reviewed and where possible changed to agents that are safer in pregnancy. In particular ACE inhibitors should be stopped, and, where treatment for hypertension is required, methyldopa substituted. Insulin regimens may be intensified – twice daily injections with biphasic preparations are unlikely to allow sufficient flexibility of dose adjustment. Only insulin aspart (NovoRapid) is licensed for use in pregnancy. Theoretical concerns about insulin glargine (Lantus ® and animal insulins mean that human isophane insulins or insulin detemir (Levemir ®) are preferred as basal insulins⁴ (though increasing evidence now supports insulin glargine use in pregnancy).

Medical Management and Care (Figure 7.3.1)

• Planned pregnancy – check if pre-pregnancy actions were carried out
  
• Unplanned pregnancy – start folic acid 5 mg daily², review insulin regimen and alter if necessary, and undertake pre-pregnancy actions
  
• Arrange retinal screening and, if retinopathy detected, arrange regular ophthalmological monitoring
  
• Advise about risk of hypoglycaemia (especially if vomiting is a problem); ensure the woman and her partner are equipped to treat hypoglycaemia – glucose tablets or drinks (GlucoGel) and glucagon injection (GlucaGen)
  
• Advise and assist the woman to achieve target blood glucose levels (<5 mmol/l pre-meals and <7 mmol/l 2 hours after meals)
  
• Advise on aspirin treatment from 12 weeks gestation¹
  
• From 20–36 weeks of gestation maternal insulin resistance increases due to placental production of counter regulatory hormones, especially human placental lactogen; insulin dose will need to be increased to deal with this
  
• Delivery should be at term unless there is any concern about fetal growth or wellbeing or if the diabetic control has been suboptimal, in which case earlier delivery may be recommended

Midwifery Management and Care

• Immediate referral to combined diabetes–obstetric antenatal clinic
  
• Maintain regular contact with specialist team either by clinic attendance or telephone every 1–2 weeks
  
• Ensure that all screening procedures concerning maternal and neonatal complications of diabetes are performed in a timely manner
  
• Advise on weight management as appropriate⁶
  
• Discuss plans for infant feeding and provide information on colostrum harvesting where appropriate
  
• Ensure plan for delivery has been made in partnership with the woman and is clearly and accurately documented in the notes
  
• Advise woman to come to the unit if she becomes unwell or has concerns about fetal movements
  
• Offer parentcraft education including advice on the management of diabetes during delivery and postpartum

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Related

Related posts:

1. MUSCULOSKELETAL DISORDERS
2. AUTOIMMUNE DISORDERS
3. NEOPLASIA
4. HAEMATOLOGICAL DISORDERS

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